A 64-year-old man presents with 6 weeks of progressive right neck swelling, drenching night sweats, and 5 kg weight loss. Excisional biopsy of the cervical lymph node shows complete effacement of nodal architecture by sheets of large lymphoid cells with vesicular nuclei and prominent nucleoli. Tingible-body macrophages are scattered throughout, producing a characteristic starry-sky pattern. The structure marked **B** in the diagram shows CD20 strongly and diffusely positive cells with a Ki-67 proliferation index of 70%. FISH studies reveal MYC translocation WITHOUT BCL2 rearrangement. Which of the following is the most appropriate first-line therapeutic approach for this patient?

Question

Accepted Answer

D. 6 cycles of R-CHOP (rituximab + cyclophosphamide + doxorubicin + vincristine + prednisone). ## Why R-CHOP is correct

The structure marked **B** shows sheets of large CD20+ B-cells effacing nodal architecture — the defining histopathology of DLBCL. The clinical presentation (B-symptoms, elevated LDH, stage IIIB), morphology (large cells with vesicular nuclei and prominent nucleoli), and immunophenotype (CD20+ with 70% Ki-67) are diagnostic of DLBCL. Critically, FISH shows MYC translocation WITHOUT concurrent BCL2 rearrangement — this is NOT a double-hit or triple-hit lymphoma, which would require intensified therapy. Per WHO 2022 and standard guidelines, standard-risk DLBCL is treated with 6 cycles of R-CHOP, which is curative in 60–70% of patients. The CD20 positivity of the neoplastic cells makes rituximab (anti-CD20 monoclonal antibody) essential for optimal outcomes.

## Why each distractor is wrong

- **DA-EPOCH-R**: This intensified regimen is reserved for high-grade B-cell lymphoma with double-hit (MYC + BCL2 and/or BCL6) or triple-hit rearrangements. This patient has MYC translocation alone, not double-hit, so standard R-CHOP is appropriate.
- **Observation with close monitoring**: DLBCL is an aggressive lymphoma with a high proliferation index (70%) and advanced stage (IIIB). Observation without chemotherapy is not appropriate and would result in rapid disease progression and poor outcomes.
- **Rituximab monotherapy with deferred chemotherapy**: While rituximab is essential (targeting CD20+ cells), monotherapy alone is insufficient for DLBCL. Combined chemoimmunotherapy (R-CHOP) is the standard of care and significantly improves survival compared to rituximab alone.

**High-Yield:** DLBCL with single MYC translocation (without BCL2/BCL6 co-rearrangement) is treated with standard R-CHOP; double-hit or triple-hit lymphomas require DA-EPOCH-R or other intensified regimens.

[cite: WHO 2022 Classification of Tumours of Haematopoietic and Lymphoid Tissues; POLARIX trial (Pola-R-CHP vs R-CHOP for DLBCL)]

Answer

A. DA-EPOCH-R (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, rituximab)

Answer

B. Observation with close monitoring until disease progression

Answer

C. Rituximab monotherapy with deferred chemotherapy

Explanation

Why R-CHOP is correct

Why each distractor is wrong

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