Hodgkin's disease expressing follicular dendritic cell marker CD21 withoutany other B-cell marker - A clinicopathologic study of nine cases

Reed-Sternberg (RS) and Hodgkin's (H) cells are considered to be the neopla stic cells in Hodgkin's disease (HD). Although most data suggest their lymp hoid origin, the nature of these cells still remains a subject of controver sy. Recently, a number of RS cells have been found to express an antigen th at is also present on follicular dendritic cells (FDCs),(11) asserting FDCs as the possible progenitor cells of H-RS cells. This prompted us to invest igate whether these CD21-positive cases had distinct clinicopathologic char acteristics. In a series of 94 examined cases of HD, we identified 9 CD21-p ositive ones (4 of 37 cases of nodular sclerosis, 1 of 41 mixed cellularity , and 4 of 12 lymphocyte depletion HD) without any other B-cell marker on p araffin sections. The patients varied in age from 16 to 82 years (median, 5 0 years) and included six men and three women. They had superficial or mese nteric lymphadenopathy without hepatosplenomegaly. Peripheral blood leukocy tosis was seen in three patients. The clinical course was indolent, and all patients but one achieved an initial complete response with HD-based treat ment regimens, although three of them relapsed. Morphologically, two subgro ups could be delineated. Six of the cases were characterized, besides by th e classic RS cells, by a varying number of the cells with the distinctive w alnutlike or cerebrumlike nuclei and cytologically with cytoplasmic process es. Their fine structural examination also revealed villous processes, but no desmosomes. The other three cases had multinucleated RS cells often with triangular nuclei, but not cytoplasmic processes. The percentage of CD21-p ositive tumor cells ranged from less than 10% to 60% among the H-RS cells. These RS cells were positive for CD30 (9 of 9), CD15 (7 of 9), CD68 (1 of 8 ), fascin (8 of 8), S-100 protein (1 of 7), and epithelial membrane antigen (2 of 8) on paraffin sections. Notably, of eight cases examined on frozen sections, two showed immunostaining for DRC1, CD35, R4/23, and Ki-M4p. Only CD35 was also detected in the other two cases. Genotypic investigation sho wed germline configuration of the T-cell receptor beta and gamma chain gene s and the immunoglobulin heavy chain gene in all eight cases examined. In s itu hybridization showed Epstein-Barr virus sequences in four cases, three of which were examined by the terminal region analysis and showed the Epste in-Barr virus to be monoclonal. We concluded that in a small proportion (9. 6%) of HD, H-RS cells might be derived from FDCs and that they appear to re present a distinct pathologic variant based on morphologic and phenotypic t raits within the framework of HD.