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Detection and distribution of hepatitis C virus-related proteins in lymph
nodes of patients with type II mixed cryoglobulinemia and neoplastic or
non-neoplastic lymphoproliferation
D Sansonno, S De Vita, V Cornacchiulo, A Carbone, M Boiocchi and F Dammacco
Department of Biomedical Sciences and Human Oncology, University of Bari
Medical School, Italy.
The role of hepatitis C virus (HCV) in the pathogenesis of type II mixed
cryoglobulinemia (MC) has been strongly emphasized in the last few years.
Although MC is a benign lymphoproliferative disorder, the risk of overt
B-cell malignancy greatly increases during its course. The occurrence of
HCV infection in 10% to 30% of patients with non- Hodgkin's lymphoma (NHL)
suggests that this virus may have a role in the development of
MC-associated B-cell malignancies. We identified 2 patients with
hyperplastic reactive lymphadenopathy (HRL) and 12 with NHL in two series
of MC patients chronically infected with HCV collected over a 5-year
period. Structural and nonstructural HCV- related proteins were
investigated in lymph node sections by immunohistochemistry and their
location and distribution were correlated with clinical and histologic
findings, viremic state, and HCV genotypes. In HRL, HCV proteins were found
in the cytoplasm of lymphoid cells, mainly in interfollicular areas.
However, occasional positive cells were found in the mantle zone and in the
germinal centers of follicles. In addition, strong reactivity was found in
the circulating mononuclear cells of capsular blood vessels. HCV
immunodeposits were found in 3 of 12 (25%) NHL cases. Positive cells were
frequently restricted to the cortex; if not, they were randomly diffused in
the neoplastic tissue. Positivity was related to the low- grade type of
NHL; in the 2 composite cases, HCV immunodetection was found in the small
cells, whereas large anaplastic cells were regularly negative. Other
viruses previously involved in lymphoproliferation, ie, human herpes
virus-6 and Epstein-Barr virus, were absent in all tissues. These data
emphasize that lymphoid organs may be a site of HCV infection. The
demonstration of HCV-related proteins in a nonmalignant condition, namely
HRL, indicates that HCV infection precedes the neoplastic transformation
and possibly plays a major role in lymphomagenesis in MC.
Volume 88,
Issue 12,
pp. 4638-4645,
12/15/1996
Copyright © 1996 by The American Society of Hematology
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