Primary mucosal melanomas of the urogenital tract: a clinical, pathological, and genetic nationwide survey of Danish patients 1990–2019

Abstract

Purpose: To describe the epidemiologic, clinical, histopathological, and genetic features of primary mucosalmelanoma of the urinary tract in a national Danish cohort with cases included from the year 1990 to2019.Material and methods: Patients of the Danish cohort were found using national databases. Only primarytumours were included in the cohort. Appropriate formalin-fixed paraffin-embedded blocks underwentnext-generation sequencing.Results: Eight cases of primary urinary bladder melanomas and 18 cases of primary urethral melanomaswere included. Bladder melanomas had an incidence of 0.05 cases/million/year. Mean age at diagnosis was67 years. The most frequent primary treatment was cystectomy. Adjuvant treatment was given in threecases and consisted of chemotherapy or radiotherapy. Mutations were found in the NF1, KRAS, ATRX, TP53,RAC1, and BRAF genes. Urethral melanomas were found to have an incidence of 0.12 cases/million/year.Average age at diagnosis was 77 years. The most frequent treatment was excision of the tumour. Adjuvanttreatment was given in nine cases and most frequently consisted of radiotherapy. Mutations were found inthe NF1, TERT PROMOTOR, NRAS, ATRX, TP53, ATM, TSC2, and CREBBP genes. The 5-year survival of patientswith bladder melanoma was 12.5% and 22.2% for patients with urethral melanoma.Conclusion: Our study highlights the rarity of urinary tract melanomas and their poor prognosis. The mostwidely used treatment for urogenital mucosal melanoma remains surgical while adjuvant therapy strategiesare evolving. Next-generation sequencing showed mutational patterns with no location-specific patterns.The most frequent mutations were in the NF1, ATRX, NRAS, and TP53 genes.