Primary mucosal melanomas of the urogenital tract: a clinical, pathological, and genetic nationwide survey of Danish patients 1990–2019
DOI:
https://doi.org/10.2340/sju.v58.8489Keywords:
Mucosal melanoma, urinary tract, pathology, geneticsAbstract
Purpose: To describe the epidemiologic, clinical, histopathological, and genetic features of primary mucosal
melanoma of the urinary tract in a national Danish cohort with cases included from the year 1990 to
2019.
Material and methods: Patients of the Danish cohort were found using national databases. Only primary
tumours were included in the cohort. Appropriate formalin-fixed paraffin-embedded blocks underwent
next-generation sequencing.
Results: Eight cases of primary urinary bladder melanomas and 18 cases of primary urethral melanomas
were included. Bladder melanomas had an incidence of 0.05 cases/million/year. Mean age at diagnosis was
67 years. The most frequent primary treatment was cystectomy. Adjuvant treatment was given in three
cases 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. Adjuvant
treatment was given in nine cases and most frequently consisted of radiotherapy. Mutations were found in
the NF1, TERT PROMOTOR, NRAS, ATRX, TP53, ATM, TSC2, and CREBBP genes. The 5-year survival of patients
with 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 most
widely used treatment for urogenital mucosal melanoma remains surgical while adjuvant therapy strategies
are 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.
Downloads
References
Chang AE, Karnell LH, Menck HR. The National Cancer Data Base report on cutaneous and noncutaneous melanoma: a summary of 84,836 cases from the past decade. The American College of Surgeons Commission on Cancer and the American Cancer Society. Cancer. 1998;83(8):1664–78. https://doi.org/10.1002/(SICI)1097-0142(19981015)83:8<1664::AID-CNCR23>3.0.CO;2-G DOI: https://doi.org/10.1002/(SICI)1097-0142(19981015)83:8<1664::AID-CNCR23>3.0.CO;2-G
Mikkelsen LH, Larsen AC, von Buchwald C, et al. Mucosal malignant melanoma – a clinical, oncological, pathological and genetic survey. APMIS. 2016;124(6):475–86. https://doi.org/10.1111/apm.12529 DOI: https://doi.org/10.1111/apm.12529
Mikkelsen LH, Heegaard S. Mucosal Melanoma. In: Riker A, editor. Melanoma. Cham: Springer; 2018. https://doi.org/10.1007/978-3-319-78310-9_15 DOI: https://doi.org/10.1007/978-3-319-78310-9_15
Newell F, Kong Y, Wilmott JS, et al. Whole-genome landscape of mucosal melanoma reveals diverse drivers and therapeutic targets. Nat Commun. 2019;10(1):3163. https://doi.org/10.1038/s41467-019-11107-x DOI: https://doi.org/10.1038/s41467-019-11107-x
Mundra PA, Dhomen N, Rodrigues M, et al. Ultraviolet radiation drives mutations in a subset of mucosal melanomas. Nat Commun. 2021;12(1):1–7. https://doi.org/10.1038/s41467-020-20432-5 DOI: https://doi.org/10.1038/s41467-020-20432-5
Piura B. Management of primary melanoma of the female urogenital tract. Lancet Oncol. 2008;9(10):973–81. https://doi.org/10.1016/S1470-2045(08)70254-7 DOI: https://doi.org/10.1016/S1470-2045(08)70254-7
McLaughlin CC, Wu XC, Jemal A, et al. Incidence of noncutaneous melanomas in the U.S. Cancer. 2005;103(5):1000–7. https://doi.org/10.1002/cncr.20866 DOI: https://doi.org/10.1002/cncr.20866
Nguyen AT, Kavolius JP, Russo P, et al. Primary genitourinary melanoma. Urology. 2001;57(4):633–8. https://doi.org/10.1016/S0090-4295(00)01107-9 DOI: https://doi.org/10.1016/S0090-4295(00)01107-9
