Correct Answer: D. t(14;18)
The clinical and morphological features described—centrocytes and centroblasts with BCL2 positivity and CD10 expression—are pathognomonic for follicular lymphoma (FL). The t(14;18) translocation is the defining cytogenetic abnormality in FL, present in 85–90% of cases. This translocation juxtaposes the BCL2 gene on chromosome 18 to the immunoglobulin heavy chain (IgH) locus on chromosome 14, resulting in constitutive BCL2 overexpression and resistance to apoptosis. The morphology reflects the germinal center origin: centrocytes (small cleaved cells) and centroblasts (large cells with open chromatin) form a nodular pattern. CD10 and BCL6 positivity confirms germinal center B-cell derivation, while BCL2 overexpression (unusual in normal germinal center cells) is the hallmark of FL. In Indian practice, FL represents 20–30% of non-Hodgkin lymphomas and typically presents in adults with painless lymphadenopathy. The t(14;18) is not only diagnostic but also prognostically relevant and guides treatment decisions per Indian lymphoma protocols.
Why the other options are wrong
A. t(11;14) — This is wrong because t(11;14) is the hallmark of mantle cell lymphoma (MCL), not follicular lymphoma. MCL presents with cyclin D1 overexpression (CCND1 gene on chromosome 11 translocates to IgH on 14), resulting in CD5+ B-cell proliferation. MCL lacks CD10 expression and typically shows diffuse infiltration rather than nodular architecture. While both are B-cell lymphomas, the immunophenotype and morphology are distinct. B. t(2;5) — This is wrong because t(2;5) defines anaplastic large cell lymphoma (ALCL), a T-cell lymphoma, not a B-cell lymphoma. This translocation involves the ALK gene and results in ALK protein overexpression. ALCL presents with large pleomorphic cells, not centrocytes and centroblasts, and is CD10-negative and BCL2-negative. The morphology and immunophenotype are completely different from follicular lymphoma. C. t(11;14) — This option is identical to option A and is incorrect for the same reason: it represents mantle cell lymphoma, not follicular lymphoma. The presence of CD10 and BCL2 positivity with centrocyte/centroblast morphology excludes MCL. This duplication in the question stem may be an NBE error, but the correct answer remains t(14;18).
High-Yield Facts
- t(14;18) is present in 85–90% of follicular lymphomas and results in BCL2 overexpression via juxtaposition to the IgH locus.
- CD10+ BCL2+ germinal center phenotype (centrocytes and centroblasts) is diagnostic of follicular lymphoma; BCL2 positivity in germinal center cells is abnormal and pathognomonic.
- Mantle cell lymphoma (t(11;14)) is CD5+ CD23+ CD10-negative, whereas follicular lymphoma is CD5-negative CD10+ BCL2+.
- Follicular lymphoma represents 20–30% of Indian NHL cases and typically presents as stage III–IV disease with nodal involvement.
- t(14;18) can be detected by PCR/FISH and has prognostic significance; presence does not always correlate with disease burden but guides monitoring.
- ALCL (t(2;5)) is ALK+ and a T-cell lymphoma, morphologically distinct with large anaplastic cells, not centrocytes/centroblasts.
Mnemonics
FL = 14:18 (Follicular = 14:18) Follicular lymphoma = t(14;18). Remember: 14 (IgH) + 18 (BCL2) = FL. The numbers are in order of chromosome number. CD10 BCL2 = Follicular When you see CD10+ BCL2+ germinal center cells → think t(14;18) and follicular lymphoma. This immunophenotype is nearly pathognomonic. MCL = 11:14 (Mantle = 11:14) Mantle cell lymphoma = t(11;14). Remember: 11 (CCND1/cyclin D1) + 14 (IgH) = MCL. Reverse order helps distinguish from FL.
NBE Trap
NBE may pair t(11;14) with germinal center morphology to trap students who confuse mantle cell lymphoma with follicular lymphoma. The key discriminator is CD10 expression (FL+, MCL−) and BCL2 overexpression (FL+, MCL−), not just the presence of small and large cells.
Clinical Pearl
In Indian practice, a patient presenting with painless generalized lymphadenopathy and a biopsy showing nodular infiltration of centrocytes/centroblasts with CD10+ BCL2+ phenotype should immediately trigger t(14;18) testing and follicular lymphoma diagnosis. This translocation is often present even in early-stage disease and guides long-term surveillance and treatment intensity.
_Reference: Robbins Ch. 13 (Lymphoid Neoplasms); Harrison Ch. 104 (Lymphomas)_