Pathologic Findings in Small Cell Bladder Carcinoma
Updated: Jun 06, 2019
Author: Zhong Jiang, MD; Chief Editor: Liang Cheng, MD
Overview of Small Cell Bladder Cancer Pathology
Small cell carcinoma of the urinary bladder is a poorly differentiated, aggressive neoplasm[1, 2, 3] that accounts for less than 1% of all bladder tumors.[4] Men are affected more than women, typically in the the seventh to eighth decades, and hematuria is the most common presenting symptom.[5]
All small cell carcinomas of the urinary system identified thus far have been located in the urinary bladder, most commonly in the dome and vesical lateral wall.[6] There is no established standard treatment modality for this neoplasm, and outcomes are generally poor.[4, 7, 8]
For more information, see Bladder Cancer, as well as Pathologic Findings in Squamous Cell Bladder Carcinoma and Cystoscopy in Bladder Cancer.
Gross and Microscopic Findings
Gross findings
Small cell carcinoma of the urinary bladder usually has a polypoid or nodular appearance and often has an ulcerated surface. Gross examination reveals a solid tumor mass that originates from the mucosa and often penetrates deeply into the bladder wall.
Microscopic findings
Sixty-eight percent of small cell carcinoma of the urinary bladder cases are mixed with classic urothelial carcinomas or adenocarcinomas of the bladder.[9] The histologic features of small cell carcinoma are the same as those in other organs. The tumor is made of sheets and nests of loosely cohesive, small, round or oval cells with very scant cytoplasm (see the image below).
Small cell carcinoma of the bladder. The tumor is made of sheets and nests of loosely cohesive, small, round or oval cells with very scant cytoplasm.
The tumor cell nuclei are hyperchromatic with coarsely granular chromatin. Nuclei molding can be seen. Mitosis is present and may be frequent. Nucleoli are absent or small. Tumor necrosis is often present. Urinary cytology often reveals single and loosely cohesive clusters of tumor cells with typical small cell carcinoma morphology.
Immunohistochemistry
Neuroendocrine markers, such as chromogranin A, synaptophysin, CD56, and neuronal specific enolase,[10] are often focal or diffusely positive for small cell bladder tumors by immunohistochemistry, and they are useful tools to help establish a diagnosis. (See the image below.)
Small cell carcinoma of the bladder. Neuroendocrine markers, such as chromogranin A, synaptophysin, CD56, and neuronal specific enolase, are often focal or diffusely positive for this tumor by immunohistochemical method and are useful to help establish a diagnosis.
However, a definitive diagnosis can be rendered based on morphology alone; even immunohistochemistry may fail to demonstrate expression of these markers. A cocktail of cytokeratin markers is often nonreactive, but low molecular cytokeratin, CAM5-2, and epithelial membrane antigen (EMA) are mostly positive.[11, 12]
Genomic Alterations
As in small cell carcinoma of other organs, that of the bladder tumor cell exhibits abundant genomic aberrations. Typically, every tumor cell has more than 10 in number. The most frequent changes include deletions of 10q, 4q, 5q, and 13q and gains of 8q, 5p, 6p, and 20q. It is also suggested that acquisitions of genomic alterations in typical invasive urothelial carcinoma lead to the development of small cell bladder carcinoma. Genomic DNA amplifications are also found in many loci where oncogenes are located.[13]
More recent investigations indicate that patterns of gene expression in small cell bladder carcinoma are associated with distinct clinical phenotypes (ie, from more indolent to aggressive disease).[14] Overexpression of DLL3 mRNA and protein frequently occurs and correlates with shorter overall survival.
Questions & Answers
Author
Zhong Jiang, MD Professor, Department of Pathology, University of Massachusetts, Memorial Medical Center
Zhong Jiang, MD is a member of the following medical societies: College of American Pathologists, United States and Canadian Academy of Pathology, International Society of Urological Pathology
Disclosure: Nothing to disclose.
Chief Editor
Liang Cheng, MD Virgil H Moon Professor of Pathology and Laboratory Medicine, Professor of Urology, Director of Molecular Diagnostics and Molecular Pathology Laboratory, Indiana University School of Medicine; Chief, Genitourinary Pathology Service, Indiana University Health
Liang Cheng, MD is a member of the following medical societies: American Association for Cancer Research, American Urological Association, Arthur Purdy Stout Society, College of American Pathologists, International Society of Urological Pathology, United States and Canadian Academy of Pathology
Disclosure: Nothing to disclose.
Additional Contributors
Di Lu, MD Clinical Associate Professor, Department of Pathology, University of Massachusetts Medical School
Disclosure: Nothing to disclose.
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