Follicular Dendritic Cell Tumor of the Liver: Evidence for an Epstein-Barr Virus-related Clonal Proliferation of Follicular Dendritic Cells

Abstract

Tumors of the follicular dendritic cell are uncommon, and most occur as primary lymph node tumors. We report a case of primary follicular dendritic cell tumor of the liver that was initially reported as an inflammatory pseudotumor. The neoplasm recurred as two separate tumor masses 30 months after complete resection of the hepatic inflammatory pseudotumor. It showed a wide spectrum of morphologic features ranging from areas with fascicles of very bland spindle cells amidst a background population of lymphocytes, reminiscent of inflammatory pseudotumor, to areas of dispersed sheets of highly pleomorphic tumor cells with a relative paucity of reactive inflammatory cells. The diagnosis was confirmed by positive immunohistochemical staining with CD21, CD35, R4/23, and Ki-M4 and by ultrastructural demonstration of convoluted interdigitating cell processes joined by desmosomes. The background lymphocytes were oligoclonal, CD8-positive T cells. In situ hybridization for Epstein-Barr virus (EBV)-encoded RNA was positive in the tumor cells in the original and recurrent tumors. More importantly, the cells showed identical episomal clonal EBV on Southern blot analysis, implying that the initial and recurrent tumors are due to clonal proliferation of EBV-positive neoplastic follicular dendritic cells. The tumor cells expressed latent membrane protein but not EBV-encoded nuclear antigen 2 (EBNA2) or ZEBRA. Such gene expression is very similar to that of Hodgkin's disease and nasopharyngeal carcinoma. The strong expression of latent membrane protein restricted to the tumor cells and the clonality of the EBV suggest that the virus may be involved in the pathogenesis of this tumor and not present merely as a bystander..