2021-03 / January 18
Contributors: Marcelo Luis Pereira de Souza Filho, Carlos Alberto dos Santos Silva, Daniel Athanazio

A man in his 80s presented with gross hematuria for the past three months. He underwent transurethral resection of a bladder tumor.


1. What is the correct diagnosis?

A. Urothelial carcinoma and small cell carcinoma

B. Prostatic adenocarcinoma and small cell carcinoma

C. Primary bladder adenocarcinoma and small cell carcinoma

D. Metastatic mixed neuroendocrine non-neuroendocrine neoplasms

1. Urothelial carcinoma and small cell carcinoma

Both urothelial and prostate carcinoma may coexist with small cell neuroendocrine carcinoma. In this case, a predominant component of small cell carcinoma coexisted with an epithelial neoplasm with villoglandular and cribriform morphology. Advanced age and cribriform morphology are suggested as indicatives of prostate adenocarcinoma, which may show papillary or pseudopapillary features. In this scenario, pathologists should have a low threshold to perform immunostains. In this case, despite cribriform morphology, the immunoprofile was supportive of urothelial carcinoma with glandular differentiation. As shown in the figures above, the villoglandular component was reactive for cytokeratins 7 and 20, and GATA3 while the solid tumor was reactive only for CD56. The entire tumor was negative for PSA and CDX2.

Based on current CAP, ICCR and NCCN guidelines, any amount of small cell carcinoma component within a urothelial carcinoma qualifies the whole tumor as small cell carcinoma since this morphology will guide treatment.

1. Athanazio DA, de Souza MF, Amaral MEP. Carcinomas in the bladder with papillary and pseudopapillary morphology – not always urothelial. Surg Exp Pathol 3, 25 (2020).
2. Gordetsky J, Epstein JI. Pseudopapillary features in prostatic adenocarcinoma mimicking urothelial carcinoma: a diagnostic pitfall. Am J Surg Pathol. 2014 Jul;38(7):941-5.
3. Lim M, Adsay NV, Grignon D, Osunkoya AO (2009) Urothelial carcinoma with villoglandular differentiation: a study of 14 cases. Mod Pathol 22: 1280-1286.
4. Miller JS, Epstein JI (2009) Noninvasive urothelial carcinoma of the bladder with glandular differentiation: report of 24 cases. Am J Surg Pathol 33:1241-1248.
5. Roy S, Smith MA, Cieply KM, Acquafondata MB, Parwani AV. Primary bladder adenocarcinoma versus metastatic colorectal adenocarcinoma: a persisting diagnostic challenge. Diagn Pathol. 2012 Nov 2;7:151.
6. International Collaboration on Cancer Reporting (ICCR) – Carcinoma of the Bladder Histopathology Reporting Guide Cystectomy, Cystoprostatectomy and Diverticulectomy Specimen.
7. National Comprehensive Cancer Network Clinical (NCCN) Practice Guidelines in Oncology – Bladder Cancer. [].
8. Paner GP, Zhou M, Srigley JR et al. College of American Pathologists. Protocol for the examination of specimens from patients with carcinoma of the urinary bladder, 2020

Marcelo Luis Pereira de Souza Filho
Hospital Universit√°rio Professor Edgard Santos
Salvador, Bahia, Brazil

Carlos Alberto dos Santos Silva
Professor of Medicine, Federal University of Bahia
Salvador, Bahia, Brazil

Daniel Athanazio
Professor of Medicine, Federal University of Bahia
Imagepat, Laboratory of Pathology
Salvador, Bahia, Brazil


Bladder; urothelial carcinoma; divergent differentiation