Nm. Jiwa et al., PRESENCE OF EPSTEIN-BARR-VIRUS HARBORING SMALL AND INTERMEDIATE-SIZEDCELLS IN HODGKINS-DISEASE - IS THERE A RELATIONSHIP WITH REED-STERNBERG CELLS, Journal of pathology, 170(2), 1993, pp. 129-136
Forty-four cases of Hodgkin's disease (HD), mostly of the nodular scle
rosing type, were investigated for the presence of Epstein-Barr virus
(EBV) by polymerase chain reaction (PCR) and DNA and RNA in situ hybri
dization (DISH, RISH), as well as by immunohistochemistry for the dete
ction of latent membrane protein-1 (LMP-1) of EBV. In situ hybridizati
on (ISH) was combined with immunohistochemistry to correlate the prese
nce and activity of the virus at the cellular level. In 18/34 (53 per
cent) cases, EBV-DNA sequences could be detected with the PCR method.
In 12/18 positive cases, DISH and RISH were also positive. In the rema
ining six EBV-PCR positive cases, two were also positive with RISH and
LMP-1, whereas no positive signal with DISH could be obtained. All DI
SH and/or RISH positive cases were also positive for LMP-1. With RISH,
not only the Reed-Sternberg cells and their mononuclear variants (RS
cells) stained positive, but also small and intermediate cells frequen
tly reacted with the EBV-specific probes (EBER-1 and -2). Double stain
ing with cellular markers (CD3, CD20, CD45, CD45RO, CD68, and the lect
in PNA) revealed that most of the smaller EBER-positive cells frequent
ly did not express T, B, or histiocytic markers, but that they, as wel
l as the RS cells, showed cytoplasmic and membranous staining with PNA
. These smaller EBER-positive cells were not found in EBV-PCR negative
HD. EBER-positive RS cells were almost always LMP-1 positive, as well
as a substantial proportion of the intermediate-sized cells, whereas
the majority of the small EBER-positive cells remained LMP-1 negative.
In EBV-PCR positive non-malignant lymph nodes, only a few EBER-1 and
-2 positive cells could be observed. As in infectious mononucleosis, t
hese cells frequently expressed the B-cell marker CD20. Although we ca
nnot exclude the fact that the majority of the smaller EBV-positive ce
lls in HD belong to reactive EBV-infected lymphocytes, our data favour
the hypothesis that at least some of these smaller cells may belong t
o the reservoir of neoplastic cells in HD.