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. 2022 Sep 15;8(3):291-301.
doi: 10.3233/BLC-211633. eCollection 2022.

Urethral Melanoma - Clinical, Pathological and Molecular Characteristics

Roy Mano  1   2 , Benedikt Hoeh  1   3 , Renzo G DiNatale  1   4   5 , Alejandro Sanchez  1   6 , Nicole E Benfante  1 , Ed Reznik  4 , Mario M Leitao  7 , Alexander N Shoushtari  8 , Alvin Goh  1 , S Machele Donat  1 , Harry W Herr  1 , Bernard H Bochner  1 , Guido Dalbagni  1 , Timothy F Donahue  1
Affiliations

Urethral Melanoma - Clinical, Pathological and Molecular Characteristics

Roy Mano et al. Bladder Cancer. .

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: Melanoma; genetics; prognosis; treatment; urethra.

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Conflict of interest statement

B.H.B. is an Editorial Board member of this journal, but was not involved in the peer-review process nor had access to any information regarding its peer-review. M.M.L. received research funds from KCI/Acelity, is an ad-hoc speaker for Intuitive Surgical, Inc. and serves in the advisory boards of JnJ/Ethicon and Takeda. A.G. is a consultant for Medtronic. R.M., B.H., R.G.D., A.S., N.E.B., E.R., A.N.S., S.M.D., H.W.H., G.D., T.F.D. declare no conflict of interests.

Figures

Fig. 1
Fig. 1
Kaplan-Meier curves of (A) local recurrence free survival of patients who underwent treatment for their loco-regional disease (n = 27), (B) metastatic free survival of patients who presented without metastatic disease (n = 30), and (C) cancer specific survival of all patients with urethral melanoma (n = 31).
Fig. 2
Fig. 2
(A) Onco-print of common genetic alterations in patients who underwent MSK-IMPACT testing of primary urethral melanomas (n = 5) and primary urethral tumors with a non-melanoma histology (n = 5), the bar-plot represents the total number of genetic alterations seen in each tumor sample; (B) Box-plot comparing total number of genetic alterations in patients with melanoma and non-melanoma urethral tumors; (C) Lollipop plot depicting mutations in the TP53 gene in patients with urethral melanoma (n = 5).
Fig. 3
Fig. 3
(A) Bar-plot comparing common genetic mutations among patients who underwent sequencing of primary urethral melanoma (n = 5 IMPACT; n = 8 specific BRAF, KIT and/or NRAS sequencing), primary cutaneous melanoma (n = 143 IMPACT) and primary vulvar and vaginal melanomas (n = 24 IMPACT) * adjusted p-value < 0.05; Box-plots comparing (B) tumor mutation burden score and (C) fraction genome altered between the different tumors.
See this image and copyright information in PMC

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