Journal of Cancer Research and Therapeutics, Vol. 5, No. 2, April-June, 2009, pp. 133-136
Small cell carcinoma of the urinary bladder: A case report and review of the literature
Ismaili Nabil, Ghanem Samia, Mellas Nawfel, Afqir Said, Taleb Meriem, Amrani Meryem, Gamra Lamia, Errihani Hassan
Department of Medical Oncology, National Institute of Oncology, Rabat
Code Number: cr09034
AbstractSmall cell carcinoma of the bladder (SCCB) is extremely rare. In this paper, we present a case of metastatic SCCB managed by chemotherapy and we would provide a brief review of the epidemiology, clinical features, diagnosis, pathologic features, staging, treatment, and prognosis of SCCB. A 52-year-old man was admitted with signs and symptoms suggestive of a bladder cancer. Computed tomography of the pelvis and abdomen showed a large tumor at the right bladder wall, measuring 10 cm in diameter, and a multinodular liver disease. Diagnosis of small cell carcinoma was established from the histological study of the transurethral resection of the bladder tumor. The patient received 12 cycles of platinum-based chemotherapy with a good partial response of bladder tumor and liver metastasis. The patient is still alive, 18 months after diagnosis.
Keywords: Bladder cancer, small cell carcinoma, chemotherapy
IntroductionSmall cell carcinoma of the bladder (SCCB) is extremely rare and accounts for less than 0.7% of all cancers arising from the bladder. , The first case was described in 1981 by Cramer et al .  SCCBs are often, but not always neuroendocrine epithelial tumors, associated with a more aggressive behavior and poorer prognosis than transitional cell bladder carcinomas, and mostly diagnosed at advanced stages. The diagnosis of SCCB is based on the criteria established by the WHO classification system, which are identical to those for small cell lung cancer (SCLC). We present a case of metastatic SCCB managed by chemotherapy and a brief review of the epidemiology, clinical features, diagnosis, pathologic features, staging, treatment, and prognosis of SCCB.
Case ReportA 52-year-old smoker man was admitted to our hospital with a 3-month history of right pelvic pain, multiples episodes of gross hematuria, dysuria, and extreme fatigue. The performance status (PS) was equal to 1. There was no mass palpable in the pelvis area. The ganglionic areas were free from the disease. A computed tomography (CT) scan of the pelvis showed a heavily tissular polycyclic tumor at the right bladder wall with intraluminal and extravesical extension without enlargement of the pelvic lymph nodes [Figure - 1]. The largest diameter of the tumor measured 10 cm. The cystoscopical examination revealed a vegetative tumor. CT of the abdomen showed a multinodular liver disease and hydronephrosis of the right kidney [Figure - 2]. The transurethral resection of the bladder tumor (TURBT) removed 20 g of the cancerous tissue. A pathological examination of the specimen revealed, through light microscopy, a tumoral process comprising sheets of noncohesive small cells. Cells were round, and the mitotic count was high. Nuclear chromatin was finely granular and evenly distributed. Numerous cells were in apoptosis [Figure - 3]. The tumor invaded the muscle of the bladder wall (pT2) [Figure - 4]. Transitional carcinomatous components were present. Immunohistochemistry showed that the tumor expressed synaptophysin [Figure - 5] and neuron-specific enolase (NSE). CT scan of the lung and bone scan were normal. The patient received 12 cycles of platinum-based chemotherapy. The chemotherapy consisted of intravenous cisplatin at 75 mg/m 2 on day 1 plus intravenous etoposide at 120 mg/m 2 on day 1, 2, and 3, repeated every 3 weeks. After twelve cycles, the clinical evaluation showed a significant improvement in symptoms. The performance status was 0. Hematuria and pain disappeared with the treatment. A CT scan of the abdomen and pelvis showed an excellent partial response of the bladder tumor and liver metastasis [Figure - 6] and [Figure - 7]. The patient is still alive, 18 months after diagnosis (TURBT).
Bladder cancer is the second most common urologic malignancy. In the western countries, it is the fourth most common cancer in men and the eighth most common cancer in women.  Up to 95% of urinary bladder tumors are of epithelial origin, from which 90% are urothelial neoplasms.  Primary SCCB is a rare disease that accounts for less than 0.7% of all bladder cancers. , The disease was initially described in 1981 by Cramer et al .  Since then, 550 cases of SCCB have been diagnosed. 
