Q. A lymphoma characterized by the presence of centrocytes and centroblasts, along with BCL2 positivity and CD10 expression, is most commonly associated with which chromosomal translocation?

Explanation

## Correct Answer: A. t(14;18) The clinical and immunophenotypic profile described—centrocytes and centroblasts with BCL2 positivity and CD10 expression—is pathognomonic for **follicular lymphoma (FL)**. This is the most common indolent non-Hodgkin lymphoma in India and the West. The hallmark translocation is **t(14;18)(q32;q21)**, which juxtaposes the BCL2 gene on chromosome 18 to the immunoglobulin heavy chain (IgH) locus on chromosome 14. This results in constitutive BCL2 overexpression, preventing apoptosis and driving lymphomagenesis. The morphology reflects a neoplastic germinal center B-cell population: centrocytes (small cleaved cells) and centroblasts (large cells with open chromatin). CD10 positivity confirms germinal center origin, while BCL2 overexpression (detected by immunohistochemistry) is the functional consequence of the translocation. In Indian practice, FL typically presents in stage III–IV disease, often with bone marrow involvement. The t(14;18) translocation is found in 85–90% of FL cases and is considered the defining genetic lesion per WHO classification. This translocation is virtually diagnostic of FL and distinguishes it from other B-cell lymphomas with overlapping morphology. ## Why the other options are wrong **B. t(11;14)** — This translocation is characteristic of **mantle cell lymphoma (MCL)**, not follicular lymphoma. MCL presents with cyclin D1 overexpression (via CCND1 gene on chromosome 11), resulting in CD5+ B-cell lymphoma with a different morphology (small lymphocytes, not centrocytes/centroblasts). MCL is typically CD10-negative and BCL2-variable. This is a common NBE trap pairing two different translocations with similar-sounding chromosome numbers. **C. t(2;5)** — This translocation is found in **anaplastic large cell lymphoma (ALCL)**, a T-cell lymphoma, not a B-cell lymphoma. t(2;5) involves the ALK gene and results in ALK protein overexpression. ALCL has a completely different morphology (large anaplastic cells, not centrocytes/centroblasts) and immunophenotype (T-cell markers, not B-cell markers with CD10). This option tests whether students confuse lymphoma subtypes by translocation alone. **D. t(11;14)** — This is a duplicate of option B (likely a typographical error in the question stem). t(11;14) remains the translocation of mantle cell lymphoma, not follicular lymphoma. The presence of two identical wrong options suggests the question may have been transcribed with an error, but the correct answer remains t(14;18) for the described FL phenotype. ## High-Yield Facts - **t(14;18)** is found in 85–90% of follicular lymphomas and is the defining translocation per WHO classification. - **BCL2 overexpression** (consequence of t(14;18)) prevents apoptosis and is detected by immunohistochemistry in FL. - **CD10 positivity** in FL confirms germinal center B-cell origin; CD10 is absent in mantle cell lymphoma. - **Centrocytes and centroblasts** are the morphologic hallmark of FL; centrocytes are small cleaved cells, centroblasts are large with open chromatin. - **Mantle cell lymphoma** (t(11;14)) is CD5+, cyclin D1+, and typically CD10-negative—key discriminator from FL. - **FL typically presents in stage III–IV** in Indian practice with bone marrow and nodal involvement; prognosis is indolent but incurable with standard therapy. ## Mnemonics **FL = 14:18 (Follicular = 14:18)** Follicular lymphoma → t(14;18) → BCL2 overexpression → germinal center B cells (CD10+). Remember: 14 (IgH heavy chain) meets 18 (BCL2 gene) → apoptosis block → indolent lymphoma. **MCL = 11:14 (Mantle = 11:14)** Mantle cell lymphoma → t(11;14) → cyclin D1 overexpression → CD5+ small B cells. Opposite chromosome order from FL; different biology (aggressive, CD5+, CD10-negative). ## NBE Trap NBE pairs t(14;18) and t(11;14) with similar chromosome numbers to trap students who memorize translocations without understanding the associated morphology and immunophenotype. The presence of BCL2 positivity and CD10 expression is the discriminating clue that rules out mantle cell lymphoma (which is CD10-negative and cyclin D1-driven, not BCL2-driven).</trap> <parameter name="textbookRef">Robbins & Cotran Pathologic Basis of Disease, Ch. 13 (Hematopoietic and Lymphoid Systems); WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (2016) ## Clinical Pearl In Indian tertiary centers, follicular lymphoma is often diagnosed at advanced stage (III–IV) with bone marrow involvement. The t(14;18) translocation can be detected by FISH or PCR in bone marrow aspirates and is useful for minimal residual disease monitoring post-treatment. Recognition of the CD10+/BCL2+ immunophenotype at diagnosis is critical for distinguishing FL from other indolent lymphomas and guides prognostication and treatment intensity.</clinicalPearl> </invoke>