Update on Merkel Cell Carcinoma

Abstract

Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma. Incidence of MCC continues to rise, and risk factors include advanced age, pale skin, chronic sun exposure, and immune suppression. Diagnosing MCC utilizes a combination of morphology and immunohistochemistry. Merkel cell polyomavirus (MCPyV) is present in approximately 70-80% of MCCs and represents a key pathogenic driver in those MCCs. In contrast, MCPyV-negative MCCs arise through progressive accumulation of ultraviolet-light induced somatic mutations. Staging of MCC proceeds according to the American Joint Commission on Cancer (AJCC) 8th Edition, which utilizes features of the primary tumor together with regional lymph node(s) (clinically and/or pathologically detected) and/or distant metastases. Many potentially useful biomarkers have been studied to refine risk stratification in MCC. In recent years, the host immune infiltrate has been leveraged as immune checkpoint blockade has emerged as an efficacious mode of treatment for patients with advanced MCC.

Keywords: Merkel cell carcinoma; Merkel cell polyoma virus; Pathogenesis; Prognostic factors; Staging.

Fig. 1

Merkel cell carcinoma a Scanning magnification reveals a diffuse proliferation of small round blue cells effacing the dermis (H&E, ×20). b The tumor consists of sheets of cells and admixed lymphocytes (H&E, ×100). c The tumor cells are tightly packed with numerous mitotic figures (solid arrowheads) and apoptotic bodies (open arrowheads). The tumor cells exhibit scant pale eosinophilic cytoplasm and enlarged oval-irregular nuclei with coarse granular chromatin (H&E, ×400; inset: H&E, ×600)

Fig. 2

Immunohistochemical profile of Merkel cell carcinoma Merkel cell carcinoma may show variable perinuclear dot-like positivity for a Cam 5.2 (×400), b CK20 (×400), c Synaptophysin (also shows diffuse cytoplasmic; ×400), and d Chromogranin (×400). The tumor cells are negative for TTF-1 (e; ×400) and LCA (f; ×400)

Fig. 3

Models for Merkel cell carcinomagenesis. Left: Merkel cell carcinoma polyomavirus (MCPyV) infection and expression of long T-antigen and short T-antigen abrogate RB functions directly and interfere with TP53-dependent pathways. Immunohistochemical studies for MCPyV T-antigen highlight T-antigen in the tumor cells (×100). Right: In MCPyV-negative MCCs, the accumulation of UV-induced mutations (most commonly affecting TP53 and RB) contribute to tumor development. Immunohistochemical studies for MCPyV T-antigen are negative in the tumor cells (×100)