Bladder, ureter & renal pelvis
Urothelial carcinoma-invasive

Topic Completed: 1 October 2015

Minor changes: 15 January 2021

Copyright: 2003-2021,, Inc.

PubMed Search: Urothelial carcinoma nested variant renal pelvis

Related Topic: Urothelial carcinoma of renal pelvis

Nicole K. Andeen, M.D.
Maria Tretiakova, M.D., Ph.D.
Page views in 2020: 1,987
Page views in 2021 to date: 190
Cite this page: Andeen NK, Tretiakova M. Nested. website. Accessed January 24th, 2021.
Definition / general
  • Morphologic variant of urothelial carcinoma characterized by unusually bland, nested pattern of invasion but with clinical outcomes similar to conventional invasive high grade urothelial carcinoma (Arch Pathol Lab Med 2007;131:1725)
Essential features
  • Cytologically bland nested pattern that could be difficult to distinguish from Florid von Brunn's nests, but more irregular and often deeply invasive
  • Clinical outcomes are similar to invasive high grade urothelial carcinoma
  • Given the rarity of nested variant of urothelial carcinoma of the renal pelvis and its morphologic similarity to the bladder site, this review includes pertinent data and images from bladder, where appropriate
  • Renal pelvis, ureter
Clinical features
  • Hematuria
Prognostic factors
  • Data in bladder demonstrates outcomes similar to conventional invasive high grade urothelial carcinoma (Mod Pathol 2003;16:1289)
Case reports
Gross description
  • Thickened, irregular renal pelvis with or without associated papillary component
Gross images

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Grey white tumor

Microscopic (histologic) description
  • Anastomosing, irregularly sized nests lacking cytoarchitectural orientation to overlying urothelium, and with more irregular projections into stroma, particularly at deep aspect (Mod Pathol 2009;22:S96)
  • The overlying urothelium is usually unremarkable
  • Cytologically bland, usually with focal atypia
  • Central lumens, which may contain necrotic cellular debris (Stanford University - Surgical Pathology Criteria)
  • Stroma may be normal or desmoplastic
  • A component of conventional urothelial carcinoma is present in 64% of cases (Hum Pathol 2010;41:163)
Microscopic (histologic) images

Contributed by Nicole K. Andeen, M.D. and Maria Tretiakova, M.D., Ph.D.

Irregularly sized nests of urothelial cells lacking cytoarchitectural orientation to overlying urothelium and with variable cytologic atypia; some nests show central necrotic debris

Positive stains
Negative stains
Molecular / cytogenetics description
  • Loss of p27, a cyclin dependent kinase inhibitor (p53 independent), may dictate the behavior: loss of p27 has been associated with increased proliferation and progression of disease (Mod Pathol 2003;16:1289)
Differential diagnosis
  • Florid von Brunn's nests: are relatively round and evenly spaced with uniform linear border at base, vs. nested carcinoma which has anastomosing, smaller irregularly sized nests lacking orientation to overlying urothelium, and more irregular projections into stroma and muscle invasion (Mod Pathol 2009;22:S96)
    • Wide variability in staining for Ki67, p53, p27 and CK20 seen in both Florid von Brunn's nests and nested variant of urothelial carcinoma (Am J Surg Pathol 2003;27:1243)
  • Inverted papilloma: has more cytoarchitectural organization within nests, cells maintain peripheral palisading
  • Nephrogenic adenoma: may be nested, tubular and have irregular stromal interface but nests are composed of only a single layer of cuboidal or flattened cells and is more likely to contain other architectural patterns (cystic, papillary) and have surrounding stromal edema and inflammatory infiltrate (Mod Pathol 2009;22:S96)
  • Paraganglioma and carcinoid: characteristic vascular pattern and chromatin features, positive for neuroendocrine markers
Additional references
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