The diagnosis of SCCB is based on the criteria established by the WHO classification system, which are identical to those for small cell lung cancer (SCLC). Histological studies of SCCB showed sheets of uniformly small, round, mitotically active cells with overlapping nuclei and evenly distributed chromatin, lacking prominent nucleoli. Nuclear molding, tumor necrosis, and crush artifact were commonly seen.  Immunostaining analysis showed that cancerous cells expressed markers of neuroendocrine differentiation, including chromogranin, NSE (neural adhesion molecule) and synaptophysin. ,,, In the majority of reported series, authors showed a higher incidence of mixed small cell carcinoma. ,, However, in another study we showed a higher incidence of pure SCCB.  In the present case, the patient had mixed histology.
The mean age at diagnosis was 67.8 (20-91) years.  Painless gross hematuria was the most common presenting symptom in SCCB due to a large polypoid, ulcerated and deeply invasive tumor. ,, Dysuria and irritative symptoms had been reported as the second most common symptoms. , Urethral obstruction, weight loss, urinary tract infection, and ectopic ACTH secretion had been reported occasionally. ,
Diagnosis of SCCB was most often accomplished via cys-toscopy and transurethral biopsy. Immunocytochemi-cal staining is helpful if light microscopy is not defini-tive. ,,, A CT scan of the abdomen and pelvis, bone scan, and chest radiograph at the time of diagnosis of SCCB, and CT scan of the brain in the presence of neurologic signs or symptoms were warranted.  The sites of metastasis were the retroperitoneal lymph nodes, the liver, the lung, the bone, and the brain. ,, Metastasis from SCCB to the thyroid gland was reported.  For staging, Bex and Pan proposed to define both limited and extensive SCCB as analogous to small cell lung carcinoma. ,
Because SCCB is rare, and in the absence of randomized controlled trials, there is no standard treatment. SCCB tends to behave aggressively, with up to 25% of patients presenting metastatic disease and up to two-thirds developing distant recurrence. Chemotherapy plays a prominent role in the management of these tumors. In a multi-institutional review of 64 patients with a muscle invasive disease, a multivariate analysis indicated that neither chemotherapy, nor radiation, nor surgery had any impact on overall survival.  The poor prognosis of patients treated by radical cystoprostatectomy alone reported by Sved et al .  supports the use of combination modality treatments. Nevertheless, in a multi-institutional retrospective study, patients with bladder transitional cell carcinoma and small cell carcinoma undergoing radical cystectomy share similar stage-specific clinical outcomes.  A retrospective study of 46 patients treated at the M. D. Anderson Cancer Centre has reported a 5-year survival of 78% for patients receiving neoadjuvant chemotherapy followed by cystectomy, versus 36% for patients undergoing cystectomy alone.  In the Mayo Clinic Study, the authors have proposed radical cystectomy for patients with locally advanced disease and adjuvant treatment for patients with stage III and VI (M0) disease.  Bastus et al . have reported on a series of five patients with locally advanced disease treated with sequential chemoradiotherapy. Four patients had long-term disease-free survival and overall survival.  Others authors expressed a realistic optimism and acknowledged a potential for long-term survival in patients with limited stage small cell cancer of the bladder treated with a combination of chemotherapy and sequential radiotherapy; the survival rate was 70% at 2 years and 44% at 5 years.  Theses results were recently confirmed by Bex et al . Median overall survival for the 17 patients treated by sequential chemoradiotherapy was equal to 32.5 months.  For stage IV disease, the chemotherapy remain the mainstay treatment. The M. D. Anderson Cancer Centre recommend the protocols used in the neuroendocrine tumors for both histological types: Pure small cell carcinoma and mixed small cell carcinoma of the bladder. , Other authors confirmed the efficacy of platinum-based chemotherapy. ,, Our patient had metastatic liver disease at diagnosis and achieved a good partial response after the end of the twelve cycles of cisplatine plus etoposide chemotherapy, and is still alive, 18 months after diagnosis.
The prognosis of SCCB is poor. The overall 5-year survival rate in all stages is 19% (16 to 25%). , The pure small cell histology was shown to have poorer outcome than the mixed small cell histology. ,
ConclusionPrimary SCCB is a very rare and aggressive tumor. In the absence of prospective study, the best treatment for this tumor cannot be established for certain. For localized disease, a combined treatment including surgery, chemotherapy, and radiotherapy, is necessary for achieving long-term disease-free and overall survival. For metastatic disease, the chemotherapy using a platinum agent is the mainstay treatment.
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