Histopathological diagnosis and variants of Merkel cell carcinoma

Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neuroendocrine tumour with increasing incidence, particularly in elderly and immunocompromised patients. Its pathogenesis involves two distinct pathways: one associated with Merkel cell polyomavirus (MCPyV) and another linked to ultraviolet (UV) radiation-induced mutations. Despite growing knowledge about its molecular basis, MCC remains a diagnostic challenge due to its clinical variability and morphological resemblance to other neoplasms. This review aims to provide a comprehensive overview of the histopathological features of MCC, highlighting its microscopic architecture, histological variants, immunohistochemical profile, and differential diagnoses. Special emphasis is placed on the histological differences between MCPyV-positive and MCPyV-negative tumours, which may have distinct prognostic implications. Key findings include the recognition of characteristic small round basophilic cells with sparse cytoplasm and granular chromatin, frequent mitotic figures, and a high proliferation index. Immunohistochemical staining is essential for accurate diagnosis, with cytokeratin 20 and MCPyV T antigen being the most specific markers. Several histological variants are described, including those with squamous, lymphomatous, melanocytic or sarcomatous differentiation, which may complicate diagnosis and impact clinical decisions. In conclusion, accurate histopathological identification of MCC, supported by immunohistochemistry (IHC), is crucial for proper patient management and prognosis. Understanding its morphological spectrum and molecular characteristics contributes to improved diagnostic precision and guides therapeutic strategies, especially with the advent of targeted immunotherapies.