wikidoc - User contributions [en]

Extranodal NK-T-cell lymphoma other diagnostic studies

2019-06-06T22:59:23Z

Ahmed Younes:

__NOTOC__
{{Extranodal NK-T-cell lymphoma}}
{{CMG}}; {{AE}} {{AS}}
==Overview==
Other diagnostic studies for extranodal NK-T-cell lymphoma include [[PCR]], [[bone marrow aspiration]], [[bone marrow biopsy]], and in situ hybridization.<ref name="cancer.gov">Extranodal NK-/T-cell lymphoma, nasal type. Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/seertools/hemelymph/51f6cf56e3e27c3994bd530f/. Accessed on February 02, 2016</ref><ref name="Hindawi">Extranodal Natural-Killer/T-Cell Lymphoma, Nasal Type. Hindawi Publishing Corporation. http://www.hindawi.com/journals/ah/2010/627401/. Accessed on February 19, 2016 </ref>
==Other Diagnostic Studies==
Other diagnostic studies for extranodal NK-T-cell lymphoma include:<ref name="cancer.gov">Extranodal NK-/T-cell lymphoma, nasal type. Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/seertools/hemelymph/51f6cf56e3e27c3994bd530f/. Accessed on February 02, 2016</ref>
* [[PCR]]: to quantify circulating plasma EBV DNA level<ref name="Hindawi">Extranodal Natural-Killer/T-Cell Lymphoma, Nasal Type. Hindawi Publishing Corporation. http://www.hindawi.com/journals/ah/2010/627401/. Accessed on February 19, 2016 </ref>
:* A high level of circulating plasma [[EBV]] [[DNA]] has correlated with:
::* High tumor load
::* Extensive disease
::* Poor response to treatment
::* Inferior survival
* [[Bone marrow aspiration]]
* [[Bone marrow biopsy]]
* In situ hybridization: to detect [[EBV]] [[RNA]]
==References==
{{reflist|2}}
[[Category:Disease]]
[[Category:Types of cancer]]

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Hematology]]
[[Category:Immunology]]

Extranodal NK-T-cell lymphoma other imaging findings

2019-06-06T22:58:45Z

Ahmed Younes: /* Other Imaging Studies */

__NOTOC__
{{Extranodal NK-T-cell lymphoma}}
{{CMG}}; {{AE}} {{AS}}
==Overview==
[[PET]] scan may be helpful in the diagnosis of extranodal NK-T-cell lymphoma.<ref name="cancer.gov">Extranodal NK-/T-cell lymphoma, nasal type. Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/seertools/hemelymph/51f6cf56e3e27c3994bd530f/. Accessed on February 02, 2016</ref>
==Other Imaging Studies==
* [[PET]] scan may be helpful in the diagnosis of extranodal NK-T-cell lymphoma.<ref name="cancer.gov">Extranodal NK-/T-cell lymphoma, nasal type. Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/seertools/hemelymph/51f6cf56e3e27c3994bd530f/. Accessed on February 02, 2016</ref>
* Fluorine-18 fluorodeoxyglucose positron emission tomography computerized tomography (18-FDG PET-CT) may be helpful in the diagnosis of extranodal NK-T-cell lymphoma.<ref name="Hindawi">Extranodal Natural-Killer/T-Cell Lymphoma, Nasal Type. Hindawi Publishing Corporation. http://www.hindawi.com/journals/ah/2010/627401/. Accessed on February 18, 2016 </ref>
==References==
{{reflist|2}}
[[Category:Disease]]
[[Category:Types of cancer]]

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Hematology]]
[[Category:Immunology]]

Extranodal NK-T-cell lymphoma natural history, complications and prognosis

2019-06-06T22:58:01Z

Ahmed Younes: /* Natural History */

__NOTOC__
{{Extranodal NK-T-cell lymphoma}}
{{CMG}}; {{AE}} {{AS}}
==Overview==
If left untreated, patients with extranodal NK-T-cell lymphoma, nasal type may progress to develop [[proptosis]] and [[hard palate]] perforation. Common complications of extranodal NK-T-cell lymphoma include [[hepatosplenomegaly]] and [[pancytopenia]]. Depending on the extent of the tumor at the time of diagnosis, the prognosis may vary. Prognosis is generally regarded as poor.<ref name="cancer.gov">Extranodal NK-/T-cell lymphoma, nasal type. Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/seertools/hemelymph/51f6cf56e3e27c3994bd530f/. Accessed on February 04, 2016</ref><ref name="Hindawi">Extranodal Natural-Killer/T-Cell Lymphoma, Nasal Type. Hindawi Publishing Corporation. http://www.hindawi.com/journals/ah/2010/627401/. Accessed on February 19, 2016 </ref>
==Natural History==
* Extranodal NK-T-cell lymphoma almost always shows an extranodal presentation.<ref name="cancer.gov">Extranodal NK-/T-cell lymphoma, nasal type. Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/seertools/hemelymph/51f6cf56e3e27c3994bd530f/. Accessed on February 04, 2016</ref><ref name="Hindawi">Extranodal Natural-Killer/T-Cell Lymphoma, Nasal Type. Hindawi Publishing Corporation. http://www.hindawi.com/journals/ah/2010/627401/. Accessed on February 19, 2016 </ref>
* Some cases may be accompanied by secondary [[lymph node]] involvement although rare instances of primary lymph node disease in the absence of extranodal involvement has been reported.
* Extension to adjacent tissues such as the [[nasopharynx]], [[paranasal sinuses]], [[orbit]], [[oral cavity]], [[palate]], and [[oropharynx]] are possible.
* Retro-orbital involvement causes [[proptosis]] and impairment of extraocular movement.
* Occasionally local extension from the nasal cavity causes destruction of the [[hard palate]] with the characteristic midline perforation, previously referred to as “lethal midline granuloma”.
* At presentation, the disease is often localized to the upper aerodigestive tract.
* Disseminated disease may have involvement of the [[lymph nodes]], [[bone marrow]] and [[peripheral blood]].
==Complications==
* Extranodal NK-T-cell lymphoma, nasal type, often develop hemophagocytic syndrome. (uncontrolled activation of certain parts of the immune system)<ref name="canadiancancer">Extranodal NK/T-cell lymphoma, nasal type. Canadian Cancer Society. http://www.cancer.ca/en/cancer-information/cancer-type/non-hodgkin-lymphoma/non-hodgkin-lymphoma/types-of-nhl/extranodal-nk-t-cell-lymphoma-nasal-type/?region=on. Accessed on February 04, 2016 </ref>

* Hemophagocytic syndrome results in
:* [[Fever]]
:* [[Hepatosplenomegaly]]
:* [[Pancytopenia]]
==Prognosis==
* The prognosis for people with extranodal NK-T-cell lymphoma is often poor and the risk for relapse is high.<ref name="canadiancancer">Extranodal NK/T-cell lymphoma, nasal type. Canadian Cancer Society. http://www.cancer.ca/en/cancer-information/cancer-type/non-hodgkin-lymphoma/non-hodgkin-lymphoma/types-of-nhl/extranodal-nk-t-cell-lymphoma-nasal-type/?region=on. Accessed on February 04, 2016 </ref>
* People with extranodal NK-T-cell lymphoma confined to the nose or nasal passages have a better prognosis than those people with more widespread disease.
* The International Prognostic Index (IPI) predicts outcome in nasal NK-T-cell lymphoma.<ref name="hindawi">Extranodal Natural-Killer/T-Cell Lymphoma, Nasal Type. Hindawi. http://www.hindawi.com/journals/ah/2010/627401/. Accessed on February 04, 2016 </ref>
* Patients with International Prognostic Index of 1 or less were shown to have a better overall survival.
* In a recent retrospective analysis of 172 patients with extranodal NK-T-cell lymphoma, nasal type 4 prognostic factors were identified :
:* Nonnasal type
:* Stage
:* Performance status
:* Number of extranodal sites
* In a Korean prognostic model, four prognostic groups have been identified depending on :
:* B-symptoms
:* Stage
:* [[LDH]] level
:* Regional [[lymphadenopathy]]

==References==
{{reflist|2}}
[[Category:Disease]]
[[Category:Types of cancer]]

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}

Extranodal NK-T-cell lymphoma pathophysiology

2019-06-06T22:57:18Z

Ahmed Younes:

Extranodal NK-T-cell lymphoma overview

2019-06-06T22:56:16Z

Ahmed Younes:

__NOTOC__
{{Extranodal NK-T-cell lymphoma}}
{{CMG}}; {{AE}} {{AS}}

==Overview==
Extranodal NK-T-cell lymphoma, nasal type, can develop in either [[T cells]] or [[natural killer cells]], but most often in the NK cells. Natural killer cells are a type of lymphocyte that are closely related to T cells and attack foreign cells. Extranodal NK-T-cell lymphoma may be classified according to [[WHO]] into 2 subtypes: NK cell-derived neoplasms, namely, aggressive NK cell leukemia and extra nodal NK-T-cell lymphoma, nasal type. Based on the organ involvement, extranodal NK-T-cell lymphoma may be classified into extranodal NK-T-cell lymphoma, nasal type and extranodal NK-T-cell lymphoma, extra nasal type. On gross pathology, angiocentric and angiodestructive pattern of growth with associated geographical [[necrosis]] and [[ulceration]] are characteristic findings of extranodal NK-T-cell lymphoma. On microscopic histopathological analysis, medium sized tumor cells and polymorphic infiltrate of nonneoplastic inflammatory cells are characteristic findings of extranodal NK-T-cell lymphoma.There are no established causes for extranodal NK-T-cell lymphoma. Extranodal NK-T-cell lymphoma must be differentiated from other diseases such as [[anaplastic large cell lymphoma]], non specific inflammatory process, [[enteropathy associated T cell lymphoma]], and [[peripheral T cell lymphoma]].Patients of all age groups may develop extranodal NK-T-cell lymphoma. Males are more commonly affected with extranodal NK-T-cell lymphoma than females. The majority of extranodal NK-T-cell lymphoma cases are reported in Asian, Central-American, and South-American countries.There are no established risk factors for extranodal NK-T-cell lymphoma. According to the the U.S. Preventive Service Task Force (USPSTF), there is insufficient evidence to recommend routine screening for extranodal NK-T-cell lymphoma.If left untreated, patients with extranodal NK-T-cell lymphoma, nasal type may progress to develop [[proptosis]] and [[hard palate]] perforation. Common complications of extranodal NK-T-cell lymphoma include [[hepatosplenomegaly]] and [[pancytopenia]]. Depending on the extent of the tumor at the time of diagnosis, the prognosis may vary. Prognosis is generally regarded as poor.<ref name="cancer.gov">Extranodal NK-/T-cell lymphoma, nasal type. Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/seertools/hemelymph/51f6cf56e3e27c3994bd530f/. Accessed on February 04, 2016</ref><ref name="Hindawi">Extranodal Natural-Killer/T-Cell Lymphoma, Nasal Type. Hindawi Publishing Corporation. http://www.hindawi.com/journals/ah/2010/627401/. Accessed on February 18, 2016 </ref>There is no established system for the staging of extranodal NK-T-cell lymphoma. A T-staging system, originally designed for sinonasal B-cell lymphoma has been adopted to overcome this problem by taking into account the extent of local tumor involvement.The most common symptoms of extranodal NK-T-cell lymphoma include [[fever]], [[weight loss]], skin rash, [[night sweats]], protrusion of eye, swelling of the face, discharge from the nose, nose bleeds, blockage of the nasal passages, chest pain, [[abdominal pain]], [[bone pain]], and painless swelling in the neck, axilla, groin, thorax, and abdomen.Common physical examination findings of extranodal NK-T-cell lymphoma include [[fever]], [[rash]], [[ulcer]], [[proptosis]], midfacial destructive lesions, [[epistaxis]], nasal obstruction due to mass, chest tenderness, abdomen tenderness, bone tenderness, [[Lymphadenopathy|peripheral lymphadenopathy]], and [[Lymphadenopathy|central lymphadenopathy]].Laboratory tests for extranodal NK-T-cell lymphoma include [[complete blood count]] (CBC), blood chemistry studies, cytogenetic analysis, [[flow cytometry]], [[immunohistochemistry]], and [[immunophenotyping]].Lymph node or extranodal tissue biopsy is diagnostic of extranodal NK-T-cell lymphoma. [[CT]] scan may be helpful in the diagnosis of extranodal NK-T-cell lymphoma. Computerized tomography (CT) may be performed to detect metastasis and assess the local extent of extranodal NK-T-cell lymphoma.[[MRI]] may be helpful in the diagnosis of extranodal NK-T-cell lymphoma.Magnetic resonance imaging (MRI) may be performed to better define local soft tissue and bony involvement of extranodal NK-T-cell lymphoma. <ref name="Hindawi">Extranodal Natural-Killer/T-Cell Lymphoma, Nasal Type. Hindawi Publishing Corporation. http://www.hindawi.com/journals/ah/2010/627401/. Accessed on February 19, 2016</ref>[[PET]] scan may be helpful in the diagnosis of extranodal NK-T-cell lymphoma.Other diagnostic studies for extranodal NK-T-cell lymphoma include [[PCR]], [[bone marrow aspiration]], [[bone marrow biopsy]], and in situ hybridization.The predominant therapy for extranodal NK-T-cell lymphoma is [[radiation therapy]]. Adjunctive [[chemotherapy]] and [[stem cell transplant]] may be required.
==Classification==
Extranodal NK-T-cell lymphoma may be classified according to [[WHO]] into 2 subtypes: NK cell-derived neoplasms, namely, aggressive NK cell leukemia and extra nodal NK-T-cell lymphoma, nasal type. Based on the organ involvement, extranodal NK-T-cell lymphoma may be classified into extranodal NK-T-cell lymphoma, nasal type and extranodal NK-T-cell lymphoma, extra nasal type.
==Pathophysiology==
Extra nodal NK-T-cell lymphoma, nasal type, can develop in either [[T cells]] or [[natural killer cells]], but most often in the NK cells. Natural killer cells are a type of lymphocyte that are closely related to T cells and attack foreign cells. On gross pathology, angiocentric and angiodestructive pattern of growth with associated geographical [[necrosis]] and [[ulceration]] are characteristic findings of extranodal NK-T-cell lymphoma. On microscopic histopathological analysis, medium sized tumor cells and polymorphic infiltrate of nonneoplastic inflammatory cells are characteristic findings of extranodal NK-T-cell lymphoma.
==Causes==
There are no established causes for extranodal NK-T-cell lymphoma.
==Differential Diagnosis==
Extranodal NK-T-cell lymphoma must be differentiated from other diseases such as [[anaplastic large cell lymphoma]], non specific inflammatory process, [[enteropathy associated T cell lymphoma]], and [[peripheral T cell lymphoma]].
==Epidemiology and Demographics==
Patients of all age groups may develop extranodal NK-T-cell lymphoma. Males are more commonly affected with extranodal NK-T-cell lymphoma than females. The majority of extranodal NK-T-cell lymphoma cases are reported in Asian, Central-American, and South-American countries.
==Risk Factors==
There are no established risk factors for extranodal NK-T-cell lymphoma.
==Screening==
According to the the U.S. Preventive Service Task Force (USPSTF), there is insufficient evidence to recommend routine screening for extranodal NK-T-cell lymphoma.
==Natural History, Prognosis, and Complications==
If left untreated, patients with extranodal NK-T-cell lymphoma, nasal type may progress to develop [[proptosis]] and [[hard palate]] perforation. Common complications of extranodal NK-T-cell lymphoma include [[hepatosplenomegaly]] and [[pancytopenia]]. Depending on the extent of the tumor at the time of diagnosis, the prognosis may vary. Prognosis is generally regarded as poor.
==Diagnosis==
===Staging===
There is no established system for the staging of extranodal NK-T-cell lymphoma. A T-staging system, originally designed for sinonasal B-cell lymphoma has been adopted to overcome this problem by taking into account the extent of local tumor involvement.
===Symptoms===
The most common symptoms of extranodal NK-T-cell lymphoma include [[fever]], [[weight loss]], skin rash, [[night sweats]], protrusion of eye, swelling of the face, discharge from the nose, nose bleeds, blockage of the nasal passages, chest pain, [[abdominal pain]], [[bone pain]], and painless swelling in the neck, axilla, groin, thorax, and abdomen.
===Physical Examination===
Common physical examination findings of extranodal NK-T-cell lymphoma include [[fever]], [[rash]], [[ulcer]], [[proptosis]], midfacial destructive lesions, [[epistaxis]], nasal obstruction due to mass, chest tenderness, abdomen tenderness, bone tenderness, [[Lymphadenopathy|peripheral lymphadenopathy]], and [[Lymphadenopathy|central lymphadenopathy]].
===Laboratory tests===
Laboratory tests for extranodal NK-T-cell lymphoma include [[complete blood count]] (CBC), blood chemistry studies, cytogenetic analysis, [[flow cytometry]], [[immunohistochemistry]], and [[immunophenotyping]].
===Biopsy===
Lymph node or extranodal tissue biopsy is diagnostic of extranodal NK-T-cell lymphoma.
===CT===
[[CT]] scan may be helpful in the diagnosis of extranodal NK-T-cell lymphoma. Computerized tomography (CT) may be performed to detect metastasis and assess the local extent of extranodal NK-T-cell lymphoma.
===MRI===
[[MRI]] may be helpful in the diagnosis of extranodal NK-T-cell lymphoma.Magnetic resonance imaging (MRI) may be performed to better define local soft tissue and bony involvement of extranodal NK-T-cell lymphoma.
===Other Imaging Studies===
[[PET]] scan may be helpful in the diagnosis of extranodal NK-T-cell lymphoma.
===Other Diagnostic Studies===
Other diagnostic studies for extranodal NK-T-cell lymphoma include [[PCR]], [[bone marrow aspiration]], [[bone marrow biopsy]], and in situ hybridization.
==Treatment==
===Medical Therapy===
The predominant therapy for extranodal NK-T-cell lymphoma is [[radiation therapy]]. Adjunctive [[chemotherapy]] and [[stem cell transplant]] may be required.

==References==
{{Reflist|2|}}
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Hematology]]
[[Category:Immunology]]

Biliary cystadenoma and cystadenocarcinoma overview

2019-06-06T22:33:34Z

Ahmed Younes:

__NOTOC__
{{Biliary cystadenoma and cystadenocarcinoma}}
{{CMG}};{{AE}}{{PSK}}
==Overview==
'''Biliary cystadenoma''' is an uncommon unilocular or multilocular cystic neoplasm that usually arises in the liver or occasionally in the extrahepatic biliary tree and gallbladder. Biliary cystadenomas constitute less than 5% of cystic lesions of the liver. On gross pathology, biliary cystadenoma is unilocular or multilocular cystic lesion filled with fluid or blood. Cystic fluid may be clear and mucinous. On microscopic histopathological analysis, presence of biliary-type [[epithelium]] wall supported by ovarian-like stroma is characteristic finding of biliary cystadenoma. The cause of biliary cystadenoma has not been identified. However, it is thought to occur either as a result of the development of ectopic foci of primitive [[foregut]] sequestered within the [[liver]] or due to the obstruction of the congenitally aberrant [[bile duct]]. Neoplastic transformation to cystadenocarcinoma is the most common complication of biliary cystadenoma. Biliary cystadenoma with mesenchymal stroma is associated with most favorable [[prognosis]]. Symptoms of biliary cystadenoma include abdominal pain in right upper quadrant, abdominal distension, abdominal mass, [[nausea]], and [[vomiting]]. Common physical examination findings of biliary cystadenoma are a palpable, tender [[mass]] in the right upper quadrant of abdomen or epigastrium, [[jaundice]], and [[ascites]]. On ultrasound, biliary cystadenoma is characterized by fluid filled multiloculated cyst with enhanced transmission. The cyst fluid may contain low level echoes from blood products, mucin, or proteinaceous fluid. Contrast-enhanced ultrasound demonstrates minimal enhancement since the tumors are largely avascular. Surgical resection of tumor is the mainstay of treatment for biliary cystadenoma. Complete enucleation of the cyst is a safe and effective treatment for biliary cystadenoma and hepatic resection is a suitable treatment option for biliary cystadenocarcinoma.

==Classification==
There is no classification system established for biliary cystadenoma and biliary cystadenocarcinoma.
==Pathophysiology==
On gross pathology, biliary cystadenoma is unilocular or multilocular cystic lesion filled with fluid. Cystic fluid may be clear and mucinous. On microscopic histopathological analysis, presence of biliary-type epithelium wall, occasional papillary projections, and ovarian-like stroma are characteristic findings of biliary cystadenoma.
==Causes==
The cause of biliary cystadenoma has not been identified. However, it is thought to occur either as a result of the development of ectopic foci of primitive [[foregut]] sequestered within the [[liver]] or due to the obstruction of the congenitally aberrant [[bile duct]].
==Differential Diagnosis==
Biliary cystadenoma and cystadenocarcinoma must be differentiated from simple liver cysts, liver hematoma, hepatic echinococcal cyst, hepatic abscess, post-traumatic cysts, and bilomas.
==Epidemiology and Demographics==
Biliary cystadenoma is a rare disease. Females are more commonly affected with biliary cystadenoma than males. The median age at diagnosis of biliary cystadenoma is 45 years.
==Risk Factors==
There are no established risk factors for biliary cystadenoma.
==Screening==
According to the the U.S. Preventive Service Task Force (USPSTF), there is insufficient evidence to recommend routine screening for biliary cystadenoma.
==Natural History, Complications and Prognosis==
Common complication of biliary cystadenoma include neoplastic transformation to biliary cystadenocarcinoma. Biliary cystadenoma with mesenchymal stroma is associated with most favorable prognosis.

==Diagnosis==
===Staging===
There is no established system for the staging of biliary cystadenoma and biliary cystadenocarcinoma.
===History and Symptoms===
Symptoms of biliary cystadenoma include abdominal pain in right upper quadrant, abdominal distension, abdominal mass, [[nausea]], and [[vomiting]].
===Physical Examination===
Common physical examination findings of biliary cystadenoma are a palpable, tender mass in the right upper quadrant of abdomen or epigastrium, jaundice, and ascites.

===Laboratory Findings===
Laboratory findings consistent with the diagnosis of biliary cystadenoma include elevation of serum [[alkaline phosphatase]], serum [[bilirubin]], and [[CA 19-9]] in cystic fluid. Some patients with biliary cystadenoma may have [[leukocytosis]] with left shift, which is usually suggestive of [[superinfection]] of the tumor.

===CT===
On CT scan, biliary cystadenoma is characterized by fluid filled multiloculated cyst with calcification of septa and cyst wall. The appearance of the cyst fluid on CT is variable depending on its composition.
===MRI===
Abdominal MRI may be helpful in the diagnosis of biliary cystadenoma, which demonstrates variability on T1-and T2-weighted images.

===Ultrasound===
On ultrasound, biliary cystadenoma is characterized by fluid filled multiloculated cyst with enhanced transmission. The cyst fluid may contain low level echoes from blood products, mucin, or proteinaceous fluid. Contrast-enhanced ultrasound demonstrates minimal enhancement since the tumors are largely avascular.
==Treatment==
===Medical Therapy===
There is no medical therapy for biliary cystadenoma and cystadenocarcinoma. The mainstay of therapy is surgical resection.

===Surgery===
Surgical resection of tumor is the mainstay of treatment for biliary cystadenoma. Complete enucleation of the cyst is a safe and effective treatment for biliary cystadenoma and hepatic resection is a suitable treatment option for biliary cystadenocarcinoma.

==References==
{{Reflist|2}}
[[Category:Disease]]
[[Category:Gastroenterology]]
{{WikiDoc Help Menu}}
{{WikiDoc Sources}}
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Hepatology]]
[[Category:Gastroenterology]]
[[Category:Surgery]]

Intravascular large B-cell lymphoma

2019-06-06T22:26:48Z

Ahmed Younes: /* Other Imaging Findings */

{{SI}}
{{CMG}}; {{AE}} {{AS}}

{{SK}} Intravascular lymphomatosis; Malignant angioendotheliomatosis; Intravascular lymphoma; Angiotropic large-cell lymphoma; Angiotropic lymphoma; IVLBCL
== Overview ==
Intravascular large B-cell lymphoma is a very rare subtype of [[diffuse large B-cell lymphoma]] (DLBCL). It is also considered a distinct type of [[non-Hodgkin lymphoma]] (NHL) in the World Health Organization ([[WHO]]) classification system. Intravascular large B-cell lymphoma affects small blood vessels. It is a rare and aggressive variant of intravascular proliferation of clonal lymphocytes with little to no parenchymal involvement. Based on the clinical presentation, intravascular large B-cell lymphoma may be classified into either Western variant or Asian variant. On microscopic histopathological analysis, diffuse infiltrate of large atypical cells with irregular nuclear contours, vesicular chromatin, and occasional prominent nucleoli are characteristic findings of intravascular large b-cell lymphoma. The incidence of intravascular large B-cell lymphoma increases with age; the median age at diagnosis is 67 years. Intravascular large B-cell lymphoma affects men and women equally. People with this type of lymphoma often have a poor prognosis. Symptoms of the intravascular large B-cell lymphoma include [[fever]], [[weight loss]], [[night sweats]], chest pain, abdominal pain, bone pain, and painless swellings in the neck, axilla, groin, thorax, and abdomen. Lymph node biopsy is diagnostic of intravascular large B-cell lymphoma. [[CT]], [[MRI]], and [[PET]] scan may be helpful in the diagnosis of intravascular large B-cell lymphoma. The predominant therapy for intravascular large B-cell lymphoma is [[chemotherapy]]. Adjunctive [[radiotherapy]] may be required.

==Classification==
Based on the clinical presentation, intravascular large B-cell lymphoma may be classified into either Western variant or Asian variant.
{| style="border: 0px; font-size: 90%; margin: 3px;" align=center
|+ '''Intravascular large B-cell lymphoma classification'''
! style="background: #4479BA;; color:#FFF;" | Name
! style="background: #4479BA;; color:#FFF;" | Description
|-
| style="text-align: center; padding: 5px 5px; background: #F5F5F5;" | Western variant
| style="padding: 5px 5px; background: #F5F5F5;" |
* Western variant characterized by symptoms related to the main organ involved, predominantly neurological or cutaneous
|-
| style="text-align: center; padding: 5px 5px; background: #F5F5F5;" | Asian variant
| style="padding: 5px 5px; background: #F5F5F5;" |
* Asian variant in which the patients present with multi-organ failure, [[hepatosplenomegaly]], [[pancytopenia]], and hemophagocytic syndrome.
* This is an aggressive lymphoma which responds poorly to [[chemotherapy]].
* The poor prognosis reflects in part frequent delays in diagnosis because of a lack of detectable tumor masses.
|}

== Pathophysiology==
Intravascular large B-cell lymphoma is characterized by a massive intravascular proliferation of atypical mononuclear cells which lodged in the lumina of small or intermediate vessels in many organs. The neoplastic lymphoid cells are large with prominent nucleoli and frequent mitotic figures. Fibrin [[thrombi]], [[haemorrhage]] and [[necrosis]] may be seen.
===Microscopic Pathology===
On microscopic histopathological analysis, diffuse infiltrate of large atypical cells with irregular nuclear contours, vesicular chromatin, and occasional prominent nucleoli are characteristic findings of intravascular large b-cell lymphoma.

==Causes==
There are no established causes for intravascular large B-cell lymphoma.
==Differentiating type page name here from other Diseases==
Intravascular large B-cell lymphoma must be differentiated from other diseases such as:
* [[Hepatosplenic T-cell lymphoma]]
* B-cell chronic lymphocytic leukemia
* [[Mantle cell lymphoma]]
* [[Splenic marginal zone lymphoma]]

== Epidemiology and Demographics ==
===Age===
The incidence of intravascular large B-cell lymphoma increases with age; the median age at diagnosis is 67 years.<ref name=seer.cancer.gov>Intravascular large B-cell lymphoma. Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/seertools/hemelymph/51f6cf5ae3e27c3994bd54a7/. Accessed on March 09, 2016 </ref>
===Gender===
Intravascular large B-cell lymphoma affects men and women equally.<ref name=seer.cancer.gov>Intravascular large B-cell lymphoma. Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/seertools/hemelymph/51f6cf5ae3e27c3994bd54a7/. Accessed on March 09, 2016 </ref>

== Risk Factors ==
There are no established risk factors for intravascular large B-cell lymphoma.

== Natural History, Complications and Prognosis==
* Intravascular large B-cell lymphoma usually affects the small blood vessels in many organs, including: central nervous system, kidneys, lungs, and skin. However, almost any site can be affected.
* People with intravascular large B-cell lymphoma have a variety of symptoms. The symptoms will depend on the tissue or organ affected when the blood vessels become occluded. This type of lymphoma is often difficult to diagnose because the symptoms can be so varied.
* Intravascular large B-cell lymphoma is a fast-growing (aggressive) lymphoma.
* People with this type of lymphoma often have a poor prognosis.
* People with this type of lymphoma can also develop a very serious condition where certain parts of the immune system are activated (hemophagocytic syndrome).<ref name=seer.cancer.gov>Intravascular large B-cell lymphoma. Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/seertools/hemelymph/51f6cf5ae3e27c3994bd54a7/. Accessed on March 09, 2016 </ref>
* Hemophagocytic syndrome causes:
:* [[Fever]]
:* Enlarged liver and spleen ([[hepatosplenomegaly]])
:* A lower number of red blood cells, white blood cells and platelets in the blood ([[pancytopenia]])

== Diagnosis ==
===Staging===
Staging for Intravascular large B-cell lymphoma is provided in the following table:<ref>{{Cite journal| doi = 10.1200/JCO.2013.54.8800| issn = 1527-7755| volume = 32| issue = 27| pages = 3059–3068| last1 = Cheson| first1 = Bruce D.| last2 = Fisher| first2 = Richard I.| last3 = Barrington| first3 = Sally F.| last4 = Cavalli| first4 = Franco| last5 = Schwartz| first5 = Lawrence H.| last6 = Zucca| first6 = Emanuele| last7 = Lister| first7 = T. Andrew| last8 = Alliance, Australasian Leukaemia and Lymphoma Group| last9 = Eastern Cooperative Oncology Group| last10 = European Mantle Cell Lymphoma Consortium| last11 = Italian Lymphoma Foundation| last12 = European Organisation for Research| last13 = Treatment of Cancer/Dutch Hemato-Oncology Group| last14 = Grupo Español de Médula Ósea| last15 = German High-Grade Lymphoma Study Group| last16 = German Hodgkin's Study Group| last17 = Japanese Lymphorra Study Group| last18 = Lymphoma Study Association| last19 = NCIC Clinical Trials Group| last20 = Nordic Lymphoma Study Group| last21 = Southwest Oncology Group| last22 = United Kingdom National Cancer Research Institute| title = Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification| journal = Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology| date = 2014-09-20| pmid = 25113753}}</ref>

{| style="border: 0px; font-size: 90%; margin: 3px;" align=center
|+ '''Revised staging system for primary nodal lymphomas (Lugano classification)'''
! style="background: #4479BA; color:#FFF;" | Stage
! style="background: #4479BA; color:#FFF;" | Involvement
! style="background: #4479BA; color:#FFF;" | Extranodal (E) status
|-
| style="padding: 5px 5px; background: #DCDCDC;" colspan=3 | '''Limited'''
|-
| style="padding: 5px 5px; background: #F5F5F5;" | Stage I
| style="padding: 5px 5px; background: #F5F5F5;" | One node or a group of adjacent nodes
| style="padding: 5px 5px; background: #F5F5F5;" | Single extranodal lesions without nodal involvement
|-
| style="padding: 5px 5px; background: #F5F5F5;" | Stage II
| style="padding: 5px 5px; background: #F5F5F5;" | Two or more nodal groups on the same side of the diaphragm
| style="padding: 5px 5px; background: #F5F5F5;" | Stage I or II by nodal extent with limited contiguous extranodal involvement
|-
| style="padding: 5px 5px; background: #F5F5F5;" | Stage II bulky
| style="padding: 5px 5px; background: #F5F5F5;" | II as above with "bulky" disease
| style="padding: 5px 5px; background: #F5F5F5;" | Not applicable
|-
| style="padding: 5px 5px; background: #DCDCDC;" colspan=3 | '''Advanced'''
|-
| style="padding: 5px 5px; background: #F5F5F5;" | Stage III
| style="padding: 5px 5px; background: #F5F5F5;" | Nodes on both sides of the diaphragm; nodes above the diaphragm with spleen involvement
| style="padding: 5px 5px; background: #F5F5F5;" | Not applicable
|-
| style="padding: 5px 5px; background: #F5F5F5;" | Stage IV
| style="padding: 5px 5px; background: #F5F5F5;" | Additional noncontiguous extralymphatic involvement
| style="padding: 5px 5px; background: #F5F5F5;" | Not applicable
|}
=== Symptoms ===
People with intravascular large B-cell lymphoma have a variety of symptoms. The symptoms will depend on the tissue or organ affected when the blood vessels become occluded. This type of lymphoma is often difficult to diagnose because the symptoms can be so varied.
Most common symptoms of the intravascular large B-cell lymphoma include:<ref name=seer.cancer.gov>Intravascular large B-cell lymphoma. Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/seertools/hemelymph/51f6cf5ae3e27c3994bd54a7/. Accessed on March 09, 2016 </ref>
* [[Fever]]
* [[Weight loss]]
* [[Night sweats]]
* Painless swellings in the neck, axilla, groin, thorax, and abdomen
* Pain in the chest, abdomen, or bones

=== Physical Examination ===
====Vitals====
* [[Fever]] is often present
====Skin====
* Skin rash
====HEENT====
* [[Lymphadenopathy|Cervical lymphadenopathy]]
====Thorax====
* Thoracic masses suggestive of [[Lymphadenopathy|central lymphadenopathy]]
====Abdomen====
* [[Abdominal mass]]es suggestive of [[Lymphadenopathy|central lymphadenopathy]]
* [[Hepatosplenomegaly]]
====Extremities====
* [[Lymphadenopathy|Peripheral lymphadenopathy]]
{| style="border: 0px; font-size: 90%; margin: 3px;" align=center
|+ '''Intravascular large B-cell lymphoma clinical features based on organ involvement'''
! style="background: #4479BA;; color:#FFF;" | Organ Involved
! style="background: #4479BA;; color:#FFF;" | Clinical features
|-
| style="text-align: center; padding: 5px 5px; background: #F5F5F5;" | Central nervous system
| style="padding: 5px 5px; background: #F5F5F5;" |
* Focal sensory or motor deficits, generalized weakness, altered sensorium, rapidly progressive [[dementia]], [[seizures]], [[hemiparesis]], [[dysarthria]], [[ataxia]], [[vertigo]], and transient visual loss
|-
| style="text-align: center; padding: 5px 5px; background: #F5F5F5;" | Cutaneous Involvement
| style="padding: 5px 5px; background: #F5F5F5;" |
* Maculopapular eruptions, [[nodules]], [[plaques]], tumors, hyperpigmented patches, palpable [[purpura]], ulcers, and infiltrative “peau d’orange”
|}

===Laboratory Findings ===
Laboratory tests for intravascular large B-cell lymphoma include:<ref name=seer.cancer.gov>Intravascular large B-cell lymphoma. Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/seertools/hemelymph/51f6cf5ae3e27c3994bd54a7/. Accessed on March 09, 2016 </ref>
* [[Complete blood count]] (CBC): [[pancytopenia]]
* Blood chemistry studies:
* Cytogenetic analysis
* [[Flow cytometry]]
* [[Immunohistochemistry]]
* [[Immunophenotyping]]
====Biopsy====
Lymph node biopsy is diagnostic of intravascular large B-cell lymphoma.
==== Other Imaging Findings ====
[[CT]], [[MRI]], and [[PET]] scan may be helpful in the diagnosis of intravascular large B-cell lymphoma.

==Treatment==
===Medical Therapy===
{| style="border: 0px; font-size: 90%; margin: 3px;" align=center
|+ '''Treatment of intravascular large B-cell lymphoma<ref name= canadiancancer>Intravascular large B-cell lymphoma. Canadian Cancer Society. http://www.cancer.ca/en/cancer-information/cancer-type/non-hodgkin-lymphoma/non-hodgkin-lymphoma/types-of-nhl/intravascular-large-b-cell-lymphoma/?region=nb. Accessed on March 9, 2016 </ref>
! style="background: #4479BA; color:#FFF;" | Therapy
! style="background: #4479BA; color:#FFF;" | Description
|-
| style="padding: 5px 5px; background: #DCDCDC;" | [[Chemotherapy]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* Combination therapy :
:* CHOP – [[Cyclophosphamide]] {{and}} [[Doxorubicin]] {{and}} [[Vincristine]] {{and}} [[Prednisone]]
|-
| style="padding: 5px 5px; background: #DCDCDC;" | [[Radiation therapy]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* [[External beam radiation therapy]] may be used.
|}

==References==
{{Reflist|2}}

[[Category:Disease]]
[[Category:Oncology]]
==Related Chapters==
* [[Richter's transformation]]
* [[T-cell lymphoma]]

{{Hematological malignancy histology}}

[[Category:Types of cancer]]
[[Category:Oncology]]
[[Category:Disease]]

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Hematology]]
[[Category:Immunology]]

Intravascular large B-cell lymphoma

2019-06-06T22:25:52Z

Ahmed Younes: /* Microscopic Pathology */

{{SI}}
{{CMG}}; {{AE}} {{AS}}

{{SK}} Intravascular lymphomatosis; Malignant angioendotheliomatosis; Intravascular lymphoma; Angiotropic large-cell lymphoma; Angiotropic lymphoma; IVLBCL
== Overview ==
Intravascular large B-cell lymphoma is a very rare subtype of [[diffuse large B-cell lymphoma]] (DLBCL). It is also considered a distinct type of [[non-Hodgkin lymphoma]] (NHL) in the World Health Organization ([[WHO]]) classification system. Intravascular large B-cell lymphoma affects small blood vessels. It is a rare and aggressive variant of intravascular proliferation of clonal lymphocytes with little to no parenchymal involvement. Based on the clinical presentation, intravascular large B-cell lymphoma may be classified into either Western variant or Asian variant. On microscopic histopathological analysis, diffuse infiltrate of large atypical cells with irregular nuclear contours, vesicular chromatin, and occasional prominent nucleoli are characteristic findings of intravascular large b-cell lymphoma. The incidence of intravascular large B-cell lymphoma increases with age; the median age at diagnosis is 67 years. Intravascular large B-cell lymphoma affects men and women equally. People with this type of lymphoma often have a poor prognosis. Symptoms of the intravascular large B-cell lymphoma include [[fever]], [[weight loss]], [[night sweats]], chest pain, abdominal pain, bone pain, and painless swellings in the neck, axilla, groin, thorax, and abdomen. Lymph node biopsy is diagnostic of intravascular large B-cell lymphoma. [[CT]], [[MRI]], and [[PET]] scan may be helpful in the diagnosis of intravascular large B-cell lymphoma. The predominant therapy for intravascular large B-cell lymphoma is [[chemotherapy]]. Adjunctive [[radiotherapy]] may be required.

==Classification==
Based on the clinical presentation, intravascular large B-cell lymphoma may be classified into either Western variant or Asian variant.
{| style="border: 0px; font-size: 90%; margin: 3px;" align=center
|+ '''Intravascular large B-cell lymphoma classification'''
! style="background: #4479BA;; color:#FFF;" | Name
! style="background: #4479BA;; color:#FFF;" | Description
|-
| style="text-align: center; padding: 5px 5px; background: #F5F5F5;" | Western variant
| style="padding: 5px 5px; background: #F5F5F5;" |
* Western variant characterized by symptoms related to the main organ involved, predominantly neurological or cutaneous
|-
| style="text-align: center; padding: 5px 5px; background: #F5F5F5;" | Asian variant
| style="padding: 5px 5px; background: #F5F5F5;" |
* Asian variant in which the patients present with multi-organ failure, [[hepatosplenomegaly]], [[pancytopenia]], and hemophagocytic syndrome.
* This is an aggressive lymphoma which responds poorly to [[chemotherapy]].
* The poor prognosis reflects in part frequent delays in diagnosis because of a lack of detectable tumor masses.
|}

== Pathophysiology==
Intravascular large B-cell lymphoma is characterized by a massive intravascular proliferation of atypical mononuclear cells which lodged in the lumina of small or intermediate vessels in many organs. The neoplastic lymphoid cells are large with prominent nucleoli and frequent mitotic figures. Fibrin [[thrombi]], [[haemorrhage]] and [[necrosis]] may be seen.
===Microscopic Pathology===
On microscopic histopathological analysis, diffuse infiltrate of large atypical cells with irregular nuclear contours, vesicular chromatin, and occasional prominent nucleoli are characteristic findings of intravascular large b-cell lymphoma.

==Causes==
There are no established causes for intravascular large B-cell lymphoma.
==Differentiating type page name here from other Diseases==
Intravascular large B-cell lymphoma must be differentiated from other diseases such as:
* [[Hepatosplenic T-cell lymphoma]]
* B-cell chronic lymphocytic leukemia
* [[Mantle cell lymphoma]]
* [[Splenic marginal zone lymphoma]]

== Epidemiology and Demographics ==
===Age===
The incidence of intravascular large B-cell lymphoma increases with age; the median age at diagnosis is 67 years.<ref name=seer.cancer.gov>Intravascular large B-cell lymphoma. Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/seertools/hemelymph/51f6cf5ae3e27c3994bd54a7/. Accessed on March 09, 2016 </ref>
===Gender===
Intravascular large B-cell lymphoma affects men and women equally.<ref name=seer.cancer.gov>Intravascular large B-cell lymphoma. Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/seertools/hemelymph/51f6cf5ae3e27c3994bd54a7/. Accessed on March 09, 2016 </ref>

== Risk Factors ==
There are no established risk factors for intravascular large B-cell lymphoma.

== Natural History, Complications and Prognosis==
* Intravascular large B-cell lymphoma usually affects the small blood vessels in many organs, including: central nervous system, kidneys, lungs, and skin. However, almost any site can be affected.
* People with intravascular large B-cell lymphoma have a variety of symptoms. The symptoms will depend on the tissue or organ affected when the blood vessels become occluded. This type of lymphoma is often difficult to diagnose because the symptoms can be so varied.
* Intravascular large B-cell lymphoma is a fast-growing (aggressive) lymphoma.
* People with this type of lymphoma often have a poor prognosis.
* People with this type of lymphoma can also develop a very serious condition where certain parts of the immune system are activated (hemophagocytic syndrome).<ref name=seer.cancer.gov>Intravascular large B-cell lymphoma. Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/seertools/hemelymph/51f6cf5ae3e27c3994bd54a7/. Accessed on March 09, 2016 </ref>
* Hemophagocytic syndrome causes:
:* [[Fever]]
:* Enlarged liver and spleen ([[hepatosplenomegaly]])
:* A lower number of red blood cells, white blood cells and platelets in the blood ([[pancytopenia]])

== Diagnosis ==
===Staging===
Staging for Intravascular large B-cell lymphoma is provided in the following table:<ref>{{Cite journal| doi = 10.1200/JCO.2013.54.8800| issn = 1527-7755| volume = 32| issue = 27| pages = 3059–3068| last1 = Cheson| first1 = Bruce D.| last2 = Fisher| first2 = Richard I.| last3 = Barrington| first3 = Sally F.| last4 = Cavalli| first4 = Franco| last5 = Schwartz| first5 = Lawrence H.| last6 = Zucca| first6 = Emanuele| last7 = Lister| first7 = T. Andrew| last8 = Alliance, Australasian Leukaemia and Lymphoma Group| last9 = Eastern Cooperative Oncology Group| last10 = European Mantle Cell Lymphoma Consortium| last11 = Italian Lymphoma Foundation| last12 = European Organisation for Research| last13 = Treatment of Cancer/Dutch Hemato-Oncology Group| last14 = Grupo Español de Médula Ósea| last15 = German High-Grade Lymphoma Study Group| last16 = German Hodgkin's Study Group| last17 = Japanese Lymphorra Study Group| last18 = Lymphoma Study Association| last19 = NCIC Clinical Trials Group| last20 = Nordic Lymphoma Study Group| last21 = Southwest Oncology Group| last22 = United Kingdom National Cancer Research Institute| title = Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification| journal = Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology| date = 2014-09-20| pmid = 25113753}}</ref>

{| style="border: 0px; font-size: 90%; margin: 3px;" align=center
|+ '''Revised staging system for primary nodal lymphomas (Lugano classification)'''
! style="background: #4479BA; color:#FFF;" | Stage
! style="background: #4479BA; color:#FFF;" | Involvement
! style="background: #4479BA; color:#FFF;" | Extranodal (E) status
|-
| style="padding: 5px 5px; background: #DCDCDC;" colspan=3 | '''Limited'''
|-
| style="padding: 5px 5px; background: #F5F5F5;" | Stage I
| style="padding: 5px 5px; background: #F5F5F5;" | One node or a group of adjacent nodes
| style="padding: 5px 5px; background: #F5F5F5;" | Single extranodal lesions without nodal involvement
|-
| style="padding: 5px 5px; background: #F5F5F5;" | Stage II
| style="padding: 5px 5px; background: #F5F5F5;" | Two or more nodal groups on the same side of the diaphragm
| style="padding: 5px 5px; background: #F5F5F5;" | Stage I or II by nodal extent with limited contiguous extranodal involvement
|-
| style="padding: 5px 5px; background: #F5F5F5;" | Stage II bulky
| style="padding: 5px 5px; background: #F5F5F5;" | II as above with "bulky" disease
| style="padding: 5px 5px; background: #F5F5F5;" | Not applicable
|-
| style="padding: 5px 5px; background: #DCDCDC;" colspan=3 | '''Advanced'''
|-
| style="padding: 5px 5px; background: #F5F5F5;" | Stage III
| style="padding: 5px 5px; background: #F5F5F5;" | Nodes on both sides of the diaphragm; nodes above the diaphragm with spleen involvement
| style="padding: 5px 5px; background: #F5F5F5;" | Not applicable
|-
| style="padding: 5px 5px; background: #F5F5F5;" | Stage IV
| style="padding: 5px 5px; background: #F5F5F5;" | Additional noncontiguous extralymphatic involvement
| style="padding: 5px 5px; background: #F5F5F5;" | Not applicable
|}
=== Symptoms ===
People with intravascular large B-cell lymphoma have a variety of symptoms. The symptoms will depend on the tissue or organ affected when the blood vessels become occluded. This type of lymphoma is often difficult to diagnose because the symptoms can be so varied.
Most common symptoms of the intravascular large B-cell lymphoma include:<ref name=seer.cancer.gov>Intravascular large B-cell lymphoma. Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/seertools/hemelymph/51f6cf5ae3e27c3994bd54a7/. Accessed on March 09, 2016 </ref>
* [[Fever]]
* [[Weight loss]]
* [[Night sweats]]
* Painless swellings in the neck, axilla, groin, thorax, and abdomen
* Pain in the chest, abdomen, or bones

=== Physical Examination ===
====Vitals====
* [[Fever]] is often present
====Skin====
* Skin rash
====HEENT====
* [[Lymphadenopathy|Cervical lymphadenopathy]]
====Thorax====
* Thoracic masses suggestive of [[Lymphadenopathy|central lymphadenopathy]]
====Abdomen====
* [[Abdominal mass]]es suggestive of [[Lymphadenopathy|central lymphadenopathy]]
* [[Hepatosplenomegaly]]
====Extremities====
* [[Lymphadenopathy|Peripheral lymphadenopathy]]
{| style="border: 0px; font-size: 90%; margin: 3px;" align=center
|+ '''Intravascular large B-cell lymphoma clinical features based on organ involvement'''
! style="background: #4479BA;; color:#FFF;" | Organ Involved
! style="background: #4479BA;; color:#FFF;" | Clinical features
|-
| style="text-align: center; padding: 5px 5px; background: #F5F5F5;" | Central nervous system
| style="padding: 5px 5px; background: #F5F5F5;" |
* Focal sensory or motor deficits, generalized weakness, altered sensorium, rapidly progressive [[dementia]], [[seizures]], [[hemiparesis]], [[dysarthria]], [[ataxia]], [[vertigo]], and transient visual loss
|-
| style="text-align: center; padding: 5px 5px; background: #F5F5F5;" | Cutaneous Involvement
| style="padding: 5px 5px; background: #F5F5F5;" |
* Maculopapular eruptions, [[nodules]], [[plaques]], tumors, hyperpigmented patches, palpable [[purpura]], ulcers, and infiltrative “peau d’orange”
|}

===Laboratory Findings ===
Laboratory tests for intravascular large B-cell lymphoma include:<ref name=seer.cancer.gov>Intravascular large B-cell lymphoma. Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/seertools/hemelymph/51f6cf5ae3e27c3994bd54a7/. Accessed on March 09, 2016 </ref>
* [[Complete blood count]] (CBC): [[pancytopenia]]
* Blood chemistry studies:
* Cytogenetic analysis
* [[Flow cytometry]]
* [[Immunohistochemistry]]
* [[Immunophenotyping]]
====Biopsy====
Lymph node biopsy is diagnostic of intravascular large B-cell lymphoma.
==== Other Imaging Findings ====
[[CT]], [[MRI]], and [[PET]] scan may be helpful in the diagnosis of intravascular large B-cell lymphoma.
<gallery widths=200px>
Image:Intravascular large B-cell lymphoma CT .jpg | Computed tomography (CT) scan of the chest showed diffuse interstitial thickening and ground glass opacities.<ref name=hindawi>Intravascular Large B-Cell Lymphoma Presenting as Interstitial Lung Disease. Hindawi Publishing Corporation. http://www.hindawi.com/journals/cripa/2014/928065/. Accessed on March 10, 2016 </ref>
</gallery>

==Treatment==
===Medical Therapy===
{| style="border: 0px; font-size: 90%; margin: 3px;" align=center
|+ '''Treatment of intravascular large B-cell lymphoma<ref name= canadiancancer>Intravascular large B-cell lymphoma. Canadian Cancer Society. http://www.cancer.ca/en/cancer-information/cancer-type/non-hodgkin-lymphoma/non-hodgkin-lymphoma/types-of-nhl/intravascular-large-b-cell-lymphoma/?region=nb. Accessed on March 9, 2016 </ref>
! style="background: #4479BA; color:#FFF;" | Therapy
! style="background: #4479BA; color:#FFF;" | Description
|-
| style="padding: 5px 5px; background: #DCDCDC;" | [[Chemotherapy]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* Combination therapy :
:* CHOP – [[Cyclophosphamide]] {{and}} [[Doxorubicin]] {{and}} [[Vincristine]] {{and}} [[Prednisone]]
|-
| style="padding: 5px 5px; background: #DCDCDC;" | [[Radiation therapy]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* [[External beam radiation therapy]] may be used.
|}

==References==
{{Reflist|2}}

[[Category:Disease]]
[[Category:Oncology]]
==Related Chapters==
* [[Richter's transformation]]
* [[T-cell lymphoma]]

{{Hematological malignancy histology}}

[[Category:Types of cancer]]
[[Category:Oncology]]
[[Category:Disease]]

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Hematology]]
[[Category:Immunology]]

Adenoma CT

2019-06-02T13:03:07Z

Ahmed Younes: /* CT */

__NOTOC__
{{Adenoma}}
{{CMG}}
==Overview==

====Unenchanced CT====

*Adrenal adenomas appear as small (<3 cm), well-defined homogeneous masses that are typically hypoattenuating relative to the liver.
*At an attenuation value of less than 0 HU at unenhanced CT, the diagnosis of an adenoma can be made with 100% confidence; however, this threshold has only 47% sensitivity.
*At cutoff of 18 HU, a diagnosis of adenoma was made with 100% specificity and 85% sensitivity, compared to the specificity:sensitivity ratio of 68%:100% with a '''more conservative cutoff of 10 HU'''.
*A rational approach advocated by some authorities is to choose the CT number threshold on the basis of the patient’s risk for metastatic disease. For example, a threshold of 10 HU could be applied to older patients or to those with known primary malignancies. A threshold of 18 HU could be applied to younger patients without underlying cancer.

