A 55-year-old man with progressive cervical lymphadenopathy for 8 months undergoes lymph node biopsy. Histology shows effacement of nodal architecture by a nodular proliferation of small, cleaved lymphocytes (centrocytes) admixed with fewer large non-cleaved cells (centroblasts). Immunohistochemistry: CD20+, CD10+, BCL-2+, BCL-6+, CD5−. Which molecular alteration is MOST responsible for the BCL-2 overexpression in this tumor?

• A Point mutation in the BCL-2 coding sequence
• B Amplification of chromosome 18q21
• C Loss of miR-15a/16 cluster on chromosome 13q14
• D t(14;18) juxtaposing BCL-2 to the immunoglobulin heavy chain enhancer ✓

Explanation

Follicular lymphoma is the prototypical B-cell lymphoma driven by t(14;18)(q32;q21), which places the BCL-2 anti-apoptotic gene under the control of the powerful immunoglobulin heavy chain enhancer, leading to constitutive BCL-2 overexpression and failure of apoptosis in germinal center B cells. BCL-2 point mutations are not characteristic; chromosome 18q21 amplification can occur but is not the primary mechanism; loss of miR-15a/16 is characteristic of CLL/SLL.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.