Primary Malignant Melanoma of the Bladder: A Rare Case Report in Asia and Review of the Literature.

BACKGROUND: Primary malignant melanoma (PMM) of the bladder is extremely rare and has a poor prognosis; just 40 cases of PMM of the bladder have been recorded in the literature. We described a case of PMM of the bladder, treatment, and a review of the literature because the recommended treatment choices are not widely known. CASE
PRESENTATION: An 80-year-old Thai female came in with a three-month history of pelvic pain and dysuria without extensive hematuria. She underwent transurethral excision of the bladder tumor and histologically reported malignant melanoma with no further primary sites of melanoma after computed tomography indicated a big heterogeneous enhancing mass on the posterior wall of the bladder. The patient eventually underwent anterior pelvic exenteration with ileal conduit, but metastatic disease occurred one year later.
CONCLUSION: Bladder melanoma has a fatal aggressive nature. Certain diagnostic features can be obtained through histopathological investigation, immunohistochemistry, clinical history, and endoscopic evaluation. Despite a wide range of treatments, people with PMM still have a bad prognosis.

Introduction

Primary malignant melanoma (PMM) of the bladder is extremely rare and has a poor prognosis; just 40 cases of PMM of the bladder have been recorded in the literature. We described a case of PMM of the bladder, treatment, and a review of the literature because the recommended treatment choices are not widely known.

Case Presentation

An 80-year-old Thai female was presented with pelvic pain and dysuria without gross hematuria for 3 months. After medical history and complete physical examination were obtained. CT abdomen was done and revealed a large heterogeneous enhancing mass 5.3×6.2 cm in size with internal calcification in the urinary bladder (Figure 1). Cystoscopy revealed a large necrotic mass that could not be identified as the ureteric orifice or the bladder base and a transurethral resection of the bladder tumor was performed. The pathological report revealed malignant melanoma spindle cell variant. Hematoxylin and eosin (H&E) staining was performed on tissue sections and S100 (+), HMB-45 (+), and Melan-A (+) were detected by immunohistochemistry (Figure 2). Complete investigations were performed to exclude other primary sites of melanoma. Dermatologic, otorhinolaryngologic, ophthalmologic and proctologic examinations were unremarkable, and upper gastrointestinal endoscopy and colonoscopy were performed and showed normal findings. Computed tomography (CT) scans of the abdomen, chest, brain and bone scans found no metastasis or other suspected primary lesions. Primary malignant melanoma of the bladder was diagnosed, and a multidisciplinary team approach suggested no further adjuvant therapy was needed because of the patient’s age, comorbidity and poor prognosis despite treatment. The patient agreed to take the risk and had an anterior pelvic exenteration with an ileal conduit performed. The pathology revealed malignant melanoma and invasion of the bladder serosa’s posterior wall, but all resection margins of the pelvic lymph nodes were negative for metastasis. After a postoperative period of one year, a computerized tomography scan showed new cardiophrenic lymph node enlargement without local recurrence (Figure 3). Tissue biopsy was performed and reported for metastasis malignant melanoma. The patient refused a metastasectomy and thus missed the follow-up.

Figure 1

Axial (A) and sagittal (B) CT scans of the whole abdomen included the pelvis with IV contrast injection demonstrated a large heterogenous enhancing mass, 5.3×6.2 cm in size with internal calcification in the urinary bladder.

Figure 2

The histological appearance of the urinary bladder melanoma tissue was composed of solid nests and groups of atypical, poorly differentiated, highly mitotically active cells with prominent nucleoli: HE x10 (A); HE x100 (B); HE x400 (C); immunohistochemistry indicating positive reaction to HMB-45 (x100) (D); Melan-A(x100) (E) and S-100 (x100) (F).

Figure 3

Axial (A) and coronal (B) CT scan of the abdomen/pelvis with IV contrast injection, demonstrated a new left cardiophrenic lymph node enlargement.

Discussion and Conclusions

Primary malignant melanoma is very rare in the genitourinary tract, and extremely rare in the bladder. We reported a case of PMM of the bladder, with previously reported 39 cases worldwide as in Table 1. The most common presenting symptom is hematuria. The diagnosis of bladder malignant melanoma requires cystoscopy and tissue biopsy. Cystoscopy revealed a dark pigmented tumor.1,2 Melanoma-like features such as melanin pigment, nests of pleomorphic cells with macronuclei, and prominent nucleoli were observed during the pathologic examination. Typically, immunohistochemical evaluations demonstrate positivity for S-100, HMB-45, MART-1/Melan-A, Tyrosinase and MITF.7 A patient history and physical examination of the skin and were also evaluated for visceral primary sites to distinguish primary from secondary melanomas of the bladder comprehensively.5

