WBR0248: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
No edit summary
m (refreshing WBR questions)
 
(14 intermediate revisions by 3 users not shown)
Line 1: Line 1:
{{WBRQuestion
{{WBRQuestion
|QuestionAuthor={{Rim}}
|QuestionAuthor= {{Rim}} (Reviewed by  {{YD}})
|ExamType=USMLE Step 1
|ExamType=USMLE Step 1
|MainCategory=Pathology
|MainCategory=Pathology
|SubCategory=Hematology, Hematology
|SubCategory=Hematology
|MainCategory=Pathology
|MainCategory=Pathology
|SubCategory=Hematology, Hematology
|SubCategory=Hematology
|MainCategory=Pathology
|MainCategory=Pathology
|SubCategory=Hematology, Hematology
|SubCategory=Hematology
|MainCategory=Pathology
|MainCategory=Pathology
|MainCategory=Pathology
|MainCategory=Pathology
|SubCategory=Hematology, Hematology
|MainCategory=Pathology
|MainCategory=Pathology
|SubCategory=Hematology, Hematology
|SubCategory=Hematology
|MainCategory=Pathology
|MainCategory=Pathology
|SubCategory=Hematology, Hematology
|SubCategory=Hematology
|MainCategory=Pathology
|MainCategory=Pathology
|SubCategory=Hematology, Hematology
|SubCategory=Hematology
|MainCategory=Pathology
|MainCategory=Pathology
|SubCategory=Hematology
|MainCategory=Pathology
|MainCategory=Pathology
|SubCategory=Hematology, Hematology
|MainCategory=Pathology
|Prompt=A 6 year old Nigerian boy presented by his mother to the physician for unexplained fever of two weeks duration. Mother complains that her child has recent weight loss with no appetite. She also notes he has excessive fatigue and malaise, associated with night sweats. Patient’s vital signs reveal a temperature measuring 39o C (102 F), pulse measuring 98 beats per minute, blood pressure measuring 110/85 mmHg. On physical examination, severe disruption of orofacial aspect and teeth was noted. An image of a patient with the same presentation is shown below. You explain to the mother that her child’s condition is best caused by a dysregulation of which gene?
|SubCategory=Hematology
|Explanation=The endemic variant of [[Burkitt's lymphoma]] occurs in equatorial Africa. It is the most common malignancy of children in this area. Children affected with the disease often also had chronic malaria, which is believed to have reduced resistance to Epstein-Barr virus ([[EBV]]), allowing it to take hold. The disease characteristically involves the jaw or other facial bone. Mutation in c-myc gene is associated with Burkitt's lymphoma.
|Prompt=A 6-year-old African boy is brought to the physician's office for a growing lesion in his jaw. Upon review of systems, the mother explains that her child has been having night sweats and weight loss. The family recently immigrated from Africa, and the patient did not receive medical care prior to the family's arrival to USA. Physical examination is remarkable for a jaw lesion with severe orofacial and teeth disruption (shown below). The child’s condition is caused by dysregulation of which gene?
 
[[Image:WBR0248.png|300px]]
|Explanation=Burkitt's lymphoma is an aggressive B-cell non-Hodgkin's lymphoma caused by a translocation that results in the expression of the ''C-MYC'' oncogene, a transcription factor that has a role in the regulation of cell cycle. The tumor has been associated with the translocation t(8;14) among the majority of cases (85%) and translocations t(2;8) or t(8;22) in fewer than 20% of cases. Burkitt's lymphoma is characterized by a high proliferative potential and rapid turnover with a doubling time that is as fast as 24-48 hours. It is considered to be one of the fastest growing tumors. Burkitt's lymphoma is also the first malignancy to be associated with a virus, where EBV has been observed to have a direct causative role in the development of the tumor by immortalising B-cells.
 
