April 2021 — Dermatopathology

The correct answer is: Merkel cell carcinoma.

This presentation with the associated IHC findings are most consistent with Merkel cell carcinoma (MCC). This neuroendocrine skin tumor is positive for synaptophysin and chromogranin. The characteristic salt and pepper chromatin is visible on the H&E stain, and one may be able to see nuclear molding and rosette-like structures. Mitoses are often abundant. MCCs typically express epithelial markers such as AE1/AE3 and CK20. CK7 may also be positive. CK20 typically shows a paranuclear “dot-like” staining pattern. MCPyV can be detected by immunohistochemistry in a subset of MCC cases. 

Development of MCC is associated with ultraviolet radiation and clonal integration of the MCPyV and is most commonly found on sun-exposed areas of skin. The tumor presents with a rapidly growing nodule, which can mimic basal cell carcinoma (BCC), squamous cell carcinoma (SCC), amelanotic melanoma, lymphoma, and others. Histologically, the differential diagnosis includes metastatic neuroendocrine tumor. While the etiology of MCC has been further elucidated, the cell of origin still remains somewhat of a mystery, despite being referred to as Merkel cell carcinoma. Because Merkel cells are terminally differentiated, it is thought that they may not be the true origin for the carcinoma. 

MCPyV is thought to be part of the commensal skin flora and commonly can be found in the general population. It is for this reason that incidence of MCC increases in immunocompromised populations and on areas of the skin where chronic sun exposure or damage is common. There may be a synergistic component to the UV damage and localized immunosuppression in combination with the presence of the MCPyV that allows for the development of MCC. 

The acronym AEIOU was developed to help aid in the recognition of the otherwise nonspecific features of MCC presentation: asymptomatic, expanding rapidly, immunosuppressed, older than age 50, and UV-exposed.

References

1. Becker JC, Stang A, DeCaprio JA, Cerroni L, Lebbé C, Veness M, Nghiem P. Merkel cell carcinoma. Nat Rev Dis Primers. 2017 Oct 26;3:17077. doi: 10.1038/nrdp.2017.77. PMID: 29072302; PMCID: PMC6054450.
2. Elder D, Massi D, Scolyer R, Willemze R et al. WHO Classification of Skin Tumours. Lyon: International Agency for Research on Cancer; 2018.