Flow cytometry of a bone marrow sample from a 70-year-old man with fatigue shows a clonal B-cell population expressing CD19+, CD5+, CD23+, CD20 (dim), CD38 (negative), with surface IgM (dim) and CD10 (negative). ZAP-70 is positive and IGHV genes are unmutated. What is the prognostic implication of unmutated IGHV status in this disease?
- A Unmutated IGHV indicates the cell of origin was a post-germinal center memory B-cell, predicting indolent disease with prolonged time to first treatment
- B Unmutated IGHV confers resistance to fludarabine-based regimens but is curable with anti-CD20 monotherapy
- C Unmutated IGHV indicates derivation from a pre-germinal center naive B-cell, associated with shorter time to progression, higher rate of del(17p) and TP53 mutation, and inferior overall survival ✓
- D Unmutated IGHV is associated with t(11;14) translocation and mantle cell lymphoma phenotype
Explanation
The immunophenotype (CD19+ CD5+ CD23+ CD20 dim, surface Ig dim, CD10–) is diagnostic of chronic lymphocytic leukemia (CLL). IGHV mutation status is a critical prognostic biomarker: unmutated IGHV (< 2% divergence from germline) indicates derivation from naive B-cells that did not undergo germinal center somatic hypermutation. This subgroup shows stronger BCR signaling, higher frequency of del(17p)/TP53 mutations, higher risk of Richter transformation, shorter progression-free survival, and inferior outcomes compared to mutated IGHV cases which arise from post-germinal center memory B-cells.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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Written and medically reviewed by the StethoPrep medical team.