Table 1

Primary Malignant Melanomas of Bladder Reported in Literature

No.	Year	Reference	Gender	Age	Management	Follow Up (Months)	Status
1	1942	Wheelock12	F	67	Partial cystectomy	36	Died
2	1962	Su and Prince13	F	61	None	2	Died
3	1976	Ainsworth et al8	F	65	Radical cystectomy	17	Alive
4	1980	Willis et al14	F	57	Radical cystectomy	36	Died
5	1982	Anichkov and Nikonov15	M	48	Radical cystectomy	12	Died
6	1982	Anichkov and Nikonov15	M	46	Radical cystectomy	3	Alive
7	1985	Ironside et al16	M	56	None	8	Died
8	1988	Goldschmidt et al17	F	53	Radical cystectomy	7	Died
9	1988	Goldschmidt et al17	F	56	none	6	Alive
10	1989	Philippe et al18	M	77	TURBT	NR	NR
11	1992	Van Ahlen et al19	M	81	Radical cystectomy, radiotherapy, interferon-alpha	24	Died
12	1992	Lund et al20	F	81	Local excision, radiotherapy, chemotherapy	15	Alive
13	1992	Kojima et al21	F	63	Chemotherapy	18	Died
14	1993	Lange-Welker et al22	M	75	Radical cystectomy	3	Died
15	1993	Mourad et al23	M	34	Radical cystectomy	12	Alive
16	1993	Niederberger and Lome24	M	53	Radical cystectomy	18	Alive
17	1995	De Torres et al25	M	44	Radical cystectomy	14	Died
18	1999	Tainio et al26	M	52	TURBT	8	Died
19	2000	Garcia Montes et al27	F	44	TURBT	144	alive
20	2001	Khalbuss et al28	F	82	Radiotherapy plus cystectomy	16	died
21	2002	Hsu and Hsu29	M	73	TURBT with intravesical Bacillus Calmette–Guérin and re TURBT at 2-7-9 months	16	alive
22	2005	Baudet et al30	F	7	Partial cystectomy	84	alive
23	2006	Pacella et al1	M	82	TURBT	9	Died
24	2011	Sundersingh et al31	M	56	Radical cystectomy with pelvic excision four months later	10	Alive
25	2011	El Ammari et al32	M	71	TURBT	5	Died
26	2013	Truong et al33	F	84	TURBT plus ipilimumab	NR	NR
27	2014	Sayar et al34	M	70	TURBT	2	Died
28	2016	Khan et al35	M	78	No	NR	Died
29	2016	Laudisio et al36	M	81	Radical cystectomy	12	Alive
30	2017	Otto et al37	M	52	TURBT plus interferon/dacarbazine	18	Died
31	2017	Buscarini et al38	M	81	TURBT	NR	NR
32	2018	Osorio et al39	M	58	Partial cystectomy	4	Died
33	2018	Barillaro et al3	M	72	Radical cystectomy plus nivolumab	16	Alive
34	2019	Bumbu et al4	M	80	TURBT	6	Died
35	2019	Kirigin et al6	M	87	TURBT	0.5	Died
36	2019	Chaus et al40	F	27	Robotic Partial Cystectomy and pembrolizumab	24	Alive
37	2020	Rubio et al41	F	39	TURBT with temozolomide	1.5	Died
38	2021	Rapisarda et al42	M	74	TURBT plus intravesical Bacillus Calmette–Guérin	6	Alive
39	2021	Snajdar et al43	F	78	Radical cystectomy with ileal conduit and bilateral pelvic lymph node dissection	14	Died
40	2021	Bejrananda et al	F	80	Anterior pelvic exenteration	12	Alive

In 1976, Ainsworth established the correct definition of bladder melanoma, including careful physical examination, including the skin with Wood’s light, together with a detailed history to exclude cutaneous melanoma, pattern of recurrence consistent with primary melanoma of the urinary bladder, histologically proved primary atypical melanocytes and also, especially, exclusion of visceral melanoma following complete evaluation.8 Malignant melanoma’s histogenesis in the urinary tract, particularly in the bladder, is unknown. There are currently two theories: one supports the idea that melanoblasts migrate from the neural cusps into the mesenchyme during embryogenesis, but they can also migrate to ectopic places, such as the developing urinary tract, where they remain inactive for a long time before transforming into malignant cells under the influence of some local factors. Another theory is that urothelial cells produced from urothelial stem cells may develop into malignant melanocytes.4 Transurethral resection of a bladder tumor, partial or radical cystectomy, radiotherapy, chemotherapy and immunotherapy are the treatment options. However, initial treatment for organ-confined tumors involves surgery for both partial and radical cystectomy with lymph node resection. If there are contraindications for surgery, chemotherapy for systemic therapy is not proper, and radiotherapy and immunotherapy with interferon-α can be administered.

Overall, reports of the treatment outcomes of patients with this tumor are still poor, despite the variety of therapies available. Most patients die due to widespread metastases within 3 years after the initial diagnosis.5,9,10 This was the case for our patient, who was diagnosed at a localized stage and received anterior pelvic exenteration, but still developed a metastatic disease within 1 year after treatment. According to a literature review, PMM of the bladder has a poor prognosis for many reasons, advanced stage as presenting symptom, difficult to diagnose by confirmed pathology and aggressiveness, with two-thirds of patients developing metastatic disease within three years.5,6 In addition, there is a lack of data suggesting the best treatment options. It appears that tumor stage and mitotic activity can help in prognosis and some authors suggest that identifying if the malignancy contains a BRAF-activating mutation for therapeutic targeting may be of benefit4,5 and previous report of BRAF mutations has shown in melanoma about 60% of cases.11 Others have suggested immunotherapy after a radical cystectomy with nivolumab as a successful treatment.3

In conclusion, primary malignant melanoma of the bladder is a very rare disease. Complete investigation to distinguish primary from secondary disease is very important. The choice of treatments should be based on overall prognosis, the patient’s factors and aggressiveness if disease. Despite the variety of therapies, the prognosis of patients with this tumor is still poor. However, local control with aggressive surgery has still shown benefits in survival.