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'''For patient information, click [[Granulocytic sarcoma (patient information)|here]]'''


{{DiseaseDisorder infobox |
{{CMG}} {{AE}} [[Parnian Jabbari]]
  Name          = Chloroma |
{{SI}}
  ICD10          = {{ICD10|C|92|3|c|81}} |
  ICD9          = {{ICD9|205.3}} |
  ICDO          = 9930/3 |
  Image          = |
  Caption        = |
  OMIM          = |
  MedlinePlus    = |
  eMedicineSubj  = |
  eMedicineTopic = |
  DiseasesDB    = |
  MeshID        = D023981 |
}}
{{Granulocytic sarcoma}}
{{CMG}}


==[[Granulocytic sarcoma overview|Overview]]==
==Overview==
Granulocytic sarcoma (GS, also known as chloroma) was first discovered by Allen Burns, a British physician, in 1811. The term chloroma was first used by King to address the greenish appearance of the tumor due to [[myeloperoxidase]]. The association of the GS with [[Acute myeloid leukemia|acute myeloid leukemia (AML)]] was first recognized by Dock in 1902. GS can be classified into two categories based on its co-occurence with other malignancies. Infiltration of the tumor with [[myeloblasts]] is the main characteristic of the tumor on [[H&E stain]]. GS rises from primitive precursors of [[granulocytes]]. The disease is an extramedullary manifestation of myeloid diseases, however, it can occur as a primary disease. Aggregation of [[myeloblasts]], [[promyelocytes]] and [[Myelocyte|myelocytes]] outside of the bone marrow presents itself as these solid tumors. Tumors can occur at any site and can appear as green, gray, white or brown masses.  GS must be differentiated from other diseases that can present as extramedullary solid tumors. All patients with GS must be evaluated for concurrent or future malignancies as GS can occur in the course of or prior to other malignancies. The prevalence of GS is approximately 2 per 1,000,000 individuals worldwide. The most important risk factor for development of GS is genetic mutations and susceptibility.  Symptoms of GS may include the following: Symptoms due to mass effect such as [[deafness]], [[ptosis]], altered vision, intestinal obstruction, headache, neck pain, abdominal pain, and constitutional symptoms. [[Chemotherapy]] is the main stain of treatment in patients with GS. Even patients with isolated GS must receive systemic treatment to better the prognosis.


==[[Granulocytic sarcoma historical perspective|Historical Perspective]]==
==Historical Perspective==
*[[File:Screenshot 2019-05-02 Myeloid sarcoma.png|thumb|Plain radiograph of femur in a patient with GS. Courtesy of image: pathology outlines (http://www.pathologyoutlines.com/topic/bonemyeloidsarcoma.html)]]Granulocytic sarcoma (GS, also known as chloroma) was first discovered by Allen Burns, a British physician, in 1811 <ref>{{Cite journal|last=Burns|first=Allen|date=|title=Observations of surgical anatomy, in Head andNeck.|url=|journal=London, England, Royce, 1811|volume=|pages=364-366|via=}}</ref>.
*The term chloroma was first used by King to address the greenish appearance of the tumor due to [[myeloperoxidase]].
*The association of the GS with [[Acute myeloid leukemia|acute myeloid leukemia (AML)]] was first recognized by Dock in 1902 <ref>{{Cite journal|last=Dock G, Warthin AS|first=|date=|title=A new case of chloroma withleukemia.|url=|journal=Trans Assoc Am Phys, 1904|volume=19:64|pages=115|via=}}</ref>.
*The term "granulocytic sarcoma" was suggested by Rappaport in 1967 to grant generalisability to it <ref>{{Cite book|title=Tumors of the hematopoietic system, inAtlas of Tumor Pathology, Section III|last=Rappaport H|first=|publisher=Fascicle 8. ArmedForces Institute of Pathology|year=1967|isbn=|location=Washington|pages=241-247}}</ref>.
==Classification==
* GS can be classified into two categories based on its co-occurence with other malignancies:
** GS associated with other myeloid diseases:
*** [[Acute leukemia|Acute leukemias]] (especially [[AML]])
*** [[Myelodysplastic syndromes]]
*** Other [[myeloproliferative diseases]]
**Isolated GS
==Pathophysiology==
* Infiltration of the tumor with [[myeloblasts]] is the main characteristic of the tumor on [[H&E stain]].
* GS rises from primitive precursors of [[granulocytes]].
* The disease is an extramedullary manifestation of myeloid diseases, however, it can occur as a primary disease.
* Aggregation of [[myeloblasts]], [[Promyelocyte|promyelocytes]] and [[Myelocyte|myelocytes]] outside of the bone marrow presents itself as these solid tumors.
* Tumors can occur at any site and can appear as green, gray, white or brown masses.
==Differentiating GS from other Diseases==
GS must be differentiated from other diseases that can present as extramedullary solid tumors, such as:
* [[Lymphoma|Large cell lymphoma]]
* Non-Hodgkin lymphoma
* [[Thymoma]]
* [[Myeloma]]
* [[Sarcoma|Esosinophilic sarcoma]]
* [[Ewing sarcoma]]
* Extramedullary sites of [[hematopoiesis]]
* [[Burkitt lymphoma]]
* [[Hypereosinophilic syndrome]]
* [[Polycythemia vera]]
All patients with GS must be evaluated for concurrent or future malignancies as GS can occur in the course of or prior to other malignancies.


