BERKELEY, CA (UroToday.com) - Penile melanoma is a rare disease that affects mainly elderly patients from the sixth decade of life, unlike cutaneous melanoma, whose incidence is higher in younger patients (40-50 years).[1] A problem in clinical practice is recognizing a pigmented penile lesion as a melanoma. As for all mucosal melanomas, risk factors for glans and urethral melanoma are not well known. Patients are usually asymptomatic, but in advanced stages, may have dysuria, obstructive symptoms, hematuria, urethral discharge, and more rarely, urinary fistula.[2] Presentation ranges from papule or plaque staining bluish-black or reddish brown with bleeding ulcer. These lesions are usually benign and completely indistinguishable clinically from primary penile melanoma.[3]
Dermoscopy may prove useful for the differential diagnosis between mucosal melanosis, other mimickers, and early melanoma. However, its potential role has been limited so far because little is known about the dermoscopic features of penile melanoma.[4] Most frequently, the lesion is located on the glans (55%), followed by foreskin (28%), penile shaft (9%) and urethral meatus (8%).[5] Due to late diagnosis and lack of well-established treatment protocols, the prognosis is generally poor. However, although it is an aggressive disease, it is possible to maximize cure with treatment in its early stages.
We reviewed the charts of 6 patients who were consecutively admitted to Brazilian National Cancer Institute to treat penile melanoma between 2004 and 2012. The preoperative staging included chest radiography and abdomen and pelvis CT. The tumor staging was based on the 2002 American Joint Committee on Cancer (AJCC) to classify melanoma (Table 1). In this system, pathological tumor stage is mainly based on the evaluation of lesion depth (Breslow) and anatomic level of invasion (Clark). Our approach for the surgical treatment of melanoma of penis is detailed in Figure 1.
Microscopic criteria as asymmetry, cell nests confluence, junctional activity, atypia, and necrosis of melanocytes are important for a conclusive diagnosis. In difficult cases we have used immunohistochemistry. Although that is not necessary in cases of well-differentiated tumors, it is indispensable in poorly differentiated tumors. The more specific markers for melanoma are melan-A (MART-1), HMB 45 and S-100 protein. Besides these, information about the aberrations of c-Kit gene in acral melanomas in mucosa or in areas of permanent sun exposure, are targeting therapeutic research, making these aberrations important markers.[6, 7, 8, 9, 10, 11]
In immunohistochemical examination the staining was strongly positive in 5 cases, both for Melan-A, and for the S100, but the amount of labeled cells was above 50% in 3 cases, and 40% in the two other cases. In the HMB45, done in 2 cases at diagnosis, intensity was strongly positive, with 30 and 20% of labeled cells in 2 cases respectively. Immunohistochemistry performed in 5 cases for c-kit was positive in more than 50% of cells with good intensity in 4 cases and negative in one (case 5 with tumor in glans, pT1b).
All tumors were evaluated for major prognostic factors. To determine the real extent and dimension of the injury, the analysis included the depth (Breslow) and size of the lesion, the presence or absence of necrosis, ulceration, and satellite nodules. We also analyzed the number of mitoses per field, presence or absence of associated in situ melanoma (Tis), and characteristics of resection (R0, complete or R1 when the margins were positive).
Local excision or partial penile amputation, with appropriate safety margin, can be effective in the control of stages T1 and T2 penile melanomas. Yet patients who had clinically proven metastases died despite surgical procedures and chemotherapy. Although it is an aggressive disease, it is likely to be cured when in the early stages, making necessary a close cooperation between urologists and dermatologists to achieve this goal. The treatment of patients without palpable lymph nodes is controversial, however, considering the aggressiveness of the disease and early metastasis, prophylactic inguinal lymphadenectomy may be considered in selected patients.
Table 1. Clinical and pathologic characteristics of the tumors studied.
Patients 1 2 3 4 5 6 Date of surgery 2004 2005 2005 2006 2007 2012 Age (years) 14 64 73 75 71 78 Site of tumor Glans Foreskin Shaft Foreskin Glans Urethral Meatus Pathologic Stage (AJCC 2002) T in situ T2bN0M0 T2bNXM0 T4bN3M1 T1bNxM0 T4NxM0 Palpable Lymph nodes Negative Negative Negative Positive Negative Negative Breslow (mm) In situ 1.9 mm 1.5 mm 10 mm 0.2 mm 7 mm Primary Therapy Local Excision Local Excision + Sentinel Lymph node Dissection Local Excision Partial Amputation + Bilateral Inguinal Lymph node Dissection Local Excision Partial Amputation Recurrence No No Yes Yes No No Adjuvant Therapy No No No Dacarbazine (30 cycles) No No Follow up (months) 96 84 12 14 3 9 (Death) (Death) (Death)
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| Figure 1: An algorithm showing our surgical treatment for patients with melanoma of penis. |
References:
- Lotem M, Anteby S, Peretz T, Ingber A, Avinoach I, Prus D: Mucosal melanoma of the female genital tract is a multifocal disorder. Gynecol Oncol. 2003; 88: 45-50.
- Oldbring J, Mikulowski P: Malignant melanoma of the penis and male urethra. Report of nine cases and review of the literature. Cancer. 1987; 59: 581-7.
- Primus G, Soyer HP, Smolle J, Mertl G, Pummer K, Kerl H: Early ‘invasive’ malignant melanoma of the glans penis and the male urethra. Report of a case and review of the literature. Eur Urol. 1990; 18: 156-9.
- Carli P, De Giorgi V, Soyer HP, Stante M, Mannone F, Giannotti B: Dermatoscopy in the diagnosis of pigmented skin lesions: a new semiology for the dermatologist. J Eur Acad Dermatol Venereol. 2000; 14: 353-69.
- Demitsu T, Nagato H, Nishimaki K, Okada O, Kubota T, Yoneda K, et al.: Melanoma in situ of the penis. J Am Acad Dermatol. 2000; 42: 386-8.
- Smalley KS, Sondak VK, Weber JS: c-KIT signaling as the driving oncogenic event in sub-groups of melanomas. Histol Histopathol. 2009; 24: 643-50.
- Abu-Abed S, Pennell N, Petrella T, Wright F, Seth A, Hanna W: KIT gene mutations and patterns of protein expression in mucosal and acral melanoma. J Cutan Med Surg. 2012; 16: 135-42.
- Weider N, Cote RJ, Suster S, Wess LM: Modern Surgical Pathology. 2ª edition 2009; cap. 49; page 1936-942. Saunders / Elsevier, Weedon D. Skin Pathology. Churchill Livingstone, second edition. 2002; pp. 821-34.
- Veronese LA, Marques MEA: Critérios anatomopatológicos para melanoma maligno cutâneo: análise qualitativa de sua eficácia e revisão da literatura. J. Bras. Patol. Med. Lab. 2004; 40: 99-112.
- Park E, Yang S, Emley A, DeCarlo K, Richards J, Mahalingam M: Lack of correlation between immunohistochemical expression of CKIT and KIT mutations in atypical acral nevi. Am J Dermatopathol. 2012; 34: 41-6.
- Curtin JA, Busam K, Pinkel D, Bastian BC: Somatic activation of KIT in distinct subtypes of melanoma. J Clin Oncol. 2006; 24: 4340-6.
Written by:
Antonio Augusto Ornellas, MD, PhD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Department of Urology, Brazilian National Cancer Institute and Mário Kröeff Hospital
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