To the Editor: Primary malignant melanoma of the bladder is rare; malignant melanomas of the bladder are usually metastatic lesions.1, 2 A recent review indicated 24 confirmed cases of metastatic melanoma of the bladder.1 Other papers reported another 27 postmortem cases of melanoma with bladder metastases.3 Because most of these autopsy cases were of asymptomatic subjects, the real incidence of secondary involvement of the bladder might be higher than generally estimated.4 The main symptom of bladder melanoma is gross hematuria.4 The diagnosis of metastatic melanoma of the bladder is often delayed and does affect the prognosis. Twenty-six cases of primary melanoma of the bladder have been reported.4 We report a case of primary bladder melanoma without involvement of other sites. In January 2015, an 81-year-old man was admitted to the Geriatrics Unit for an episode of gross hematuria in the previous month in the absence of any symptoms. His medical history included hypertension, hypothyroidism treated with L-thyroxine, peripheral arterial disease, and corneal transplantation at the age of 74. Urine cytology identified atypical cells, but analysis was not conclusive. He underwent cystoscopy, with evidence of three exophytic lesions, on which multiple biopsies were performed. Histology revealed groups of neoplastic cells with focal intracytoplasmatic melanin pigmentation. Immunohistochemistry revealed positivity for HMB45, melanoma antigen recognized by T cells 1 (MART-1), and S-100, and a diagnosis of bladder melanoma was made. At a further cutaneous examination, two nevi were detected and surgically removed; both were dysplastic without any sign of melanoma. Positron emission tomography–computed tomography did not reveal any further neoplastic site. Gastrointestinal endoscopy was also negative. Ophthalmic examination with fundus oculi exam did not indicate retinal melanoma. Radical cystectomy with ileal conduit was performed. Anatomical and histological examination showed two ulcerated lesions (2.5 and 1 cm in diameter, respectively) on the posterior wall. The lesions showed a proliferation of epithelioid-like cells characterized by ample eosinophilic cytoplasm, nuclear irregularity, and pleomorphism, with conspicuous nucleolus and arranged in solid nests. The neoplasia involved the mucosa and muscular and adipose tissue of the bladder wall. Pigment deposits were also present in the neoplastic tissue. Immunohistochemistry was performed using the streptavidin biotin method. Immunohistochemical analysis showed positivity of neoplastic cells for HMB45 and MART1 and focally for S100 protein, confirming the diagnosis of malignant melanoma (Figure 1). Prostate cancer with a Gleason score of 7 (4 + 3) was also diagnosed. During the postoperative course, the man experienced wound dehiscence, sepsis, and respiratory insufficiency. At his and his family's wishes, because of his age and comorbidity, no further therapies were administered. After 12 months, he was still alive, independent in activities of daily living, and disease free. Primary malignant melanoma is uncommon in the genitourinary tract, especially in the bladder.5 Age at presentation of primary bladder melanoma ranges from 7 to 91 (59 ± 17).4 The origin of malignant melanoma in the bladder is unclear. According to the ectopic theory, melanocytes would migrate from the neural crest through the mesenchyme toward the skin and hair follicles, possibly stopping in ectopic locations, including a developing bladder.6 Another hypothesis is that argyrophil urothelial cells are derived from urothelial stem cells with differentiation in the direction of neoplastic melanocytes.7 In the absence of a clinical history of melanoma, other lesions with an infiltrative growth pattern and similar cytomorphology may be considered. The possible list of differential diagnoses includes high-grade urothelial carcinoma, prostatic carcinoma in men, Mullerian carcinomas in women, lung carcinoma, breast carcinoma, and rare entities such as paraganglioma and sarcomatoid carcinoma.8 There is no consensus regarding the best treatment for the management of primary malignant melanoma of the urinary bladder, perhaps because of the small number of reported cases. The prognosis with primitive malignant melanoma is poor.4 Trials involving treatment options aimed at increasing survival and improving quality of life are urgent. From this perspective, this case report seems of special interest because the man described, although frail and multimorbid, successfully underwent major surgery. He was disease free and in good clinical status after 1 year. In conclusion, this case report shows that bladder melanoma, although rare, should be suspected at any age and may be amenable to radical treatment even in very old and frail individuals. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: AL, RG: study and data analyses. AL, RP, RAI: drafting the manuscript. AL, CT, GM, RAI: study design. All authors read and approved the final manuscript. Sponsor's Role: None.
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