Endometriosis-associated primary clear cell adenocarcinoma of the urinary bladder: A case report and literature review

Abstract

Primary clear cell adenocarcinoma (CCA) of the urinary bladder is a rare and aggressive malignancy. Few reports in the literature describe this presentation, as associated with malignant transformation of endometriosis. This case highlights the complex etiology of this variant of CCA, initially diagnosed using comprehensive imaging and genetic analysis, and subsequently confirmed through extensive surgical intervention and chemotherapy.

1 Introduction

Bladder cancer is one of the most common types of cancer in the United States, representing 4.2 % of all new cancer cases, and predominantly manifests as urothelial carcinoma in over 90 % of cases. ^, . Notably, about 25 % of these urothelial carcinoma cases exhibit variant histological features, which have been thoroughly documented in existing literature. . However, clear cell adenocarcinoma (CCA) of the urinary bladder remains a notably rare histological subtype of bladder cancer, often affecting females. ^, . The pathogenesis of CCA is thought to involve Mullerian elements within the bladder, rendering it histo-genetically similar to cancers of the female genital tract, or as a unique expression of urothelial carcinoma with gland differentiation. ^, . CCA has emerged as the malignant transformation of endometriosis with the bladder being involved in less than 1 % of extragonadal endometriosis. . Literature on CCA stemming specifically from bladder endometriosis is scant, with only a handful of published cases. Here, we present a case of a 50-year-old female patient with irregular bleeding found to have a bladder mass concerning for primary CCA of the urinary bladder, possibly secondary to malignant transformation of endometriosis.

2 Case presentation

This patient is a 50-year-old female with no pertinent medical history who presented for her annual gynecologic examination in July 2023 with complaints of irregular bleeding. Her last menstrual period had been in September 2020, and she had normal, routine Papanicolou test results to date. A transvaginal ultrasound (TVUS) ( Fig. 1 A) revealed a fibroid uterus with a suspicious, lobulated bladder mass with color flow, which required a referral to a urologist. A computed tomography of the abdomen/pelvis (CT A/P) ( Fig. 1 B) showed a large enhancing pedunculated mass along the posterior wall of the bladder measuring up to 4.6 x 7.8 cm. Radiologist assessment suggested a fat plane between the bladder and uterus but no discernible fat plane between the bladder and vagina, indicating possible extension of the mass directly into the vagina. Bilateral pelvic sidewall lymph nodes measuring up to 1.2 cm were also noted.

Due to clinical symptoms of gross hematuria and imaging findings, the patient underwent cystoscopy and transurethral resection of the bladder tumor (TURBT) with fulguration in November 2023. The surgery revealed an extremely vascular, pedunculated tumor with multiple lobulations involving half of the bladder. Pathological examination confirmed CCA with extensive infiltration of the subepithelial connective tissue but no muscularis propria invasion. Genetic analysis of the tumor identified mutations in several oncogenes including KRAS, PIK3CA, ARID1A, SDHA, KMT2C, DDX11, BRCA1, and CHEK2. After her procedure, the patient was discharged and followed up in the outpatient clinic.

At the discretion of the urologic oncologist, multiple imaging studies were completed to determine the extent of potential vaginal invasion and lymphadenopathy. A positron emission tomography (PET)/CT scan showed F-18-fluorodeoxyglucose (FDG)-avid retroperitoneal and right pelvic lymph nodes highly suspicious for metastatic disease ( Fig. 2 A). A magnetic resonance imaging (MRI) of the pelvis with and without contrast showed pelvic lymphadenopathy and a fibroid uterus, with an indeterminate complex pelvic mass measuring 4.1× 2.5 cm anterior to the uterus and to the right of the midline ( Fig. 2 B). This lesion was noted to be stable compared to prior CT scans dating back to August 2015, suggesting a benign finding. Given the rarity and aggressive nature of CCA of the bladder, it determined a neoadjuvant chemotherapy regimen would not be appropriate for the patient’s disease.

In February 2024, the patient underwent robotic-assisted laparoscopic radical cystectomy with ileal conduit creation, anterior vaginectomy, bilateral extended lymphadenectomy, total urethrectomy, transureteroureterostomy, total hysterectomy, and bilateral salpingo-oophorectomy. Powder burn lesions in the pelvis, specifically on the posterior bladder wall, consistent with endometriosis were noted. 6 × 80 mm bilateral ureteral stents and a pelvic drain were placed. Postoperative recovery followed the enhanced recovery after surgery (ERAS) protocol with the patient maintaining stable vital signs and demonstrating good recovery indicators, such as bowel function resumption and adequate urine output through her ureterostomy. JP creatinine on postoperative day three was consistent with serum and removed. The final pathology ( Fig. 3 ) confirmed CCA predominantly involving the bladder trigone, with complete excision and negative margins (pT1). Seven of the 22 lymph nodes were positive for metastatic carcinoma (pN2). Endometriosis in the posterior urinary bladder wall was also noted, where it was fibrously adhered to the uterus. The patient began adjuvant chemotherapy with carboplatin, paclitaxel, and pembrolizumab, completing six cycles without evidence of recurrence or metastasis at six months post-surgery.