Abstract: Primary melanoma of the glans or male urethra is a rare malignant tumor with high mortality. We searched PubMed and found 129 articles reporting on 220 patients. All articles were case reports or case series. Median patient age was 65 years. Median survival was 28 months, with 5-year survival in approximately 10%. All patients who survived over 5 years had a localized disease (stage I/A) with invasion depth <3-3.5 mm. Wide local excision with sentinel lymph node biopsy is the treatment of choice for patients with localized disease. For advanced disease, the prognosis is poor. Primary melanoma of the glans or male urethra is a rare malignant tumor with high mortality. We searched PubMed and found 129 articles reporting on 220 patients. All articles were case reports or case series. Median patient age was 65 years. Median survival was 28 months, with 5-year survival in approximately 10%. All patients who survived over 5 years had a localized disease (stage I/A) with invasion depth <3-3.5 mm. Wide local excision with sentinel lymph node biopsy is the treatment of choice for patients with localized disease. For advanced disease, the prognosis is poor. Primary malignant melanomas of the glans penis and male urethra are rare tumors that occur in <0.1% of all melanomas.1Iversen K. Robins R.E. Mucosal malignant melanomas.Am J Surg. 1980; 139: 660-664Abstract Full Text PDF PubMed Scopus (95) Google Scholar, 2Oliva E. Quinn T.R. Amin M.B. et al.Primary malignant melanoma of the urethra: a clinicopathologic analysis of 15 cases.Am J Surg Pathol. 2000; 24: 785-796Crossref PubMed Scopus (79) Google Scholar, 3Stillwell T.J. Zincke H. Gaffey T.A. et al.Malignant melanoma of the penis.J Urol. 1988; 140: 72-75PubMed Google Scholar According to the American Cancer Society, approximately 1500 cases of penile cancer are diagnosed in the US each year. Less than 2% of those are melanomas, meaning that approximately 20 new cases of penile melanoma occur each year.4American Cancer Society. Penile cancer. Available at: http://www.cancer.org/cancer/penilecancer/detailedguide/penile-cancer-what-is-penile-cancer. Accessed 10 May 2013.Google Scholar Together with sarcoma, melanoma comprises approximately 5% of all tumors of the urethra.5Swartz M.A. Porter M.P. Lin D.W. et al.Incidence of primary urethral carcinoma in the United States.Urology. 2006; 68: 1164-1168Abstract Full Text Full Text PDF PubMed Scopus (147) Google Scholar One survey found that urethral carcinoma has an annual incidence of 4.3 per million men in the US.5Swartz M.A. Porter M.P. Lin D.W. et al.Incidence of primary urethral carcinoma in the United States.Urology. 2006; 68: 1164-1168Abstract Full Text Full Text PDF PubMed Scopus (147) Google Scholar This would mean that approximately 650 cases of urethral cancer and, subsequently, approximately 15 cases of urethral melanoma occur in male population each year in the US. Melanomas arise from malignant transformation of melanocytes, which are derived from the neuroectoderm. According to the origin of the tumor, melanomas situated on the penis may be cutaneous or mucosal. If they appear on the penile shat skin, they are classified as cutaneous and treated accordingly. Melanomas that occur on the glans, meatus, or urethra are mucosal melanomas. Melanomas in the corona or inner prepuce should also be classified as mucosal and those on the outer prepuce as cutaneous because the embryologic border of the penile mucosa and skin is located in the line between the inner and outer prepuce.6Cold C.J. Taylor J.R. The prepuce.BJUI. 1999; 83: 34-44PubMed Google Scholar This difference in origin is important because it has been shown that mucosal melanomas have several important differences from the cutaneous form (Table 1).7Seetharamu N. Ott P.A. Pavlick A.C. Mucosal melanomas: a case-based review of the literature.Oncologist. 2010; 15: 772-781Crossref PubMed Scopus (72) Google Scholar The primary cause of cutaneous melanoma is ultraviolet light exposure crossed with the amount of skin pigmentation in the population. Sunlight is not a causative factor for mucosal melanomas, and their etiology is unknown.7Seetharamu N. Ott P.A. Pavlick A.C. Mucosal melanomas: a case-based review of the literature.Oncologist. 2010; 15: 772-781Crossref PubMed Scopus (72) Google Scholar Despite the mentioned differences, the mainstay of cutaneous and mucosal melanoma treatment is wide excision, which can be curable for localized disease.7Seetharamu N. Ott P.A. Pavlick A.C. Mucosal melanomas: a case-based review of the literature.Oncologist. 