CLINICAL DERMATOLOGY AND DERMATITIS (ISSN:2631-6714)

Primary urethral mucosal melanoma is a rare but aggressive melanoma that affects patients in their sixth and seventh decade of life. The tumor appears as a black nodule or polyp but can also be amelanotic. One of the prognostic factors is the size of the tumor. Surgery seems to be the only effective treatment, Treatments add to surgery, more particularly chemotherapy, seem to improve the prognosis and prevent recurrences, this in the absence of guidelines and clear consensus in the treatment of mucosal melanomas. The survival rate largely depends on the lymph node and visceral metastases of the disease.

Melanoma; Vaginal; Urethral; Mucosa; Hematuria

Genital mucosal melanomas are extremely rare, about 1% of all melanoma localizations, most frequently localized on the vulva [1]. Exceptional on the vagina or on the urogenital tract [2], generally these melanomas are diagnosed late due to their localization. Thus, they are associated with a poor prognosis. This article intends to discuss a case of primitive ureter melanoma.

Observations

A female patient 41 years-old, single; complaining of hematuria, presenting a polypoid and pigmented tumor on the urethral orifice. Clinical examination of the teguments didn’t show any suspected skin lesion or lymph nodes. The examination under anesthesia showed a pigmented umefaction on the peri-ureteral area, extending to the urethral orifice, the ureter and to the vagina, extends over 4 cm intra vaginally. A biopsy confirmed the diagnosis of melanoma. The cancer is inoperable; the radiological extension assessment revealed showed the presence of enlarged lymph nodes and metastatic localizations. The patient was put on chemotherapy in the absence of surgical indication. The evolution was marked by the patient’s deaths after 6 months of chemotherapy (Figure 1).

The urogenital tract melanoma is a very aggressive and rare disease, an early diagnosis is essential to an adequate treatment strategy, since the scarcity of data and guidelines regarding treatment measures, is making the management of this disease very difficult and challenging.

Urogenital tract melanomas are very rare and extremely aggressive. Vagina melanomas represent about 0.3% of all malignant melanomas end less than 3% of vagina cancers [3,4]. Urethral localizations are even rarer, there are only 121 cases described in the literature since 1966 [5,6], generally originate in the distal urethra, They represent only 0.1% of all malignant melanomas and about 2% of malignant tumors affecting female ureters [7-10]. The physiopathology is not yet quite understood, but many theories and risk factors are proposed to explain this ailment, among these, the CKIT gene mutation is highly incriminated [11]. Another theory suggests that the causal factor could be microenvironmental factors and not associated with ultraviolet radiation vue [12]. The disease affects people between 38 and 90 years old, often in women in their sixth to seventh decade [13], generally discovered as a polypoid pigmented and hemorrhagic mass, sometimes ulcerated. Amelanotic tumors have also been reported in patients, which often leads to misdiagnosis and delayed treatment [3,14]. This often leads to delayed diagnosis, treatment, and affect badly the prognosis. The confirmation of the diagnosis is based on immunehistochemistry, which is S-100 +, mélanA +, HMB-45 + and vimentin + [5,15]. The investigation is the same as skin melanoma. Nodal metastasis and distant metastasis are frequent, 50% and 20% respectively [16]. There are no well-established guidelines concerning the treatment. When the cancer is resectable, surgery is recommended [17], with surgical safety margins varying between 1 to 2 cm [3]. Radical surgery associated with lymph nodes dissection, chemotherapy or radiation therapy exclusive or additional to other treatments, are all options for advanced-stage malignant primitive vagina melanomas [4,18,19]. The urogenital localization is associated with very poor prognosis even if it’s a locally evolutive lesion [14]. The current treatment strategy includes surgery, chemotherapy, immunotherapy, and palliative care [5]. The available data suggest a survival rate of a relative 5 years survival rate between 0 to 25%, in case of primitive vagina melanoma regardless of the treatment strategy [16].

