CD5+ B-cell Lymphoproliferative Disorders: Beyond Chronic Lymphocytic Leukemia (CLL) and Mantle Cell Lymphoma (MCL)
D Jevremovic, RS Dronca, WG Morice, ED Remstein, PJ Kurtin, CS Zent, CA Hanson. Mayo Clinic, Rochester, MN
Background: Flow cytometric (FC) analysis of peripheral blood (PB) and bone marrow (BM) is a common method for evaluating B-cell lymphoproliferative disorders (B-LPDs). CD5 positivity is usually considered characteristic of either CLL or MCL, depending on co-expression of CD23, intensity of surface immunoglobulin (sIg) and CD20, and the protein or genetic status of cyclin D1. However, other neoplastic B-LPDs may express CD5, albeit infrequently. In this study we have reviewed the tissue pathology of CD5+ B-LPDs that do not fulfill diagnostic criteria for CLL or MCL on FC studies of PB or BM.
Design: We identified, using PB or BM FC analysis, 75 patients with a CD5+ B-LPD that were seen at the Mayo Clinic between 1996 and 2008 and met the following inclusion criteria: (1) lack of typical CLL FC profile (dim sIg, dim CD20, uniform CD5, coexpression of CD23); (2) cyclin D1/IgH negative (by FISH or immunohistochemistry); and (3) available concurrent non-BM tissue biopsy for review.
Results: The median age at diagnosis was 68 yrs (range= 42-91); M:F=45:30. 47 patients had a lymph node biopsy following the PB or BM FC study; 22 had splenectomy; the remaining tissue biopsies were from lacrimal gland, epiglottis, lung, pleura, small bowel, omentum, liver, bone, and skin. Tissue review showed that 33 of 75 patients (44%) had involvement by CLL/small lymphocytic lymphoma, despite lack of prototypic flow cytometric findings in PB or BM, based on typical morphology and immunophenotype; no MCL were identified. Marginal zone lymphoma (MZL) was diagnosed in 24 patients (32%); of these 8 had typical histologic features of splenic marginal zone lymphoma, 3 of mucosa-associated lymphoid tissue lymphoma, and the remaining 13 were unspecified. Lymphoplasmacytic lymphoma (LPL) was detected in 7 patients (9%) and large cell lymphoma in 6 (8%). 1 patient had a high grade B-cell lymphoma, unspecified, with CDK6 translocation. The remaining 4 patients (5%) were diagnosed with a low grade B-cell lymphoma, NOS.
Conclusions: Although CD5 positivity is most commonly associated with CLL and MCL, a significant minority of cases do not fall into these 2 categories. Phenotypically unusual CLL, MZL and LPL were the most common diagnoses in this group of patients. Applying strict FC criteria, using genetic studies, and deferring to a lymph node/tissue diagnosis in non-classical cases is critical for accurate diagnosis and classification of CD5+B-LPDs.
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 126, Tuesday Morning