Merkel cell polyomavirus and Langerhans cell neoplasm

Abstract

BackgroundThe relationship between various external agents such as pollen, food, and infectious agents and human sensitivity exists and is variable depending upon individual’s health conditions. For example, we believe that the pathogenetic potential of the Merkel cell polyomavirus (MCPyV), the resident virus in skin, is variable and depends from the degree of individual’s reactivity. MCPyV as well as Epstein-Barr virus, which are normally connected with humans under the form of subclinical infection, are thought to be involved at various degrees in several neoplastic and inflammatory diseases. In this review, we cover two types of Langerhans cell neoplasms, the Langerhans cell sarcoma (LCS) and Langerhans cell histiocytosis (LCH), represented as either neoplastic or inflammatory diseases caused by MCPyV.MethodsWe meta-analyzed both our previous analyses, composed of quantitative PCR for MCPyV-DNA, proteomics, immunohistochemistry which construct IL-17 endocrine model and interleukin-1 (IL-1) activation loop model, and other groups’ data.ResultsWe have shown that there were subgroups associated with the MCPyV as a causal agent in these two different neoplasms. Comparatively, LCS, distinct from the LCH, is a neoplastic lesion (or sarcoma) without presence of inflammatory granuloma frequently observed in the elderly. LCH is a proliferative disease of Langerhans-like abnormal cells which carry mutations of genes involved in the RAS/MAPK signaling pathway. We found that MCPyV may be involved in the development of LCH.ConclusionWe hypothesized that a subgroup of LCS developed according the same mechanism involved in Merkel cell carcinoma pathogenesis. We proposed LCH developed from an inflammatory process that was sustained due to gene mutations. We hypothesized that MCPyV infection triggered an IL-1 activation loop that lies beneath the pathogenesis of LCH and propose a new triple-factor model.

Epstein–Barr Virus-Positive Langerhans Cell Sarcoma: Is There a Link? A Case Report

“…The inflammatory nature of LCH lesions raises the possibility that infection and immune dysregulation may be the mechanisms of pathogenesis ( 52 ). Several viruses have been studied as potential etiological factors of LCH, including EBV ( 53 ), human herpesvirus 6 (HHV-6) ( 54 ), cytomegalovirus (CMV) ( 55 ), herpes simplex virus (HSV) ( 56 ), and Merkel-cell polyoma virus (MCV or MCPyV) ( 57 ). Murakami reported that MCV-related molecules are present in more than half of LCH cases, and in some dermatopathy lymphadenopathy cases ( 58 ), and that three LCS cases were positive for viral DNA sequences ( 59 ).…”

A mutation in POLR3E impairs antiviral immune response and RNA polymerase III

“…In the former model, LCH is classified as an inflammatory myeloid neoplasm predominantly caused by mutations in the MEK/ERK pathway, frequently affecting BRAF and MAP2K1 (50,(53)(54)(55)(56). A role of viral infections in LCH pathogenesis has been previously considered, but without having definitive conclusions (57,58). LCH patients have not been reported to display innate immunodeficiency or defined susceptibility to infectious agents (59).…”

The Role of Histone Post-Translational Modifications in Merkel Cell Carcinoma

“…Despite MCCN tumor having a high mutational burden, MCCP harbours a 100-fold lower mutational load (17). According to the Surveillance, Epidemiology, and End Results (SEER) Program, the MCC 5-year survival rate is 76, 53 and 19% for localized, regional and distant disease, respectively, with an overall combined rate of 63% (18)(19)(20)(21). MCC global incidence ranges 0.1-1.6 cases/100,000 individuals (22).…”