We describe the diagnostic and stepwise multimodal therapy of an amelanotic melanoma of the anal margin.

A 71 year-old otherwise healthy female patient presented with a mildly itching mass at the anal margin, with was occasionally bleeding. It was detected about 3 months before, not responding to an over the counter “hemorrhoid ointment”. The patient described a mild fecal urge incontinence.

The physical exam showed a rosy exophytic nodular tumor of about 1x1 cm at the anal margin with an irregular surface, and a diagnostic R0-resection was performed timely. Histology showed an ulcerated amelanotic melanoma, pT4 Clark IV Breslow 5.2, mitotic index > 10/mm2. The classical melanoma markers were positive; KIT, NRAS and BRAF as well as GIST-markers (CD34 and c-kit) were negative. No synchronous distant metastases were detected by PET-CT and cerebral MRI. Because of the high-risk histological profile, the initial scar was re-resected with a security margin of 2 cm (histology: tumor-free), and a sentinel lymph node excision (left inguinal and sciatic nerve region) was negative. The patient was included into a Pembrozilumab (anti-PD1) vs Placebo study, initially receiving placebo treatment. Two years later, a generalized perianal melanosis appeared, and a gluteal metastasis was diagnosed. The perianal skin was excised circumferentially, and the gluteal metastasis was resected. The patient then received anti-PD1 therapy. One year later, a PET-CT control revealed an iliac metastasis, and local radiotherapy was initiated.

Anal margin amelanotic melanoma is rare and can easily be confounded with benign lesions. This case underlines the need for diagnostic resection and histologic examination of all excised lesions. The treatment needs to be multidisciplinary, involving surgeons, oncologists, dermatologists, radio-oncologists and the pathologist. Surgical options include large excision, metastasectomy and abdomino-perineal amputation.