A 35-year-old woman presents with mediastinal mass, fever, and night sweats. Biopsy shows large lacunar cells and rare Reed-Sternberg cells in a fibrous background. Immunohistochemistry: CD15+, CD30+, CD45-, PAX5 dim+, EBV-. The translocation most commonly seen in this specific Hodgkin lymphoma subtype is:
- A t(14;18) involving BCL2 and IGH loci
- B t(2;5) involving ALK and NPM1
- C t(11;14) involving CCND1 and IGH
- D Amplification of chromosome 9p24.1 involving JAK2, PDL1 (CD274), and PDL2 ✓
Explanation
Nodular sclerosis classical Hodgkin lymphoma (NSCHL) — characterized by lacunar cells, fibrous bands, and mediastinal involvement in young women — frequently shows amplification of 9p24.1, a locus containing JAK2, CD274 (PDL1), and CD273 (PDL2). This amplification activates JAK-STAT6 signaling via JAK2 and upregulates PDL1/PDL2 expression, which mediates immune evasion by suppressing cytotoxic T-cells in the tumor microenvironment. This finding is the molecular basis for the exceptional response of CHL to pembrolizumab (anti-PD1). t(14;18) is follicular lymphoma; t(2;5) is ALCL; t(11;14) is mantle 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.