Small cell neuroendocrine carcinoma of the urinary bladder: an immunohistochemical and ultrastructural evaluation of 3 cases with a review of the literature

Small cell carcinoma with the histological appearance of pulmonary small cell carcinoma is a rare tumour in the urinary bladder. In previous case reports the neuroendocrine nature of small cell bladder carcinoma has been accepted, but on review the evidence for true neuroendocrine differentiation appears unsatisfactory. In this study the histological, immunohistochemical and ultrastructural characteristics of three cases of small cell carcinoma of the urinary bladder are described. Ultrastructurally, the cytoplasm of all three tumours contained neurosecretory-type granules and each of the tumours demonstrated positive immunoreaction for two or more neuroendocrine markers, from a panel including neuron-specific enolase, chromogranin A, Leu-7, bombesin and synaptophysin. Although the combination of ultrastructural and immunohistochemical examination obviously offers the strongest evidence in establishing neuroendocrine differentiation, it is argued that immunohistochemistry alone may also yield important information in demonstrating a neuroendocrine nature, provided that at least neuron-specific enolase and synaptophysin are included as markers. The clinical relevance of identifying neuroendocrine differentiation in small cell bladder carcinoma is suggested by the favourable response to combination chemotherapy in two of our cases.