Hepatitis C virus-related lymphoproliferative disorders encompass a broader clinical and morphological spectrum than previously recognized: a clinicopathological study

Abstract

We describe a retrospective series of B-cell lymphoproliferative disorders associated with hepatitis C virus infection. In addition to splenic marginal zone lymphoma, follicular lymphoma and diffuse large B-cell lymphoma, all of which showed some specific features, we found two poorly described groups of cases. The first featured disseminated marginal zone lymphoma without splenic marginal zone lymphoma features, defying the current marginal zone lymphoma classification; the other consisted of monoclonal B lymphocytes in the peripheral blood, bone marrow or other tissues, with no clinical or histological evidence of lymphoma, and exhibiting a pattern that requires proper identification in order to avoid the misdiagnosis of the lymphoma. Diagnosis of hepatitis C virus infection-associated lymphoproliferative disorders requires the integration of clinical, pathological and molecular findings to establish an adequate diagnosis and decide the appropriate therapy to be applied.

The NOTCH pathway is recurrently mutated in diffuse large B-cell lymphoma associated with hepatitis C virus infection

“…The majority of clinical and biological investigations have focused on HCV-positive MZL, 19,22 but less attention has been paid to HCV-positive DLBCL. 23 In the available series of HCV-positive DLBCL, a predilection for extranodal presentation, including spleen tissue, has been observed.…”

Polyclonal and monoclonal B lymphocytes response in HCV‐infected patients treated with direct‐acting antiviral agents

“…9 Moreover, the high prevalence of monoclonal lymphocytosis in HCV-infected patients supports the notion that neoplastic transformation could be caused by chronic antigenic stimulation and clonal selection. 10,11 Yet, the response of B-NHLs to antiviral treatment provides the strongest evidence for a potential causative role of HCV in lymphomagenesis. This was initially observed in nine patients with splenic lymphoma who underwent interferon (IFN)α-based antiviral treatment.…”

“…Moreover, the high prevalence of monoclonal lymphocytosis in HCV‐infected patients supports the notion that neoplastic transformation could be caused by chronic antigenic stimulation and clonal selection …”

Expert Opinion on Managing Chronic HCV in Patients with Non-Hodgkin Lymphoma and other Extrahepatic Malignancies

“…HCV-infected patients with DLBCL have unique characteristics that make their lymphoma more difficult to treat than HCV-negative patients [31,32]. Also, in specific situations such as splenic marginal zone lymphoma (SMZL), a reliable diagnosis can be established based on bone marrow histology and phenotype, as determined by immunohistochemistry and flow cytometry, without need of splenectomy [33].…”