A 35-year-old woman presents with fever, lymphadenopathy and splenomegaly. Biopsy shows large CD30+ cells with bilobed nuclei and prominent 'owl-eye' eosinophilic nucleoli, accompanied by a background of eosinophils, plasma cells, and reactive T-cells. Immunophenotyping shows CD15+ CD30+ CD45– EBV-LMP1+. Which of the following chromosomal or molecular findings is most characteristically associated with this entity?

• A t(14;18) causing BCL2 overexpression in the Reed-Sternberg cells
• B Constitutive NF-κB activation via genetic inactivation of TNFAIP3 (A20), a negative regulator of NF-κB, in Reed-Sternberg cells ✓
• C t(8;14) c-MYC translocation driving rapid cell cycle progression in Hodgkin cells
• D JAK2 V617F mutation causing erythroid hyperplasia in the surrounding reactive marrow

Explanation

This describes classic Hodgkin lymphoma, mixed cellularity subtype with EBV positivity. A hallmark of Reed-Sternberg (RS) cells is constitutive NF-κB activation, which provides survival signals. One key mechanism in EBV-positive cases is viral LMP1 mimicking CD40 signaling, activating IKK. Additionally, genetic alterations in A20 (TNFAIP3), a ubiquitin-editing enzyme that normally terminates NF-κB signaling, are found in a subset of cases, sustaining RS cell survival. t(14;18) is characteristic of follicular lymphoma, and t(8;14) is characteristic of Burkitt 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.