====Enhanced CT====

*Lipid-poor adenomas are more difficult to diagnose because the CT numbers increase and approach those of soft tissue.
*Contrast-enhanced imaging with '''10-minute-delayed CT scans''' may be helpful in these cases.
**By using a threshold of 30 HU, the sensitivity and specificity for delayed contrast-enhanced CT in the characterization of benign disease are 80% and 100%, respectively.
**A relative percentage washout of more than 50% in the delayed study represents a sensitivity and specificity of 98% and 100%, respectively, for the detection of adenoma.

==References==

{{reflist|2}}

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]

Adenoma pathophysiology

2019-06-02T13:02:04Z

Ahmed Younes: /* Microscopic Pathology */

__NOTOC__
{{CMG}}; {{AE}} {{SM}}
{{Adenoma}}
==Pathophysiology ==
Adenoma is a benign epithelial tumor arising in epithelium of mucosa (stomach, small intestine and bowel), glands (endocrine and exocrine) and ducts.
In hollow organs (digestive tract) the adenoma grows upwards into the lumen - adenomatous polyp (or polypoid adenoma).

Depending on the type of the insertion base, adenoma may be pedunculated lobular head with a long slender stalk, covered by normal mucosa or sessile (broad base).

The adenomatous proliferation is characterized by different degrees of cell dysplasia (atypia or loss of normal differentiation of epithelium) irregular cells with hyperchromatic nuclei, (pseudo)stratified nuclei, nucleolus, decreased mucosecretion and mitosis.
The architecture may be tubular, villous or tubulo-villous. Basement membrane and muscularis mucosae are intact.

===Locations===
==== Colon ====

Adenomas of the colon are quite prevalent. They are found commonly at colonoscopy. They are removed because of their tendency to become malignant and lead to colon cancer.

====Renal====
This is a tumor which is most often small and asymptomatic and its derived from renal tubules. It may be a precursor lesion to renal carcinoma.

====Adrenal ====
Adrenal adenomas are common, 1 in 10 people have them malignant and asymptomatic. They are often found on of the abdomen, usually not as the focus of investigation; they are usually incidental findings. About one in 10,000 is malignant. Thus, a biopsy is rarely called for, especially if the lesion is homogeneous and smaller than 3 centimeters. Follow-up images in three to six months can confirm the stability of the growth.

While some adrenal adenomas do not secrete hormones at all , often some secrete [[cortisol]] causing [[Cushing_syndrome|Cushing's syndrome]], [[aldosterone]] causing [[Conn_syndrome|Conn's syndrome]] or [[androgens]] causing [[hyperandrogenism]].

====Thyroid ====
About one in 10 people are found to have solitary thyroid nodules. Investigation is required because a small percentage of these are malignant. Biopsy usually confirms the growth to be an adenoma, but sometimes, excision at surgery is required, especially when the cells found at biopsy are of the follicular type.

====Pituitary====
Pituitary adenomas are commonly seen in 10% of the neurological patients. A lot of them remain undiagnosed. Treatment is usually surgical, to which patients generally respond well. The most common subtype, prolactinoma, is seen more often in women, and is frequently diagnosed during pregnancy as the hormone progesterone increases its growth. Medical therapy bromocriptine generally suppresses prolactinomas; progesterone antagonist therapy has not proven to be successful.

====Liver====
Hepatocellular adenoma, Hepatic adenomas are a rare benign tumour of the liver, which may present with hepatomegaly or other symptoms.

====Breast====
Breast adenomas are called fibroadenomas. They are often very small and difficult to detect. Often there are no symptoms. Treatments can include a needle biopsy, and/or removal.

====Appendix====
Adenomas can also appear in the appendix. The condition is extremely rare and most physicians will never encounter an actual case, but they do happen. The most common version is called cystadenoma. They are usually discovered in the course of examination of the tissue following an appendectomy. If the appendix has ruptured and a tumor is present this presents challenges, especially if malignant cells have formed and thus spread to the abdomen. In 1995 Former Vice President Dan Quayle was found to have cystadenoma in the appendix.

===Gross Pathology===
<gallery>
Image:colon_polyp_face.jpg|Adenomatous polyp of the colon. Courtesy of Ed Uthman, MD
Image:tvp_enface.jpg|Tubulovillous polyp of the colon. Courtesy of Ed Uthman, MD
Image:villaden_dry.jpg|Villous adenoma of the colon. Courtesy of Ed Uthman, MD
</gallery>

===Microscopic Pathology===
Shown below is a micrograph of a colorectal tubular adenoma with high grade dysplasia.(H&E stain)

The lesional tissue, i.e. dysplastic epithelium, is seen on the left of the image and characterized by:

* Nuclear hyperchromatism (i.e. dark purple nuclei) - that extends to the surface,
* Nuclear crowding (i.e. nuclei are bunched-up),
* Elliptical/cigar-shaped nuclei and loss of goblet cells/reduction in the number of goblet cells.

Normal colonic type epithelium is seen on the right of the image and characterized by small round nuclei and abundant goblet cells.

===Video===
Shown below is a video describing microscopic features of a tubular adenoma.
{{#ev:youtube|XGyjOw6jePY}}

==References==

{{reflist|2}}

[[Category:Needs overview]]
[[Category:Disease]]
[[Category:Pathology]]

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]

Osteosarcoma CT

2019-06-01T20:08:35Z

Ahmed Younes: /* CT */

__NOTOC__

{{CMG}}; {{AE}}[[User:DrMars|Mohammadmain Rezazadehsaatlou[2]]].
{{Osteosarcoma}}
==Overview==
CT scan in osteosarcoma may be helpful in [[biopsy]] and [[Cancer staging|staging]]. CT scan adds little to plain [[radiography]] and MRI in direct assessment of the tumor.

==CT==
A CT scan of the primary [[osteosarcoma]] lesion helps delineate the location and extent of the tumor and is critical for surgical planning<ref name="pmid26304877">{{cite journal |vauthors=Isakoff MS, Bielack SS, Meltzer P, Gorlick R |title=Osteosarcoma: Current Treatment and a Collaborative Pathway to Success |journal=J. Clin. Oncol. |volume=33 |issue=27 |pages=3029–35 |date=September 2015 |pmid=26304877 |pmc=4979196 |doi=10.1200/JCO.2014.59.4895 |url=}}</ref><ref name="pmid28808701">{{cite journal |vauthors=Sue M, Oda T, Sasaki Y, Kameta A, Okada Y, Ogura I |title=Osteosarcoma of the Mandible: a Case Report with CT, MRI and Scintigraphy |journal=Chin J Dent Res |volume=20 |issue=3 |pages=169–172 |date=2017 |pmid=28808701 |doi=10.3290/j.cjdr.a38772 |url=}}</ref><ref name="pmid27836366">{{cite journal |vauthors=Heaton TE, Hammond WJ, Farber BA, Pallos V, Meyers PA, Chou AJ, Price AP, LaQuaglia MP |title=A 20-year retrospective analysis of CT-based pre-operative identification of pulmonary metastases in patients with osteosarcoma: A single-center review |journal=J. Pediatr. Surg. |volume=52 |issue=1 |pages=115–119 |date=January 2017 |pmid=27836366 |pmc=5384104 |doi=10.1016/j.jpedsurg.2016.10.034 |url=}}</ref><ref name="pmid28391820">{{cite journal |vauthors=Huang L, Xia W, Zhang B, Qiu B, Gao X |title=MSFCN-multiple supervised fully convolutional networks for the osteosarcoma segmentation of CT images |journal=Comput Methods Programs Biomed |volume=143 |issue= |pages=67–74 |date=May 2017 |pmid=28391820 |doi=10.1016/j.cmpb.2017.02.013 |url=}}</ref><ref name="pmid25058144">{{cite journal |vauthors=Xia T, Guan Y, Chen Y, Li J |title=Askin tumor: CT and FDG-PET/CT imaging findings and follow-up |journal=Medicine (Baltimore) |volume=93 |issue=6 |pages=e42 |date=July 2014 |pmid=25058144 |pmc=4602428 |doi=10.1097/MD.0000000000000042 |url=}}</ref>:
*CT scan in osteosarcoma may be helpful in [[biopsy]] and [[Cancer staging|staging]].
*CT scan adds little to plain [[radiography]] and [[MRI]] in direct assessment of the tumor.
*The exception to this rule is predominantly [[Lytic|lytic lesions]] in which small amounts of mineralised material may be inapparent on both plain film and MRI.
*CT scan is used to:
:*Observe the extent of the bone tumor.
:*Observe if the tumor has spread into nearby tissues.
:*Guide a [[biopsy]] needle to the tumor (CT-guided biopsy).
:*Observe if the [[bone cancer]] has spread to the [[lung]] (metastasis).

==References==
{{Reflist|2}}

{{WH}}
{{WS}}

[[Category:Disease]]
[[Category:Musculoskeletal Disease]]
[[Category:Orthopedics]]
[[Category:Mature chapter]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Orthopedics]]

Osteosarcoma x ray

2019-06-01T20:07:20Z

Ahmed Younes: Undo revision 1570621 by Ahmed Younes (talk)

__NOTOC__

{{CMG}}; {{AE}}[[User:DrMars|Mohammadmain Rezazadehsaatlou[2]]].
{{Osteosarcoma}}
==Overview==
On x-ray, osteosarcoma is characterized by [[medullary]] and [[cortical bone]] destruction, [[periosteal reaction]], tumor matrix [[calcification]], and soft tissue mass.<ref name="radio2">Osteosarcoma. Dr Amir Rezaee ◉ and Dr Frank Gaillard ◉ et al. Radiopaedia.org 2015. http://radiopaedia.org/articles/osteosarcoma</ref>

==X Ray<ref name="pmid6425164">{{cite journal |vauthors=Gürtler KF, Riebel T, Beron G, Heller M, Euler A |title=[Comparison of x-ray plain films, x-ray tomograms and computed tomograms in lung nodules in children and adolescents] |language=German |journal=Rofo |volume=140 |issue=4 |pages=416–20 |date=April 1984 |pmid=6425164 |doi=10.1055/s-2008-1052998 |url=}}</ref><ref name="pmid3022331">{{cite journal |vauthors=Riebel T, Knop J, Winkler K, Delling G |title=[Comparative x-ray and nuclear medical studies of osteosarcomas to evaluate the effectiveness of preoperative chemotherapy] |language=German |journal=Rofo |volume=145 |issue=4 |pages=365–72 |date=October 1986 |pmid=3022331 |doi=10.1055/s-2008-1048952 |url=}}</ref><ref name="pmid3889998">{{cite journal |vauthors=Dinkel E, Uhl H, Roeren T |title=[Lung metastases--limitations and possibilities of radiologic diagnosis] |language=German |journal=Radiologe |volume=25 |issue=4 |pages=158–65 |date=April 1985 |pmid=3889998 |doi= |url=}}</ref><ref name="pmid7042255">{{cite journal |vauthors=Kesselring FO, Penn W |title=Radiological aspects of 'classic' primary osteosarcoma: value of some radiological investigations: A review |journal=Diagn Imaging |volume=51 |issue=2 |pages=78–92 |date=1982 |pmid=7042255 |doi= |url=}}</ref><ref name="pmid27229874">{{cite journal |vauthors=Kubo T, Furuta T, Johan MP, Adachi N, Ochi M |title=Percent slope analysis of dynamic magnetic resonance imaging for assessment of chemotherapy response of osteosarcoma or Ewing sarcoma: systematic review and meta-analysis |journal=Skeletal Radiol. |volume=45 |issue=9 |pages=1235–42 |date=September 2016 |pmid=27229874 |doi=10.1007/s00256-016-2410-y |url=}}</ref><ref name="pmid27154292">{{cite journal |vauthors=Rothermundt C, Seddon BM, Dileo P, Strauss SJ, Coleman J, Briggs TW, Haile SR, Whelan JS |title=Follow-up practices for high-grade extremity Osteosarcoma |journal=BMC Cancer |volume=16 |issue= |pages=301 |date=May 2016 |pmid=27154292 |pmc=4859955 |doi=10.1186/s12885-016-2333-y |url=}}</ref>==
Conventional radiography continues to play an important role in diagnosis of osteosarcoma. Typical appearances of conventional high grade osteosarcoma include:<ref name="radio2">Osteosarcoma. Dr Amir Rezaee ◉ and Dr Frank Gaillard ◉ et al. Radiopaedia.org 2015. http://radiopaedia.org/articles/osteosarcoma</ref>
*[[Medullary]] and [[cortical bone]] destruction.
*Wide zone of transition, permeative or moth-eaten appearance.
*Aggressive [[periosteal reaction]] characterized by:
:*Sunburst appearance
:*[[Codman triangle]]
:*Lamellated (onion skin) reaction: less frequently seen
*Soft-tissue mass.
*Tumor matrix [[ossification]]/[[calcification]].
:*Variable: reflects a combination of the amount of tumor bone production, calcified matrix, and [[osteoid]].
:*Ill-defined fluffy or cloud-like cf. to the rings and arcs of chondroid lesions.

<gallery perrow="3">
File:Osteosarcoma-of-the-distal-femur.jpg
File:Osteosarcoma-of-the-distal-femur (1).jpg
File:Pathological-femur-fracture (1).jpg
File:Pathological-femur-fracture.jpg
File:Osteosarcoma-of-the-fibula (1).jpg
File:Osteosarcoma-of-the-fibula.jpg
</gallery>

*The following table illustrates the findings on x-ray for the subtypes of osteosarcoma:<ref name="radio2">Osteosarcoma.Radiopaedia.org 2015. http://radiopaedia.org/search?utf8=%E2%9C%93&q=osteosarcoma&scope=all</ref>

{| style="border: 0px; font-size: 90%; margin: 3px; width: 1000px" align="center"
| valign="top" |
|+
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Subtype}}
! style="background: #4479BA; width: 400px;" | {{fontcolor|#FFF|X-Ray findings}}
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
:Intracortical osteosarcoma
| style="padding: 5px 5px; background: #F5F5F5;" |
*Presents as an oval intracortical geographic osteolytic lesion in the diaphysis with surrounding sclerosis.
*Measures approximately 4 cm in length.
*Multiple calcific foci can be seen within the lytic region, suggesting osteoid matrix.
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
:Parosteal osteosarcoma
| style="padding: 5px 5px; background: #F5F5F5;" |
*Large lobulated exophytic, 'cauliflower-like' mass with central dense ossification adjacent to the bone.
*String sign: Thin radiolucent line separating the tumor from cortex, observed in 30% of cases.
*Tumor stalk: Grows within tumor in late stages and obliterates the radiolucent cleavage plane.
*+/- soft tissue mass.
*Cortical thickening without aggressive periosteal reaction is often seen.
*Tumor extension into medullary cavity is frequently observed.
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
:Periosteal osteosarcoma
| style="padding: 5px 5px; background: #F5F5F5;" |
*Typically seen as a broad-based surface soft-tissue mass causing extrinsic erosion of thickened underlying diaphyseal cortex and perpendicular periosteal reaction extending into the soft-tissue component.
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
:Telangiectatic osteosarcoma
| style="padding: 5px 5px; background: #F5F5F5;" |
*Typically seen as an expansile lytic metaphyseal bony lesion.
*Geographic bony destruction with wide zone of transition tends to be more common than permeative bony destruction.
*Less osteoid matrix compared from conventional type.
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
:Low grade osteosarcoma
| style="padding: 5px 5px; background: #F5F5F5;" |
*Because the [[fibrous dysplasia]] and central low-grade osteosarcoma are so similar histologically, the radiographic features are an extremely important part of the diagnosis.
*Radiographic features of low grade osteosarcomas are variable.
*Most common pattern is as a large intracompartmental expansile lytic fibro-osseous lesion with coarsely thick or thin incomplete trabeculations. Another less common pattern is as a dense sclerotic lesion.
*Cortical erosion and soft tissue extension is also a common feature.
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
:Extra skeletal osteosarcoma
| style="padding: 5px 5px; background: #F5F5F5;" |
*Soft tissue density with variable amount of calcification which represents osteoid matrix formation, and is seen in approximately 50% of cases.
|-
|}

==References==

{{Reflist|2}}

{{WH}}
{{WS}}

[[Category:Disease]]
[[Category:Musculoskeletal Disease]]
[[Category:Orthopedics]]
[[Category:Mature chapter]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Orthopedics]]

Osteosarcoma x ray

2019-06-01T20:06:16Z

Ahmed Younes: /* X Ray{{cite journal |vauthors=Gürtler KF, Riebel T, Beron G, Heller M, Euler A |title=[Comparison of x-ray plain films, x-ray tomograms and computed tomograms in lung nodules in children and adolescents] |language=German |journal=Rofo |volume=140 |...

Osteosarcoma overview

2019-06-01T20:03:00Z

Ahmed Younes:

__NOTOC__

{{CMG}}; {{AE}}[[User:DrMars|Mohammadmain Rezazadehsaatlou[2]]].
{{Osteosarcoma}}
==Overview==
Bone cancer is a malignant (cancerous) tumor of the bone that destroys normal bone tissue. Osteosarcoma is the most common type of malignant bone cancer, accounting for 35% of primary bone malignancies. It is a malignant tumor that is characterized by the direct formation of bone or osteoid tissue by the tumor cells. Malignant tumors that begin in bone tissue are called primary bone cancer. Osteosarcoma may be classified according to the [[World Health Organization]]’s histologic classification of bone tumors into three groups. The osteosarcomas may be localized at the end of the long bones (commonly in the [[metaphysis]]). Most often it affects the upper end of the [[tibia]], [[humerus]], or lower end of the [[femur]]. On [[gross pathology]], areas of bone formation, [[hemorrhage]], [[fibrosis]], and cystic degeneration on cut surface are characteristic findings of osteosarcoma. On microscopic [[histopathological]] analysis, presence of [[osteoid]] within the tumor, [[pleomorphic]] cells, [[anaplastic]] cells, and atypical [[mitoses]] are characteristic findings of osteosarcoma. There are no established causes for osteosarcoma. The common risk factors in the development of osteosarcoma are [[radiation]] to bones, [[alkylating antineoplastic agents]], [[Paget disease]], multiple hereditary [[osteochondromas]], [[fibrous dysplasia]], [[Bloom syndrome]], [[Rothmund-Thomson syndrome]], and [[Li-Fraumeni syndrome]]. Common complications of osteosarcoma include pathologic fracture and [[metastasis]]. The most common symptoms of osteosarcoma include [[bone pain]] that may be worse at night, [[swelling]], and redness at the site of the tumor. On x-ray, osteosarcoma is characterized by [[medullary]] and [[Cortical bone|cortical]] bone destruction, [[periosteal reaction]], tumor matrix [[calcification]], and soft tissue mass. On MRI, osteosarcoma is characterized by intermediate intensity of soft tissue and low signal intensity of [[ossified]] components on T1. High signal intensity of soft tissue and low signal intensity of ossified components on [[Magnetic resonance imaging|T2]]. The predominant therapy for osteosarcoma is [[neoadjuvant]] [[chemotherapy]] ([[chemotherapy]] given before surgery) followed by surgical resection. The most common drugs used to treat osteosarcoma are [[cisplatin]], [[doxorubicin]] and high-dose [[methotrexate]].

== Historical perspective ==
[[Osteosarcoma]] is known as the most common bone malignant tumor. [[Osteosarcoma]] is an ancient disease and is not completely understood, yet. Nobody knows when and who discovered Osteosarcoma, but recent Paleontology discoveries revealed that [[Osteosarcoma]] has a long story in planet earth. Resent discoverers in Germany revealed a 240 million-year-old highly malignant tumor in the fossilized leg bone of a stem turtle. Its been found that osteosarcoma is the earliest case of human cancer which was found on the 1.7 million-year-old fossil of an early ancestor of mankind in Swartkrans cave in South Africa. In 1990, a thousand-year-old mummy of a woman in her mid-30s of age had with a malignant tumor in her upper-left arm which that mass had grown so large that it might burst through her skin while she was still alive.

==Classification==
[[Osteosarcoma]] (OS) is a rare bone cancer which affects both adolescents and young adults. Osteosarcoma was classified as primary and secondary. Later the the [[World Health Organization]] sub-typed as intramedullry/central and surface osteosarcoma with a number of sub-types under each group.

==Pathophysiology==
Traditionally, our knowledge about osteosarcoma has been mostly anatomical but it should be noted that [[Osteosarcoma|it]] arises most commonly in the metaphyseal region of long bones, within the medullary cavity, then [[Osteosarcoma|it]] involves the bone cortex; consequently a pseudocapsule forms around the penetrating tumor. Osteosarcoma is characterised as a highly cellular tumor consisted of: pleomorphic spindle-shaped cells responsible for the producing an osteoid matrix. However, recent developments in the field of medical sciences and the molecular biology have provided huge insights regarding the molecular pathogenesis of [[osteosarcoma]].

==Causes==
There are no established causes for osteosarcoma. However, some studies show that an increased level of [[C-Fos|c-fos]] [[proto-oncogene]] expression can lead to osteosarcoma.

==Differential Diagnosis==
Osteosarcoma must be differentiated from other diseases such as: any type of bone lesions caused by infection and/or tumors. Features such as the eccentric location of the tumor in the metaphyseal portion of the bone and the skeletal location help to distinguish osteosarcoma from Ewing sarcoma. Bone metastases from other primary tumours, less frequent in the young than in adult patients, should also be considered.

==Epidemiology and Demographics==
Osteosarcoma is the most common nonhematologic primary malignant bone neoplasm causing 35% of primary bone malignancies and occurs at any age, it usually affects patients in the second and third decade of life with a peak incidence between 13 and 16 years of age. It is the 8th leading cancer in children under age 15, comprising 2.4% of all malignancies in pediatric patients and about 20% of all primary bone cancers. The overall incidence of osteosarcoma in U.S. population under 24 years of age are estimated at 0.44 cases for 100,000 individuals. Osteosarcoma is slightly more common in males than in females. Primary osteosarcoma typically occurs in young patients (10-20 years) with 75% occurring before the age of 20. Secondary osteosarcoma occurs in elderly patients.
==Risk Factors==
Common risk factors in the development of osteosarcoma are radiation to bones, alkylating antineoplastic agents, Paget disease, multiple hereditary osteochondromas, fibrous dysplasia, Bloom syndrome,Rothmund-Thomson syndrome, and Li-Fraumeni syndrome.

==Screening==
According to the the U.S. Preventive Service Task Force (USPSTF), there is insufficient evidence to recommend routine screening for osteosarcoma.

==Natural History, Complications and Prognosis==
Common [[Complication (medicine)|complications]] of osteosarcoma include [[Bone fracture|pathologic fracture]] and [[metastasis]]. Pre-treatment factors that influence outcome of the osteosarcoma are primary tumor site, size of the primary tumor, and site of [[metastasis]]. After administration of preoperative [[chemotherapy]], factors that influence outcome of the osteosarcoma are adequacy of tumor resection and [[necrosis]] following induction or [[neoadjuvant chemotherapy]]. The 5 year survival rate of osteosarcoma after adequate therapy is approximately 60-80%.

==Diagnosis==
===Staging===
According to the American Joint Committee on Cancer (AJCC), there are four stages of osteosarcoma based on the size of primary tumor, [[metastasis]], involvement of [[lymph nodes]], and grade of the tumor. For the purpose of treatment, there are only two stages of high-grade osteosarcoma: [[Localized disease|localized]] osteosarcoma and [[metastatic]] osteosarcoma.

===History and Symptoms===
The most common symptoms of osteosarcoma include [[bone pain]] that may worse at night, [[swelling]], and [[redness]] at the site of the tumor. The affected bone is not as strong as normal bones and may fracture with minor trauma (a pathological fracture).

===Physical Examination===
Physical examination findings will depend on the location of the osteosarcoma. Common physical examination findings of osteosarcoma are localized [[swelling]] and [[tenderness]] at the site of the tumor.

===Laboratory Findings===
Laboratory tests for osteosarcoma include [[complete blood count]] (CBC), serum [[alkaline phosphatase]] and [[lactate dehydrogenase]].

===Biopsy===
[[Biopsy]] of osteosarcoma is important for confirming the diagnosis and for determining the histologic subtype.<ref>Osteosarcoma. surgwiki. http://www.surgwiki.com/wiki/Diseases_of_bone_and_joints#SURGERY_4 </ref> Biopsy may be performed [[percutaneously]] with either a fine-needle, or a wide-bore needle, or through a formal incision.

===X Ray ===
On x-ray, osteosarcoma is characterized by [[medullary]] and [[cortical bone]] destruction, [[periosteal reaction]], tumor matrix [[calcification]], and soft tissue mass.

===CT ===
CT scan in osteosarcoma may be helpful in [[biopsy]] and [[Cancer staging|staging]]. CT scan adds little to plain [[radiography]] and MRI in direct assessment of the tumor.

===MRI===
On MRI, osteosarcoma is characterized by intermediate intensity of soft tissue and low signal intensity of ossified components on T1. High signal intensity of soft tissue and low signal intensity of ossified components on T2. Considerable contrast enhancement of solid components on T1 contrast.

===Other Imaging Findings===
Bone scan in osteosarcoma is used to observe abnormal areas of bone and [[metastasis]].

===Other Diagnostic Studies===
Bone scan in osteosarcoma is used to observe abnormal areas of bone and metastasis.

==Treatment==
===Medical Therapy===
The predominant therapy for osteosarcoma is [[neoadjuvant]] [[chemotherapy]] ([[chemotherapy]] given before surgery) followed by [[surgical resection]]. The most common drugs used to treat osteosarcoma are [[cisplatin]], [[doxorubicin]] and high-dose [[methotrexate]]. [[Ifosfamide]] can be used as an [[adjuvant treatment]] if the [[necrosis]] rate is low. [[Samarium]] is a radioactive drug that targets areas where bone cells are growing, such as tumor cells in the bone. It helps relieve bone pain.

===Surgery===
The mainstay of therapy for osteosarcoma is [[surgical resection]]. Rather than using the standard staging system, a simpler system is often used when planning treatment for osteosarcoma. This system divides osteosarcomas into 2 groups: [[Localized disease|localized]] osteosarcoma and [[metastatic]] osteosarcoma.

==References==
{{Reflist|2}}

{{WH}}
{{WS}}

[[Category:Disease]]
[[Category:Musculoskeletal Disease]]
[[Category:Orthopedics]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Orthopedics]]

Osteoma CT

2019-06-01T19:58:32Z

Ahmed Younes: /* Gallery */

__NOTOC__
{{Osteoma}}
{{CMG}}{{AE}}{{MV}}
==Overview==

On CT scan, osteomas demonstrate a well circumscribed mass of variable density, varying from very dense (similar in density to normal cortical bone) to less dense with a ground-glass appearance.<ref name="radio"> Paranasal sinus osteoma. Radiopedia.http://radiopaedia.org/articles/paranasal-sinus-osteoma Accessed on January 18, 2016</ref>

==CT==
CT scan findings include:

* Well-circumscribed mass of variable density
* Ground-glass appearance
* Exophytical mass growing out of a sinus.

==Gallery==
<div align="left">
<gallery heights="175" widths="175">
Image:Osteoma-of-orbital-roof.jpg|Large exophytic osteoma<ref name="radio"> Paranasal sinus osteoma. Radiopedia.http://radiopaedia.org/articles/paranasal-sinus-osteoma Accessed on January 18, 2016</ref>
Image:Ivory-osteoma.jpg|Coronal view exophytic osteoma<ref name="radio"> Paranasal sinus osteoma. Radiopedia.http://radiopaedia.org/articles/paranasal-sinus-osteoma Accessed on January 18, 2016</ref>
</gallery>
</div>

==References==
{{reflist|2}}

{{WH}}
{{WS}}

[[Category:Disease]]
[[Category:Oncology]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Orthopedics]]

Osteoma physical examination

2019-06-01T19:57:37Z

Ahmed Younes: /* Gallery */

__NOTOC__
{{Osteoma}}
{{CMG}}{{AE}}{{MV}}

==Overview==
Common physical examination findings of osteoma include the [[nasal discharge]], facial tenderness, and facial deformity.<ref name="pmid8272884">{{cite journal |vauthors=Greenspan A |title=Benign bone-forming lesions: osteoma, osteoid osteoma, and osteoblastoma. Clinical, imaging, pathologic, and differential considerations |journal=Skeletal Radiol. |volume=22 |issue=7 |pages=485–500 |year=1993 |pmid=8272884 |doi= |url=}}</ref>

==Physical Examination==

===Appearance===
*Patients are usually well-appearing

===HEENT===
*General examination may show facial tenderness
*Looking in the [[nose]] for signs of obstruction and nasal discharge
*Shining a light against the [[sinus]] (transillumination) for signs of [[inflammation]]
*Tapping over a [[sinus]] area to find dull sound
*Physical deformity over mastoid, or facial area

==References==
{{reflist|2}}

{{WH}}
{{WS}}

[[Category:Disease]]
[[Category:Oncology]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Orthopedics]]

Osteoma overview

2019-06-01T19:56:03Z

Ahmed Younes:

__NOTOC__
{{Osteoma}}
{{CMG}}{{AE}}{{MV}}

==Overview==

'''Osteoma''' (also known as ''Osteomata'') is a slow growing benign tumor of bone, occurring most commonly in the [[craniofacial]] skeletal structures, primarily in the nasal and [[paranasal]] (75-90%) cavities. Osteoma arises from bone overgrowth, which is normally composed of [[connective tissue]]. Osteomas are slow growing tumors composed of compact or mature [[trabecular bone]] limited to craniofacial bones. Osteoma may be incidentally identified as a mass in the [[skull]], [[mandible]], or as the underlying cause of [[sinusitis]] or [[mucocele]] formation within the [[paranasal sinuses]]. When they are multiple, Gardner syndrome should be considered. Osteoma represents the most common benign neoplasm of the nose and paranasal sinuses. The causes remain uncertain, but commonly accepted theories propose embryologic, traumatic, or infectious causes. Osteomas are usually asymptomatic. Excision may be performed if osteoma is responsible for symptoms.

==Historical Perspective==
In 1898, Paul Schulze, was the first to describe a craniofacial skeletal osteoma.

==Classification==
Osteoma may be classified into either sporadic or multiple forms. The different subtypes of osteoma include: ivory osteoma, mature osteoma, and mixed osteoma.

==Pathophysiology==
Osteoma is a slow growing benign tumor of bone, occurring most commonly in the [[craniofacial]] skeletal structures, primarily in the nasal and [[paranasal]] (75-90%) cavities. Osteoma arises from bone overgrowth, which is normally composed of [[connective tissue]]. Osteomas are slow growing tumors composed of compact or mature [[trabecular bone]] limited to craniofacial bones. The most common gene affected in multiple osteoma is the [[APC]] gene.

==Causes==
The cause of an osteoma has not been identified, but commonly accepted theories propose embryological, traumatic, or infective causes.

==Differentiating Osteoma from other Diseases==
Osteoma must be differentiated from other diseases that cause sinus or facial pain, headache, and changes to or loss of sense of smell, such as other osteogenic tumours, fibrous displasia, and chronic sinusitis.

==Epidemiology and Demographics==
Osteoma is the most common benign neoplasm of the nose and paranasal sinuses. The prevalence of osteoma is 3% in general population. It mainly affects adults and children. The mean age at diagnosis is 37 years. Men are more commonly affected than women, with a 3:2 ratio.

==Risk Factors==
The risk factors of osteoma remain unknown.

==Screening==
Screening for multiple osteomas is recommended among patients with [[family history]] or/and a confirmed diagnosis of Gardner syndrome. [[Thyroid]] exam and annual ultrasound, should be performed starting at age 10 to 12 years.

==Natural History, Complications and Prognosis==

If left untreated, osteoma progression occurs slowly and is then followed by facial distortion. Common sites of location include paranasal sinuses. Complications of osteoma are usually related to tumor size. The prognosis is regarded as excellent after surgical excision. Features associated with worse [[prognosis]] after surgery are [[tumor]] location, depth, and size.

==Diagnosis==

===Staging===

There is no established system for the staging of osteoma.

===History and Symptoms===
The hallmark of osteoma is facial pain and [[headache]]. A positive history of [[Gardner syndrome]] is suggestive of multiple osteomas. Symptoms related with osteoma will vary depending on the size and location of the tumor. Small osteomas are asymptomatic and usually incidental findings. Conversely, common symptoms of large paranasal sinus osteomas may be [[headache]], [[nasal congestion]], and [[anosmia]].

===Physical Examination===
Common physical examination findings of osteoma include the [[nasal discharge]], facial [[tenderness]], and facial deformity.

===Laboratory Findings===
There are no diagnostic laboratory findings associated with osteoma.

===X Ray===
On x-ray, osteoma demonstrates a dense well circumscribed mass with varying amounts of central lucency. Caldwell and Waters view are the radiographic positions of choice for the evaluation of osteomas.

===CT===
On CT scan, osteomas demonstrate a well circumscribed mass of variable density, varying from very dense (similar in density to normal cortical bone) to less dense with a ground-glass appearance.

===MRI===
On MRI, ivory osteomas are low on all sequences. Mature osteomas may demonstrate some marrow signal, but are also predominantly low on all sequences.

===Ultrasound===
There are no ultrasound findings associated with osteoma.

===Other Imaging Findings===
There are no other imaging findings associated with osteoma.

===Other Diagnostic Studies===
Other diagnostic study for osteoma is nasal endoscopy. Biopsy may be obtained with nasal endoscopy, depending on the location of the tumor.

==Treatment==

===Medical Therapy===
There is no medical treatment for osteoma; the mainstay of therapy is surgery.

===Surgery===
Surgery is the mainstay of therapy. Surgical intervention is only recommended for the management of symptomatic osteoma.

==Primary Prevention==
There is no primary prevention for osteoma.

==Secondary Prevention==

Secondary prevention for osteoma includes screening for multiple osteomas among patients with family history or/and a confirmed diagnosis of Gardner syndrome. Thyroid exam and annual ultrasound, should be performed starting at age 10 to 12 years.

==References==
{{reflist|2}}

{{WH}}
{{WS}}

[[Category:Disease]]
[[Category:Oncology]]
[[Category:Disease]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Orthopedics]]

Osteochondroma MRI

2019-06-01T19:01:22Z

Ahmed Younes: /* Gallery */

__NOTOC__
{{Osteochondroma}}
{{CMG}}{{AE}}{{MV}}

==Overview==
On MRI, osteochondroma shows [[cartilage]] thickness (and thus assessing for malignant transformation), presence of [[edema]] in [[bone]] or adjacent [[soft tissue]]s, and visualization of neurovascular structures. MRI is the imaging modality of choice to assess malignant transformation of osteochondroma.<ref name= "radio"> Osteochondroma. Dr Yuranga Weerakkody. Radiopedia. http://radiopaedia.org/articles/osteochondroma Accessed on January 28, 2016</ref>

==MRI==
*MRI is the imaging modality of choice to assess [[malignant]] transformation of osteochondroma.<ref name= "radio"> Osteochondroma. Dr Yuranga Weerakkody. Radiopedia. http://radiopaedia.org/articles/osteochondroma Accessed on January 28, 2016</ref>
*MRI findings of osteochondroma, include:
:*[[Cartilage]] thickness (and thus assessing for malignant transformation)
:*Presence of [[edema]] in [[bone]] or adjacent [[soft tissue]]s
:*Visualization of neurovascular structures

==References==
{{reflist|1}}

{{WH}}
{{WS}}

[[Category:Disease]]
[[Category:Oncology]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Orthopedics]]

Osteochondroma CT

2019-06-01T19:00:13Z

Ahmed Younes: /* Gallery */

__NOTOC__
{{Osteochondroma}}
{{CMG}}{{AE}}{{MV}}

==Overview==
On CT scan, osteochondroma shows the same findings as on radiograph, but it has better accuracy to demonstrate medullary continuity and the cartilage cap.<ref name= "radio"> Osteochondroma. Dr Yuranga Weerakkody. Radiopedia. http://radiopaedia.org/articles/osteochondroma Accessed on January 28, 2016</ref>

==CT==

CT findings associated with osteochondroma, include:<ref name= "radio"> Osteochondroma. Dr Yuranga Weerakkody. Radiopedia. http://radiopaedia.org/articles/osteochondroma Accessed on January 28, 2016</ref>
*Visualization of the mineralization in the cartilage cap
*Evaluation of the marrow continuity of the lesion

==References==
{{reflist|1}}

[[Category:Disease]]
[[Category:Oncology]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Orthopedics]]

Osteochondroma x ray

2019-06-01T18:59:37Z

Ahmed Younes: /* Gallery */

__NOTOC__
{{Osteochondroma}}
{{CMG}}{{AE}}{{MV}}

==Overview==
On conventional radiography, characteristic findings of osteochondroma include: sessile or pedunculated bony growth, located at the metaphyseal region, bone growth projecting away from the epiphysis, and widening of the metaphysis.<ref name= "radio"> Osteochondroma. Dr Yuranga Weerakkody. Radiopedia. http://radiopaedia.org/articles/osteochondroma Accessed on January 28, 2016</ref>

==X Ray==

*The appearance of solitary osteochondroma in long bones, is pathognomonic.<ref name="pmid10992031">{{cite journal |vauthors=Murphey MD, Choi JJ, Kransdorf MJ, Flemming DJ, Gannon FH |title=Imaging of osteochondroma: variants and complications with radiologic-pathologic correlation |journal=Radiographics : a Review Publication of the Radiological Society of North America, Inc |volume=20 |issue=5 |pages=1407–34 |year=2000 |pmid=10992031 |doi=10.1148/radiographics.20.5.g00se171407 |url=http://pubs.rsna.org/doi/10.1148/radiographics.20.5.g00se171407?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed}}</ref>
*Findings associated with osteochondroma, include:<ref name= "radio"> Osteochondroma. Dr Yuranga Weerakkody. Radiopedia. http://radiopaedia.org/articles/osteochondroma Accessed on January 28, 2016</ref>
:*Sessile or pedunculated bony growth
:*Metaphyseal region location
:*Bone growth projecting away from the epiphysis
:*Widening of the metaphysis

==References==
{{reflist|2}}

[[Category:Disease]]
[[Category:Oncology]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Orthopedics]]

Osteochondroma physical examination

2019-06-01T18:58:43Z

Ahmed Younes: /* Gallery */

__NOTOC__
{{Osteochondroma}}
{{CMG}}{{AE}}{{MV}}

==Overview==
Physical examination findings of osteochondroma will depend on the location of the tumor. Physical examination of patients with osteochondroma is usually remarkable for [[bone]] deformity, limited range of limb [[motion]], [[loss of pulse]], and color change.<ref name="pmid18853760">{{cite journal |vauthors=Kitsoulis P, Galani V, Stefanaki K, Paraskevas G, Karatzias G, Agnantis NJ, Bai M |title=Osteochondromas: review of the clinical, radiological and pathological features |journal=In Vivo (Athens, Greece) |volume=22 |issue=5 |pages=633–46 |year=2008 |pmid=18853760 |doi= |url=http://iv.iiarjournals.org/cgi/pmidlookup?view=long&pmid=18853760}}</ref>

==Physical Examination==

The following physical examination findings may be present among patients with osteochondroma:<ref name="pmid18853760">{{cite journal |vauthors=Kitsoulis P, Galani V, Stefanaki K, Paraskevas G, Karatzias G, Agnantis NJ, Bai M |title=Osteochondromas: review of the clinical, radiological and pathological features |journal=In Vivo (Athens, Greece) |volume=22 |issue=5 |pages=633–46 |year=2008 |pmid=18853760 |doi= |url=http://iv.iiarjournals.org/cgi/pmidlookup?view=long&pmid=18853760}}</ref>

===Appearance===
*Patients are usually well-appearing

===Vital Signs===
*Weak [[pulse]] in affected extremity
*[[Hypothermia]] may be present

===Skin===
*[[Pallor]] of affected extremity may be present

===Extremities===
*A hard, immobile, and painless palpable [[mass]] may be appreciated on physical examination.
*[[Muscle atrophy]] and palpable [[tenderness]] may be present.
*The assessment of osteochondroma during physical examination, should include:<ref name=“wikibook">Diagnostic Radiology: Musculoskeletal Imaging: Osteochondroma. WikiBooks.(2015)https://en.wikibooks.org/wiki/Diagnostic_Radiology/Musculoskeletal_Imaging/Tumors_Basic/Osteochondroma Accessed on January 28, 2016 </ref>
:*Location
:*[[Edema]]
:*Increased [[sweating]]
:*Increased [[skin]] [[temperature]]

===Neuromuscular===

*Unilateral upper/lower extremity [[weakness]]

==References==
{{reflist|2}}

{{WS}}
{{WH}}

[[Category:Disease]]
[[Category:Oncology]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Orthopedics]]

Chondrosarcoma pathophysiology

2019-06-01T18:47:07Z

Ahmed Younes: /* Mesenchymal chondrosarcoma */

__NOTOC__
{{Chondrosarcoma}}

{{CMG}}; {{AE}} {{Rohan}}

==Overview==
The exact [[pathogenesis]] of chondrosarcoama is not fully understood. Multiple genes have been implicated in [[pathogenesis]] of chondrosarcoma. [[Cytogenetics|Cytogenetic]] analysis of chondrosarcomas revealed that structural abnormalities of [[Chromosome 1|chromosomes 1]], [[Chromosome 6|6]], [[Chromosome 9|9]], [[Chromosome 12|12]] and [[Chromosome 15|15]] and numerical abnormalities of chromosomes [[Chromosome 5|5]], [[Chromosome 7|7]], [[Chromosome 8|8]] and [[Chromosome 18|18]] are most frequent associated. Anomalies associated with [[chromosome 9]](9p12-22) are more commonly seen in central chondrosarcomas. [[Germline]] mutations in the exostosin (EXT1 or EXT2) genes, [[TP53]] or [[Retinoblastoma protein|pRb]] pathway, [[isocitrate dehydrogenase]]-1 and [[Isocitrate dehydrogenase|isocitrate dehydrogenase-]] 2 genes and gene encoding the receptor for [[Parathyroid gland|parathyroid]] have been implicated. On [[gross pathology]], greyish-white lobulated mass, [[necrosis]], [[calcification]], and mucoid degeneration are characteristic findings of chondrosarcoma. On microscopic [[Histopathology|histopathological]] analysis abnormal [[cartilage]], increased cellularity, and [[nuclear]] [[atypia]] are characteristic findings of chondrosarcoma. Chondrosarcoma may be divided into three grades based on cancer cells [[morphology]] under [[microscope]] and growth rate of [[tumor]].

==Pathophysiology==
===Physiology===
*[[Cartilaginous]] [[Tumor|tumors]] are seen in bones that arise from enchondral [[ossification]].<ref name="pmid20535132">{{cite journal| author=Bovée JV, Hogendoorn PC, Wunder JS, Alman BA| title=Cartilage tumours and bone development: molecular pathology and possible therapeutic targets. | journal=Nat Rev Cancer | year= 2010 | volume= 10 | issue= 7 | pages= 481-8 | pmid=20535132 | doi=10.1038/nrc2869 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20535132 }} </ref>
*There is [[hypertrophy]] of the resting zone of [[chondrocytes]] due to [[proliferation]] and [[differentiation]] within the normal growth plate.<ref name="pmid20535132">{{cite journal| author=Bovée JV, Hogendoorn PC, Wunder JS, Alman BA| title=Cartilage tumours and bone development: molecular pathology and possible therapeutic targets. | journal=Nat Rev Cancer | year= 2010 | volume= 10 | issue= 7 | pages= 481-8 | pmid=20535132 | doi=10.1038/nrc2869 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20535132 }} </ref>
*These cells the undergo [[apoptosis]] resulting in invasion of [[vessels]] and [[Osteoblast|osteoblasts]] that start to form [[bone]] and lead to longitudinal [[bone]] growth.
*This [[Physiology|physiologic]] process is regulated by components of the Indian [[Hedgehog signaling pathway|hedgehog]] (IHH)/[[parathyroid hormone]] related (PTHRP) protein signaling pathway.

===Pathogenesis===
*The exact [[pathogenesis]] of chondrosarcoma is not full understood.<ref>{{cite book | last = Peabody | first = Terrance | title = Orthopaedic oncology : primary and metastatic tumors of the skeletal system | publisher = Springer | location = Cham | year = 2014 | isbn = 9783319073224 }}</ref>
*Multiple [[Gene|genes]] have been implicated in [[pathogenesis]] of chondrosarcoma.

===Genetics===
*[[Cytogenetics|Cytogenetic]] analysis of chondrosarcomas revealed that structural abnormalities of [[Chromosome 1|chromosomes 1]], [[Chromosome 6|6]], [[Chromosome 9|9]], [[Chromosome 12|12]] and [[Chromosome 15|15]].<ref name="pmid10502322">{{cite journal| author=Bovée JV, Cleton-Jansen AM, Kuipers-Dijkshoorn NJ, van den Broek LJ, Taminiau AH, Cornelisse CJ et al.| title=Loss of heterozygosity and DNA ploidy point to a diverging genetic mechanism in the origin of peripheral and central chondrosarcoma. | journal=Genes Chromosomes Cancer | year= 1999 | volume= 26 | issue= 3 | pages= 237-46 | pmid=10502322 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10502322 }} </ref>
*Also, numerical abnormalities of chromosomes [[Chromosome 5|5]], [[Chromosome 7|7]], [[Chromosome 8|8]] and [[Chromosome 18|18]] were most frequent associated with chondrosarcoma.<ref name="pmid10629543">{{cite journal| author=Bovée JV, Cleton-Jansen AM, Rosenberg C, Taminiau AH, Cornelisse CJ, Hogendoorn PC| title=Molecular genetic characterization of both components of a dedifferentiated chondrosarcoma, with implications for its histogenesis. | journal=J Pathol | year= 1999 | volume= 189 | issue= 4 | pages= 454-62 | pmid=10629543 | doi=10.1002/(SICI)1096-9896(199912)189:4<454::AID-PATH467>3.0.CO;2-N | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10629543 }} </ref>
*Anomalies associated with [[chromosome 9]](9p12-22) are more commonly seen in central chondrosarcomas.<ref name="pmid11763313">{{cite journal| author=Bovée JV, Sciot R, Dal Cin P, Debiec-Rychter M, van Zelderen-Bhola SL, Cornelisse CJ et al.| title=Chromosome 9 alterations and trisomy 22 in central chondrosarcoma: a cytogenetic and DNA flow cytometric analysis of chondrosarcoma subtypes. | journal=Diagn Mol Pathol | year= 2001 | volume= 10 | issue= 4 | pages= 228-35 | pmid=11763313 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11763313 }} </ref>
*Patients with multiple [[osteochondromas]] seem to have [[germline]] mutations in the exostosin (EXT1 or EXT2) genes.<ref name="pmid21804604">{{cite journal| author=de Andrea CE, Reijnders CM, Kroon HM, de Jong D, Hogendoorn PC, Szuhai K et al.| title=Secondary peripheral chondrosarcoma evolving from osteochondroma as a result of outgrowth of cells with functional EXT. | journal=Oncogene | year= 2012 | volume= 31 | issue= 9 | pages= 1095-104 | pmid=21804604 | doi=10.1038/onc.2011.311 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21804604 }} </ref>
*This result is decreased [[EXT1 gene|EXT]] expression and decreased biosynthesis and release of [[heparan sulfate]] [[proteoglycans]] (HSPGs), which are essential for cell signaling through [[IHH]]/PTHLH pathways.<ref name="pmid17341731">{{cite journal| author=Hameetman L, Szuhai K, Yavas A, Knijnenburg J, van Duin M, van Dekken H et al.| title=The role of EXT1 in nonhereditary osteochondroma: identification of homozygous deletions. | journal=J Natl Cancer Inst | year= 2007 | volume= 99 | issue= 5 | pages= 396-406 | pmid=17341731 | doi=10.1093/jnci/djk067 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17341731 }} </ref><ref name="pmid9620772">{{cite journal| author=McCormick C, Leduc Y, Martindale D, Mattison K, Esford LE, Dyer AP et al.| title=The putative tumour suppressor EXT1 alters the expression of cell-surface heparan sulfate. | journal=Nat Genet | year= 1998 | volume= 19 | issue= 2 | pages= 158-61 | pmid=9620772 | doi=10.1038/514 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9620772 }} </ref><ref name="pmid17226760">{{cite journal| author=Hameetman L, David G, Yavas A, White SJ, Taminiau AH, Cleton-Jansen AM et al.| title=Decreased EXT expression and intracellular accumulation of heparan sulphate proteoglycan in osteochondromas and peripheral chondrosarcomas. | journal=J Pathol | year= 2007 | volume= 211 | issue= 4 | pages= 399-409 | pmid=17226760 | doi=10.1002/path.2127 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17226760 }} </ref>
*This in turn decreases normal [[chondrocyte]] proliferation and differentiation within the normal human [[growth plate]].
*Furthermore, the [[Genetics|genetic]] [[Mutation|mutations]] in the [[TP53]] or [[Retinoblastoma protein|pRb]] pathway are implied in the [[malignant]] transformation from [[osteochondroma]] to [[secondary]] peripheral chondrosarcoma.
*In [[Enchondroma|enchondromas]] and central chondrosarcomas, point [[Mutation|mutations]] in [[isocitrate dehydrogenase]]-1 and [[isocitrate dehydrogenase]] - 2 genes ([[IDH1]] and [[IDH2]]) have been suggested.
*In addition, the [[Ollier disease]] and [[Maffucci syndrome]] are also result of [[somatic]] [[Mosaic (genetics)|mosaic]] [[Mutation|mutations]] in [[IDH1]] and [[IDH2]]. <ref name="pmid22057234">{{cite journal| author=Pansuriya TC, van Eijk R, d'Adamo P, van Ruler MA, Kuijjer ML, Oosting J et al.| title=Somatic mosaic IDH1 and IDH2 mutations are associated with enchondroma and spindle cell hemangioma in Ollier disease and Maffucci syndrome. | journal=Nat Genet | year= 2011 | volume= 43 | issue= 12 | pages= 1256-61 | pmid=22057234 | doi=10.1038/ng.1004 | pmc=3427908 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22057234 }} </ref>
*[[Isocitrate dehydrogenase]] is the necessary [[enzyme]] required for conversion of [[isocitrate]] to [[Alpha-ketoglutaric acid|alpha-ketoglutarate]] in the [[tricarboxylic acid cycle]].
*Mutations in [[IDH1]] and [[IDH2]] cause elevated levels of the oncometabolite D-2-hydroxyglutarate (D-2-HG) which promotes [[chondrogenesis]] and inhibit [[Osteogenic Sarcoma|osteogenic]] differentiation of [[mesenchymal stem cells]] as well as causes DNA hypermethylation and [[histone]] modification, all resulting in decreased differentiation.<ref name="pmid21598255">{{cite journal| author=Amary MF, Bacsi K, Maggiani F, Damato S, Halai D, Berisha F et al.| title=IDH1 and IDH2 mutations are frequent events in central chondrosarcoma and central and periosteal chondromas but not in other mesenchymal tumours. | journal=J Pathol | year= 2011 | volume= 224 | issue= 3 | pages= 334-43 | pmid=21598255 | doi=10.1002/path.2913 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21598255 }} </ref>
*A [[missense mutation]] (R150C) in the [[gene]] encoding the receptor for PTHRP ([[PTH|PTH-1]] receptor or PTH1R) has been associated to [[Enchondroma|enchondromatosis]] in patients with [[Ollier disease]], and decreased receptor function.<ref name="pmid11140704">{{cite journal| author=Bovée JV, van den Broek LJ, Cleton-Jansen AM, Hogendoorn PC| title=Up-regulation of PTHrP and Bcl-2 expression characterizes the progression of osteochondroma towards peripheral chondrosarcoma and is a late event in central chondrosarcoma. | journal=Lab Invest | year= 2000 | volume= 80 | issue= 12 | pages= 1925-34 | pmid=11140704 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11140704 }} </ref><ref name="pmid15685701">{{cite journal| author=Rozeman LB, Hameetman L, Cleton-Jansen AM, Taminiau AH, Hogendoorn PC, Bovée JV| title=Absence of IHH and retention of PTHrP signalling in enchondromas and central chondrosarcomas. | journal=J Pathol | year= 2005 | volume= 205 | issue= 4 | pages= 476-82 | pmid=15685701 | doi=10.1002/path.1723 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15685701 }} </ref><ref name="pmid11850620">{{cite journal| author=Hopyan S, Gokgoz N, Poon R, Gensure RC, Yu C, Cole WG et al.| title=A mutant PTH/PTHrP type I receptor in enchondromatosis. | journal=Nat Genet | year= 2002 | volume= 30 | issue= 3 | pages= 306-10 | pmid=11850620 | doi=10.1038/ng844 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11850620 }} </ref>
*Low-grade chondrosarcomas are near-[[diploid]] and have very few karyotypic abnormalities.<ref name="pmid11793371">{{cite journal| author=Tallini G, Dorfman H, Brys P, Dal Cin P, De Wever I, Fletcher CD et al.| title=Correlation between clinicopathological features and karyotype in 100 cartilaginous and chordoid tumours. A report from the Chromosomes and Morphology (CHAMP) Collaborative Study Group. | journal=J Pathol | year= 2002 | volume= 196 | issue= 2 | pages= 194-203 | pmid=11793371 | doi=10.1002/path.1023 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11793371 }} </ref>
*On the other hand, high grade chondrosarcomas are [[aneuploid]] and have complex [[Karyotype|karyotypes]].<ref name="pmid11793371">{{cite journal| author=Tallini G, Dorfman H, Brys P, Dal Cin P, De Wever I, Fletcher CD et al.| title=Correlation between clinicopathological features and karyotype in 100 cartilaginous and chordoid tumours. A report from the Chromosomes and Morphology (CHAMP) Collaborative Study Group. | journal=J Pathol | year= 2002 | volume= 196 | issue= 2 | pages= 194-203 | pmid=11793371 | doi=10.1002/path.1023 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11793371 }} </ref>
*The progression of chondrosarcoma has been linked to the [[CDKN2A]] (p16) [[tumor suppressor gene]] present at 9p21 and by [[mutation]] in [[p53]].<ref name="pmid14991902">{{cite journal| author=van Beerendonk HM, Rozeman LB, Taminiau AH, Sciot R, Bovée JV, Cleton-Jansen AM et al.| title=Molecular analysis of the INK4A/INK4A-ARF gene locus in conventional (central) chondrosarcomas and enchondromas: indication of an important gene for tumour progression. | journal=J Pathol | year= 2004 | volume= 202 | issue= 3 | pages= 359-66 | pmid=14991902 | doi=10.1002/path.1517 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14991902 }} </ref><ref name="pmid12271817">{{cite journal| author=Rozeman LB, Hogendoorn PC, Bovée JV| title=Diagnosis and prognosis of chondrosarcoma of bone. | journal=Expert Rev Mol Diagn | year= 2002 | volume= 2 | issue= 5 | pages= 461-72 | pmid=12271817 | doi=10.1586/14737159.2.5.461 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12271817 }} </ref>
*[[Mutation|Mutations]] in [[COL2A1]] have also been hypothesized in [[pathogenesis]] of chondrosarcomas.<ref name="pmid23770606">{{cite journal| author=Tarpey PS, Behjati S, Cooke SL, Van Loo P, Wedge DC, Pillay N et al.| title=Frequent mutation of the major cartilage collagen gene COL2A1 in chondrosarcoma. | journal=Nat Genet | year= 2013 | volume= 45 | issue= 8 | pages= 923-6 | pmid=23770606 | doi=10.1038/ng.2668 | pmc=3743157 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23770606 }} </ref>
*In addition, amplification of the [[c-myc]] and fos/[[Jun dimerization protein|jun]] protien has also been implicated in the [[pathogenesis]] of chondrosarcoma.<ref name="pmid1342971">{{cite journal| author=Castresana JS, Barrios C, Gómez L, Kreicbergs A| title=Amplification of the c-myc proto-oncogene in human chondrosarcoma. | journal=Diagn Mol Pathol | year= 1992 | volume= 1 | issue= 4 | pages= 235-8 | pmid=1342971 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1342971 }} </ref><ref name="pmid9672192">{{cite journal| author=Franchi A, Calzolari A, Zampi G| title=Immunohistochemical detection of c-fos and c-jun expression in osseous and cartilaginous tumours of the skeleton. | journal=Virchows Arch | year= 1998 | volume= 432 | issue= 6 | pages= 515-9 | pmid=9672192 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9672192 }} </ref>
*A specific HEY1-NCOA2 fusion product due to an intra-chromosomal rearrangement of chromosome arm [[Chromosome 8|8]]<nowiki/>q result in [[mesenchymal]] chondrosarcoma.
*With extraskeletal myxoid chondrosarcomas, the t(9;22)(q22;q12) [[Translocations|translocation]] is common.<ref name="pmid12378528">{{cite journal| author=Panagopoulos I, Mertens F, Isaksson M, Domanski HA, Brosjö O, Heim S et al.| title=Molecular genetic characterization of the EWS/CHN and RBP56/CHN fusion genes in extraskeletal myxoid chondrosarcoma. | journal=Genes Chromosomes Cancer | year= 2002 | volume= 35 | issue= 4 | pages= 340-52 | pmid=12378528 | doi=10.1002/gcc.10127 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12378528 }} </ref>
===Gross Pathology===
Characteristic features of chondrosarcoma on gross pathology are:<ref name="pmid8478391">{{cite journal| author=Simon MA, Biermann JS| title=Biopsy of bone and soft-tissue lesions. | journal=J Bone Joint Surg Am | year= 1993 | volume= 75 | issue= 4 | pages= 616-21 | pmid=8478391 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8478391 }} </ref><ref name="pmid26883651">{{cite journal| author=Roitman PD, Farfalli GL, Ayerza MA, Múscolo DL, Milano FE, Aponte-Tinao LA| title=Is Needle Biopsy Clinically Useful in Preoperative Grading of Central Chondrosarcoma of the Pelvis and Long Bones? | journal=Clin Orthop Relat Res | year= 2017 | volume= 475 | issue= 3 | pages= 808-814 | pmid=26883651 | doi=10.1007/s11999-016-4738-y | pmc=5289157 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26883651 }} </ref>
*Greyish-white lobulated mass
*[[Necrosis]]
*[[Calcification]]
*Mucoid degeneration

