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Other carcinomas

Small cell carcinoma

Reviewer: Nat Pernick, M.D., PathologyOutlines.com, Inc. (see Reviewers page)
Revised: 30 June 2011, last major update June 2011
Copyright: (c) 2003-2011, PathologyOutlines.com, Inc.


● Rare bladder tumor resembling counterparts in lung and elsewhere
● A type of poorly differentiated carcinoma
● A morphologic diagnosis - neuroendocrine differentiation is not required


● Also called poorly differentiated small cell carcinoma


● Rare, 0.5 to 1.0% of all bladder malignancies
● No age, sex or clinical differences from usual type urothelial carcinoma


● In at least some cases, arises from urothelial carcinoma in situ (Hum Pathol 2008;39:1258)
● May arise from totipotent stem cells in submucosa (Semin Oncol 2007;34:15)

Clinical features

● Pure or with urothelial carcinoma or other carcinomas (diagnose as small cell if any appreciable component, because prognosis is affected by presence of small cell component)
● Occasionally associated with hypercalcemia and ectopic ACTH production
● Most cases are advanced at diagnosis; 65% have metastases at or soon after diagnosis
● Very aggressive with rapid development of metastases to regional nodes, liver, bones and peritoneal cavity
● Median survival 11 months in recent study (Cancer 2011 May 12 [Epub ahead of print]); presence of distant metastases may be most important prognostic factor
● 5 year survival of 8-16% (Cancer 2004;101:957)
● Rarely co-exists with tumor cells exhibiting skeletal muscle differentiation (Am J Surg Pathol 2000;24:223)

Case reports

● 52 year old man (J Cancer Res Ther 2009;5:133)
● 55 year old woman with tumor secreting ACTH (Hum Pathol 1985;16:313)
● 73 year old man with combined small cell carcinoma and high grade papillary urothelial carcinoma (Arch Pathol Lab Med 2004;128:1055)


● Radical cystectomy unless metastatic disease is present - then need systemic therapy (Cancer 2005;103:1172)
● High response rate to chemotherapy (similar to that used for lung tumors), but overall prognosis is still poor (BJU Int 2009;103:747)

Gross description

● Usually large, polypoid mass anywhere in bladder

Micro description

● Tumors with any appreciable small cell component should be classified as small cell carcinoma
● Resembles small cell carcinoma of lung
● Loosely cohesive sheets or nests of small to intermediate sized cells with minimal cytoplasm, hyperchromatic nuclei, stippled or coarsely granular chromatin, indistinct nucleoli and no nuclear overlapping
● Mitotic activity and necrosis are common
● Often co-exists with other forms of in situ or invasive carcinoma

Micro images

Sheets of small cells with scant cytoplasm in lamina propria with unremarkable urothelium


Ill defined nests of cells

Invasion of muscularis propria

Cords or nests of cells with molding, scant cytoplasm, hyperchromatic nuclei with fine chromatin and mitotic activity

Low power shows uniform cells, suggesting lymphoma or sarcoma

High power shows numerous mitoses and lack of prominent nucleoli

With low grade papillary urothelial carcinoma #1, #2, #3


Mixed small cell and classic urothelial carcinoma shows synaptophysin+ in small cell component


Cytology description

● Numerous tumor cells in loose clusters, cells are larger than lymphocytes, have scant cytoplasm, eccentric nuclei with evenly dispersed but coarse chromatin, indistinct nucleoli

Cytology images


Mixed small cell and undifferentiated urothelial carcinoma


Positive stains

● EMA, CAM 5.2 (dot-like perinuclear pattern)
● Usually neuron-specific enolase, synaptophysin (frequently has neuroendocrine features, Am J Surg Pathol 1987;11:606)
● Variable c-kit (27%, Mod Pathol 2005;18:320), chromogranin (weak/focal if present), CK7 (Hum Pathol 2005;36:718), TTF1+ (Mod Pathol 2000;13:238)
Note: neuroendocrine stains are considered of questionable value by many since this is a morphologic diagnosis

Negative stains

● CEA, CK20
● HPV (Am J Surg Pathol 2004;28:901)

Electron microscopy description

● Few dense core granules

Differential diagnosis

High grade urothelial carcinoma: by definition, should lack any appreciable small cell component; p63+, synaptophysin- (Appl Immunohistochem Mol Morphol 2011 May 25 [Epub ahead of print])
Lymphoma: tumor cells are smaller, positive for CD45, B or T cell markers
Metastatic small cell carcinoma: usually no associated urothelial carcinoma, need clinical information

Additional references


End of Bladder > Other carcinomas > Small cell carcinoma

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