Burkitt's lymphoma is common among children. It is classified into 3 types based on the geographical distribution, its association with infectious agents, and clinical presentation: The sporadic type is the most common type in USA and Europe and is rarely associated with EBV. It usually manifests with an abdominal or pelvic tumor; and patients typically complain of vague abdominal pain, nausea, and early satiety. The endemic type is common in regions with malaria endemicity (e.g. central Africa) and has been associated with EBV in almost all cases. Manifestations of endemic-type Burkitt's lymphoma usually include jaw or periorbital swelling, especially among children between the age 3 to 7 years. Finally, the immunodeficiency-type is common among patients with early HIV infection (CD4  > 200 cells/mm<sup>3</sup>). In this vignette, the patient is most likely diagnosed with endemic-type Burkitt's lymphoma given his age, his recent immigration from Africa, and the location of his tumor involving the jaw.


Educational objective: Mutation in [[c-myc]] proto-oncogene is associated with [[Burkitt's lymphoma]].
On histopathological analysis, Burkitt's lymphoma appears as monomorphic, medium-sized cells that have a high rate of turnover. A "starry sky" appearance is observed due to the presence of apoptotic tumor cells within tingible-body-laden macrophages on microscopy. Tumor cells are usually B-cells that express CD10, CD20, and CD79a. EBV RNA may also be expressed and identified on fluorescence in-situ hybridisation (FISH). The prognosis of Burkitt's lymphoma is mainly based on the stage of the tumor at diagnosis. Treatment of localized disease consists of surgical resection and chemotherapy, whereas more advanced cases require chemotherapy only.
|AnswerA=C-kit
|AnswerA=''L-MYC''
|AnswerAExp=[[C-kit]] oncogene is associated with [[GIST]].
|AnswerAExp=The ''L-MYC'' oncogene is associated with lung cancers.
|AnswerB=Ret
|AnswerB=''RET''
|AnswerBExp=[[Ret gene|Ret oncogene]] is associated with [[MEN|MEN syndrome]] type IIa and IIb.
|AnswerBExp=The ''[[RET]]'' oncogene is associated with [[multiple endocrine neoplasia]] (MEN) syndromes type 2A and 2B.
|AnswerC=Abl
|AnswerC=''N-MYC''
|AnswerCExp=[[Abl gene|Abl oncogene]] is associated with CML.
|AnswerCExp=''[[N-MYC]]'' oncogene is associated with neuroblastoma.
|AnswerD=Ras
|AnswerD=''HER2''
|AnswerDExp=[[Ras]] oncogene is associated with colon carcinoma.
|AnswerDExp=''[[HER2]]'' oncogene is associated with breast, ovarian, and gastric cancers.
|AnswerE=C-myc
|AnswerE=''C-MYC''
|AnswerEExp=C-myc is associated with [[Burkitt's lymphoma]].
|AnswerEExp=''[[C-MYC]]'' oncogene is associated with [[Burkitt's lymphoma]].
|EducationalObjectives=Burkitt's lymphoma is an aggressive B-cell non-Hodgkin's lymphoma caused by a translocation that results in the expression of the ''C-MYC'' oncogene, a transcription factor that has a role in the regulation of cell cycle.
|References=Molyneux EM, Rochford R, Griffin B, et al. Burkitt's lymphoma. Lancet. 2012; 379:1234-44.<br>
First Aid 2014 page 232
|RightAnswer=E
|RightAnswer=E
|Approved=No
|WBRKeyword=Burkitt's lymphoma, C-myc, Oncogene, Hematologic malignancy, Translocation, Transcription factor
|Approved=Yes
}}
}}

Latest revision as of 23:54, 27 October 2020
Author [[PageAuthor::Rim Halaby, M.D. [1] (Reviewed by Yazan Daaboul, M.D.)]]
Exam Type ExamType::USMLE Step 1
Main Category MainCategory::Pathology
Sub Category SubCategory::Hematology
Prompt [[Prompt::A 6-year-old African boy is brought to the physician's office for a growing lesion in his jaw. Upon review of systems, the mother explains that her child has been having night sweats and weight loss. The family recently immigrated from Africa, and the patient did not receive medical care prior to the family's arrival to USA. Physical examination is remarkable for a jaw lesion with severe orofacial and teeth disruption (shown below). The child’s condition is caused by dysregulation of which gene?

