A Rare Case of Adenocarcinoma of the Urinary Bladder

ABSTRACT

Adenocarcinomas account for less than 2% of primary epithelial malignancies of the urinary bladder. The authors report a rare case of adenocarcinoma of the urinary bladder in a 65-year-old male patient who presented with frank hematuria. Extensive growth infiltration in paravesical fat planes was revealed by computed tomography imaging. The biopsy showed well-differentiated adenocarcinoma of the bladder with muscle involvement. The patient received bacille Calmette-Guérin (BCG) adjuvant therapy and later chemotherapy with poor response. Subsequently, he underwent total radical cystectomy with ileal conduit diversion. The aim of this report was to determine the anatomoclinical and therapeutic characteristics of this rare tumor.

KEYWORDS: Adenocarcinoma; Hematuria; Computed Tomography; Radical and Adjuvant BCG; Cystoprostectotomy

CORRESPONDENCE: Dr. Saleem M. Wani, Sher-I-Kashmir Institute of Medical Sciences, Department of Urology, Ward 4A, Srinagar, 190011, India ().

CITATION: Urotoday Int J. 2009 Dec;2(6). doi:110.3834/uij.1944-5784.2009.12.15

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INTRODUCTION

Bladder cancer (urothelial carcinoma) accounts for approximately 5% of all cancers and is the fifth most common cancer in industrialized countries [1]. The America Cancer Society estimates that 70,980 adults will be diagnosed with bladder cancer, leading to 14,330 adult deaths in the United States in 2009. Bladder cancer is the fourth most common cancer in males and ninth most common in females. In the United States, over 67,000 new cases are diagnosed per year [2] and over 350,000 cases are diagnosed world-wide [3].

Bladder tumors are grouped into several types according to the way they appear under a microscope. The 3 main types of cancers that affect the bladder are transitional cell carcinoma (TCC), squamous cell carcinoma, and adenocarcinoma. More than 95% of all muscle-invasive and muscle noninvasive bladder cancers in the United States and Europe are transitional cell carcinomas originating in the urothelium that forms the bladder lining [4]. Only about 1% to 2% of bladder cancers are adenocarcinomas. The cells share commonalities with gland-forming cells of intestinal cancers. Nearly all adenocarcinomas of the bladder are invasive [5]. In the bladder, the adenocarcinoma usually develops from sequential changes in the surface transitional epithelium initiated by chronic inflammation and cystitis.

CASE REPORT

A 65-year-old male from an urban population reported to the author's institute with frank hematuria. He was a retired policeman. The patient had previously diagnosed hypertension and diabetes mellitus. He was an active smoker for the last approximately 50 years. In 2004, he had an ischemic stroke for which he had been managed.

The patient had undergone transurethral resection (TUR) of the bladder in 2006. The histopathological report revealed transitional cell carcinoma (intermediate grade and stage pT1). He had received 6 cycles of intravesical bacille Calmette-Guérin (BCG) adjuvant immunotherapy (120 mg weekly for 6 weeks) immediately after the TUR was done. Hematuria had ceased and the patient was oligosymptomatic for 2 years. After histological confirmation of adenocarcinoma, gastrointestinal radiographic studies, rectosigmoidoscopy, and lung computed tomography (CT) were performed to exclude other possible extravesical primary lesions. The patient had no other kind of malignancy or family history of any type of cancer.

In 2008, the patient was readmitted with a chief complaint of hematuria. Cysto-panendoscopy (CPE) was performed. It revealed recurrence of the more aggressive broad-based sessile mass at the left posterior lateral wall of the bladder neck and another between the 6 o'clock and 7 o'clock positions. The patient's CT showed extensive left lateral wall bladder growth infiltrating paravesical fat planes, seminal vesicles, and the ureteric orifice. The left kidney showed grade-I hydronephrosis with a hydroureter, but there was no metastasis. The biopsy was taken and reported as well-differentiated adenocarcinoma, between stage pT2b-pT3 (Figure 1; Figure 2). The patient's other clinical parameters revealed anemia (hemoglobin = 8.8 g/dL) and neutrophilia, possibly due to chronic inflammation or infection.

