Nokea
You are seeing a 12-year-old boy in the survivorship program who presented at 2 years old with a desmoplastic nodular medulloblastoma. You note the child recently underwent germline genetic testing and was found to have nevoid basal cell carcinoma syndrome. In which gene is the child most likely to have a pathogenic variant?
- A. PTEN
- B. CDKN2A
- C. SUFU
- D. SMARCB1
Correct Answer: C
Rationale: Rationale: The correct answer is C: SUFU. Nevoid basal cell carcinoma syndrome, also known as Gorlin syndrome, is associated with pathogenic variants in the SUFU gene. SUFU is a tumor suppressor gene involved in the sonic hedgehog signaling pathway, which plays a role in medulloblastoma and basal cell carcinoma development. PTEN (A) is associated with Cowden syndrome, CDKN2A (B) with familial atypical multiple mole melanoma syndrome, and SMARCB1 (D) with rhabdoid tumor predisposition syndrome, but not specifically linked to nevoid basal cell carcinoma syndrome.
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When assessing a newly admitted patient, the nurse notes pallor of the skin and nail beds. The nurse should ensure that which laboratory test has been ordered?
- A. Platelet count
- B. Neutrophil count
- C. White blood cell count
- D. Hemoglobin (Hgb) level
Correct Answer: D
Rationale: The correct answer is D: Hemoglobin (Hgb) level. Pallor of the skin and nail beds indicates possible anemia, which is a condition characterized by low levels of hemoglobin. Thus, checking the hemoglobin level is crucial to confirm the suspicion of anemia. Platelet count (choice A) assesses for clotting ability, neutrophil count (choice B) and white blood cell count (choice C) are indicators of infection or inflammation, which are not directly related to pallor. Hemoglobin level directly correlates with the observed symptom of pallor, making it the most appropriate laboratory test to order.
A 13-year-old Hispanic girl is found to have a WBC count of 6,500/mm3 with 40% Auer rod–containing granular blasts that, by flow cytometry, express very bright CD33 but are negative for human leukocyte antigen–DR isotype (HLA-DR). She is oozing blood around her peripheral IV site. Coagulation studies reveal an international normalized ratio (INR) of 3.4, a fibrinogen of 170, and a markedly elevated D-dimer. Marrow aspirate shows nearly 90% blasts with a similar morphology. You send the marrow to the fluorescence in situ hybridization (FISH) lab and request STAT testing for the most likely recurrent genetic abnormality based on the clinical presentation. How do you plan to initiate therapy?
- A. Perform a lumbar puncture to determine leukemic involvement, then proceed with induction chemotherapy.
- B. Begin therapy with all-trans retinoic acid (ATRA) immediately while aggressively managing coagulopathy with blood product support.
- C. Start dexamethasone and hydroxyurea immediately while aggressively managing coagulopathy with blood product support.
- D. Start induction chemotherapy, obtain HLA typing, and start a donor search because of the poor prognosis associated with this leukemic phenotype.
Correct Answer: B
Rationale: The correct answer is B: Begin therapy with all-trans retinoic acid (ATRA) immediately while aggressively managing coagulopathy with blood product support. The patient's presentation is consistent with acute promyelocytic leukemia (APL), indicated by the presence of Auer rod-containing blasts, very bright CD33 expression, and coagulopathy (elevated INR, low fibrinogen, elevated D-dimer). APL is associated with a specific genetic abnormality involving the PML-RARA fusion gene. ATRA is the mainstay of induction therapy for APL as it induces differentiation of leukemic promyelocytes. Aggressive management of coagulopathy is crucial to prevent life-threatening bleeding complications.
Incorrect answers:
A: Performing a lumbar puncture is not necessary at this stage as the patient's symptoms and laboratory findings point towards APL, not central nervous system involvement.
C: Dexamethasone and hydroxyurea are not
An otherwise healthy 18-year-old female is diagnosed with high-risk neuroblastoma after presenting with fatigue and bony pain. Imaging findings demonstrate a left adrenal mass with multiple osseous metastases. She successfully completes standard therapy for high-risk neuroblastoma, but experiences several episodes of disease recurrence and ultimately dies of her disease 10 years after her initial diagnosis. During her treatment, her tumor was sent for molecular analysis. Of the following, what molecular aberration was most likely to have been detected?
- A. ETV6-NTRK3 gene fusion
- B. PTPN11 mutation
- C. ATRX mutation
- D. WT1 mutation
Correct Answer: C
Rationale: The correct answer is C: ATRX mutation. In neuroblastoma, ATRX mutations are associated with poor prognosis and increased risk of disease recurrence. This mutation disrupts chromatin remodeling, leading to genomic instability and aggressive tumor behavior. ETV6-NTRK3 gene fusion (Choice A) is more commonly associated with pediatric mesenchymal tumors. PTPN11 mutation (Choice B) is typically found in Noonan syndrome and other malignancies, not neuroblastoma. WT1 mutation (Choice D) is more commonly seen in Wilms tumor, not neuroblastoma. In summary, the ATRX mutation is the most likely molecular aberration detected in this case based on the clinical presentation and outcomes of the patient.
Thrombocytopenia is absent in:
- A. DIC
- B. Wiskott Aldrich syndrome
- C. Henoch Schonlein purpura
- D. myelosclerosis
Correct Answer: C
Rationale: Thrombocytopenia is absent in Henoch Schonlein purpura because it primarily involves vasculitis, not platelet destruction or consumption. In DIC (A), there is widespread activation of coagulation leading to thrombocytopenia. Wiskott Aldrich syndrome (B) is characterized by low platelet counts due to defective platelet function. Myelosclerosis (D) is a bone marrow disorder causing decreased platelet production, leading to thrombocytopenia.
Bone marrow responds to iron therapy by increasing erythropoietic activity. Which of the following in bone marrow would most likely indicate erythropoiesis?
- A. Myelocytes
- B. Reticulocytes
- C. Ring sideroblasts
- D. Target cells
Correct Answer: B
Rationale: The correct answer is B: Reticulocytes. Reticulocytes are immature red blood cells released by the bone marrow into the bloodstream in response to increased erythropoietic activity. They indicate ongoing erythropoiesis as they mature into fully functional red blood cells. Myelocytes (A) are immature granulocytic precursors, not involved in erythropoiesis. Ring sideroblasts (C) are seen in conditions like sideroblastic anemia and indicate abnormal iron metabolism. Target cells (D) are red blood cells with a central bull's eye appearance and are associated with conditions like liver disease and thalassemias, not specifically erythropoiesis.