Molecular Cytogenetic Evidence of t(14;18)(IGH;BCL2) in a Substantial Proportion of Primary Cutaneous Follicle Center Lymphomas

Abstract

In contrast to nodal follicular lymphoma, limited data exist on genetic changes in primary cutaneous follicular lymphoma (primary cutaneous follicle center lymphoma according to WHO-EORTC). The detection rate of the BCL2 rearrangement, representing the characteristic t(14;18)(q32;q21) underlying follicular lymphoma, by polymerase chain reaction (PCR) has been reported to vary over a wide range (0%-41%), and only a few cases have been studied by molecular cytogenetic techniques such as fluorescence in situ hybridization (FISH). In this study, 27 primary cutaneous follicle center lymphomas were analyzed by FISH and the results compared with those obtained by PCR. FISH demonstrated translocations affecting the immunoglobulin heavy chain locus (IGH) in 14 of 27 cases (52%): a t(14;18)(q32;q21) involving BCL2 was found in 11 cases (41%), a t(3;14)(q27;q32) affecting BCL6 in 2 cases (7%), and in 1 case the partner gene of IGH could not be identified. Interestingly, PCR did not detect BCL2 rearrangement in any case. These data suggest that the t(14;18)(q32;q21) frequently occurs in primary cutaneous follicular lymphoma. The reason(s) why BCL2 rearrangements escape the detection by PCR is (are) not clear but could be due to BCL2 mutations, breakpoints outside the amplified DNA, or a high load of somatic mutations.

Duodenal follicular lymphoma lacks AID but expresses BACH2 and has memory B-cell characteristics

“…These facts suggest that gastric FL may be similar to primary cutaneous follicle center lymphoma. 33,34 In conclusion, we suggest that duodenal FL is a distinct entity among gastrointestinal FLs, by virtue of AID loss but BACH2 expression, displaying a specific CD21 pattern, and high frequency of CD27 expression.…”

A distinctive subtype of t(14;18)-negative nodal follicular non-Hodgkin lymphoma characterized by a predominantly diffuse growth pattern and deletions in the chromosomal region 1p36

“…2,3,31,32 The site of origin itself may also predict for the t(14;18) status in FL: Although primary duodenal and intestinal FL, for example, are t(14;18) positive in the most cases, primary cutaneous FL are BCL2 rearranged in less than 50% of cases. 33,34 Ideally, malignant tumors with similar morphologic and immunophenotypic features and comparable clinical presentations also display similar genetic features. This is the case for the so-called primary translocations in certain NHL subtypes thus defining biologic entities, such as the t(14;18) in FL, the t(11;14) in MCL, or the t(3q27)/BCL6 rearrangement in DLBCL.…”

The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications

“…108,109 A follicular variant of T-cell lymphoma has been recognized that also seems to originate from these cells, with some cases carrying the t(5;9) translocation, fusing ITK to SYK. 110,111 However, it is not clear if all PTCL-expressing follicular Th markers correspond to the same entity. 112 Despite the recognition of some specific subtypes, most PTCLs still remain under a broad category of NOS.…”