A 38-year-old woman presents with fever, night sweats, and a mediastinal mass. Biopsy shows large cells with bilobed nuclei, prominent 'owl eye' nucleoli, and a background of T-lymphocytes, plasma cells, and eosinophils. Flow cytometry shows CD30+, CD15+, CD20-, PAX5 dim positive. Which translocation/molecular alteration is most characteristically found in the neoplastic cells?
- A t(14;18) causing BCL-2 overexpression
- B t(8;14) with MYC-IGH fusion
- C Amplification of chromosome 9p24.1 involving JAK2, PD-L1, and PD-L2 ✓
- D t(2;5) with NPM-ALK fusion
Correct answer: C. Amplification of chromosome 9p24.1 involving JAK2, PD-L1, and PD-L2
Explanation
Classical Hodgkin lymphoma (cHL) Reed-Sternberg cells frequently harbor amplification of chromosome 9p24.1, which includes JAK2, PD-L1 (CD274), and PD-L2 (PDCD1LG2). This leads to constitutive JAK-STAT signaling and upregulation of immune checkpoint ligands, explaining the efficacy of PD-1 blockade (pembrolizumab) in relapsed/refractory cHL. t(14;18) is characteristic of follicular lymphoma; t(8;14) is Burkitt lymphoma; t(2;5) is ALK-positive anaplastic large cell lymphoma.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.