2010; 15: 772-781Crossref PubMed Scopus (72) Google ScholarTable 1Differences between cutaneous and mucosal melanomasAdapted from reference 7Seetharamu N. Ott P.A. Pavlick A.C. Mucosal melanomas: a case-based review of the literature.Oncologist. 2010; 15: 772-781Crossref PubMed Scopus (72) Google Scholar.Cutaneous FormMucosal FormMean age at presentation55 y67 yPatients presenting with advanced diseaseApproximately 30%More than 50%Risk factorSun exposureNot yet establishedAmelanotic2%-8%20%-25%RaceWhite 94%, black 1%White 85%, black 7%c-KIT mutations5%15%-20%BRAFV600E50%-60%Rare Open table in a new tab The first case of melanoma of the penis was reported by Muchnison in 1859 (according to Gross8Gross S.D. A System of Surgery.6th ed. W.B.Saunders, Philadelphia1882Google Scholar), and the first description of the melanoma of the male urethra was by Tyrell9Tyrell H.J. Melanotic tumor of the urethra.Proc Pathol Soc Dublin. 1871; 4: 194Google Scholar in 1871. Since then, many articles have been published on the topic in "case-report and literature review" form with several larger case series. Therefore, we decided to conduct a literature review and analyze available patient data. A literature search was conducted in PubMed to identify relevant articles on the topic of melanoma of the glans and male urethra published until June 2012. The search terms included "urethra", "glans", and "penis" combined with "melanoma", "melanosarcoma", "cancer" and "tumor". All retrieved articles were analyzed and all articles written in English and all articles that had abstracts written in English and that contained adequate patient data were included in the review. Reports on patients with cutaneous melanoma appearing on the penile shaft skin were not included. Also, we did not include patients with melanoma metastasis to the penis or urethra. Our search returned 129 articles from 1962 to 2012 reporting on 220 patients with primary melanoma of the penis and urethra (Table 2). We excluded 36 articles that had no abstract, that had abstract but without data that could be analyzed, or those reporting on penile cutaneous melanoma. The data from the remaining 93 articles were analyzed. Several case series reported on patients with mucosal and cutaneous melanomas, and 1 series reported on patients with penile and scrotal melanoma. All retrieved articles were case reports or case series. The largest series were of Geel et al10van Geel A.N. den Bakker M.A. Kirkels W. et al.Prognosis of primary mucosal penile melanoma: a series of 19 Dutch patients and 47 patients from the literature.Urology. 2007; 70: 143-147Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar from 2007 (19 patients), Stillwell3Stillwell T.J. Zincke H. Gaffey T.A. et al.Malignant melanoma of the penis.J Urol. 1988; 140: 72-75PubMed Google Scholar et al from 1988 (11 patients), Sanchez-Ortiz11Sánchez-Ortiz R. Huang S.F. Tamboli P. et al.Melanoma of the penis, scrotum and male urethra: a 40-year single institution experience.J Urol. 2005; 173: 1958-1965Abstract Full Text Full Text PDF PubMed Scopus (87) Google Scholar et al from 2005 (10 patients), Oliva et al2Oliva E. Quinn T.R. Amin M.B. et al.Primary malignant melanoma of the urethra: a clinicopathologic analysis of 15 cases.Am J Surg Pathol. 2000; 24: 785-796Crossref PubMed Scopus (79) Google Scholar from 2000 (9 patients), and Oldbring et al12Oldbring J. Mikulowski P. Malignant melanoma of the penis and male urethra. Report of nine cases and review of the literature.Cancer. 1987; 59: 581-587Crossref PubMed Scopus (49) Google Scholar from 1987 (9 patients). The total number of reported cases is difficult to estimate. For example, the series of Sanchez-Ortiz et al from 2005 counted <100 patients with penile melanoma since the initial report in 1859 but another report counted 135 cases of penile and 52 cases of urethral melanoma in the same period and none of the articles specified literature search methodology.13Hankins C.L. Weston P. Re: Melanoma of the penis, scrotum and male urethra: a 40-year single institution experience. R. Sánchez-Ortiz, S. F. Huang, P. Tamboli, V. C. Prieto, G. Hester and C. A. Pettaway.J Urol. 2006; 175: 1574-1575Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar Penile cutaneous and mucosal melanomas are often