Bcl‐2 oncoprotein is widespread in lymphoid tissue and lymphomas but its differential expression in benign versus malignant follicles and monocytoid B‐cell proliferations is of diagnostic value

Abstract

The distribution of Bcl‐2 oncoprotein was studied immunohistochemically in formaldehyde‐fixed and paraffin‐embedded reactive and neoplastic lymphoid tissue. The potential of Bcl‐2 for the differential diagnosis of follicular lesions was emphasized, and the results on follicular lesions were correlated with those of polymerase chain reaction (PCR) assay of the immunoglobulin heavy chain gene rearrangement. In hyperplastic lymphoid tissue, Bcl‐2 reactivity was widespread, including germinal center surroundings, scattered cells within the germinal centers, and the T‐cell areas in general. Distinctively negative lymphoid populations included the majority of germinal center cells, and the negative staining pattern was maintained in cases of florid hyperplasia. In contrast, follicular lymphoma cells were consistently Bcl‐2 positive. The immunohistochemical Bcl‐2 reactivity of lymphoma follicles correlated with the clonal PCR amplification pattern of the immunoglobulin heavy chain gene; all Bcl‐2‐negative hyperplasias revealed a non‐clonal pattern. Clusters of monocytoid B cells were Bcl‐2 negative, whereas monocytoid B‐cell lymphomas and closely related MALT lymphomas were positive. All other small cell non‐Hodgkin's lymphomas of B‐cell types showed nearly uniform Bcl‐2 reactivity, whereas large cell B‐cell lymphomas were variably positive (74%). In Hodgkin's cells, Bcl‐2 reactivity was seen in the neoplastic populations of most cases of nodular sclerosis and mixed cellularity types, whereas the L&H and Reed‐Sternberg cells in lymphocyte predominance Hodgkin's disease were negative in most cases. Bcl‐2 immunohistochemistry thus appears very valuable in the differential diagnosis of follicular hyperplasia and neoplasia, and it may help to distinguish between reactive and neoplastic monocytoid B cells. However, Bcl‐2 immunohistochemistry is not useful in the subtyping of B‐cell lymphomas.

Clinical implications of nodal marginal zone B‐cell lymphoma among Japanese: study of 65 cases

“…The neoplastic nature of the cases was demonstrated by Bcl-2 or CD43 positivity (n = 61), or by light chain restriction of marginal zone B lymphocytes (n = 4) by immunostaining, (19)(20)(21) light chain restriction by flow cytometric studies or immunoglobulin heavy chain rearrangement by polymerase chain reaction analysis. (18) Clinical presentation.…”

“…If necessary, genomic DNA was extracted from formalin-fixed tissues after dewaxing of paraffin sections, and analyzed for immunoglobulin heavy chain rearrangement by polymerase chain reaction as described previously. (18) When the lymph node lesions were histologically suspected of being NMZL, cases in which atypical lymphoid cells lacked bcl-2 or CD43 expression (19)(20)(21) or those in which there was an absence of monoclonal nature by immunostaining, flow cytometry or Ig heavy chain rearrangement by polymerase chain reaction, were excluded from this study. In situ hybridization with EpsteinBarr virus (EBV)-encoded small RNA oligonucleotides was carried out to test for the presence of EBV small RNA in formalin-fixed paraffin-embedded sections also using a Ventana automated (BenchMark) stainer.…”

Nodular lymphocyte-predominant Hodgkin lymphoma with nodules resembling T-cell/histiocyte-rich B-cell lymphoma: differential diagnosis between nodular lymphocyte-predominant Hodgkin lymphoma and T-cell/histiocyte-rich B-cell lymphoma

“…20,25 Both CD79a and bcl-2 were more frequently expressed in T/HRBCL than in NLPHL. 26,27 In contrast, PU.1, a transcription factor necessary in early B-cell differentiation, was expressed in NLPHL but reduced in, or absent from, T/HRBCL. 21,28 Interestingly, the subtle disparity between the phenotypes of tumor cells seems to reflect their relationship to FDC meshworks.…”

Biology, Clinical Course and Management of Nodular Lymphocyte-Predominant Hodgkin Lymphoma

“…6 Regarding the immunophenotype, both CD79a and bcl-2 are more frequently expressed in T/HRBCL than in NLPHL. 20,21 In contrast, PU.1, a transcription factor necessary in early B-cell differentiation, is expressed in NLPHL but reduced in, or absent from, T/HRBCL. 22,23 Interestingly, the subtle disparity between the phenotypes of tumor cells seems to reflect their relationship to follicular dendritic cells (FDC) meshworks.…”