Subsequently, the patient underwent radical cystoprostatectomy with ileal conduit diversion. The operative findings revealed growth in the bladder trigone, ureteric orifice, paravesical fat planes, and both seminal vesicles. Lymph nodes were present on the right and left obturator fossa. The surgery was followed by adjuvant chemotherapy. He had 4 cycles with the combination of cisplatin and gemcitabine every 21 days, which rendered him morbid at home. He died at home approximately 1 year later; the cause of death is unknown.

DISCUSSION

Adenocarcinoma is an uncommon tumor of the urinary bladder, accounting for 0.5% to 2.0% of all bladder malignancies [6,7]. However, it is the most commonly reported malignancy of the exstrophic bladder [8] as well as enterocystoplasty [9]. In areas where bilharzias are endemic the incidence of adenocarcinoma is higher, ranging from 5% to 11.4% [10,11,12]. It is believed that these tumors result from metaplastic changes of potentially unstable urothelium [13]. Peterson et al [14] reviewed the literature in 1985 and found 321 cases. Since 1955, various studies that included at least 10 cases have been reported in the English literature [15,16,17,18,19,20,21]. The largest was a 64-case series [22].

Adenocarcinoma of the bladder may represent primary metaplasia within a transitional cell carcinoma, an urachal carcinoma, a metastasis, or an adenocarcinoma arising from metaplastic glandular epithelium of a normal or exstrophic bladder. A primary vesicle adenocarcinoma arises de novo from transitional epithelium that has undergone glandular metaplasia. These lesions result from metaplasia of epithelial cell nests of Von Brunn and may be enhanced by urinary infection. Subsequent metaplasia of the urothelial lining of these cysts to columnar mucin-producing cells results in the production of cystitis glandularis, which is a premalignant lesion [23]. Chronic vesical irritation and infection are the predisposing causes of these changes. This explains, at least partly, the higher incidence of these tumors among patients with bilharzial cystitis.

Genetic studies to date have attempted to identify the spectrum of genetic changes that occur during urothelial transformation and to elucidate the natural history of bladder tumors with different clinical outcome. Several known oncogenes and tumor suppressor genes are mutated in bladder cancer. These include the genes encoding several key G1 checkpoint proteins (p16, p14ARF) retinoblastoma protein (Rb), p53, and cyclinD1, which are altered in many other tumor types. Several genetic changes may occur in bladder cancer, but a mutation in the fibroblast growth factor receptor 3 (FGFR3) gene is the most common and most specific genetic abnormality in bladder cancer. Interestingly, these mutations were associated with bladder tumors of low stage and grade [24]. This makes the FGFR3 mutation the first marker that can be used for diagnosis of noninvasive bladder tumors.

Genetic studies to date have attempted to identify the spectrum of genetic changes that occur during urothelial transformation and to elucidate the natural history of bladder tumors with different clinical outcome. Several known oncogenes and tumor suppressor genes are mutated in bladder cancer. These include the genes encoding several key G1 checkpoint proteins (p16, p14ARF) retinoblastoma protein (Rb), p53, and cyclinD1, which are altered in many other tumor types. Several genetic changes may occur in bladder cancer, but a mutation in the fibroblast growth factor receptor 3 (FGFR3) gene is the most common and most specific genetic abnormality in bladder cancer. Interestingly, these mutations were associated with bladder tumors of low stage and grade [24]. This makes the FGFR3 mutation the first marker that can be used for diagnosis of noninvasive bladder tumors.

A review of previous reports revealed that overall prognosis of adenocarcinoma of the bladder is poor when compared with TCC. The 5-year survival rate is approximately 18%. Tumor differentiation in adenocarcinoma is associated with survival; 5-year and 10-year survival rates for patients with moderately and well-differentiated tumors are 26% and 18%, respectively, compared with 13% and 5% for the poorly differentiated lesions [25].

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