==[[Granulocytic sarcoma pathophysiology|Pathophysiology]]==
==Epidemiology and Demographics==
* The prevalence of GS is approximately 2 per 1,000,000 individuals worldwide.
* Most of the cases of GS are case reports and the disease is extremely rare.
===Age===
* Patients of all age groups may develop GS.
* GS associated with [[AML]] occurs more commonly in children.


==[[Granulocytic sarcoma causes|Causes]]==
===Gender===
* GS affects both men and women.
* Due to the rarity of the disease it is not clear whether there is a gender predilection for it.
===Race===
* There is no racial predilection for GS.
==Risk Factors==
* Risk factors for GS are usually chromosomal aberrations and include<ref name=":0">{{Cite journal|last=Daniela Dörfel et al.|first=|date=2016|title=Cardiac Myeloid Sarcoma: Multimodality Radiologic Imaging Features and Pathologic Correlation|url=https://www.amjmed.com/article/S0002-9343(16)30356-4/fulltext|journal=The American Journal of Medicine|volume=129|pages=e117-e120|via=}}</ref>:
** [[Trisomy 8]]
** Monosomy 7
** MLL gene rearrangement
** [[NPM1]] mutations
** [[FLT3]] mutations


==[[Granulocytic sarcoma epidemiology and demographics|Epidemiology and Demographics]]==
== Natural History, Complications and Prognosis==
* GS evolve over time, that depends on the co-occurence of the disease with other malignancies.
* GS may present before evidences of other malignancies manifest or after these malignancies are evident.
* Symptoms of the isolated GS depends on the location and the site of the tumor.
* Majority of cases are associated with [[AML]] or other [[myeloproliferative]]/[[Myelodysplastic syndrome|myelodysplastic syndromes]].
* Majority of GS tumors are found in the soft tissues such as the peritoneum, lymph nodes, CNS and skin. They are also found in bone and [[periosteum]]. 
* Early clinical features include weight loss, fatigue. Other manifestations of the tumor depend on its size and location.
* Prognosis of GS depends on its association with other malignacies. In cases of isolated GS the prognosis is good. However, GS associated with [[myeloproliferative disorders]] has poor prognosis.
* Prognosis of isolated GS with chromosome 8 abnormalities is worse than other cases of isolated GS.


==[[Granulocytic sarcoma risk factors|Risk Factors]]==
== Diagnosis ==
===Diagnostic Criteria===
* There are no predefined criteria for diagnosis of granulocytic sarcoma.
* Granulocytic sarcoma must be suspected in patients with [[AML]] or [[Myelodysplastic syndrome|myelodysplastic syndromes]]. Diagnosis must be confirmed with histopathologic study of the specimen.


