Fluorescence Immunophenotyping and Interphase Cytogenetics (FICTION) Detects BCL6 Abnormalities, Including Gene Amplification, in Most Cases of Nodular Lymphocyte-Predominant Hodgkin Lymphoma

Abstract

Context.— BCL6 translocations are a frequent finding in B-cell lymphomas of diverse subtypes, including some cases of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). However, reliable analysis of BCL6 rearrangements using fluorescence in situ hybridization is difficult in NLPHL because of the relative paucity of neoplastic cells. Combined immunofluorescence microscopy and fluorescence in situ hybridization, or fluorescence immunophenotyping and interphase cytogenetics as a tool for the investigation of neoplasms (FICTION), permits targeted analysis of neoplastic cells. Objective.—To better define the spectrum of BCL6 abnormalities in NLPHL using FICTION analysis. Design.—We performed an optimized FICTION analysis of 24 lymph nodes, including 11 NLPHL, 5 follicular hyperplasia with prominent progressive transformation of germinal centers, and 8 follicular hyperplasia without progressive transformation of germinal centers. Results.— BCL6 rearrangement was identified in 5 of 11 cases of NLPHL (46%). In addition, BCL6 gene amplification, with large clusters of BCL6 signals in the absence of chromosome 3 aneuploidy, was detected in 3 of 11 cases of NLPHL (27%). One NLPHL showed extra copies of BCL6 present in conjunction with multiple copies of chromosome 3. Altogether, we detected BCL6 abnormalities in 9 of 11 cases of NLPHL (82%). None of the progressive transformation of germinal centers or follicular hyperplasia cases showed BCL6 abnormalities by FICTION. Conclusions.—To our knowledge, this is the first report of BCL6 gene amplification in NLPHL. Our optimized protocol for FICTION permits detection of cytogenetic abnormalities in most NLPHL cases and may represent a useful ancillary diagnostic technique.

Lymphocyte predominant cells of nodular lymphocyte predominant Hodgkin lymphoma interact with rosetting T cells in an immunological synapse

“…The strong constitutive expression of BCL6 due to genomic aberrations in LP cells [41][42][43] Moraxella-reactive LP cells. 10 However, in the present study, we did not observe a restriction of this phenomenon to IgD + cases.…”

“…The strong constitutive expression of BCL6 due to genomic aberrations in LP cells 41‐43 probably hampers LP cell precursors exit from the germinal center and prevents LP cell differentiation towards memory B or plasma cells. Thus, the deregulated BCL6 expression in the LP cells may be a major factor contributing to this prolonged antigen presentation by the LP cells.…”

The t(14;18) translocation is absent from endothelial and follicular dendritic cells of follicular lymphoma (FL) and shows heterogeneous presence in preserved FL mantle zones

“…FICTION is a powerful technique [ 12 – 14 ], which has been used extensively in haematopoietic malignancies, e.g. to identify BCL6 imbalances in nodular lymphocyte predominant Hodgkin lymphoma [ 15 ] or 14q32 chromosomal rearrangements in multiple myeloma [ 16 ].…”

Cytologic Differential Diagnosis of Malignant Mesothelioma and Reactive Mesothelial Cells With FISH Analysis of p16

“…It is uncertain whether cells without HD of p16 are mesothelioma cells or inflammatory cells. There are few reports on combined immunofluorescence and FISH . In this study, we reduced the digestion time of the cells during the FISH preparation process, and a fluorescently labeled anti‐EMA was simultaneously applied to the cell block section.…”