Significance of cyclin D1 overexpression for the diagnosis of mantle cell lymphoma: a clinicopathologic comparison of cyclin D1-positive MCL and cyclin D1-negative MCL-like B-cell lymphoma

Mantle cell lymphoma (MCL) is a distinct clinicopathologic entity of non-Ho dgkin's lymphoma, characterized by a monotonous proliferation of small to m edium-sized lymphocytes with co-expression of CD5 and CD20, an aggressive a nd incurable clinical course, and frequent t(11; 14)(q13;q32) translocation , We examined 151 cases of lymphoma with MCL morphology from a viewpoint of cyclin D1 overexpression, which is now easily detectable by immunohistoche mistry. 128 cases (85%) showed positive nuclear staining for cyclin D1, whi le the remaining 23 (15%) were negative. Except for cyclin D1 immunohistoch emistry, current diagnostic methods, including morphological and phenotypic al examinations, could not make this distinction. Although both the cyclin D1-positive and -negative groups were characterized by male predominance, a dvanced stages of the disease, frequent extranodal involvement, and low CD2 3 reactivity, the cyclin D1-positive group showed a higher age distribution (P=.04), larger cell size (P =.02), higher mitotic index (P =.01), more fr equent gastrointestinal involvement (P =.05), higher international prognost ic index score (P =.05), and lower p27(KIP1) expression (P <.0001). Of part icular interest is that cyclin D1-positive MCL showed significantly worse s urvival than cyclin D1-negative lymphoma (5-year survival: 30% versus 86%, P =.0002), which was confirmed by multivariate analysis to be independent o f other risk factors. These data suggest that cyclin D1-positive and -negat ive groups may represent different entities and that the former closely fit s the characteristics of classical, typical MCL. We therefore propose that cyclin DI-positivity should be included as one of the standard criteria for MCL, and that innovative therapies for this incurable disease should be ex plored on the basis of the new criteria. (Blood. 2000;95:2253-2261 (C) 2000 by The American Society of Hematology.