==[[Granulocytic sarcoma screening|Screening]]==
=== Symptoms ===
Symptoms of GS may include the following:
* Symptoms due to mass effect such as [[deafness]], [[ptosis]], altered vision, intestinal obstruction, etc.
* [[Headache]], neck pain, abdominal pain,etc. based on the site of the tumor
* Constitutional symptoms such as fever, fatigue, etc.
=== Physical Examination ===
Patients with GS can present with varying presentations.


==[[Granulocytic sarcoma differential diagnosis|Differentiating Granulocytic sarcoma from other Diseases]]==
Physical examination may be remarkable for:
* [[Lymphadenopathy]] (in cases associated with [[AML]] and other [[Myeloproliferative syndrome|myeloproliferative syndromes]])
* Skin lesions (of varying colors such as green, grey, brown, etc.)
* Organ enlargement such as [[hepatosplenomegaly]]
* [[Petechiae]] in patients with [[thrombocytopenia]]
* [[Hearing loss]]
* [[Heart murmurs]] in cases with heart chamber masses
* [[Crackles]] on lung auscultation
* [[Abdominal distension|Abdominal distention]]/tenderness in cases with intestinal obstruction
* Limb swelling due to different pathologies such as [[Deep vein thrombosis|deep vein thrombosis (DVT)]]


==[[Granulocytic sarcoma natural history|Natural History, Complications and Prognosis]]==
=== Laboratory Findings ===
* In cases associated with [[AML]]/[[CML]], [[anemia]], [[thrombocytopenia]] with normal, low or high white blood cells can be present.
* In cases associated with [[Polycythemia vera CT|polycythemia vera]], [[thrombocytosis]] and high levels of hemoglobin is present in complete blood count (CBC).
* High [[eosinophil]] levels can be present in CBC.


==Diagnosis==
===Imaging Findings===
[[Granulocytic sarcoma history and symptoms|History and Symptoms]] | [[Granulocytic sarcoma physical examination|Physical Examination]] | [[Granulocytic sarcoma laboratory tests|Laboratory Findings]] | [[Granulocytic sarcoma chest x ray|Chest X Ray]] | [[Granulocytic sarcoma CT|CT]] | [[Granulocytic sarcoma MRI|MRI]] | [[Granulocytic sarcoma echocardiography or ultrasound|Echocardiography or Ultrasound]] | [[Granulocytic sarcoma other imaging findings|Other Imaging Findings]] | [[Granulocytic sarcoma other diagnostic studies|Other Diagnostic Studies]]


==Treatment==
* In cases of CNS involvement, magnetic resonance imaging (MRI) or CT scan of the CNS can reveal extra-axial masses.
[[Granulocytic sarcoma medical therapy|Medical Therapy]] | [[Granulocytic sarcoma surgery|Surgery]] | [[Granulocytic sarcoma primary prevention|Primary Prevention]] | [[Granulocytic sarcoma secondary prevention|Secondary Prevention]] | [[Granulocytic sarcoma cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Granulocytic sarcoma future or investigational therapies|Future or Investigational Therapies]]
* In cases with soft tissue involvement, sonogram of the tissue can reveal the mass.
GS appears as<ref>{{Cite journal|last=Guermazi et al.|first=|date=2002|title=Granulocytic sarcoma (chloroma): imaging findings in adults and children|url=https://www.ajronline.org/doi/full/10.2214/ajr.178.2.1780319|journal=American Journal of Roentgenology|volume=178|pages=319-25|via=}}</ref>:
* Hyperdense/isodence to brain/muscle in CT scan without enhancement
* Isointense/hyperintense on T2-weighted MRI
* Isointemse/hypointense on T1-weighted MRI
[[File:Chloroma histopathology micrograph (H&E stain).jpeg|thumb|Histopathologic micrograph of GS. Infiltration with myeloblasts which can be seen in the course of AML. Courtesy of image: Wikipedia (By Nephron - Own work, CC BY-SA 3.0, <nowiki>https://commons.wikimedia.org/w/index.php?curid=15893726</nowiki>)]]Abdominal plain radiogram can reveal obstruction, [[intussusception]], etc.


