Monoclonal Plasma Cell Proliferations in Castleman Disease: Clinicopathologic and Molecular Analysis
Nadine S Aguilera, Bong K Kim, Lynn Barron, Lynn V Abruzzo, Aaron Auerbach, Rachel L Sargent. Joint Pathology Center, Silver Spring, MD; Armed Forces Institute of Pathology, Washington, DC; University of Texas, M.D. Anderson Cancer Center, Houston, TX
Background: Castleman disease represents a heterogenous group of lymphoproliferative disorders. Although clonal plasma cells can be seen in the plasma cell variant of Castleman disease (PCCD), they have also been described in HHV-8 related multicentric Castleman disease (MCCD), POEMS syndrome and plasmacytoma of the lymph node. Distinction between these entities often presents a diagnostic challenge as definitive histopathologic criteria for their accurate differentiation are not well defined.
Design: 6/24 cases diagnosed as follicular hyperplasia with Castleman-like features from 1993 to 2005 showed monoclonal plasma cell proliferations and were used in this study. Cases which could be classified as other reactive processes or malignant lymphomas were excluded. Immunohistochemistry for CD20, CD79a, CD3, CD5, CD10, CD43, CD21, CD23, CD123, CD138, HHV8, EGFR, and k/l as well as IGH@ gene rearrangement and IGVH mutational analysis were performed. Available clinical and flow cytometric data were also reviewed.
Results: Patients were 31-69 years old (M:F- 4:2, median 55.5 years). Lymph node biopsies in all cases were HHV8 negative, showed classic atretic follicles with multiple germinal centers in at least one follicle and increased interfollicular vascularity. One case showed CD123+ plasmacytoid dendritic cells surrounding the follicles. 3/4 cases showed EGFR positive follicular dendritic cell meshworks. Lambda monoclonal hilar plasma cell proliferations were seen in all cases with discrete masses in 3/6 cases. Molecular analysis showed monoclonal IGH@ gene rearrangements in 1/3 cases and IGVH somatic mutation (VH3-74) in 1/5 cases. All cases showed indolent courses and an absence of polyneuropathy, organomegaly, endocrinopathy and/or skin changes. A documented monoclonal serum immunoglobulin was present in 2/6 cases.
Conclusions: Our study shows that cases of Castleman disease with plasma cell proliferations have a male predominance and typically present in the 5th decade of life with an indolent clinical course. All of our cases showed l restriction. Although HHV-8 related MCCD and POEMS could be excluded as a diagnosis for all cases based on the clinicohistopathologic findings, 50% of cases showed discrete monoclonal plasma cell masses illustrating the overlap between plasmacytoma and PCCD. In these cases the clinical data and IGVH mutation status and usage may be helpful for distinction.
Monday, March 19, 2012 1:00 PM
Poster Session II # 229, Monday Afternoon