Clinicopathologic, Immunophenotypic, and Molecular Cytogenetic Fluorescence In Situ Hybridization Analysis of Primary and Secondary Cutaneous Follicular Lymphomas

Abstract

Although primary cutaneous follicular lymphoma (FL) is considered a distinct variant of FL in the World Health Organization classification ("cutaneous follicle center lymphoma"), its biologic relationship to nodal FL remains controversial. The clinical, morphologic, immunophenotypic, and molecular cytogenetic features of 17 patients with primary cutaneous FL were studied and compared with 16 patients with secondary cutaneous FL. The head and neck region was the most frequent site at initial skin presentation in both the primary and secondary cases. Among the primary cases, 29% of the 31 biopsies were grade 1, 48% grade 2, 13% grade 3, and 10% grade 3 with diffuse large B-cell (DLBCL) areas. Among the secondary cases, 38% of the 29 skin biopsies were grade 1, 45% grade 2, 3% grade 3, and 7% grade 3 with DLBCL areas with two not evaluable. A floral-like pattern was observed in 32% of primary FL but only 5% of secondary cases. Histologic progression was found in 21% of patients. CD10 expression was demonstrated in 90% (27 of 30) of primary cases and 96% (22 of 23) of secondary cases. Bcl-6 was expressed in all cases tested. Bcl-2 expression was detected in 57% (17 of 30) of the primary cases (100% of grade 1, 43% of grade 2, 40% of grade 3), whereas all secondary cases were bcl-2 positive (P=0.0002). The t(14;18) translocation was identified by interphase fluorescence in situ hybridization (FISH) in biopsies from 31% (4 of 13) of the patients with primary FL compared with 77% (10 of 13) of those with secondary lymphoma (P <0.05). Seven of the 17 (41%) patients with primary disease had cutaneous relapse, including 1 who also developed nodal disease. Bcl-2 positivity was seen in 4 of these 7 patients. Eight of the 16 (50%) patients with secondary FL had cutaneous relapse. Primary and secondary cutaneous FL share many clinical and phenotypic features, but primary cases may have some distinctive morphologic features, more frequently lack bcl-2 protein, and often lack the t(14;18) translocation. These findings suggest that primary cutaneous FL are distinctive and often but not always have a pathogenesis different from most of nodal and secondary cutaneous FL.

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.…”

“…35 Likewise, the formation of an isochromosome 7q is a characteristic finding in hepatosplenic T-cell lymphoma. In B-cell malignancies, however, numerical imbalances that can serve as characteristic and tumor-specific alterations usually are not encountered, with the possible exception of certain chromosomal imbalances in MZBCL recently defined by array or conventional CGH, 34,36 such as the 7q32 deletion encountered in some cases of splenic MZBCL. 37 In this study, we have documented that deletions in chromosomal band 1p36 are a recurring genetic aberration in predominantly diffuse FL.…”

Early lymphoid lesions: conceptual, diagnostic and clinical challenges

“…Centrocytes, which may be large, often predominate, and grading is not required. BCL2 expression, if positive, is weak and variable 72,73 but the t(14;18)(IGH-BCL2) translocation is usually negative, and if present, should raise concern for secondary cutaneous involvement. 74 Clonal immunoglobulin gene rearrangements can be detected in more than 90% of cases.…”

″Minor″ BCL2 Breakpoints in Follicular Lymphoma

“…In that extranodal site, there is a suggestion that the frequency of the translocation may be geographical, occurring more commonly in North American studies than in European studies. [31][32][33][34][35] In summary, this study emphasizes the importance of including minor breakpoints, especially ones located at the icr cluster, in PCR diagnostic techniques of follicular lymphomas. Furthermore, FISH is a useful technique to confirm BCL2 and BCL6 translocations in PCR-negative cases.…”