Bcl-6 protein expression by follicle center lymphomas. A marker for differentiating follicle center lymphomas from other low-grade lymphoproliferative disorders.

Low-grade lymphoproliferative disorders are a heterogeneous group of lymphoid neoplasms with wide variation in histologic features, immunologic phenotype, and molecular abnormalities. Subclassification of these disorders with small lymphocytic proliferation may be difficult on the basis of morphologic findings alone. The bcl-6 gene, originally cloned from a tumor with 3q27 translocation, is commonly expressed in large cell lymphomas. In humans, bcl-6 encodes for a Krüppel-type zinc finger protein and is believed to be important in germinal center formation. Bcl-6 protein is expressed mainly by follicle center cells and a few interfollicular T lymphocytes. We analyzed Bcl-6 expression with immunologic methods in common low-grade lymphoproliferative disorders as an aid to differentiation of tumors with follicle center origin. We analyzed Bcl-6 staining of formalin-fixed paraffin-embedded tissue from 72 indolent lymphomas including 31 grade I and II follicle center lymphomas (FCL). 13 small lymphocytic lymphomas (SLL), 12 mantle cell lymphomas (MCL), and 16 marginal zone lymphomas (MZL) including lymphomas of mucosa-associated lymphoid tissue and spleen. All of 31 FCL were positive for Bcl-6 expression. One of 13 SLL and 1 of 12 MCL were positive, whereas none of 16 MZL were positive. Bcl-6 was also detected in 5 of 5 FCL and 1 of 3 MZL but in no SLL or MCL by Western blot analysis in 14 cases with lymphoid disorders. Our study demonstrates that Bcl-6 expression is common in low-grade FCL but is rare in other indolent B-cell lymphoid disorders, and may be a useful adjunct in classification of indolent lymphomas.