==Case Studies==
Echocardiogram may reveal mobile masses in any heart chamber in cases of heart involvement.
[[Granulocytic sarcoma case study one|Case#1]]


==Related chapters==
Chest radiographs can show lymph node enlargement and consolidation.
*[[Acute myeloid leukemia]]
{{Hematological malignancy histology}}


[[Category:Disease]]
=== Other Diagnostic Studies ===
[[Category:Hematology|Chloroma]]
* Peripheral blood smear can reveal circulating [[Blast|blasts]].
[[Category:Types of cancer|Chloroma]]
* [[Flow cytometry]] can help differentiate [[AML]] from [[Acute lymphoblastic leukemia|acute lymphoblastic leukemia (ALL)]].
[[Category:Oncology]]
* Histopathologic analysis of biopsy specimen retrieved by excision or [[fine needle aspiration]] shows abundant [[myeloblasts]].
* Histopathologic analysis of GS lesions reveals high infiltration with [[myeloblasts]].


{{WikiDoc Help Menu}}
== Treatment ==
{{WikiDoc Sources}}
=== Medical Therapy ===
* [[Chemotherapy]] is the main stain of treatment in patients with GS. Even patients with isolated GS must receive systemic treatment to better the prognosis.
* Patients receiving [[cytarabine]] have better prognosis<ref name=":0" />.
* Patients with chemotherpeutic regimens accepted for [[AML]] had longer period of progression to [[AML]].
Treatment includes different regimens<ref>{{Cite journal|last=Yilmaz, A. F., Saydam, G., Sahin, F., & Baran, Y.|first=|date=2013|title=Granulocytic sarcoma: a systematic review|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3875275/|journal=American Journal of Blood Research|volume=|pages=|via=}}</ref>:
* Idarubicine and [[cytarabine]]
* [[Fludarabine]] and [[cytarabine]]
* Idarubicine and [[G-CSF]]
* [[Cyclophosphamide]], [[cytarabine]], [[topotecan]] and [[G-CSF]]
All of these therapeutic agents act through DNA damage and interferes with DNA synthesis.
 
===Bone marrow transplantation===
* [[Hematopoietic stem cell transplantation]] can be considered as a treatment option following induction [[chemotherapy]] in patients with [[AML]].<ref name=":1">{{Cite journal|last=Richard L. Bakst, Martin S. Tallman, Dan Douer and Joachim Yahalom|first=|date=2011|title=How I treat extramedullary acute myeloid leukemia|url=http://www.bloodjournal.org/content/118/14/3785?sso-checked=true|journal=Blood|volume=118|pages=3785-3793|via=}}</ref>
 
===Radiation===
* Radiation can be considered as an adjunctive therapy<ref name=":1" />.
* Combination of chemotherapy and radiotherapy can be considered in patients with CNS involvement or when rapid regression of symptoms is required.
=== Surgery ===
* Surgery alone is not a good treatment strategy for GS.
* Surgery can be considered prior to chemotherapy in patients where debulking can better the prognosis and help with symptom relief.<ref>{{Cite journal|last=Antic D et al.|first=|date=2013|title=Is there a "gold" standard treatment for patients with isolated myeloid sarcoma?|url=https://www.sciencedirect.com/science/article/abs/pii/S0753332212001060?via%3Dihub|journal=Biomed Pharmacother|volume=67|pages=72-77|via=}}</ref>
* Surgery can also have a diagnostic role in cases where excision of the mass provides specimen for histopatjologic diagnosis.
 
=== Prevention ===
* There are no primary preventive measures available for GS.
 
