Morphologic diagnosis of leukaemic B-lymphoproliferative disorders and the role of cyclin D1 expression

Purpose: This study analysed the morphologic differences between leukaemic mantle cell lymphoma, follicular lymphoma, nodal marginal zone lymphoma, and diffuse large B-cell lymphoma in peripheral blood. Additionally, we investigated the role of cyclin D1 expression in B-lymphoproliferative disorders. Methods: The morphologic analysis of the leukaemic cells was performed on cytocentrifuge preparations after separation of mononuclear cells from peripheral blood using a Ficoll-Hypaque density gradient. Cyclin D1 protein expression was studied with the catalyzed signal amplification system. The expression of other markers (CD5, CD23, light chain immunoglobulins) was analysed by the APAAP method. Results: We describe in detail the morphology of the lymphoma cells in eight patients with mantle cell lymphoma, six patients with follicular lymphoma, 11 patients with nodal marginal zone lymphoma, and seven patients with diffuse large B-cell lymphoma. The morphological distinction between these lymphoma cells is a challenge for the haematologist. The investigation of cytocentrifuge preparations of mononuclear cells allows the detection of lymphoma cells also in cases with nondiagnostic white cell differential. Additionally, the immunotype (light chain restriction, CD5, CD23, and cyclin D1) of 108 patients with leukaemic B-lymphoproliferative disorders was studied. Diffuse nuclear expression of cyclin D1 protein (>20%) was specific for mantle cell lymphoma. However, only 6/8 patients showed cyclin-D1 positivity. Conclusions: The morphologic analysis of lymphoma cells in cytocentrifuge preparations of mononuclear leukocytes in combination with immunocytochemical investigation allows the detection of mantle cells, centrocytes of follicular lymphoma, marginal zone cells, and cells of the diffuse large B-cell lymphoma in peripheral blood. The positivity of cyclin D1 protein improves the differentiation of mantle cells from other lymphoma cells