A 54-year-old patient presents to the outpatient department with fatigue, tiredness, and cervical lymphadenopathy. The TLC and DLC were regular. No immature cells. A lymph node biopsy showed diffuse effacement of the lymph node architecture, cells with an indented nucleus, prominent nucleolus, and are atypical. CD10 and BCL2 are positive. What is the likely diagnosis?

Correct Answer: B. Follicular lymphoma

Follicular lymphoma is a CD10+ and BCL2+ B-cell non-Hodgkin lymphoma arising from germinal center B cells. The key discriminating features here are the dual positivity for CD10 and BCL2, which is pathognomonic for follicular lymphoma. CD10 (CALLA antigen) marks germinal center origin, while BCL2 positivity indicates the t(14;18) translocation characteristic of this lymphoma. The histology showing diffuse effacement of lymph node architecture with atypical cells bearing indented (cleaved) nuclei and prominent nucleoli describes the classic appearance of centrocytes and centroblasts. The regular TLC and DLC with no immature cells rules out acute leukemia and suggests a mature lymphoid malignancy. Follicular lymphoma is the most common indolent lymphoma in India and the West, typically presenting in middle-aged to older adults with painless lymphadenopathy and constitutional symptoms like fatigue. The t(14;18) translocation juxtaposes the BCL2 gene to the immunoglobulin heavy chain locus, leading to BCL2 overexpression and resistance to apoptosis. This is the hallmark of follicular lymphoma and explains its indolent course with long survival but incurable nature in most cases.

Why the other options are wrong

A. Burkitt lymphoma — Burkitt lymphoma is CD10+ but BCL2-negative (lacks t(14;18)), presents with rapidly progressive disease and high LDH, and shows a starry-sky histology with uniform medium-sized blasts, not cleaved nuclei. It is associated with t(8;14) translocation involving MYC, not BCL2. The regular TLC and absence of immature cells also argue against Burkitt's aggressive presentation. C. Chronic myeloid leukemia — CML is a myeloid malignancy characterized by Philadelphia chromosome (t(9;22)) and BCR-ABL fusion, not a lymphoid process. It would show elevated TLC with left shift and immature myeloid cells (blasts, myelocytes) on DLC, not a normal TLC. Lymph node biopsy showing lymphoid cells with CD10/BCL2 positivity is incompatible with CML, which is primarily a bone marrow disorder. D. Mycosis fungoides — Mycosis fungoides is a cutaneous T-cell lymphoma (CD4+ T cells), not a B-cell lymphoma. It presents with skin lesions (patches, plaques, tumors) and is CD10-negative and BCL2-negative. The immunophenotype (CD10+, BCL2+) and presentation with cervical lymphadenopathy without skin involvement rule out mycosis fungoides entirely. It is a CD4+ T-cell process, not a germinal center B-cell lymphoma.

High-Yield Facts

Mnemonics

Follicular Lymphoma = 10-2 Rule CD10+ BCL2+ = Follicular lymphoma. Remember: 10 (CD10) and 2 (BCL2) are the twin markers. t(14;18) is the genetic hallmark. Indolent vs Aggressive B-cell Lymphomas Indolent (Follicular, SLL/CLL, Lymphoplasmacytic): slow, long survival, incurable. Aggressive (Burkitt, DLBCL, Lymphoblastic): fast, short survival, potentially curable. Follicular is the prototype indolent.

NBE Trap

NBE may pair CD10+ status with Burkitt lymphoma to trap students who remember CD10 as a germinal center marker but forget that Burkitt is BCL2-negative and shows a starry-sky pattern, not cleaved nuclei. The dual CD10+BCL2+ combination is the key discriminator.

Clinical Pearl

In Indian practice, follicular lymphoma often presents late (stage III–IV) because early asymptomatic lymphadenopathy is often missed. The indolent course and long survival mean many patients live 8–10 years with watchful waiting; transformation to DLBCL occurs in ~10% and signals aggressive disease requiring immediate chemotherapy (R-CHOP or R-CVP).

_Reference: Robbins Ch. 13 (Lymphoid Neoplasms); Harrison Ch. 104 (Lymphomas)_