A 25-year-old man presents with mediastinal mass, fever, and night sweats. Biopsy shows Reed-Sternberg cells positive for CD15, CD30, and EBV-LMP1, with background mixed cellularity pattern. Which genetic alteration is CHARACTERISTICALLY seen in the Reed-Sternberg cells of classic Hodgkin lymphoma?
- A t(14;18) translocation causing BCL2 overexpression
- B MYC amplification and overexpression
- C Constitutive NF-κB activation via somatic mutations in TNFAIP3 (A20) or NFKBIA ✓
- D BCL6 rearrangement and aberrant somatic hypermutation
Explanation
In classic Hodgkin lymphoma (cHL), Reed-Sternberg cells are derived from germinal-centre B cells that have lost normal B-cell phenotype (CD19-, CD20 dim/negative) but gained CD15+ and CD30+. A hallmark molecular feature is constitutive NF-κB pathway activation, often through mutations in TNFAIP3 (encoding the NF-κB inhibitor A20) or NFKBIA, allowing RS cells to evade apoptosis and secrete immunosuppressive cytokines. t(14;18)/BCL2 is characteristic of follicular lymphoma. MYC amplification is seen in Burkitt and DLBCL subtypes. BCL6 rearrangement is characteristic of GCB-type DLBCL.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.