Microscopic description:

The tumor shows two cell populations. One type of cells have increased nuclear to cytoplasmic ratio, salt and pepper chromatin and prominent nucleoli. Adjacent to that, there is another population of cells with eosinophilic cytoplasm and nuclear atypia consistent with urothelial carcinoma.

IHC show positive synaptophysin for one population of cells and positive GATA3, CK7 and CK 20 for another population of cells. These features are consistent with diagnosis of urothelial carcinoma with small cell/neuroendocrine features and conventional features.


Small cell neuroendocrine carcinoma as a primary tumour of bladder may be pure, although at least half of cases in most series are mixed with non‐small cell components, such as urothelial or glandular elements. Primary SCCB is a rare and aggressive tumour with poor prognosis.

Approximately 400 cases have been reported in the literature.

The mean age of presentation is 67.8 years and there is a striking male predisposition—5:1.

More than 90% of patients present with hematuria; rare cases present with paraneoplastic syndromes including hypercalcemia, Cushing’s syndrome and sensory neuropathy.

Molecular genetic evidence suggests a common clonal evidence for small-cell carcinoma and coexistent urothelial carcinoma.

The tumor usually has a patternless pattern of diffuse growth, although occasionally and focally some nesting may be present. The cells have scant cytoplasm and consequently show nuclear crowding and molding. Nucleoli are inconspicuous and the chromatin is finely stippled.

Tumors are positive for chromogranin A and synaptophysin (greater than 60% of cases) and frequently show a dot-like positivity for pan-cytokeratin. TTF-1 may be positive in almost 40% of the cases.68 Other reported markers include p53 (75%), c-kit (27%) and EGFR (27%). Cytokeratin CAM5.2 is present in both urothelial carcinoma and small-cell carcinoma, but the pattern of staining is punctate along the membrane in the first case, and perinuclear in the latter.

Differential diagnosis includes lymphoma, lymphoepithelial-like carcinoma from the lung, metastases from another neuroendocrine tumor (lung), neuroendocrine carcinoma of the prostate infiltrating the bladder, rhabdomyosarcoma (in children).


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