While metastatic melanoma to the genitourinary tract outside the kidneys is a rare entity, the literature includes cases of clinically apparent metastasis to kidneys (4), ureters (5, 6), bladder (3), urethra, testes (7) and spermatic cord (8). On autopsy studies melanoma deposits to the urinary tract are common and found in up to 45% of patients with metastatic melanoma (3). Isolated metastatic disease to the genitourinary tract is rare, and the presence of urinary tract metastases is commonly associated with metastases in multiple distant sites (9).  

The presentation can range from being completely asymptomatic and detected incidentally on imaging to microscopic hematuria, painless macroscopic hematuria, dysuria (10), as well as a palpable lump. There are no distinct imaging features and suspicion of metastatic disease is usually based on the background diagnosis of melanoma.

Historically, before the era of molecular and immunotherapy the prognosis of metastatic melanoma was poor. Molecular (BRAF-targeted) therapy and immune checkpoint inhibition has changed medical management of patients with metastatic melanoma and several retrospective studies suggest favorable survival of the metastatic melanoma patients who underwent metastasectomy along with systemic therapy (11, 12, 13), particularly increased median overall survival if there has been response to targeted molecular therapy or immunotherapy (2). This increases the importance of identifying metastases on routine follow-up. Unfortunately, no randomised trial data has been published yet, and the data from existing retrospective studies does not distinguish melanoma metastases in the urinary tract from other sites, making the prognostication in these patients difficult. Multidisciplinary and case-specific approach  is required in most cases. The SUMMIST trial is underway and aims to evaluate if surgical removal of residual disease adds survival benefit in stage IV melanoma patients with partial response or stable disease after a minimum of 9 months of first-line immunotherapy (14).

There are different treatment options available for the different anatomical sites. This can span from observation or transurethral resection to more radical approaches such as penectomy and cystectomy. The aggressiveness of surgical management needs to be made in the context of presence of metastatic disease elsewhere and the wider prognosis (15).

Please find below the case summary for each patient:

Patient 1:

A patient in his 40s presented initially with a left flank melanoma 7 years prior. He had a positive sentinel lymph node and subsequent axillary node clearance. There was a recurrence at the site of the scar a year later. He was treated with nivolumab and ipilimumab after this. A second melanoma recurrence occurred in the left flank while on treatment.

7 years after initial diagnosis he presented with an 8-week history of what was described as hematuria, but was small volumes of bloody discharging from the tip of the penis and penile pain. A focally pigmented mid penile urethral lesion was demonstrated during cystoscopy. Biopsy was positive for melanoma markers consistent with metastasis. The immunophenotype showed positive for melanoma markers S100, HMB45 and Sox 10. Negative for cytokeratin MNF116.

He proceeded to an elective urethrectomy and formation of perineal urethrostomy. He recovered well and was discharged with suprapubic and urethral catheters.

Fig 1: Patient 1: Saggital T1 and B1400 DWI images through the penis, following administration of Caverjet (Alprostadil). There are two distinct lesions within the urethra. The high T1 is in keeping with melanin. There was high DWI signal with corresponding restriction on the ADC map.

Fig 2: Patient 1: Axial images through the lesion show high T1 signal and intermediate T2 signal within the lesion. The thin rim of high T2 signal indicates its intra-urethral location.

Fig 3: Patient 1: FDG Pet scan showing avidity within the penile lesion

Patient 2:

A  male patient in his 60s initially presented for investigation a shoulder cutaneous lesion, which was subsequently diagnosed as melanoma. The CT at the time of diagnosis showed a polypoid bladder lesion. The patient was asymptomatic. There was also a single brain metastasis at the time of diagnosis.

Treatment involved a flexible cystoscopy and laser enucleation of bladder the tumor. He also received stereotactic radiosurgery to frontal lobe brain metastasis. Initially medical management involved ipilimumab and nivolumab. He was then moved to single agent nivolumab. 2 years after initial diagnosis he remains alive with no evidence of recurrence on subsequent CT imaging.

Fig 4: Patient 2: CT scan performed for staging of scapula region melanoma. This identified a polypoid lesion within the bladder, thought to be a TCC. Histology proved it to be a melanoma metastasis.

Fig 5: Patient 2: The lesion can be seen to extend 1.3cm into the bladder lumen.

Patient 3:

A male patient in his 70s presented initially with a cutanous malignant melanoma that was resected. The breslow thickness was 1.7mm, Stage 1B. 3 Years later he developed metastatic melanoma to brain and was put on pembrolizumab immunotherapy. At the same time he had an US for macroscopic haematuria on a background of lower urinary tract symptoms. This identified a polypoid lesion. He proceeded to transurethral resection. At cystoscopy a solid pedunculated lesion on the anterior bladder wall was identified. It was resected to the base of the lesion and biopsies were taken. Mitomycin was instilled at the same time.  Biopsy result showed focally necrotic sheets of poorly differentiated epithelioid cells with pleomorphic nuclei, forming of vague papillary architecture. Positive for S100 and HMB45. Negative for MNF116, CK 7 and CK 20, neuroendocrine markers and lymphoid markers CD45. Features in keeping with metastatic malignant melanoma. 

He has remained on immunotherapy and is alive with stable disease 6 years after initial presentation. 

Fig 6: Patient 3: US imaging of the bladder showed a hyperechoic polypoid lesion projecting into the bladder. This was performed for painless macroscopic haematuria on a background of long standing lower urinary tract symptoms.

Fig 7: Patient 3: Doppler US image through the bladder. The lesion showed no doppler signal.

Fig 8: Patient 3: The subsequent CT with urographic phase contrast did not clearly demonstrate the lesion. It is possibly only visible in retrospect when correlated with the cystoscopy report.

Patient 4:

A female patient in her 70s presented with primary urethral malignant melanoma 2014. She proceeded to radical cysto-urethrectomy, total abdominal hysterectomy, bilateral salpingo-oophorectomy, vulvectomy and vulvovaginal reconstruction that year.  5 years later she had a vulvo-vaginal recurrence treated with ipilimumab and nivolumab. She developed treatment associated colitis. There was progressive vulvovaginal disease requiring 36Gy to the vulva, 6 years after initial diagnosis. She went on to have a pelvic nodal recurrence 1 year later and was treated with Dacarbazine. She developed brain metastasis treated with stereotactic radiosurgery, 9 years after initial diagnosis.

Fig 9: Patient 4: T2 STIR, T1 and T2 images showing an intraurethral intermediate T1 and T2 signal lesion, which was later identified to be a primary urethral melanoma deposit.

Patient 5:

A male patient in his 60s initially presented with a melanoma on his right elbow, which was excised. 3 years later he developed hemoptysis, and a CT scan showed pulmonary metastases. He was initially treated with ipilimumab but did not respond. 1 year later a CT scan showed pulmonary, large quantity intra-abdominal and subcutaneous disease. He was subsequently commenced on pembrolizumab. He attended the US department with a new right spermatic cord lesion and was imaged with contrast enhanced US. He passed away 7 years after the initial diagnosis.

Fig 10: Patient 5: US imaging showed an echo poor nodule lying immediately lateral to the spermatic cord at the base of the scrotum. No internal flow on doppler imaging was demonstrated.

Fig 11: Patient 5: CEUS showed peripheral enhancement, but no central enhancement as seen on the SMI doppler imaging.