Insights from a whole cystectomy specimen--association of primary small cell carcinoma of the bladder with transitional cell carcinoma in situ.

Small cell carcinoma of the urinary bladder is a rare entity known as an aggressive tumor. As it is rarely associated with transitional cell carcinoma in situ but more commonly with invasive transitional cell carcinoma, its origin is not well understood. We report a case of small cell carcinoma with coexisting transitional cell carcinoma in situ, where histologic mapping and parallel immunohistochemical and molecular analyses (TP53 mutation analyses, loss of heterozygosity) were performed. Immunohistochemical characterization (synaptophysin, thyroid transcription factor-1, chromogranin A, neuron specific enolase, CD56, CK, CK7, CK20, CD44v6, and p53) emphasized the morphology. Identical point mutations of TP53 were identified in invasive small cell carcinoma and transitional cell carcinoma in situ. No loss of heterozygosity of microsatellite markers D3S3050, D9S303, D9S304, D9S171, D9S775, D9S1748, D9S1751, D17S786, D17S918, and TP53alu was found in either component. We provide, for the first time, molecular evidence for the development of invasive small cell carcinoma out of transitional cell carcinoma in situ.