WBR0753
| Author | [[PageAuthor::Rim Halaby, M.D. [1]]] |
|---|---|
| Exam Type | ExamType::USMLE Step 1 |
| Main Category | MainCategory::Genetics, MainCategory::Pathology |
| Sub Category | SubCategory::Musculoskeletal/Rheumatology |
| Prompt | [[Prompt::A 15 year old Caucasian boy is brought by his mother to the physician's clinic for right thigh pain. The child explains that the pain has been progressively worsening and is waking him at night. His mother adds that he has been having low-grade fevers and unintentional weight loss. Bone MRI and FDG-PET scan show a mass in the femoral diaphysis with no involvement of lymph nodes or distal metastasis. Biopsy of the mass is shown in the image below. Molecular studies confirm a chromosomal translocation. Which of the following is the most likely molecular etiology of the patient's condition?
|
| Answer A | AnswerA::t(11,22) |
| Answer A Explanation | AnswerAExp::Ewing's sarcoma is a t(11,22) translocation. |
| Answer B | AnswerB::t(8,14) |
| Answer B Explanation | AnswerBExp::t(8,14) translocation is associated with Burkitt's lymphoma. |
| Answer C | AnswerC::t(15,17) |
| Answer C Explanation | AnswerCExp::t(15,17) translocation is associated with M3 type of acute myelogenous leukemia (AML). |
| Answer D | AnswerD::t(12,21) |
| Answer D Explanation | AnswerDExp::t(12,21) translocation is associated with good prognosis in patients with acute lymphoblastic leukemia (ALL). |
| Answer E | AnswerE::t(11,14) |
| Answer E Explanation | AnswerEExp::t(11,14) is associated with Mantle cell lymphoma. |
| Right Answer | RightAnswer::A |
| Explanation | [[Explanation::The patient is most likely diagnosed with Ewing's sarcoma. Ewing's sarcoma is the second most common bone tumor in children and adolescents, mostly located in the diaphysis of the long bones. It is considered a malignant condition with high rates of metastasis. Ewing's sarcoma is part of Ewing's sarcoma family of tumors (ESFT), which includes several tumors: Ewing's sarcoma, Askin tumor, and peripheral primitive neuroectodermal tumor. Chemotherapy has greatly contributed to the survival of patients with Ewing's sarcoma. Before chemotherapy, only 10% of patients survived, but now more than 75% of patients with primary local tumors survive.
Ewing's sarcoma is best diagnosed by biopsy of the mass. The biopsy of the patient shows small round blue "onion" cells. Molecular findings in Ewing's sarcoma show a chromosomal translocation: t(11,22) that results in EWS-FL11 gene fusion. The EWS gene (22) encodes for RNA-binding proteins. FL11 gene (11) encodes for a protein with a DNA-binding domain that fuses with EWS protein. Educational Objective: Chromosomal translocation t(11,22) of Ewing's sarcoma results in EWS-FL11 fusion gene. Reference:
Balamuth N, Womer RB. Ewing's sarcoma. Lancet Oncol. 2011; 11:184-92. |
| Approved | Approved::No |
| Keyword | WBRKeyword::ewing's, WBRKeyword::sarcoma, WBRKeyword::ewing, WBRKeyword::Ewing, WBRKeyword::Ewing's, WBRKeyword::childhood, WBRKeyword::bone, WBRKeyword::tumor, WBRKeyword::primary, WBRKeyword::neuroectodermal, WBRKeyword::PNET, WBRKeyword::small, WBRKeyword::round, WBRKeyword::blue, WBRKeyword::cells, WBRKeyword::onion, WBRKeyword::diaphysis, WBRKeyword::t(11, WBRKeyword::22), WBRKeyword::translocation, WBRKeyword::EWS, WBRKeyword::FL11, WBRKeyword::EWS-FL11, WBRKeyword::fusion, WBRKeyword::gene, WBRKeyword::translocation, WBRKeyword::genetic |
| Linked Question | Linked:: |
| Order in Linked Questions | LinkedOrder:: |
