How do you recommend differentiating between localized cutaneous melanoma of the perianal skin versus mucosal melanoma of anal canal?
Although perianal melanomas arise within squamous epithelium, I think it is better to characterize these as mucosal melanomas. I think of it as being similar to melanomas that arise within the cutaneous surface (i.e. squamous epithelium) of the vulva but are still considered to be mucosal melanomas. In many case series when looking at anorectal melanomas, the perianal melanomas are often included in those cohorts. Due to the rare incidence though, I don't think there is a way to definitively characterize by histologic or genetic testing. You could consider performing a large multi-gene NGS panel that can find an SF3B1 mutation. As SF3B1 has a hotspot mutation at codon 625 that has been associated with mucosal melanomas of all sites. For clinical decision-making, I would treat a patient with a perianal melanoma as a mucosal melanoma.
References:
1. Socik et al., PMID 27304981.
2. Dodds et al., PMID 30497801.
3. Nassar and Tan, PMID 31655118.