Synapse - Urethral melanoma - Clinical, pathological and molecular characteristics

Urethral melanoma - Clinical, pathological and molecular characteristics Review

Authors:	Mano, R.; Hoeh, B.; DiNatale, R. G.; Sanchez, A.; Benfante, N. E.; Reznik, E.; Leitao, M. M.; Shoushtari, A. N.; Goh, A.; Donat, S. M.; Herr, H. W.; Bochner, B. H.; Dalbagni, G.; Donahue, T. F.
Review Title:	Urethral melanoma - Clinical, pathological and molecular characteristics
Abstract:	BACKGROUND: Mucosal melanoma involving the urethra is a rare disease with distinct clinical and molecular characteristics and poor outcomes. Our current knowledge is limited by the small number of reports regarding this disease. OBJECTIVE: To describe the clinical, pathological, and molecular characteristics of urethral melanoma. METHODS: We summarized the clinicopathologic data for 31 patients treated for urethral melanoma from 1986-2017 at our institution. Genomic data from our institutional sequencing platform MSK-IMPACT (n = 5) and gene-specific PCR data on BRAF, KIT, and/or NRAS (n = 8) were compared to genomic data of cutaneous melanomas (n = 143), vulvar/vaginal melanomas (n = 24), and primary non-melanoma urethral tumors (n = 5) from our institutional database. RESULTS: Twenty-three patients were diagnosed with localized disease, 7 had regional/nodal involvement and one had metastases. Initial treatment included surgery in 25 patients; seven had multimodal treatment. Median follow-up was 46 months (IQR 33-123). Estimated 5-year cancer-specific survival was 45%. No significant change in survival was observed based on a year of treatment. Primary urethral melanomas showed a higher frequency of TP53 mutations compared to cutaneous (80.0% vs. 18.2%, p = 0.006) and vulvar/vaginal melanomas (80.0 vs. 25.0%, p = 0.04). BRAF mutations were absent in urethral primaries (0% vs. 46% in cutaneous melanoma, p = 0.02). Tumor mutation burden was higher in cutaneous than urethral melanomas (p = 0.04). Urethral melanomas had a higher number of somatic alterations compared to non-melanoma urethral tumors (median 11 vs. 5, p = 0.03). CONCLUSIONS: Our findings support a unique mutational landscape of urethral melanoma compared to cutaneous melanoma. Survival remains poor and is unchanged over the time studied.
Keywords:	genetics; treatment; ipilimumab; melanoma; safety; therapy; urethra; primary malignant-melanoma; efficacy; kit mutations; prognosis; mucosal melanomas
Journal Title:	Bladder Cancer
Volume:	8
Issue:	3
ISSN:	2352-3727
Publisher:	IOS Press
Date Published:	2022-01-01
Start Page:	291
End Page:	301
Language:	English
ACCESSION:	WOS:000856715400005
DOI:	10.3233/blc-211633
PROVIDER:	wos
PMCID:	PMC9536426
PUBMED:	36277327
Notes:	Article -- Source: Wos