Background Merkel cell carcinoma is a rare malignancy of the skin. Integration of Merkel cell polyomavirus (MCPyV) DNA to the tumor genome is frequent in these cancers. The clinical consequences of MCPyV infection are unknown. Methods We analyzed formalin-fixed paraffin-embedded Merkel cell carcinoma tissue samples from 114 of 207 patients diagnosed with Merkel cell carcinoma in Finland from 1979 to 2004 for the presence of MCPyV DNA with the use of polymerase chain reaction (PCR), quantitative PCR, and DNA sequencing and examined associations between tumor MCPyV DNA status and histopathologic factors and survival. The median follow-up time after Merkel cell carcinoma diagnosis for subjects who were alive was 9.9 years (range = 4.9–21.9 years). All P values are two-sided. Results MCPyV DNA was present in 91 carcinomas (79.8%). Compared with MCPyV DNA–negative cancers, MCPyV DNA–positive cancers were more often located in a limb (40.7% vs 8.7%, P = .015) and less frequent in patients who had regional nodal metastases at diagnosis (6.6% vs 21.7%, P = .043). Patients with MCPyV DNA–positive tumors had better overall survival than those with MCPyV DNA–negative tumors (5-year survival: 45.0% vs 13.0%, respectively; P < .001, two-sided log-rank test). Conclusions MCPyV infection is associated with clinical outcomes in patients with Merkel cell carcinoma. These findings lend support to the hypothesis that viral infection is frequently associated with the pathogenesis of Merkel cell carcinoma.

Purpose: Merkel cell carcinoma (MCC) is rare skin cancer that is often associated with Merkel cell polyomavirus (MCPyV) infection. Polyomaviruses repress tumor suppressor proteins, thus influencing cell-cycle progression, but the effect of MCPyV on the key cell-cycle regulating proteins is poorly understood.

Purpose: Merkel cell carcinoma (MCC) is a rare skin cancer that often harbors Merkel cell polyomavirus (MCPyV) DNA. The clinical importance of intratumoral immune cells and their associations with MCPyV infection are poorly understood. Experimental Design: We identified T lymphocytes (CD3-positive cells), T-cell subsets (CD4, CD8, and FoxP3-positive cells), natural killer cells (small CD16-positive cells), and macrophages (CD68 and CD163-positive cells) in tumors of 116 individuals diagnosed with MCC in Finland from 1979 to 2004 using immunohistochemistry and detected MCPyV DNA with quantitative PCR. The associations between immune cell counts, MCPyV DNA, patient and tumor characteristics, and patient outcome were examined. Results: MCPyV DNA-positive cancers contained higher numbers of CD3+, CD8+, CD16+, FoxP3+, and CD68+ cells as compared with MCPyV DNA-negative carcinomas (all P values < 0.05). High intratumoral numbers of CD3+, CD8+, or FoxP3+ cells, and high CD8+/CD4+ or FoxP3+/CD4+ ratios, were significantly associated with favorable overall survival. Individuals with a high tumor CD3+ count had metastases less often and survived longer, irrespective of the tumor MCPyV status. Tumor CD3+ count and MCPyV DNA status had independent influence on survival in a Cox multivariable model that also included presence of locoregional metastases at diagnosis and gender as covariates. Conclusions: High intratumoral T-lymphocyte counts are associated with favorable survival in MCC. Although the numbers of T cells are generally higher in MCPyV-positive than in MCPyV-negative MCC, high intratumoral T-cell counts are also associated with favorable survival in MCPyV-negative MCC. Clin Cancer Res; 18(10); 2872–81. ©2012 AACR.

Immunosuppression and Merkel-cell polyomavirus (MCPyV) infection may have a role in the pathogenesis of Merkel-cell carcinoma (MCC), a rare neuroendocrine carcinoma of the skin. We studied incidence of chronic lymphocytic leukaemia (CLL) and MCC from the files of the Finnish Cancer Registry and the largest hospital of Finland, Helsinki University Central Hospital, from 1979 to 2006. Presence of MCPyV DNA in MCCs was investigated by quantitative PCR. We identified 4164 patients diagnosed with CLL and 172 diagnosed with MCC. Six patients diagnosed with both diseases were found; CLL was the first diagnosis in four cases and MCC in two. The standardised incidence ratio (SIR) for CLL after the diagnosis of MCC was highly elevated, 17.9 (95% confidence interval (CI), 2.2–64.6; P<0.001), and the SIR for MCC after the diagnosis of CLL was also elevated, 15.7 (3.2–46.0, P<0.01). Merkel-cell polyomavirus DNA was present in all five MCCs with tumour tissue available for analysis. We conclude that patients diagnosed with CLL have a substantially increased risk for MCC, and vice versa. Merkel-cell polyomavirus DNA is frequently present in MCCs that occur in CLL patients. Immunosuppression related with CLL and viral infection might explain the association between CLL and MCC.

The aim of this study was to investigate the causes of death in patients with burns using both medicolegal autopsy reports and clinical data collected