===Microscopic Pathology===
In general chondrosarcomas are multi-lobulated (due to [[hyaline cartilage]] [[Nodule (medicine)|nodules]]) with central high water content and peripheral enchondral [[ossification]]. Characteristic features on microscopic analysis are variable depending on the chondrosarcoma subtype:

====Clear cell chondrosarcoma====
*[[Lobules]] of uniform to [[polymorphic]] densely-packed large cells.<ref>McCarthy EF, Hogendoorn PCW. Clear cell chondrosarcoma. In: World Health Organization classification of tumours of soft tissue and bone, 4th, Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F (Eds), IARC, Lyon 2013. p.273.</ref><ref name="pmid17522879">{{cite journal| author=Donati D, Yin JQ, Colangeli M, Colangeli S, Bella CD, Bacchini P et al.| title=Clear cell chondrosarcoma of bone: long time follow-up of 18 cases. | journal=Arch Orthop Trauma Surg | year= 2008 | volume= 128 | issue= 2 | pages= 137-42 | pmid=17522879 | doi=10.1007/s00402-007-0353-4 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17522879 }} </ref><ref name="pmid16239809">{{cite journal| author=Itälä A, Leerapun T, Inwards C, Collins M, Scully SP| title=An institutional review of clear cell chondrosarcoma. | journal=Clin Orthop Relat Res | year= 2005 | volume= 440 | issue= | pages= 209-12 | pmid=16239809 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16239809 }} </ref>
*Well defined pushing borders.
*Clear to intensively [[acidophilic]] granular [[cytoplasm]] with [[Vacuole|vacuoles]].
*Central [[nuclei]] with occasional prominent [[nucleoli]].
*Low mitotic rate.
*Clear cell areas lack production of [[hyaline]] chondroid matrix.
*Areas with [[osteoclast]]-type [[giant cells]] mixed with small [[Trabecula|trabeculae]] of reactive bone.
*May contain conventional low-grade chondrosarcoma.
*May have secondary [[aneurysmal bone cyst]] changes.
{| align=""
|- valign="top"
| [[Image:800px-Bone Chondrosarcoma ClearCell HP PA.jpg|thumb|350px|High grade round cells with cytoplasmic clearing. Source Wikimedia common.]]
| [[Image:800px-Bone Chondrosarcoma ClearCell MP PA.jpg|thumb|350px|The lesion also had areas of more conventional chondrosarcoma. Source Wikimedia common.]]
|}

====Mesenchymal chondrosarcoma====
Mesenchymal chondrosarcoma is a [[malignant tumor]] with a characteristic biphasic pattern:<ref>Nakashima Y, de Pinieux G, Ladanyi M. Mesenchymal chondrosarcoma. In: WHO classification of tumours of soft tissue and bone, 4th, Fletcher CDM, Bridge JA, Hogendoorn CDW, Mertens F (Eds), IARC, Lyon 2013. p.271.</ref><ref name="pmid25529371">{{cite journal| author=Frezza AM, Cesari M, Baumhoer D, Biau D, Bielack S, Campanacci DA et al.| title=Mesenchymal chondrosarcoma: prognostic factors and outcome in 113 patients. A European Musculoskeletal Oncology Society study. | journal=Eur J Cancer | year= 2015 | volume= 51 | issue= 3 | pages= 374-81 | pmid=25529371 | doi=10.1016/j.ejca.2014.11.007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25529371 }} </ref><ref name="pmid18438777">{{cite journal| author=Dantonello TM, Int-Veen C, Leuschner I, Schuck A, Furtwaengler R, Claviez A et al.| title=Mesenchymal chondrosarcoma of soft tissues and bone in children, adolescents, and young adults: experiences of the CWS and COSS study groups. | journal=Cancer | year= 2008 | volume= 112 | issue= 11 | pages= 2424-31 | pmid=18438777 | doi=10.1002/cncr.23457 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18438777 }} </ref>
*Poorly differentiated small round blue cells
*Islands of well-differentiated [[hyaline cartilage]]
**Progressive [[maturation]] of [[cartilage]] towards the center
**Central [[calcification]] or bone formation
*Can have a hemangiopericytomatous vascular pattern.

====Myxoid chondrosarcoma====
*It shows [[myxoid]] background.<ref name="pmid9781944">{{cite journal| author=Antonescu CR, Argani P, Erlandson RA, Healey JH, Ladanyi M, Huvos AG| title=Skeletal and extraskeletal myxoid chondrosarcoma: a comparative clinicopathologic, ultrastructural, and molecular study. | journal=Cancer | year= 1998 | volume= 83 | issue= 8 | pages= 1504-21 | pmid=9781944 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9781944 }} </ref>
*In addition, small cells with eosinophilic [[cytoplasm]] are seen.<ref name="pmid14657948">{{cite journal| author=Aigner T, Oliveira AM, Nascimento AG| title=Extraskeletal myxoid chondrosarcomas do not show a chondrocytic phenotype. | journal=Mod Pathol | year= 2004 | volume= 17 | issue= 2 | pages= 214-21 | pmid=14657948 | doi=10.1038/modpathol.3800036 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14657948 }} </ref>
{| align=""
|- valign="top"
| [[Image:790px-Bone Chondrosarcoma Myxoid MP2 PA.JPG|thumb|350px|Anastomizing chords of small neoplastic cells surround mucin pools. Source Wikimedia common.]]
| [[Image:800px-Bone Chondrosarcoma Myxoid MP PA.JPG|thumb|350px|Chords of neoplastic cells surround mucin pools. Source Wikimedia common.]]
|}

====Dedifferentiated chondrosarcoma====
*Poorly differentiated [[mesenchymal]] [[malignancy]].<ref>Inwards C, Hogendoorn PCW. Dedifferentiated chondrosarcoma In: WHO classification of tumours of soft tissue and bone, 4th, Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F (Eds), IARC, Lyon 2013. p.269.</ref>
*Well-differentiated [[cartilaginous]] component

==Histological Grading==
*Chondrosarcomas can be classified into the following three [[Histologic|histologic grades]], depending on findings of cellularity, [[atypia]], and [[pleomorphism]]:<ref name="pmid17260660">{{cite journal| author=Ryzewicz M, Manaster BJ, Naar E, Lindeque B| title=Low-grade cartilage tumors: diagnosis and treatment. | journal=Orthopedics | year= 2007 | volume= 30 | issue= 1 | pages= 35-46; quiz 47-8 | pmid=17260660 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17260660 }} </ref><ref name="pmid4064409">{{cite journal| author=Mirra JM, Gold R, Downs J, Eckardt JJ| title=A new histologic approach to the differentiation of enchondroma and chondrosarcoma of the bones. A clinicopathologic analysis of 51 cases. | journal=Clin Orthop Relat Res | year= 1985 | volume= | issue= 201 | pages= 214-37 | pmid=4064409 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4064409 }} </ref>

'''Grade 1'''
*Chondrosarcoma grows relatively slowly, has cells whose [[histological]] appearance is quite similar to cells of normal [[cartilage]].
*Mostly chondroid [[matrix]], little if any myxoid.
*Mild-to-moderate increase of cellularity +/- binucleated cells.
*Have much less aggressive [[invasive]] and [[metastatic]] properties.
{| align=""
|- valign="top"
| [[Image:800px-Bone Chondrosarcoma Grade1 HP2 PA.JPG|thumb|350px|Grade 1 - Somewhat cellular cartilage with binucleation. Source Wikimedia common.]]
|}

'''Grade 2'''
*Intermediate grade chondrosarcoma
*Little chondroid [[matrix]], [[necrosis]] and more common prominent myxoid.
{| align=""
|- valign="top"
| [[Image:800px-Bone Chondrosarcoma Grade2 HP PA.jpg|thumb|350px|Grade 2 - Very cellular cartilage with obvious hyperchromasia and nuclear atypia. Source Wikimedia common.]]
|}

'''Grade 3'''
*Grade 3 chondrosarcoma is increasingly faster-growing cancer, with more varied and abnormal-looking cells.
*Characterized by myxoid [[stroma]], [[nuclear]] [[pleomorphism]] and [[mitoses]].
*Absent chondroid [[matrix]].
*These are much more likely to infiltrate surrounding tissues, [[lymph nodes]], and [[organs]].
{| align=""
|- valign="top"
| [[Image:800px-Bone Chondrosarcoma Grade3 HP PA.JPG|thumb|350px|Grade 3 - Even more cellular neoplastic cartilage with high grade nuclear atypia. Source Wikimedia common.]]
|}

==References==
{{Reflist|2}}

[[Category: Orthopedics]]
[[Category: Oncology]]
[[Category: Up-To-Date]]

Chondrosarcoma overview

2019-06-01T18:45:59Z

Ahmed Younes: /* Historical Perspective */

{{Chondrosarcoma}}
{{CMG}};{{AE}} {{Rohan}}

==Overview==
Chondrosarcoma is the second most common [[malignant]] primary [[tumor]] of [[bone]]. it is most frequently diagnosed in patients in their 4th and 5th decades of life.Men are slightly more affected with chondrosarcoma than women. There is no racial predilection to chondrosarcoma. Jaffe and Lichtenstein first described chondrosarcoma in 1948. Chondrosarcoma may be classified based on histological findings and location. The exact [[pathogenesis]] of chondrosarcoama is not fully understood. Multiple genes have been implicated in [[pathogenesis]] of chondrosarcoma. [[Cytogenetics|Cytogenetic]] analysis of chondrosarcomas revealed that structural abnormalities of [[Chromosome 1|chromosomes 1]], [[Chromosome 6|6]], [[Chromosome 9|9]], [[Chromosome 12|12]] and [[Chromosome 15|15]] and numerical abnormalities of chromosomes [[Chromosome 5|5]], [[Chromosome 7|7]], [[Chromosome 8|8]] and [[Chromosome 18|18]] are most frequent associated. Anomalies associated with [[chromosome 9]](9p12-22) are more commonly seen in central chondrosarcomas. Germline mutations in the exostosin (EXT1 or EXT2) genes, [[TP53]] or [[Retinoblastoma protein|pRb]] pathway, [[Isocitrate dehydrogenase|isocitrate dehydrogenase-1]] and [[Isocitrate dehydrogenase|isocitrate dehydrogenase 2]] genes and gene encoding the receptor for [[Parathyroid gland|parathyroid]] have been implicated. On gross [[pathology]], greyish-white lobulated mass, [[necrosis]], [[calcification]], and mucoid degeneration are characteristic findings of chondrosarcoma. On microscopic [[histopathological]] analysis abnormal [[cartilage]], increased cellularity, and nuclear atypia are characteristic findings of chondrosarcoma. Chondrosarcoma may be divided into three grades based on cancer cells morphology under microscope and growth rate of tumor. There are no established causes for chondrosarcoma. Common risk factors in the development of chondrosarcoma are benign cartilage tumors such as [[Enchondroma|enchondromas]], [[osteochondromas]], multiple exostoses, [[Enchondroma|Ollier's disease]], and [[Maffucci syndrome|Maffucci's syndrome]]. Chondrosarcoma must be differentiated from other diseases such as [[chondroma]], [[enchondroma]], [[osteochondroma]], and [[osteosarcoma]]. Complications that can develop as a result of chondrosarcoma are [[metastasis]] and recurrence. The prognosis of chondrosarcoma correlates with the grade and stage of the lesion at the time of diagnosis. Chondrosarcoma is associated with a 5 year survival rate of 70%. The presence of grade 3 lesions are associated with a particularly poor prognosis. [[Biopsy]] is the gold standard test for the diagnosis of chondrosarcoma. Open [[biopsy]] is carried out for chondrosarcoma. The tumor is then staged based on Enneking system for chondrosarcoma. The most common symptoms of chondrosarcoma include [[pain]] and [[swelling]] in the area of [[tumor]]. Patients with chondrosarcoma usually appear [[lethargic]] and emaciated. Physical examination of patients with chondrosarcoma is usually remarkable for palpable mass, [[tenderness]] and decreased [[range of motion]]. On [[x-ray]], chondrosarcoma is characterized by [[lytic]] lesion, intralesional [[calcification]], endosteal scalloping, and cortical remodeling. On [[Computed tomography|CT scan]] chondrosarcoma is characterized by matrix [[calcification]], endosteal [[calcification]], cortical breach, and heterogenous contrast enhancement. On [[MRI]], chondrosarcoma is characterized by low to intermediate signal on T1, very high intensity in [[Calcification|calcified]] portions on T2, and moderate to intense contrast enhancement on T1 contrast. [[Bone scan]] shows very hot uptake in all grades of chondrosarcoma. [[Chemotherapy]] and [[Radiation therapy|radiotherapy]] are indicated for chondrosarcoma as [[Adjuvant therapy|adjuvant therap]]<nowiki/>y or [[palliative treatment]] in surgically inaccessible areas. [[Surgery]] is the mainstay of treatment for chondrosarcoma. [[Chemotherapy|Adjunctive chemotherapy]] and [[Radiation therapy|radiation]] may be required. Recurrence rate depends on the grade of chondrosarcoma.

==Historical Perspective==
*In 1948, Jaffe and Lichtenstein described chondrosarcoma for the first time.

==Classification==
Chondrosarcoma may be classified based on histological findings and location.

==Pathophysiology==
The exact [[pathogenesis]] of chondrosarcoama is not fully understood. Multiple genes have been implicated in [[pathogenesis]] of chondrosarcoma. [[Cytogenetics|Cytogenetic]] analysis of chondrosarcomas revealed that structural abnormalities of [[Chromosome 1|chromosomes 1]], [[Chromosome 6|6]], [[Chromosome 9|9]], [[Chromosome 12|12]] and [[Chromosome 15|15]] and numerical abnormalities of chromosomes [[Chromosome 5|5]], [[Chromosome 7|7]], [[Chromosome 8|8]] and [[Chromosome 18|18]] are most frequent associated. Anomalies associated with [[chromosome 9]](9p12-22) are more commonly seen in central chondrosarcomas. [[Germline]] mutations in the exostosin (EXT1 or EXT2) genes, [[TP53]] or [[Retinoblastoma protein|pRb]] pathway, [[isocitrate dehydrogenase]]-1 and [[Isocitrate dehydrogenase|isocitrate dehydrogenase-]] 2 genes and gene encoding the receptor for [[Parathyroid gland|parathyroid]] have been implicated. On [[gross pathology]], greyish-white lobulated mass, [[necrosis]], [[calcification]], and mucoid degeneration are characteristic findings of chondrosarcoma. On microscopic [[Histopathology|histopathological]] analysis abnormal [[cartilage]], increased cellularity, and [[nuclear]] [[atypia]] are characteristic findings of chondrosarcoma. Chondrosarcoma may be divided into three grades based on cancer cells [[morphology]] under [[microscope]] and growth rate of [[tumor]].

==Causes==
The cause of chondrosarcoma has not been identified.

==Differentiating chondrosarcoma from other Diseases==
Chondrosarcoma must be differentiated from other diseases such as [[chondroma]], [[enchondroma]], [[osteochondroma]], and [[osteosarcoma]].

==Epidemiology and Demographics==
Chondrosarcoma is the second most common [[malignant]] primary [[tumor]] of [[bone]]. It is most frequently diagnosed in patients in their 4th and 5th decades of life. Men are slightly more affected by chondrosarcoma than women. There is no racial predilection to chondrosarcoma.

==Risk Factors==
Common risk factors in the development of chondrosarcoma are benign [[cartilage]] tumors such as [[enchondromas]], [[osteochondromas]], multiple [[exostoses]], [[Ollier's disease]], and [[Maffucci's syndrome]].

==Natural History, Complications, and Prognosis==
Complications that can develop as a result of chondrosarcoma are [[metastasis]] and recurrence. The [[prognosis]] of chondrosarcoma correlates with the grade and stage of the lesion at the time of [[diagnosis]]. Chondrosarcoma is associated with a 5 year survival rate of 70%. The presence of grade 3 lesions are associated with a particularly poor [[prognosis]].

== Diagnostic Study of Choice ==
[[Biopsy]] is the gold standard test for the diagnosis of chondrosarcoma. Open [[biopsy]] is carried out for chondrosarcoma. The [[tumor]] is then staged based on Enneking system for chondrosarcoma.

==History and Symptoms==
The most common symptoms of chondrosarcoma include [[pain]] and [[swelling]] in the area of [[tumor]].

==Physical Examination==
Patients with chondrosarcoma usually appear [[Fatigue|lethargic]] and emaciated. Physical examination of patients with chondrosarcoma is usually remarkable for palpable [[mass]], [[tenderness]] and decreased [[range of motion]].

==Laboratory findings==
There are no specific laboratory tests for the diagnosis of chondrosarcoma.

==Electrocardiogram==
There are no ECG findings associated with chondrosarcoma.

==X Ray==
On x-ray, chondrosarcoma is characterized by [[lytic]] lesion, intralesional [[calcification]], endosteal scalloping, and [[Cortical bone|cortical]] remodeling.

==Echocardiography/Ultrasound==
There are no echocardiography/ultrasound findings associated with Chondrosarcoma.

==CT==
On CT scan chondrosarcoma is characterized by [[Calcification|matrix calcification]], endosteal [[calcification]], [[Cortical bone|cortical]] breach, and heterogenous contrast enhancement.

==MRI==
On MRI, chondrosarcoma is characterized by low to intermediate signal on T1, very high intensity in [[Calcification|calcified]] portions on T2, and moderate to intense contrast enhancement on T1 contrast.

==Other imaging findings==
Bone scan shows very hot uptake in all grades of chondrosarcoma.

==Other Diagnostic Studies==
There are no other diagnostic studies associated with chondrosarcoma.

==Medical Therapy==
[[Chemotherapy]] and [[radiotherapy]] are indicated for chondrosarcoma as [[adjuvant therapy]] or [[Palliative care|palliative]] treatment in surgically inaccessible areas. [[Surgery]] is the mainstay of treatment for chondrosarcoma.

==Surgery==
[[Surgery]] is the mainstay of treatment for chondrosarcoma. Adjunctive [[chemotherapy]] and [[radiation]] may be required. Recurrence rate depends on the grade of chondrosarcoma.

==Primary prevention==
There are no established measures for the primary prevention of chondrosarcoma.

==Secondary prevention==
There are no established measures for the secondary prevention of chondrosarcoma.

==References==
{{reflist|2}}

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Orthopedics]]

Chondroblastoma

2019-06-01T18:43:15Z

Ahmed Younes: /* Biopsy */

__NOTOC__
{{SI}}
'''For patient information click [[{{PAGENAME}} (patient information)|here]]'''

{{CMG}};{{AE}} {{Rohan}}

{{SK}} Codman tumor; Codman's tumor; Codman tumour; Codmans tumor; Chondroblastomas; Benign chondroblastoma; Epiphyseal chondroblastoma

==Overview==
Chondroblastoma is a [[benign]] [[Cartilage|cartilaginous]] [[tumor]] that account for 1% of all [[bone tumors]]. Chondroblastoma typically occurs in children and adolescents between 10 and 25 years of age. Male are more commonly affected with chondroblastoma than female. The male to female ratio is approximately 2:1. The [[epiphysis]] of the distal [[femur]], proximal [[tibia]], and proximal [[humerus]] are the most common sites. In 1928, Codman first described chondroblastoma as [[epiphyseal]] chondromatous [[Giant cell tumor|giant cell tumors]] of the proximal [[humerus]]. The exact pathogenesis of chondroblastoma is not fully understood. Various theories have been postulated such as chondroblastoma arising from [[osteoid]] matrix–containing [[type I collagen]] and there is absence of true [[cartilage]] matrix production ([[type II collagen]]). Recently, a specific mutation in the [[histone]] 3 gene [[H3F3B (gene)|H3F3B]] (K36M), was identified in approximately 95% of chondroblastoma. The hallmark of chondroblastoma is [[pain]], limping, [[tenderness]] and restricted [[range of motion]]. If left untreated, few patients with chondroblastoma may progress to develop [[lung]] [[metastasis]]. The mainstay of treatment for chondroblastoma is surgery in form of [[curettage]] and [[bone grafting]].

==Historical Perspective==
*In 1928, Codman first described chondroblastoma as [[epiphyseal]] chondromatous [[Giant cell tumor|giant cell tumors]] of the proximal [[humerus]].
*In 1942, Jaffe and Lichenstein later recognized it as a distinct entity due to its chondorid matrix.<ref name="FitzgeraldBroehm2014">{{cite journal|last1=Fitzgerald|first1=Judd|last2=Broehm|first2=Cory|last3=Chafey|first3=David|last4=Treme|first4=Gehron|title=Chondroblastoma of the Knee Treated with Resection and Osteochondral Allograft Reconstruction|journal=Case Reports in Orthopedics|volume=2014|year=2014|pages=1–7|issn=2090-6749|doi=10.1155/2014/543959}}</ref>

==Classification==
Chondroblastoma can be classified based on imaging findings.

===Enneking (MSTS) Staging System===
*The Enneking surgical staging system (also known as the MSTS system) for benign [[Musculoskeletal system|musculoskeletal]] [[Tumor|tumors]] is based on [[radiographic]] characteristics of the [[tumor]] host margin.<ref name="pmid20333492">{{cite journal| author=Jawad MU, Scully SP| title=In brief: classifications in brief: enneking classification: benign and malignant tumors of the musculoskeletal system. | journal=Clin Orthop Relat Res | year= 2010 | volume= 468 | issue= 7 | pages= 2000-2 | pmid=20333492 | doi=10.1007/s11999-010-1315-7 | pmc=2882012 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20333492 }} </ref>
*It is widely accepted and routinely used classification.

{| align="center" style="border: 0px; font-size: 90%; margin: 3px; width: 1000px"
|-
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Stages}}
! style="background: #4479BA; width: 300px;" | {{fontcolor|#FFF|Description}}
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |1
| style="padding: 5px 5px; background: #F5F5F5;" | Latent: Well demarcated borders
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |2
| style="padding: 5px 5px; background: #F5F5F5;" | Active: Indistinct borders
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |3
| style="padding: 5px 5px; background: #F5F5F5;" | Aggressive: Indistinct borders
|}

==Pathophysiology==
*The exact [[pathogenesis]] of chondroblaroma is not fully understood.<ref>{{cite book | last = Peabody | first = Terrance | title = Orthopaedic oncology : primary and metastatic tumors of the skeletal system | publisher = Springer | location = Cham | year = 2014 | isbn = 9783319073224 }}</ref>
*Various theories have been proposed concerning the [[pathogenesis]] of chondroblastomas:
**Chondroblastoma tumors are of chondrogenic origin.<ref name="pmid8001922">{{cite journal| author=Mii Y, Miyauchi Y, Morishita T, Miura S, Honoki K, Aoki M et al.| title=Ultrastructural cytochemical demonstration of proteoglycans and calcium in the extracellular matrix of chondroblastomas. | journal=Hum Pathol | year= 1994 | volume= 25 | issue= 12 | pages= 1290-4 | pmid=8001922 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8001922 }} </ref>
**Chondroblastoma arises from [[osteoid]] matrix–containing [[type I collagen]] and the absence of true [[cartilage]] matrix production ([[type II collagen]]).<ref name="pmid10629544">{{cite journal| author=Aigner T, Loos S, Inwards C, Perris R, Perissinotto D, Unni KK et al.| title=Chondroblastoma is an osteoid-forming, but not cartilage-forming neoplasm. | journal=J Pathol | year= 1999 | volume= 189 | issue= 4 | pages= 463-9 | pmid=10629544 | doi=10.1002/(SICI)1096-9896(199912)189:4<463::AID-PATH476>3.0.CO;2-N | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10629544 }} </ref>
**Chondroblastoma arises from an intraosseous proliferation of [[tendon sheath]] cells that have a predilection for chondroid formation.<ref name="pmid7610417">{{cite journal| author=Brien EW, Mirra JM, Ippolito V| title=Chondroblastoma arising from a nonepiphyseal site. | journal=Skeletal Radiol | year= 1995 | volume= 24 | issue= 3 | pages= 220-2 | pmid=7610417 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7610417 }} </ref>
*Chondroblastomas typically occur in the [[Epiphysis|epiphyses]] and [[apophysis]] of the [[Long bone|long bones]].
*The bones often involved by [[epiphyseal]] chondroblastomas are [[femur]], [[tibia]], and [[humerus]].<ref name="pmid27298978">{{cite journal| author=Punit A, Nadkarni S, Doomra T| title=Chondroblastoma of Diaphysis of Radius in a Seven Year Old Child. | journal=J Orthop Case Rep | year= 2014 | volume= 4 | issue= 3 | pages= 32-5 | pmid=27298978 | doi=10.13107/jocr.2250-0685.191 | pmc=4719322 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27298978 }} </ref>

===Genetics===
*Chondroblastoma may have association with genetic abnormalities on chromosome 5 and 8.
*Recently, a specific mutation in the [[histone]] 3 gene [[H3F3B (gene)|H3F3B]] (K36M), was identified in approximately 95% of chondroblastomas.<ref name="pmid26844533">{{cite journal| author=Amary MF, Berisha F, Mozela R, Gibbons R, Guttridge A, O'Donnell P et al.| title=The H3F3 K36M mutant antibody is a sensitive and specific marker for the diagnosis of chondroblastoma. | journal=Histopathology | year= 2016 | volume= 69 | issue= 1 | pages= 121-7 | pmid=26844533 | doi=10.1111/his.12945 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26844533 }} </ref><ref name="pmid24162739">{{cite journal| author=Behjati S, Tarpey PS, Presneau N, Scheipl S, Pillay N, Van Loo P et al.| title=Distinct H3F3A and H3F3B driver mutations define chondroblastoma and giant cell tumor of bone. | journal=Nat Genet | year= 2013 | volume= 45 | issue= 12 | pages= 1479-82 | pmid=24162739 | doi=10.1038/ng.2814 | pmc=3839851 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24162739 }} </ref>

==Causes==
There are no established causes for chondroblastoma.<ref>{{cite book | last = Peabody | first = Terrance | title = Orthopaedic oncology : primary and metastatic tumors of the skeletal system | publisher = Springer | location = Cham | year = 2014 | isbn = 9783319073224 }}</ref>

==Differentiating Chondroblastoma from Other Diseases==
*Chondroblastoma must be differentiated from following bone disorders:
{|
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Disease
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Epiphyseal lesion
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Benign lesion that may metastasize to lung
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Diagnosis
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Treatment is curretage and bone grafting
|-
! align="center" style="background:#DCDCDC;" + |Chondroblastoma
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |[[Radiology]] and [[biopsy]]
| align="center" style="background:#F5F5F5;" + | +
|-
! align="center" style="background:#DCDCDC;" + |[[Giant Cell Tumor]]
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |[[Radiology]] and [[biopsy]]
| align="center" style="background:#F5F5F5;" + | +
|-
! align="center" style="background:#DCDCDC;" + |[[Aneurysmal bone cyst]]
| align="center" style="background:#F5F5F5;" + | -
| align="center" style="background:#F5F5F5;" + | -
| align="center" style="background:#F5F5F5;" + |[[Radiology]] and [[biopsy]]
| align="center" style="background:#F5F5F5;" + | +
|-
! align="center" style="background:#DCDCDC;" + |[[Osteoblastoma]]
| align="center" style="background:#F5F5F5;" + | -
| align="center" style="background:#F5F5F5;" + | -
| align="center" style="background:#F5F5F5;" + |[[Biopsy]]
| align="center" style="background:#F5F5F5;" + | +
|-
! align="center" style="background:#DCDCDC;" + |Chondromyxoid Fibroma
| align="center" style="background:#F5F5F5;" + | -
| align="center" style="background:#F5F5F5;" + | -
| align="center" style="background:#F5F5F5;" + |[[Radiology]] and [[biopsy]]
| align="center" style="background:#F5F5F5;" + | +
|}

==Epidemiology and Demographics==
*Chondroblastoma is a rare benign bone tumor accounting for approximately 1% of all [[benign]] [[bone tumors]].<ref name="pmid5051664">{{cite journal| author=Dahlin DC, Ivins JC| title=Benign chondroblastoma. A study of 125 cases. | journal=Cancer | year= 1972 | volume= 30 | issue= 2 | pages= 401-13 | pmid=5051664 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=5051664 }} </ref>
*Adolescents and children are most affected by chondroblastoma.
*The age distribution of chondroblastoma is between 10-25 years with the mean age being 22 years.<ref name="pmid18290384">{{cite journal| author=Bulanov DV, Semenova LA, Makhson AN, Bulycheva IV| title=[Chondrosarcoma of the larynx]. | journal=Arkh Patol | year= 2007 | volume= 69 | issue= 6 | pages= 50-2 | pmid=18290384 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18290384 }} </ref><ref name="pmid8253461">{{cite journal| author=Turcotte RE, Kurt AM, Sim FH, Unni KK, McLeod RA| title=Chondroblastoma. | journal=Hum Pathol | year= 1993 | volume= 24 | issue= 9 | pages= 944-9 | pmid=8253461 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8253461 }} </ref>
*Men are more commonly affected than women, with a 2:1 ratio.
*There is no racial predilection to chondroblastoma.

==Risk Factors==
There are no established risk factors for chondroblastoma.

==Screening==
There is insufficient evidence to recommend routine screening for chondroblastoma.

==Natural History, Complications, and Prognosis==
*If left untreated, few patients with chondroblastoma may progress to develop [[lung]] [[metastasis]].<ref name="pmid4023729">{{cite journal| author=Bloem JL, Mulder JD| title=Chondroblastoma: a clinical and radiological study of 104 cases. | journal=Skeletal Radiol | year= 1985 | volume= 14 | issue= 1 | pages= 1-9 | pmid=4023729 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4023729 }} </ref>
*Common complications of chondroblastoma include:<ref name="FitzgeraldBroehm2014">{{cite journal|last1=Fitzgerald|first1=Judd|last2=Broehm|first2=Cory|last3=Chafey|first3=David|last4=Treme|first4=Gehron|title=Chondroblastoma of the Knee Treated with Resection and Osteochondral Allograft Reconstruction|journal=Case Reports in Orthopedics|volume=2014|year=2014|pages=1–7|issn=2090-6749|doi=10.1155/2014/543959}}</ref><ref name="pmid4023729">{{cite journal| author=Bloem JL, Mulder JD| title=Chondroblastoma: a clinical and radiological study of 104 cases. | journal=Skeletal Radiol | year= 1985 | volume= 14 | issue= 1 | pages= 1-9 | pmid=4023729 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4023729 }} </ref><ref name="pmid9229417">{{cite journal| author=Brien EW, Mirra JM, Kerr R| title=Benign and malignant cartilage tumors of bone and joint: their anatomic and theoretical basis with an emphasis on radiology, pathology and clinical biology. I. The intramedullary cartilage tumors. | journal=Skeletal Radiol | year= 1997 | volume= 26 | issue= 6 | pages= 325-53 | pmid=9229417 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9229417 }} </ref>
**Pathological [[fracture]]
**Premature [[Epiphyseal|epiphysea]]<nowiki/>l closure
***Limb-length discrepancy
***Angular deformity
**[[Malignant]] transformation
**[[Metastasis]] to other organs
***[[Metastasis]] most frequently involves the [[lungs]] and tends to occur at the time of primary tumor recurrence.
***Other sites of metastasis are secondary bone sites, soft tissue, skin, or [[liver]].
*Depending on the extent of the tumor at the time of diagnosis, the prognosis may vary. However, the [[prognosis]] is generally regarded as excellent.<ref name="pmid1449941">{{cite journal| author=Caterini R, Manili M, Spinelli M, Santori FS, Ippolito E| title=Epiphyseal chondroblastoma of bone. Long-term effects on skeletal growth and articular function in 15 cases treated surgically. | journal=Arch Orthop Trauma Surg | year= 1992 | volume= 111 | issue= 6 | pages= 327-32 | pmid=1449941 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1449941 }} </ref>
*Factors that influence the outcome of the chondroblastoma include:
**Extent of the tumor
**Size and location of the tumor
**Pulmonary [[metastasis]]
**Tumor response to the therapy

==Diagnosis==
===Diagnostic Study of Choice===
*X-ray is the diagnostic study of choice for the diagnosis of chondroblastoma.
*X-ray findings include:
**Well-circumscribed eccentric oval or round [[lytic]] lesion that usually involves the adjacent [[bone cortex]] without [[periosteal reaction]].
**A [[Sclerotic ring|sclerotic]] margin can be observed in some cases.
**For long bone chondroblastoma the tumor is typically contained to the [[epiphysis]] or apophysis but may extend through the [[epiphyseal plate]].
**A mottled appearance on the [[Radiography|radiograph]] indicates areas of [[calcification]] which is commonly associated with skeletally immature patients.
**In cases involving older patients or flat bones, typical [[Radiography|radiographic]] presentation is not as common and may mimic aggressive processes.

===History and Symptoms===
Symptoms of chondroblastoma include:<ref name="TonogaiTakahashi2013">{{cite journal|last1=Tonogai|first1=Ichiro|last2=Takahashi|first2=Mitsuhiko|last3=Manabe|first3=Hiroaki|last4=Nishisho|first4=Toshihiko|last5=Iwamoto|first5=Seiji|last6=Takao|first6=Shoichiro|last7=Kagawa|first7=Seiko|last8=Kudo|first8=Eiji|last9=Yasui|first9=Natsuo|title=A Massive Chondroblastoma in the Proximal Humerus Simulating Malignant Bone Tumors|journal=Case Reports in Orthopedics|volume=2013|year=2013|pages=1–5|issn=2090-6749|doi=10.1155/2013/673576}}</ref><ref name="FitzgeraldBroehm2014">{{cite journal|last1=Fitzgerald|first1=Judd|last2=Broehm|first2=Cory|last3=Chafey|first3=David|last4=Treme|first4=Gehron|title=Chondroblastoma of the Knee Treated with Resection and Osteochondral Allograft Reconstruction|journal=Case Reports in Orthopedics|volume=2014|year=2014|pages=1–7|issn=2090-6749|doi=10.1155/2014/543959}}</ref>
*Localized bone [[pain]] with activity and rest
**Pain often present for months or years; frequently misdiagnosed as chronic synovitis
*Localized [[swelling]]
*Decreased [[range of motion]] of the affected joint
*[[Limp]]

===Physical Examination===
*Patients with chondroblastoma usually appears well.
*Common physical examination findings of chondroblastoma include:<ref>{{cite book | last = Peabody | first = Terrance | title = Orthopaedic oncology : primary and metastatic tumors of the skeletal system | publisher = Springer | location = Cham | year = 2014 | isbn = 9783319073224 }}</ref>
**[[Tenderness]] to [[palpation]]
{| align="right"
|
[[File:Xray chondroblastoma of tibia.jpg|200px|thumb| X-ray of Knee: Chondroblastoma of proximal tibia.[https://radiopaedia.org/cases/chondroblastoma-2?lang=us Source: Case courtesy of Radswiki, Radiopaedia.org, rID: 11302]]]
|}

**Soft tissue [[swelling]]
**Decreased [[range of motion]]
**[[Muscle atrophy]]
**Joint effusion

===Laboratory Findings===
There are no diagnostic laboratory findings associated with chondroblastoma.

===Electrocardiogram===
There are no ECG findings associated with chondroblastoma.

===X-ray===
*Three views of affected [[bone]] or [[joint]] are recommended.
*X-ray findings include:
**Well-circumscribed [[epiphyseal]] [[lytic]] lesion with thin rim of [[Sclerotic ring|sclerotic]] bone that is sharply demarcated from normal medullary cavity .
**Lesions often cross physis into [[Metaphysis|metaphysis.]]
**Stippled [[Calcification|calcifications]] within the lesion may or may not be present (25%-45%).
**Cortical expansion may be present.
**Soft tissue expansion rare.
{| align="right"
|
[[File:Chondroblastoma CT scan.jpg|200px|thumb| CT scan of Knee: Chondroblastoma is subchondral, lytic, having geographic appearance, narrow transitional zone and surrounding sclerosis..[https://radiopaedia.org/cases/chondroblastoma-5?lang=us Source:Case courtesy of Dr Ali Abougazia, Radiopaedia.org, rID: 25725]]]
|}

'''Chest X-Ray'''
*Chest [[Radiography|radiograph]] should be done to look for benign pulmonary [[metastasis]] which may occasionally may occur with chondroblastoma.

===Echocardiography or Ultrasound===
There are no echocardiography/ultrasound findings associated with chondroblastoma.

===CT scan===
CT findings for chondroblastoma include:
*Lacelike matrix [[Mineralization (biology)|mineralization]] along with scalloped borders.
*[[Periosteal reaction]].
*It also defines bony extent of the lesion.

===MRI===
*MRI of chondroblastoma is ideal for the evaluation of transphyseal or transcortical extension, and for demonstrating associated surrounding [[bone marrow]] and soft tissue [[edema]], which is observed in a large proportion of cases.
*MRI Findings include:<ref name="pmid27299121">{{cite journal| author=Tiwari M, Chaturvedi H, Patel V, Matti R| title=Chondroblastoma of the Medial Malleolus: A Case Report of A Rare Tumor at an Extremely Uncommon Site. | journal=J Orthop Case Rep | year= 2016 | volume= 6 | issue= 1 | pages= 29-32 | pmid=27299121 | doi=10.13107/jocr.2250-0685.370 | pmc=4845405 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27299121 }} </ref>
{| align="right"
|
[[File:MRI CHondroblastoma.jpg|200px|thumb| MRI scan of Knee: High T2 signals with a thin sclerotic rim and surrounding marrow edema..[https://radiopaedia.org/cases/chondroblastoma-5?lang=us Source:Case courtesy of Dr Ali Abougazia, Radiopaedia.org, rID: 25725]]]
|}
**The lesions have signal typical of [[cartilage]]:
***T1: low to intermediate signal
***T2: intermediate to high signal
**Focal lobules of low, intermediate, and high signal intensity most likely correspond to [[calcification]], chondroid matrix, and fluid in the lesion.
**MRI may also reveal an effusion of the [[joint]].
**Fluid-fluid levels may occasionally be observed presumably due to an associated [[aneurysmal bone cyst]].

===Other Imaging Findings===
There are no other imaging findings associated with chondroblastoma.

===Other Diagnostic Studies===
===Biopsy===
*Biopsy may be helpful in the diagnosis of chondroblastoma.
*Biopsy grossly demonstrates the following features:
**Irregularly lobulated, [[hemorrhagic]], bluish gray, and gritty lesions that expands the [[epiphysis]].

*On histological examination:
**Chondroblasts arranged in "cobblestone" or "chickenwire" pattern may be present.
**Scattered multinucleated [[giant cells]] with focal areas of chondroid matrix.
**Occasional multinucleated [[giant cells]] may be present.
**[[Mononuclear cells|Mononuclear]] stromal cells are distinct, [[S100+]] cells with large central nuclei.
***Nuclei have longitudinal groove resembling coffee bean.
**One-third of chonroblastomas have areas of secondary [[aneurysmal bone cyst]].

==Treatment==
===Medical Therapy===
There is no treatment for chondroblastoma; the mainstay of therapy is [[surgery]].

===Surgery===
Surgery is the mainstay of treatment for chondroblastoma.<ref name="TonogaiTakahashi2013">{{cite journal|last1=Tonogai|first1=Ichiro|last2=Takahashi|first2=Mitsuhiko|last3=Manabe|first3=Hiroaki|last4=Nishisho|first4=Toshihiko|last5=Iwamoto|first5=Seiji|last6=Takao|first6=Shoichiro|last7=Kagawa|first7=Seiko|last8=Kudo|first8=Eiji|last9=Yasui|first9=Natsuo|title=A Massive Chondroblastoma in the Proximal Humerus Simulating Malignant Bone Tumors|journal=Case Reports in Orthopedics|volume=2013|year=2013|pages=1–5|issn=2090-6749|doi=10.1155/2013/673576}}</ref><ref name="FitzgeraldBroehm2014">{{cite journal|last1=Fitzgerald|first1=Judd|last2=Broehm|first2=Cory|last3=Chafey|first3=David|last4=Treme|first4=Gehron|title=Chondroblastoma of the Knee Treated with Resection and Osteochondral Allograft Reconstruction|journal=Case Reports in Orthopedics|volume=2014|year=2014|pages=1–7|issn=2090-6749|doi=10.1155/2014/543959}}</ref><ref name="pmid26041854">{{cite journal| author=Xu H, Nugent D, Monforte HL, Binitie OT, Ding Y, Letson GD et al.| title=Chondroblastoma of bone in the extremities: a multicenter retrospective study. | journal=J Bone Joint Surg Am | year= 2015 | volume= 97 | issue= 11 | pages= 925-31 | pmid=26041854 | doi=10.2106/JBJS.N.00992 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26041854 }} </ref><ref name="pmid26726978">{{cite journal| author=Cho HS, Park YK, Oh JH, Lee JH, Han I, Kim HS| title=Proximal Tibia Chondroblastoma Treated With Curettage and Bone Graft and Cement Use. | journal=Orthopedics | year= 2016 | volume= 39 | issue= 1 | pages= e80-5 | pmid=26726978 | doi=10.3928/01477447-20151222-04 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26726978 }} </ref><ref name="pmid20364261">{{cite journal| author=Lehner B, Witte D, Weiss S| title=Clinical and radiological long-term results after operative treatment of chondroblastoma. | journal=Arch Orthop Trauma Surg | year= 2011 | volume= 131 | issue= 1 | pages= 45-52 | pmid=20364261 | doi=10.1007/s00402-010-1099-y | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20364261 }} </ref>

===Extended Intralesional Curettage and Bone Grafting===

'''Indications'''
*Symptomatic individuals.

'''Technique'''
*Local adjuvant treatment with [[phenol]] or [[cryotherapy]] to decrease local recurrence.

===Radiofrequency Ablation===
*Another procedure that may be used for the management of chondroblastoma is [[radiofrequency ablation]] which is less invasive and has less recovery time.
*[[Radiofrequency ablation]] is typically most successful for small chondroblastoma lesions about 1.5 cm.

===Surgical Resection===

'''Indications'''
*Pulmonary [[metastasis]].

===Recurrence===
*Local recurrence rate is 10-15% after treatment.

===Primary Prevention===
There are no established measures for the primary prevention of chondroblastoma.

===Secondary Prevention===
There are no established measures for the secondary prevention of chondroblastoma.

==References==
{{reflist|2}}

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}

Adamantinoma

2019-06-01T18:41:43Z

Ahmed Younes:

{{SI}}

{{CMG}}; {{AE}}{{MA}} [mailto:malihash@bidmc.harvard.edu] [mailto:malihash@bidmc.harvard.edu] [mailto:malihash@bidmc.harvard.edu] [mailto:malihash@bidmc.harvard.edu]

{{SK}}

==Overview==
* Adamantinoma was first discovered by Fischer in 1913. Adamantinoma is classified into 2 distinct types: classic and differentiated (Osteofibrous dysplasia (OFD) - like). Adamantinoma is a low grade, [[malignant]] bone tumor. This tumor is predominantly located in [[tibia]] ( most in mid-portion of [[tibia]]). Most locations of the tumor include [[tibia]], ipsilateral [[fibula]], [[humerus]], [[ulna]], [[femur]], [[fibula]]. It is a Yellow gray or grayish white [[tumor]]. In microscopic examination admixture of both [[Epithelium|epithelial]] and osteofibrous component can be seen. Adamantinoma may be caused by displacement of basal [[epithelium]] of skin during [[embryogenesis]], traumatic implantation. Adamantinoma is a rare bone cancer ( 0.1–0.5% of all primary [[bone]] [[Tumor|tumors]] ). Risk factors in the development of adamantinoma may include benign [[osteofibrous dysplasia]]. If left untreated, 15-30% of patients with adamantinoma may metastasize to other parts of the body such as [[lungs]] or nearby [[Lymph node|lymph nodes]]. The diagnosis of adamantinoma is based on the findings of radiologic studies such as [[x-ray]], CT, and [[Magnetic resonance imaging|MRI]]. The most common symptoms of adamantinoma include [[swelling]] with or without pain. Less common symptoms of adamantinoma include pathological fracture. Adamantinoma may present with bowing deformity of the [[tibia]]. There is no medical therapy for adamantinoma. [[Radiation therapy]] and [[chemotherapy]] are not effective. Surgery is the mainstay of treatment for adamantinoma.

==Historical Perspective==
Adamantinoma was first discovered by Fischer in 1913.<ref name="pmid182795172">{{cite journal |vauthors=Jain D, Jain VK, Vasishta RK, Ranjan P, Kumar Y |title=Adamantinoma: a clinicopathological review and update |journal=Diagn Pathol |volume=3 |issue= |pages=8 |date=February 2008 |pmid=18279517 |pmc=2276480 |doi=10.1186/1746-1596-3-8 |url=}}</ref>

==Classification==

Adamantinoma is classified into 2 distinct types: classic and differentiated (Osteofibrous dysplasia (OFD) - like)

{| class="wikitable"
|+
!
{| class="wikitable"
| colspan="1" rowspan="1" |Features
|}
!Classic
!Differentiated
!
|-
|Age
|>20 years
|<20 years, Children
|
|-
|Radiology
|Soft tissue or intramedullary involvement
|Intra cortical
|
|-
|Histopathology
|Both epithelial and osteofibrous component, solid nests of basaloid cells
|OFD (Osteofibrous dysplasia) like pattern, Scattered positivity of epithelial elements for cytokeratin
|
|-
|Behavior
|Aggressive
|Relatively benign
|
|}

==Pathophysiology==
Adamantinoma is a low grade, [[malignant]] bone tumor. This tumor is predominatly located in tibia ( most in mid-portion of tibia). <ref name="pmid2743266">{{cite journal |vauthors=Keeney GL, Unni KK, Beabout JW, Pritchard DJ |title=Adamantinoma of long bones. A clinicopathologic study of 85 cases |journal=Cancer |volume=64 |issue=3 |pages=730–7 |date=August 1989 |pmid=2743266 |doi= |url=}}</ref> It is a biphasic tumor including [[Epithelium|epithelial]] and osteofibrous components.<ref name="pmid16906392">{{cite journal |vauthors=Van Rijn R, Bras J, Schaap G, van den Berg H, Maas M |title=Adamantinoma in childhood: report of six cases and review of the literature |journal=Pediatr Radiol |volume=36 |issue=10 |pages=1068–74 |date=October 2006 |pmid=16906392 |doi=10.1007/s00247-006-0272-5 |url=}}</ref>.

