Conflict of interest: Nothing to report
Bone Marrow Update
Bone marrow trephine biopsy findings in myeloma with small-lymphoid cells and CCND1 translocation†
Article first published online: 2 SEP 2011
Copyright © 2011 Wiley-Liss, Inc.
American Journal of Hematology
Volume 86, Issue 12, page 1038, December 2011
How to Cite
Abdalla, S., May, P. C., Garimberti, E. and Naresh, K. N. (2011), Bone marrow trephine biopsy findings in myeloma with small-lymphoid cells and CCND1 translocation. Am. J. Hematol., 86: 1038. doi: 10.1002/ajh.22128
- Issue published online: 16 NOV 2011
- Article first published online: 2 SEP 2011
- Accepted manuscript online: 14 JUL 2011 08:21PM EST
- Manuscript Accepted: 6 JUL 2011
- Manuscript Received: 1 JUL 2011
A woman in her fifties presented with three episodes of epistaxis, occasional headaches, and episodic tiredness. Examination was unremarkable apart from pallor. Her hemoglobin measured 8.4 g/dL and rest of the blood counts were normal. The erythrocyte sedimentation rate was >120 mm/hr. An IgG lambda paraprotein of 74 g/L was detected. The beta-2-microglobulin was 2.8 mg/L. On serum free light chain evaluation, the kappa light chain measured 1.3 mg/L, and the lambda light chain measured 403 mg/L with a kappa:lambda light chain ratio of 0.003. The plasma viscosity was elevated at 3.72 MPa. The bone marrow aspirate showed extensive infiltration with small lymphoid appearing plasma cells amounting to 66% of all nucleated cells in the marrow. These cells had round nuclei of uniform size and coarse chromatin. Cytoplasm was variable in amount, but mostly scanty. Overall, the cells had a lymphoid or lymphoplasmacytic appearance (a&b; Giemsa ×1000). The bone marrow trephine biopsy showed hypercellular marrow (90% cellularity) (c; H&E ×40). There were sheets of small to medium sized lymphoid-like atypical plasma cells amounting to >90% of the marrow cells (d; H&E ×600). There were few binucleate forms as well. The cells expressed CD138 (e; ×600), CD79a, CD20 (f; ×600), cyclin D1 (g; ×600), CD56 and epithelial membrane antigen. There was lambda light chain restriction. Interphase fluorescent in-situ hybridization analysis on the bone marrow aspirate smear using a probe specific for IGH/CCND1 revealed a fusion signal, consistent with an IGH/CCND1 [t(11;14)] rearrangement, in 57 of the 100 cells analyzed (h).
CCND1 gene overexpression is seen in nearly 50% of myeloma. About half of cases with cyclin D1 overexpression are associated with t(11;14). A small cell morphology of the tumor cells along with a strong cyclin D1 expression in a high percentage of tumor cells is highly indicative of t(11;14). About one-fifth to a third of myelomas express CD20, and the expression is associated with a mature small cell morphology of the neoplastic cells and with the presence of t(11;14). Such cases can be mistaken for small B-cell lymphomas, especially lymphoplasmacytic lymphoma, particularly if CD138 and cyclin D1 immunostains have not been performed. It is important to remember that lymphoplasmacytic lymphomas are negative for cyclin D1 expression.CCND1 is a crucial cellcycle gene located on chromosome band 11q13, which is overexpressed via chromosomal translocation t(11;14)(q13;q32) (leading to transcriptional deregulation), amplification, and other alterations. Studies of the prognostic significance of t(11;14) or of cyclin D1 overexpression in myeloma have yielded conflicting results [1, 2].