Merkel cell carcinoma, chronic lymphocytic leukemia and other lymphoproliferative disorders: an old bond with possible new viral ties

Abstract

Merkel cell carcinoma (MCC) is a rare and aggressive skin tumor. The link between tumorigenesis and immunosuppression is well known and the increased prevalence of MCC in human immunodeficiency virus carriers and organ transplant recipients and in patients with hemato-oncological neoplasias is now well recognized over the past decade. In this respect, chronic lymphocytic leukemia (CLL) seems to be the most frequent neoplasia associated with the development of MCC. Very recently, a newly described virus, the Merkel cell polyomavirus, was found in ∼80% of MCC tumor samples and is in fact the first member of the polyomavirus family to be associated with human tumors. The virus appears to play a role in the pathogenesis of MCC and may constitute the missing link between immunosuppression and the development of MCC. This review summarizes the current knowledge relating to MCC and its pathogenesis, stressing the link with hematologic neoplasias in general and to CLL in particular. We describe the permissive immunologic environment, which enables the virus-containing tumor cells to survive and proliferate in disorders like CLL. More studies are still needed to confirm this appealing theory in a more convincing manner.

Merkel cell carcinoma of lymph node with unknown primary has a significantly lower association with Merkel cell polyomavirus than its cutaneous counterpart

“…Development of cutaneous Merkel cell carcinoma may be related to ultraviolet light irradiation and immunosupression. [45][46][47][48] In our study, 8 of 22 (36%) patients had a history of other aggressive or systemic tumors prior to the diagnosis of nodal Merkel cell carcinoma, and 3 of them had chronic lymphocytic leukemia/small lymphocytic lymphoma. Approximately 27% of patients with cutaneous Merkel cell carcinoma had other invasive non-Merkel cell carcinoma malignancies, with chronic lymphocytic leukemia/small lymphocytic lymphoma the most common one, accounting for 45% of all tumors.…”

Latitude gradients for lymphoid neoplasm subtypes in Australia support an association with ultraviolet radiation exposure

“…40 However, the latitude gradient observed for ENNKTL in this study does not reflect the geographical distribution of the East Asian population in Australia, arguing against substantial confounding by race. 41 Incidence also decreased with distance from the equator for CLL/SLL, for which infectious agents, including the Merkel cell polyomavirus, 42 have been implicated. Bacterial infection, evidenced by antibiotic use, might also be important in CLL/SLL pathogenesis.…”

Rationale For Immune-Based Therapies in Merkel Polyomavirus-Positive and -Negative Merkel Cell Carcinomas

“…While 90% of MCC patients do not have clinically apparent immune dysfunction, patients on immunosuppressive regimens following organ transplantation or with compromised cell-mediated immunity (such as those with chronic lymphocytic leukemia and HIV/AIDs) are 10-30-fold more likely to develop MCC and suffer a higher MCC-specific mortality rate than the general population [5,[31][32][33][34]. This suggests that impaired cellular immunity predisposes individuals to not only developing MCC, but also to poorly controlling their disease.…”