Most locations of the tumor include:<ref name="pmid27432662">{{cite journal |vauthors=Keeney GL, Unni KK, Beabout JW, Pritchard DJ |title=Adamantinoma of long bones. A clinicopathologic study of 85 cases |journal=Cancer |volume=64 |issue=3 |pages=730–7 |date=August 1989 |pmid=2743266 |doi= |url=}}</ref>
* [[Tibia]] ( 80 to 85 percent of cases)
* Ipsilateral [[fibula]] (10 to15% of cases)
* [[Humerus]]
* [[Ulna]]
* [[Femur]]
* [[Fibula]]
* [[Radius]]
* [[Rib|Ribs]]
* [[Spine]]
* Small bones of the [[hand]] and [[foot]]

====== Gross pathology: <ref name="pmid4426036">{{cite journal |vauthors=Unni KK, Dahlin DC, Beabout JW, Ivins JC |title=Adamantinomas of long bones |journal=Cancer |volume=34 |issue=5 |pages=1796–805 |date=November 1974 |pmid=4426036 |doi= |url=}}</ref> ======
* Yellow [[gray]] or grayish white tumor
* Fleshy or firm in consistency
* Some OFD like adamantinomas are solid
* Macroscopic cysts containing blood like fluid, occasionally

====== Microscopic examanination: <ref name="pmid27432663">{{cite journal |vauthors=Keeney GL, Unni KK, Beabout JW, Pritchard DJ |title=Adamantinoma of long bones. A clinicopathologic study of 85 cases |journal=Cancer |volume=64 |issue=3 |pages=730–7 |date=August 1989 |pmid=2743266 |doi= |url=}}</ref> ======
* Admixture of both [[Epithelium|epithelial]] and osteofibrous component, most commonly solid nests of basaloid cells in classic adamantinoma
* [[Nuclear]] [[atypia]] in a few cases
* Several patterns of growth including
** [[Tubular]]
** Basaloid
** Squamous
** Spindle-cell
** Osteofibrous dysplasia-like variant

* A few cases from a large series have exhibited [[nuclear]] [[atypia]]
* Foci of [[calcification]], [[giant cells]] <ref name="pmid5909059">{{cite journal |vauthors=Donner R, Dikland R |title=Adamantinoma of the tibia. A long-standing case with unusual histological features |journal=J Bone Joint Surg Br |volume=48 |issue=1 |pages=138–44 |date=February 1966 |pmid=5909059 |doi= |url=}}</ref>
* Foci of [[xanthoma]] and [[spindle cells]]<ref name="pmid852865">{{cite journal |vauthors=Weiss SW, Dorfman HD |title=Adamantinoma of long bone. An analysis of nine new cases with emphasis on metastasizing lesions and fibrous dysplasia-like changes |journal=Hum. Pathol. |volume=8 |issue=2 |pages=141–53 |date=March 1977 |pmid=852865 |doi= |url=}}</ref>

====== Immunohistochemistry: ======
* Positives for [[keratins]] 14 and 19<ref name="pmid11107052">{{cite journal |vauthors=Maki M, Saitoh K, Kaneko Y, Fukayama M, Morohoshi T |title=Expression of cytokeratin 1, 5, 14, 19 and transforming growth factors-beta1, beta2, beta3 in osteofibrous dysplasia and adamantinoma: A possible association of transforming growth factor-beta with basal cell phenotype promotion |journal=Pathol. Int. |volume=50 |issue=10 |pages=801–7 |date=October 2000 |pmid=11107052 |doi= |url=}}</ref>

==Causes==

Adamantinoma may be caused by: <ref name="pmid20777206">{{cite journal |vauthors=Ryrie BJ |title=ADAMANTINOMA OF THE TIBIA: AETIOLOGY AND PATHOGENESIS |journal=Br Med J |volume=2 |issue=3752 |pages=1000–1020.1 |date=December 1932 |pmid=20777206 |pmc=2522231 |doi= |url=}}</ref>
* Displacement of basal [[epithelium]] of skin during embrogenesis
* Traumatic implantation
* [[Synovial]] origin

==Differentiating Adamantinoma from Other Diseases==
Adamantinoma must be differentiated from aneurrysmal bone [[cyst]], unicameral bone cyst, fibrous [[dysplasia]], [[chondromyxoid fibroma]], [[eosinophilic granuloma]], [[Giant cell tumor of bone|giant cell tumor]], chondromyxoid fibroma, [[osteomyelitis]], [[chondrosarcoma]], epithelial [[metastasis]], [[hemangioendothelioma]], nonossifying fibromas, [[angiosarcoma]].

==Epidemiology and Demographics==
Adamantinoma is a rare bone cnacer ( 0.1–0.5% of all primary bone tumors ).<ref name="pmid182795177">{{cite journal |vauthors=Jain D, Jain VK, Vasishta RK, Ranjan P, Kumar Y |title=Adamantinoma: a clinicopathological review and update |journal=Diagn Pathol |volume=3 |issue= |pages=8 |date=February 2008 |pmid=18279517 |pmc=2276480 |doi=10.1186/1746-1596-3-8 |url=}}</ref>

The [[prevalence]] of Adamantinoma is approximately 0.11 per 100000 individuals in Europe.

The [[incidence]] of Adamantinoma was estimated to be less than 300 cases worldwide.

Patients of all age groups may develop adamantinoma. The median age at diagnosis is 25 to 35 years.

Men are more commonly affected by adamantinoma than women. The men to women ratio is approximately 5 to 4.<ref name="pmid3514033">{{cite journal |vauthors=Moon NF, Mori H |title=Adamantinoma of the appendicular skeleton--updated |journal=Clin. Orthop. Relat. Res. |volume= |issue=204 |pages=215–37 |date=March 1986 |pmid=3514033 |doi= |url=}}</ref>

==Risk Factors==

Risk factors in the development of adamantinoma may include benign [[osteofibrous dysplasia]]. It maybe a precursor of adamantinoma.<ref name="pmid166365232">{{cite journal |vauthors=Hatori M, Watanabe M, Hosaka M, Sasano H, Narita M, Kokubun S |title=A classic adamantinoma arising from osteofibrous dysplasia-like adamantinoma in the lower leg: a case report and review of the literature |journal=Tohoku J. Exp. Med. |volume=209 |issue=1 |pages=53–9 |date=May 2006 |pmid=16636523 |doi= |url=}}</ref>

==Screening==
There is insufficient evidence to recommend routine screening for adamantinoma.

==Natural History, Complications, and Prognosis==

If left untreated, 15-30% of patients with adamantinoma may metastasize to other parts of the body such as [[lungs]] or nearby [[lymph nodes]]. <ref name="pmid35140332">{{cite journal |vauthors=Moon NF, Mori H |title=Adamantinoma of the appendicular skeleton--updated |journal=Clin. Orthop. Relat. Res. |volume= |issue=204 |pages=215–37 |date=March 1986 |pmid=3514033 |doi= |url=}}</ref>. Adamantinoma has mortality rate of 13%to 18%. <ref name="pmid27432665">{{cite journal |vauthors=Keeney GL, Unni KK, Beabout JW, Pritchard DJ |title=Adamantinoma of long bones. A clinicopathologic study of 85 cases |journal=Cancer |volume=64 |issue=3 |pages=730–7 |date=August 1989 |pmid=2743266 |doi= |url=}}</ref>

Complications of adamantinoma include metastases to the [[lungs]].

Prognosis is generally good. Male patint, short duration of symtoms, young age ( less than 20 years) and lack of [[Squamous epithelium|squamous]] differentiantion of tumor are related with unfavorable clinical outcome. <ref name="pmid182795175">{{cite journal |vauthors=Jain D, Jain VK, Vasishta RK, Ranjan P, Kumar Y |title=Adamantinoma: a clinicopathological review and update |journal=Diagn Pathol |volume=3 |issue= |pages=8 |date=February 2008 |pmid=18279517 |pmc=2276480 |doi=10.1186/1746-1596-3-8 |url=}}</ref>

==Diagnosis==
===Diagnostic Study of Choice===

The diagnosis of adamantinoma is based on the findings of radiologic studies such as [[X-rays|x-ray]], [[CT-scans|CT]], and [[Magnetic resonance imaging|MRI]].

===History and Symptoms===

The initial symptoms of adamantinoma are often nonspecific. The most common symptoms of adamantinoma include [[swelling]] with or without pain. Less common symptoms of adamantinoma include pathological fracture( 23% of patients) <ref name="pmid10954102">{{cite journal |vauthors=Qureshi AA, Shott S, Mallin BA, Gitelis S |title=Current trends in the management of adamantinoma of long bones. An international study |journal=J Bone Joint Surg Am |volume=82-A |issue=8 |pages=1122–31 |date=August 2000 |pmid=10954102 |doi= |url=}}</ref> and neurological symptoms in spinal lesions.<ref name="pmid16883154">{{cite journal |vauthors=Dini LI, Mendonça R, Adamy CA, Saraiva GA |title=Adamantinoma of the spine: case report |journal=Neurosurgery |volume=59 |issue=2 |pages=E426; discussion E426 |date=August 2006 |pmid=16883154 |doi=10.1227/01.NEU.0000223497.06588.4A |url=}}</ref>

===Physical Examination===
Adamantinoma may present with bowing deformity of the [[tibia]].<ref name="pmid109541022">{{cite journal |vauthors=Qureshi AA, Shott S, Mallin BA, Gitelis S |title=Current trends in the management of adamantinoma of long bones. An international study |journal=J Bone Joint Surg Am |volume=82-A |issue=8 |pages=1122–31 |date=August 2000 |pmid=10954102 |doi= |url=}}</ref>

Spinal lesions may be manifested by neurologic symptoms in addition to pain.

===Laboratory Findings===
Paraneoplastic [[hypercalcemia]] can be seen in [[tibial]] adamantinoma and [[pulmonary]] [[metastasis]]<ref name="pmid7161313">{{cite journal |vauthors=Altmannsberger M, Poppe H, Schauer A |title=An unusual case of adamantinoma of long bones |journal=J. Cancer Res. Clin. Oncol. |volume=104 |issue=3 |pages=315–20 |date=1982 |pmid=7161313 |doi= |url=}}</ref>

===Electrocardiogram===
There are no [[ECG]] findings associated with adamantinoma.

===X-ray===
An [[x-ray]] may be helpful in the diagnosis of adamantinoma. Findings on an x-ray suggestive of adamantinoma include [[central]] or [[Eccentric Lesion|eccentric]], multilocular lesion in [[tibia]]. The tumor is found in the diaphyseal location. [[Metaphyseal]] extention or only involvement of [[metaphysis]] is seen occationally. The lesions are well circumscribed surrounded ring-shaped densities ( soap -bubble appearance). The lesion are more intra-cortical, but if they destroy [[cortex]], extracortical soft tisuue invasion can be seen. The [[periosteal reaction]] can be minimal to prominnet.<ref name="pmid169063923">{{cite journal |vauthors=Van Rijn R, Bras J, Schaap G, van den Berg H, Maas M |title=Adamantinoma in childhood: report of six cases and review of the literature |journal=Pediatr Radiol |volume=36 |issue=10 |pages=1068–74 |date=October 2006 |pmid=16906392 |doi=10.1007/s00247-006-0272-5 |url=}}</ref>

===Echocardiography or Ultrasound===
There are no [[echocardiography]]/[[ultrasound]] findings associated with adamantinoma.

===CT scan===

[[CT scan]] may be helpful in the diagnosis of adamantinoma. Findings on [[CT scan]] suggestive of adamantinoma include [[Cortical bone|cortical]] involvement and the soft tissue extension if it exist.

Chest CT scan can detect pulmonary [[metastasis]]. <ref name="pmid169063922">{{cite journal |vauthors=Van Rijn R, Bras J, Schaap G, van den Berg H, Maas M |title=Adamantinoma in childhood: report of six cases and review of the literature |journal=Pediatr Radiol |volume=36 |issue=10 |pages=1068–74 |date=October 2006 |pmid=16906392 |doi=10.1007/s00247-006-0272-5 |url=}}</ref>

===MRI===
[[MRI]] is helpful in the diagnosis of adamantinoma. It is useful in detection distant cortical foci, [[soft tissue]], and [[intramedullary]] extension. [[MRI]] is a very important diagnostic study for stating of tumor and tumor-free margins. Findings on MRI suggestive of adamantinoma include a [[solitary]] lobulated focus or multiple small nodules in one or more foci. Tumors demonstrate low signal intensity on T1-weighted images and high signal on T2-weighted images.<ref name="pmid15547221">{{cite journal |vauthors=Van der Woude HJ, Hazelbag HM, Bloem JL, Taminiau AH, Hogendoorn PC |title=MRI of adamantinoma of long bones in correlation with histopathology |journal=AJR Am J Roentgenol |volume=183 |issue=6 |pages=1737–44 |date=December 2004 |pmid=15547221 |doi=10.2214/ajr.183.6.01831737 |url=}}</ref>

===Other Imaging Findings===
[[Bone scan]] may be helpful in the diagnosis of adamantinoma. Findings on a [[nuclear medicine]] suggestive of adamantioma include:<ref name="pmid182795174">{{cite journal |vauthors=Jain D, Jain VK, Vasishta RK, Ranjan P, Kumar Y |title=Adamantinoma: a clinicopathological review and update |journal=Diagn Pathol |volume=3 |issue= |pages=8 |date=February 2008 |pmid=18279517 |pmc=2276480 |doi=10.1186/1746-1596-3-8 |url=}}</ref>
* Increased blood flow in the region of the [[tumor]]
* Increased accumulation of [[technetium-99m]] methylene diphosphate in the area of the [[tumor]]

===Other Diagnostic Studies===
There are no other diagnostic studies associated with adamantinoma.

==Treatment==
===Medical Therapy===
There is no medical therapy for adamantinoma. Radition therapy and [[chemotherapy]] are not effective. <ref name="pmid111070522">{{cite journal |vauthors=Maki M, Saitoh K, Kaneko Y, Fukayama M, Morohoshi T |title=Expression of cytokeratin 1, 5, 14, 19 and transforming growth factors-beta1, beta2, beta3 in osteofibrous dysplasia and adamantinoma: A possible association of transforming growth factor-beta with basal cell phenotype promotion |journal=Pathol. Int. |volume=50 |issue=10 |pages=801–7 |date=October 2000 |pmid=11107052 |doi= |url=}}</ref>

===Surgery===
Surgery is the mainstay of treatment for adamantinoma.
* Tumor [[resection]] with wide operative margins and then limb reconstruction <ref name="pmid27432664">{{cite journal |vauthors=Keeney GL, Unni KK, Beabout JW, Pritchard DJ |title=Adamantinoma of long bones. A clinicopathologic study of 85 cases |journal=Cancer |volume=64 |issue=3 |pages=730–7 |date=August 1989 |pmid=2743266 |doi= |url=}}</ref>
* [[Amputation]]<ref name="pmid16826129">{{cite journal |vauthors=Khan MH, Darji R, Rao U, McGough R |title=Leg pain and swelling in a 22-year-old man |journal=Clin. Orthop. Relat. Res. |volume=448 |issue= |pages=259–66 |date=July 2006 |pmid=16826129 |doi=10.1097/01.blo.0000195924.36103.11 |url=}}</ref>

===Primary Prevention===
There are no established measures for the primary prevention of adamantinoma.

===Secondary Prevention===
There are no established measures for the secondary prevention of adamantinoma.

==References==
{{reflist|2}}

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}

Synovial sarcoma

2019-06-01T18:40:30Z

Ahmed Younes: /* MRI */

__NOTOC__
{{SI}}
{{CMG}} {{AE}} {{MV}}

{{SK}} Malignant synovioma

==Overview==

Synovial sarcoma (also known as [[malignant]] synovioma) is a very rare form of [[soft tissue]] [[sarcoma]], which usually occurs near the [[Joint|joints]] in upper and lower [[Limb (anatomy)|extremities]]. Synovial sarcoma was first discovered by Pack and Tabah in 1955. Synovial sarcoma may be classified according to histopathological findings into 4 sub-types: biphasic, monophasic [[fibrous]] (most common), monophasic [[Epithelium|epithelial]], and poorly differentiated. The [[pathogenesis]] of synovial sarcoma is characterized by the dysregulation of [[gene expression]] of SYT-SSX [[gene]]. The most common locations for the occurrence of synovial sarcoma include [[Knee]], adjacent to large [[Joint|joints]], and [[Popliteal fossa]]. The SYT-SSX fusion [[gene]] (located in [[chromosome]] 18) has been associated with the development of synovial sarcoma. There are no established causes for synovial sarcoma. Synovial sarcoma must be differentiated from other [[Disease|diseases]] that cause [[Arthralgia|joint pain]], mass growth, and limited [[range of motion]], such as [[Malignant fibrous histiocytoma|malignant fibrous histiocytoma (MFH)]]-[[fibrosarcoma]], [[Liposarcoma]], [[Osteosarcoma]], and [[Chondrosarcoma]]. The [[prevalence]] of synovial sarcoma remains unknown. Synovial sarcomas account for 2.5 - 10% of all [[soft tissue]] sarcomas. Synovial sarcoma is more commonly observed among [[Patient|patients]] aged 15 - 40 years old. There is no racial predilection for synovial sarcoma. There are no known [[Risk factor|risk factors]] associated with the development of synovial sarcoma. There is insufficient evidence to recommend routine [[Screening (medicine)|screening]] for synovial sarcoma. The majority of [[Patient|patients]] with synovial sarcoma remain [[asymptomatic]] for years. If left untreated, [[Patient|patients]] with synovial sarcoma may progress to develop [[Metastasis|metastases]]. [[Prognosis]] is generally poor, and the [[median]] survival rate of [[Patient|patients]] with synovial sarcoma is approximately 35% to 60%. The [[diagnosis]] of synovial sarcoma is typically made based on [[histology]] and is confirmed by the presence of t(X;18). There are no specific [[Medical laboratory|laboratory]] findings associated with synovial sarcoma. [[Patient|Patients]] with synovial sarcoma usually are well-appearing. There are no specific [[Medical laboratory|laboratory]] findings associated with synovial sarcoma. There are no [[The electrocardiogram|ECG]] findings associated with synovial sarcoma. Plain [[X-rays|x-ray]] can be normal unless the [[tumor]] is large in size or has [[Dystrophic calcification|dystrophic calcifications]]. On [[ultrasound]], characteristic findings of synovial sarcoma include heterogeneity and hypo-echoic mass. On [[Computed tomography|CT scan]], characteristic findings of synovial sarcoma include [[Soft tissue]] mass, [[Calcification|calcifications]], and [[Heterogeneous]] [[density]] and enhancement. [[Magnetic resonance imaging|MRI]] is the [[imaging]] modality of choice for synovial sarcoma. [[Medicine|Medical]] [[therapy]] include [[Doxorubicin]], [[ifosfamide]], and [[gemcitabine]]. [[Surgery]] is the mainstay of [[therapy]]. [[Surgery|Surgical]] [[resection]] in conjunction with [[chemotherapy]] or [[Radiation therapy|radiation]] is the most common approach to the treatment of synovial sarcoma. There are no established measures for the [[Prevention (medical)|prevention]] of synovial sarcoma.

==Historical Perspective==
*Synovial sarcoma was first discovered by Pack and Tabah in 1955.<ref name="pmid19865558">{{cite journal |vauthors=Gomatos IP, Alevizos L, Kafiri G, Bramis J, Leandros E |title=Management of a small incidentally discovered retroperitoneal synovial sarcoma |journal=Can J Surg |volume=52 |issue=5 |pages=E199–200 |year=2009 |pmid=19865558 |pmc=2769101 |doi= |url=}}</ref>

==Classification==
*Synovial sarcoma may be [[Classification|classified]] according to [[Histopathology|histopathological]] findings into 4 sub-types:<ref name="pmid9930576">{{cite journal |vauthors=Fisher C |title=Synovial sarcoma |journal=Ann Diagn Pathol |volume=2 |issue=6 |pages=401–21 |year=1998 |pmid=9930576 |doi= |url=}}</ref>
:*Biphasic
:*Monophasic [[fibrous]] (most common)
:*Monophasic [[Epithelium|epithelial]]
:*Poorly differentiated

==Pathophysiology==
*The [[pathogenesis]] of synovial sarcoma is characterized by the dysregulation of [[gene expression]] of SYT-SSX [[gene]].<ref name="pmid9930576">{{cite journal |vauthors=Fisher C |title=Synovial sarcoma |journal=Ann Diagn Pathol |volume=2 |issue=6 |pages=401–21 |year=1998 |pmid=9930576 |doi= |url=}}</ref>
*The most common locations for the occurrence of synovial sarcoma include:<ref name="pmid19865558">{{cite journal |vauthors=Gomatos IP, Alevizos L, Kafiri G, Bramis J, Leandros E |title=Management of a small incidentally discovered retroperitoneal synovial sarcoma |journal=Can J Surg |volume=52 |issue=5 |pages=E199–200 |year=2009 |pmid=19865558 |pmc=2769101 |doi= |url=}}</ref>
:*[[Knee]]
:*Adjacent to large [[Joint|joints]]
:*[[Popliteal fossa]]
*The SYT-SSX fusion [[gene]] (located in [[chromosome]] 18) has been associated with the development of synovial sarcoma.
*On [[gross pathology]], characteristic findings of synovial sarcoma include:
:*Solid often [[Lobule|lobulated]]
:*Grey-yellow
:*Pushing border to ill-defined border
*On [[microscopic]] [[Histopathology|histopathological]] [[analysis]], characteristic findings of synovial sarcoma include:<ref name="pmid9930576">{{cite journal |vauthors=Fisher C |title=Synovial sarcoma |journal=Ann Diagn Pathol |volume=2 |issue=6 |pages=401–21 |year=1998 |pmid=9930576 |doi= |url=}}</ref>
:*Non-specific appearances
:*Well or poorly defined [[heterogeneous]] masses
:*Frequent areas of [[Bleeding|hemorrhage]]
:*[[Necrosis]]

==Causes==
* There are no established causes for synovial sarcoma.

==Differentiating Synovial Sarcoma from Other Diseases==
*Synovial sarcoma must be differentiated from other [[Disease|diseases]] that cause [[Arthralgia|joint pain]], mass growth, and limited [[range of motion]], such as:<ref name="pmid9930576">{{cite journal |vauthors=Fisher C |title=Synovial sarcoma |journal=Ann Diagn Pathol |volume=2 |issue=6 |pages=401–21 |year=1998 |pmid=9930576 |doi= |url=}}</ref>
:*[[Malignant fibrous histiocytoma|Malignant fibrous histiocytoma (MFH)]]-[[fibrosarcoma]]
:*[[Liposarcoma]]
:*[[Osteosarcoma]]
:*[[Chondrosarcoma]]

==Epidemiology and Demographics==
* The [[prevalence]] of synovial sarcoma remains unknown.<ref name="pmid9930576">{{cite journal |vauthors=Fisher C |title=Synovial sarcoma |journal=Ann Diagn Pathol |volume=2 |issue=6 |pages=401–21 |year=1998 |pmid=9930576 |doi= |url=}}</ref>
* Synovial sarcomas account for 2.5 - 10% of all [[soft tissue]] sarcomas.
===Age===
*Synovial sarcoma is more commonly observed among [[Patient|patients]] aged 15 - 40 years old.
*Synovial sarcoma is more commonly observed among [[Adolescence|adolescents]] and young [[Adult|adults]].

===Gender===
* [[Male|Males]] are more commonly affected with synovial sarcoma than [[Female|females]].
* The [[male]] to [[female]] ratio is approximately 1.2 to 1.

===Race===
*There is no racial predilection for synovial sarcoma.<ref name="pmid9930576">{{cite journal |vauthors=Fisher C |title=Synovial sarcoma |journal=Ann Diagn Pathol |volume=2 |issue=6 |pages=401–21 |year=1998 |pmid=9930576 |doi= |url=}}</ref>

==Risk Factors==
*There are no known [[Risk factor|risk factors]] associated with the development of synovial sarcoma.<ref name="pmid19865558">{{cite journal |vauthors=Gomatos IP, Alevizos L, Kafiri G, Bramis J, Leandros E |title=Management of a small incidentally discovered retroperitoneal synovial sarcoma |journal=Can J Surg |volume=52 |issue=5 |pages=E199–200 |year=2009 |pmid=19865558 |pmc=2769101 |doi= |url=}}</ref>

== Screening ==
* There is insufficient evidence to recommend routine [[Screening (medicine)|screening]] for synovial sarcoma.

== Natural History, Complications, and Prognosis==
*The majority of [[Patient|patients]] with synovial sarcoma remain [[asymptomatic]] for years.
*Early [[clinical]] feature includes a soft [[Palpation|palpable]] mass.
*If left untreated, [[Patient|patients]] with synovial sarcoma may progress to develop [[Metastasis|metastases]].
*The most common [[Complication (medicine)|complication]] of synovial sarcoma is [[Lung|pulmonary]] cannonball [[Metastasis|metastases]].
*[[Prognosis]] is generally poor, and the [[median]] survival rate of [[Patient|patients]] with synovial sarcoma is approximately 35% to 60%.
*The table below demonstrates the good and poor [[Prognosis|prognostic]] factors for [[Patient|patients]] with synovial sarcoma.<ref name="pmid9930576">{{cite journal |vauthors=Fisher C |title=Synovial sarcoma |journal=Ann Diagn Pathol |volume=2 |issue=6 |pages=401–21 |year=1998 |pmid=9930576 |doi= |url=}}</ref>
:{| class="wikitable"
! style="font-weight: bold;" | Poor prognosis
! style="font-weight: bold;" | Good prognosis
|-
|
*Large size (> 5 cm): most important factor
*Located in the [[trunk]] or [[head]] and [[neck]]
*Older [[Patient|patients]]
*[[Cyst|Cystic]]/[[hemorrhagic]] components
*Marked [[Heterogeneous|heterogeneity]]
*[[Histology]]
:*Poorly differentiated [[histology]]
:*Extensive [[tumor]] [[necrosis]]
:*High [[Cell nucleus|nuclear]] grade
:*[[p53]] [[Mutation|mutations]]
:*High [[Mitosis|mitotic]] rate (> 10 [[Mitosis|mitoses]] per 10 high-power field)
|
*Small size
*Located in extremity
*Younger age < 20 years of age
*Solid [[Homogeneity|homogenous]] mass
*Presence of [[calcification]]
*Biphasic [[histology]] (controversial)
|}

== Diagnosis ==
===Diagnostic Study of Choice===
* The [[diagnosis]] of synovial sarcoma is typically made based on [[histology]] and is confirmed by the presence of t(X;18).<ref name="pmid9930576">{{cite journal |vauthors=Fisher C |title=Synovial sarcoma |journal=Ann Diagn Pathol |volume=2 |issue=6 |pages=401–21 |year=1998 |pmid=9930576 |doi= |url=}}</ref>

=== History and Symptoms ===
*Synovial sarcoma is usually [[asymptomatic]].
*[[Symptom|Symptoms]] of synovial sarcoma may include the following:<ref name="pmid9930576">{{cite journal |vauthors=Fisher C |title=Synovial sarcoma |journal=Ann Diagn Pathol |volume=2 |issue=6 |pages=401–21 |year=1998 |pmid=9930576 |doi= |url=}}</ref>
:*[[Soft tissue]] mass
:*Localized [[pain]]
:*Limited [[range of motion]]
*Specific areas of focus when obtaining the history include:
:*Localized [[pain]]
:*Accompanying local swelling or mass, progressive [[pain]] that is not relieved with rest, night [[pain]]
:*Recent [[weight loss]] (or [[failure to thrive]])
:*Personal history of [[cancer]]
:*[[Family history]] of [[Bone tumor|bone tumors]]

=== Physical Examination ===
*[[Patient|Patients]] with synovial sarcoma usually are well-appearing.
*[[Physical examination]] may be remarkable for:
:*[[Tenderness]] to [[palpation]]
:*[[Soft tissue]] [[swelling]]
:*Decreased [[range of motion]]
:*[[Muscle atrophy]]
:*[[Joint]] effusion

=== Laboratory Findings ===
*There are no specific [[Medical laboratory|laboratory]] findings associated with synovial sarcoma.

=== Electrocardiogram ===
* There are no [[The electrocardiogram|ECG]] findings associated with synovial sarcoma.

=== X-ray ===
* Plain [[X-rays|x-ray]] can be normal unless the [[tumor]] is large in size or has [[Dystrophic calcification|dystrophic calcifications]].<ref>{{Cite journal
| author = [[Mark D. Murphey]], [[Michael S. Gibson]], [[Bryan T. Jennings]], [[Ana M. Crespo-Rodriguez]], [[Julie Fanburg-Smith]] & [[Donald A. Gajewski]]
| title = From the archives of the AFIP: Imaging of synovial sarcoma with radiologic-pathologic correlation
| journal = [[Radiographics : a review publication of the Radiological Society of North America, Inc]]
| volume = 26
| issue = 5
| pages = 1543–1565
| year = 2006
| month = September-October
| doi = 10.1148/rg.265065084
| pmid = 16973781
}}</ref>

=== Echocardiography or Ultrasound ===
* There are no [[echocardiography]] findings associated with synovial sarcoma.
* On [[ultrasound]], characteristic findings of synovial sarcoma include:<ref name="pmid9930576">{{cite journal |vauthors=Fisher C |title=Synovial sarcoma |journal=Ann Diagn Pathol |volume=2 |issue=6 |pages=401–21 |year=1998 |pmid=9930576 |doi= |url=}}</ref>
:*Non-specific
:*[[Heterogeneous]]
:*Hypoechoic mass

=== CT scan ===
*On [[Computed tomography|CT scan]], characteristic findings of synovial sarcoma include:
:*Non-specific
:*[[Soft tissue]] mass
:*[[Heterogeneous]] [[density]] and enhancement
:*[[Calcification|Calcifications]]

===MRI===
*[[Magnetic resonance imaging|MRI]] is the [[imaging]] modality of choice for synovial sarcoma.
*On [[Magnetic resonance imaging|MRI]], characteristic findings of synovial sarcoma include:<ref name="pmid9930576">{{cite journal |vauthors=Fisher C |title=Synovial sarcoma |journal=Ann Diagn Pathol |volume=2 |issue=6 |pages=401–21 |year=1998 |pmid=9930576 |doi= |url=}}</ref>
:*'''T1:''' iso- (slightly hyper-) intense to [[muscle]]/[[heterogeneous]]
:*'''T2:''' mostly hyperintense, markedly [[heterogeneous]] appearance of synovial sarcomas on [[fluid]] sensitive sequences result in so called "triple sign" which is due to areas of [[necrosis]] and [[Cyst|cystic]] degeneration with very high signal, relatively high signal [[soft tissue]] components, and areas of low signal intensity due to [[Dystrophic calcification|dystrophic calcifications]] and fibrotic bands, due to high tendency of [[Lesion|lesions]] to [[Bleeding|bleed]].
:*'''T1 C + (Gd):''' enhancement is usually prominent and can be diffuse (40%) [[heterogeneous]] (40%) or peripheral (20%)
*The image below demonstrates an [[Magnetic resonance imaging|MRI]] image of synovial sarcoma.

==Other Imaging Findings==
There are no other [[imaging]] findings associated with synovial sarcoma.

==Other Diagnostic studies==
There are no other [[Diagnosis|diagnostic]] studies associated with synovial sarcoma.

== Treatment ==
=== Medical Therapy ===
*The mainstay of [[therapy]] for synovial sarcoma includes:<ref name="pmid9930576">{{cite journal |vauthors=Fisher C |title=Synovial sarcoma |journal=Ann Diagn Pathol |volume=2 |issue=6 |pages=401–21 |year=1998 |pmid=9930576 |doi= |url=}}</ref>
:*[[Doxorubicin]]
:*[[Ifosfamide]]
:*[[Gemcitabine]]

=== Surgery ===
*[[Surgery]] is the mainstay of [[therapy]] for synovial sarcoma.<ref name="pmid19865558">{{cite journal |vauthors=Gomatos IP, Alevizos L, Kafiri G, Bramis J, Leandros E |title=Management of a small incidentally discovered retroperitoneal synovial sarcoma |journal=Can J Surg |volume=52 |issue=5 |pages=E199–200 |year=2009 |pmid=19865558 |pmc=2769101 |doi= |url=}}</ref>
*[[Surgery|Surgical]] [[resection]] in conjunction with [[chemotherapy]] or [[Radiation therapy|radiation]] is the most common approach to the treatment of synovial sarcoma.<ref name="pmid9930576">{{cite journal |vauthors=Fisher C |title=Synovial sarcoma |journal=Ann Diagn Pathol |volume=2 |issue=6 |pages=401–21 |year=1998 |pmid=9930576 |doi= |url=}}</ref>

=== Primary Prevention ===
*There are no established measures for the [[Prevention (medical)|primary prevention]] of synovial sarcoma.

===Secondary Prevention===
There are no established measures for the [[Prevention (medical)|secondary prevention]] of synovial sarcoma.

==References==
{{Reflist|2}}

[[Category: Oncology]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Orthopedics]]

Sacrococcygeal teratoma CT

2019-06-01T18:38:50Z

Ahmed Younes: /* CT Examples of Sacrococcygeal Teratoma */

__NOTOC__
{{Sacrococcygeal teratoma}}
{{CMG}}{{AE}}{{MGS}}

==Overview==
CT scan is not part of the routine investigation of sacrococcygeal teratoma. On CT scan, sacrococcygeal teratoma is characterized by bone, fat, and cystic components.<ref name = CT>Sacrococcygel Teratoma. Radiopedia (2015) http://radiopaedia.org/articles/sacrococcygeal-teratoma Accessed on December 15, 2015</ref>

==Key CT Findings in Sacrococcygeal Teratoma==
*CT scan is done postnatally to determine the extend of the tumor.
*Identifies bone, fat and cystic components.<ref name = CT>Sacrococcygel Teratoma. Radiopedia (2015) http://radiopaedia.org/articles/sacrococcygeal-teratoma Accessed on December 15, 2015</ref>
*Calcification may again be seen.

==References==
{{reflist|2}}

{{WH}}
{{WS}}

[[Category:Disease]]
[[Category:Congenital disorders]]
[[Category:Obstetrics]]
[[Category:Pediatrics]]
[[Category:Types of cancer]]
[[Category:Rare diseases]]
[[Category:Pediatric cancers]]
[[Category:Mature chapter]]
[[es:Teratoma sacrococcígeo]]
[[fr:Tératome sacro-coccygien]]
{{WikiDoc Help Menu}}
{{WikiDoc Sources}}
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Orthopedics]]

Thyroid adenoma pathophysiology

2019-06-01T18:32:27Z

Ahmed Younes: /* Microscopic Pathology */

__NOTOC__
{{Thyroid adenoma}}
{{CMG}}; {{AE}} {{Ammu}}
==Overview==
[[Thyroid]] [[adenoma]] arises from the [[epithelial cell]]s of the [[thyroid]] gland, which are normally involved in secretion of [[thyroxine]] hormone. The most common [[gene]] involved in the [[pathogenesis]] of [[thyroid]] [[adenoma]] is ''THADA'' [[gene]].

==Pathogenesis==
[[Thyroid]] [[adenoma]] are lumps which commonly arise within an otherwise normal [[thyroid|thyroid gland]]. They indicate a [[thyroid]] neoplasm.<ref name="pmid16728572">{{cite journal |vauthors=Niedziela M |title=Pathogenesis, diagnosis and management of thyroid nodules in children |journal=Endocr. Relat. Cancer |volume=13 |issue=2 |pages=427–53 |date=June 2006 |pmid=16728572 |doi=10.1677/erc.1.00882 |url=}}</ref>
* Sometimes a [[thyroid]] [[nodule]] presents as a fluid-filled cavity called a [[thyroid]] cyst. Often, solid components are mixed with the fluid. [[Thyroid]] [[cysts]] most commonly result from degenerating [[thyroid adenoma]]s, which are benign, but they occasionally contain [[malignant]] solid components.
* [[Thyroid]] [[adenoma]] may be clinically silent, or it may be a "functional" [[tumor]], producing excessive [[thyroid hormone]]. In this case, it may result in symptomatic [[hyperthyroidism]], and may be referred to as a toxic thyroid adenoma.
===Colloid Nodules===
Colloid [[nodules]] are non-neoplastic [[benign]] [[nodules]] occurring within the [[thyroid]] gland. They form the vast majority of nodular thyroid disease. Colloid [[nodules]] are composed of irregularly enlarged follicles containing abundant [[colloid]]. Some [[colloid]] [[nodules]] can be cystic ([[cystic]] colloid [[nodule]]), and may contain areas of [[necrosis]], [[hemorrhage]], and [[calcification]]. [[Colloid nodule|Colloid nodules]] may be single or multiple and can vary considerably in size.<ref name="pmid9484634">{{cite journal| author=Zacks JF, de las Morenas A, Beazley RM, O'Brien MJ| title=Fine-needle aspiration cytology diagnosis of colloid nodule versus follicular variant of papillary carcinoma of the thyroid. | journal=Diagn Cytopathol | year= 1998 | volume= 18 | issue= 2 | pages= 87-90 | pmid=9484634 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9484634 }}</ref>

==Genetics==
* The target [[gene]] associated with [[thyroid]] [[adenoma]] has been identified and referred to as ''[[thyroid]] [[adenoma]] associated'' (''THADA'') gene.<ref name="pmid12955091">{{cite journal| author=Rippe V, Drieschner N, Meiboom M, Murua Escobar H, Bonk U, Belge G et al.| title=Identification of a gene rearranged by 2p21 aberrations in thyroid adenomas. | journal=Oncogene | year= 2003 | volume= 22 | issue= 38 | pages= 6111-4 | pmid=12955091 | doi=10.1038/sj.onc.1206867 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12955091 }} </ref><ref name="KlothBelge2011">{{cite journal|last1=Kloth|first1=Lars|last2=Belge|first2=Gazanfer|last3=Burchardt|first3=Käte|last4=Loeschke|first4=Siegfried|last5=Wosniok|first5=Werner|last6=Fu|first6=Xin|last7=Nimzyk|first7=Rolf|last8=Mohamed|first8=Salah A|last9=Drieschner|first9=Norbert|last10=Rippe|first10=Volkhard|last11=Bullerdiek|first11=Jörn|title=Decrease in thyroid adenoma associated (THADA) expression is a marker of dedifferentiation of thyroid tissue|journal=BMC Clinical Pathology|volume=11|issue=1|year=2011|pages=13|issn=1472-6890|doi=10.1186/1472-6890-11-13}}</ref>
* In thyroid adenomas, [[protein]] associated with ''THADA'' was frequently found to be truncated.
* While competing with the full-length [[protein]] translated from the normal [[allele]] of ''THADA'', the altered [[protein]] derived from the truncated [[gene]] might lead to an impaired induction of [[apoptosis]], and subsequently give rise to an increased [[cell]] [[proliferation]] leading to benign [[thyroid]] [[Tumor|tumors]] with 2p21 [[translocations]], without significant changes of the expression level.

==Associated Conditions==
* [[Hyperthyroidism]]
* [[Multinodular goiter]]
==Gross Pathology==
Thyroid follicular [[adenoma]] ranges in diameter from 3 cm on an average, but sometimes is larger (up to 10 cm) or smaller. The typical [[thyroid]] [[adenoma]] is a solitary, spherical, and encapsulated lesion that is well demarcated from the surrounding parenchyma.<ref name="pmid17703450">{{cite journal |vauthors=Deveci MS, Deveci G, LiVolsi VA, Gupta PK, Baloch ZW |title=Concordance between thyroid nodule sizes measured by ultrasound and gross pathology examination: effect on patient management |journal=Diagn. Cytopathol. |volume=35 |issue=9 |pages=579–83 |date=September 2007 |pmid=17703450 |doi=10.1002/dc.20714 |url=}}</ref>The color ranges from gray-white to red-brown, depending upon:
# The cellularity of the [[adenoma]]
# The colloid content

==Microscopic Pathology==
* Areas of [[hemorrhage]], [[fibrosis]], [[calcification]], and cystic change similar to what is found in [[multinodular goiter]]<nowiki/>s, are common in [[thyroid]] (follicular) [[adenoma]], particularly in larger lesions.
* Encapsulated [[tumor]]s without evidence of infiltration may be found.
* [[Colloid]] nodules are distinguished by an apparently gelatinous mass of [[colloid]] both surrounding and contained within [[follicular cell]]s. Colloid [[nodules]] are not surrounded by a fibrous [[capsule]] of compressed [[tissue]]. However, they are surrounded by flattened [[epithelium|epithelial]] cells.<ref>{{cite web |url=http://rcpa.tv/parts/educational/anatomical/Dr_Alpha_Tsui/Thyroid_cytology.pdf |title=Thyroid cytology |author=Dr. Alpha Tsui |date=10 October 2010 |publisher=thyroidmanager.org |accessdate=26 September 2011}}</ref> Both the number of cells and the type of colloid may vary considerably.<ref>{{cite web |url=http://www.thyroidmanager.org/chapter%206d/fnabiopsy-frame.htm |title=Fine-Needle Aspiration Biopsy of the Thyroid Gland, Chapter 6d. |author=Diana S. Dean, M.D. Hossein Gharib, M.D. |date=10 October 2010 |publisher=thyroidmanager.org |accessdate=26 September 2011}}</ref>
 

==Reference==
{{Reflist|2}}
[[Category:Disease]]
[[Category:Endocrinology]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Endocrinology]]
[[Category:Surgery]]

Thymoma overview

2019-05-31T23:11:37Z

Ahmed Younes:

__NOTOC__
{{Thymoma}}
I{{CMG}}; {{AE}} {{AM}} {{AAM}}

==Overview==
* Thymoma is a [[benign]] thymic neoplasm located in the [[anterior mediastinum]], behind the sternum and in front of the great vessels that involutes during [[puberty]], it takes part in [[lymphocytes]] maturation throughout adulthood.
* The incidence of thymoma is approximately 0.13 per 100,000 individuals.
* Thymic neoplasm can be divided into two major groups: [[thymoma]] and [[thymic carcinoma]]thymoma
* Thymoma is the most common tumor of the anterior [[mediastinum]], consisting of any type of thymic [[epithelial cell]] as well as [[lymphocyte]]s that are usually abundant and probably not [[neoplastic]].
* Thymoma usually is [[benign]], and frequently encapsulated uncommon tumor, best known for its association with the autoimmune disorder such as [[myasthenia gravis]]. Thymoma is found in 15% of patients with [[myasthenia gravis]].
* Once diagnosed, thymomas may be removed surgically. If left untreated thymoma may progress to invade the [[mediastinum]] and the surrounding structure.
* Depending on the stage of the tumor at the time of diagnosis, the prognosis may vary. However, the prognosis is generally regarded as good.
* Common complications of the thymoma include the pressure effect of the mass itself, [[autoimmune diseases]], and rarely, [[malignancy]]. [[Metastasis]] is extremely rare. In the rare case of a [[malignant tumor]], [[chemotherapy]] may be used.
* Malignant [[lymphomas]] that involve the [[thymus]], e.g., [[lymphosarcoma]], [[Hodgkin's disease]] (termed "granulomatous thymoma" in the past), should not be regarded as thymoma.
* Thymomas associated with autoimmune disorders usually are benign. Malignant thymomas can [[metastasis|metastasize]], generally to [[pleura]], [[kidney]], [[bone]], [[liver]], or [[brain]].

==Historical Perspective==
* The thymic epithelial tumors staging was initially proposed by Bergh and his colleagues in 1978, modified by Wilkins and Castleman in 1979, and advanced by Masaoka et al. in 1981.

==Classification==
* In 1999, a World Health Organization (WHO) Working group suggested a non-committal terminology (Masaoka classification), preserving the distinct categories of the histogenetic classification, but using letters and numbers to designate tumour entities.
* Recently, it has been very well accepted as it provides an easy comparison of clinical, pathological and immunological studies.

==Pathology==
* On [[gross pathology]], well circumscribed [[mass]], that is locally invasive is a characteristic finding of thymoma.
* On microscopic [[histopathological]] analysis, round cells, with ample vacuolated [[cytoplasm]]s, and fat droplets are characteristic findings of thymoma.

==Causes==
* There are no established causes for thymoma.

==Differential Diagnosis==
Thymoma must be differentiated from other thymic diseases such as
* [[thymic carcinoma]]
* Thymic [[cyst]]
* Thymic [[hyperplasia]]
* [[germ cell tumors]].

==Epidemiology and Demographic==
* The incidence of thymoma is approximately 0.13 per 100,000 individuals.
* Thymic [[neoplasms]] are the most common tumors located in the [[anterior mediastinum]] (20%).
* [[Incidence]] increases in middle age, and peaks in the seventh decade of life.
* Men and women are equally affected.

==Risk Factors==
* There are no established risk factors for thymoma.

==Natural History, Complication and Prognosis==
* If left untreated thymoma may progress to invade the [[mediastinum]] and the surrounding structure. Depending on the stage of the tumor at the time of diagnosis, the prognosis may vary.
* The prognosis is generally regarded as good.
* Common complications of the thymoma include the pressure effect of the mass itself, [[autoimmune diseases]], and rarely, [[malignancy]].

==Diagnosis==
===History and symptoms===
Symptoms of thymoma include
* [[muscle weakness]]
* [[cough]]
* [[wheezing]]
* [[dysphagia]].
In addition to the symptoms of associated immune syndromes such as,
* [[anemia]]
* [[arthralgia]]
* [[skin rash]].

===Physical examination===
Patients with thymoma usually appear asymptomatic. Physical examination of patients with thymoma is may be remarkable for,
* Neck lump,
* Facial [[swelling]]
* [[wheezing]].

===Staging===
* Staging of thymic epithelial tumors was initially proposed by Bergh and his colleagues in 1978, modified by Wilkins and Castleman in 1979, and advanced by Masaoka et al. in 1981.
* Modified Masaoka staging grouped with TNM classification is the most widely adopted system for thymic epithelial tumors currently in use.

===Laboratory Findings===
Laboratory findings associated with thymoma may include,
* A[[antibodies|ntibodies]] to the [[acetylcholine receptor]],
* Abnormal [[electrolyte]]s, [[renal]], and [[liver function]] tests.

===X-Ray===
* On chest x-ray, thymoma is characterized by oval to rounded, well demarcated, asymmetric, homogeneous mass of soft tissue density on one side of the midline.

===CT Scan===
* [[Computed Tomography]] scan may be diagnostic of thymoma. The tumor is generally located inside the thymus, and can be calcified.
* Increased vascular enhancement can be indicative of malignancy, as can be pleural deposits.

===MRI===
* On [[thoracic]] MRI, thymoma is characterized by increased heterogenous signal on T2WI.

===Ultrasound===
* Ultrasound is used to guide [[fine needle aspiration]] or core [[needle biopsy]] in patients with thymoma.

===Other Imaging Studies===
* [[PET scan]] may be used in the diagnosis of thymoma.

===Other Diagnostic Studies===
Other diagnostic studies for Thymoma include
* CT scan guided core needle [[biopsy]]
* CT scan guided [[fine needle aspiration]]
* [[mediastinoscopy]]
* Videothoracoscopy.

==Treatment==
===Medical Therapy===
* [[Chemotherapy]] and [[radiotherapy]] are used as [[adjuvant therapy|adjuvant]] or [[neoadjuvant therapy|neoadjuvant therapies]].
* Neoadjuvant therpy may be administered prior to surgery to make the tumor resectable.

===Surgery===
* Surgery is the mainstay of treatment of thymoma.

===Primary Prevention===
* There are no primary preventive measures available for thymoma.

===Secondary Prevention===
* Complete surgical resection may help to prevent the recurrence of thymoma.

==References==
{{Reflist|2}}
[[Category:Types of cancer]]
[[Category:Rare diseases]]
[[Category:Disease]]
{{WikiDoc Help Menu}}
{{WikiDoc Sources}}
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Hematology]]
[[Category:Immunology]]
[[Category:Surgery]]

Parathyroid adenoma

2019-05-31T15:21:03Z

Ahmed Younes: /* Gallery */

__NOTOC__
{{Parathyroid adenoma}}
{{CMG}}; {{AE}

{{SK}} Adenoma of parathyroid gland
==Overview==
A parathyroid adenoma is a [[adenoma|benign tumor]] of the [[parathyroid gland]]. Parathyroid adenoma can be associated with overexpression of the ''[[cyclin D1]]'' gene. An elevated concentration of
serum calcium and serum parathyroid hormone is diagnostic of parathyroid gland. A specific test for parathyroid adenoma is [[sestamibi parathyroid scintigraphy]], the sestamibi scan. Surgery is the mainstay of treatment for parathyroid cancer.
== Pathophysiology==
* A parathyroid adenoma is a [[adenoma|benign tumor]] of the [[parathyroid gland]]. It generally causes [[hyperparathyroidism]]; there are very few reports of parathyroid adenomas that were not associated with hyperparathyroidism.<ref name=sekine>{{cite journal |author=Sekine O, Hozumi Y, Takemoto N, Kiyozaki H, Yamada S, Konishi F |title=Parathyroid adenoma without hyperparathyroidism |journal=Japanese Journal of Clinical Oncology |volume=34 |issue=3 |pages=155–8 |date=March 2004 |pmid=15078912 |doi=10.1093/jjco/hyh028}}</ref>
* A human being usually has four parathyroid glands located on the back surface of the [[thyroid]] in the neck. The parathyroids secrete [[parathyroid hormone]] (PTH), which increases the concentration of [[calcium]] in the blood by inducing the [[bone]]s to release calcium into the blood and the [[kidney]]s to reabsorb it from the urine. When a parathyroid adenoma causes hyperparathyroidism, more parathyroid hormone is secreted, causing the calcium concentration of the blood to rise, resulting in [[Hypercalcaemia|hypercalcemia]].<ref name=fel>{{cite journal |author=Felsenfeld AJ, Rodríguez M, Aguilera-Tejero E |title=Dynamics of parathyroid hormone secretion in health and secondary hyperparathyroidism |journal=Clinical Journal of the American Society of Nephrology |volume=2 |issue=6 |pages=1283–305 |date=November 2007 |pmid=17942777 |doi=10.2215/CJN.01520407}}</ref>
=== Genetics ===
* Parathyroid adenoma can be associated with overexpression of the [[cyclin D1]] gene.<ref>{{cite journal |author=Hsi ED, Zukerberg LR, Yang WI, Arnold A |title=Cyclin D1/PRAD1 expression in parathyroid adenomas: an immunohistochemical study |journal=The Journal of Clinical Endocrinology and Metabolism |volume=81 |issue=5 |pages=1736–9 |date=May 1996 |pmid=8626826 |doi=10.1210/jcem.81.5.8626826}}</ref>
===Gallery===
<gallery>
Image:Adenoma 01.jpg|Intermediate/Low magnification micrograph of parathyroid adenoma. H&E stain. Features: Single cell population forming a single mass. Thin capsule. No adipose tissue. +/-Glandular architecture (which may lead to confusion with thyroid tissue). Normal parathyroid gland with prominent adipose tissue is seen on the right of the image.<ref>Parathyroid adenoma. Wikipedia(2015). https://en.wikipedia.org/wiki/Parathyroid_adenoma Accessed on December 29, 2015</ref>
</gallery>

== Risk Factors ==
* The following risk factors may increase a person’s chance of developing a parathyroid adenoma:
:* [[Multiple endocrine neoplasia type 1]] (MEN 1)<ref>Parathyroid adenoma. Canadian cancer society(2015). http://www.cancer.ca/en/cancer-information/cancer-type/parathyroid/parathyroid-cancer/benign-tumours/?region=on Accessed on December 29, 2015</ref>
:* Familial isolated hyperparathyroidism(FIHP)
:* [[Hyperparathyroidism]]–jaw tumour (HPT-JT) syndrome
:* [[Radiation therapy]] to the head or neck

==Diagnosis==
===Diagnostic Criteria===
[[Hyperparathyroidism]] is confirmed by blood tests such as calcium and parathormone levels.<ref>Parathyroid adenoma. Wikipedia(2015). https://en.wikipedia.org/wiki/Parathyroid_adenoma Accessed on December 29, 2015</ref>

=== Symptoms ===
* [[Fatigue]]
* [[Confusion]]
* [[Nausea]]
* [[Constipation]]
* [[Kidney stones]]
* [[Muscle aches]]
* [[Bone fracture]]

===CT===
* CT can be very useful for localising the lesion when the site is not known. Shows increased uptake with agents such as Technetium (Tc) 99m Sestamibi (MIBI) (commonly used agent) and Tc-99m tetrofosmin. The nuclear medicine scan can be fused with the CT scan as a SPECT scan increase diagnostic accuracy.
:* In the past CT was more commonly used in the setting of a failed parathyroidectomy for the detection of suspected ectopic glands (often mediastinal). However, in recent years, 4D-CT has emerged as valuable modality especially in the era of minimally invasive parathyroidectomy. This type of surgery requires precise localization with anatomical detail and a confident diagnosis of parathyroid adenoma. 4DCT has been shown to be more sensitive than sonography and scintigraphy for preoperative localisation of parathyroid adenomas.
* Enhancement on 4D-CT
:* On 4D-CT parathyroid adenomas typically demonstrate intense enhancement on arterial phase, washout of contrast on delayed phase, and low attenuation on non-contrast imaging.
* Secondary signs include:
:* The polar vessel which represents an enlarged feeding artery or draining vein to the hypervascular parathyroid adenoma
:* A larger lesion size increases the confidence of diagnosis
:* Parathyroid adenomas can also have cystic change

===MRI===
* MRI is infrequently utilized in initial work up because of lower spatial resolution and artifacts. Adenomas can show variable signal intensity on MRI. Reported signal characteristics include:
* T1
:* Typically intermediate to low signal
:* Subacute haemorrhage can cause high signal intensiy
:* Fibrosis or old haemorrhage can cause low signal intensity
* T2
:* Typically hyperintense
:* Subacute haemorrhage can cause high signal intensity
:* Fibrosis or old haemorrhage can cause low signal intensity
* Since most lesions demonstrate high T2 signal intensity, the addition of contrast for MR scanning does not significantly increase detection.

