Small cell carcinoma of the bladder: Review of pathogenesis, presentation, and management

Abstract

Small cell carcinoma of the bladder (SCCB) is a rare, aggressive malignancy that accounts for less than 1% of all bladder cancers. In this report, we highlight the clinical manifestations of SCCB (including epidemiology, cystoscopic and imaging findings), summarize insights into the molecular mechanisms underlying its pathophysiology, detail current methods of staging, review local and systemic treatment, and explore novel agents currently in clinical development. Most of the regimens used for SCCB treatment are extrapolated from small cell lung cancer, a more common cancer that shares the neuroendocrine and aggressive clinical phenotype of SCCB. Greater preclinical research can help to elucidate pertinent similarities and differences between SCCB and other neuroendocrine cancers as well as reveal new therapeutic targets, while increased participation of patients with SCCB in clinical trials may provide additional treatment options for patients with this aggressive cancer.

Keywords: high grade neuroendocrine carcinoma; rare genitourinary malignancy; small cell carcinoma of the bladder.

Figure 1.

Schematic depicting common presentation of small cell carcinoma intermixed with urothelial carcinoma.

Figure 2.

(A) H&E stain of a small cell carcinoma of the bladder. Tumor infiltrates the muscularis propria. Cells are small with scant cytoplasm and prominent nuclei. X200×. (B) H&E stain of tumor with mixed small cell carcinoma (less cytoplasm and high mitotic activity - yellow box) and urothelial carcinoma components (cytologic atypia and abundant cytoplasm - red box) X40×.

Figure 3.

Three different presentations of small cell carcinoma of the bladder. Images 1 and 2 demonstrate asymmetric bladder wall thickening (thin red arrows). Image 3 demonstrates a soft tissue mass (thick red arrow) protruding into the bladder lumen and contiguous asymmetric bladder wall thickening (thin red arrow).

Figure 4.

Axial CT images A and B are from a 49-yo male with SCCB. Image A depicts a large tumor mass encasing the right ureterovesical junction (short red arrows), including a right bladder wall diverticulum (long yellow arrow). A significantly decreased tumor burden (short red arrows) is noted on follow-up. Image B, 7 months post-treatment indicating a robust response to initial systemic treatment. Axial CT images C and D are from an 81-yo male with SCCB. Image C demonstrates tumor, manifested as a large filling defect, largely confined to a left lateral wall bladder diverticulum (red arrows). Image D, obtained after initial tumor resection but no interval systemic therapy, depicts a 3-month follow-up CT image demonstrating marked interval tumor growth (red arrows) into the bladder lumen, the bladder wall, and the left pelvis perivesicular soft tissues.

Figure 5.

82-yo M with metastatic small cell carcinoma of the bladder. 18F-FDG-PET maximal intensity projection and fused PET/CT images demonstrate multiple hypermetabolic liver metastases and a porta hepatis lymph node (arrows). Tracer contamination is noted at the anterior right chest due to Port-a-Cath injection.