presented together although the nature and prognosis of the diseases are different. In our search, we excluded all reports on melanomas that occurred on the penile shaft skin.Table 2Summary of the review findings on male glans and urethral melanomaNumber of retrieved articles129Number of reported patients220Age at presentation65 y (range, 13-88)IncidenceVery rare, <0.1% of all melanomas; incidence difficult to estimateRisk factorsNot yet establishedLocation Glans78 (54.5)Meatus22Corona7 Urethra52 (36.4)Distal urethra/fossa navicularis38Penile urethra4Bulbous4Membranous/prostatic urethra6 Prepuce and frenulum N (%)13 (9.1)Multifocal tumor2%. Five cases: 3 on the glans, 1 in the meatus and 1 in the urethraUlceration Glans27/69 (39.1) Urethra25/39 (64.1) Prepuce N (%)5/13 (38.5)Depth of invasion (mm) Glans2.6 (0.3-10) Urethra median (range)5.0 (0.5-10)TreatmentNo generally accepted surgical approach; surgery combined with chemotherapy and radiotherapy5-y survival Glans22.5 Urethra %10.0 Open table in a new tab As for all mucosal melanomas, risk factors for glans and urethral melanoma are not well known. We did not find any articles that associated urethral melanoma occurrence with genetic predisposition or any specific agent. We could not estimate the influence of circumcision on glans melanoma occurrence because most reports did not mention if the patient is circumcised. The percentage of glans melanomas arising from longstanding precursor nevi is <20% (3 of 16 and 3 of 11 in 2 largest series).3Stillwell T.J. Zincke H. Gaffey T.A. et al.Malignant melanoma of the penis.J Urol. 1988; 140: 72-75PubMed Google Scholar, 10van Geel A.N. den Bakker M.A. Kirkels W. et al.Prognosis of primary mucosal penile melanoma: a series of 19 Dutch patients and 47 patients from the literature.Urology. 2007; 70: 143-147Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar Median patient age was 65 years (range, 13-88). Appropriate data were available for 105 patients. This is similar to other reports on mucosal melanomas.7Seetharamu N. Ott P.A. Pavlick A.C. Mucosal melanomas: a case-based review of the literature.Oncologist. 2010; 15: 772-781Crossref PubMed Scopus (72) Google Scholar Several series that analyzed male and female urethral melanoma patients have reported that urethral melanoma is more common in female population, with an approximate 1.5-3:1 ratio. This is similar to other urethral malignancies.2Oliva E. Quinn T.R. Amin M.B. et al.Primary malignant melanoma of the urethra: a clinicopathologic analysis of 15 cases.Am J Surg Pathol. 2000; 24: 785-796Crossref PubMed Scopus (79) Google Scholar Our search returned 52 cases of male urethral melanoma, and in our previous report, we found 112 reported cases of female urethral melanoma, which gives a ratio of approximately 2:1.14Papeš D. Altarac S. Melanoma of the female urethra.Med Oncol. 2013; 30: 329Crossref PubMed Scopus (13) Google Scholar Glans melanoma typically presents as a colored lesion. The color of the tumor varies from black, blue, and brown to amelanotic. Ulceration occurs in 39% of cases. Melanomas situated on the meatus have also presented as asymptomatic protruding polypoid tumor or by spraying urinary stream. Urethral melanoma is characterized by lack of visibility and nonspecific symptoms during early stages, so the diagnosis is often delayed. Most common symptoms include urethral bleeding or hematuria because of ulceration that occurred in 64% of patients, followed by obstruction, spraying urinary stream, dysuria, and pain. One patient presented with urethrocutaneous fistula, and 1 melanoma was accidentally discovered during transurethral prostate resection. Ulceration is more common in urethral melanoma (64%) than in glans melanomas (39%, P = .02). Adequate information on clinical appearance was available in 121 reports. The shape of the tumor can be macular or polypoid, and the size varies from several millimeters to the largest reported being >5 cm in diameter. Approximately 20% of patients have nodal involvement at initial presentation.3Stillwell T.J. Zincke H. Gaffey T.A. et al.Malignant melanoma of the penis.J Urol. 1988; 140: 72-75PubMed Google Scholar, 10van Geel A.N. den Bakker M.A. Kirkels W. et al.Prognosis of primary mucosal penile melanoma: a series of 19 Dutch patients and 47 patients from the literature.Urology. 