===Ultrasound===
* Ultrasound is one of most commonly used initial imaging modalities.
:* Greyscale
::* Most nodules need to be >1cm to be confidently seen on ultrasound
::* Parathyroid adenomas tend to be homogeneously hypoechoic to the overlying thyroid gland
::* An echogenic thyroid capsule separating the thyroid from the parathyroid may be seen
* Doppler ultrasound
:* Can commonly show a characteristic extrathyroidal feeding vessel (typically a branch off the inferior thyroidal artery), which enters the parathyroid gland at one of the poles. Internal vascularity is also commonly seen in a peripheral distribution. This feeding artery tends to branch around the periphery of the gland before penetration. This feature can give a characteristic arc or rim of vascularity. The overlying thyroid gland may also show an area of asymmetric hypervascularity that may help to locate an underlying adenoma.

===Other Imaging Findings===
* A specific test for parathyroid adenoma is sestamibi parathyroid scintigraphy, the sestamibi scan. This [[Nuclear medicine|nuclear imaging technique]] reveals the presence and location of pathological parathyroid tissue.<ref>{{cite journal |author=Goldstein RE, Billheimer D, Martin WH, Richards K |title=Sestamibi scanning and minimally invasive radioguided parathyroidectomy without intraoperative parathyroid hormone measurement |journal=Annals of Surgery |volume=237 |issue=5 |pages=722–30; discussion 730–1 |date=May 2003 |pmid=12724639 |pmc=1514518 |doi=10.1097/01.SLA.0000064362.58751.59}}</ref>
===Gallery===
<gallery>
Image:Parathyroid adenoma ultrasound.jpg|Sharply marginated, hypoechogenic lesion at the dorsal lower pole of the left thyroid lobe.<ref name=radio01>Image courtesy of Dr Roberto Schubert. [http://www.radiopaedia.org Radiopaedia] (original file [http://radiopaedia.org/cases/parathyroid-adenoma-5 ‘’here’’]). [http://radiopaedia.org/licence Creative Commons BYSANC]</ref>

Image:Tc99m MIBI scintigraphy.jpg|High magnification micrograph of a parathyroid adenoma. H&E stain. Features: Single cell population forming a single mass. Thin capsule. No adipose tissue. +/-Glandular architecture (which may lead to confusion with thyroid tissue). Normal parathyroid gland with prominent adipose tissue is seen on the right of the image<ref name=radio01> Image courtesy of Dr Roberto Schubert. [http://www.radiopaedia.org Radiopaedia] (original file [http://radiopaedia.org/cases/parathyroid-adenoma-5 ‘’here’’]). [http://radiopaedia.org/licence Creative Commons BYSANC]</ref>

Image:Parathyroid-adenoma-001.jpg|Parathyroid adenoma<ref name=radio01> Image courtesy of Dr Roberto Schubert. [http://www.radiopaedia.org Radiopaedia] (original file [http://radiopaedia.org/cases/parathyroid-adenoma-5 ‘’here’’]). [http://radiopaedia.org/licence Creative Commons BYSANC]</ref>

Image:Parathyroid-adenoma-002.jpg|Parathyroid adenoma<ref name=radio01> Image courtesy of Dr Roberto Schubert. [http://www.radiopaedia.org Radiopaedia] (original file [http://radiopaedia.org/cases/parathyroid-adenoma-5 ‘’here’’]). [http://radiopaedia.org/licence Creative Commons BYSANC]</ref>

Image:Parathyroid-adenoma-101.jpg|Parathyroid adenoma<ref name=radio01> Image courtesy of Dr Roberto Schubert. [http://www.radiopaedia.org Radiopaedia] (original file [http://radiopaedia.org/cases/parathyroid-adenoma-5 ‘’here’’]). [http://radiopaedia.org/licence Creative Commons BYSANC]</ref>

Image:Parathyroid-adenoma-102.jpg|Parathyroid adenoma<ref name=radio01> Image courtesy of Dr Roberto Schubert. [http://www.radiopaedia.org Radiopaedia] (original file [http://radiopaedia.org/cases/parathyroid-adenoma-5 ‘’here’’]). [http://radiopaedia.org/licence Creative Commons BYSANC]</ref>

Image:Parathyroid-adenoma-103.jpg|Parathyroid adenoma<ref name=radio01> Image courtesy of Dr Roberto Schubert. [http://www.radiopaedia.org Radiopaedia] (original file [http://radiopaedia.org/cases/parathyroid-adenoma-5 ‘’here’’]). [http://radiopaedia.org/licence Creative Commons BYSANC]</ref>

</gallery>

== Treatment ==
===Surgery===
* [[Surgery]] is the only cure for parathyroid adenomas.<ref name=ds/> It is successful about 95% of the time. [[Parathyroidectomy]] is the removal of the affected gland(s). The standard of treatment of primary hyperparathyroidism was formerly a surgical technique called bilateral neck exploration, in which the neck was opened on both sides, the parathyroids were identified, and the affected tissue was removed.<ref name=bell>{{cite journal |author=Bellantone R, Raffaelli M, DE Crea C, Traini E, Lombardi CP |title=Minimally-invasive parathyroid surgery |journal=Acta Otorhinolaryngologica Italica |volume=31 |issue=4 |pages=207–15 |date=August 2011 |pmid=22065831 |pmc=3203720}}</ref> By the 1980s, unilateral exploration became more common.<ref name=bell/> Parathyroidectomy can now be performed in a minimally invasive fashion, mainly because imaging techniques can pinpoint the location of the tissue.<ref name=bell/> Minimally invasive techniques include smaller open procedures, radio-guided and video-assisted procedures, and totally [[Endoscopy|endoscopic]] surgery.<ref name=bell/>
* Before surgery is attempted, the affected glandular tissue must be located. Though the parathyroid glands are usually located on the back of the thyroid, their position is variable. Some people have one or more parathyroid glands elsewhere in the neck anatomy or in the chest. About 10% of parathyroid adenomas are [[Ectopia (medicine)|ectopic]], located not along the back of the thyroid but elsewhere in the body, sometimes in the [[mediastinum]] of the chest.<ref name=ds>{{cite journal |doi=10.4103/0973-0354.96061 |title=Ectopic parathyroid adenoma |journal=Thyroid Research and Practice |volume=9 |issue=2 |pages=68–70 |year=2012 |last1=Dsouza |first1=Caren |last2=Gopalakrishnan |last3=Bhagavan |first3=KR |last4=Rakesh |first4=K}}</ref> This can make them difficult to locate, so various imaging techniques are used, such as the sestamibi scan, single-photon emission computed tomography (SPECT), [[Medical ultrasonography|ultrasound]], [[Magnetic resonance imaging|MRI]],<ref name=ds/> and CT scans.<ref name=ds/><ref>{{cite journal |author=Zald PB, Hamilton BE, Larsen ML, Cohen JI |title=The role of computed tomography for localization of parathyroid adenomas |journal=The Laryngoscope |volume=118 |issue=8 |pages=1405–10 |date=August 2008 |pmid=18528308 |doi=10.1097/MLG.0b013e318177098c}}</ref>

==References==
{{Reflist|2}}

[[Category:Disease]]
[[Category:Oncology]]
[[Category:Endocrine system]]
[[Category:Endocrinology]]
[[Category:Otolaryngology]]
[[Category:Disease]]
[[Category:Genetic disorders]]

==Related Chapters==
*[[Hyperparathyroidism]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Endocrinology]]
[[Category:Surgery]]

Multiple endocrine neoplasia type 2 CT

2019-05-30T22:49:04Z

Ahmed Younes: /* Pheochromocytoma */

__NOTOC__
{{Multiple endocrine neoplasia type 2}}
{{CMG}}; {{AE}} {{Ammu}}

==Overview==
Neck [[CT]] scan may be helpful in the [[diagnosis]] of multiple endocrine neoplasia type 2. Findings on [[CT]] scan suggestive of multiple endocrine neoplasia type 2 include irregular dense calcific foci within [[thyroid]], [[ectopic]] [[Mediastinum|mediastinal]] [[gland]], and heterogeneous masses with areas of [[necrosis]] within [[adrenal gland]].

==CT==
===Medullary Thyroid Carcinoma===
* Both primary and [[metastatic]] lesions usually have irregular dense calcific foci within.<ref name="pmid7046403">{{cite journal| author=McCook TA, Putman CE, Dale JK, Wells SA| title=Review: Medullary carcinoma of the thyroid: radiographic features of a unique tumor. | journal=AJR Am J Roentgenol | year= 1982 | volume= 139 | issue= 1 | pages= 149-55 | pmid=7046403 | doi=10.2214/ajr.139.1.149 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7046403 }} </ref>
* In the [[chest]], bullae formation and [[pulmonary fibrosis]] might happen as a result of a [[desmoplastic]] reaction.

===Parathyroid Carcinoma===
* Three-dimensional [[Single photon emission tomography|single-photon emission CT]] ([[Single photon emission computed tomography|SPECT]]) is used for preoperative [[adenoma]] localization.
* In the past [[CT]] was more commonly used in the setting of a failed [[parathyroidectomy]] for the detection of suspected [[ectopic]] [[gland]]s (often [[Mediastinum|mediastinal]]).<ref name="pmid17515397">{{cite journal| author=Johnson NA, Tublin ME, Ogilvie JB| title=Parathyroid imaging: technique and role in the preoperative evaluation of primary hyperparathyroidism. | journal=AJR Am J Roentgenol | year= 2007 | volume= 188 | issue= 6 | pages= 1706-15 | pmid=17515397 | doi=10.2214/AJR.06.0938 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17515397 }} </ref>
* However, in recent years, [[Hyperparathyroidism CT|4D-CT]] has emerged as valuable modality especially in the era of [[Hyperparathyroidism surgery|minimally invasive parathyroidectomy]]. This type of [[surgery]] requires precise localization with anatomical detail and a confident [[diagnosis]] of [[parathyroid adenoma]]. [[Hyperparathyroidism CT|4D-CT]] has been shown to be more sensitive than [[sonography]] and [[scintigraphy]] for preoperative localisation of [[parathyroid adenoma]]s.<ref name="Radiopaedia">{{cite web | title = Radiopedia 2015 Parathyroid adenoma [Dr Bruno Di Muzio and Dr Yuranga Weerakkody]| url = http://radiopaedia.org/articles/parathyroid-adenoma }}</ref>
====Enhancement on 4D-CT====
* On 4D-[[CT]] [[parathyroid adenoma]]s typically demonstrate intense enhancement on arterial phase, washout of contrast on delayed phase and low attenuation on non-contrast imaging.
* Secondary signs include the following:
:* The polar [[vessel]] which represents an enlarged feeding [[artery]] or draining [[vein]] to the hypervascular [[parathyroid adenoma]].
:* A larger [[lesion]] size increases the confidence of [[diagnosis]].
:* [[Parathyroid adenoma]]s can also have [[cystic]] change.

===Pheochromocytoma===
* [[CT]] is the first imaging modality to be used, with an overall [[Sensitivity (tests)|sensitivity]] of 89%. This is on account of 98% of [[tumor]]s being located within the [[abdomen]] and 90% limited to the [[adrenal gland]]s.<ref>{{cite book | last = Blake | first = Michael | title = Adrenal imaging | publisher = Humana Press | location = Totowa, NJ | year = 2009 | isbn = 193411586X }}</ref><ref name="Radiopaedia">{{cite web | title = Radiopedia 2015 Pheochromocytoma [Dr Matt A. Morgan and Dr Frank Gaillard]| url = http://radiopaedia.org/articles/pheochromocytoma-2 }}</ref>
* [[Pheochromocytoma]] is usually large, heterogeneous masses with areas of [[necrosis]] and [[cystic]] change.
* [[Pheochromocytoma]] typically enhance avidly.<ref name="pmid15486252">{{cite journal| author=Blake MA, Kalra MK, Maher MM, Sahani DV, Sweeney AT, Mueller PR et al.| title=Pheochromocytoma: an imaging chameleon. | journal=Radiographics | year= 2004 | volume= 24 Suppl 1 | issue= | pages= S87-99 | pmid=15486252 | doi=10.1148/rg.24si045506 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15486252 }} </ref>
* [[Pheochromocytoma]] tend to enhance more on the [[Portal venous system|portal venous]] phase than the [[arterial]] phase.
* 110 HU of enhancement on the [[arterial]] phase is compatible with [[pheochromocytoma]]; hypervascular [[metastases]] could also be considered in an appropriate setting.
* It should be noted, that in patients with suspected [[pheochromocytoma]]s contrast may be contraindicated as it could precipitate a [[hypertensive crisis]].
<gallery>
Image:Pheochromocytoma CT.jpg|Pheochromocytoma Image courtesy of Dr Paresh K Desai<ref name=radio01>Image courtesy of Dr Paresh K Desai. [http://www.radiopaedia.org Radiopaedia] (original file[http://radiopaedia.org/cases/6819‘’here’’]).[http://radiopaedia.org/licence Creative Commons BY-SA-NC]</ref>
[http://radiopaedia.org/licence Creative Commons BY-SA-NC]</ref>
Image:Pheochromocytoma CT 2.jpg|Pheochromocytoma Image courtesy of Dr Frank Gaillard<ref name=radio02>Image courtesy of Dr Frank Gaillard. [http://www.radiopaedia.org Radiopaedia] (original file[http://radiopaedia.org/cases/6478‘’here’’]).[http://radiopaedia.org/licence Creative Commons BY-SA-NC]</ref>
Image:Pheochromocytoma CT 04.jpg|Image courtesy of Dr Roberto Schubert<ref name=radio04>Image courtesy of Dr Roberto Schubert. [http://www.radiopaedia.org Radiopaedia] (original file[http://radiopaedia.org/cases/16148‘’here’’]).[http://radiopaedia.org/licence Creative Commons BY-SA-NC]</ref>
Image:Pheochromocytoma CT 05.jpg|Image courtesy of Dr Nafisa Shakir Batta.<ref name=radio03>Image courtesy of Dr Nafisa Shakir Batta. [http://www.radiopaedia.org Radiopaedia] (original file[http://radiopaedia.org/cases/29512‘’here’’]).[http://radiopaedia.org/licence Creative Commons BY-SA-NC]</ref>
</gallery>

==References==
{{reflist|2}}
[[Category:Endocrinology]]
[[Category:Oncology]]
[[Category:Diseases]]
[[Category:Medicine]]
[[Category:Endocrinology]]
[[Category:Up-To-Date]]
[[Category:Radiology]]]

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Endocrinology]]
[[Category:Surgery]]

Multiple endocrine neoplasia type 2 physical examination

2019-05-30T22:46:06Z

Ahmed Younes: /* HEENT */

__NOTOC__
{{Multiple endocrine neoplasia type 2}}
{{CMG}}; {{AE}} {{Ammu}}

==Overview==
Patients with multiple endocrine neoplasia type 2 usually appear tall with disproportionately elongated extremities. Physical examination of patients with multiple endocrine neoplasia type 2 is usually remarkable for episodic [[hypertension]], [[thyromegaly]], and [[anxiety]].

==Physical Examination==
===Appearance of the Patient===
* Patient may be tall and thin. The patient may have "[[Marfan syndrome|marfanoid]]" body build with disproportionately elongated extremities.

===Vitals===
*[[Fever]]

*[[Tachycardia]]

*The [[pulse]] is irregularly irregular

*Episodic [[hypertension]]

*[[Tachypnea]]

===Skin===
* Swelling of neck

===HEENT===

* Numerous yellowish-white, sessile, painless nodules on the [[sclera]] and eyelids
* Dry [[eye]]s may be present
* [[Lymph nodes]]
* [[Thyromegaly]]
* [[Dysphagia]]

===Heart===
*A [[thrill]] may be present

===Neurologic===
* [[Altered mental status]]
* [[Anxiety]]

==References==
{{reflist|2}}
[[Category:Endocrinology]]
[[Category:Oncology]]
[[CAtegory:Diseases]]
[[Category:Medicine]]
[[Category:Endocrinology]]
[[Category:Up-To-Date]]

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Endocrinology]]
[[Category:Surgery]]

Multiple endocrine neoplasia type 2 pathophysiology

2019-05-30T22:44:33Z

Ahmed Younes: /* Medullary Carcinoma of Thyroid */

__NOTOC__
{{Multiple endocrine neoplasia type 2}}
{{CMG}}; {{AE}} {{Ammu}}

==Overview==
Development of multiple endocrine neoplasia type 2 is the result of genetic [[mutation]]s. The pathogenesis of multiple endocrine neoplasia type 2 involves a mutation of the [[RET protooncogene|''RET'' gene]].

==Pathogenesis==
The common feature among the three subtypes of multiple endocrine neoplasia type 2 is a high propensity to develop [[medullary thyroid carcinoma]].
===Multiple Endocrine Neoplasia type 2A===
* Multiple endocrine neoplasia type 2 (MEN2) generally occur in [[endocrine organ]]s (e.g. [[thyroid]], [[parathyroid]], and [[Adrenal gland|adrenals]]), but may also occur in [[endocrine]] [[tissues]] of organs not classically thought of as [[endocrine]].<ref name="Moline">{{cite journal | author = Moline J, Eng C. | title = Multiple endocrine neoplasia type 2: an overview. | journal = Genet Med. | year=2011 | volume=9 | issue=13 | pages=755–64 | pmid = 21552134 | doi =10.1097/GIM.0b013e318216cc6d}}</ref>
* Although many different types of [[hormone]]-producing [[tumor]]s are associated with multiple endocrine neoplasia type 2, the most common manifestation is a form of [[thyroid]] [[cancer]] called [[thyroid cancer#medullary thyroid cancer (MTC)|medullary thyroid carcinoma]]. This [[tumor]] secretes an inactive [[hormone]] called [[calcitonin]]. Many people with this disorder also develop [[pheochromocytoma]], which is a [[tumor]] of the [[adrenal gland]]s (located above each [[kidney]]) that can cause dangerously high [[blood pressure]]. In addition, overactivity of the [[parathyroid gland]] ([[hyperparathyroidism]]) occurs in some cases of [[multiple endocrine neoplasia type 2]]. [[Hyperparathyroidism]] disrupts the normal balance of [[calcium]] in the [[blood]], which can lead to [[kidney stones]], thinning of [[bone]]s, [[weakness]], and [[fatigue]].
* In multiple endocrine neoplasia type 2, primary [[hyperparathyroidism]] occurs in only 10–30% and is usually diagnosed after the third decade of life. It can occur in children but this is rare. It may be the sole clinical manifestation of this syndrome but this is unusual.
* Multiple endocrine neoplasia type 2 associates [[medullary thyroid carcinoma]] with [[pheochromocytoma]] in about 20–50% of cases and with primary [[hyperparathyroidism]] in 5–20% of cases.
* In familial isolated [[medullary thyroid carcinoma]] the other components of the [[disease]] are absent.

===Multiple Endocrine Neoplasia type 2B===
* Multiple endocrine neoplasia type 2B is associated with [[medullary thyroid carcinoma]] and [[pheochromocytoma]] as well as with marfanoid habitus and with [[mucosal]] and [[digestive]] [[neurofibromatosis]].
{| style="border: 0px; font-size: 90%; margin: 3px;" align="center"
|+'''''Clinical features of multiple endocrine neoplasia syndrome'''''
! style="background: #4479BA; width: 120px;" | {{fontcolor|#FFF|Subtype}}
! style="background: #4479BA; width: 550px;" | {{fontcolor|#FFF|Medullary Thyroid Carcinoma}}
! style="background: #4479BA; width: 550px;" | {{fontcolor|#FFF|Pheochromocytoma}}
! style="background: #4479BA; width: 550px;" | {{fontcolor|#FFF|Parathyroid Disease}}
|-
! style="background: #F5F5F5;" | Multiple endocrine neoplasia type 2A
! style="background: #F5F5F5;" | 95%
! style="background: #F5F5F5;" | 50%
! style="background: #F5F5F5;" | 20% to 30%
|-
! style="background: #F5F5F5;" | Multiple endocrine neoplasia type 2B
! style="background: #F5F5F5;" | 100%
! style="background: #F5F5F5;" | 50%
! style="background: #F5F5F5;" | Uncommon
|-
! style="background: #F5F5F5;" | Familial medullary thyroid carcinoma
! style="background: #F5F5F5;" | 100%
! style="background: #F5F5F5;" | 0%
! style="background: #F5F5F5;" | 0%
|}

===Genetics===
[[Image:autodominant2.jpg|thumb|center|500px|Autosomal dominent pattern of inheritance - By nih.gov, Public Domain, https://commons.wikimedia.org/w/index.php?curid=1098109]]
* Most cases of multiple endocrine neoplasia type 2 are inherited in an [[autosomal dominant]] pattern, which means affected people may have affected siblings and relatives in successive generations (such as parents and children). An affected person usually has one parent with the condition. Some cases, however, result from new [[mutation]]s in the [[RET proto-oncogene|''RET'' proto-oncogene]]. These cases occur in people with no history of the disorder in their family.
[[File:RET kinase domain.jpg|thumb|center|500px|RET kinase domain - [http://www.scielo.br/scielo.php?script=sci_abstract&pid=S1807-59322012001300014&lng=en&nrm=iso&tlng=en Source: Molecular mechanisms of RET receptor-mediated oncogenesis in multiple endocrine neoplasia 2 (Clinics)]]]
* Germline [[mutation]]s are responsible for sporadic multiple endocrine neoplasia type 2, while [[mutation]]s in the [[cysteine]] residues in the [[exon]]s of the [[RET gene|RET]] protein product are common in familial multiple endocrine neoplasia type 2.
* Most cases of multiple endocrine neoplasia type 2, derive from a variation in the [[RET proto-oncogene|''RET'' proto-oncogene]], and are specific for cells of [[neural crest]] origin.
* The [[protein]] produced by the [[RET proto-oncogene|''RET'' proto-oncogene]] plays an important role in the [[TGF-beta]] ([[transforming growth factor beta]]) signaling system. Because the [[TGF-beta]] system operates in [[nervous tissue]]s throughout the [[body]], variations in the [[RET proto-oncogene|''RET'' proto-oncogene]] can have effects in [[nervous tissue]]s throughout the [[body]].
* The [[RET proto-oncogene|''RET'' protooncogene]] is a 21-[[exon]] [[gene]] and encodes for a [[tyrosine kinase]] transmembrane receptor located on [[chromosome]] 10q11.2.<ref>C. Romei, E. Pardi, F. Cetani, and R. Elisei, “Genetic and Clinical Features of Multiple Endocrine Neoplasia Types 1 and 2,” Journal of Oncology, vol. 2012, Article ID 705036, 15 pages, 2012. doi:10.1155/2012/705036</ref>
* Four different ligands have so far been recognized: The [[glial cell line-derived neutrophilic factor]] (GDNF), [[neurturin]] (NTN), persepin (PNS) and [[artemin]] (ART). The interaction is mediated by a ligand-specific coreceptor (e.g., the GFRα-1 is the co-[[receptor]] for the GDNF).
* The receptor is composed of an extracellular domain (EC), with a distal [[cadherin]]-like region and a juxtamembrane [[cysteine]]-rich region, a transmembrane domain (TM) and an [[intracellular]] domain with tyrosine-kinase activity (TK).
The table below summarizes specific ''RET'' codons and their functions.<ref name="pmid22584710">{{cite journal| author=Wagner SM, Zhu S, Nicolescu AC, Mulligan LM| title=Molecular mechanisms of RET receptor-mediated oncogenesis in multiple endocrine neoplasia 2. | journal=Clinics (Sao Paulo) | year= 2012 | volume= 67 Suppl 1 | issue= | pages= 77-84 | pmid=22584710 | doi= | pmc=PMC3328826 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22584710 }} </ref>

{| style="border: 0px; font-size: 90%; margin: 3px;" align="center"
|+'''''Molecular effects of RET mutations in multiple endocrine neoplasia type2'''''
! style="background: #4479BA; width: 120px;" | {{fontcolor|#FFF|Mutation location}}
! style="background: #4479BA; width: 550px;" | {{fontcolor|#FFF|RET codons}}
! style="background: #4479BA; width: 550px;" | {{fontcolor|#FFF|Function of wild type codon}}
! style="background: #4479BA; width: 550px;" | {{fontcolor|#FFF|Mutated effects}}
! style="background: #4479BA; width: 550px;" | {{fontcolor|#FFF|Phenotype}}
|-
! rowspan="2" style="background: #DCDCDC;" |Extracellular [[cysteine]] rich location
! style="background: #F5F5F5;" |
:c609
:c611
:c618
:c620
:c630
! style="background: #F5F5F5;" |Helps to form teritiary structure with the help of disulfide bonds
! style="background: #F5F5F5;" |Alteration in protein folding and maturation
! style="background: #F5F5F5;" |Multiple endocrine neoplasia type 2A and familial [[medullary thyroid carcinoma]] (FMTC)
|-
! style="background: #F5F5F5;" |c634
! style="background: #F5F5F5;" |Formation of intramolecular disulfide bonds
! style="background: #F5F5F5;" |[[Ligand]] independant dimerization of [[receptor]] molecules
! style="background: #F5F5F5;" |Multiple endocrine neoplasia type 2A
|-
! rowspan="6" style="background: #DCDCDC;" |Intracellular [[tyrosine kinase]] domain
! style="background: #F5F5F5;" |
:L790
:Y791
! style="background: #F5F5F5;" |Terminal lobe of ''[[RET proto-oncogene|RET]]'' kinase
! style="background: #F5F5F5;" |Affects [[ATP]] binding and interlobe flexibility
! style="background: #F5F5F5;" |Multiple endocrine neoplasia type 2A and familial medullary thyroid carcinoma (FMTC)
|-
! style="background: #F5F5F5;" |
:E768
! style="background: #F5F5F5;" |Close proximity with [[ATP]] binding site
! style="background: #F5F5F5;" |Alters interactions within the region
! style="background: #F5F5F5;" |Familial [[medullary thyroid carcinoma]] (FMTC)
|-
! style="background: #F5F5F5;" |
:V804
! style="background: #F5F5F5;" |Gatekeeper residue that regulates access to [[ATP]] binding site
! style="background: #F5F5F5;" |Alters interactions within the region
! style="background: #F5F5F5;" |Familial [[medullary thyroid carcinoma]] (FMTC)
|-
! style="background: #F5F5F5;" |
:S891
! style="background: #F5F5F5;" |C terminal lobe of [[kinase]]
! style="background: #F5F5F5;" |Alters activation of loop conformation
! style="background: #F5F5F5;" |Multiple endocrine neoplasia type 2A and familial [[medullary thyroid carcinoma]] (FMTC)
|-
! style="background: #F5F5F5;" |
:A883
! style="background: #F5F5F5;" |Situated next to activated loop
! style="background: #F5F5F5;" |Local conformational change
! style="background: #F5F5F5;" |Multiple endocrine neoplasia type 2B
|-
! style="background: #F5F5F5;" |
:M918
! style="background: #F5F5F5;" |Substrate binding pocket of the kinase
! style="background: #F5F5F5;" |Alters [[protein]] conformation
! style="background: #F5F5F5;" |Multiple endocrine neoplasia type 2B
|}
* Multiple endocrine neoplasia type 2 generally results from a gain-of-function variant of a ''[[RET proto-oncogene|RET]]'' gene. Other [[disease]]s, such as [[Hirschsprung disease]], result from loss-of-function variants.
* When inherited, multiple endocrine neoplasia type 2 is transmitted in an [[autosomal dominant]] pattern, which means affected people have one affected parent, and possibly-affected siblings and children. Some cases, however, result from spontaneous new mutations in the [[RET gene|''RET'' gene]]. These cases occur in people with no family history of the disorder. In multiple endocrine neoplasia type 2B, for example, about half of all cases arise as spontaneous new [[mutation]]s.
* Activating germline [[point mutation]]s of the ''RET'' [[proto-oncogene]] are causative events in multiple endocrine neoplasia type 2A, multiple endocrine neoplasia type 2B, and familial [[medullary thyroid carcinoma]] (FMTC). ''[[RET]]'' mutations have been found to be widely distributed not only among the 5 [[cysteine]] codons 609, 611, 618, 620, and 634 but also in other noncysteine codons, such as codon 804 in exon 14, codon 883 in exon 15, and others.
* The following figure depicts the structure and mutation of RET receptor.<ref name="pmid22584710">{{cite journal| author=Wagner SM, Zhu S, Nicolescu AC, Mulligan LM| title=Molecular mechanisms of RET receptor-mediated oncogenesis in multiple endocrine neoplasia 2. | journal=Clinics (Sao Paulo) | year= 2012 | volume= 67 Suppl 1 | issue= | pages= 77-84 | pmid=22584710 | doi= | pmc=PMC3328826 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22584710 }} </ref>
[[File:Genetics of MEN 2.png|thumb|center|500px|Structure, activation and oncogenic mutation of RET receptor. Figure A depicts location of oncogenic mutations of RET recpetor. RET protein has cystine rich extracellular domain, cadherin homology domain, transmembrane domain and an intracellular tyrosine kinase domain. FIgure B depicts RET activation - [http://www.scielo.br/scielo.php?script=sci_abstract&pid=S1807-59322012001300014&lng=en&nrm=iso&tlng=en Source: Molecular mechanisms of RET receptor-mediated oncogenesis in multiple endocrine neoplasia 2 (Clinics)]]]

===RET Activation===
* Dimerization of [[RET proto-oncogene|''RET'' proto-oncogene]] mediated through formation of multicomponent complex. [[RET proto-oncogene|''RET'' proto-oncogene]] is activated by binding both a soluble ligand and a non signaling [[extracellular]] co-receptor. ''[[RET gene|RET]]'' activation leads to phosphorylation of multiple [[intracellular]] [[tyrosine kinase]].
[[File:Mutations specificities.jpg|thumb|center|500px|MEN type 2 mutations - [http://www.scielo.br/scielo.php?script=sci_abstract&pid=S1807-59322012001300014&lng=en&nrm=iso&tlng=en Source: Molecular mechanisms of RET receptor-mediated oncogenesis in multiple endocrine neoplasia 2 (Clinics)]]]

==Associated Conditions==
* Some of the [[disease]]s specific to the [[gene]]s of multiple endocrine neoplasia type 2 are as follows.<ref name="pmid22584710">{{cite journal| author=Wagner SM, Zhu S, Nicolescu AC, Mulligan LM| title=Molecular mechanisms of RET receptor-mediated oncogenesis in multiple endocrine neoplasia 2. | journal=Clinics (Sao Paulo) | year= 2012 | volume= 67 Suppl 1 | issue= | pages= 77-84 | pmid=22584710 | doi= | pmc=PMC3328826 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22584710 }} </ref>
{| style="border: 0px; font-size: 90%; margin: 3px;" align="center"
|+'''''Associated tumors'''''
! style="background: #4479BA; width: 120px;" | {{fontcolor|#FFF|Subtype}}
! style="background: #4479BA; width: 550px;" | {{fontcolor|#FFF|Associated diseases}}
|-
! style="background: #F5F5F5;" |Multiple endocrine neoplasia type 2A
! style="background: #F5F5F5;" |Cutaneous lichen [[amyloidosis]], [[Hirschsprung disease]]
|-
! style="background: #F5F5F5;" |Multiple endocrine neoplasia type 2B
! style="background: #F5F5F5;" |Ganglioneuromatosis, marfanoid habitus
|-
! style="background: #F5F5F5;" |Familial medullary thyroid carcinoma (FMTC)
! style="background: #F5F5F5;" |Rare diseases
|}

===Gross Pathology===
<gallery>
Image:Bilateral pheo MEN2.jpg|ADRENAL GLAND: BILATERAL PHEOCHROMOCYTOMA Cross section of bilateral pheochromocytomas from a 30-year-old man with MEN syndrome type IIa. The right adrenal tumor weighed 168 g and the left 220 g. Note the distinct multinodular, multicentric pattern of growth on both sides [https://upload.wikimedia.org/wikipedia/commons/5/5f/Bilateral_pheo_MEN2.jpg Source: Wikimedia Commons]
Image:Pheochromocytoma 03.jpeg|Pheochromocytoma, Image courtesy of Dr Frank Gaillard<ref name=radio02>Image courtesy of Dr Frank Gaillard. [http://www.radiopaedia.org Radiopaedia] (original file[http://radiopaedia.org/cases/10816‘’here’’]).[http://radiopaedia.org/licence Creative Commons BY-SA-NC]</ref>
Image:Pheochromocytoma 04.JPG|Pheochromocytoma, Image courtesy of Dr Frank Gaillard<ref name=radio02>Image courtesy of Dr Frank Gaillard. [http://www.radiopaedia.org Radiopaedia] (original file[http://radiopaedia.org/cases/10816‘’here’’]).[http://radiopaedia.org/licence Creative Commons BY-SA-NC]</ref>
</gallery>

===Microscopic Pathology===
====Medullary Carcinoma of Thyroid====
* Nests of [[C cell]]s invading the [[basement membrane]] and infiltrating [[thyroid]] follicles
<gallery>
Image:Pheochromocytoma histology.jpg|Pheochromocytoma, Case courtesy of Dr Andrew Ryan, [http://radiopaedia.org/ Radiopaedia.org From the case <a href="http://radiopaedia.org/cases/22683">rID: 22683]
</gallery>

===Histopathological Video===
====Video====
{{#ev:youtube|P2uPUbDPbuI}}

{{#ev:youtube|7yjxG3KmX98}}

{{#ev:youtube|crwGfnWKEZ8}}

==References==
{{reflist|2}}
[[Category:Endocrinology]]
[[Category:Oncology]]
[[CAtegory:Diseases]]
[[Category:Medicine]]
[[Category:Endocrinology]]
[[Category:Up-To-Date]]

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Endocrinology]]
[[Category:Surgery]]

Insulinoma

2019-05-30T22:38:38Z

Ahmed Younes:

__NOTOC__
{{Insulinoma}}

'''For patient information click [[{{PAGENAME}} (patient information)|here]]'''

{{CMG}}; {{AE}}{{ADS}}

{{SK}} Pancreatic beta cell tumor; tumor of beta cells; beta cell tumor; cancer of beta cells
==[[Insulinoma overview|Overview]]==

==[[Insulinoma historical perspective|Historical Perspective]]==

==[[Insulinoma classification|Classification]]==

==[[Insulinoma pathophysiology|Pathophysiology]]==

==[[Insulinoma causes|Causes]]==

==[[Insulinoma differential diagnosis|Differentiating Insulinoma from other Diseases]]==

==[[Insulinoma epidemiology and demographics|Epidemiology and Demographics]]==

==[[Insulinoma risk factors|Risk Factors]]==

==[[Insulinoma screening|Screening]]==

==[[Insulinoma natural history, complications and prognosis|Natural History, Complications and Prognosis]]==

==Diagnosis==
[[Insulinoma staging|Staging]] | [[Insulinoma history and symptoms|History and Symptoms]] | [[Insulinoma physical examination|Physical Examination]] | [[Insulinoma laboratory tests|Laboratory Findings]] | [[Insulinoma CT|CT]] | [[Insulinoma MRI|MRI]] | [[Insulinoma ultrasound|Ultrasound]] | [[Insulinoma other imaging findings|Other Imaging Findings]] | [[Insulinoma other diagnostic studies|Other Diagnostic Studies]]

==Treatment==
[[Insulinoma medical therapy|Medical Therapy]] | [[Insulinoma surgery|Surgery]] | [[Insulinoma primary prevention|Primary Prevention]] | [[Insulinoma secondary prevention|Secondary Prevention]] | [[Insulinoma cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Insulinoma future or investigational therapies|Future or Investigational Therapies]]

==Case Studies==
[[Case study one|Case #1]]

==Related Chapters==
*[[Hypoglycemia]]
*[[Causes of hypoglycemia]]
*[[Pancreas]]
{{Tumor morphology}}
[[de:Insulinom]]
[[es:Insulinoma]]
[[he:אינסולינומה]]
[[ja:インスリノーマ]]
[[nl:Insulinoom]]
[[pl:Guz insulinowy]]
[[pt:Insulinoma]]
[[fi:Insulinooma]]
{{WikiDoc Help Menu}}
{{WikiDoc Sources}}

[[Category:Disease]]
[[Category:Medicine]]
[[Category:Endocrinology]]
[[Category:Oncology]]
[[Category:Mature chapter]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Gastroenterology]]
[[Category:Surgery]]

Glucagonoma other imaging findings

2019-05-30T22:34:18Z

Ahmed Younes: /* Octreoscan */

__NOTOC__
{{Glucagonoma}}
{{CMG}}; {{AE}} {{PSD}}, {{MAD}}
==Overview==
Other imaging studies for glucagonoma include [[positron emission tomography]] scan and somatostatin receptor [[scintigraphy]]. Scintigraphy is less sensitive than [[Positron emission tomography|PET]] scan but still useful.

==Other Imaging Findings==

===Positron Emission Tomography===
* When performing a [[PET scan]], a small amount of a [[radioactive]] medium is injected into the body and absorbed by the [[organs]] or [[tissues]].
* This [[radioactive]] substance gives off energy which in turn is used to produce the images.
* [[Positron emission tomography]] can provide more helpful information than either [[CT-scans|CT]] or [[MRI]] scans. It is useful to see if [[cancer]] has spread to the [[lymph nodes]] and it is also useful to locate where [[cancer]] has spread.

=== Octreoscan ===
* Many glucagonoma's express high levels of [[somatostatin]] receptors and can be imaged with a [[Radiolabel|radiolabeled]] form of the [[somatostatin]] analog [[octreotide]].<ref name="pmid12021920">{{cite journal| author=Papotti M, Bongiovanni M, Volante M, Allìa E, Landolfi S, Helboe L et al.| title=Expression of somatostatin receptor types 1-5 in 81 cases of gastrointestinal and pancreatic endocrine tumors. A correlative immunohistochemical and reverse-transcriptase polymerase chain reaction analysis. | journal=Virchows Arch | year= 2002 | volume= 440 | issue= 5 | pages= 461-75 | pmid=12021920 | doi=10.1007/s00428-002-0609-x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12021920 }}</ref>

* It is less [[Sensitivity (test)|sensitive]] than Ga DOTATATE [[PET scan]] with [[gadolinium]] but still useful if Ga DOTATATE is not available.
<gallery>

Image:Neuroendocrine-tumour-pancreas.jpg|Octreoscan.Case courtesy of Radswiki rID: 11670

</gallery>

==References==
{{reflist|2}}
{{WH}}
{{WS}}
[[Category:Medicine]]
[[Category:Endocrinology]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Gastroenterology]]
[[Category:Surgery]]

Glucagonoma ultrasound

2019-05-30T22:33:33Z

Ahmed Younes: /* Ultrasound */

__NOTOC__
{{Glucagonoma}}
{{CMG}}; {{AE}} {{PSD}}, {{MAD}}

==Overview==
The abdominal ultrasound scan may be helpful in the diagnosis of glucagonoma. Finding on ultrasound scan suggestive of glucagonoma is a hypoechoic [[tumor]] in the distal [[pancreas]]. US-guided [[fine-needle aspiration]] biopsy is a non-operative histologic diagnosis. Intraoperative ultrasonography is used as an adjunct to intraoperative palpation.

==Ultrasound==
The ultrasound findings associated with glucagonoma are:<ref name="pmid21964743">{{cite journal| author=Atiq M, Bhutani MS, Bektas M, Lee JE, Gong Y, Tamm EP et al.| title=EUS-FNA for pancreatic neuroendocrine tumors: a tertiary cancer center experience. | journal=Dig Dis Sci | year= 2012 | volume= 57 | issue= 3 | pages= 791-800 | pmid=21964743 | doi=10.1007/s10620-011-1912-7 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21964743 }}</ref><ref name="pmid12918465">{{cite journal| author=Koike N, Hatori T, Imaizumi T, Harada N, Fukuda A, Takasaki K et al.| title=Malignant glucagonoma of the pancreas diagnoses through anemia and diabetes mellitus. | journal=J Hepatobiliary Pancreat Surg | year= 2003 | volume= 10 | issue= 1 | pages= 101-5 | pmid=12918465 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12918465 }} </ref><ref name="pmid16231278">{{cite journal| author=Hellman P, Hennings J, Akerström G, Skogseid B| title=Endoscopic ultrasonography for evaluation of pancreatic tumours in multiple endocrine neoplasia type 1. | journal=Br J Surg | year= 2005 | volume= 92 | issue= 12 | pages= 1508-12 | pmid=16231278 | doi=10.1002/bjs.5149 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16231278 }}</ref>
* [[Endoscopic]] ultrasonography can detect lesions as small as 2 mm.
* It is more [[Sensitive Skin|sensitive]] than CT or transabdominal [[ultrasonography]] for detection of glucagonoma.
* US-guided [[fine-needle aspiration]] biopsy is a good non-operative way to [[histologically]] diagnose glucagonoma.
* Finding of a hypoechoic [[tumor]] in the distal pancreas on ultrasound is suggestive of glucagonoma.
* Intraoperative [[ultrasonography]] is used as an adjunct to intraoperative palpation.

==References==
{{reflist|2}}
{{WH}}
{{WS}}
[[Category:Medicine]]
[[Category:Endocrinology]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Gastroenterology]]
[[Category:Surgery]]

Glucagonoma CT

2019-05-30T22:32:24Z

Ahmed Younes: /* CT */

__NOTOC__
{{Glucagonoma}}
{{CMG}}; {{AE}} {{PSD}}

==Overview==
Findings on abdominal CT scan suggestive of glucagonoma include a reinforced mass in the [[Arterial|arterial phase]] of the [[CT scan|enhanced CT scan]]. Symptomatic but non functioning glucagonomas are usually large (>3 cm) at the time of diagnosis.

==CT==
The [[CT scan]] findings associated with glucagonoma include:<ref name="pmid25789004">{{cite journal| author=Lv WF, Han JK, Liu X, Wang SC, Pan BO, Xu AO| title=Imaging features of glucagonoma syndrome: A case report and review of the literature. | journal=Oncol Lett | year= 2015 | volume= 9 | issue= 4 | pages= 1579-1582 | pmid=25789004 | doi=10.3892/ol.2015.2930 | pmc=PMC4356379 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25789004 }} </ref><ref name="pmid21067742">{{cite journal| author=Khashab MA, Yong E, Lennon AM, Shin EJ, Amateau S, Hruban RH et al.| title=EUS is still superior to multidetector computerized tomography for detection of pancreatic neuroendocrine tumors. | journal=Gastrointest Endosc | year= 2011 | volume= 73 | issue= 4 | pages= 691-6 | pmid=21067742 | doi=10.1016/j.gie.2010.08.030 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21067742 }}</ref><ref name="pmid9423664">{{cite journal| author=Paulson EK, McDermott VG, Keogan MT, DeLong DM, Frederick MG, Nelson RC| title=Carcinoid metastases to the liver: role of triple-phase helical CT. | journal=Radiology | year= 1998 | volume= 206 | issue= 1 | pages= 143-50 | pmid=9423664 | doi=10.1148/radiology.206.1.9423664 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9423664 }}</ref><ref name="pmid9574609">{{cite journal| author=Legmann P, Vignaux O, Dousset B, Baraza AJ, Palazzo L, Dumontier I et al.| title=Pancreatic tumors: comparison of dual-phase helical CT and endoscopic sonography. | journal=AJR Am J Roentgenol | year= 1998 | volume= 170 | issue= 5 | pages= 1315-22 | pmid=9574609 | doi=10.2214/ajr.170.5.9574609 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9574609 }}</ref><ref name="pmid20231629">{{cite journal| author=Wang SC, Parekh JR, Zuraek MB, Venook AP, Bergsland EK, Warren RS et al.| title=Identification of unknown primary tumors in patients with neuroendocrine liver metastases. | journal=Arch Surg | year= 2010 | volume= 145 | issue= 3 | pages= 276-80 | pmid=20231629 | doi=10.1001/archsurg.2010.10 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20231629 }}</ref>
* CT scans are used to determine the location of the [[tumor]], show the [[organs]] nearby, determining the stage of [[cancer]] and in determining whether [[surgery]] is a good treatment option.
* Spiral multi phasic contrast-enhanced CT is recommended.
* [[Sensitivity]] is greater than 80 percent but it is decreased for [[tumors]] smaller than 2 cm.
* With contrast, glucagonomas often enhance with [[iodinated contrast]] during the early [[arterial]] phase with washout during the [[portal vein|portal venous]] imaging phase.
* [[Liver]] [[metastases]] may appear isodense with the [[liver]] on a non-contrasted study.
* [[Symptomatic]] but [[Nonfunctioning adenoma|nonfunctioning]] glucagonomas are usually large (>3 cm) at the time of diagnosis.

==References==
{{reflist|2}}

{{WH}}
{{WS}}
[[Category:Medicine]]
[[Category:Endocrinology]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Gastroenterology]]
[[Category:Surgery]]

Glucagonoma history and symptoms

2019-05-30T22:31:22Z

Ahmed Younes: /* Less common symptoms include: */

__NOTOC__
{{Glucagonoma}}
{{CMG}}; {{AE}} {{PSD}}, {{MAD}}

==Overview==
Symptoms of glucagonoma include [[necrolytic migratory erythema]], [[weight loss]], [[glucose intolerance]], [[cheilosis]], [[stomatitis]], [[diarrhea]], [[polyuria]], and [[polydipsia]]. A positive family history of [[multiple endocrine neoplasia type 1]] may be present.

==History==
* When evaluating a patient for glucagonoma, you should take a detailed history of the presenting symptom (onset, duration, and progression), other associated symptoms, and a thorough review of past medical history.
* Other specific areas of focus when obtaining the history include the family history of predisposing [[genetic disorders]] such as [[multiple endocrine neoplasia type 1|multiple endocrine neoplasia type 1.]]

==Symptoms==

===Common symptoms of glucagonoma===
Common symptoms of glucagonoma include:<ref name="pmid8606627">{{cite journal| author=Wermers RA, Fatourechi V, Wynne AG, Kvols LK, Lloyd RV| title=The glucagonoma syndrome. Clinical and pathologic features in 21 patients. | journal=Medicine (Baltimore) | year= 1996 | volume= 75 | issue= 2 | pages= 53-63 | pmid=8606627 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8606627 }} </ref><ref name="pmid4793623">{{cite journal| author=Wilkinson DS| title=Necrolytic migratory erythema with carcinoma of the pancreas. | journal=Trans St Johns Hosp Dermatol Soc | year= 1973 | volume= 59 | issue= 2 | pages= 244-50 | pmid=4793623 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4793623 }}</ref><ref name="pmid86066272">{{cite journal| author=Wermers RA, Fatourechi V, Wynne AG, Kvols LK, Lloyd RV| title=The glucagonoma syndrome. Clinical and pathologic features in 21 patients. | journal=Medicine (Baltimore) | year= 1996 | volume= 75 | issue= 2 | pages= 53-63 | pmid=8606627 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8606627 }}</ref><ref name="pmid6268399">{{cite journal| author=Stacpoole PW| title=The glucagonoma syndrome: clinical features, diagnosis, and treatment. | journal=Endocr Rev | year= 1981 | volume= 2 | issue= 3 | pages= 347-61 | pmid=6268399 | doi=10.1210/edrv-2-3-347 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6268399 }}</ref>
*[[Necrolytic migratory erythema]] (NME) is a classical symptom observed in patients with glucagonoma and is present in 80% of cases. Associated NME is characterized by the spread of [[Erythematous rash|erythematous blisters]] and swelling across areas subject to greater friction and pressure, including the lower [[abdomen]], [[buttock]]s, [[perineum]], and [[groin]].
*[[Weight loss]]
*[[Glucose intolerance|Glucose intolerance]]

=== Less common symptoms include: ===
Less common symptoms of glucagonoma include:<ref name="pmid62683992">{{cite journal| author=Stacpoole PW| title=The glucagonoma syndrome: clinical features, diagnosis, and treatment. | journal=Endocr Rev | year= 1981 | volume= 2 | issue= 3 | pages= 347-61 | pmid=6268399 | doi=10.1210/edrv-2-3-347 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6268399 }}</ref><ref name="pmid15201270">{{cite journal| author=Chang-Chretien K, Chew JT, Judge DP| title=Reversible dilated cardiomyopathy associated with glucagonoma. | journal=Heart | year= 2004 | volume= 90 | issue= 7 | pages= e44 | pmid=15201270 | doi=10.1136/hrt.2004.036905 | pmc=1768315 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15201270 }}</ref><ref name="pmid22350605">{{cite journal| author=Cheema A, Weber J, Strosberg JR| title=Incidental detection of pancreatic neuroendocrine tumors: an analysis of incidence and outcomes. | journal=Ann Surg Oncol | year= 2012 | volume= 19 | issue= 9 | pages= 2932-6 | pmid=22350605 | doi=10.1245/s10434-012-2285-7 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22350605 }}</ref>
*[[Cheilosis]]
*[[Hemorrhage retroperitoneal|Intraabdominal hemorrhage]]
*[[Venous thrombosis]]
*[[Stomatitis]]
*[[Diarrhea]]
*[[Polyuria]]
*[[Polydipsia]]
*[[Polyphagia]]
*[[Blurred vision]]
*[[Neuropsychiatric|Neuropsychiatric manifestations]] include [[depression]], [[dementia]], [[psychosis]], and [[agitation]]
*[[Dilated cardiomyopathy]]

* Some patients do not present with [[Hormonal|hormonal symptoms]] but present with [[Metastasis|metastatic symptoms]] in other [[organs]] and mainly the [[liver]].
**These symptoms include [[jaundice]], [[edema]], and [[abdominal pain]].
**There is usually high level of substances such as [[Chromogranin|chromogranins]], [[enolase]], [[pancreatic polypeptide]], and [[ghrelin]] in patients with [[Metastasis|metastases]].

* Some [[tumors]] can develop additional syndromes subsequently due to secretion of more than one [[hormone]].

==References==
{{reflist|2}}
{{WH}}
{{WS}}
[[Category:Medicine]]
[[Category:Endocrinology]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Gastroenterology]]
[[Category:Surgery]]

Glucagonoma pathophysiology

2019-05-30T22:28:15Z

Ahmed Younes: /* Images */

__NOTOC__
{{Glucagonoma}}
{{CMG}}; {{AE}} {{PSD}} {{MAD}}

==Overview==
''Glucagonoma'' is a tumor of the [[alpha cells]] of the [[pancreas]] characterized by the excessive secretion of [[glucagon]] and [[necrolytic migratory erythema]]. Glucagonoma causes hyperglucagonemia, [[zinc deficiency]], [[fatty acid]] deficiency, [[Aminoacid|hypoaminoacidemia]] that may cause [[necrolytic migratory erythema]]. Glucagonoma may be a part of [[MEN1 syndrome|type 1 multiple endocrine neoplasia]]. It is an autosomal dominant syndrome that is usually caused by mutations in the [[MEN1 syndrome|''MEN1'' gene]]. [[MEN1 syndrome|''MEN1'' gene]] is a [[tumor suppressor gene]] and causes [[MEN1 syndrome|type 1 multiple endocrine neoplasia]] by [[Knudson hypothesis|Knudson's "two hits" model]] for [[tumor]] development. All glucagonomas are located in the pancreas, 50–80% occur in the pancreatic tail, 32.2% in the body and 21.9% in the head. Glucagonoma can metastasize mainly to the liver. Glucagonomas consist of [[Pleomorphism|pleomorphic]] cells containing granules that stain for other peptides, most frequently [[pancreatic polypeptide]]. [[Immunoperoxidase|Immunoperoxidase staining]] can detect glucagon within the tumor cells and [[Glucagon|glucagon.]]

