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

The distribution of Bcl-2 oncoprotein was studied immunohistochemicall y 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 l esions were correlated with those of polymerase chain reaction (PCR) a ssay of the immunoglobulin heavy chain gene rearrangement. In hyperpla stic lymphoid tissue, Bcl-2 reactivity was widespread, including germi nal center surroundings, scattered cells within the germinal centers, and the T-cell areas in general. Distinctively negative lymphoid popul ations included the majority of germinal center cells, and the negativ e staining pattern was maintained in cases of florid hyperplasia. In c ontrast, follicular lymphoma cells were consistently Bcl-2 positive. T he immunohistochemical Bcl-2 reactivity of lymphoma follicles correlat ed with the clonal PCR amplification pattern of the immunoglobulin hea vy chain gene; all Bcl-2-negative hyperplasias revealed a non-clonal p attern. Clusters of monocytoid B cells were Bcl-2 negative, whereas mo nocytoid B-cell lymphomas and closely related MALT lymphomas were posi tive. All other small cell non-Hodgkin's lymphomas of B-cell types sho wed nearly uniform Bcl-2 reactivity, whereas large cell B-cell lymphom as were variably positive (74%). In Hodgkin's cells, Bcl-2 reactivity was seen in the neoplastic populations of most cases of nodular sclero sis and mixed cellularity types, whereas the L&H and Reed-Sternberg ce lls in lymphocyte predominance Hodgkin's disease were negative in most cases. Bcl-2 immunohistochemistry thus appears very valuable in the d ifferential diagnosis of follicular hyperplasia and neoplasia, and it may help to distinguish between reactive and neoplastic monocytoid B c ells. However, Bcl-2 immunohistochemistry is not useful in the subtypi ng of B-cell lymphomas.