A rare case of primary clear cell adenocarcinoma of the urinary bladder
A rare case of primary clear cell adenocarcinoma is a rare form of bladder cancer, comprising only 2% of cases, with various histological patterns and levels of differentiation. Clear cell adenocarcinoma is the least common of these.
In contrast to the other subtypes, clear cell adenocarcinoma of the bladder has been shown to have a female predominance, and usually presents at the age of 60 years after being discovered incidentally on radiological and urological studies.
However, signs and symptoms such as visible and non-visible hematuria, and signs and symptoms of a urinary tract infection refractory to antibiotic treatment may occur and may provide clues to the diagnosis. Although imaging can reveal and characterize the lesion, definitive diagnosis requires cystoscopy with biopsy.
Treatment of bladder adenocarcinoma often requires surgical resection, with adjuvant chemotherapy used in a subset of patients.
We report a 79-year-old patient presenting with gross hematuria. Ultrasound was performed and showed a calcified mass on the dome of the bladder, which was confirmed by computerized tomography of the abdomen and pelvis.
Subsequent cystoscopy confirmed the diagnosis of clear-cell adenocarcinoma and the tumor was resected using a trans-urethral approach. Radical cystectomy with regional lymphadenectomy and adjuvant chemotherapy was used as the primary therapeutic modality
Primary clear cell adenocarcinoma (CCA) of the bladder is an extremely rare form of bladder cancer, accounting for less than 1% of cases . Its aggressive nature and limited understanding due to its rarity have contributed to a lack of comprehensive knowledge regarding its clinical behavior and optimal treatment strategies.
Urothelial carcinoma is the most common type of bladder tumor, whereas adenocarcinoma and squamous cell carcinoma are less common . Given its distinctive clinical, pathologic, and therapeutic features, CCA holds significant importance as a subject of investigation in the field of urologic oncology.
A 79-year-old woman presented to the outpatient clinic complaining of painless visible hematuria of unknown duration. She denied experiencing any other symptoms such as urgency, frequency, dysuria or constitutional symptoms. Her medical history includes diabetes mellitus, hypertension and ischemic heart disease. physical examination was unremarkable
Laboratory tests revealed a normal metabolic panel and a hemoglobin level of 11.5 g/dL (12.1 to 15.1 g/dL) with a creatinine level. Urine analysis showed no significant abnormalities except for the presence of many red blood cells. Radiological imaging including pelvic ultrasound revealed a polyp-like mass measuring approximately 1.4×1.4 cm on the right side of the dome of the bladder, which demonstrated punctate calcification and increased vascularity.
Subsequently, a contrast-enhanced computed tomography (CT) scan was performed, revealing a 1 cm prominently enlarged polypoid lesion radiating from the dome of the bladder (Figure 1). Another non-enhancing lesion was seen within the bladder, consisting of dense spaces, indicating a bladder clot. Cystoscopy confirmed the presence of a papillary mass with a smooth surface located in the dome of the bladder.
Transurethral resection of the tumor was performed with biopsy for further investigation.
Figure 1: CT scan of the urinary tract showing a polypoid lesion extending from the dome of the bladder.
CT scan of the urinary tract approximately 1 cm from the dome of the bladder.
(1) arterial phase – coronal segment; (2) Delayed phase – sagittal segment.
Postoperatively, the resected tissue sample was examined histologically and showed a highly vascularized tumor composed of cuboidal cells arranged in a tubulocystic pattern with large hyperchromatic nuclei (Figure 2). The neoplastic cells were positive for PAX8 and CK7 (focal) immunostains (Figure 3). GATA3 immunostain highlighted scattered immunoreactive cells, whereas P63 and CK20 immunostains were negative. These findings supported the diagnosis of bladder clear-cell adenocarcinoma.
Figure 2: Microscopic view of resected cystic neoplasm.
hematoxylin and eosin stain; Microscopic examination reveals the tumor to be composed of tubulocystic structures lined by cuboidal cells with abundant clear cytoplasm.
(1) low power microscopic view; (2) High power microscope.
Figure 3: Immunohistochemical staining of neoplastic cells.
The neoplastic cells displayed positivity for PAX8 and CK7 immunostains, as well as the presence of immunoreactive cells scattered with the GATA3 immunostain.
(1) PAX3 immunostain; (2) CK7 immunostain; (3) GATA3 immunostain.
Further management and staging of the patient’s tumor was performed. The stage of the tumor according to the TNM system was T2N1M0. Partial cystectomy was offered, however, the patient refused the procedure because of the strict follow-up required after surgery. In light of her age and medical history, radical cystectomy with regional lymphadenectomy was performed.
The urinary diversion method used was a percutaneous uretero-ureterostomy. The postoperative histopathology report revealed two positive lymph nodes. The patient was then given cisplatin-based chemotherapy. The patient was followed up six months and one year later with no clinical or radiological evidence of tumor recurrence.
Primary clear cell adenocarcinoma of the bladder is a rare tumor, with fewer than 50 cases documented in the literature . Of all subtypes, transitional cell carcinoma is the most common type of bladder neoplasm, accounting for 90% of cases, whereas squamous cell carcinoma and adenocarcinoma together make up approximately 9% of cases . Adenocarcinoma has several subtypes based on histological appearance, including clear cell, enteric
Adenocarcinoma not otherwise specified (NOS), signet ring cell, mucinous, hepatoid, and mixed subtypes . Furthermore, the female-to-male ratio in clear cell adenocarcinoma is 3:2, with a median age of presentation of approximately 60 years (range 19–83 years) .
Primary clear cell adenocarcinoma of the bladder is an extremely rare, aggressive and unfavorable neoplasm with a poor prognosis. The tumor often presents at an advanced stage, making it challenging to treat with a high probability of disease progression, metastasis, and recurrence.
The treatment of clear cell adenocarcinoma of the bladder often involves a multimodal approach, with surgical resection being the primary approach. This case demonstrates the importance of excluding clear cell adenocarcinoma in the differentiation of bladder malignancies and the importance of histopathological evaluation in guiding further management.