==Pathogenesis==
* Glucagonoma is a rare tumor of the [[alpha cells]] of the [[pancreas]] that results in the overproduction of the hormone [[glucagon]]. Glucagonomas are [[neuroendocrine tumors]] derived from [[Stem cells|multipotential stem cells]].<ref name="pmid9113318">{{cite journal| author=Frankton S, Bloom SR| title=Gastrointestinal endocrine tumours. Glucagonomas. | journal=Baillieres Clin Gastroenterol | year= 1996 | volume= 10 | issue= 4 | pages= 697-705 | pmid=9113318 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9113318 }}</ref><ref name="pmid6127984">{{cite journal| author=Braverman IM| title="Cutaneous manifestations of internal malignant tumors" by Becker, Kahn and Rothman, June 1942. Commentary: Migratory necrolytic erythema. | journal=Arch Dermatol | year= 1982 | volume= 118 | issue= 10 | pages= 784-98 | pmid=6127984 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6127984 }}</ref><ref>Necrolytic migratory erythema. Wikipedia. https://en.wikipedia.org/wiki/Necrolytic_migratory_erythema. Accessed on October 13, 2015.</ref><ref name="pmid9591806">{{cite journal| author=Mullans EA, Cohen PR| title=Iatrogenic necrolytic migratory erythema: a case report and review of nonglucagonoma-associated necrolytic migratory erythema. | journal=J Am Acad Dermatol | year= 1998 | volume= 38 | issue= 5 Pt 2 | pages= 866-73 | pmid=9591806 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9591806 }} </ref><ref name="pmid13978995">{{cite journal| author=STURZBECHER M| title=[8 letters of Ferdinand von HEBRAS on his contributin to Virchow's Handbuch der Speziellen Pathologie and Therapie]. | journal=Z Haut Geschlechtskr | year= 1963 | volume= 34 | issue= | pages= 281-6 | pmid=13978995 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13978995 }}</ref><ref name="pmid14356022">{{cite journal| author=Wilson LA, Kuhn JA, Corbisiero RM, Smith M, Beatty JD, Williams LE et al.| title=A technical analysis of an intraoperative radiation detection probe. | journal=Med Phys | year= 1992 | volume= 19 | issue= 5 | pages= 1219-23 | pmid=1435602 | doi=10.1118/1.596754 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1435602 }}</ref>
** [[Glucagon]] increases [[glycogenolysis]], [[gluconeogenesis]] from amino acid substrates and inhibits [[glycolysis]]. This causes weight loss due to the [[Catabolism|catabolic]] action of [[glucagon]].
** When [[glucagon]] is secreted by a tumor, it becomes independent and is no longer influenced by feedback control mechanisms.
** Glucagonoma causes hyperglucagonemia, [[zinc deficiency]], [[fatty acid]] deficiency, [[Aminoacid|hypoaminoacidemia]] that may cause [[necrolytic migratory erythema]].
** The mechanism for [[necrolytic migratory erythema]] involves excessive inflammation in the epidermis in response to trauma and to the necrolysis.
** [[Necrolytic migratory erythema]] (NME) probably results from hyponutrition and [[amino acid]] deficiency. It can be caused by the loss of [[tryptophan]] in cutaneous tissues as a result of the excess circulating [[glucagon]]. [[Tryptophan]] is responsible for [[niacin]] function, which regulates cell turnover and the maturation of the epidermis and mucosal epithelia.
** [[Diarrhea]] may result from the secretion of [[gastrin]] which occurs with glucagonoma.

== Genetics ==
Glucagonoma may be part of [[MEN1 syndrome|type 1 multiple endocrine neoplasia]]. It is an autosomal dominant syndrome that is usually caused by mutations in the [[MEN1 syndrome|''MEN1'' gene]].[[Multiple endocrine neoplasia type 1 pathophysiology#cite note-wikipedia-1|[1]]][[Multiple endocrine neoplasia type 1 pathophysiology#cite note-pmid17014705-2|[2]]][[Multiple endocrine neoplasia type 1 pathophysiology#cite note-pmid2894610-3|[3]]][[Multiple endocrine neoplasia type 1 pathophysiology#cite note-pmid2568587-4|[4]]][[Multiple endocrine neoplasia type 1 pathophysiology#cite note-pmid2568586-5|[5]]][[Multiple endocrine neoplasia type 1 pathophysiology#cite note-pmid1968641-6|[6]]][[Multiple endocrine neoplasia type 1 pathophysiology#cite note-pmid7902574-7|[7]]]
* It is characterized by the development of the following tumors:
** [[Pituitary adenoma|Pituitary adenomas]]
** [[Islet cell tumor|Islet cell tumors]] of the [[pancreas]] (commonly [[gastrinoma]] and glucagonoma)
**[[Parathyroid]] [[hyperplasia]] with resulting [[hyperparathyroidism]]
* The [[gene]] [[locus]] causing [[multiple endocrine neoplasia type 1]] has been localized to [[chromosome]] 11q13 by studies of [[loss of heterozygosity]] on [[multiple endocrine neoplasia type 1]]-associated [[Tumor|tumors]] and by linkage analysis in [[multiple endocrine neoplasia type 1]] families. ''MEN1'', spans about 10 Kb and consists of ten exons encoding a 610 [[amino acid]] nuclear protein, named menin.
* ''MEN1'' [[gene]] is a [[tumor suppressor gene]] and causes type 1 multiple endocrine neoplasia by Knudson's "two hits" model for [[tumor]] development.
* Two hits model for [[tumor]] development suggests that there is a [[germline mutation]] present in all [[Cell|cells]] at birth and the second [[mutation]] is a somatic [[mutation]] that occurs in the predisposed [[endocrine]] [[cell]] and leads to loss of the remaining wild type [[allele]]. This "two hits" model gives [[Cell|cells]] the survival advantage needed for [[tumor]] development.

== Gross Pathology ==
The gross pathology of glucagonoma may show:<ref name="pmid21859461">{{cite journal| author=Castro PG, de León AM, Trancón JG, Martínez PA, Alvarez Pérez JA, Fernández Fernández JC et al.| title=Glucagonoma syndrome: a case report. | journal=J Med Case Rep | year= 2011 | volume= 5 | issue= | pages= 402 | pmid=21859461 | doi=10.1186/1752-1947-5-402 | pmc=PMC3171381 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21859461 }} </ref><ref name="pmid9880781">{{cite journal| author=Soga J, Yakuwa Y| title=Glucagonomas/diabetico-dermatogenic syndrome (DDS): a statistical evaluation of 407 reported cases. | journal=J Hepatobiliary Pancreat Surg | year= 1998 | volume= 5 | issue= 3 | pages= 312-9 | pmid=9880781 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9880781 }}</ref><ref name="pmid25152626">{{cite journal| author=Fang S, Li S, Cai T| title=Glucagonoma syndrome: a case report with focus on skin disorders. | journal=Onco Targets Ther | year= 2014 | volume= 7 | issue= | pages= 1449-53 | pmid=25152626 | doi=10.2147/OTT.S66285 | pmc=PMC4140234 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25152626 }} </ref>

* Large tumors at diagnosis with a mean diameter of 5 cm. About 50 to 82% have evidence of [[Metastasis|metastatic]] spread at presentation.

* Nearly all glucagonomas are located in the [[pancreas]], 50–80% occur in the pancreatic tail, 32.2% in the body and 21.9% in the head.
* In few patients, location can be [[extrapancreatic]], such as in [[Kidney|kidney,]] [[duodenum]], [[lung]], [[Accessory pancreas|accessory pancreatic tissue]].

* Metastasis usually occurs to [[Liver|the liver]]. Other sites are [[Lymph node|lymph nodes]], [[bone]], [[lung]], and [[Adrenal gland|adrenals]].

*Tumors smaller than 2 cm in diameter are associated with a very low chance of [[malignancy]].

==Microscopic Pathology==
The microscopic pathology of glucagonoma tumors in [[pancreas]] usually show intense staining for [[glucagon]].<ref name="pmid6295622">{{cite journal| author=Warner TF, Block M, Hafez GR, Mack E, Lloyd RV, Bloom SR| title=Glucagonomas. Ultrastructure and immunocytochemistry. | journal=Cancer | year= 1983 | volume= 51 | issue= 6 | pages= 1091-6 | pmid=6295622 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6295622 }}</ref><ref name="pmid1973365">{{cite journal| author=Mozell E, Stenzel P, Woltering EA, Rösch J, O'Dorisio TM| title=Functional endocrine tumors of the pancreas: clinical presentation, diagnosis, and treatment. | journal=Curr Probl Surg | year= 1990 | volume= 27 | issue= 6 | pages= 301-86 | pmid=1973365 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1973365 }}</ref>
* Many glucagonomas are [[Pleomorphism|pleomorphic]] with cells containing [[granules]] that stain for other [[peptides]], most frequently [[pancreatic polypeptide]].
* [[Immunoperoxidase|Immunoperoxidase staining]] can detect glucagon within the tumor cells and glucagon [[mRNA]] also may be detected.
* [[Electron|Electron microscopy]] shows secretory granules indicating the origin of glucagonoma from [[alpha cells]].
* Benign tumors are usually fully granulated and [[malignant]] cells have fewer granules.
*[[Skin biopsy]] may depict [[Epidermal|epidermal necrosis]].

===Images===
<gallery>Image:800px-Confluent epidermal necrosis - high mag.jpg|'''Histology of confluent epidermal necrosis''' '''(high mag)''',Source:By Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=16874054<ref name=picture>Glucagonoma. Wikimedia Commons. https://commons.wikimedia.org/wiki/File:Confluent_epidermal_necrosis_-_high_mag.jpg</ref>

Image:1024px-Confluent epidermal necrosis - very high mag.jpg|'''Histology of confluent epidermal necrosis (very high mag)'''Source:By Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=16874054<ref name=picture>Glucagonoma. Wikimedia Commons. https://commons.wikimedia.org/wiki/File:Confluent_epidermal_necrosis_-_high_mag.jpg</ref>

Image:1024px-Confluent epidermal necrosis - intermed mag.jpg|'''Histology of confluent epidermal necrosis''' '''(intermed mag)'''Source:By Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=16874054<ref name=picture>Glucagonoma. Wikimedia Commons. https://commons.wikimedia.org/wiki/File:Confluent_epidermal_necrosis_-_high_mag.jpg</ref>

</gallery>

==References==
{{reflist|2}}

{{WH}}
{{WS}}
[[Category:Medicine]]
[[Category:Endocrinology]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Gastroenterology]]
[[Category:Surgery]]

Glucagonoma pathophysiology

2019-05-30T22:27:22Z

Ahmed Younes: /* Images */

__NOTOC__
{{Glucagonoma}}
{{CMG}}; {{AE}} {{PSD}} {{MAD}}

==Overview==
''Glucagonoma'' is a tumor of the [[alpha cells]] of the [[pancreas]] characterized by the excessive secretion of [[glucagon]] and [[necrolytic migratory erythema]]. Glucagonoma causes hyperglucagonemia, [[zinc deficiency]], [[fatty acid]] deficiency, [[Aminoacid|hypoaminoacidemia]] that may cause [[necrolytic migratory erythema]]. Glucagonoma may be a part of [[MEN1 syndrome|type 1 multiple endocrine neoplasia]]. It is an autosomal dominant syndrome that is usually caused by mutations in the [[MEN1 syndrome|''MEN1'' gene]]. [[MEN1 syndrome|''MEN1'' gene]] is a [[tumor suppressor gene]] and causes [[MEN1 syndrome|type 1 multiple endocrine neoplasia]] by [[Knudson hypothesis|Knudson's "two hits" model]] for [[tumor]] development. All glucagonomas are located in the pancreas, 50–80% occur in the pancreatic tail, 32.2% in the body and 21.9% in the head. Glucagonoma can metastasize mainly to the liver. Glucagonomas consist of [[Pleomorphism|pleomorphic]] cells containing granules that stain for other peptides, most frequently [[pancreatic polypeptide]]. [[Immunoperoxidase|Immunoperoxidase staining]] can detect glucagon within the tumor cells and [[Glucagon|glucagon.]]

==Pathogenesis==
* Glucagonoma is a rare tumor of the [[alpha cells]] of the [[pancreas]] that results in the overproduction of the hormone [[glucagon]]. Glucagonomas are [[neuroendocrine tumors]] derived from [[Stem cells|multipotential stem cells]].<ref name="pmid9113318">{{cite journal| author=Frankton S, Bloom SR| title=Gastrointestinal endocrine tumours. Glucagonomas. | journal=Baillieres Clin Gastroenterol | year= 1996 | volume= 10 | issue= 4 | pages= 697-705 | pmid=9113318 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9113318 }}</ref><ref name="pmid6127984">{{cite journal| author=Braverman IM| title="Cutaneous manifestations of internal malignant tumors" by Becker, Kahn and Rothman, June 1942. Commentary: Migratory necrolytic erythema. | journal=Arch Dermatol | year= 1982 | volume= 118 | issue= 10 | pages= 784-98 | pmid=6127984 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6127984 }}</ref><ref>Necrolytic migratory erythema. Wikipedia. https://en.wikipedia.org/wiki/Necrolytic_migratory_erythema. Accessed on October 13, 2015.</ref><ref name="pmid9591806">{{cite journal| author=Mullans EA, Cohen PR| title=Iatrogenic necrolytic migratory erythema: a case report and review of nonglucagonoma-associated necrolytic migratory erythema. | journal=J Am Acad Dermatol | year= 1998 | volume= 38 | issue= 5 Pt 2 | pages= 866-73 | pmid=9591806 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9591806 }} </ref><ref name="pmid13978995">{{cite journal| author=STURZBECHER M| title=[8 letters of Ferdinand von HEBRAS on his contributin to Virchow's Handbuch der Speziellen Pathologie and Therapie]. | journal=Z Haut Geschlechtskr | year= 1963 | volume= 34 | issue= | pages= 281-6 | pmid=13978995 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13978995 }}</ref><ref name="pmid14356022">{{cite journal| author=Wilson LA, Kuhn JA, Corbisiero RM, Smith M, Beatty JD, Williams LE et al.| title=A technical analysis of an intraoperative radiation detection probe. | journal=Med Phys | year= 1992 | volume= 19 | issue= 5 | pages= 1219-23 | pmid=1435602 | doi=10.1118/1.596754 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1435602 }}</ref>
** [[Glucagon]] increases [[glycogenolysis]], [[gluconeogenesis]] from amino acid substrates and inhibits [[glycolysis]]. This causes weight loss due to the [[Catabolism|catabolic]] action of [[glucagon]].
** When [[glucagon]] is secreted by a tumor, it becomes independent and is no longer influenced by feedback control mechanisms.
** Glucagonoma causes hyperglucagonemia, [[zinc deficiency]], [[fatty acid]] deficiency, [[Aminoacid|hypoaminoacidemia]] that may cause [[necrolytic migratory erythema]].
** The mechanism for [[necrolytic migratory erythema]] involves excessive inflammation in the epidermis in response to trauma and to the necrolysis.
** [[Necrolytic migratory erythema]] (NME) probably results from hyponutrition and [[amino acid]] deficiency. It can be caused by the loss of [[tryptophan]] in cutaneous tissues as a result of the excess circulating [[glucagon]]. [[Tryptophan]] is responsible for [[niacin]] function, which regulates cell turnover and the maturation of the epidermis and mucosal epithelia.
** [[Diarrhea]] may result from the secretion of [[gastrin]] which occurs with glucagonoma.

== Genetics ==
Glucagonoma may be part of [[MEN1 syndrome|type 1 multiple endocrine neoplasia]]. It is an autosomal dominant syndrome that is usually caused by mutations in the [[MEN1 syndrome|''MEN1'' gene]].[[Multiple endocrine neoplasia type 1 pathophysiology#cite note-wikipedia-1|[1]]][[Multiple endocrine neoplasia type 1 pathophysiology#cite note-pmid17014705-2|[2]]][[Multiple endocrine neoplasia type 1 pathophysiology#cite note-pmid2894610-3|[3]]][[Multiple endocrine neoplasia type 1 pathophysiology#cite note-pmid2568587-4|[4]]][[Multiple endocrine neoplasia type 1 pathophysiology#cite note-pmid2568586-5|[5]]][[Multiple endocrine neoplasia type 1 pathophysiology#cite note-pmid1968641-6|[6]]][[Multiple endocrine neoplasia type 1 pathophysiology#cite note-pmid7902574-7|[7]]]
* It is characterized by the development of the following tumors:
** [[Pituitary adenoma|Pituitary adenomas]]
** [[Islet cell tumor|Islet cell tumors]] of the [[pancreas]] (commonly [[gastrinoma]] and glucagonoma)
**[[Parathyroid]] [[hyperplasia]] with resulting [[hyperparathyroidism]]
* The [[gene]] [[locus]] causing [[multiple endocrine neoplasia type 1]] has been localized to [[chromosome]] 11q13 by studies of [[loss of heterozygosity]] on [[multiple endocrine neoplasia type 1]]-associated [[Tumor|tumors]] and by linkage analysis in [[multiple endocrine neoplasia type 1]] families. ''MEN1'', spans about 10 Kb and consists of ten exons encoding a 610 [[amino acid]] nuclear protein, named menin.
* ''MEN1'' [[gene]] is a [[tumor suppressor gene]] and causes type 1 multiple endocrine neoplasia by Knudson's "two hits" model for [[tumor]] development.
* Two hits model for [[tumor]] development suggests that there is a [[germline mutation]] present in all [[Cell|cells]] at birth and the second [[mutation]] is a somatic [[mutation]] that occurs in the predisposed [[endocrine]] [[cell]] and leads to loss of the remaining wild type [[allele]]. This "two hits" model gives [[Cell|cells]] the survival advantage needed for [[tumor]] development.

== Gross Pathology ==
The gross pathology of glucagonoma may show:<ref name="pmid21859461">{{cite journal| author=Castro PG, de León AM, Trancón JG, Martínez PA, Alvarez Pérez JA, Fernández Fernández JC et al.| title=Glucagonoma syndrome: a case report. | journal=J Med Case Rep | year= 2011 | volume= 5 | issue= | pages= 402 | pmid=21859461 | doi=10.1186/1752-1947-5-402 | pmc=PMC3171381 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21859461 }} </ref><ref name="pmid9880781">{{cite journal| author=Soga J, Yakuwa Y| title=Glucagonomas/diabetico-dermatogenic syndrome (DDS): a statistical evaluation of 407 reported cases. | journal=J Hepatobiliary Pancreat Surg | year= 1998 | volume= 5 | issue= 3 | pages= 312-9 | pmid=9880781 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9880781 }}</ref><ref name="pmid25152626">{{cite journal| author=Fang S, Li S, Cai T| title=Glucagonoma syndrome: a case report with focus on skin disorders. | journal=Onco Targets Ther | year= 2014 | volume= 7 | issue= | pages= 1449-53 | pmid=25152626 | doi=10.2147/OTT.S66285 | pmc=PMC4140234 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25152626 }} </ref>

* Large tumors at diagnosis with a mean diameter of 5 cm. About 50 to 82% have evidence of [[Metastasis|metastatic]] spread at presentation.

* Nearly all glucagonomas are located in the [[pancreas]], 50–80% occur in the pancreatic tail, 32.2% in the body and 21.9% in the head.
* In few patients, location can be [[extrapancreatic]], such as in [[Kidney|kidney,]] [[duodenum]], [[lung]], [[Accessory pancreas|accessory pancreatic tissue]].

* Metastasis usually occurs to [[Liver|the liver]]. Other sites are [[Lymph node|lymph nodes]], [[bone]], [[lung]], and [[Adrenal gland|adrenals]].

*Tumors smaller than 2 cm in diameter are associated with a very low chance of [[malignancy]].

==Microscopic Pathology==
The microscopic pathology of glucagonoma tumors in [[pancreas]] usually show intense staining for [[glucagon]].<ref name="pmid6295622">{{cite journal| author=Warner TF, Block M, Hafez GR, Mack E, Lloyd RV, Bloom SR| title=Glucagonomas. Ultrastructure and immunocytochemistry. | journal=Cancer | year= 1983 | volume= 51 | issue= 6 | pages= 1091-6 | pmid=6295622 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6295622 }}</ref><ref name="pmid1973365">{{cite journal| author=Mozell E, Stenzel P, Woltering EA, Rösch J, O'Dorisio TM| title=Functional endocrine tumors of the pancreas: clinical presentation, diagnosis, and treatment. | journal=Curr Probl Surg | year= 1990 | volume= 27 | issue= 6 | pages= 301-86 | pmid=1973365 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1973365 }}</ref>
* Many glucagonomas are [[Pleomorphism|pleomorphic]] with cells containing [[granules]] that stain for other [[peptides]], most frequently [[pancreatic polypeptide]].
* [[Immunoperoxidase|Immunoperoxidase staining]] can detect glucagon within the tumor cells and glucagon [[mRNA]] also may be detected.
* [[Electron|Electron microscopy]] shows secretory granules indicating the origin of glucagonoma from [[alpha cells]].
* Benign tumors are usually fully granulated and [[malignant]] cells have fewer granules.
*[[Skin biopsy]] may depict [[Epidermal|epidermal necrosis]].

===Images===
<gallery>Image:800px-Confluent epidermal necrosis - high mag.jpg|'''Histology of confluent epidermal necrosis''' '''(high mag)''',Source:By Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=16874054<ref name=picture>Glucagonoma. Wikimedia Commons. https://commons.wikimedia.org/wiki/File:Confluent_epidermal_necrosis_-_high_mag.jpg</ref>

Image:1024px-Confluent epidermal necrosis - very high mag.jpg|'''Histology of confluent epidermal necrosis (very high mag)'''Source:By Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=16874054<ref name=picture>Glucagonoma. Wikimedia Commons. https://commons.wikimedia.org/wiki/File:Confluent_epidermal_necrosis_-_high_mag.jpg</ref>

Image:1024px-Confluent epidermal necrosis - intermed mag.jpg|'''Histology of confluent epidermal necrosis''' '''(intermed mag)'''Source:By Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=16874054<ref name=picture>Glucagonoma. Wikimedia Commons. https://commons.wikimedia.org/wiki/File:Confluent_epidermal_necrosis_-_high_mag.jpg</ref>

Image:800px-Confluent epidermal necrosis - low mag.jpg|'''Histology of confluent epidermal necrosis (low mag)'''Source:By Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=16874054<ref name=picture>Glucagonoma. Wikimedia Commons. https://commons.wikimedia.org/wiki/File:Confluent_epidermal_necrosis_-_high_mag.jpg</ref>
Image:1752-1947-5-402-1.jpg|(A) Skin lesions affecting pretibial area. (B) Skin biopsy in necrolytic migratory erythema showing a zone of necrolysis and vacuolated keratinocytes<ref name="pmid21859461">{{cite journal| author=Castro PG, de León AM, Trancón JG, Martínez PA, Alvarez Pérez JA, Fernández Fernández JC et al.| title=Glucagonoma syndrome: a case report. | journal=J Med Case Rep | year= 2011 | volume= 5 | issue= | pages= 402 | pmid=21859461 | doi=10.1186/1752-1947-5-402 | pmc=PMC3171381 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21859461 }} </ref>
Image:NEM111.jpg|Skin biopsy in necrolytic migratory erythema showing a large zone of necrolysis in the upper epidermis (arrow)<ref name="pmid25152626">{{cite journal| author=Fang S, Li S, Cai T| title=Glucagonoma syndrome: a case report with focus on skin disorders. | journal=Onco Targets Ther | year= 2014 | volume= 7 | issue= | pages= 1449-53 | pmid=25152626 | doi=10.2147/OTT.S66285 | pmc=PMC4140234 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25152626 }} </ref>

</gallery>

==References==
{{reflist|2}}

{{WH}}
{{WS}}
[[Category:Medicine]]
[[Category:Endocrinology]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Gastroenterology]]
[[Category:Surgery]]

Follicular thyroid cancer biopsy

2019-05-30T22:24:06Z

Ahmed Younes: /* Biopsy Exams of Follicular Thyroid Cancer */

__NOTOC__
{{Follicular thyroid cancer}}
{{CMG}}; {{AE}} {{Ammu}}

==Overview==
On biopsy, follicular thyroid cancer is characterized by trabecular or solid follicular tumor cells that invade tumor capsule and surrounding vascular structures.
==Key Biopsy Findings in Follicular Thyroid Cancer==
===Fine Needle Aspiration Biopsy===
* The removal of thyroid tissue using a thin needle. The needle is inserted through the skin into the thyroid. Several tissue samples are removed from different parts of the thyroid.
===Surgical Biopsy===
* Surgical biopsy is the removal of the thyroid nodule or one lobe of the thyroid during surgery.
* On microscopic examination, trabecular follicular tumor cells that invade tumor capsule or surrounding vascular structures are found.

==Biopsy Exams of Follicular Thyroid Cancer==
<gallery>
Image:Metastatic follicular thyroid carcinoma - Case 264 (8558730243).jpg|Metastatic follicular carcinoma<ref> Follicular thyroid cancer librepathology
(2015). http://librepathology.org/wiki/index.php/File:Metastatic_follicular_thyroid_carcinoma_-_Case_264_(8558730243).jpg Accessed on October, 29 2015</ref>
Image:Metastatic follicular thyroid carcinoma - Case 264.jpg|Metastatic follicular carcinoma<ref> Follicular thyroid cancer librepathology
(2015). http://librepathology.org/wiki/index.php/File:Metastatic_follicular_thyroid_carcinoma_-_Case_264_(8559837390).jpg Accessed on October, 29 2015</ref>
</gallery>

==References==
{{Reflist|2}}

[[Category:Endocrine system]]
[[Category:Endocrinology]]
[[Category:Otolaryngology]]
[[Category:Disease]]
[[Category:Genetic disorders]]
[[Category:Types of cancer]]
[[Category:Hereditary cancers]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Endocrinology]]
[[Category:Surgery]]

Follicular thyroid cancer other imaging findings

2019-05-30T22:23:18Z

Ahmed Younes: /* Key Examples of Radioiodine scan in Follicular Thyroid Cancer */

__NOTOC__
{{Follicular thyroid cancer}}
{{CMG}}; {{AE}} {{Ammu}}
==Overview==
Other imaging findings for follicular thyroid cancer include radioiodine scan, which demonstrates increased uptake of radioactive iodine at the areas of metastases and [[laryngoscopy]] which demonstrates vocal cord immobility.
==Key Findings in Radioiodine scan in Follicular Thyroid Cancer==
* [[Metastases]] can be detected by radioiodine scan of the whole body as locations of increased uptake of radioactive iodine.
==Key Findings in Laryngoscopy==
* [[Laryngoscopy]] is a procedure in which the doctor checks the larynx (voice box) with a mirror or with a [[laryngoscope]]. A [[laryngoscope]] is a thin, tube-like instrument with a light and a lens for viewing. A thyroid tumor may press on [[vocal cord|vocal cords]]. The [[laryngoscopy]] is done to see if the vocal cords are moving normally.
* The findings in laryngoscopy are:
:* Vocal cord immobility
:* Air way compression

==References==
{{Reflist|2}}

[[Category:Endocrine system]]
[[Category:Endocrinology]]
[[Category:Otolaryngology]]
[[Category:Disease]]
[[Category:Genetic disorders]]
[[Category:Types of cancer]]
[[Category:Hereditary cancers]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Endocrinology]]
[[Category:Surgery]]

Follicular thyroid cancer CT

2019-05-30T22:22:12Z

Ahmed Younes: /* CT Examples of follicular thyroid cancer */

__NOTOC__
{{Follicular thyroid cancer}}
{{CMG}}; {{AE}} {{Ammu}}
==Overview==
CT scan may be helpful in the diagnosis of diffuse follicular thyroid cancer.
==Key CT Findings in follicular thyroid cancer==
CT scan may be helpful in the diagnosis of diffuse follicular thyroid cancer.
==CT Examples of follicular thyroid cancer==

[[File:Follicular thyroid cancer lung metastasis.jpeg|thumb|center|CT scan of lung showing metastasis<ref name=radio> Image courtesy of Dr Frank Gaillard. [http://www.radiopaedia.org Radiopaedia] (original file [http://radiopaedia.org/cases/35835 ‘’here’’].[http://radiopaedia.org/licence Creative Commons BY-SA-NC]</ref>]]

[[File:CT Brain metastasis.jpg|thumb|center|CT scan of brain showing metastasis<ref name=radio02> Image courtesy of Dr Paresh K Desai. [http://www.radiopaedia.org Radiopaedia] (original file [http://radiopaedia.org/cases/7702 ‘’here’’].[http://radiopaedia.org/licence Creative Commons BY-SA-NC]</ref>]]

==References==
{{Reflist|2}}

[[Category:Endocrine system]]
[[Category:Endocrinology]]
[[Category:Otolaryngology]]
[[Category:Disease]]
[[Category:Genetic disorders]]
[[Category:Types of cancer]]
[[Category:Hereditary cancers]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Endocrinology]]
[[Category:Surgery]]

Follicular thyroid cancer physical examination

2019-05-30T22:21:09Z

Ahmed Younes: /* Head */

__NOTOC__
{{Follicular thyroid cancer}}
{{CMG}}; {{AE}} {{Ammu}}
==Overview==
Patients with follicular thyroid cancer usually appear thin and cachectic. Physical examination of patients with follicular thyroid cancer is usually remarkable for [[thyromegaly]], [[lymphadenopathy]] and [[anxiety]].
==Physical Examination==
===Appearance of the Patient===
* Patient may be thin and cachectic
===Vitals===
====Temperature====
*A [[fever]] is often present
====Pulse====
=====Rate=====
*[[Tachycardia]]
=====Rhythm=====
*The [[pulse]] is irregularly irregular
====Blood Pressure====
*[[Hypertension]]
====Respiratory Rate====
*[[Tachypnea]] may be present
===Skin===
Moist, warm skin
===Head===

===Eyes===
* Numerous yellowish-white, sessile, painless nodules on the [[sclera]] and eyelids
* Dry [[eye]]s may be present

===Neck===
* [[Lymphadenopathy]]
* [[Thyromegaly]]
* [[Dysphagia]]

===Heart===
*A [[thrill]] may be present
===Neurologic===
* Mental status may be altered
* [[Anxiety]]
===Video===
{{#ev:youtube|lmEus_ZDipg}}

==References==
{{reflist|2}}

[[Category:Endocrine system]]
[[Category:Endocrinology]]
[[Category:Otolaryngology]]
[[Category:Disease]]
[[Category:Genetic disorders]]
[[Category:Types of cancer]]
[[Category:Hereditary cancers]]
{{WikiDoc Help Menu}}
{{WikiDoc Sources}}
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Endocrinology]]
[[Category:Surgery]]

Follicular thyroid cancer staging

2019-05-30T22:20:19Z

Ahmed Younes: /* Stage IV Follicular Thyroid Cancer */

__NOTOC__
{{Follicular thyroid cancer}}
{{CMG}}; {{AE}} {{Ammu}}
==Overview==
According to the American Joint Committee on Cancer (AJCC)<ref> Stage Information for Thyroid Cancer Cancer.gov
(2015). http://www.cancer.gov/types/thyroid/hp/thyroid-treatment-pdq#link/stoc_h2_2- Accessed on October, 29 2015</ref> there are 4 stages of follicular thyroid cancer based on the clinical features and findings on imaging. Each stage is assigned a letter and a number that designate the tumor size, number of lymph node regions involved, and metastasis.

==Staging==
 
{| style="border: 0px; font-size: 90%; margin: 3px;" align=center
|+'''''Thyroid TNM staging'''''
! style="background: #4479BA; width: 120px;" | {{fontcolor|#FFF|Stage}}
! style="background: #4479BA; width: 550px;" | {{fontcolor|#FFF|Description}}
|-
! style="background: #DCDCDC;" |TX
! style="background: #F5F5F5;" |Primary [[tumor]] cannot be assessed
|-
! style="background: #DCDCDC;" |T0
! style="background: #F5F5F5;" |No evidence of primary [[tumor]]
|-
! style="background: #DCDCDC;" |T1
! style="background: #F5F5F5;" |[[Tumor]] ≤2 cm in greatest dimension limited to the [[thyroid]]
|-
! style="background: #DCDCDC;" |T1a
! style="background: #F5F5F5;" |[[Tumor]] ≤1 cm, limited to the [[thyroid]]
|-
! style="background: #DCDCDC;" |T1b
! style="background: #F5F5F5;" |[[Tumor]] >1 cm but ≤2 cm in greatest dimension, limited to the [[thyroid]]
|-
! style="background: #DCDCDC;" |T2
! style="background: #F5F5F5;" |[[Tumor]] >2 cm but ≤4 cm in greatest dimension, limited to the [[thyroid]]
|-
! style="background: #DCDCDC;" |T3
! style="background: #F5F5F5;" |[[Tumor]] >4 cm in greatest dimension limited to the [[thyroid]] or any [[tumor]] with minimal extrathyroid extension (e.g., extension to [[sternothyroid muscle]] or perithyroid soft tissues)
|-
! style="background: #DCDCDC;" rowspan=2|T4a
! style="background: #F5F5F5;" |Moderately advanced [[disease]]
|-
! style="background: #F5F5F5;" |[[Tumor]] of any size extending beyond the thyroid capsule to invade subcutaneous [[soft tissue]]s, [[larynx]], [[trachea]], [[esophagus]], or [[recurrent laryngeal nerve]]
|-
! style="background: #DCDCDC;" rowspan=2|T4b
! style="background: #F5F5F5;" |Very advanced [[disease]]
|-
! style="background: #F5F5F5;" |[[Tumor]] invades prevertebral fascia or encases [[carotid artery]] or mediastinal vessel
|}
 
{| style="border: 0px; font-size: 90%; margin: 3px;" align=center
|+'''''Regional Lymph Nodes (N)'''''
! style="background: #4479BA; width: 120px;" | {{fontcolor|#FFF|Stage}}
! style="background: #4479BA; width: 550px;" | {{fontcolor|#FFF|Description}}
|-
! style="background: #DCDCDC;" |NX
! style="background: #F5F5F5;" |Regional [[lymph node]] cannot be assessed
|-
! style="background: #DCDCDC;" |N0
! style="background: #F5F5F5;" |No regional lymph node metastasis
|-
! style="background: #DCDCDC;" |N1
! style="background: #F5F5F5;" |Regional [[lymph node]] metastasis
|-
! style="background: #DCDCDC;" |N1a
! style="background: #F5F5F5;" |[[Metastases]] to Level VI (pretracheal, paratracheal, and prelaryngeal/Delphian lymph nodes)
|-
! style="background: #DCDCDC;" |N1b
! style="background: #F5F5F5;" |[[Metastases]] to unilateral, bilateral, or contralateral cervical (Levels I, II, III, IV, or V) or retropharyngeal or superior mediastinal lymph nodes (Level VII)
|}

{| style="border: 0px; font-size: 90%; margin: 3px;" align=center
|+'''''Distant Metastasis (M)'''''
! style="background: #4479BA; width: 120px;" | {{fontcolor|#FFF|Stage}}
! style="background: #4479BA; width: 550px;" | {{fontcolor|#FFF|Description}}
|-
! style="background: #DCDCDC;" |M0
! style="background: #F5F5F5;" |No distant [[metastasis]]
|-
! style="background: #DCDCDC;" |M1
! style="background: #F5F5F5;" |Distant [[metastasis]]
|}

{| style="border: 0px; font-size: 90%; margin: 3px;" align=center
|+'''''Anatomic Stage/Prognostic Groups'''''
! style="background: #4479BA; width: 120px;" | {{fontcolor|#FFF|Stage}}
! style="background: #4479BA; width: 550px;" | {{fontcolor|#FFF|T}}
! style="background: #4479BA; width: 550px;" | {{fontcolor|#FFF|N}}
! style="background: #4479BA; width: 550px;" | {{fontcolor|#FFF|M}}
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" colspan=4 align=center| '''Follicular thyroid carcinoma'''
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" colspan=4 | '''YOUNGER THAN 45 YEARS'''
|-
! style="background: #DCDCDC;" |I
! style="background: #F5F5F5;" |Any T

! style="background: #F5F5F5;" |Any N

! style="background: #F5F5F5;" |M0
|-
! style="background: #DCDCDC;" |II
! style="background: #F5F5F5;" |Any T

! style="background: #F5F5F5;" |Any N

! style="background: #F5F5F5;" |M1

|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" colspan=4 | '''45 YEARS AND OLDER'''
|-
! style="background: #DCDCDC;" |I
! style="background: #F5F5F5;" |T1
! style="background: #F5F5F5;" |Any N
! style="background: #F5F5F5;" |M1
|-
! style="background: #DCDCDC;" |II
! style="background: #F5F5F5;" |T2
! style="background: #F5F5F5;" |N0
! style="background: #F5F5F5;" |M0
|-

! style="background: #DCDCDC;" |III
! style="background: #F5F5F5;" |T3
! style="background: #F5F5F5;" |N0
! style="background: #F5F5F5;" |M0

|-

! style="background: #DCDCDC;" |
! style="background: #F5F5F5;" |T1
! style="background: #F5F5F5;" |N1a
! style="background: #F5F5F5;" |M0

|-

! style="background: #DCDCDC;" |
! style="background: #F5F5F5;" |T2
! style="background: #F5F5F5;" |N1a
! style="background: #F5F5F5;" |M0

|-

! style="background: #DCDCDC;" |
! style="background: #F5F5F5;" |T3
! style="background: #F5F5F5;" |N1a
! style="background: #F5F5F5;" |M0

|-

! style="background: #DCDCDC;" |IVA
! style="background: #F5F5F5;" |T4a
! style="background: #F5F5F5;" |N0
! style="background: #F5F5F5;" |M0

|-

! style="background: #DCDCDC;" |
! style="background: #F5F5F5;" |T4a
! style="background: #F5F5F5;" |N1a
! style="background: #F5F5F5;" |M0

|-

! style="background: #DCDCDC;" |
! style="background: #F5F5F5;" |T1
! style="background: #F5F5F5;" |N1b
! style="background: #F5F5F5;" |M0

|-

! style="background: #DCDCDC;" |
! style="background: #F5F5F5;" |T2
! style="background: #F5F5F5;" |N1b
! style="background: #F5F5F5;" |M0

|-

! style="background: #DCDCDC;" |
! style="background: #F5F5F5;" |T3
! style="background: #F5F5F5;" |N1b
! style="background: #F5F5F5;" |M0

|-

! style="background: #DCDCDC;" |
! style="background: #F5F5F5;" |T4a
! style="background: #F5F5F5;" |N1b
! style="background: #F5F5F5;" |M0

|-

! style="background: #DCDCDC;" |IVB
! style="background: #F5F5F5;" |T4b
! style="background: #F5F5F5;" |Any N
! style="background: #F5F5F5;" |M0

|-

! style="background: #DCDCDC;" |Stage IVC
! style="background: #F5F5F5;" |Any T
! style="background: #F5F5F5;" |Any N
! style="background: #F5F5F5;" |M1
|}

===Follicular Thyroid Cancer===
====Stage I Follicular Thyroid Cancer====
* Stage I follicular carcinoma is localized to the [[thyroid gland]]. Follicular thyroid carcinoma must be distinguished from follicular adenomas, which are characterized by their lack of invasion through the [[capsule]] into the surrounding [[thyroid|thyroid tissue]].
====Stage II Follicular Thyroid Cancer====
* Stage II follicular carcinoma is defined as either [[tumor]] that has spread distantly in patients younger than 45 years, or [[tumor]] that is larger than 2 cm but smaller than 4 cm and is limited to the [[thyroid gland]] in patients older than 45 years. The presence of lymph node metastases does not worsen the prognosis among patients younger than 45 years. Follicular thyroid carcinoma must be distinguished from follicular adenomas, which are characterized by their lack of invasion through the capsule into the surrounding thyroid tissue. While follicular cancer has a good prognosis, it is less favorable than that of papillary carcinoma. The 10-year survival is better for patients with follicular carcinoma without vascular invasion than for patients with vascular invasion.
====Stage III Follicular Thyroid Cancer====
* Stage III follicular carcinoma in patients older than 45 years is defined as tumor larger than 4 cm and limited to the thyroid or with minimal extrathyroid extension, or lymph node involvement limited to the pretracheal, paratracheal, or prelaryngeal/Delphian nodes.
====Stage IV Follicular Thyroid Cancer====
* Stage IV follicular carcinoma in patients older than 45 years is defined as tumors with extension beyond the thyroid capsule to the soft tissues of the neck, cervical lymph node metastases, or distant metastases. The lungs and bone are the most frequent sites of spread. Follicular carcinomas more commonly have blood vessel invasion and tend to metastasize hematogenously to the lungs and to the bone rather than through the lymphatic system.

==Reference==
{{Reflist|2}}

[[Category:Endocrine system]]
[[Category:Endocrinology]]
[[Category:Otolaryngology]]
[[Category:Disease]]
[[Category:Genetic disorders]]
[[Category:Types of cancer]]
[[Category:Hereditary cancers]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Endocrinology]]
[[Category:Surgery]]

Follicular thyroid cancer pathophysiology

2019-05-30T22:19:08Z

Ahmed Younes: /* Microscopic Pathology */

__NOTOC__
{{Follicular thyroid cancer}}
{{CMG}}; {{AE}} {{Ammu}}
==Overview==
Follicular thyroid cancer arises from follicular cells of thyroid, which are secretory cells that are normally involved in production and secretion of [[thyroid hormones]], [[thyroxine]] (T4) and triiodothyronine (T3). [[Gene|Genes]] involved in the pathogenesis of follicular thyroid cancer include [[Ras|''RAS'']], ''PAX8/PPARγ'', and [[PTEN|''PTEN'']].
==Pathogenesis==
* Follicular thyroid cancer is the second most common type of [[cancer]]. It constitutes about 15% of thyroid cancers.
[[File:Follicular thyroid carcinoma pathogenesis 2.0.jpg|thumb|left|700px|Pathogenesis of follicular thyroid carcinoma]]
 
* Follicular thyroid cancer occurs more commonly in women of over 50 years old.
* [[Thyroglobulin]] (Tg) can be used as a [[tumor marker]] for well-differentiated follicular thyroid cancer.
* Follicular carcinoma tends to metastasize to the [[lung]]s and [[bone]] via the [[bloodstream]]. Follicular thyroid cancer metastasize late to [[lymph node|lymph nodes]], with only 5-10% of patients having nodal [[metastases]] at the time of diagnosis. Hematogenous spread is however much more common with 20% of patients having distant hematogenous metastases at at the time of diagnosis.<ref name=Radiopaedia 2015 Papillary thyroid cancer
>{{cite web | title = Radiopedia 2015 Follicular thyroid cancer [Dr Matt A. Morgan and Dr Frank Gaillard]| url = http://radiopaedia.org/articles/follicular-thyroid-cancer }}</ref>
* A Hürthle cell (also known as '''Askanazy cell''') is an [[large cell|oncocytic cell]] in the thyroid that is often associated with [[Hashimoto's thyroiditis]] as well as [[follicular thyroid cancer]]. Hürthle cells are characterized as enlarged epithelial cells with abundant eosinophilic granular cytoplasm as a result of altered mitochondria.<ref name="Hurthle Cell Carcinoma">{{cite web|url=http://www.emedicine.com/med/topic1045.htm |title=Hurthle Cell Carcinoma |author=Aytug, Serhat |publisher=[[eMedicine]] |date=[[June 13]], 2006}}</ref> They generally stain pink and are prominently found in histological sections of thyroid glands affected with Hashimoto's.

==Genetics==
* The [[ras|''Ras'' oncogene]] is positive in a significant proportion of individuals. The [[ras|''Ras'' oncogene]] acts through the RAF-MEK-MAPK kinase pathway.
* Other [[gene|genes]] involved in the pathogenesis of follicular thyroid cancer are:
:* ''RET/PTC'' (translocation) associated with MAPK and PI3K-AKT signaling pathways

:* [[HRAS|''HRAS'']], [[KRAS|''KRAS'']], [[Neuroblastoma RAS viral oncogene homolog|''NRAS'']] (mutation) associated with [[mitogen-activated protein kinase]] and PI3K-AKT signaling pathways

:* ''PAX8/PPARγ'' (translocation) associated with [[PAX8|''PAX8'']]-associated nuclear transcription signaling pathways. [[PAX8|''PAX8'']] is responsible for follicular cell differentiation.

:* [[PTEN|''PTEN'']] (mutation) associated with PI3K-AKT signaling pathways

:* [[PTEN|''PTEN'']] (deletion) associated with PI3K-AKT signaling pathways

:* ''IDH1'' (mutation) assciated with IDH1-associated metabolic pathways signaling pathways
* Phosphatase and tensin homologue suppressor gene and the phosphatidylinositol 3-kinase pathway are also involved in the pathogenesis of follicular thyroid tumor.
* [[P53 (protein)]], [[Myc|''c-myc'']], [[C-Fos|''c-fos'']], and the thyrotropin (TSH) receptor are some other factors involved in the pathogenesis of follicular thyroid cancer.
* [[microRNA|MicroRNAs]] namely miR-192, miR-197, miR-328, and miR-346 have increased expression in follicular cell carcinoma.
[[File:Thyroid cancer carcinogensis.jpg|thumb|center|Schema of key pathways in the development and progression of thyroid cancer.]]

