Sansonno D, De Vita S, Cornacchiulo V, Carbone A, Boiocchi M, Dammacco F
Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, Italy.
Blood. 1996 Dec 15;88(12):4638-45.
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.
在过去几年中，丙型肝炎病毒（HCV）在II型混合性冷球蛋白血症（MC）发病机制中的作用已得到强烈强调。尽管MC是一种良性淋巴增殖性疾病，但在其病程中，发生明显B细胞恶性肿瘤的风险会大大增加。10%至30%的非霍奇金淋巴瘤（NHL）患者存在HCV感染，这表明该病毒可能在与MC相关的B细胞恶性肿瘤的发生中起作用。我们在5年期间收集的两组慢性感染HCV的MC患者中，发现了2例增生性反应性淋巴结病（HRL）患者和12例NHL患者。通过免疫组织化学研究了淋巴结切片中与HCV相关的结构蛋白和非结构蛋白，并将它们的定位和分布与临床和组织学发现、病毒血症状态以及HCV基因型相关联。在HRL中，HCV蛋白存在于淋巴细胞的细胞质中，主要在滤泡间区域。然而，在套区和滤泡生发中心偶尔也能发现阳性细胞。此外，在包膜血管的循环单核细胞中发现了强反应性。在12例NHL病例中有3例（25%）发现了HCV免疫沉积物。阳性细胞通常局限于皮质；若不是，则随机散布于肿瘤组织中。阳性与低级别NHL类型相关；在2例复合病例中，在小细胞中发现了HCV免疫检测阳性，而大的间变性细胞则始终为阴性。所有组织中均未发现先前与淋巴增殖有关的其他病毒，即人类疱疹病毒6型和爱泼斯坦-巴尔病毒。这些数据强调淋巴器官可能是HCV感染的部位。在非恶性疾病即HRL中证明存在与HCV相关蛋白，表明HCV感染先于肿瘤转化，并且可能在MC的淋巴瘤发生中起主要作用。
