Bladder & ureters
Urothelial carcinoma-invasive
Urothelial carcinoma with glandular differentiation

Topic Completed: 1 December 2014

Minor changes: 26 June 2019

Copyright: 2003-2019,, Inc.

PubMed Search: Urothelial carcinoma with glandular differentiation[title]

Rugvedita Parakh, M.D.
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Cite this page: Parakh R. Urothelial carcinoma with glandular differentiation. website. Accessed May 29th, 2020.
Definition / general
  • Predominant features of urothelial carcinoma, but with distinct glands (i.e. a mixed tumor)
  • Similar to urothelial carcinoma with gland-like lumens (not a WHO diagnosis, but considered by AFIP Series 4 to be the same as microcystic variant)
Clinical features
  • 7% of urothelial carcinomas have squamous or glandular differentiation, which is associated with higher stage at presentation (Int Urol Nephrol 2001;33:631, Int Urol Nephrol 2007;39:803)
  • Note: mucoid cytoplasmic inclusions are present in up to 37% of urothelial carcinomas, often high grade, but this is not considered to represent glandular differentiation (Hum Pathol 1992;23:860)
  • Report as urothelial carcinoma with glandular differentiation, and estimate the percentage of the glandular component
  • 50% of noninvasive tumors with glandular differentiation became invasive, but none developed adenocarcinoma (Am J Surg Pathol 2009;33:1241)
Microscopic (histologic) description
  • Urothelial carcinoma with focal true glands with goblet cells or colonic epithelium and mucin
  • Distinction between true glands with glandular lumens (with colonic epithelium or goblet cells) and gland-like lumens (lacking these cells) appears to have no clinical significance if overlying pattern is clearly urothelial
Microscopic (histologic) images

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Fig 1D: H&E

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Fig 4: CK7+

Positive stains
Negative stains
Differential diagnosis
  • Adenocarcinoma: no urothelial component; tumor of pure glandular components with glands lined by goblet cells or intestinal cells, not flattened urothelial-like cells; usually deeply invasive, high grade
  • Colonic adenocarcinoma: CK7-, villin+ (Arch Pathol Lab Med 2002;126:1057)
  • Cystitis cystica / glandularis: glands in lamina propria lined by columnar, cuboidal or intestinal epithelium; no atypia, no mitotic figures, no necrosis
  • M├╝llerianosis: presence of 2 of 3 (endocervicosis, endometriosis or endosalpingiosis); no atypia, no mitotic figures
  • Nephrogenic metaplasia / adenoma: small hollow tubules similar to mesonephric tubules, usually lined by single layer of bland cuboidal or hobnail cells, surrounding eosinophilic or basophilic secretions; no/minimal atypia or mitotic figures; no true invasion
  • Urothelial carcinoma, microcystic variant: not true glands, lumens are lined by flattened or columnar epithelium, not goblet cells or colonic epithelium; lumens contain granular debris or necrotic cells, occasionally mucin
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