==Associated Conditions==
* [[Cowden disease]]
* [[Carney complex]], type I

==Gross Pathology==
* Encapsulated tumors
[[Image:Follicular adenoma of the thyroid.jpg|thumb|center|Gross pathological section of a follicular thyroid carcinoma (tumor at the bottom).]]
==Microscopic Pathology==
* It is not possible to distinguish between follicular adenoma and carcinoma on cytological grounds. If fine needle aspiration cytology (FNAC) suggests follicular neoplasm, thyroid lobectomy should be performed to establish th [[Histopathology|histopathological]] diagnosis.
* On microscopic examination, trabecular, solid, follicular tumor cells that invade [[capsule|tumor capsule]] or surrounding vascular structures are found.
<gallery>
Image:Metastatic follicular thyroid carcinoma - Case 264 (8558730243).jpg|Metastatic follicular carcinoma<ref> Follicular thyroid cancer librepathology
(2015). http://librepathology.org/wiki/index.php/File:Metastatic_follicular_thyroid_carcinoma_-_Case_264_(8558730243).jpg Accessed on October, 29 2015</ref>
Image:Metastatic follicular thyroid carcinoma - Case 264.jpg|Metastatic follicular carcinoma<ref> Follicular thyroid cancer librepathology
(2015). http://librepathology.org/wiki/index.php/File:Metastatic_follicular_thyroid_carcinoma_-_Case_264_(8559837390).jpg Accessed on October, 29 2015</ref>
</gallery>

==Histopathological Video==
===Video===
{{#ev:youtube|3_eCHeOkdgg}}
==References==
{{Reflist|2}}

[[Category:Endocrine system]]
[[Category:Endocrinology]]
[[Category:Otolaryngology]]
[[Category:Disease]]
[[Category:Genetic disorders]]
[[Category:Types of cancer]]
[[Category:Hereditary cancers]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Endocrinology]]
[[Category:Surgery]]

Mycosis fungoides differential diagnosis

2019-05-30T16:15:39Z

Ahmed Younes:

__NOTOC__
[[Image:Home_logo1.png|right|250px|link=https://www.wikidoc.org/index.php/Mycosis_fungoides]]
{{CMG}}; {{AE}} {{S.G.}}, {{AS}}
==Overview==
Cutaneous T cell lymphoma must be differentiated from other diseases such as [[eczema]] and [[psoriasis]].
==Differentiating Cutaneous T cell lymphoma from other Diseases==
*Mycosis fangoides must be differentiated from any [[Disease|diseases]] with cutaneous patch or plaque that not respond to first- and second-line treatment ssuch as:<ref name="pmid23197199">{{cite journal |vauthors=Yamashita T, Abbade LP, Marques ME, Marques SA |title=Mycosis fungoides and Sézary syndrome: clinical, histopathological and immunohistochemical review and update |journal=An Bras Dermatol |volume=87 |issue=6 |pages=817–28; quiz 829–30 |date=2012 |pmid=23197199 |pmc=3699909 |doi= |url=}}</ref><ref name="pmid249363243">{{cite journal |vauthors=Olek-Hrab K, Silny W |title=Diagnostics in mycosis fungoides and Sezary syndrome |journal=Rep Pract Oncol Radiother |volume=19 |issue=2 |pages=72–6 |date=March 2014 |pmid=24936324 |pmc=4054990 |doi=10.1016/j.rpor.2013.11.001 |url=}}</ref><ref name="pmid18652582">{{cite journal |vauthors=Klemke CD, Brade J, Weckesser S, Sachse MM, Booken N, Neumaier M, Goerdt S, Nebe TC |title=The diagnosis of Sézary syndrome on peripheral blood by flow cytometry requires the use of multiple markers |journal=Br. J. Dermatol. |volume=159 |issue=4 |pages=871–80 |date=September 2008 |pmid=18652582 |doi=10.1111/j.1365-2133.2008.08739.x |url=}}</ref><ref name="pmid21985996">{{cite journal |vauthors=Scala E, Abeni D, Palazzo P, Liso M, Pomponi D, Lombardo G, Picchio MC, Narducci MG, Russo G, Mari A |title=Specific IgE toward allergenic molecules is a new prognostic marker in patients with Sézary syndrome |journal=Int. Arch. Allergy Immunol. |volume=157 |issue=2 |pages=159–67 |date=2012 |pmid=21985996 |doi=10.1159/000327553 |url=}}</ref><ref name="pmid3528307">{{cite journal |vauthors=Chu AC, Robinson D, Hawk JL, Meacham R, Spittle MF, Smith NP |title=Immunologic differentiation of the Sézary syndrome due to cutaneous T-cell lymphoma and chronic actinic dermatitis |journal=J. Invest. Dermatol. |volume=86 |issue=2 |pages=134–7 |date=February 1986 |pmid=3528307 |doi= |url=}}</ref><ref name="TidwellMalone2016">{{cite journal|last1=Tidwell|first1=W. James|last2=Malone|first2=Janine|last3=Callen|first3=Jeffrey P.|title=Cutaneous T-Cell Lymphoma Misdiagnosed as Lipodermatosclerosis|journal=JAMA Dermatology|volume=152|issue=4|year=2016|pages=487|issn=2168-6068|doi=10.1001/jamadermatol.2015.6106}}</ref>
** Sezaruy syndrome
***Sezaruy syndrome(SS) is more symptoI contrast to patch or [[plaque]] mycosis fungoides, SS is much more [[symptomatic]]. Sezary syndrome [[Patient|patients]] tend to present with [[diffuse]] [[skin]] involvement,not like mycosis fungoides usually evolve through patches and [[Plaque|plaques]] to [[erythroderma]] <ref name="pmid27407986">{{cite journal |vauthors=Chand K, Sayal SK, Chand S |title=Cutaneous T-Cell Lymphoma (Mycosis Fungoides) |journal=Med J Armed Forces India |volume=63 |issue=2 |pages=188–90 |date=April 2007 |pmid=27407986 |pmc=4925357 |doi=10.1016/S0377-1237(07)80076-1 |url=}}</ref>
***In Sezary syndrome [[Infiltration (medical)|infiltration]] of [[skin]] is generally much less dense than [[plaque]] in mycosis fungoides (MF)
** [[Eczema]]
** [[Adult T cell leukemia/lymphoma|Adult T cell leukemia/lymphma]]
** [[Psoriasis]]
** [[Pityriasis rubra pilaris]]
** [[dermatitis]]
** [[Hypereosinophilic syndrome]]
** [[Adult T-cell leukemia]]
** [[Atopic Dermatitis|Atopic dermatitis]]
** [[Contact dermatitis]] ( [[Allergy|Allergic]], [[irritant]])
** [[Chronic (medical)|Chronic]] [[actinic]] [[dermatitis]]
** [[Scabies]]
** [[Subcutaneous]] [[panniculitis]] like [[T-cell lymphoma|T cell lymphoma]] (SPTCL)
** [[Drug eruption]]
** [[Graft-versus-host disease|Graft versus host disease]]
** [[Lichen planus]]
** [[Pediatrics|Pediatric]] [[atopic dermatitis]]
** [[Tinea corporis]]
** Primary [[cutaneous]] [[Anaplastic large cell lymphoma (patient information)|anaplastic large cell lymphoma]] ([[Anaplastic large cell lymphoma|ALCL]])
** [[Cutaneous]] [[Gamma/delta T cells|gamma/delta]] [[T-cell lymphoma|T cell lymphoma]] (G/D TCL)

{| class="wikitable"
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Disease
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Rash Characteristics
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Signs and Symptoms
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Associated Conditions
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Rash Appearance
|-
|[[Cutaneous T cell lymphoma]]/[[Mycosis fungoides]]<ref name="urlMycosis Fungoides and the Sézary Syndrome Treatment (PDQ®)—Patient Version - National Cancer Institute">{{cite web |url=https://www.cancer.gov/types/lymphoma/patient/mycosis-fungoides-treatment-pdq |title=Mycosis Fungoides and the Sézary Syndrome Treatment (PDQ®)—Patient Version - National Cancer Institute |format= |work= |accessdate=}}</ref>
|
* Premycotic phase: A scaly, red [[rash]] in areas of the [[body]] that usually are not exposed to the sun. This [[rash]] does not cause [[Symptom|symptoms]] and may last for months or years.
* Patch phase: Thin, reddened, [[eczema]] -like [[rash]].
* [[Plaque]] phase: Small raised [[Bumps on skin|bumps]] ([[Papule|papules]]) or hardened [[Lesion|lesions]] on the [[skin]], which may be reddened.
* [[Tumor]] phase: [[Tumor|Tumors]] form on the [[skin]]. These [[Tumor|tumors]] may develop [[Ulcer|ulcers]]<nowiki/> and the [[skin]] may get [[infected]].
|
* [[Epidermis (skin)|Epidermal]] [[atrophy]] or poikiloderma

* Generalized [[itching]] ([[pruritus]])
* [[Pain]] in the affected area of the skin.
* [[Insomnia]]
* Red ([[erythematous]]) patches scattered over the [[skin]] of the [[trunk]] and the [[extremities]]
* [[Tumor]]-like lobulated outgrowths form on the [[skin]] in the latter part of the [[disease]]
* [[Weight loss]]
* [[Lymphadenopathy]]
* [[Malaise]] and [[fatigue]]
* [[Anemia]]
* May progress to [[Sezary syndrome]] ([[Skin]] involvement plus hematogenous dissemination)
|
* [[Sezary syndrome]]
|
|-
|[[Pityriasis rosea]]<ref name="pmid27512182">{{cite journal |vauthors=Mahajan K, Relhan V, Relhan AK, Garg VK |title=Pityriasis Rosea: An Update on Etiopathogenesis and Management of Difficult Aspects |journal=Indian J Dermatol |volume=61 |issue=4 |pages=375–84 |year=2016 |pmid=27512182 |pmc=4966395 |doi=10.4103/0019-5154.185699 |url=}}</ref>
|
* Pink or salmon in colour, which may be scaly, termed as "herald patch"
* [[Oval]] in shape
* Long axis oriented along the clevage lines
* Distributed on the [[trunk]] and [[proximal extremities]]
* [[Squamous]] marginal collarette and a “fir-tree” or “Christmas tree” distribution on the posterior trunk
* Develops after [[viral infection]]
* Resolves spontaneously after 6-8 weeks
|
* Preceded by a prodrome of:
** [[Sore throat]]
** [[Gastrointestinal tract|Gastrointestinal]] disturbance
** [[Fever]]
** [[Arthralgia]]
|
* [[Infection]] by any of the following:<ref name="pmid19997691">{{cite journal |vauthors=Prantsidis A, Rigopoulos D, Papatheodorou G, Menounos P, Gregoriou S, Alexiou-Mousatou I, Katsambas A |title=Detection of human herpesvirus 8 in the skin of patients with pityriasis rosea |journal=Acta Derm. Venereol. |volume=89 |issue=6 |pages=604–6 |year=2009 |pmid=19997691 |doi=10.2340/00015555-0703 |url=}}</ref>
** [[Human herpesvirus 6|HHV-6]]
** [[HHV-7]]
** [[HHV-8]]
|
|-
|[[Pityriasis lichenoides chronica]]
|
* Recurrent [[Lesion|lesions]] are usually less evenly scattered than psoriasis
* Brownish red or orange-brown color
* Lesions are capped by a single detachable opaque mica-like scale
* Often leave [[Hypopigmented area|hypopigmented]] [[Macule|macules]]
|
* High [[fever]]
* [[Malaise]]
* [[Myalgias]]
* [[Skin]] burning
* [[Pruritis]]
|
* [[Infection]] by any of the following:<ref name="pmid9109005">{{cite journal |vauthors=Smith KJ, Nelson A, Skelton H, Yeager J, Wagner KF |title=Pityriasis lichenoides et varioliformis acuta in HIV-1+ patients: a marker of early stage disease. The Military Medical Consortium for the Advancement of Retroviral Research (MMCARR) |journal=Int. J. Dermatol. |volume=36 |issue=2 |pages=104–9 |year=1997 |pmid=9109005 |doi= |url=}}</ref>
** [[Epstein Barr virus|Epstein-Barr virus]] ([[EBV]])
** ''[[Toxoplasma gondii]]''
** [[Human Immunodeficiency Virus (HIV)|Human immunodeficiency virus]] ([[Human Immunodeficiency Virus (HIV)|HIV]])
|
|-
|[[Nummular dermatitis]]<ref name="pmid23517392">{{cite journal |vauthors=Jiamton S, Tangjaturonrusamee C, Kulthanan K |title=Clinical features and aggravating factors in nummular eczema in Thais |journal=Asian Pac. J. Allergy Immunol. |volume=31 |issue=1 |pages=36–42 |year=2013 |pmid=23517392 |doi= |url=}}</ref>
|
* Multiple coinshaped [[Eczematous Scaling|eczematous]] lesions
* Commonly affecting the [[extremities]] (lower>upper) and [[trunk]]
* May ooze [[fluid]] and become dry and crusty
|
* Often appears after a skin injury, such as a [[burn]], [[abrasion]] (from friction), or [[insect bite]]

* Lesions commonly relapse after occasional remission or may persist for long periods
* [[Pruritis]]
|
* Associated with:
** Dry [[skin]]
** [[Emotional]] [[Stress (medicine)|stress]]
** [[Allergen|Allergens]](rubber [[chemicals]], [[formaldehyde]], [[neomycin]], chrome, [[Mercury (element)|mercury]] and [[nickel]])
** [[Staphylococcus]] [[infection]]
** Seasonal variation
** [[Alcohol]]
** [[Drugs]]
** [[Atopy]]
|
|-
|[[Secondary syphilis]]<ref name="urlSTD Facts - Syphilis">{{cite web |url=https://www.cdc.gov/std/syphilis/stdfact-syphilis.htm |title=STD Facts - Syphilis |format= |work= |accessdate=}}</ref>
|
* Round coppery red color [[Lesion|lesions]] on [[Hand|palms]] and [[Sole (foot)|soles]]
* [[Papule|Papules]] with collarette of scales
|
* [[Fever]]
* [[Lymphadenopathy|Generalized lymphadenopathy]]
* [[Sore throat]]
* [[Hair loss|Patchy hair loss]]
* [[Headaches]]
* [[Weight loss]]
* [[Myalgia]]
* [[Fatigue]]
|
* Associated with:
** [[Condyloma latum|Condylomata lata]]
** Corona verinata
** Positive [[Venereal disease research laboratory (VDRL) test|VDRL]] test
|
|-
|[[Bowen’s disease]]<ref name="pmid28523295">{{cite journal |vauthors=Neagu TP, Ţigliş M, Botezatu D, Enache V, Cobilinschi CO, Vâlcea-Precup MS, GrinŢescu IM |title=Clinical, histological and therapeutic features of Bowen's disease |journal=Rom J Morphol Embryol |volume=58 |issue=1 |pages=33–40 |year=2017 |pmid=28523295 |doi= |url=}}</ref>
|
* [[Erythematous]] little scaly [[plaque]], which enlarges over time in an erratic manner
* Scale is usually yellow or white and it is easily detachable without producing any [[bleeding]]
* Well defined margins
|
* [[Pruritis]]
* [[Pain]]
* [[Bleeding]] [[Lesion|lesions]]
|
* Associated with:<ref name="pmid25201325">{{cite journal |vauthors=Murao K, Yoshioka R, Kubo Y |title=Human papillomavirus infection in Bowen disease: negative p53 expression, not p16(INK4a) overexpression, is correlated with human papillomavirus-associated Bowen disease |journal=J. Dermatol. |volume=41 |issue=10 |pages=878–84 |year=2014 |pmid=25201325 |doi=10.1111/1346-8138.12613 |url=}}</ref>
** [[Erythroplasia of Queyrat]] ([[Bowen's disease]] of the [[penis]])
** [[Squamous cell carcinoma]]
** Solar radiation and [[ultraviolet]] ([[UV]]) exposure
** [[Radiation therapy|Radiotherapy]]
** [[Immunosuppression]]
** [[Arsenic]] exposure
** [[Human papillomavirus|Human papilloma virus]] ([[HPV]]) type 16
** [[Polyomavirus|Merkel cell polyomavirus]]
** [[Sjögren's syndrome|Sjögren’s syndrome]]
|
|-
|[[Exanthematous pustulosis]]<ref name="pmid26354880">{{cite journal |vauthors=Szatkowski J, Schwartz RA |title=Acute generalized exanthematous pustulosis (AGEP): A review and update |journal=J. Am. Acad. Dermatol. |volume=73 |issue=5 |pages=843–8 |year=2015 |pmid=26354880 |doi=10.1016/j.jaad.2015.07.017 |url=}}</ref>
|
* Numerous small, primarily non-follicular, sterile [[pustules]], arising within large areas of [[Edema|edematous]] [[erythema]]
|
* [[Fever]]
* [[Leukocytosis]]
* Intracorneal, subcorneal, and/or intraepidermal [[pustules]] with [[papillary]] [[dermal]] [[edema]] containing [[neutrophils]] and [[eosinophils]]
|
* Associated with:<ref name="pmid12466124">{{cite journal |vauthors=Schmid S, Kuechler PC, Britschgi M, Steiner UC, Yawalkar N, Limat A, Baltensperger K, Braathen L, Pichler WJ |title=Acute generalized exanthematous pustulosis: role of cytotoxic T cells in pustule formation |journal=Am. J. Pathol. |volume=161 |issue=6 |pages=2079–86 |year=2002 |pmid=12466124 |pmc=1850901 |doi=10.1016/S0002-9440(10)64486-0 |url=}}</ref>
** [[Antibiotic|Antibiotics]] ([[Penicillin|penicillins]], [[sulfonamides]], [[tetracyclines]])
** [[Carbamazepine]]
** [[Calcium channel blocker|Calcium channel blockers]]([[Diltiazem]])
** [[Hydroxychloroquine]]
|
|-
|[[Lichen planus|Hypertrophic lichen planus]]<ref name="pmid27222766">{{cite journal |vauthors=Ankad BS, Beergouder SL |title=Hypertrophic lichen planus versus prurigo nodularis: a dermoscopic perspective |journal=Dermatol Pract Concept |volume=6 |issue=2 |pages=9–15 |year=2016 |pmid=27222766 |pmc=4866621 |doi=10.5826/dpc.0602a03 |url=}}</ref>
|
* Classically involves [[shin]] and ankles and is characterized by [[Hyperkeratosis|hyperkeratotic]] [[Plaque|plaques]] and [[Nodule (medicine)|nodules]] covered by a scale
* [[Lesion|Lesions]] may transform into [[Hyperkeratosis|hyperkeratotic]] thickened elevated purplish or reddish [[Plaque|plaques]] and [[nodules]]
|
* [[Chronic (medical)|Chronic]] [[pruritis]]
* Scaling
* May be [[asymptomatic]]
|
* Associated with [[Hepatitis C virus]] [[infection]]<ref name="pmid19770446">{{cite journal |vauthors=Shengyuan L, Songpo Y, Wen W, Wenjing T, Haitao Z, Binyou W |title=Hepatitis C virus and lichen planus: a reciprocal association determined by a meta-analysis |journal=Arch Dermatol |volume=145 |issue=9 |pages=1040–7 |year=2009 |pmid=19770446 |doi=10.1001/archdermatol.2009.200 |url=}}</ref>
|
|-
|Sneddon–Wilkinson [[disease]]<ref name="pmid9564592">{{cite journal |vauthors=Lutz ME, Daoud MS, McEvoy MT, Gibson LE |title=Subcorneal pustular dermatosis: a clinical study of ten patients |journal=Cutis |volume=61 |issue=4 |pages=203–8 |year=1998 |pmid=9564592 |doi= |url=}}</ref>
|
* [[Flaccid]] [[pustules]] that are often generalized and have a tendency to involve the flexural areas
* Have an annular configuration
|
* [[Pruritis]]
* May be [[asymptomatic]]
|
* Associated with:
** [[Monoclonal gammopathy]], usually an IgA paraproteinemia<ref name="pmid3056995">{{cite journal |vauthors=Kasha EE, Epinette WW |title=Subcorneal pustular dermatosis (Sneddon-Wilkinson disease) in association with a monoclonal IgA gammopathy: a report and review of the literature |journal=J. Am. Acad. Dermatol. |volume=19 |issue=5 Pt 1 |pages=854–8 |year=1988 |pmid=3056995 |doi= |url=}}</ref>
** [[Crohn's disease]]<ref name="pmid1357895">{{cite journal |vauthors=Delaporte E, Colombel JF, Nguyen-Mailfer C, Piette F, Cortot A, Bergoend H |title=Subcorneal pustular dermatosis in a patient with Crohn's disease |journal=Acta Derm. Venereol. |volume=72 |issue=4 |pages=301–2 |year=1992 |pmid=1357895 |doi= |url=}}</ref>
** [[Osteomyelitis]]
** [[Adalimumab]]<ref name="pmid23489057">{{cite journal |vauthors=Sauder MB, Glassman SJ |title=Palmoplantar subcorneal pustular dermatosis following adalimumab therapy for rheumatoid arthritis |journal=Int. J. Dermatol. |volume=52 |issue=5 |pages=624–8 |year=2013 |pmid=23489057 |doi=10.1111/j.1365-4632.2012.05707.x |url=}}</ref>
|
|-
|[[Parapsoriasis|Small plaque parapsoriasis]]<ref name="pmid7026622">{{cite journal |vauthors=Lambert WC, Everett MA |title=The nosology of parapsoriasis |journal=J. Am. Acad. Dermatol. |volume=5 |issue=4 |pages=373–95 |year=1981 |pmid=7026622 |doi= |url=}}</ref>
|
* [[Erythematous]] [[plaques]] which are covered with fine scale.
* May present with elongated, finger-like [[Patched|patches]] symmetrically distributed on the flanks, also known as digitate [[dermatosis]]
|
* [[Lesion|Lesions]] may be [[asymptomatic]]
* May be mildly [[Itch|pruritic]]
* May fade or disappear after sun exposure during the summer season, but typically recur during the winter
|
* May progress to [[mycosis fungoides]]<ref name="pmid16191852">{{cite journal |vauthors=Väkevä L, Sarna S, Vaalasti A, Pukkala E, Kariniemi AL, Ranki A |title=A retrospective study of the probability of the evolution of parapsoriasis en plaques into mycosis fungoides |journal=Acta Derm. Venereol. |volume=85 |issue=4 |pages=318–23 |year=2005 |pmid=16191852 |doi=10.1080/00015550510030087 |url=}}</ref>
|
|-
|[[Intertrigo]]<ref name="pmid16156342">{{cite journal |vauthors=Janniger CK, Schwartz RA, Szepietowski JC, Reich A |title=Intertrigo and common secondary skin infections |journal=Am Fam Physician |volume=72 |issue=5 |pages=833–8 |year=2005 |pmid=16156342 |doi= |url=}}</ref>
|
* Red and fleshy looking lesion in [[skin]] folds
* [[Itching]]
* Oozing
* May be [[sore]]
|
* [[Pruritis]]
* Musty odor
|
* Associated with:
** [[Infections]] ([[Fungal]], [[bacterial]], [[Virus|viral]])
** [[Allergies]]
** [[Diabetes Mellitus|Diabetes]]
** [[Obesity]]
|
|-
|[[Langerhans cell histiocytosis]]<ref name="pmid18577030">{{cite journal |vauthors=Satter EK, High WA |title=Langerhans cell histiocytosis: a review of the current recommendations of the Histiocyte Society |journal=Pediatr Dermatol |volume=25 |issue=3 |pages=291–5 |year=2008 |pmid=18577030 |doi=10.1111/j.1525-1470.2008.00669.x |url=}}</ref>
|
* Scaling and crusting of the [[scalp]]
|
* [[Pathological]] [[fractures]]<ref name="pmid1636041">{{cite journal |vauthors=Stull MA, Kransdorf MJ, Devaney KO |title=Langerhans cell histiocytosis of bone |journal=Radiographics |volume=12 |issue=4 |pages=801–23 |year=1992 |pmid=1636041 |doi=10.1148/radiographics.12.4.1636041 |url=}}</ref>
* Visceromegaly ([[hepatomegaly]], [[spleenomegaly]])
* [[Chronic cough, severe cold|Chronic cough]]
* [[Dyspnea]]<ref name="pmid17527085">{{cite journal |vauthors=Sholl LM, Hornick JL, Pinkus JL, Pinkus GS, Padera RF |title=Immunohistochemical analysis of langerin in langerhans cell histiocytosis and pulmonary inflammatory and infectious diseases |journal=Am. J. Surg. Pathol. |volume=31 |issue=6 |pages=947–52 |year=2007 |pmid=17527085 |doi=10.1097/01.pas.0000249443.82971.bb |url=}}</ref>
* [[Lymphadenopathy]]
|
* Associated with:
** [[Diabetes insipidus]]<ref name="pmid16047354">{{cite journal |vauthors=Grois N, Pötschger U, Prosch H, Minkov M, Arico M, Braier J, Henter JI, Janka-Schaub G, Ladisch S, Ritter J, Steiner M, Unger E, Gadner H |title=Risk factors for diabetes insipidus in langerhans cell histiocytosis |journal=Pediatr Blood Cancer |volume=46 |issue=2 |pages=228–33 |year=2006 |pmid=16047354 |doi=10.1002/pbc.20425 |url=}}</ref>
** [[Pancytopenia]]
|
|-
|[[Tinea manuum]]/pedum/capitis<ref name="pmid15050029">{{cite journal |vauthors=Al Hasan M, Fitzgerald SM, Saoudian M, Krishnaswamy G |title=Dermatology for the practicing allergist: Tinea pedis and its complications |journal=Clin Mol Allergy |volume=2 |issue=1 |pages=5 |year=2004 |pmid=15050029 |pmc=419368 |doi=10.1186/1476-7961-2-5 |url=}}</ref>
|
* [[Scaling skin|Scaling]], flaking, and sometimes [[Blister|blistering]] of the affected areas
* [[Hair]] loss with a black dot on [[scalp]] in case of [[tinea capitis]]
|
* [[Pruritis]]
* [[KOH]] preparation of the lesions confirms [[fungal infection]]
|
* Associated with:
** [[Diabetes mellitus|Diabetes]]
** [[Immunosupression]]
** Intimate contact with [[infected]] person
** May lead to [[asthma]] exacerbation
|
|-
|[[Seborrheic dermatitis]]
|
* [[Papulosquamous]], scaly, flaky, [[itchy]], and red [[rash]] found particularly at [[sebaceous gland]]-rich areas of the [[Human body|body]]
|
|
* Associated with:<ref name="pmid16848386">{{cite journal |vauthors=Schwartz RA, Janusz CA, Janniger CK |title=Seborrheic dermatitis: an overview |journal=Am Fam Physician |volume=74 |issue=1 |pages=125–30 |year=2006 |pmid=16848386 |doi= |url=}}</ref>
** [[AIDS]]
** [[Stress]]<ref name="pmid18033062">{{cite journal |vauthors=Misery L, Touboul S, Vinçot C, Dutray S, Rolland-Jacob G, Consoli SG, Farcet Y, Feton-Danou N, Cardinaud F, Callot V, De La Chapelle C, Pomey-Rey D, Consoli SM |title=[Stress and seborrheic dermatitis] |language=French |journal=Ann Dermatol Venereol |volume=134 |issue=11 |pages=833–7 |year=2007 |pmid=18033062 |doi= |url=}}</ref>
** [[Fungal infection]]
** [[Fatigue]]
** [[Sleep deprivation]]
** Change of season
** [[Parkinson's disease|Parkinson's]] [[disease]]
** [[Biotin]] deficiency
|
|}

==References==
{{Reflist|2}}

[[Category:Disease]]
[[Category:Types of cancer]]
[[Category:Hematology]]

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Hematology]]
[[Category:Immunology]]

Mycosis fungoides pathophysiology

2019-05-30T16:08:26Z

Ahmed Younes: /* Microscopic Pathology */

__NOTOC__
{{Mycosis fungoides}}
{{CMG}};{{AE}} {{S.G.}}
==Overview==
Mycosis fungoides arises from [[T-cell]] lymphocytes, which are normally involved in the cell mediated [[Immunity (medical)|immune]] response. On [[microscopic]] [[histopathological]] [[analysis]], atypical [[lymphoid]] [[Cell (biology)|cells]], [[polymorphous]] [[inflammatory]] infiltrate in the [[dermis]], and [[lymphocytes]] with cerebroid [[nuclei]] are characteristic findings of mycosis fungoides.
==Pathophysiology==
* Mycosis fungoides arises from [[T-cell]] [[Lymphocyte|lymphocytes]], which are normally involved in the [[Cell (biology)|cell]] mediated [[immune]] response.<ref name="pmid26607183">{{cite journal |vauthors=Wilcox RA |title=Cutaneous T-cell lymphoma: 2016 update on diagnosis, risk-stratification, and management |journal=Am. J. Hematol. |volume=91 |issue=1 |pages=151–65 |date=January 2016 |pmid=26607183 |pmc=4715621 |doi=10.1002/ajh.24233 |url=}}</ref>
* The [[tumor]] [[Cell (biology)|cells]] originate from [[memory T cells]] or [[skin]] homing [[CD4+ T cells]] expressing [[cutaneous]] [[lymphocyte]] [[antigen]] (CLA) and [[chemokine]] [[receptors]] [[CCR4]] and CCR7.<ref name="pmid9353122">{{cite journal |vauthors=Fuhlbrigge RC, Kieffer JD, Armerding D, Kupper TS |title=Cutaneous lymphocyte antigen is a specialized form of PSGL-1 expressed on skin-homing T cells |journal=Nature |volume=389 |issue=6654 |pages=978–81 |date=October 1997 |pmid=9353122 |doi=10.1038/40166 |url=}}</ref>
* It is understood that maycosis fungoides is the result of [[malignant]] T cell that derived from a mature CD41 CD45RO1 [[memory T cells]].<ref name="FossGirardi2017">{{cite journal|last1=Foss|first1=Francine M.|last2=Girardi|first2=Michael|title=Mycosis Fungoides and Sezary Syndrome|journal=Hematology/Oncology Clinics of North America|volume=31|issue=2|year=2017|pages=297–315|issn=08898588|doi=10.1016/j.hoc.2016.11.008}}</ref>
* [[Malignant]] [[T cell]] express [[adhesion]] [[Molecule|molecules]] such as [[CCR4]] and [[CLA]].<ref name="FossGirardi2017">{{cite journal|last1=Foss|first1=Francine M.|last2=Girardi|first2=Michael|title=Mycosis Fungoides and Sezary Syndrome|journal=Hematology/Oncology Clinics of North America|volume=31|issue=2|year=2017|pages=297–315|issn=08898588|doi=10.1016/j.hoc.2016.11.008}}</ref>
* [[Immunohistochemistry]] shows [[expression]] [[T cell|T-cell]] [[Antigen|antigens]] such as [[CD7]], [[CD5]], CD26, [[CD2]] and [[CD3 (immunology)|CD3]].<ref name="FossGirardi2017" />
* Mycosis fungoides is [[T cell|T-cell]] [[Lymphoma|lymphomas]] that primary manifest as multiple [[cutaneous]] [[Lesion|lesions]].<ref name="BagheraniSmoller2016">{{cite journal|last1=Bagherani|first1=Nooshin|last2=Smoller|first2=Bruce R.|title=An overview of cutaneous T cell lymphomas|journal=F1000Research|volume=5|year=2016|pages=1882|issn=2046-1402|doi=10.12688/f1000research.8829.1}}</ref>
* Mycosis Fungoides is the most common type of [[cutaneous T cell lymphoma]].<ref name="MahalingamReddy2015">{{cite journal|last1=Mahalingam|first1=Meera|last2=Reddy|first2=Vijaya B.|title=Mycosis Fungoides, Then and Now… Have We Travelled?|journal=Advances In Anatomic Pathology|volume=22|issue=6|year=2015|pages=376–383|issn=1072-4109|doi=10.1097/PAP.0000000000000092}}</ref>

==Microscopic Pathology==
* Mycosis fungoides pathological course may be divided into three main stages:<ref name="SongWillemze2013">{{cite journal|last1=Song|first1=Sophie X.|last2=Willemze|first2=Rein|last3=Swerdlow|first3=Steven H.|last4=Kinney|first4=Marsha C.|last5=Said|first5=Jonathan W.|title=Mycosis Fungoides|journal=American Journal of Clinical Pathology|volume=139|issue=4|year=2013|pages=466–490|issn=1943-7722|doi=10.1309/AJCPOBDP2OQAJ5BR}}</ref><ref name="VoraAnjaneyan2012">{{cite journal|last1=Vora|first1=Rita|last2=Anjaneyan|first2=Gopikrishnan|last3=Mubashir|first3=Syed|last4=Talavia|first4=Parag|title=Mycosis Fungoides: Tumour d′emblee|journal=Indian Dermatology Online Journal|volume=3|issue=2|year=2012|pages=122|issn=2229-5178|doi=10.4103/2229-5178.96709}}</ref><ref name="Tirumalae2013">{{cite journal|last1=Tirumalae|first1=Rajalakshmi|title=Psoriasiform dermatoses: Microscopic approach|journal=Indian Journal of Dermatology|volume=58|issue=4|year=2013|pages=290|issn=0019-5154|doi=10.4103/0019-5154.113945}}</ref>
:* Premycotic stage
:* [[Mycotic]] stage
:* Tumoros stage
* The premycotic stage
:* Non-diagnostic and represented by chronic nonspecific dermatisis associated with psoriasiform changes in [[epidermis]]
* The mycotic stage
:* Shows a [[polymorphous]] [[inflammatory]] infiltrate in the [[dermis]] that contains small numbers of frankly atypical [[lymphoid]] [[cells]]
:* These cells may line up individually along the [[Epidermis (skin)|epidermal]] basal layer
:* The presence of spongiosis is highly suggestive of mycosis fungoides
* Tumoros stage
:* Expansion of the [[dermis]] due to dense [[Infiltration (medical)|infiltration]] by medium sized [[lymphocytes]] that are typically characterized by a [[[cerebroid]] [[nuclei]].
 

==Genetics==
* Development of mycosis fungoides [[disease]] is the result of multiple [[genetic mutations]].<ref name="ShinMonti2007">{{cite journal|last1=Shin|first1=J.|last2=Monti|first2=S.|last3=Aires|first3=D. J.|last4=Duvic|first4=M.|last5=Golub|first5=T.|last6=Jones|first6=D. A.|last7=Kupper|first7=T. S.|title=Lesional gene expression profiling in cutaneous T-cell lymphoma reveals natural clusters associated with disease outcome|journal=Blood|volume=110|issue=8|year=2007|pages=3015–3027|issn=0006-4971|doi=10.1182/blood-2006-12-061507}}</ref><ref name="WongMishra2011">{{cite journal|last1=Wong|first1=Henry K.|last2=Mishra|first2=Anjali|last3=Hake|first3=Timothy|last4=Porcu|first4=Pierluigi|title=Evolving Insights in the Pathogenesis and Therapy of Cutaneous T-cell lymphoma (Mycosis Fungoides and Sezary Syndrome)|journal=British Journal of Haematology|volume=155|issue=2|year=2011|pages=150–166|issn=00071048|doi=10.1111/j.1365-2141.2011.08852.x}}</ref><ref name="Wilcox2011">{{cite journal|last1=Wilcox|first1=Ryan A.|title=Cutaneous T-cell lymphoma: 2011 update on diagnosis, risk-stratification, and management|journal=American Journal of Hematology|volume=86|issue=11|year=2011|pages=928–948|issn=03618609|doi=10.1002/ajh.22139}}</ref><ref name="Whittaker2006">{{cite journal|last1=Whittaker|first1=Sean|title=Biological Insights into the Pathogenesis of Cutaneous T-Cell Lymphomas (CTCL)|journal=Seminars in Oncology|volume=33|year=2006|pages=3–6|issn=00937754|doi=10.1053/j.seminoncol.2005.12.015}}</ref><ref>{{Cite journal
| author = [[Henry K. Wong]]
| title = Novel biomarkers, dysregulated epigenetics, and therapy in cutaneous T-cell lymphoma
| journal = [[Discovery medicine]]
| volume = 16
| issue = 87
| pages = 71–78
| year = 2013
| month = September
| pmid = 23998443
}}</ref>

* Genes involved in the [[pathogenesis]] of mycosis fungoides include:<ref name="KarenkoHahtola2005">{{cite journal|last1=Karenko|first1=Leena|last2=Hahtola|first2=Sonja|last3=Päivinen|first3=Suvi|last4=Karhu|first4=Ritva|last5=Syrjä|first5=Sanna|last6=Kähkönen|first6=Marketta|last7=Nedoszytko|first7=Boguslaw|last8=Kytölä|first8=Soili|last9=Zhou|first9=Ying|last10=Blazevic|first10=Vesna|last11=Pesonen|first11=Maria|last12=Nevala|first12=Hanna|last13=Nupponen|first13=Nina|last14=Sihto|first14=Harri|last15=Krebs|first15=Inge|last16=Poustka|first16=Annemarie|last17=Roszkiewicz|first17=Jadwiga|last18=Saksela|first18=Kalle|last19=Peterson|first19=Pärt|last20=Visakorpi|first20=Tapio|last21=Ranki|first21=Annamari|title=Primary Cutaneous T-Cell Lymphomas Show a Deletion or Translocation AffectingNAV3, the HumanUNC-53Homologue|journal=Cancer Research|volume=65|issue=18|year=2005|pages=8101–8110|issn=0008-5472|doi=10.1158/0008-5472.CAN-04-0366}}</ref>
** [[Deletion (genetics)|Deletions]] or [[translocations]] involving a [[gene]], NAV3, at 12q2 (helicaselike activity)
** [[Deletion (genetics)|Deletion]] in 42 regions and [[amplification]] in 21 observed with meaningful amplifications of 8q (MYC) and 17q ([[STAT3]]) and [[Deletion (genetics)|deletions]] of 17p ([[TP53]]) and 10 ([[PTEN (gene)|PTEN]], FAS)<ref name="LinPasero2012">{{cite journal|last1=Lin|first1=Yea-Lih|last2=Pasero|first2=Philippe|title=Interference Between DNA Replication and Transcription as a Cause of Genomic Instability|journal=Current Genomics|volume=13|issue=1|year=2012|pages=65–73|issn=13892029|doi=10.2174/138920212799034767}}</ref>

*Other [[Deletion (genetics)|deletion]] such as: [[ZEB1]], [[ARID1A]], DNMT3A, [[CDKN2A]], FAS, [[ATM]], [[CTCF]], [[STAT5B]], [[PRKCQ]] and [[somatic]] [[Mutation|mutations]] ([[NFKB2]], [[CD28]], [[RHOA]]) observed in [[gene]] [[sequencing]].<ref name="ChoiGoh2015">{{cite journal|last1=Choi|first1=Jaehyuk|last2=Goh|first2=Gerald|last3=Walradt|first3=Trent|last4=Hong|first4=Bok S|last5=Bunick|first5=Christopher G|last6=Chen|first6=Kan|last7=Bjornson|first7=Robert D|last8=Maman|first8=Yaakov|last9=Wang|first9=Tiffany|last10=Tordoff|first10=Jesse|last11=Carlson|first11=Kacie|last12=Overton|first12=John D|last13=Liu|first13=Kristina J|last14=Lewis|first14=Julia M|last15=Devine|first15=Lesley|last16=Barbarotta|first16=Lisa|last17=Foss|first17=Francine M|last18=Subtil|first18=Antonio|last19=Vonderheid|first19=Eric C|last20=Edelson|first20=Richard L|last21=Schatz|first21=David G|last22=Boggon|first22=Titus J|last23=Girardi|first23=Michael|last24=Lifton|first24=Richard P|title=Genomic landscape of cutaneous T cell lymphoma|journal=Nature Genetics|volume=47|issue=9|year=2015|pages=1011–1019|issn=1061-4036|doi=10.1038/ng.3356}}</ref>

* The development of cutaneous T cell lymphoma is the result of multiple genetic mutations such as (There is not a classic chromosomal translocation in cutaeous T cell lymphoma( MF and SS ) significant):<ref>{{Cite journal
| author = [[Leena Karenko]], [[Sonja Hahtola]], [[Suvi Paivinen]], [[Ritva Karhu]], [[Sanna Syrja]], [[Marketta Kahkonen]], [[Boguslaw Nedoszytko]], [[Soili Kytola]], [[Ying Zhou]], [[Vesna Blazevic]], [[Maria Pesonen]], [[Hanna Nevala]], [[Nina Nupponen]], [[Harri Sihto]], [[Inge Krebs]], [[Annemarie Poustka]], [[Jadwiga Roszkiewicz]], [[Kalle Saksela]], [[Part Peterson]], [[Tapio Visakorpi]] & [[Annamari Ranki]]
| title = Primary cutaneous T-cell lymphomas show a deletion or translocation affecting NAV3, the human UNC-53 homologue
| journal = [[Cancer research]]
| volume = 65
| issue = 18
| pages = 8101–8110
| year = 2005
| month = September
| doi = 10.1158/0008-5472.CAN-04-0366
| pmid = 16166283
}}</ref><ref>{{Cite journal
| author = [[Yaohua Zhang]], [[Yang Wang]], [[Richard Yu]], [[Yuanshen Huang]], [[Mingwan Su]], [[Cheng Xiao]], [[Magdalena Martinka]], [[Jan P. Dutz]], [[Xuejun Zhang]], [[Zhizhong Zheng]] & [[Youwen Zhou]]
| title = Molecular markers of early-stage mycosis fungoides
| journal = [[The Journal of investigative dermatology]]
| volume = 132
| issue = 6
| pages = 1698–1706
| year = 2012
| month = June
| doi = 10.1038/jid.2012.13
| pmid = 22377759
}}</ref><ref>{{Cite journal
| author = [[Alexander Ungewickell]], [[Aparna Bhaduri]], [[Eon Rios]], [[Jason Reuter]], [[Carolyn S. Lee]], [[Angela Mah]], [[Ashley Zehnder]], [[Robert Ohgami]], [[Shashikant Kulkarni]], [[Randall Armstrong]], [[Wen-Kai Weng]], [[Dita Gratzinger]], [[Mahkam Tavallaee]], [[Alain Rook]], [[Michael Snyder]], [[Youn Kim]] & [[Paul A. Khavari]]
| title = Genomic analysis of mycosis fungoides and Sezary syndrome identifies recurrent alterations in TNFR2
| journal = [[Nature genetics]]
| volume = 47
| issue = 9
| pages = 1056–1060
| year = 2015
| month = September
| doi = 10.1038/ng.3370
| pmid = 26258847
}}</ref><ref>{{Cite journal
| author = [[Jaehyuk Choi]], [[Gerald Goh]], [[Trent Walradt]], [[Bok S. Hong]], [[Christopher G. Bunick]], [[Kan Chen]], [[Robert D. Bjornson]], [[Yaakov Maman]], [[Tiffany Wang]], [[Jesse Tordoff]], [[Kacie Carlson]], [[John D. Overton]], [[Kristina J. Liu]], [[Julia M. Lewis]], [[Lesley Devine]], [[Lisa Barbarotta]], [[Francine M. Foss]], [[Antonio Subtil]], [[Eric C. Vonderheid]], [[Richard L. Edelson]], [[David G. Schatz]], [[Titus J. Boggon]], [[Michael Girardi]] & [[Richard P. Lifton]]
| title = Genomic landscape of cutaneous T cell lymphoma
| journal = [[Nature genetics]]
| volume = 47
| issue = 9
| pages = 1011–1019
| year = 2015
| month = September
| doi = 10.1038/ng.3356
| pmid = 26192916
}}</ref>
*chromosomal instability has been noted. Losses on 1p, 10q, 13q, and 17p and gains of 4, 17q, and 18 have been identified <ref name="MaoOrchard2003">{{cite journal|last1=Mao|first1=Xin|last2=Orchard|first2=Guy|last3=Lillington|first3=Debra M.|last4=Russell-Jones|first4=Robin|last5=Young|first5=Bryan D.|last6=Whittaker|first6=Sean|title=Genetic alterations in primary cutaneous CD30+ anaplastic large cell lymphoma|journal=Genes, Chromosomes and Cancer|volume=37|issue=2|year=2003|pages=176–185|issn=10452257|doi=10.1002/gcc.10184}}</ref>
**[[Deletion (genetics)|Deletions]] and [[translocations]] in different [[chromosomes]] or [[chromosomal]] segments
**[[Chromosomal]] [[amplification]] of JunB at 19p12 observed in mycosis fungoides and Sezary syndrome.<ref name="MaoOrchard2003">{{cite journal|last1=Mao|first1=Xin|last2=Orchard|first2=Guy|last3=Lillington|first3=Debra M.|last4=Russell-Jones|first4=Robin|last5=Young|first5=Bryan D.|last6=Whittaker|first6=Sean|title=Genetic alterations in primary cutaneous CD30+ anaplastic large cell lymphoma|journal=Genes, Chromosomes and Cancer|volume=37|issue=2|year=2003|pages=176–185|issn=10452257|doi=10.1002/gcc.10184}}</ref>

==References==
{{Reflist|2}}

[[Category:Disease]]
[[Category:Types of cancer]]
[[Category:Hematology]]

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Hematology]]
[[Category:Immunology]]

Sezary syndrome

2019-05-30T16:05:16Z

Ahmed Younes:

__NOTOC__
{{Sezary syndrome}}
{{CMG}} {{AE}} {{S.G.}}
==Overview==
Sezary syndrome (SS) is one of the most common subtypes of [[cutaneous T cell lymphoma]] ([[Cutaneous T cell lymphoma|CTCL]]). Sezary syndrome is an erythrodermic [[Cutaneous T cell lymphoma|cutaneous T-cell lymphoma]] with a [[leukemic]] involvement of [[malignant]] [[T cell|T cells]] with or without lymphnod and [[visceral]] [[Organ (anatomy)|organ]] involvement. SS is closely related to mycosis fungoides (MF), and the two [[Disorder (medicine)|disorders]] are [[Diagnosis|diagnosed]] and staged by the same [[criteria]] .[[Cutaneous]] [[T-cell lymphoma|T cell lymphoma]] arises from [[T-cell]] [[Lymphocyte|lymphocytes]], which are normally involved in the [[Cell (biology)|cell]] mediated [[immune]] response. Sezary Syndrome constitute the broad [[spectrum]] of [[cutaneous T cell lymphoma]].

==Historical Perspective==
* Sezary syndrome (SS) was first described by Albert Sézary in 1938.<ref name="pmid16871044">{{cite journal |vauthors=Steffen C |title=The man behind the eponym dermatology in historical perspective: Albert Sézary and the Sézary syndrome |journal=Am J Dermatopathol |volume=28 |issue=4 |pages=357–67 |date=August 2006 |pmid=16871044 |doi= |url=}}</ref>
* The association between cell count of [[Lymphocyte|lymphocytes]] in the peripheral [[blood]] with [[Groove for sigmoid sinus|grooved]], lobulated (that is, “cerebriform”) [[nuclei]] and Sezary syndrome was made in the early to mid-20th century.<ref name="pmid266071834">{{cite journal |vauthors=Wilcox RA |title=Cutaneous T-cell lymphoma: 2016 update on diagnosis, risk-stratification, and management |journal=Am. J. Hematol. |volume=91 |issue=1 |pages=151–65 |date=January 2016 |pmid=26607183 |pmc=4715621 |doi=10.1002/ajh.24233 |url=}}</ref>
*
==Classification==
* The staging of sezazry syndrome is based on the TNMB:<ref name="TrautingerEder2017">{{cite journal|last1=Trautinger|first1=Franz|last2=Eder|first2=Johanna|last3=Assaf|first3=Chalid|last4=Bagot|first4=Martine|last5=Cozzio|first5=Antonio|last6=Dummer|first6=Reinhard|last7=Gniadecki|first7=Robert|last8=Klemke|first8=Claus-Detlev|last9=Ortiz-Romero|first9=Pablo L.|last10=Papadavid|first10=Evangelia|last11=Pimpinelli|first11=Nicola|last12=Quaglino|first12=Pietro|last13=Ranki|first13=Annamari|last14=Scarisbrick|first14=Julia|last15=Stadler|first15=Rudolf|last16=Väkevä|first16=Liisa|last17=Vermeer|first17=Maarten H.|last18=Whittaker|first18=Sean|last19=Willemze|first19=Rein|last20=Knobler|first20=Robert|title=European Organisation for Research and Treatment of Cancer consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome – Update 2017|journal=European Journal of Cancer|volume=77|year=2017|pages=57–74|issn=09598049|doi=10.1016/j.ejca.2017.02.027}}</ref>
* Sezary syndrome is defined by [[Enterobacteria phage T4|T4]] [[erythroderma]] of [[body surface area]] (BSA) more than of 80 percent, Sezary [[Cell (biology)|cell]] is more than 1000 cells/microL in B2 involvement of peripheral [[blood]] staged of Sezary syndrome is based on the presence of [[Nodal marginal zone lymphoma|nodal]] and/or [[visceral]] involvement<ref name="pmid17540844">{{cite journal |vauthors=Olsen E, Vonderheid E, Pimpinelli N, Willemze R, Kim Y, Knobler R, Zackheim H, Duvic M, Estrach T, Lamberg S, Wood G, Dummer R, Ranki A, Burg G, Heald P, Pittelkow M, Bernengo MG, Sterry W, Laroche L, Trautinger F, Whittaker S |title=Revisions to the staging and classification of mycosis fungoides and Sezary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC) |journal=Blood |volume=110 |issue=6 |pages=1713–22 |date=September 2007 |pmid=17540844 |doi=10.1182/blood-2007-03-055749 |url=}}</ref>
{| class="wikitable"
|+
! colspan="3" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Staging for mycosis fungoides and Sezary syndrome
|-
! colspan="3" style="background: #B0C4DE; color: #FFFFFF; text-align: center;" |'''[[Skin]] (T)'''
|-
| align="center" style="background:#ADD8E6;" |T1
|Limited patches, [[Papule|papules]], and/or [[Plaque|plaques]] covering <10% of the [[skin]] [[Surface area|surface]]. May further stratify into T1a ([[Patched|patch]] only) versus T1b ([[plaque]] [[Patched|patch]])
|-
| align="center" style="background:#ADD8E6;" |T2
|Patches, [[Papule|papules]], [[or]] [[Plaque|plaques]] covering 10% of the [[skin]] [[Surface area|surface]]. May further stratify into T2a (patch only) versus T2b ([[plaque]] patch).
|-
| align="center" style="background:#ADD8E6;" |T3
|One or more [[Tumor|tumours]] (1-cm diameter)
|-
| align="center" style="background:#ADD8E6;" |T4
|Confluence of [[erythema]] covering 80% [[body surface area]]
|-
! colspan="3" style="background: #B0C4DE; color: #FFFFFF; text-align: center;" |'''Node (N)'''
|-
| align="center" style="background:#ADD8E6;" |N0
|No [[Clinical|clinically]] [[abnormal]] [[T-cell lymphoma classification|peripheral]] [[Lymph node|lymph nodes]]; [[biopsy]] not required
|-
| align="center" style="background:#ADD8E6;" |N1
|Clinically [[abnormal]] [[Lymph node|lymph nodes]]; [[histopathology]] Dutch grade 1 or [[NCI]] LN0-2
|-
| align="center" style="background:#ADD8E6;" |N1a
|[[Clone]] negative
|-
| align="center" style="background:#ADD8E6;" |N1b
|[[Clone]] posetive
|-
| align="center" style="background:#ADD8E6;" |N2
|[[Clinical|Clinically]] [[abnormal]] [[T-cell lymphoma classification|peripheral]] [[Lymph node|lymph nodes]]; [[histopathology]] Dutch grade 2 or [[NCI]] LN3
|-
| align="center" style="background:#ADD8E6;" |N2a
|[[Clone]] negatove
|-
| align="center" style="background:#ADD8E6;" |N2b
|[[Clone]] posetive
|-
| align="center" style="background:#ADD8E6;" |N3
|[[Clinical|Clinically]] [[abnormal]] [[T-cell lymphoma classification|peripheral]] [[Lymph node|lymph nodes]]; [[histopathology]] Dutch grades 3e4 or [[NCI]] LN4; [[clone]] positive or negative
|-
| align="center" style="background:#ADD8E6;" |NX
|[[Clinical|Clinically]] [[abnormal]] [[T-cell lymphoma classification|peripheral]] [[Lymph node|lymph nodes]]; no [[histologic]] confirmation
|-
! colspan="3" style="background: #B0C4DE; color: #FFFFFF; text-align: center;" |[[Visceral|'''Visceral''']] ('''M''')
|-
| align="center" style="background:#ADD8E6;" |M0
|No [[visceral]] [[Organ (anatomy)|organ]] involvement
|-
| align="center" style="background:#ADD8E6;" |M1
|[[Visceral]] involvement (must have [[pathology]] confirmation and [[Organ (anatomy)|organ]] involved should be specified)
|-
! colspan="3" style="background: #B0C4DE; color: #FFFFFF; text-align: center;" |[[Blood|'''Blood''']] '''(B)'''
|-
| align="center" style="background:#ADD8E6;" |B0
|0 Absence of significant [[blood]] involvement: 5% of [[T-cell lymphoma classification|peripheral]] [[blood]] [[Lymphocyte|lymphocytes]] are atypical (Sezary) [[Cell (biology)|cell]]<nowiki/>s B0a [[Clone]] negative B0b [[Clone (cell biology)|Clone]] positive
|-
| align="center" style="background:#ADD8E6;" |B1
|Low [[blood]] [[Tumor|tumour]] burden: >5% of [[T-cell lymphoma classification|peripheral]] [[blood]] [[Lymphocyte|lymphocytes]] are atypical (Sezary) cells but does not meet the [[criteria]] of B2 B1a Clone negative B1b [[Clone (cell biology)|Clone]] positive
|-
| align="center" style="background:#ADD8E6;" |B2
|High [[blood]] tumour burden: 1000/mL Sezary [[Cell (biology)|cells]] with positive clone
|}

The staging of [[Sezary syndrome]] is based on the [[clinical]] stages:<ref name="TrautingerEder2017" /><ref name="JawedMyskowski2014">{{cite journal|last1=Jawed|first1=Sarah I.|last2=Myskowski|first2=Patricia L.|last3=Horwitz|first3=Steven|last4=Moskowitz|first4=Alison|last5=Querfeld|first5=Christiane|title=Primary cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome)|journal=Journal of the American Academy of Dermatology|volume=70|issue=2|year=2014|pages=205.e1–205.e16|issn=01909622|doi=10.1016/j.jaad.2013.07.049}}</ref>

{| class="wikitable"
|+
! colspan="6" style="background: #4479BA; color: #FFFFFF; text-align: center;" !colspan="3" |clinical stages
|-
| align="center" style="background:#6495ED;" |Stage
! colspan="1" style="background: #B0C4DE; color:#FFFFFF; text-align: center;" |T
! colspan="1" style="background: #B0C4DE; color:#FFFFFF; text-align: center;" |N
! colspan="1" style="background: #B0C4DE; color:#FFFFFF; text-align: center;" |M
! colspan="1" style="background: #B0C4DE; color:#FFFFFF; text-align: center;" |B
! colspan="1" style="background: #B0C4DE; color:#FFFFFF; text-align: center;" |DDS
|-
| align="center" style="background:#ADD8E6;" |IA
|1
|0
|0
|0/1
|98
|-
| align="center" style="background:#ADD8E6;" |IB
|2
|0
|0
|0/1
|89
|-
| align="center" style="background:#ADD8E6;" |IIA
|1.2
|1.2
|0
|0/1
|89
|-
| align="center" style="background:#ADD8E6;" |IIB
|3
|0-2
|0
|0/1
|56
|-
| align="center" style="background:#ADD8E6;" |IIIA
|4
|0-2
|0
|0
|54
|-
| align="center" style="background:#ADD8E6;" |IIIB
|4
|0-2
|0
|1
|48
|-
| align="center" style="background:#ADD8E6;" |IVA1
|1-4
|0-2
|0
|2
|41
|-
| align="center" style="background:#ADD8E6;" |IVA2
|1-4
|3
|0
|0-2
|23
|-
| align="center" style="background:#ADD8E6;" |IVB
|1-4
|0-3
|1
|0-2
|18
|}

*[5-year [[disease]] free [[survival]] (DSS)]