==References==
{{Reflist|2}}
[[Category:Pick One of 28 Approved]]
 
{{WS}}
{{WH}}

Latest revision as of 18:52, 15 May 2019


Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Parnian Jabbari

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Overview

Granulocytic sarcoma (GS, also known as chloroma) was first discovered by Allen Burns, a British physician, in 1811. The term chloroma was first used by King to address the greenish appearance of the tumor due to myeloperoxidase. The association of the GS with acute myeloid leukemia (AML) was first recognized by Dock in 1902. GS can be classified into two categories based on its co-occurence with other malignancies. Infiltration of the tumor with myeloblasts is the main characteristic of the tumor on H&E stain. GS rises from primitive precursors of granulocytes. The disease is an extramedullary manifestation of myeloid diseases, however, it can occur as a primary disease. Aggregation of myeloblasts, promyelocytes and myelocytes outside of the bone marrow presents itself as these solid tumors. Tumors can occur at any site and can appear as green, gray, white or brown masses. GS must be differentiated from other diseases that can present as extramedullary solid tumors. All patients with GS must be evaluated for concurrent or future malignancies as GS can occur in the course of or prior to other malignancies. The prevalence of GS is approximately 2 per 1,000,000 individuals worldwide. The most important risk factor for development of GS is genetic mutations and susceptibility. Symptoms of GS may include the following: Symptoms due to mass effect such as deafness, ptosis, altered vision, intestinal obstruction, headache, neck pain, abdominal pain, and constitutional symptoms. Chemotherapy is the main stain of treatment in patients with GS. Even patients with isolated GS must receive systemic treatment to better the prognosis.

Historical Perspective

  • Plain radiograph of femur in a patient with GS. Courtesy of image: pathology outlines (http://www.pathologyoutlines.com/topic/bonemyeloidsarcoma.html)
    Granulocytic sarcoma (GS, also known as chloroma) was first discovered by Allen Burns, a British physician, in 1811 [1].
  • The term chloroma was first used by King to address the greenish appearance of the tumor due to myeloperoxidase.
  • The association of the GS with acute myeloid leukemia (AML) was first recognized by Dock in 1902 [2].
  • The term "granulocytic sarcoma" was suggested by Rappaport in 1967 to grant generalisability to it [3].

Classification

Pathophysiology

  • Infiltration of the tumor with myeloblasts is the main characteristic of the tumor on H&E stain.
  • GS rises from primitive precursors of granulocytes.
  • The disease is an extramedullary manifestation of myeloid diseases, however, it can occur as a primary disease.
  • Aggregation of myeloblasts, promyelocytes and myelocytes outside of the bone marrow presents itself as these solid tumors.
  • Tumors can occur at any site and can appear as green, gray, white or brown masses.

Differentiating GS from other Diseases

GS must be differentiated from other diseases that can present as extramedullary solid tumors, such as:

All patients with GS must be evaluated for concurrent or future malignancies as GS can occur in the course of or prior to other malignancies.

Epidemiology and Demographics

  • The prevalence of GS is approximately 2 per 1,000,000 individuals worldwide.
  • Most of the cases of GS are case reports and the disease is extremely rare.

Age

  • Patients of all age groups may develop GS.
  • GS associated with AML occurs more commonly in children.

Gender

  • GS affects both men and women.
  • Due to the rarity of the disease it is not clear whether there is a gender predilection for it.

Race

  • There is no racial predilection for GS.

Risk Factors

  • Risk factors for GS are usually chromosomal aberrations and include[4]:

Natural History, Complications and Prognosis

  • GS evolve over time, that depends on the co-occurence of the disease with other malignancies.
  • GS may present before evidences of other malignancies manifest or after these malignancies are evident.
  • Symptoms of the isolated GS depends on the location and the site of the tumor.
  • Majority of cases are associated with AML or other myeloproliferative/myelodysplastic syndromes.
  • Majority of GS tumors are found in the soft tissues such as the peritoneum, lymph nodes, CNS and skin. They are also found in bone and periosteum.
  • Early clinical features include weight loss, fatigue. Other manifestations of the tumor depend on its size and location.
  • Prognosis of GS depends on its association with other malignacies. In cases of isolated GS the prognosis is good. However, GS associated with myeloproliferative disorders has poor prognosis.
  • Prognosis of isolated GS with chromosome 8 abnormalities is worse than other cases of isolated GS.