El-Safadi S, Estel R, Mayser P, et al. Primary malignant melanoma of the urethra: a systematic analysis of the current literature. Arch Gynecol Obstet. 2014;289(5):935–43. https://doi.org/10.1007/s00404-013-3130-3 DOI: https://doi.org/10.1007/s00404-013-3130-3
Barillaro F, Camilli M, Dessanti P, et al. Primary melanoma of the bladder: case report and review of the literature. Arch Ital Urol Androl. 2018;90(3):224–6. https://doi.org/10.4081/aiua.2018.3.224 DOI: https://doi.org/10.4081/aiua.2018.3.224
Tingsgaard JK, Henriksen A, Mikkelsen LH, et al. Primary and secondary mucosal melanoma of the small intestine – a clinical, pathological, and genetic nationwide survey of Danish patients between 1980 and 2014. J Pathol Microbiol Immunol. 2018;126(9):739–45. https://doi.org/10.1111/apm.12883 DOI: https://doi.org/10.1111/apm.12883
Larsen AC. Conjunctival malignant melanoma in Denmark. Epidemiology, treatment and prognosis with special emphasis on tumorigenesis and genetic profile. Acta Ophthalmol. 2016;94(8):842. https://doi.org/10.1111/aos.13207 DOI: https://doi.org/10.1111/aos.13207
Lawaetz M, Birch-Johansen F, Friis S, et al. Primary mucosal melanoma of the head and neck in Denmark, 1982–2012: demographic and clinical aspects. A retrospective DAHANCA study. Acta Oncol (Madr). 2016;55(8):1001–8. https://doi.org/10.3109/0284186X.2016.1143117 DOI: https://doi.org/10.3109/0284186X.2016.1143117
Pandey PK, Vijay MK, Goel H, et al. Primary malignant melanoma of female urethra: a rare neoplasm. J Cancer Res Ther. 2014;10(3):758–60. https://doi.org/10.4103/0973-1482.136027 DOI: https://doi.org/10.4103/0973-1482.136027
Oliva E, Quinn TR, Amin MB, et al. Primary malignant melanoma of the urethra a clinicopathologic analysis of 15 cases. Am J Surg Pathol. 2000;24(6):785–96. https://doi.org/10.1097/00000478-200006000-00003 DOI: https://doi.org/10.1097/00000478-200006000-00003
Dimarco DS, Dimarco CS, Zincke H, et al. Outcome of surgical treatment for primary malignant melanoma of the female urethra. J Urol. 2004;171(2 I):765–7. https://doi.org/10.1097/01.ju.0000104671.20863.47 DOI: https://doi.org/10.1097/01.ju.0000104671.20863.47
Hori T, Kato T, Komiya A, et al. Primary melanoma of the urinary bladder identified by urine cytology: a rare case report. Diagn Cytopathol. 2014;42(12):1091–5. https://doi.org/10.1002/dc.23074 DOI: https://doi.org/10.1002/dc.23074
Papeš D, Altarac S, Arslani N, et al. Melanoma of the glans penis and urethra. Urology. 2014;83(1):6–11. https://doi.org/10.1016/j.urology.2013.07.009 DOI: https://doi.org/10.1016/j.urology.2013.07.009
Heppt MV, Roesch A, Weide B, et al. Prognostic factors and treatment outcomes in 444 patients with mucosal melanoma. Eur J Cancer. 2017;81:36–44. https://doi.org/10.1016/j.ejca.2017.05.014 DOI: https://doi.org/10.1016/j.ejca.2017.05.014
Zhu H, Dong D, Li F, et al. Clinicopathologic features and prognostic factors in patients with non-cutaneous malignant melanoma: a single-center retrospective study of 71 cases. Int J Dermatol. 2015;54(12):1390–5. https://doi.org/10.1111/ijd.12745 DOI: https://doi.org/10.1111/ijd.12745
Additional Files
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 Victoria K. Znaider, Lauge H. Mikkelsen, Christian Fuglesang S. Jensen, Jens Sønksen, Steffen Heegaard
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Acta Chirurgica Scandinavica Society owns the copyright for all material published until Volume 57 (2023) unless otherwise specified. As from Volume 59 (2024) all published articles, unless otherwise specified, are published under CC-BY licences, allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, with the condition of proper attribution to the original work.
