What is the predominant etiological factor for Merkel cell carcinoma in Turkey: viral infection or sun exposure?

Abstract

Background: Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin carcinoma. The pathogenesis involves Merkel cell polyomavirus (MCPyV) and ultraviolet radiation exposure. Studies on MCC in Turkey are scarce, with essential data on local etiopathogenic and prognostic factors still lacking. We aimed to analyze the clinical and histopathologic features, biomarkers, and to evaluate these findings alongside Turkish literature to infer the etiopathogenesis, prognosis, and possible treatment options for the disease.

Methods: We analyzed the clinicopathologic features of 7 MCC patients diagnosed at the Pathology Department of Pamukkale University between 2003 and 2024 in this retrospective study. Clinical data was retrieved from the hospital's electronic records. Formalin-fixed, paraffin-embedded tumor specimens stained with hematoxylin-eosin were examined microscopically. MCPyV, Retinoblastoma 1 (RB1), p53, PRAME, PD-L1, and MMR proteins were evaluated immunohistochemically. Research on MCC from Turkey was sourced from Turkish databases (ULAKBIM, Turkiye Atif Dizini, DergiPark, Turk Medline) and international databases (Pubmed, Google Scholar, Scopus, Embase). The literature review identified original research, case reports, theses, and conference presentations.

Results: The patients in our series, all aged over 50 (mean age 76.1 ± 14.8), with a slight predominance of one gender (F: M = 1.33:1). During a mean follow-up of 16.1 months, 42.9% (3/7) had lymph node metastases, and 57.1% (4/7) showed distant metastases. PRAME was positive in 42.9% of the cases (3/7). The total number of MCC cases reported from Turkey was estimated at 227 ± 46, with MCPyV status available in a subset, showing a positivity rate of 70.3%. PD-L1 expression was observed in the tumor microenvironment in 55% of virus-positive MCC cases from Turkey.

Conclusions: The 9% incidence of gluteal localization in Turkish MCC cases, considering its geographical significance, is noteworthy. Notably, all MCC cases from Turkey in which microsatellite instability status has been assessed were found to be microsatellite stable. PRAME should be investigated in larger series for its potential role in the shared oncogenic pathways of MCC.