2007; 70: 143-147Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar, 12Oldbring J. Mikulowski P. Malignant melanoma of the penis and male urethra. Report of nine cases and review of the literature.Cancer. 1987; 59: 581-587Crossref PubMed Scopus (49) Google Scholar Of glans melanomas, 28% were located at the meatus, 9% in the corona, and the rest (63%) on the dorsal or ventral glans. Adequate data were available in 78 reports. Most common location of urethral melanomas is fossa navicularis (73%), followed by prostatic urethra (11%), bulbous urethra (8%), and penile urethra (8%). Adequate data were available in 52 reports. This is similar to female urethral melanomas where approximately 80% were also located at urethral meatus and distal urethra.14Papeš D. Altarac S. Melanoma of the female urethra.Med Oncol. 2013; 30: 329Crossref PubMed Scopus (13) Google Scholar We found 5 reported cases of multifocal melanomas. Three were situated on the glans, 1 in the meatus, and 1 in the urethra. There are no standard guidelines for adequate staging in mucosal melanoma. For glans and penile melanoma most investigators use a 3-stage system as follows15Bracken R.B. Diokno A.C. Melanoma of the penis and the urethra: 2 case reports and review of the literature.J Urol. 1974; 111: 198-200PubMed Google Scholar:Stage I – disease confined to the penis,Stage II – disease spreading to the regional lymph nodes, andStage III – disseminated disease. For urethral melanomas, most reports use the staging proposed by Levine for urethral cancer16Levine R.L. Urethral cancer.Cancer. 1980; 45: 1965-1972PubMed Google Scholar:Stage A – tumor confined to the submucosa,Stage B – tumor infiltrating the corpus spongiosum in men and the periurethral muscle in women,Stage C – tumor extending beyond the corpus spongiosum in men or periurethral invasion including vagina, bladder, labia, or clitoris in women, andStage D – tumor with metastasis to lymph nodes. Also, some investigators used American Joint Committee on Cancer staging system that is based on the TNM system (tumor size, lymph nodes, and metastatis).11Sánchez-Ortiz R. Huang S.F. Tamboli P. et al.Melanoma of the penis, scrotum and male urethra: a 40-year single institution experience.J Urol. 2005; 173: 1958-1965Abstract Full Text Full Text PDF PubMed Scopus (87) Google Scholar, 17American Joint Committee on CancerAJCC Cancer Staging Manual.6th ed. Springer-Verlag, New York1997Google Scholar Standard Breslow staging based on invasion depth is not used for primary urethral melanomas. After the diagnosis has been confirmed, serum lactate dehydrogenase levels are determined and computed tomography imaging of brain, chest, abdomen, and pelvis or positron emission tomography scans, or a combination of both, are undertaken to evaluate the stage and extent of disease. Testing for c-KIT mutation is useful because it may influence the choice of chemotherapy.7Seetharamu N. Ott P.A. Pavlick A.C. Mucosal melanomas: a case-based review of the literature.Oncologist. 2010; 15: 772-781Crossref PubMed Scopus (72) Google Scholar Penile and urethral malignant melanomas (along with all mucosal melanomas) generally carry a worse prognosis than the cutaneous form.7Seetharamu N. Ott P.A. Pavlick A.C. Mucosal melanomas: a case-based review of the literature.Oncologist. 2010; 15: 772-781Crossref PubMed Scopus (72) Google Scholar This may be because of several factors. First, in urethral melanoma, the delay in diagnosis is common and many patients present with advanced disease. Other possible reason is the frequent finding of a vertical growth phase in glans and urethral melanomas, similar as in nodular form of cutaneous melanoma. The incidence of vertical growth phase at diagnosis is 70%-100% in several larger series.2Oliva E. Quinn T.R. Amin M.B. et al.Primary malignant melanoma of the urethra: a clinicopathologic analysis of 15 cases.Am J Surg Pathol. 2000; 24: 785-796Crossref PubMed Scopus (79) Google Scholar, 10van Geel A.N. den Bakker M.A. Kirkels W. et al.Prognosis of primary mucosal penile melanoma: a series of 19 Dutch patients and 47 patients from the literature.Urology. 2007; 70: 143-147Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar, 12Oldbring J. Mikulowski P. Malignant melanoma of the penis and male urethra. Report of nine cases and review of the literature.Cancer. 