Diagnosis

Diagnostic Criteria

  • There are no predefined criteria for diagnosis of granulocytic sarcoma.
  • Granulocytic sarcoma must be suspected in patients with AML or myelodysplastic syndromes. Diagnosis must be confirmed with histopathologic study of the specimen.

Symptoms

Symptoms of GS may include the following:

  • Symptoms due to mass effect such as deafness, ptosis, altered vision, intestinal obstruction, etc.
  • Headache, neck pain, abdominal pain,etc. based on the site of the tumor
  • Constitutional symptoms such as fever, fatigue, etc.

Physical Examination

Patients with GS can present with varying presentations.

Physical examination may be remarkable for:

Laboratory Findings

Imaging Findings

  • In cases of CNS involvement, magnetic resonance imaging (MRI) or CT scan of the CNS can reveal extra-axial masses.
  • In cases with soft tissue involvement, sonogram of the tissue can reveal the mass.

GS appears as[5]:

  • Hyperdense/isodence to brain/muscle in CT scan without enhancement
  • Isointense/hyperintense on T2-weighted MRI
  • Isointemse/hypointense on T1-weighted MRI
Histopathologic micrograph of GS. Infiltration with myeloblasts which can be seen in the course of AML. Courtesy of image: Wikipedia (By Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=15893726)

Abdominal plain radiogram can reveal obstruction, intussusception, etc.

Echocardiogram may reveal mobile masses in any heart chamber in cases of heart involvement.

Chest radiographs can show lymph node enlargement and consolidation.

Other Diagnostic Studies

Treatment

Medical Therapy

  • Chemotherapy is the main stain of treatment in patients with GS. Even patients with isolated GS must receive systemic treatment to better the prognosis.
  • Patients receiving cytarabine have better prognosis[4].
  • Patients with chemotherpeutic regimens accepted for AML had longer period of progression to AML.

Treatment includes different regimens[6]:

All of these therapeutic agents act through DNA damage and interferes with DNA synthesis.

Bone marrow transplantation

Radiation

  • Radiation can be considered as an adjunctive therapy[7].
  • Combination of chemotherapy and radiotherapy can be considered in patients with CNS involvement or when rapid regression of symptoms is required.

Surgery

  • Surgery alone is not a good treatment strategy for GS.
  • Surgery can be considered prior to chemotherapy in patients where debulking can better the prognosis and help with symptom relief.[8]
  • Surgery can also have a diagnostic role in cases where excision of the mass provides specimen for histopatjologic diagnosis.

Prevention

  • There are no primary preventive measures available for GS.

References

  1. Burns, Allen. "Observations of surgical anatomy, in Head andNeck". London, England, Royce, 1811: 364–366.
  2. Dock G, Warthin AS. "A new case of chloroma withleukemia". Trans Assoc Am Phys, 1904. 19:64: 115.
  3. Rappaport H (1967). Tumors of the hematopoietic system, inAtlas of Tumor Pathology, Section III. Washington: Fascicle 8. ArmedForces Institute of Pathology. pp. 241–247.
  4. 4.0 4.1 Daniela Dörfel; et al. (2016). "Cardiac Myeloid Sarcoma: Multimodality Radiologic Imaging Features and Pathologic Correlation". The American Journal of Medicine. 129: e117–e120.
  5. Guermazi; et al. (2002). "Granulocytic sarcoma (chloroma): imaging findings in adults and children". American Journal of Roentgenology. 178: 319–25.
  6. Yilmaz, A. F., Saydam, G., Sahin, F., & Baran, Y. (2013). "Granulocytic sarcoma: a systematic review". American Journal of Blood Research.
  7. 7.0 7.1 Richard L. Bakst, Martin S. Tallman, Dan Douer and Joachim Yahalom (2011). "How I treat extramedullary acute myeloid leukemia". Blood. 118: 3785–3793.
  8. Antic D; et al. (2013). "Is there a "gold" standard treatment for patients with isolated myeloid sarcoma?". Biomed Pharmacother. 67: 72–77.

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