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All cases of lymphocytic lymphoma of intermediate differentiation (IDL) referred to the National Cancer Institute were reviewed in order to define the histopathologic spectrum of the disease and to investigate morphologic and immunophenotypic features with potential prognostic relevance. Thirty-three cases were classified as IDL according to histologic criteria. Immunophenotypic analysis was performed in 27 cases, and clinical records were available for 22 patients. The median age was 58 years, and the male-to-female ratio, 3.4:1. All patients presented with stage III or IV disease, and five had extranodal presentations. Median survival was 56.3 months, with only three patients having a prolonged relapse-free survival (>2 years). Morphologically, 14 cases were diffuse or only vaguely nodular; 18 cases showed a mantle zone pattern with naked germinal centers. There was a trend toward prolonged median survival for patients with the mantle zone (77.4 months, p = 0.098). The neoplastic population was composed of irregular or cleaved small lymphoid cells with a mitotic rate ranging from 5 to 62 per 20 high-power fields (hpf). A histologically distinctive variant with blastic cytologic features was identified (seven cases). The blastic variant was associated with a higher mitotic index (51.3 versus 19.0) and shortened survival (24.9 months). In contrast to the histologic progression often observed in follicular lymphomas, in no case was transformation to a large-cell or small noncleaved lymphoma observed. All cases had a mature B-cell pheno-type demonstrating monoclonal Ig and B-cell surface antigens. Seventy-eight percent were CD5 positive; theree of six CD5-negative cases presented in mucosal-associated extranodal sites. CD10 and CD25 were expressed in 52% and 44%, respectively, but did not show clinical correltions. The proliferative rate measured by Ki-67 positivity correlated with the mitotic index, but neither of these parameters had a statistically significant influence on survival.