]]

Answer A AnswerA::''L-MYC''
Answer A Explanation AnswerAExp::The ''L-MYC'' oncogene is associated with lung cancers.
Answer B AnswerB::''RET''
Answer B Explanation [[AnswerBExp::The RET oncogene is associated with multiple endocrine neoplasia (MEN) syndromes type 2A and 2B.]]
Answer C AnswerC::''N-MYC''
Answer C Explanation [[AnswerCExp::N-MYC oncogene is associated with neuroblastoma.]]
Answer D AnswerD::''HER2''
Answer D Explanation [[AnswerDExp::HER2 oncogene is associated with breast, ovarian, and gastric cancers.]]
Answer E AnswerE::''C-MYC''
Answer E Explanation [[AnswerEExp::C-MYC oncogene is associated with Burkitt's lymphoma.]]
Right Answer RightAnswer::E
Explanation [[Explanation::Burkitt's lymphoma is an aggressive B-cell non-Hodgkin's lymphoma caused by a translocation that results in the expression of the C-MYC oncogene, a transcription factor that has a role in the regulation of cell cycle. The tumor has been associated with the translocation t(8;14) among the majority of cases (85%) and translocations t(2;8) or t(8;22) in fewer than 20% of cases. Burkitt's lymphoma is characterized by a high proliferative potential and rapid turnover with a doubling time that is as fast as 24-48 hours. It is considered to be one of the fastest growing tumors. Burkitt's lymphoma is also the first malignancy to be associated with a virus, where EBV has been observed to have a direct causative role in the development of the tumor by immortalising B-cells.

Burkitt's lymphoma is common among children. It is classified into 3 types based on the geographical distribution, its association with infectious agents, and clinical presentation: The sporadic type is the most common type in USA and Europe and is rarely associated with EBV. It usually manifests with an abdominal or pelvic tumor; and patients typically complain of vague abdominal pain, nausea, and early satiety. The endemic type is common in regions with malaria endemicity (e.g. central Africa) and has been associated with EBV in almost all cases. Manifestations of endemic-type Burkitt's lymphoma usually include jaw or periorbital swelling, especially among children between the age 3 to 7 years. Finally, the immunodeficiency-type is common among patients with early HIV infection (CD4 > 200 cells/mm3). In this vignette, the patient is most likely diagnosed with endemic-type Burkitt's lymphoma given his age, his recent immigration from Africa, and the location of his tumor involving the jaw.

On histopathological analysis, Burkitt's lymphoma appears as monomorphic, medium-sized cells that have a high rate of turnover. A "starry sky" appearance is observed due to the presence of apoptotic tumor cells within tingible-body-laden macrophages on microscopy. Tumor cells are usually B-cells that express CD10, CD20, and CD79a. EBV RNA may also be expressed and identified on fluorescence in-situ hybridisation (FISH). The prognosis of Burkitt's lymphoma is mainly based on the stage of the tumor at diagnosis. Treatment of localized disease consists of surgical resection and chemotherapy, whereas more advanced cases require chemotherapy only.
Educational Objective: Burkitt's lymphoma is an aggressive B-cell non-Hodgkin's lymphoma caused by a translocation that results in the expression of the C-MYC oncogene, a transcription factor that has a role in the regulation of cell cycle.
References: Molyneux EM, Rochford R, Griffin B, et al. Burkitt's lymphoma. Lancet. 2012; 379:1234-44.
First Aid 2014 page 232]]

Approved Approved::Yes
Keyword WBRKeyword::Burkitt's lymphoma, WBRKeyword::C-myc, WBRKeyword::Oncogene, WBRKeyword::Hematologic malignancy, WBRKeyword::Translocation, WBRKeyword::Transcription factor
Linked Question Linked::
Order in Linked Questions LinkedOrder::
Retrieved from "https://www.wikidoc.org/index.php?title=WBR0248&oldid=1671501"