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Unexpected Long Survival in Primary Malignant Melanoma of the Male Urethra

A case of primary malignant melanoma of the urethra in a 60-year-old male is presented. Despite multiple adverse prognostic factors and against expectations, after a follow-up of 5.5 years he is still alive.


Introduction
Primary malignant melanoma of the urethra is rare, representing less than 1% of all melanomas [1,2], which means that it is often misdiagnosed and treatment can be delayed. Given its poor prognosis, early diagnosis is essential, and clinicians need to include it in their differential diagnosis when working up a patient with genitourinary complaints.
A working knowledge of the varied presentations associated with primary urethral melanoma as well as its histopathological features is an important component to early diagnosis and effective treatment. Many adverse prognostic factors exist such as age ≥60 years, thickness ≥3.5 mm, ulceration and diameter ≥15 mm [3,4]. However, the presence or absence of lymph node metastasis is the most significant prognostic factor for survival, as survival rates are approximately halved by the presence of nodal metastasis [2,4].
Individual management according to the clinical presentation has to be based on extrapolation of evidence for other melanoma treatments. Due to the low occurrence of urethral melanoma, the optimum therapy has not been established in the urological field, and surgery remains the mainstay of primary therapy; adjuvant local-regional and systemic therapies are needed [5][6][7].
According to the patient's history, there was a continuous urethral discharge, predominantly after sexual intercourse, known since September 2003. At that time he was empirically treated for prostatitis with Permixon (a compound lipid extract from the fruit of the American dwarf palm tree, Serenoa repens) and Nimesulid (non-steroidal anti-inflammatory drug). Subsequently, the patient was lost for follow-up. Anamnestically, he drank one liter of wine and smoked half a package of cigarettes per day.
In March 2004, a smear-test of the urethra was negative and cystourethroscopy revealed red, slightly bleeding lesions in the distal urethra involving the colliculus seminalis. Antibiotic therapy (ciprofloxacin 250 mg orally twice a day for 12 days) and biopsy were recommended, which were declined by the patient.
Again he failed to attend follow-up appointments until 6 months later. At that time (in September 2004), he was willing to undergo a transurethral biopsy because of increasing symptoms. Histopathological examination of the biopsy specimens revealed a solid, poorly differentiated neoplasia with large pleomorphic, fusiform and anaplastic cells, which were high-grade according to the WHO's classification and highly suspicious for malignant melanoma. The diagnosis was supported by immunohistochemical staining with a marker for melanoma (anti-Vimentin+, ProteinS-100+, HMB-45+, MelanA+; AE1/AE3+, CD20+). Atypical pigmented melanocytic cells were also noted in urinary cytologic samples.
The metastatic workup, including physical examination, PET total body scan, total body CT-scan and bone scintigraphy showed palpable bilateral clinically pathological inguinal lymph nodes (2.5 × 2 cm in diameter, round), with some lymph nodes in the mediastinum (pretracheal and near the bifurcation of the trachea) and bilateral axillae. A PET-scan revealed higher metabolic activity in the left inguinal region, and the patient was referred to a tertiary referral center for deep bilateral ilioinguinal, external iliac and obturator lymph node dissection in December 2004. One in 10 ilioinguinal lymph nodes showed metastatic disease involving the lymph node capsule, and 9 iliac and obturator lymph nodes showed reactive changes on the left side. On the right side, 13 ilioinguinal lymph nodes and 6 external iliac lymph nodes showed reactive changes. Postoperative complications included wound infection and chronic lymphedema, which were treated with antibiotics and lymph drainage therapy.
A PET-scan in April 2005 showed a high activity in the liver, raising suspicion of hepatic metastatic disease in segment VIII. This was confirmed by ultrasonographic examination and CT-scan (diameter of 4.6 × 3.8 × 4.5 cm).
Cystourethroscopy was performed in May 2005 because of a weak urinary stream and showed an urethral recurrence situated in the distal part of the urethra. The patient underwent distal urethral resection of the lesion, which was histologically a relapse of the primary melanoma that was confined to the mucosa.

Discussion
Primary malignant melanomas of the genitourinary system are rare, representing less than 1% of all melanomas [1,2]. Regarding urethral melanoma, mucosal sites are known to be associated with aggressive behavior, and from the onset of symptoms to the patient's seeking medical care, there is often a considerable delay [8]. Therefore, biopsy of all pigmented urethral lesions is recommended [2].
The urethra, especially the distal urethra, including fossa navicularis and urethral meatus, is the most common location of melanomas of the urinary tract, and about 30% of patients already have metastasis at the time of diagnosis [7] and have reached dangerous limits (e.g., depth of invasion or thickness at the time of diagnosis) [9]. Adverse prognostic factors are known, such as thickness (significant cutoff ≥3.5 mm), ulceration and diameter (significant cutoff ≥15 mm) [3,4].
Cancers of the anterior urethra preferentially drain into superficial inguinal lymph nodes. Those of the posterior urethra generally drain into pelvic lymphatic channels [7]. However, the presence or absence of lymph node metastasis is the most significant prognostic factor for survival, as survival rates are approximately halved by the presence of nodal metastasis [2,4].
The prognosis of malignant melanoma of the urethra is poor (2-year-survival is about 63% and 5-year-survival is 31% [3]) because of delayed diagnosis and treatment initiation.
Because of the low occurrence of malignant melanoma in the urethra, no therapy has been established in the urologic field. Prevention of disease progression by surgery alone is not successful and requires effective postoperative adjuvant therapy [6,10], such as lymph node dissection [2,11], immunochemotherapy [12,13] or adjuvant radiotherapy.