Introduction

Adenocarcinoma is a malignant neoplasm derived from the urothelium with a histologically pure glandular phenotype. Primary adenocarcinoma of the urinary bladder is uncommon, accounting for 0.5%–2% of all malignant tumours. It affects adults, with a peak incidence in the sixth decade of life, and is more common in men.¹ The enteric type of adenocarcinoma is identical to its gastrointestinal counterpart. Our aim is to show a rare case of urinary bladder adenocarcinoma with bilateral ovaries metastases.

Clinical Case

This is a 26-year-old female patient who presented with a 6-month history of hematuria. A transurethral resection of the bladder was performed in another institution, the result of which showed a moderately differentiated adenocarcinoma. She had an upper gastrointestinal endoscopy and a colonoscopy without lesions.

Figure 1. CT scan showing a voluminous lesion.

A CT scan demonstrated a 50 # 40 # 80 mm, sessile, heterogeneous lesion in the bladder (Fig. 1), together with polylobulated formations with cystic and solid areas in the right hemiabdomen (130 # 80 # 30 mm) and left pelvis (180 # 110 # 200 mm), ascitic fluid, and pulmonary images compatible with secondary disease. Serum markers showed β-human chorionic gonadotropin <1 mIU/ml, alpha-fetoprotein <3.5 mg/ml, carcinoembryonic antigen 30.2 mg/ml, cancer antigen-125 40.9 U/ml, and cancer antigen 19-9 177.2 U/ml. An exploratory laparotomy was performed, showing peritoneal carcinomatosis and a large tumor mass in the ovaries (Figs. 2 and 3), bladder (Fig. 4), and greater omentum. Bilateral oophorectomy, omentectomy, cystectomy, and cutaneous ureterostomies were performed. The pathological findings were a moderately differentiated intestinal-type adenocarcinoma in the dome of the bladder, presence of cystic cystitis, and ovaries with infiltration of adenocarcinoma. Immunohistochemistry
showed negative pax8 and absence of β-catenin. These findings rule out ovarian and colorectal origin and favor bladder origin.

Figure 2. Polylobulated formations.

After 2 weeks, the patient was rehospitalized with severe metrorragia (hemoglobin dropped to 4.7 gm/dl) that needed a vaginal packing and was interpreted as hormonal deprivation. A speculoscopy was performed showing evidence of a clot in the distal third of the vagina. She was started on hormonal replacement therapy and did not repeat the leak.

The patient was scheduled by clinical oncology to receive oxaliplatin and capacitabine in the next weeks.

Discussion

Adenocarcinoma is an uncommon malignancy in the urinary bladder which may arise primarily in the bladder as well as secondarily from a number of other organs² and has a poor prognosis, largely because it is usually diagnosed at an advanced stage.³

Primary adenocarcinoma of the bladder is derived from the urothelium of the bladder but exhibits a pure glandular phenotype. It is most common in the sixth and seventh decade of life with male predominance and hematuria is the main symptom. Several risk factors have been described: 10% of all bladder cancers are adenocarcinomas in areas where schistosomiasis is endemic, chronic irritation, obstruction, cystocele, and endometriosis.

Primary bladder adenocarcinoma exhibits several different growth patterns, including enteric, mucinous, signet-ring cell, not otherwise specified, and mixed patterns. Urachal adenocarcinoma demonstrates similar histological features but it can be distinguished from bladder adenocarcinoma on careful pathological examination, and immunohistochemical study is valuable in identifying the origin of secondary adenocarcinomas.²

The criteria for making a diagnosis of urachal carcinoma includes tumor in the absence of cystitis cystica and cystitis glandularis, predominant invasion of the muscularis or deeper tissues with a sharp demarcation between the tumor and the surface bladder epithelium, the presence of urachal remnants within the tumor, extension of tumor into the bladder wall with involvement of the space of Rezius, the anterior abdominal wall or the umbilicus, and no evidence of primary neoplasm elsewhere.⁴ As our patient showed cystic cystitis in the biopsy, urachal origin was ruled out.

Figure 3. Left ovary.

Figure 4. Bladder.

Histologically, bladder adenocarcinoma exhibits various growth patterns: enteric (colonic or intestinal); mucinous; signet ring cell; not otherwise specified, and mixed patterns.¹ The enteric pattern is composed of intestinal-type glands with pseudostratified columnar cells and nuclear atypia, closely resembling colorectal adenocarcinoma. ­Colo­rectal adenocarcinoma is the most ­frequent metastasis in the bladder. It is important to differentiate primary bladder adenocarcinoma from secondary colorectal adenocarcinoma.

Primary bladder adenocarcinoma usually lacks GATA3 staining, rendering this stain useless in differential diagnosis from secondary colorectal adenocarcinoma. A panel of immunostains, including CK7, CK20, thrombomodulin, and beta-catenin, is of diagnostic value in differentiating primary bladder adenocarcinoma from secondary adenocarcinoma of colorectal origin. A nuclear β-catenin and CK20 positive stain favors colorectal origin, while primary bladder adenocarcinoma is usually positive for CK7 and shows membranous staining for β-catenin.^3,5 The immunohistochemistry in our patient’s biopsy favored bladder origin.

The best treatment is surgery with or without adjuvant radiation or chemotherapy. Radical or partial cystectomy with or without node dissection is the commonly used surgical procedure.¹ The most important prognostic factor is tumor stage.⁶

Finally, the importance of early diagnosis of this disease should be highlighted to improve the survival of the patients.