Case 4 -

Mantle Cell Lymphoma (MCL), with Peripheral Blood Involvement Judith Ferry Massachusetts General Hospital Boston, MA

Case History: 50-year-old female with diffuse lymphadenopathy and a peripheral blood lymphocytosis. WBC= 64,100 with predominance of atypical lymphoid cells, hematocrit= 29%, platelets = 28,000. An inguinal lymph node was biopsied. Flow cytometry showed a population of CD19+, CD20+, CD5+, CD10-, CD23- B cells expressing bright monotypic lambda light chain. Immunoperoxidase stains on paraffin sections showed a predominance of B cells (CD20+) expressing dim CD5 and cyclin D1, associated with patchy CD21+ dendritic staining. Case 4 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Diagnosis: Mantle cell lymphoma (MCL), with peripheral blood involvement ("mantle cell leukemia") Discussion MCL accounts for about 5-6% of adult non-Hodgkin's lymphoma in the U.S. and Europe. It occurs in older adults, affecting men much more often than women. It is usually widespread at diagnosis. The sites most commonly involved are lymph nodes, spleen, Waldeyer's ring, bone marrow, blood and the GI tract where it often takes the form of multiple lymphomatous polyposis. The median survival ranges from 3-5 years. Progression from MCL of the usual type to the blastoid variant occurs, although transformation to a large cell lymphoma composed of centroblast and/or immunoblast-like cells is not a feature of MCL. MCL usually has a diffuse or vaguely nodular pattern. The tumor may involve the mantle zones of some reactive follicles. MCL is typically composed exclusively of small to medium-sized lymphoid cells, usually slightly larger than normal lymphocytes, with dispersed chromatin, scant pale cytoplasm and inconspicuous nucleoli. The nuclei are usually irregular. In some cases the cells are nearly round and since they may also be small they may mimic normal lymphocytes. Large transformed cells with basophilic cytoplasm (centroblast or immunoblast-like cells) are rare or absent. A minority of cases have larger nuclei with more dispersed chromatin, and a high proliferation fraction reminiscent of lymphoblastic lymphoma, and the term "blastoid" variant has been applied to these cases. Many cases contain individually scattered epithelioid histiocytes, creating a "starry-sky" appearance at low magnification. Bone marrow involvement is most often in the form of infiltrative interstitial collections or nodular aggregates of small irregular lymphoid cells that are more often intertrabecular than paratrabecular. Less frequently, marrow involvement is diffuse. The neoplastic cells are usually recognizable on the aspirate smear when the core biopsy shows lymphoma. In aspirate smears and in the peripheral blood, MCL has the appearance of small to intermediate-sized lymphoid cells (7 - 10 microns) with round, slightly irregular or cleaved nuclei, condensed chromatin, sometimes 1 to 2 small, inconspicuous nucleoli and scant cytoplasm. MCL in the spleen may be confined to the white pulp. Neoplastic cells are: IgM+, IgD+, λ>κ, B-cell associated antigen CD20+, CD5+, CD10-, CD23-, nuclear cyclin D1+. A prominent, disorganized meshwork of follicular dendritic cells (FDC) may be demonstrated using antibodies to CD21 or CD23. Among reactive and neoplastic lymphoid proliferations, with rare exceptions (including some cases of hairy cell leukemia and plasma cell myeloma), nuclear cyclin D1 expression is unique to MCL. In most cases, a chromosomal translocation t(11;14) involving IgH and bcl-1 genes can be demonstrated. This translocation is associated with overexpression of cyclin D1 protein [1, 2, 3, 4]. The differential diagnosis includes other histologically low-grade B-cell lymphoma, including CLL, follicular lymphoma, and marginal zone lymphoma. References Bertoni F, Rinaldi A, Zucca E, Cavalli F. Update on the molecular biology of mantle cell lymphoma. Hematological Oncology 2006;24(1):22-7. Jaffe E, Harris N, Stein H, Vardiman J. Tumours of the Haematopoietic and Lymphoid Tissues. 1 ed. Lyon: IARC Press; 2001. Rosenberg C, Wong E, Petty E, Bale A, Tsujimoto Y, Harris N, et al. Overexpression of PRAD1, a candidate BCL1 breakpoint region oncogene, in centrocytic lymphomas. Proc Natl Acad Sci USA 1991;88:9638-9642. Zukerberg LR, Yang W-I, Arnold A, Harris NL. Cyclin D1 expression in non-Hodgkin's lymphomas. Detection by immunohistochemistry. Am J Clin Pathol 1995;103:756-760.