Primary malignant melanoma of the female urethra: 10-year survival

Abstract

Dear Editor, In 2001, we have treated a 65-year-old female who was referred due to a urethral mass with a gross appearance of a polypous caruncle. The tumor was pendular, round, 3 cm in diameter, dark blue with ulceration. The tumor was excised. Histopathological analysis showed the characteristics for malignant melanoma, and the invasion of malignant cells was through the lamina propria. In addition, HMB-45 antigen immunohistochemical stains were positive for malignant cells. We performed low third resection of distal urethra with bilateral inguinal lymphadenectomy. Further evaluation (serum lactate dehydrogenase level, CT imaging of brain, chest, abdomen, and pelvis) revealed no evident local or distant metastases so the disease was staged as grade I (local disease). After 10 years of close follow-up, the patient is alive without signs of the disease. To our knowledge, this is the first case of survival over 10 years described in the literature so far. Urethral melanoma is a rare tumor and accounts for 2% of all urethral malignant tumors. Survival over 5 years has been reported in less than 20 patients so far (PubMed search). The origin of the nevus cells found in mucosal membranes, from which the tumor arises, is still a point of debate. The occurrence of nevus cells in mucosal membranes could be a result of aberrant migration of melanocytes that migrate from the neural crest to the epithelium through peripheral nerves during fetal life. Another widespread belief is that nevus cells have a dual origin, and more specifically, it has been suggested that some nevus cells are derived from neural structures, specifically Schwann’s cells as they share morphological and functional features with both neurons and Schwann cells [1]. The mechanism of so called melanogenic or melanocytic metaplasia has also been suggested and means metaplasia of squamous and glandular epithelium into pigment-producing cells [2]. Mucosal melanomas (including urethral melanomas) show several important differences compared to cutaneous melanomas: up to 20% exhibit c-KIT mutation, and rarely exhibit BRAF mutation, they occur approximately 10 years later (mean age at presentation 67 years), up to 25% are amelanotic (compared to 8% in cutaneous form), more than 50% of patients present in advanced stages of the disease (compared to less than one-third in cutaneous form), and sun exposure is not a risk factor [3]. Symptoms of urethral melanomas develop quickly and are not specific. They include urethral mass, perineal pain, dysuria, frequency, incontinence, difficult voiding, irregular urinary stream, hematuria, or local bleeding. The color of the tumor varies from black to blue, brown or amelanotic. Approximately, 75% of urethral melanomas occur on the anterior urethra, and they have slightly better prognosis. Different treatment options have been proposed for urethral melanoma including local excision, urethrectomy, and anterior pelvic exenteration, with or without inguinal lymph node dissection, but none has shown advantages over others in long-term survival, and there are no randomized trials studying different treatment modalities. Most authors agree that less radical, organ preserving surgery is the method of choice because it shows similar results as more radical approach, and adjuvant radiation to the primary sites and lymph node regions is also recommended. Diagnostic methods, including CT and PET scan, should be used to exclude possible metastases because most patients present at an advanced stage [3]. Interferon-a2b is often used in S. Altarac D. Papes (&) Department of Surgery and Urology, Zabok General Hospital, Bracak 8, 49210 Zabok, Croatia e-mail: dinopapes@gmail.com