An 11-year-old boy presents with localized pain, swelling over his tibia, and intermittent fevers for the past month. Radiographs reveal a primarily lytic bone lesion with a multi-laminar periosteal reaction described as “onion-skinning.” Which diagnostic molecular finding would be most specific for the suspected diagnosis of Ewing sarcoma?
A 12-year-old girl with a history of multiple, soft, compressible cutaneous nodules presents with recurrent episodes of hematochezia leading to severe iron deficiency anemia that requires multiple blood transfusions. An endoscopy reveals numerous venous malformations throughout her small intestine. Genetic testing of affected tissue reveals a gain-of-function somatic pathogenic variant in TIE2/TEK. Which of the following syndromes best fits this clinical and genetic profile?
A 15-year-old phenotypical female with a known Y chromosome and a history of incompletely masculinized external genitalia is being evaluated for an ovarian mass found on ultrasound. The mass is surgically resected. Which type of tumor is specifically associated with her underlying condition of gonadal dysgenesis?
A 16-year-old male is diagnosed with stage IV rhabdomyosarcoma with lung metastases. Molecular testing of the tumor is performed to help determine his prognosis and guide potential inclusion in clinical trials. Which of the following molecular findings is associated with the poorest prognosis in patients with metastatic rhabdomyosarcoma?
A 4-year-old girl presents with new-onset pubic hair, clitoromegaly, and facial plethora. Her blood pressure is elevated. An abdominal magnetic resonance imaging scan identifies a large right adrenal mass. This clinical presentation of a functional adrenocortical tumor is most strongly associated with which of the following hereditary tumor predisposition syndromes?
A 4-year-old boy is diagnosed with precursor B-cell acute lymphoblastic leukemia. His initial white blood cell count is 8,200/μL, and flow cytometry shows a hyperdiploid karyotype with 55 chromosomes. On day 8 of induction, his peripheral blood is cleared of blasts, and on day 29, minimal residual disease (MRD) testing by flow cytometry shows a level of 0.05%. Cytogenetic testing reveals an additional finding of t(9;22)(q34;q11.2). Which of the following is most strongly associated with a poor prognosis in this patient?
A 2-year-old boy presents with a high fever of 39.4°C (103°F), splenomegaly, and pancytopenia (hemoglobin 8.5 g/dL, platelets 70 x 10³/mL, neutrophils 0.8 x 10³/mL). Laboratory studies are significant for a ferritin level of 8,000 ng/mL and hypofibrinogenemia. According to the Histiocyte Society diagnostic criteria, which of the following additional findings would be most supportive of the most likely diagnosis?
A 6-year-old girl with B-cell acute lymphoblastic leukemia is receiving maintenance therapy with 6-mercaptopurine. She develops severe myelosuppression despite being on a standard dose. Genetic testing reveals a polymorphism in an enzyme that catalyzes the methylation of 6-mercaptopurine, leading to increased accumulation of cytotoxic thioguanine nucleotides. Which gene is most likely affected?
A 16-year-old is diagnosed with a paraganglioma. His family history is significant for a paternal uncle with a pheochromocytoma. A genetic predisposition is suspected, and testing is likely to reveal a pathogenic variant in a gene encoding which of the following?
A 14-year-old boy is diagnosed with anaplastic large cell lymphoma. Molecular analysis of the tumor cells reveals a t(2;5) translocation. This translocation results in a fusion gene encoding a constitutively active kinase, which presents a potential target for specific inhibitor therapy. What is the protein product of this fusion gene?