1987; 59: 581-587Crossref PubMed Scopus (49) Google Scholar For comparison, nodular melanoma accounts for approximately 15% of all cases of cutaneous melanomas, which suggests a more aggressive nature of mucosal melanomas.18Mar V. Roberts H. Wolfe R. et al.Nodular melanoma: A distinct clinical entity and the largest contributor to melanoma deaths in Victoria, Australia.J Am Acad Dermatol. 2013; 68: 568-575Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar Factors that have been shown to have an adverse effect on prognosis include tumor thickness of >3.5 mm, presence of ulceration and microsatellites, and tumor diameter >15 mm.10van Geel A.N. den Bakker M.A. Kirkels W. et al.Prognosis of primary mucosal penile melanoma: a series of 19 Dutch patients and 47 patients from the literature.Urology. 2007; 70: 143-147Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar In our analysis, we found the median depth of invasion to be 2.6 mm in glans melanomas and 5 mm in urethral melanomas (P = .036). Of melanomas situated on the glans, 3 were in situ melanomas. Median survival in the 5 largest series was 28 months (range, 2-276). We found and analyzed data on 14 patients who survived over 5 years (Table 3)2Oliva E. Quinn T.R. Amin M.B. et al.Primary malignant melanoma of the urethra: a clinicopathologic analysis of 15 cases.Am J Surg Pathol. 2000; 24: 785-796Crossref PubMed Scopus (79) Google Scholar, 3Stillwell T.J. Zincke H. Gaffey T.A. et al.Malignant melanoma of the penis.J Urol. 1988; 140: 72-75PubMed Google Scholar, 11Sánchez-Ortiz R. Huang S.F. Tamboli P. et al.Melanoma of the penis, scrotum and male urethra: a 40-year single institution experience.J Urol. 2005; 173: 1958-1965Abstract Full Text Full Text PDF PubMed Scopus (87) Google Scholar, 12Oldbring J. Mikulowski P. Malignant melanoma of the penis and male urethra. Report of nine cases and review of the literature.Cancer. 1987; 59: 581-587Crossref PubMed Scopus (49) Google Scholar, 19Guinn G.A. Ayala A.G. Male urethral cancer: report of 15 cases including a primary melanoma.J Urol. 1970; 103: 176-179PubMed Google Scholar, 20Gincherman Y. Weiss J. Elder D. et al.A unique case of long-term survival in a male patient with malignant melanoma of the distal urethra.Cutis. 1996; 57: 44-46PubMed Google Scholar, 21Ander H. Esen T. Tellaloglu S. et al.Successful management of malignant melanoma of male urethra with local excision and adjuvant radiochemotherapy.Prog Clin Biol Res. 1991; 370: 379-383PubMed Google Scholar, 22Bobin J.Y. Gaude J.M. Bailly C. et al.Les melanomes malins primitifs de l'urethre: a propos de 4 cas.J Urol (Paris). 1983; 89: 105-109PubMed Google Scholar, 23Fernandez Madrigal F. Junquera Villa J.M. Melanoma primario de uretra masculina. Revision de la literatura.Acta Urol Es. 1984; 8: 221-224PubMed Google Scholar, 24Nguyen A.T. Kavolius J.P. Russo P. et al.Primary genitourinary melanoma.Urology. 2001; 57: 633-638Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar but the total number of such patients reported in the published data is higher because Geel reported an 18% survival rate in their series of 19 patients, but no data on those patients were available.10van Geel A.N. den Bakker M.A. Kirkels W. et al.Prognosis of primary mucosal penile melanoma: a series of 19 Dutch patients and 47 patients from the literature.Urology. 2007; 70: 143-147Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar In addition, many reports had a follow-up period shorter than 5 years, so the outcome of those patients is unknown. Although the sample is too small for statistical analysis, the presented data suggest that disease stage or invasion depth was predictive of long-term survival in this group because all patients were stage I/stage A, and the median invasion depth was 2 mm (range, 0-3.2 mm). Data on invasion depth were not available for 3 patients, and their treatment and outcome differs from the rest because 2 were treated only by radiotherapy, experienced local recurrence, and died of disease. Those patients were from older reports which may explain the nonstandard treatment. Also, it can be noticed that almost all melanomas were located at the glans or distal urethra; so all patients underwent organ-sparing surgery (wide local excision, glans, or partial penile amputation). Only 1 melanoma was in the bulbar urethra and that patient underwent radiotherapy. Three patients underwent lymphadenectomy, which was negative.Table 3Male patients with glans or urethral melanoma and reported survival over 5 yearsAuthorAgeLocationStage (Invasion Depth)TherapyRecurrenceSurvival (mo)StatusOliva2Oliva E. Quinn T.R. Amin M.B. et al.Primary malignant melanoma of the urethra: a clinicopathologic analysis of 15 cases.Am J Surg Pathol. 