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World J Gastroenterol. Nov 28, 2013; 19(44): 7874-7879
Published online Nov 28, 2013. doi: 10.3748/wjg.v19.i44.7874
Relationships between lymphomas linked to hepatitis C virus infection and their microenvironment
Antonino Carbone, Annunziata Gloghini
Antonino Carbone, Department of Pathology, Centro di Riferimento Oncologico Aviano, Istituto Nazionale Tumori, IRCCS, Aviano and Pordenone Hospital, 33081 Aviano, Italy
Antonino Carbone, Member of WHO IARC Monograph Working Group on Biological Agents, 2009 Lyon, France
Annunziata Gloghini, Department of Diagnostic Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milano, Italy
Author contributions: Carbone A designed the review; Carbone A and Gloghini A wrote the paper.
Supported by An Institutional grant from Centro di Riferimento Oncologico Aviano for an intramural project “Agenti Infettivi e Tumori” to Carbone A; and an Institutional grant from the Fondazione IRCSS Istituto Nazionale Tumori Milano “Validation of a new algorithm for HPV status assessment in head and neck carcinoma” to Gloghini A
Correspondence to: Antonino Carbone, MD, Chairman of the Department of Pathology, Centro di Riferimento Oncologico Aviano, Istituto Nazionale Tumori, IRCCS, Via F. Gallini 2, 33081 Aviano, Italy. acarbone@cro.it
Telephone: +39-0434-659085 Fax: +39-0434-659370
Received: August 20, 2013
Revised: October 31, 2013
Accepted: November 12, 2013
Published online: November 28, 2013
Processing time: 113 Days and 15.1 Hours
Abstract

The relationships between lymphomas and their microenvironment appear to follow 3 major patterns: (1) an independent pattern; (2) a dependent pattern on deregulated interactions; and (3) a dependent pattern on regulated coexistence. Typical examples of the third pattern are hepatitis C virus (HCV)-associated marginal zone lymphomas (MZLs) and mucosa-associated lymphoid tissue lymphomas. In these lymphomas, a regulated coexistence of the malignant cells and the microenvironmental factors usually occurs. At least initially, however, tumor development and cell growth largely depend on external signals from the microenvironment, such as viral antigens, cytokines, and cell-cell interactions. The association between HCV infection and B-cell lymphomas is not completely defined, although this association has been demonstrated by epidemiological studies. MZL and diffuse large B-cell lymphoma are the histotypes most frequently associated with HCV infection. Many mechanisms have been proposed for explaining HCV-induced lymphomagenesis; antigenic stimulation by HCV seems to be fundamental in establishing B-cell expansion as observed in mixed cryoglobulinemia and in B-cell lymphomas. Recently, antiviral treatment has been proved to be effective in the treatment of HCV-associated indolent lymphomas. Importantly, clinically responses were linked to the eradication of the HCV-RNA, providing a strong argument in favor of a causative link between HCV and lymphoproliferation.

Keywords: Hepatitis C virus-infection; B-cell lymphomas; Marginal zone lymphoma; Mucosa-associated lymphoid tissue lymphomas; Diffuse large B-cell lymphomas; Microenvironment

Core tip: The relationships between lymphomas and their microenvironment appear to follow 3 major patterns: (1) an independent pattern; (2) a dependent pattern on deregulated interactions; and (3) a dependent pattern on regulated coexistence. The association between hepatitis C virus infection and B-cell lymphomas is not completely defined, although this association has been demonstrated by epidemiological studies.