Recent nucleic acid hybridization studies have implied that Reed-Sternberg/Hodgkin (RS/H) cells are infected with Epstein-Barr virus (EBV) before malignant transformation, and hence, that Hodgkin's disease could develop as a consequence of malignant transformation of an EBV-infected cell. This study is a detailed immunohistochemical and in situ hybridization characterization of the various lymphoid cells in nine cases of infectious mononucleosis (IM), the acute manifestation of EBV infection. The RS/H-like cells of IM were similar in most respects to their morphologically identical counterparts in Hodgkin's disease; they expressed the EBV-encoded protein LMP1, EBV EBER1 transcripts, and CD30 and rarely, if ever, expressed CD45/LCA or T cell markers. Dissimilarities were limited to CD15 negativity and the absence of a collarette of T cells around the RS/H-like cells of IM compared with their Hodgkin's counterparts. Expression of the immortalizing bcl-2 oncoprotein was variable in the RS/H-like cells of IM, as has been demonstrated in the RS/H cells of Hodgkin's disease by other investigators. An apoptosis assay suggested that many apoptotic cells in IM were EBV-infected T cells, in keeping with the previous in vitro observation that IM-derived T cells succumb to apoptosis. Additionally, the apoptosis assay suggested that RS/H-like cells of IM can succumb to programmed cell death, reminiscent of the mummified RS/H cells seen in Hodgkin's disease. The accumulation of evidence suggests that RS/H-like cells of IM are more similar to true RS/H cells than previously recognized.
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