2000; 24: 785-796Crossref PubMed Scopus (79) Google Scholar68Distal urethraStage A2.2 mmUrethrectomy84ANEDStillwell3Stillwell T.J. Zincke H. Gaffey T.A. et al.Malignant melanoma of the penis.J Urol. 1988; 140: 72-75PubMed Google Scholar58GlansStage A2.5 mmAmputation of glans282DNEDStillwell3Stillwell T.J. Zincke H. Gaffey T.A. et al.Malignant melanoma of the penis.J Urol. 1988; 140: 72-75PubMed Google Scholar65MeatusStage AWide local excision96DWDStillwell3Stillwell T.J. Zincke H. Gaffey T.A. et al.Malignant melanoma of the penis.J Urol. 1988; 140: 72-75PubMed Google Scholar66GlansStage A2 mmPartial penectomy126DNEDStillwell3Stillwell T.J. Zincke H. Gaffey T.A. et al.Malignant melanoma of the penis.J Urol. 1988; 140: 72-75PubMed Google Scholar70MeatusIn situWide local excision192ANEDStillwell3Stillwell T.J. Zincke H. Gaffey T.A. et al.Malignant melanoma of the penis.J Urol. 1988; 140: 72-75PubMed Google Scholar70MeatusStage AAmputation of glans78DNEDSanchez-Ortiz11Sánchez-Ortiz R. Huang S.F. Tamboli P. et al.Melanoma of the penis, scrotum and male urethra: a 40-year single institution experience.J Urol. 2005; 173: 1958-1965Abstract Full Text Full Text PDF PubMed Scopus (87) Google Scholar69GlansStage A1.5 mmPartial penectomy101DWDOldbring12Oldbring J. Mikulowski P. Malignant melanoma of the penis and male urethra. Report of nine cases and review of the literature.Cancer. 1987; 59: 581-587Crossref PubMed Scopus (49) Google Scholar58GlansStage A2.9 mmPartial amputation, lymhadenectomy168ANEDGuinn20Gincherman Y. Weiss J. Elder D. et al.A unique case of long-term survival in a male patient with malignant melanoma of the distal urethra.Cutis. 1996; 57: 44-46PubMed Google Scholar53Bulbar urethra?Radiotherapy10 y, local28 mo, local156DODGincherman21Ander H. Esen T. Tellaloglu S. et al.Successful management of malignant melanoma of male urethra with local excision and adjuvant radiochemotherapy.Prog Clin Biol Res. 1991; 370: 379-383PubMed Google Scholar58Distal urethraStage A1 mmDistal urethrectomy, lymhadenectomy180ANEDAnder22Bobin J.Y. Gaude J.M. Bailly C. et al.Les melanomes malins primitifs de l'urethre: a propos de 4 cas.J Urol (Paris). 1983; 89: 105-109PubMed Google Scholar72Fossa navicularisStage A2 mmLocal excision7 mo, local96ANEDBobin23Fernandez Madrigal F. Junquera Villa J.M. Melanoma primario de uretra masculina. Revision de la literatura.Acta Urol Es. 1984; 8: 221-224PubMed Google Scholar72Distal urethra?Radiotherapy3 mo, local132DODFernandez-Madrigal24Nguyen A.T. Kavolius J.P. Russo P. et al.Primary genitourinary melanoma.Urology. 2001; 57: 633-638Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar33Meatus?Distal penectomy, lymphadenectomy, immunotherapy24 mo, distant metastases70AWDNguyen25Geelhoed G.W. Myers G.H. Primary melanoma of the male urethra.J Urol. 1973; 109: 634-637PubMed Google Scholar70GlansStage A3.2 mmPartial penectomy126AWDANED, alive, no evidence of disease; AWD, alive with disease; DOD, died of disease; DNED, died no evidence of disease; DWD, died with disease. Open table in a new tab ANED, alive, no evidence of disease; AWD, alive with disease; DOD, died of disease; DNED, died no evidence of disease; DWD, died with disease. Different surgical approaches have been proposed for the treatment of penile mucosal melanoma depending on the location and stage of the disease. As for all melanomas, wide local excision with adequate margins is the mainstay of treatment. For stage I/stage A melanomas located on the glans and distal urethra, organ-sparing surgery (local excision, urethrectomy, glans amputation or partial penectomy) is sufficient.3Stillwell T.J. Zincke H. Gaffey T.A. et al.Malignant melanoma of the penis.J Urol. 1988; 140: 72-75PubMed Google Scholar, 10van Geel A.N. den Bakker M.A. Kirkels W. et al.Prognosis of primary mucosal penile melanoma: a series of 19 Dutch patients and 47 patients from the literature.Urology. 