Merkel Cell Carcinoma

Abstract

Merkel cell carcinoma (MCC) encompasses neuroendocrine carcinomas primary to skin and occurs most commonly in association with clonally integrated Merkel cell polyomavirus with related retinoblastoma protein sequestration or in association with UV radiation–induced alterations involving the TP53 gene and mutations, heterozygous deletion, and hypermethylation of the Retinoblastoma gene. Molecular genetic signatures may provide therapeutic guidance. Morphologic features, although patterned, are associated with predictable diagnostic pitfalls, usually resolvable by immunohistochemistry. Therapeutic options for MCC, traditionally limited to surgical intervention and later chemotherapy and radiation, are growing, given promising early results of immunotherapeutic regimens.

Histologic Mimics of Basal Cell Carcinoma

“…107,113 Stromal fibrosis and inflammation may also be present in MCC. 105 However, despite that overlap in stromal features, the classic BCC myxoinflammatory stroma is not observed in MCC.…”

“…Although less than 1% of malignant skin tumors are MCCs, 104 it is a significant cause of death from skin cancer, with a mortality rate of 30% to 75%. 105 About one-third of patients will have metastatic disease at the time of diagnosis. 106 Because of the increased mortality and high metastatic potential of MCC, it must be distinguished from less-aggressive lesions, such as BCC.…”

“…[108][109][110][111] Both MCC and BCC may have focal or extensive squamous differentiation. 105 Peripheral palisading may be identified in a few MCC tumors but is typically focal. 107,[112][113][114][115] Clefts between aggregates of MCC and adjacent stroma are not infrequently identified in MCC (Figure 8, C).…”

“…Although tumor cells of BCC are characteristically elongated with hyperchromatic nuclei, visible cytoplasm, and scattered mitotic activity and necrosis, tumor cells of MCC have a homogenous salt-and-pepper chromatin pattern, nuclear molding, scant cytoplasm, and abundant mitotic activity and necrosis. 105 Merkel cell carcinoma cells share antigenic profiles of both epithelial and neuroendocrine cells. They express epithelial markers, such as low-molecular-weight keratins and EMA, as well as neuroendocrine markers, including chromogranin and synaptophysin.…”

“…there is membranous or cytoplasmic cytokeratin staining, with or without paranuclear dots. 105,117 Most MCCs express CK20, whereas that stain is negative in BCC. 114 Merkel cell polyomavirus large T-antigen protein, expressed in approximately 70% to 80% of MCCs, is a highly specific marker for distinguishing MCC from BCC.…”