==Pathophysiology==
* The exact [[pathogenesis]] of Sezary syndrome is not fully understood.<ref name="SauliteHoetzenecker2016">{{cite journal|last1=Saulite|first1=Ieva|last2=Hoetzenecker|first2=Wolfram|last3=Weidinger|first3=Stephan|last4=Cozzio|first4=Antonio|last5=Guenova|first5=Emmanuella|last6=Wehkamp|first6=Ulrike|title=Sézary Syndrome and Atopic Dermatitis: Comparison of Immunological Aspects and Targets|journal=BioMed Research International|volume=2016|year=2016|pages=1–15|issn=2314-6133|doi=10.1155/2016/9717530}}</ref>
* Sezary syndrome is an [[Erythroderma|erythrodermic]] [[cutaneous]] [[T-cell lymphoma]] with a [[leukemic]] involvement of [[malignant]] [[T cell|T cells]].<ref name="pmid12859741">{{cite journal |vauthors=Balfour EM, Glusac EJ, Heald P, Talley LL, Smoller BR |title=Sezary syndrome: cutaneous immunoperoxidase double-labeling technique demonstrates CD4/CD8 ratio non-specificity |journal=J. Cutan. Pathol. |volume=30 |issue=7 |pages=437–42 |date=August 2003 |pmid=12859741 |doi= |url=}}</ref>
* [[Cutaneous]] [[T-cell lymphoma|T cell lymphoma]] arises from [[T-cell]] [[Lymphocyte|lymphocytes]], which are normally involved in the [[Cell (biology)|cell]] mediated [[immune]] response.<ref name="pmid26607183">{{cite journal |vauthors=Wilcox RA |title=Cutaneous T-cell lymphoma: 2016 update on diagnosis, risk-stratification, and management |journal=Am. J. Hematol. |volume=91 |issue=1 |pages=151–65 |date=January 2016 |pmid=26607183 |pmc=4715621 |doi=10.1002/ajh.24233 |url=}}</ref>
* Sezary syndrome's [[Patient|patients]] have [[Immunodeficiency|suppressed]] [[Immunity (medical)|immunity]], as the [[malignant]] [[Cell (biology)|cells]] produce type-2, [[T cell|T-cell]] ([[T helper cell|Th2]]) [[Cytokine|cytokines]] which suppress [[T helper cell|Th1]] [[Immunity (medical)|immunity]] by decreasing the production of [[Interleukin 12|IL-12]]. The role of [[Interleukin 12|IL-12]] is to stimulate the production of [[interferon]] [[gamma]] and [[tumor necrosis factor-alpha]] ([[TNF-alpha|TNF-a]]), thus protecting against [[Tumor|tumors]].<ref name="SauliteHoetzenecker2016">{{cite journal|last1=Saulite|first1=Ieva|last2=Hoetzenecker|first2=Wolfram|last3=Weidinger|first3=Stephan|last4=Cozzio|first4=Antonio|last5=Guenova|first5=Emmanuella|last6=Wehkamp|first6=Ulrike|title=Sézary Syndrome and Atopic Dermatitis: Comparison of Immunological Aspects and Targets|journal=BioMed Research International|volume=2016|year=2016|pages=1–15|issn=2314-6133|doi=10.1155/2016/9717530}}</ref>
* The [[tumor]] [[Cell (biology)|cells]] originate from [[memory T cells]] or [[skin]] homing [[CD4+ T cells]] expressing [[cutaneous]] [[lymphocyte]] [[antigen]] (CLA) and [[chemokine]] [[receptors]] [[CCR4]] and CCR7.<ref name="pmid9353122">{{cite journal |vauthors=Fuhlbrigge RC, Kieffer JD, Armerding D, Kupper TS |title=Cutaneous lymphocyte antigen is a specialized form of PSGL-1 expressed on skin-homing T cells |journal=Nature |volume=389 |issue=6654 |pages=978–81 |date=October 1997 |pmid=9353122 |doi=10.1038/40166 |url=}}</ref>
* A few [[Patient|patients]] of Sezary syndrome are associated with human [[T cell|T]]-lymphotropic virus types 1 and 2 (HTLV1 and HTLV2) In Japan, Caribbean islands, and the Middle East.<ref name="pmid24982574">{{cite journal |vauthors=Graham RL, Burch M, Krause JR |title=Adult T-cell leukemia/lymphoma |journal=Proc (Bayl Univ Med Cent) |volume=27 |issue=3 |pages=235–8 |date=July 2014 |pmid=24982574 |pmc=4059578 |doi= |url=}}</ref><ref name="pmid21145619">{{cite journal |vauthors=Olsen EA, Rook AH, Zic J, Kim Y, Porcu P, Querfeld C, Wood G, Demierre MF, Pittelkow M, Wilson LD, Pinter-Brown L, Advani R, Parker S, Kim EJ, Junkins-Hopkins JM, Foss F, Cacchio P, Duvic M |title=Sézary syndrome: immunopathogenesis, literature review of therapeutic options, and recommendations for therapy by the United States Cutaneous Lymphoma Consortium (USCLC) |journal=J. Am. Acad. Dermatol. |volume=64 |issue=2 |pages=352–404 |date=February 2011 |pmid=21145619 |doi=10.1016/j.jaad.2010.08.037 |url=}}</ref>
* In Sezary syndrome's [[Patient|patients]] [[blood]] [[flow]] cytometry shown [[measurement]] of the [[CD4+]]CD26- population of [[Lymphocyte|lymphocytes]] is a valuable tool for monitoring and CD26 seen in >90% of [[Patient|patients]] and [[CD7]] loss in 50% of [[patients]]. <ref name="pmid16112348">{{cite journal |vauthors=Introcaso CE, Hess SD, Kamoun M, Ubriani R, Gelfand JM, Rook AH |title=Association of change in clinical status and change in the percentage of the CD4+CD26- lymphocyte population in patients with Sézary syndrome |journal=J. Am. Acad. Dermatol. |volume=53 |issue=3 |pages=428–34 |date=September 2005 |pmid=16112348 |doi=10.1016/j.jaad.2005.06.001 |url=}}</ref><ref name="GorczycaWeisberger2002">{{cite journal|last1=Gorczyca|first1=Wojciech|last2=Weisberger|first2=James|last3=Liu|first3=Z.|last4=Tsang|first4=Patricia|last5=Hossein|first5=Monowar|last6=Wu|first6=C. Daniel|last7=Dong|first7=Henry|last8=Wong|first8=John Y.L.|last9=Tugulea|first9=Sorina|last10=Dee|first10=Simpson|last11=Melamed|first11=Myron R.|last12=Darzynkiewicz|first12=Zbigniew|title=An approach to diagnosis of T-cell lymphoproliferative disorders by flow cytometry|journal=Cytometry|volume=50|issue=3|year=2002|pages=177–190|issn=0196-4763|doi=10.1002/cyto.10003}}</ref>
* In majority of Sezary syndrome's patients peripheral [[blood]] [[T cell]] seen [[CD3 (immunology)|CD3+]], [[CD4|CD4+]], [[CD7|CD7-]], [[CD26]]-, [[CD8|CD8-]].<ref name="pmid28802499">{{cite journal |vauthors=Pulitzer M |title=Cutaneous T-cell Lymphoma |journal=Clin. Lab. Med. |volume=37 |issue=3 |pages=527–546 |date=September 2017 |pmid=28802499 |pmc=5710803 |doi=10.1016/j.cll.2017.06.006 |url=}}</ref>
* In some Sezary syndrome [[Patient|patients]] [[CD8|CD8+]] [[phenotype]] seen with [[retroviral]] [[Infection|infections]] ([[Human T-lymphotropic virus|HTLV-1]]/2 or HIV).<ref name="pmid15841167">{{cite journal |vauthors=Kim EJ, Hess S, Richardson SK, Newton S, Showe LC, Benoit BM, Ubriani R, Vittorio CC, Junkins-Hopkins JM, Wysocka M, Rook AH |title=Immunopathogenesis and therapy of cutaneous T cell lymphoma |journal=J. Clin. Invest. |volume=115 |issue=4 |pages=798–812 |date=April 2005 |pmid=15841167 |pmc=1070436 |doi=10.1172/JCI24826 |url=}}</ref><ref name="KashanchiCoelho-dos-Reis2013">{{cite journal|last1=Kashanchi|first1=Fatah|last2=Coelho-dos-Reis|first2=Jordana Grazziela Alves|last3=Passos|first3=Livia|last4=Duarte|first4=Mariana Costa|last5=Araújo|first5=Marcelo Grossi|last6=Campi-Azevedo|first6=Ana Carolina|last7=Teixeira-Carvalho|first7=Andréa|last8=Peruhype-Magalhães|first8=Vanessa|last9=Trindade|first9=Bruno Caetano|last10=dos Santos Dias|first10=Raquel|last11=Martins|first11=Marina Lobato|last12=Carneiro-Proietti|first12=Anna Barbara de Freitas|last13=Guedes|first13=Antônio Carlos|last14=Gonçalves|first14=Denise Utsch|last15=Martins-Filho|first15=Olindo Assis|title=Immunological Profile of HTLV-1-Infected Patients Associated with Infectious or Autoimmune Dermatological Disorders|journal=PLoS Neglected Tropical Diseases|volume=7|issue=7|year=2013|pages=e2328|issn=1935-2735|doi=10.1371/journal.pntd.0002328}}</ref><ref name="Myskowski1991">{{cite journal|last1=Myskowski|first1=Patricia L.|title=Cutaneous T-Cell Lymphoma and Human Immunodeficiency Virus|journal=Archives of Dermatology|volume=127|issue=7|year=1991|pages=1045|issn=0003-987X|doi=10.1001/archderm.1991.01680060119017}}</ref>
* Sezary syndrome cells are [[T-cells]] that have pathological quantities of [[Mucopolysaccharide|mucopolysaccharides]].
* When Sezary cells move from the [[blood]] into the [[skin]], the skin problem is seen and Sezary cells are finded in [[rash]].
* In sezary syndrome maybe one or more [[chromosomal]] [[abnormalities]], such as the loss or gain of [[Genetics|genetic]].<ref name="pmid271214732">{{cite journal |vauthors=Woollard WJ, Pullabhatla V, Lorenc A, Patel VM, Butler RM, Bayega A, Begum N, Bakr F, Dedhia K, Fisher J, Aguilar-Duran S, Flanagan C, Ghasemi AA, Hoffmann RM, Castillo-Mosquera N, Nuttall EA, Paul A, Roberts CA, Solomonidis EG, Tarrant R, Yoxall A, Beyers CZ, Ferreira S, Tosi I, Simpson MA, de Rinaldis E, Mitchell TJ, Whittaker SJ |title=Candidate driver genes involved in genome maintenance and DNA repair in Sézary syndrome |journal=Blood |volume=127 |issue=26 |pages=3387–97 |date=June 2016 |pmid=27121473 |doi=10.1182/blood-2016-02-699843 |url=}}</ref><ref name="pmid266071832">{{cite journal |vauthors=Wilcox RA |title=Cutaneous T-cell lymphoma: 2016 update on diagnosis, risk-stratification, and management |journal=Am. J. Hematol. |volume=91 |issue=1 |pages=151–65 |date=January 2016 |pmid=26607183 |pmc=4715621 |doi=10.1002/ajh.24233 |url=}}</ref>

==Microscopic pathology==
* '''Light microscopic findings''' : On [[microscopic]] [[Histopathology|histopathological]] [[analysis]], movement of the atypical [[Lymphocyte|lymphocytes]] into the [[Epidermis (skin)|epidermis]], atypical [[Cell (biology)|cells]] in intra [[Epidermis (skin)|epidermal]], and infiltrate of [[Inflammation|inflammatory]] [[T cell|T cells]] are characteristic findings of Sezary syndrome.<ref name="pmid22496939">{{cite journal |vauthors=Arafah M, Zaidi SN, Kfoury HK, Al Rikabi A, Al Ghamdi K |title=The Histological Spectrum of Early Mycosis Fungoides: A Study of 58 Saudi Arab patients |journal=Oman Med J |volume=27 |issue=2 |pages=134–9 |date=March 2012 |pmid=22496939 |pmc=3321345 |doi=10.5001/omj.2012.28 |url=}}</ref>
* Sezary cells are aypical [[mononuclear cells]] with moderately to highly grooved [[nuclei]], termed seen in prepheral [[blood]] [[morphology]]<ref name="pmid2653459">{{cite journal |vauthors=Chu AC, Morris JF |title=Sézary cell morphology induced in peripheral blood lymphocytes: re-evaluation |journal=Blood |volume=73 |issue=6 |pages=1603–7 |date=May 1989 |pmid=2653459 |doi= |url=}}</ref>, Sezary [[Cell (biology)|cell]] is large than normal [[Lymphocyte|lymphocyt]] [[Cell (biology)|cell]].<ref name="pmid11756953">{{cite journal |vauthors=Vonderheid EC, Bernengo MG, Burg G, Duvic M, Heald P, Laroche L, Olsen E, Pittelkow M, Russell-Jones R, Takigawa M, Willemze R |title=Update on erythrodermic cutaneous T-cell lymphoma: report of the International Society for Cutaneous Lymphomas |journal=J. Am. Acad. Dermatol. |volume=46 |issue=1 |pages=95–106 |date=January 2002 |pmid=11756953 |doi= |url=}}</ref>
* '''Clonality of the T cell receptor (TCR) gene rearrangement''' : [[Clone (cell biology)|Clonality]] of the [[T cell receptor]] ([[T cell receptor|TCR]]) [[gene]] [[rearrangement]] by [[polymerase]] chain [[reaction]].<ref name="pmid16172316">{{cite journal |vauthors=Guitart J |title=Beyond clonal detection: defining the T-cell clone |journal=Arch Dermatol |volume=141 |issue=9 |pages=1159–60 |date=September 2005 |pmid=16172316 |doi=10.1001/archderm.141.9.1159 |url=}}</ref>
* High throughput [[T cell receptor|TCR]] sequen is more sensitive technique than [[T cell receptor]] ([[TCR]]).<ref name="pmid26446955">{{cite journal |vauthors=Kirsch IR, Watanabe R, O'Malley JT, Williamson DW, Scott LL, Elco CP, Teague JE, Gehad A, Lowry EL, LeBoeuf NR, Krueger JG, Robins HS, Kupper TS, Clark RA |title=TCR sequencing facilitates diagnosis and identifies mature T cells as the cell of origin in CTCL |journal=Sci Transl Med |volume=7 |issue=308 |pages=308ra158 |date=October 2015 |pmid=26446955 |pmc=4765389 |doi=10.1126/scitranslmed.aaa9122 |url=}}</ref>

==Causes==
* The cause of Sezary syndrome has not been identified.<ref name="pmid21883142">{{cite journal |vauthors=Wong HK, Mishra A, Hake T, Porcu P |title=Evolving insights in the pathogenesis and therapy of cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome) |journal=Br. J. Haematol. |volume=155 |issue=2 |pages=150–66 |date=October 2011 |pmid=21883142 |pmc=4309373 |doi=10.1111/j.1365-2141.2011.08852.x |url=}}</ref><ref name="pmid27121473">{{cite journal |vauthors=Woollard WJ, Pullabhatla V, Lorenc A, Patel VM, Butler RM, Bayega A, Begum N, Bakr F, Dedhia K, Fisher J, Aguilar-Duran S, Flanagan C, Ghasemi AA, Hoffmann RM, Castillo-Mosquera N, Nuttall EA, Paul A, Roberts CA, Solomonidis EG, Tarrant R, Yoxall A, Beyers CZ, Ferreira S, Tosi I, Simpson MA, de Rinaldis E, Mitchell TJ, Whittaker SJ |title=Candidate driver genes involved in genome maintenance and DNA repair in Sézary syndrome |journal=Blood |volume=127 |issue=26 |pages=3387–97 |date=June 2016 |pmid=27121473 |doi=10.1182/blood-2016-02-699843 |url=}}</ref>
* Sezary syndrome might have one or more of the [[chromosomal]] [[abnormalities]], such as the loss or gain of [[Genetics|genetic]].<ref name="pmid271214732" /><ref name="pmid266071832" />

==Clinical Features==
===History===
* The majority of sezary syndrome [[Patient|patients]] present with developing [[lymphadenopathy]] and [[erythroderma]] for weeks to months.<ref name="pmid266071835">{{cite journal |vauthors=Wilcox RA |title=Cutaneous T-cell lymphoma: 2016 update on diagnosis, risk-stratification, and management |journal=Am. J. Hematol. |volume=91 |issue=1 |pages=151–65 |date=January 2016 |pmid=26607183 |pmc=4715621 |doi=10.1002/ajh.24233 |url=}}</ref>
* [[Cutaneous]] [[T-cell lymphoma|T cell lymphoma]] is usually initially seen by dermatologists with [[Patient|patients]] presenting with [[skin]] [[Lesion|lesions]] such as [[erythematous]] patches or [[plaque]].<ref name="pmid26759546">{{cite journal |vauthors=Sokołowska-Wojdyło M, Olek-Hrab K, Ruckemann-Dziurdzińska K |title=Primary cutaneous lymphomas: diagnosis and treatment |journal=Postepy Dermatol Alergol |volume=32 |issue=5 |pages=368–83 |date=October 2015 |pmid=26759546 |pmc=4692822 |doi=10.5114/pdia.2015.54749 |url=}}</ref>
* Sezary syndrome is known as [[leukemic]] form of [[cutaneous T cell lymphoma]] ([[Cutaneous T cell lymphoma|CTCL]]) that associated with [[erythroderma]].
*Early clinical features of Sezary syndrome include:<ref name="pmid231971992">{{cite journal |vauthors=Yamashita T, Abbade LP, Marques ME, Marques SA |title=Mycosis fungoides and Sézary syndrome: clinical, histopathological and immunohistochemical review and update |journal=An Bras Dermatol |volume=87 |issue=6 |pages=817–28; quiz 829–30 |date=2012 |pmid=23197199 |pmc=3699909 |doi= |url=}}</ref>
:*Mimic [[psoriasis]]
:*[[Chronic (medical)|Chronic]] [[eczema]]
:*[[Atopic dermatitis (patient information)|Atopic dermatitis]]
:*[[Leprosy]]
:*Lichenoid [[pityriasis]]
* In Sezary syndrome single or multiple [[Lesion|lesions]]( thin [[erythematous]] [[Plaque|plaques]] or flat patche) is a typucal [[skin]] involvement in the [[gluteal]] region or [[Thigh|thighs]]. <ref name="Olsen2015">{{cite journal|last1=Olsen|first1=Elise A.|title=Evaluation, Diagnosis, and Staging of Cutaneous Lymphoma|journal=Dermatologic Clinics|volume=33|issue=4|year=2015|pages=643–654|issn=07338635|doi=10.1016/j.det.2015.06.001}}</ref>
* The [[Lesion|lesions]] of Sezary syndrome can be [[Pruritic disorders|pruritic]] or remain stable for many years, go into remission, or grow slowly<ref name="Panda2007">{{cite journal|last1=Panda|first1=Saumya|title=Mycosis fungoides: Current trends in diagnosis and management|journal=Indian Journal of Dermatology|volume=52|issue=1|year=2007|pages=5|issn=0019-5154|doi=10.4103/0019-5154.31918}}</ref>
* [[Patient|Patients]] with Sezary syndrome have a positive history of [[Pruritis|pruritic]], [[infection]], second [[malignancy]] such as [[Hodgkin's lymphoma|hodgkin lymphoma]], [[non-Hodgkin lymphoma]], [[melanoma]], [[urinary]] [[cancer]].<ref name="pmid29853749">{{cite journal |vauthors=Kim YJ, Shin HJ, Won CH, Chang SE, Lee MW, Choi JH, Lee WJ |title=The Incidence of Other Primary Cancers in Patients with Cutaneous Lymphoma |journal=Ann Dermatol |volume=30 |issue=3 |pages=335–341 |date=June 2018 |pmid=29853749 |pmc=5929952 |doi=10.5021/ad.2018.30.3.335 |url=}}</ref>
* [[Patient|Patients]] with Sezary syndrome often have a history of several years of [[Eczema|eczematous]] or [[dermatitis]] [[skin]] [[Lesion|lesions]] before the [[diagnosis]] is finally established.<ref name="pmid23074497">{{cite journal |vauthors= |title=Extracorporeal photophoresis: an evidence-based analysis |journal=Ont Health Technol Assess Ser |volume=6 |issue=6 |pages=1–82 |date=2006 |pmid=23074497 |pmc=3379535 |doi= |url=}}</ref>
* The [[skin]] [[Lesion|lesions]] then progress from the patch stage to the [[plaque]] stage to [[cutaneous]] [[Tumor|tumors]], [[skin]] is often [[Pruritis|pruritic]] and affected on quality of life of [[Patient|patients]].<ref name="pmid17048251">{{cite journal |vauthors=Demierre MF, Gan S, Jones J, Miller DR |title=Significant impact of cutaneous T-cell lymphoma on patients' quality of life: results of a 2005 National Cutaneous Lymphoma Foundation Survey |journal=Cancer |volume=107 |issue=10 |pages=2504–11 |date=November 2006 |pmid=17048251 |doi=10.1002/cncr.22252 |url=}}</ref>

===Signs===
Common signs of Sezary syndrome include:<ref name="pmid249363242">{{cite journal |vauthors=Olek-Hrab K, Silny W |title=Diagnostics in mycosis fungoides and Sezary syndrome |journal=Rep Pract Oncol Radiother |volume=19 |issue=2 |pages=72–6 |date=March 2014 |pmid=24936324 |pmc=4054990 |doi=10.1016/j.rpor.2013.11.001 |url=}}</ref>
*Widespread [[erythema]]
**In Sezary syndrome widespread [[erythema]] can be finely scaly, indurated, or even resemble livido [[reticularis]]
*
*[[Indurated]]
*Resemble livido [[reticularis]]
*[[Erythema]](Not seen in some [[Patient|patients]])<ref name="ThompsonKillian2017">{{cite journal|last1=Thompson|first1=Agnieszka K.|last2=Killian|first2=Jill M.|last3=Weaver|first3=Amy L.|last4=Pittelkow|first4=Mark R.|last5=Davis|first5=Mark D.P.|title=Sézary syndrome without erythroderma: A review of 16 cases at Mayo Clinic|journal=Journal of the American Academy of Dermatology|volume=76|issue=4|year=2017|pages=683–688|issn=01909622|doi=10.1016/j.jaad.2016.10.029}}</ref>
*The severity of [[erythema]] [[body surface area]] (BSA) involved may wax and wane(>80% of BSA)

===Skin lesions===
The other [[skin]] [[lesion]] [[Symptom|symptoms]] of Sezary syndrome are:
*Patches and [[Plaque|plaques]] to [[erythroderma]]
*[[Keratosis pilaris]]
*[[Alopecia]] ([[hair loss]])
*[[Ectropion]]
*[[Keratoderma]]
*[[Hypertrophy (medical)|Hypertrophic]] [[Nail (anatomy)|nails]]
*Erosions
*[[Lichenification]]
*[[Trouble]] regulating [[Body Temperature|body temperature]]
*[[Abnormal|Abnormalities]] of [[fingernails]] and [[toenails]]
*
===Other Signs===
Some patients with Sezary syndrome have<ref name="pmid3408055">{{cite journal |vauthors=Sausville EA, Eddy JL, Makuch RW, Fischmann AB, Schechter GP, Matthews M, Glatstein E, Ihde DC, Kaye F, Veach SR |title=Histopathologic staging at initial diagnosis of mycosis fungoides and the Sézary syndrome. Definition of three distinctive prognostic groups |journal=Ann. Intern. Med. |volume=109 |issue=5 |pages=372–82 |date=September 1988 |pmid=3408055 |doi= |url=}}</ref><ref name="pmid15949023">{{cite journal |vauthors=Beylot-Barry M, Parrens M, Delaunay M, Thiebault R, Vergier B, DeMascarel A, Dubus P, Beylot C, Merlio JP |title=Is bone marrow biopsy necessary in patients with mycosis fungoides and Sézary syndrome? A histological and molecular study at diagnosis and during follow-up |journal=Br. J. Dermatol. |volume=152 |issue=6 |pages=1378–9 |date=June 2005 |pmid=15949023 |doi=10.1111/j.1365-2133.2005.06621.x |url=}}</ref>
* [[Lymphadenopathy]]
* [[Viscera|Viscer]]

==Differentiating Sezary syndrome from other Diseases==
*Sezary syndrome must be differentiated from other [[Disease|diseases]] that cause:<ref name="pmid23197199">{{cite journal |vauthors=Yamashita T, Abbade LP, Marques ME, Marques SA |title=Mycosis fungoides and Sézary syndrome: clinical, histopathological and immunohistochemical review and update |journal=An Bras Dermatol |volume=87 |issue=6 |pages=817–28; quiz 829–30 |date=2012 |pmid=23197199 |pmc=3699909 |doi= |url=}}</ref><ref name="pmid249363243">{{cite journal |vauthors=Olek-Hrab K, Silny W |title=Diagnostics in mycosis fungoides and Sezary syndrome |journal=Rep Pract Oncol Radiother |volume=19 |issue=2 |pages=72–6 |date=March 2014 |pmid=24936324 |pmc=4054990 |doi=10.1016/j.rpor.2013.11.001 |url=}}</ref><ref name="pmid18652582">{{cite journal |vauthors=Klemke CD, Brade J, Weckesser S, Sachse MM, Booken N, Neumaier M, Goerdt S, Nebe TC |title=The diagnosis of Sézary syndrome on peripheral blood by flow cytometry requires the use of multiple markers |journal=Br. J. Dermatol. |volume=159 |issue=4 |pages=871–80 |date=September 2008 |pmid=18652582 |doi=10.1111/j.1365-2133.2008.08739.x |url=}}</ref><ref name="pmid21985996">{{cite journal |vauthors=Scala E, Abeni D, Palazzo P, Liso M, Pomponi D, Lombardo G, Picchio MC, Narducci MG, Russo G, Mari A |title=Specific IgE toward allergenic molecules is a new prognostic marker in patients with Sézary syndrome |journal=Int. Arch. Allergy Immunol. |volume=157 |issue=2 |pages=159–67 |date=2012 |pmid=21985996 |doi=10.1159/000327553 |url=}}</ref><ref name="pmid3528307">{{cite journal |vauthors=Chu AC, Robinson D, Hawk JL, Meacham R, Spittle MF, Smith NP |title=Immunologic differentiation of the Sézary syndrome due to cutaneous T-cell lymphoma and chronic actinic dermatitis |journal=J. Invest. Dermatol. |volume=86 |issue=2 |pages=134–7 |date=February 1986 |pmid=3528307 |doi= |url=}}</ref>
** Mycosis fangoides
***Sezaruy syndrome is more symptoI contrast to patch or plaque MF, SS is much more symptomatic. Sezary syndrome patients tend to present with diffuse skin involvement,not like mycosis fungoides usually evolve through patches and plaques to erythroderma <ref name="pmid27407986">{{cite journal |vauthors=Chand K, Sayal SK, Chand S |title=Cutaneous T-Cell Lymphoma (Mycosis Fungoides) |journal=Med J Armed Forces India |volume=63 |issue=2 |pages=188–90 |date=April 2007 |pmid=27407986 |pmc=4925357 |doi=10.1016/S0377-1237(07)80076-1 |url=}}</ref>
***In Sezary syndrome infiltration of skin is generally much less dense than plaque in mycosis fungoides (MF)
** [[Eczema]]
** [[Psoriasis]]
** [[Pityriasis rubra pilaris]]
** [[dermatitis]]
** [[Hypereosinophilic syndrome]]
** [[Adult T-cell leukemia]]
** [[Atopic Dermatitis|Atopic dermatitis]]
** [[Contact dermatitis]]
** [[Chronic (medical)|Chronic]] [[actinic]] [[dermatitis]]
** [[Scabies]]
** [[Drug eruption]]
** [[Graft-versus-host disease|Graft versus host disease]]

==Epidemiology and Demographics==
* The prevalence of Sezary syndrome is exact unknown.<ref name="pmid266071833">{{cite journal |vauthors=Wilcox RA |title=Cutaneous T-cell lymphoma: 2016 update on diagnosis, risk-stratification, and management |journal=Am. J. Hematol. |volume=91 |issue=1 |pages=151–65 |date=January 2016 |pmid=26607183 |pmc=4715621 |doi=10.1002/ajh.24233 |url=}}</ref>
* In 2005 and 2009 the incidence of Sezary syndrome was estimated to be 0/08 and 0/09 cases per 100,000 individuals in the United States.<ref name="pmid19279331">{{cite journal |vauthors=Bradford PT, Devesa SS, Anderson WF, Toro JR |title=Cutaneous lymphoma incidence patterns in the United States: a population-based study of 3884 cases |journal=Blood |volume=113 |issue=21 |pages=5064–73 |date=May 2009 |pmid=19279331 |pmc=2686177 |doi=10.1182/blood-2008-10-184168 |url=}}</ref><ref name="pmid18808419">{{cite journal |vauthors=Saunes M, Nilsen TI, Johannesen TB |title=Incidence of primary cutaneous T-cell lymphoma in Norway |journal=Br. J. Dermatol. |volume=160 |issue=2 |pages=376–9 |date=February 2009 |pmid=18808419 |doi=10.1111/j.1365-2133.2008.08852.x |url=}}</ref>

===Age===
*The median age at diagnosis of [[Sézary syndrome]] is 60 years of age(SS).<ref name="Wilcox2016">{{cite journal|last1=Wilcox|first1=Ryan A.|title=Cutaneous T-cell lymphoma: 2016 update on diagnosis, risk-stratification, and management|journal=American Journal of Hematology|volume=91|issue=1|year=2016|pages=151–165|issn=03618609|doi=10.1002/ajh.24233}}</ref>
*Sezary syndrome is more commonly observed among [[Old age|elderly]] [[Patient|patients]].<ref name="pmid24421750">{{cite journal |vauthors=Al Hothali GI |title=Review of the treatment of mycosis fungoides and Sézary syndrome: A stage-based approach |journal=Int J Health Sci (Qassim) |volume=7 |issue=2 |pages=220–39 |date=June 2013 |pmid=24421750 |pmc=3883611 |doi= |url=}}</ref>

===Gender===
*[[Male|Males]] are more commonly affected with Sezary syndrome than [[Female|females]](2:1).<ref name="pmid25386354">{{cite journal |vauthors=Horesh N, Horowitz NA |title=Does gender matter in non-hodgkin lymphoma? Differences in epidemiology, clinical behavior, and therapy |journal=Rambam Maimonides Med J |volume=5 |issue=4 |pages=e0038 |date=October 2014 |pmid=25386354 |pmc=4222427 |doi=10.5041/RMMJ.10172 |url=}}</ref>

===Race===
*Sezary syndrome usually affects individuals of the whites race.<ref name="pmid17638728">{{cite journal |vauthors=Criscione VD, Weinstock MA |title=Incidence of cutaneous T-cell lymphoma in the United States, 1973-2002 |journal=Arch Dermatol |volume=143 |issue=7 |pages=854–9 |date=July 2007 |pmid=17638728 |doi=10.1001/archderm.143.7.854 |url=}}</ref>
*Sezary syndrome is rare [[disease]] that tends to affect Whites <ref name="pmid17638728" /> but in this study African american has more percentage<ref name="pmid25458019">{{cite journal |vauthors=Desai M, Liu S, Parker S |title=Clinical characteristics, prognostic factors, and survival of 393 patients with mycosis fungoides and Sézary syndrome in the southeastern United States: a single-institution cohort |journal=J. Am. Acad. Dermatol. |volume=72 |issue=2 |pages=276–85 |date=February 2015 |pmid=25458019 |doi=10.1016/j.jaad.2014.10.019 |url=}}</ref>
==Risk Factors==
*Common [[Risk factor|risk factors]] in the developme Sezary syndrome are [[HIV AIDS|AIDS]], [[Pneumonia|pneumonias]] , [[bacterial]] [[cutaneous]] [[Infection|infections]] were [[Frequency|frequen]].<ref name="pmid300980162">{{cite journal |vauthors=Blaizot R, Ouattara E, Fauconneau A, Beylot-Barry M, Pham-Ledard A |title=Infectious events and associated risk factors in mycosis fungoides/Sézary syndrome: a retrospective cohort study |journal=Br. J. Dermatol. |volume= |issue= |pages= |date=August 2018 |pmid=30098016 |doi=10.1111/bjd.17073 |url=}}</ref>

== Complications and Prognosis==
*Common [[Complication (medicine)|complications]] of Sezary syndrome include [[infection]], second [[Malignancies|malignancies (]] [[Hodgkin lymphoma]], [[Non-Hodgkin lymphoma]], [[melanoma]], [[urinary]] [[cancer]]) and especially [[Lymphomas|lymphoma]].<ref name="pmid17224541">{{cite journal |vauthors=Huang KP, Weinstock MA, Clarke CA, McMillan A, Hoppe RT, Kim YH |title=Second lymphomas and other malignant neoplasms in patients with mycosis fungoides and Sezary syndrome: evidence from population-based and clinical cohorts |journal=Arch Dermatol |volume=143 |issue=1 |pages=45–50 |date=January 2007 |pmid=17224541 |doi=10.1001/archderm.143.1.45 |url=}}</ref><ref name="pmid19481294">{{cite journal |vauthors=Herro E, Dicaudo DJ, Davis MD, Weaver AL, Swanson DL |title=Review of contemporaneous mycosis fungoides and B-cell malignancy at Mayo Clinic |journal=J. Am. Acad. Dermatol. |volume=61 |issue=2 |pages=271–5 |date=August 2009 |pmid=19481294 |doi=10.1016/j.jaad.2009.03.033 |url=}}</ref><ref name="pmid6609176">{{cite journal |vauthors=Olsen EA, Delzell E, Jegasothy BV |title=Second malignancies in cutaneous T cell lymphoma |journal=J. Am. Acad. Dermatol. |volume=10 |issue=2 Pt 1 |pages=197–204 |date=February 1984 |pmid=6609176 |doi= |url=}}</ref>
*[[Prognosis]] is depended on stage of [[disease]], elevated [[LDH]], [[race]], sex ([[male]]), peripheral [[eosinophilia]] and generally is poor.<ref name="pmid28540671">{{cite journal |vauthors=Berg S, Villasenor-Park J, Haun P, Kim EJ |title=Multidisciplinary Management of Mycosis Fungoides/Sézary Syndrome |journal=Curr Hematol Malig Rep |volume=12 |issue=3 |pages=234–243 |date=June 2017 |pmid=28540671 |doi=10.1007/s11899-017-0387-9 |url=}}</ref>

== Diagnosis ==
*The [[diagnosis]] of Sezary syndrome is made through examination of total [[body surface area]] (BSA) and the following of result of [[blood]] tests, [[biopsy]] of [[Lymph node biopsy|lymph node]] and [[bone marrow]] should be done.
*[[Patient|Patients]] are presenting with maycosis fangoides (MF) may evolve to Sezary syndrome (SS) after 6-30 monthes. <ref name="pmid26763453">{{cite journal |vauthors=Hurabielle C, Michel L, Ram-Wolff C, Battistella M, Jean-Louis F, Beylot-Barry M, d'Incan M, Bensussan A, Bagot M |title=Expression of Sézary Biomarkers in the Blood of Patients with Erythrodermic Mycosis Fungoides |journal=J. Invest. Dermatol. |volume=136 |issue=1 |pages=317–20 |date=January 2016 |pmid=26763453 |doi=10.1038/JID.2015.360 |url=}}</ref>
*The ISCL/EORTC recommends [[diagnostic criteria]]:<ref>{{Cite journal
| author = [[Elise Olsen]], [[Eric Vonderheid]], [[Nicola Pimpinelli]], [[Rein Willemze]], [[Youn Kim]], [[Robert Knobler]], [[Herschel Zackheim]], [[Madeleine Duvic]], [[Teresa Estrach]], [[Stanford Lamberg]], [[Gary Wood]], [[Reinhard Dummer]], [[Annamari Ranki]], [[Gunter Burg]], [[Peter Heald]], [[Mark Pittelkow]], [[Maria-Grazia Bernengo]], [[Wolfram Sterry]], [[Liliane Laroche]], [[Franz Trautinger]] & [[Sean Whittaker]]
| title = Revisions to the staging and classification of mycosis fungoides and Sezary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC)
| journal = [[Blood]]
| volume = 110
| issue = 6
| pages = 1713–1722
| year = 2007
| month = September
| doi = 10.1182/blood-2007-03-055749
| pmid = 17540844
}}</ref>
# [[Erythroderma]] covering [[body surface area]] (BSA) >80%
# By [[Polymerase chain reaction|PCR]] or [[southern blot]] [[analysis]] a clonal [[TCR]] [[rearrangement]] identified in [[blood]]
#Sezary [[Cell (biology)|cell]] count >1000 cells/microL or one of the following two [[criteria]] :
##Increased [[CD4]]+ or [[CD3 (immunology)|CD3]]+ cells with a [[CD4]] to [[CD8]] ≥ 10
##Increased [[CD4]]+ cells with an [[abnormal]] [[phenotype]] ( [[CD4]]+[[CD7]]- ≥40 % or [[CD4]]+CD26- ≥30%)

* [[CT-scans|CT scan]] may be helpful in the [[diagnosis]] of Sezary syndrome. Findings on [[CT scan]] a node larger than 1.5 cm.<ref name="pmid280121572">{{cite journal |vauthors=Haththotuwa R, Zilinskiene L, Oliff J, Vydianath B, Amel-Kashipaz R, Stevens A, Shah F, Chaganti S, Scarisbrick J |title=Biopsy correlation of surface area vs. single-axis measurements on computed tomography scan of lymph nodes in patients with erythrodermic mycosis fungoides and Sézary syndrome |journal=Br. J. Dermatol. |volume=177 |issue=3 |pages=877–878 |date=September 2017 |pmid=28012157 |doi=10.1111/bjd.15266 |url=}}</ref>

== Symptoms==

*Symptoms of Sezary syndrome may include the following:
**Most common symtom of Sezary syndrome is [[pruritus]].
***There is not related between [[pruritis]] and the degree of [[blood]] involvement or the extent and depth of [[erythema]] .<ref name="pmid22788808">{{cite journal |vauthors=Vij A, Duvic M |title=Prevalence and severity of pruritus in cutaneous T cell lymphoma |journal=Int. J. Dermatol. |volume=51 |issue=8 |pages=930–4 |date=August 2012 |pmid=22788808 |doi=10.1111/j.1365-4632.2011.05188.x |url=}}</ref>
***[[Pruritus]] may exacerbate sleep [[dysfunction]], [[anxiety]], and [[depression]].<ref name="pmid27386050">{{cite journal |vauthors=Ferreira BI, Abreu JL, Reis JP, Figueiredo AM |title=Psoriasis and Associated Psychiatric Disorders: A Systematic Review on Etiopathogenesis and Clinical Correlation |journal=J Clin Aesthet Dermatol |volume=9 |issue=6 |pages=36–43 |date=June 2016 |pmid=27386050 |pmc=4928455 |doi= |url=}}</ref>

== Physical Examination ==
*Patients with Sezary syndrome usually appear with [[skin]] [[Medical sign|signs]] and [[Symptom|symptoms]].
*[[Physical examination]] may be remarkable for:
:*[[Skin lesion|Skin lesions]]
:*[[Enlarged lymph nodes]]
:*[[Fingernails]] and [[toenails]] [[abnormalities]]
:*lower eyelides
:*[[trouble]] regulating [[body temperature]]
:*[[Splenomegaly]]
:*[[Hepatomegaly]]
:*[[Gastrointestinal tract|Gastrointestinal trac]]
:*

== Laboratory Findings ==
*In sezary syndrome, B0, sezary [[Cell (biology)|cells]] are defined less than 5.
*A majority of number atypical [[mononuclear cells]] with moderately to highly groove [[nuclei]], termed Sezary [[Cell (biology)|cells]] [[concentration]] of peripheral [[blood]] of Sezary syndrome [[Patient|patients]] .<ref name="pmid24936324">{{cite journal |vauthors=Olek-Hrab K, Silny W |title=Diagnostics in mycosis fungoides and Sezary syndrome |journal=Rep Pract Oncol Radiother |volume=19 |issue=2 |pages=72–6 |date=March 2014 |pmid=24936324 |pmc=4054990 |doi=10.1016/j.rpor.2013.11.001 |url=}}</ref>
*Other [[laboratory]] findings consistent with the [[diagnosis]] of Sezary syndrome include [[Polymerase chain reaction|PCR]], [[southern blot]], and High [[Throughput rate|throughput]] [[TCR]] [[sequencing]], [[immunophenotyping]] confirming [[T cell]] [[origin]] ([[CD3 (immunology)|CD3]]+, [[CD4]]+), [[lymph node biopsy]], peripheral blood test ([[morphology]], felow cytometry)
[[Laboratory medicine|Laboratory]] tests for cutaneous [[T-cell lymphoma|T cell lymphoma]] include:<ref name="seer.cancer">Cutaneous T cell lymphoma. Surveillance, Epidemiology, and End Results . http://seer.cancer.gov/seertools/hemelymph/51f6cf56e3e27c3994bd52f7/ Accessed on January 19, 2016</ref>
* [[Complete blood count]] ([[CBC]])
* [[Peripheral blood smear]]
:* Atypical [[T cell|T-cells]] (Sezary cells)
* [[Blood]] [[chemistry]] studies
* [[Flow cytometry]]
* [[Immunohistochemistry]]
* [[Immunophenotyping]]: Beta F1+, [[CD2]]-/+, [[CD3]]+, [[CD3]]- ([[CD4]]-positive variant), [[CD4]]+ ([[CD4]]-positive variant), [[CD4]]-, [[CD5]]-, [[CD7]]+/-, [[CD8]]+, [[CD8]]- ([[CD4]]-positive variant), [[Granzyme]] B+, and [[Perforin]]+
* Bon marrow<ref name="FossGirardi2017">{{cite journal|last1=Foss|first1=Francine M.|last2=Girardi|first2=Michael|title=Mycosis Fungoides and Sezary Syndrome|journal=Hematology/Oncology Clinics of North America|volume=31|issue=2|year=2017|pages=297–315|issn=08898588|doi=10.1016/j.hoc.2016.11.008}}</ref>
**In advanced [[disease]] of Sezary syndrome, [[bone marrow]] involvement can be seen.
**Considered as a [[leukemic]] phase of [[cutaneous]] [[T-cell lymphoma]] without any [[bone marrow]] compromise.<ref name="SibaudBeylot-Barry2003">{{cite journal|last1=Sibaud|first1=Vincent|last2=Beylot-Barry|first2=Marie|last3=Thiébaut|first3=Rodolphe|last4=Parrens|first4=Marie|last5=Vergier|first5=Béatrice|last6=Delaunay|first6=Michèle|last7=Beylot|first7=Claire|last8=Chêne|first8=Geneviève|last9=Ferrer|first9=Jacky|last10=de Mascarel|first10=Antoine|last11=Dubus|first11=Pierre|last12=Merlio|first12=Jean Philippe|title=Bone Marrow Histopathologic and Molecular Staging in Epidermotropic T-Cell Lymphomas|journal=American Journal of Clinical Pathology|volume=119|issue=3|year=2003|pages=414–423|issn=0002-9173|doi=10.1309/QH6XLRF3MVUF2M8M}}</ref>
*[[Biopsy]]:
**More than 4 cm of [[Punch biopsy|punch]]

== Treatment ==
The mainstay of [[therapy]] for Sezarey syndrome (SS) is similar to treatment for [[mycosis fungoides]] (MF).<ref name="JanigaKentley2018">{{cite journal|last1=Janiga|first1=Jenna|last2=Kentley|first2=Jonathan|last3=Nabhan|first3=Chadi|last4=Abdulla|first4=Farah|title=Current systemic therapeutic options for advanced mycosis fungoides and Sézary syndrome|journal=Leukemia & Lymphoma|volume=59|issue=3|year=2018|pages=562–577|issn=1042-8194|doi=10.1080/10428194.2017.1347650}}</ref><ref name="pmid211456193">{{cite journal |vauthors=Olsen EA, Rook AH, Zic J, Kim Y, Porcu P, Querfeld C, Wood G, Demierre MF, Pittelkow M, Wilson LD, Pinter-Brown L, Advani R, Parker S, Kim EJ, Junkins-Hopkins JM, Foss F, Cacchio P, Duvic M |title=Sézary syndrome: immunopathogenesis, literature review of therapeutic options, and recommendations for therapy by the United States Cutaneous Lymphoma Consortium (USCLC) |journal=J. Am. Acad. Dermatol. |volume=64 |issue=2 |pages=352–404 |date=February 2011 |pmid=21145619 |doi=10.1016/j.jaad.2010.08.037 |url=}}</ref><ref name="pmid14696593">{{cite journal |vauthors=Whittaker SJ, Marsden JR, Spittle M, Russell Jones R |title=Joint British Association of Dermatologists and U.K. Cutaneous Lymphoma Group guidelines for the management of primary cutaneous T-cell lymphomas |journal=Br. J. Dermatol. |volume=149 |issue=6 |pages=1095–1107 |date=December 2003 |pmid=14696593 |doi= |url=}}</ref>

===Medical Therapy ===
* [[Pharmacologic]] [[medical]] [[therapy]] is recommende [[radiotherapy]], [[biological therapy|biological therap]]<nowiki/>[[biological therapy|y]] [[mycosis fungoides]] (MF) for Sezary syndrome (SS) plus [[photopheresis]] (ECP) and low [[dose]] [[alemtuzumab]], and the need for [[adjuvant treatment]] to control [[pruritus]].<ref name="pmid14996105">{{cite journal |vauthors=Quaglino P, Fierro MT, Rossotto GL, Savoia P, Bernengo MG |title=Treatment of advanced mycosis fungoides/Sézary syndrome with fludarabine and potential adjunctive benefit to subsequent extracorporeal photochemotherapy |journal=Br. J. Dermatol. |volume=150 |issue=2 |pages=327–36 |date=February 2004 |pmid=14996105 |doi= |url=}}</ref>
**In [[Patient|patients]] with severe [[pruritus]]; [[topical]] and [[systemic]] anti pruritics are recommended.<ref name="pmid211456192">{{cite journal |vauthors=Olsen EA, Rook AH, Zic J, Kim Y, Porcu P, Querfeld C, Wood G, Demierre MF, Pittelkow M, Wilson LD, Pinter-Brown L, Advani R, Parker S, Kim EJ, Junkins-Hopkins JM, Foss F, Cacchio P, Duvic M |title=Sézary syndrome: immunopathogenesis, literature review of therapeutic options, and recommendations for therapy by the United States Cutaneous Lymphoma Consortium (USCLC) |journal=J. Am. Acad. Dermatol. |volume=64 |issue=2 |pages=352–404 |date=February 2011 |pmid=21145619 |doi=10.1016/j.jaad.2010.08.037 |url=}}</ref>
* [[Systemic]] [[treatments]] are generally required in the [[leukemic]] [[blood]] involvement Sezary syndrome [[Patient|patients]].<ref name="pmid211456192" />
* In new [[Diagnosis|diagnosed]] Sezary syndrome [[Patient|patients]] with slowly progressive [[disease]] munomodulatory therapies are recommended.<ref name="pmid211456192" />
* [[Pharmacologic]] [[medical]] therapies for Sezary syndrome include primary treatment and secodanry treatment and allogenic [[hematopoietic]] [[Cell (biology)|cell]] [[transplantation]]
**Primary: Extracorporeal photopheresis (ECP), [[Retinoid|Retinoids]] ([[bexarotene]], [[acitretin]], [[isotretinoin]], [[all-trans retinoic acid]]), [[Histone deacetylase]] (HDAC) inhibitors ([[vorinostat]], [[romidepsin]]), Low [[dose]] [[methotrexate]]
**Secondary: [[Pegylated]] [[liposomal]] [[doxorubicin]],[[Gemcitabine]], [[Alemtuzumab]], [[Chlorambucil]], [[Fludarabine]], [[Cladribine]], [[Pentostatin]], Intermediate [[dose]] [[methotrexate]], [[Pralatrexate]] (low dose) , [[Brentuximab vedotin]], [[Pembrolizumab]]
{| class="wikitable"
|+
! colspan="3" style="background: #4479BA; color: #FFFFFF; text-align: center;" |'''Primary [[Treatment groups|treatment]]'''
|-
! colspan="1" style="background: #B0C4DE; color: #FFFFFF; text-align: center;" |Agent
! colspan="1" style="background: #B0C4DE; color: #FFFFFF; text-align: center;" |[[Combination therapy]]
! colspan="1" style="background: #B0C4DE; color: #FFFFFF; text-align: center;" |Comment
|-
|ECP
|
* [[Systemic]] [[therapy]] can be combined with ECP:
* [[Retinoid]], low dose [[methotrexate]], [[HDAC inhibitors|HDAC inhibitor]], [[interferon]]
* [[skin]] directed [[therapy]] ([[phototherapy]], topicals, TSEBT)
|this [[therapy]] is only in some specialized centers.
|-
|[[Retinoids]] ([[bexarotene]], [[acitretin]], [[isotretinoin]], [[all-trans retinoic acid]])
|[[Systemic]] [[therapy]] can be combined such as:
* ECP
* [[Interferon]]
* [[Skin]] direct [[therapy]]( [[PUVA]], TSEBT)
|
* [[Teratogenic]]
* [[Adverse effect (medicine)|Side effects]] such as:
# [[Hyperlipoproteinemia|Hyperlipidemia]]
# [[Central]] [[hypothyroidism]] ([[bexarotene]])

|-
|[[Interferon-alpha|Interferon alpha]]

[[Interferon gamma]]
|[[Systemic]] [[therapy]] can be combined :
* ECP
* [[Bexarotene]]
* ECP
[[Skin]] directed [[therapy]]: Topicals, [[PUVA]]
|
* It is useful for concomitant [[Autoimmunity|autoimmune]] conditions or solid [[transplant]] [[Patient|patients]]
|-
|[[Methotrexate]] (Low [[dose]])
|[[Systemic]] [[therapy]] can be combined:
* ECP
* [[Interferon]]
* [[HDAC inhibitor]]
[[Skin]] directed [[therapy]]
|Side effects:
* [[Teratogenic]]
* Mild generalized [[immunosuppression]]
* [[liver]] toxcity
|-
|[[Histone deacetylase]] [[Histone deacetylase inhibitor|HDAC inhibitors]] ([[vorinostat]], [[romidepsin]])
|[[Systemic]] [[therapy]] can be combined:
* IECP
* [[Interferon]]
* [[Skin]] directed (TSEBT) [[therapy]]
|Side effect:
* [[Fatigue]]
* [[Nausea]]
* [[Diarrhea]]
* [[Thrombocytopenia]]
* Nonspecific [[electrocardiogram]] effects
|-
! colspan="3" style="background: #4479BA; color: #FFFFFF; text-align: center;" |'''Secondary treatment'''
|-
| colspan="3" |Secondary treatment recomanded after inadequate response, [[refractory]] [[disease]] or progression despite primary treatment ( [[Pegylated]] [[liposomal]] [[doxorubicin]], [[Gemcitabine]], [[Alemtuzumab]], [[Chlorambucil]], [[Fludarabine]], [[Cladribine]], [[Pentostatin]], [[Methotrexate]](intermediate dose), Low dose [[pralatrexate]], [[Brentuximab vedotin]], [[Pembrolizumab]])
|}
* For immediate control in [[Patient|patients]] with rapidly progressive [[disease]], [[chemotherapeutic agents]] or [[Targeted therapy|targeted therapies]] are recommanded. If possible [[Immunity (medical)|immune]] enhancing or preserve agent recommanded to use before chemotherapy.<ref name="pmid211456192" />
* The predominant [[therapy]] for [[cutaneous T cell lymphoma]] is [[PUVA]]. Adjunctive [[chemotherapy]], [[radiotherapy]], [[biological therapy]], [[retinoid]] [[therapy]], and photophoresis may be required <ref name="canadiancancer">Cutaneous T cell lymphoma. Canadian Cancer Society. http://www.cancer.ca/en/cancer-information/cancer-type/non-hodgkin-lymphoma/non-hodgkin-lymphoma/types-of-nhl/cutaneous-t-cell-lymphoma/?region=on Accessed on January 19, 2016</ref>

=== Prevention ===
*There are no primary preventive measures available for [disease name].

*Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

*Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].
*[[Pneumococcal]] [[vaccination]] ld be systematically recommended
*[[Prophylaxis]] with [[co-trimoxazole]] and [[valaciclovir]] is when the [[CD4]] count is < 0·2 × 109 cells L-1

==References==
{{Reflist|2}}

[[Category:Pick One of 28 Approved]]

{{WS}}
{{WH}}

Dermoid cyst other imaging findings

2019-05-30T16:01:24Z

Ahmed Younes: /* Gallery */

__NOTOC__
{{Dermoid cyst}}
{{CMG}}{{AE}} {{STM}}

==Overview==
[[Scintigraphy]] may be performed to differentiate a [[submental]] dermoid cyst from an [[ectopic]] [[thyroid]] tissue swelling.<ref name="pmid21922020">{{cite journal| author=Makos C, Noussios G, Peios M, Gougousis S, Chouridis P| title=Dermoid cysts of the floor of the mouth: two case reports. | journal=Case Rep Med | year= 2011 | volume= 2011 | issue= | pages= 362170 | pmid=21922020 | doi=10.1155/2011/362170 | pmc=PMC3172983 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21922020 }} </ref>

==Scintigraphy==
*[[Scintigraphy]] may be performed to differentiate a [[submental]] dermoid cyst from an [[ectopic]] [[thyroid]] tissue swelling.
*The scintigraphy scan of the submental area with a Tc99m shows no evidence of the existence of [[ectopic]] [[thyroid]] tissue.<ref name="pmid21922020">{{cite journal| author=Makos C, Noussios G, Peios M, Gougousis S, Chouridis P| title=Dermoid cysts of the floor of the mouth: two case reports. | journal=Case Rep Med | year= 2011 | volume= 2011 | issue= | pages= 362170 | pmid=21922020 | doi=10.1155/2011/362170 | pmc=PMC3172983 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21922020 }} </ref>

==References==
{{Reflist|2}}

[[Category:Dermatology]]
[[Category:Gynecology]]
[[Category:Oncology]]
[[Category:Ophthalmology]]
[[Category:Types of cancer]]

{{WikiDoc Help Menu}}
{{WikiDoc Sources}}
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Dermatology]]
[[Category:Surgery]]