1. Goldemberg DC, Thuler LCS, Andreia Cristina de Melo. An Updateon Mucosal Melanoma: Future Directions. Acta Dermatovenerol Croat. 2019 Mar;27(1):11-15.
2. Ballester Sanchez R, de Unamuno Bustos B, Navarro MiraM, Botella Estrada R. Mucosal melanoma: an update. Actas Dermosifiliogr. 2015 Mar;106(2):96-103.
3. Kalampokas E, kalampokas T, damaskos C. Primary VaginalMelanoma, A Rare and Aggressive Entity. A Case Report andReview of the Literature. In Vivo. 2017 Jan-Feb;31(1):133–140.
4. Gokaslan H, Sismanoglu A, Pekin T, Kaya H, Ceyhan N. mélanome malin primaire du vagin: un rapport de cas et une revue des optionsde traitement actuelles. Eur J ObstetGynecolReprodBiol. 2005; 12:243-248.
5. Lin LT, Liu CB, Chen SN, Chiang AJ, Liou WS, et al. Primary malignant melanoma of the vagina with repeated local recurrences and brain metastasis. J Chin Med Assoc 2011;74(8): 376-379.
6. DiMarco DS, DiMarco CS, Zincke H, MJ Webb, GL Keeney, etal. Résultat du traitement chirurgical pour le mélanome malinprimaire de l’urètre feminine (Outcome of surgical treatment for primary malignant melanoma of the female urethra). J Urol. 2004Feb;171(2 Pt 1):765-767.
7. Namita Bhutani, Pradeep Kajal, Devendra Pawar. Primary malignant melanoma of the female urethra: Report of a rare neoplasm of the urinary tract. Int J Surg Case Rep. 2017; 41: 319-322.
8. Gupta R, Bhatti SS, Dinda A K, Singh M K. Primary melanoma of the urethra: a rare neoplasm of the urinary tract. Int Urol Nephrol.2007;39(3):833-836.
9. Das P, Kumar N, Ahuja A, Jain A, Ray R, et al. Primary malignantmelanoma at unusual sites: an institutional experience withreview of literature. Melanoma Res.2010 Jun; 20(3):233-239.
10. Akbas A, Akman T, Erdem MR, Antar B, Kilicarslan I, et al. Female urethral malignant melanoma with vesical invasion: a casereport. Kaohsiung J Med Sci. 2010 Feb;26(2):96-98.
11. Whiteman DC, Pavan WJ, Bastian BC. The melanomas: a synthesis of epidemiological, clinical, histopathological, genetic, and biological aspects, supporting distinct subtypes, causal pathways, and cells of origin. Pigment Cell Melanoma Res. 2011Oct;24(5):879-897. 
12. Hu DN, Yu GP, McCormick SA. Population-based incidence ofvulvar and vaginal melanoma in various races and ethnic groupswith comparisons to other site-specific melanomas. MelanomaRes. 2010 Apr;20(2):153-158.
13. Baloglu A, Bezircioglu I, Cetinkaya B, Yavuzcan A. Primary malignant melanoma of the vagina. Arch Gynecol Obstet. 2009Nov;280(5):819-822. 
14. Androutsopoulos G, Terzakis E, Ioannidou G, Tsamandas A, Decavalas G. Vaginal primary malignant melanoma: a rare and aggressive tumor. Case Rep Obstet Gynecol. 2013;2013:137908.
15. Chen L, Xiong Y, Wang H, Liang L, Shang H, et al. Malignant melanoma of the vagina: A case report and review of the literature. Oncol Lett. 2014 Oct;8(4):1585–1588.
16. Kuhn F, Dieterich M, Klar E, Gerber B, Prinz C. Primary malignant vaginal melanoma – case report and review of the literature. Geburtshilfe Frauenheilkd.2012 Aug;72(8):740–743.
17. Schmidt M, Honig A, Schwab M, Adam P, Dietl J. Primary vaginal melanoma: a case report and literature review. Eur J GynaecolOncol. 2008;29(3):285-288.
18. Samolis S, Panagopoulos P, Kanellopoulos N, Papastefanou I,Karadaglis S, et al. Primary melanoma of the vagina: a case report.Eur J Gynaecol Oncol. 2010;31(2):233-234. 
19. Seifried S, Haydu LE, Quinn MJ, Scolyer RA, Stretch JR, et al.Melanoma of the vulva and vagina: principles of staging and theirrelevance to management based on a clinicopathologic analysisof 85 cases Ann Surg Oncol. 2015 NOV;22(6):1959-1966.