Genetic Translocations: Mantle Cell vs Follicular Lymphoma
Mantle cell lymphoma is defined by t(11;14)(q13;q32) involving CCND1-IGH, while follicular lymphoma is characterized by t(14;18)(q32;q21) involving BCL2-IGH—these are the key distinguishing translocations between these two entities. 1
Mantle Cell Lymphoma Translocations
Primary translocation:
- t(11;14)(q13;q32) [IGH::CCND1] is the hallmark genetic alteration present in the vast majority of cases, resulting in cyclin D1 overexpression 1, 2, 3
- Variant translocations involving immunoglobulin light chains: t(2;11)(p11;q13) [IGK::CCND1] and t(11;22)(q13;q11) [IGL::CCND1] 1
Alternative cyclin translocations (rare):
- t(12;22)(p13;q21) [IGL::CCND2], t(2;12)(p12;p13) [IGK::CCND2], and t(12;14)(p13;q32) [IGH::CCND2] involving cyclin D2 1
- t(6;14)(p21;q32) [IGH::CCND3] involving cyclin D3 1
Secondary translocations:
- 8q24 [MYC] rearrangements can occur, creating "double-hit" MCL with highly aggressive clinical course 1, 2
- 3q27 [BCL6] rearrangements are occasionally present 1, 4
Follicular Lymphoma Translocations
Primary translocation:
- t(14;18)(q32;q21) [IGH::BCL2] is the characteristic translocation, leading to BCL2 overexpression 1
- Variant translocations: t(2;18)(p12;q21) [IGK::BCL2] and t(18;22)(q21;q11.2) [IGL::BCL2] 1
Secondary translocations:
- 3q27 [BCL6] rearrangements occur frequently 1
- 8q24 [MYC] rearrangements can develop, particularly in transformation to higher grade 1
- 6p25 [IRF4] rearrangements should be examined in BCL2-negative cases in the appropriate clinical setting 1
Clinical Diagnostic Implications
FISH testing recommendations:
- For suspected MCL: IGH::CCND1 fusion probes are essential, especially in cases with atypical immunophenotype (CD23 dim/negative, CD20 bright, surface immunoglobulin bright) to differentiate from chronic lymphocytic leukemia 1
- For suspected follicular lymphoma: BCL2-IGH translocation testing is standard, with additional IRF4 and TNFRSF14 assessment in BCL2-negative cases 1, 5
Prognostic significance:
- In MCL, complex karyotypes and TP53 loss (17p13) are associated with unfavorable prognosis 1, 5
- MYC rearrangements in either entity indicate more aggressive behavior and require different treatment approaches 1
Critical pitfall: The t(14;18) translocation can involve either BCL2 or MALT1 genes at 18q21, which are cytogenetically identical but represent different disease entities (follicular lymphoma vs MALT lymphoma)—FISH is required to distinguish between them 1