2007; 70: 143-147Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar Although some investigators, mostly in older reports, advocated radical surgery for such lesions (total penectomy, groin and pelvic lymphadenectomy and cystoprostatectomy), such approach does not seem to improve survival according to the available data and is not indicated.25Geelhoed G.W. Myers G.H. Primary melanoma of the male urethra.J Urol. 1973; 109: 634-637PubMed Google Scholar, 26Pow-Sang J.M. Klimberg I.W. Hackett R.L. et al.Primary malignant melanoma of the male urethra.J Urol. 1988; 139: 1304-1306PubMed Google Scholar Mostly, radical approach has been suggested because of apparently high percentage of local recurrences in certain reports. One report analyzed 5 cases of distal urethral lesions treated by partial penectomy and found 3 local recurrences (60%)26Pow-Sang J.M. Klimberg I.W. Hackett R.L. et al.Primary malignant melanoma of the male urethra.J Urol. 1988; 139: 1304-1306PubMed Google Scholar but detailed analysis showed that 1 patient was actually treated by total penectomy,25Geelhoed G.W. Myers G.H. Primary melanoma of the male urethra.J Urol. 1973; 109: 634-637PubMed Google Scholar and the other 2 had advanced disease (inguinal metastasis at presentation and tumor infiltrating corpus cavernosum),19Guinn G.A. Ayala A.G. Male urethral cancer: report of 15 cases including a primary melanoma.J Urol. 1970; 103: 176-179PubMed Google Scholar, 27Girgis A.S. Bergman H. Rosenthal H. et al.Unusual penile malignancies in circumcised Jewish men.J Urol. 1973; 110: 696-702PubMed Google Scholar so radical surgery would have had no benefit on the outcome. Stage A melanomas situated in the proximal penile, bulbar, or prostatic urethra also require wide local excision which may in effect result in radical surgery because of the anatomic location of the tumor (e.g. total penectomy will be necessary for proximal penile urethral lesion and prostatectomy or cystoprostatectomy for proximal bulbar and prostatic melanomas). We found that local recurrence rate after surgery is approximately 15% but reaches 30% in some series, which is similar to previous reports.10van Geel A.N. den Bakker M.A. Kirkels W. et al.Prognosis of primary mucosal penile melanoma: a series of 19 Dutch patients and 47 patients from the literature.Urology. 2007; 70: 143-147Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar There are several factors that may lead to local recurrence (deep invasion reaching highly vascular urethral submucosa, multifocal tumor, and inadequate resection margin). For example, Geel et al found that 8 of their 19 patients (42%) had a positive margin after wide local excision. The optimal width of excision cannot be determined because it is not specified in almost any of the reports, but concluding from female urethral melanoma, a margin of 2.5 cm should be sufficient for stage A urethral melanomas.14Papeš D. Altarac S. Melanoma of the female urethra.Med Oncol. 2013; 30: 329Crossref PubMed Scopus (13) Google Scholar As in cutaneous melanomas, if deep invasion is present, a wider excision will most likely not result in longer survival or reduce local recurrence. Lymphadenectomy (groin and pelvic) has been used in many reports but the benefit remains questionable. Lymphatic drainage of the male urethra and glans penis follows an established pattern. Preprostatic, prostatic, and membranous urethra drain into the pelvic lymph nodes associated with the iliac vessels and obturator fossa, and penile urethra and glans drain into the deep inguinal lymph nodes.28Cabanas R.M. Anatomy and biopsy of sentinel lymph nodes.Urol Clin North Am. 1992; 19: 267-276PubMed Google Scholar, 29Wood H.M. Angermeier K.W. Anatomic considerations of the penis, lymphatic drainage, and biopsy of the sentinel node.Urol Clin North Am. 2010; 37: 327-334Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar Drainage to 1 or both sides is possible.28Cabanas R.M. Anatomy and biopsy of sentinel lymph nodes.Urol Clin North Am. 1992; 19: 267-276PubMed Google Scholar In stage I mucosal melanoma, similar to cutaneous form, there is no indication for routine lymph node dissection because there is no evidence of survival benefit and it carries considerable morbidity.13Hankins C.L. Weston P. Re: Melanoma of the penis, scrotum and male urethra: a 40-year single institution experience. R. Sánchez-Ortiz, S. F. Huang, P. Tamboli, V. C. Prieto, G. Hester and C. A. Pettaway.J Urol. 2006; 175: 1574-1575Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar However, for patients with groin lymph node metastases, some investigators suggest that an ilioinguinal lymph node dissection should be undertaken.3Stillwell T.J. Zincke H. Gaffey T.A. et al.Malignant melanoma of the penis.J Urol. 1988; 140: 72-75PubMed Google Scholar, 10van Geel A.N. den Bakker M.A. Kirkels W. et al.Prognosis of primary mucosal penile melanoma: a series of 19 Dutch patients and 47 patients from the literature.Urology. 