Lack of cytogenetic abnormalities in Castleman's disease

BACKGROUND: Castleman's disease (CD) is a distinctive type of atypical lymph node hyperplasia that is often clonal. In a previously reported series of CD, clonal populations of plasma cells were detected by immunohistology in 4 of 39 cases (10%, lambda restricted), and immunoglobulin gene rearrangements were detected by paraffin polymerase chain reaction (PCR) analysis in 10 of 37 cases (27%). Cytogenetic analysis has been used to detect clonal proliferations of plasma cells in myeloma and clonal proliferations of lymphocytes in lymphomas and has identified critical gene loci that are important in the histopathogenesis of these disorders. Cytogenetic studies have not been done on a large series of patients with CD. Thus, we reviewed the archives of our institution for cases of CD and lymphoma that had had cytogenetic analysis. METHODS: The cytogenetic and lymphoma archives of our institution (a tertiary care center) from 1985 to 1998 were reviewed for the diagnoses of CD and lymphoma. There were 21,006 lymphomas, 701 of which had cytogenetic analysis (400 abnormal). There were 162 cases of CD, 7 of which had cytogenetic analysis. The frequency of cytogenetic abnormalities in CD was compared with that in lymphoma. The sensitivity of cytogenetics for defining clonality in CD was compared with immunohistology and paraffin PCR-amplified immunoglobulin heavy-chain gene rearrangement. RESULTS: From 1985 to 1998, 162 cases of CD and 21,006 cases of lymphoma were diagnosed. Cytogenetic analysis yielded adequate numbers of metaphases for analysis of 4 cases of CD and 701 lymphomas. Cytogenetic abnormalities were not identified in CD but were identified in 400 lymphomas (57%). Although 1 of 4 cases of CD was clonal by immunohistology (lambda restricted), no immunoglobulin gene rearrangements were detected by paraffin PCR analysis. CONCLUSIONS: The frequency of cytogenetic abnormalities in lymphomas and the lack of cytogenetic abnormalities in CD suggest that cytogenetic abnormalities, as detected by conventional cytogenetic analysis, are important in the pathogenesis of lymphoma but not CD. The lack of cytogenetic abnormalities in CD supports the hypothesis that CD is an interleukin-6-driven lymphoproliferative disorder.