病例報告：原發性惡性膀胱黑色素細胞瘤
李懿文1、康智雄1、宋明澤2
1高雄長庚紀念醫院泌尿科、2高雄長庚紀念醫院病理科
Cases Report: Primary malignant melanoma of the urinary bladder
I-Wen Lee1, Chih-Hsiung Kang1, Ming-Tse Sung2
1Department of Urology, Chang Gung Memorial Hospital, 2Department of Pathology, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Kaohsiung, Taiwan.
Introduction:
Primary melanoma of the genitourinary tract is extremely rare, accounting for only 0.2% of all melanomas. The urethra and the penis are the most common sites of origin within the urogenital tract, while urinary bladder and ureter are infrequent. Clinical presentation of bladder melanoma can be gross hematuria, dysuria or even no symptom. No standard treatment has been established for primary bladder melanoma to date. Surgical interventions such as trans urethral resection of the bladder tumor (TURBt), partial or radical cystectomy could be an option based on the entity of tumor stage. The adjuvant therapy with systemic/intravesical chemotherapy, interferon or immune checkpoint inhibitor were only reported by a few cases. Thus, we present a case with primary malignant melanoma of the urinary bladder and received adjuvant therapy with Pembrolizumab.
[Case history]
A 49-year-old Asian male with a past medical history of hypertension and recovered pulmonary tuberculosis. He presented to the local medical department with painless gross hematuria for 3 months and underwent bladder ultrasound that revealed intravesical mass lesion. The patient was referred to the Outpatient Department (OPD) of Urology in our hospital under the first impression of bladder cancer.
The physical examination did not show further positive findings. Urine cytology was negative for malignant cells. Renal echography showed no sign of hydronephrosis, stone or any suspicious mass lesion. Flexible cystography demonstrated a huge ovoid mass lesion over left anterior wall of the bladder (Fig.1). Subsequent Computed Tomography of Urography (CTU) discovered a urinary bladder mass (34 mm) attaching to the left anterior wall (Fig.2,3). The preoperative clinical stage is cT1-2N0Mx. After obtaining informed consent, we performed a TURBt with deep layer tissue harvest. During the procedure, a huge white ovoid tumor with blood clots covered over left posterior wall about 3.5 cm in diameter was resected with unipolar resectoscope. The patient discharged smoothly at the postoperative day (POD) 4 after removal of the Foley Catheter.
The immunohistochemical (IHC) staining of the resected specimen revealed the tumor cells are negative for epithelial and neuroendocrine markers, and positive for Vimentin, Melan-A (Fig.4) and S-100 (focally) (Fig.5), most likely a malignant melanoma. The final pathology was bladder malignant melanoma with muscularis propria invasion. The examination of skin pigment lesion by dermatologist was negative finding. The fluorodeoxyglucose (FDG) Positron Emission Tomography-Computed Tomography (PET-CT) was performed 50 days later after TUR. There was no definite FDG-avid tumor or metastasis can be detected in the body of the patient. The final diagnosis was primary malignant melanoma of bladder, pT2N0M0.
The patient currently received 3 doses of self-paid programmed cell death (PD-1) immune checkpoint inhibitor with Pembrolizumab 100mg for each dose since POD 10. The duration of each dose of Pembrolizumab were about 14 days. No subjective adverse event of Pembrolizumab was told by the patient. The patient underwent follow-up cystoscope one month later after Pembrolizumab use and we discovered a less than 0.5 cm sized bladder mass was located at dome with sessile appearance. The mass was biopsied and resected by biopsy forceps and unipolar resectoscope. Histopathology of resected or biopsied tissue all demonstrated acute and chronic inflammation, no recurrent bladder melanoma was found by far.
Discussion and Conclusion:
Primary bladder melanoma is extremely rare and its histogenesis is still unclear. In already published 40 cases of primary bladder melanoma from 1942 to 2021, very poor prognosis was found, and two-thirds of cases developed a metastatic disease within 3 years from first diagnosis. There is also no established guideline of treatment for this disease. TUR, partial or radical cystectomy are feasible surgical interventions and TUR is the most conservative treatment for this patient. Due to the high risk of recurrence and metastasis for bladder melanoma, adjuvant therapy was recommended for this patient. Pembrolizumab is a PD-1 immune checkpoint inhibitor and it is now used for treating advanced stage or metastatic cutaneous melanoma, non-small cell lung cancer (NSCLC) or advanced upper tract urothelial cancer (UTUC). The standard protocol of Pembrolizumab for cutaneous melanoma is 200mg every 3 weeks or 400mg every 6 weeks and the treatment continued for up to 24 months. However, the patient could only afford Pembrolizumab 100 mg every 2 weeks for 3 doses owing to personal financial situation. The cystoscope for follow up one month after first TUR revealed no recurrent or residual tumor. In conclusion, it is still a challenge to treat a patient with primary bladder melanoma and we wound like to provide this rare case and experience to better understand this disease in the future.