2007; 70: 143-147Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar The reasons for lymphadenectomy are that in some patients regional nodal involvement may be the only area of metastatic disease so the removal of such metastasis could be curative. Also, removal of nodal metastasis may be palliative in reducing local complications (pain, tumor mass effect, and tumor fungation). Sentinel node biopsy may be used for obtaining staging data. However, this procedure will most likely not improve prognosis, and currently gives only predictive information. For stage II/stage B glans and urethral melanomas, the prognosis is poor. In patients with lymph node involvement, the reported 2-year survival rate was nearly 0% despite various treatment modalities used,10van Geel A.N. den Bakker M.A. Kirkels W. et al.Prognosis of primary mucosal penile melanoma: a series of 19 Dutch patients and 47 patients from the literature.Urology. 2007; 70: 143-147Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar and we found only 1 patient who survived over 2 years but died from the disease 4 years after the diagnosis.3Stillwell T.J. Zincke H. Gaffey T.A. et al.Malignant melanoma of the penis.J Urol. 1988; 140: 72-75PubMed Google Scholar Instead of radical surgery, tumor excision combined with chemoimmunotherapy can be used with equal result and lesser postoperative morbidity. Radiotherapy has shown no special benefit in glans and urethral melanomas. Regarding chemotherapy, different agents and adjuvant immunotherapy have been used but their effect on survival cannot be estimated because of the small number of patients. Most commonly used agent is dacarbazine combined with interleukin 2. Adjuvant immunotherapy with interferon alfa has been used with reported response rates ranging from 3% to 23%.2Oliva E. Quinn T.R. Amin M.B. et al.Primary malignant melanoma of the urethra: a clinicopathologic analysis of 15 cases.Am J Surg Pathol. 2000; 24: 785-796Crossref PubMed Scopus (79) Google Scholar However, interferon alone is not sufficiently active and, if used, it should be used together with chemotherapy because synergy between interferon and chemotherapy has been reported.30Kim C.J. Pak K. Hamaguchi A. et al.Primary malignant melanoma of the female urethra.Cancer. 1993; 71: 448-451Crossref PubMed Scopus (45) Google Scholar Because up to 20% of mucosal melanomas exhibit c-KIT mutations,7Seetharamu N. Ott P.A. Pavlick A.C. Mucosal melanomas: a case-based review of the literature.Oncologist. 2010; 15: 772-781Crossref PubMed Scopus (72) Google Scholar c-KIT tyrosine kinase inhibitors can also be tried if c-KIT mutation is confirmed positive response in patients with mucosal melanoma has been reported.31Satzger I. Küttler U. Völker B. et al.Anal mucosal melanoma with KIT-activating mutation and response to imatinib therapy–case report and review of the literature.Dermatology. 2010; 220: 77-81Crossref PubMed Scopus (66) Google Scholar, 32Quintas-Cardama A. Lazar A.J. Woodman S.E. et al.Complete response of stage IV anal mucosal melanoma expressing KIT Val560Asp to the multikinase inhibitor sorafenib.Nat Clin Pract Oncol. 2008; 5: 737-740Crossref PubMed Scopus (100) Google Scholar Glans and urethral melanoma is a rare neoplasm with high mortality. Owing to the small number of patients and absence of key information in some reports, only approximate conclusions may be drawn. Recommendations regarding treatment can only be given on the basis of small case series/reports (level of evidence 4, grade of recommendation C), by following general oncologic principles and by concluding from data on female patients with urethral melanoma and patients with cutaneous melanoma. Wide local excision with and sentinel lymph node biopsy is an option for patients with localized disease (stage I). There is no indication for radical surgery or routine lymphadenectomy in such cases because they will not improve prognosis. Also, in advanced disease (stage II/III), radical surgery will not improve survival significantly and will result in high morbidity. The prognosis mostly depends on tumor stage. Stage I/A disease with invasion depth <3-3.5 mm is potentially curable by wide excision. Although there is no direct evidence of benefit, chemotherapy and immunotherapy are often used.