Bladder & urothelial tract

Urothelial carcinoma - invasive


Last author update: 12 July 2021
Last staff update: 4 October 2023

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PubMed Search: Bladder nested urothelial carcinoma

See Also: Urothelial carcinoma of renal pelvis

Megan L. Brown, M.D.
Maria Tretiakova, M.D., Ph.D.
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Cite this page: Brown ML, Tretiakova M. Nested. website. Accessed February 26th, 2024.
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 (Virchows Arch 2014;465:199)
Essential features
  • Cytologically bland nested pattern that could be difficult to distinguish from florid von Brunn nests; particularly challenging in superficial biopsies
  • Often deeply invasive with increasing irregularity in the deeper portion
  • Clinical outcomes are similar to invasive high grade urothelial carcinoma of matched clinical stage
ICD coding
  • Location based ICD-10 coding:
    • Renal pelvis, including pelviureteric junction and renal calyces
      • C65.1 - malignant neoplasm of right renal pelvis
      • C65.2 - malignant neoplasm of left renal pelvis
      • C65.9 - malignant neoplasm of unspecified renal pelvis
    • Ureter, including ureteric orifice of bladder
      • C66.1 - malignant neoplasm of right ureter
      • C66.2 - malignant neoplasm of left ureter
      • C66.9 - malignant neoplasm of unspecified ureter
    • Bladder
      • C67.0 - malignant neoplasm of trigone of bladder
      • C67.1 - malignant neoplasm of dome of bladder
      • C67.2 - malignant neoplasm of lateral wall of bladder
      • C67.3 - malignant neoplasm of anterior wall of bladder
      • C67.4 - malignant neoplasm of posterior wall of bladder
      • C67.5 - malignant neoplasm of bladder neck
      • C67.6 - malignant neoplasm of ureteric orifice
      • C67.7 - malignant neoplasm of urachus
      • C67.8 - malignant neoplasm of overlapping sites of bladder
      • C67.9 - malignant neoplasm of bladder, unspecified
    • Other, unspecified urinary organs
      • C68.0 - malignant neoplasm of urethra
      • C68.1 - malignant neoplasm of paraurethral glands
      • C68.8 - malignant neoplasm of overlapping sites of urinary organs
      • C68.9 - malignant neoplasm of urinary organ, unspecified
  • Renal pelvis, ureter, bladder
  • No specific risk factors to development of nested variant reported
  • General risks factors for urothelial carcinoma: smoking, aromatic amine exposure, arsenic exposure
Clinical features
  • Cystoscopy
  • CT scan
  • MRI
  • Hematuria
Radiology description
  • Bladder with irregular wall thickening and little protrusion into the bladder lumen with gradual contrast enhancement on dynamic contrast enhanced MRI (Abdom Radiol (NY) 2020;45:2279)
Prognostic factors
Case reports
Gross description
  • Thickened, irregular renal pelvis with or without associated papillary component
Gross images

Images hosted on other servers:
Missing Image

Gray-white tumor

Frozen section description
  • Not typically diagnosed on frozen section
Microscopic (histologic) description
Microscopic (histologic) images

Contributed by Megan L. Brown, M.D., Maria Tretiakova, M.D., Ph.D. and @SueEPig on Twitter
von Brunn-like appearance

von Brunn-like appearance

Irregular projections and occasional lumens

Irregular projections and occasional lumens

Muscularis propria

Invasion into muscularis propria

Large nested carcinoma

Large nested carcinoma

Nested urothelial carcinoma Nested urothelial carcinoma Nested urothelial carcinoma Nested urothelial carcinoma

Nested urothelial carcinoma

Positive stains
Negative stains
Molecular / cytogenetics description
Sample pathology report
  • Bladder, transurethral resection:
    • High grade urothelial carcinoma with nested growth (60%) (see comment)
    • Comment: Invasive of lamina propria (pT1)
    • Angiolymphatic invasion absent
    • Muscularis propria present, no tumor
Differential diagnosis
  • Florid von Brunn nests:
    • Relatively round and evenly spaced with uniform linear border at base versus 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 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
Board review style question #1
Nested variant of urothelial carcinoma is most commonly identified in which patients?

  1. Women aged 30 - 50
  2. Women older than 80
  3. Men older than 60
  4. Men younger than 50
  5. Pediatric populations (< 18)
Board review style answer #1
C. Men older than 60. The nested variant of urothelial carcinoma is most commonly identified in men older than 60 with a similar occurrence to that of classic urothelial carcinoma.

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Reference: Nested urothelial carcinoma
Board review style question #2

A 65 year old man with flank pain and hematuria presents with bladder wall thickening on MRI. Transurethral resection of bladder tumor is performed (see above image). What is the diagnosis?

  1. Florid von Brunn nests
  2. Inverted papilloma
  3. Nephrogenic adenoma
  4. Urothelial carcinoma, nested variant
Board review style answer #2
D. Urothelial carcinoma, nested variant

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Reference: Nested urothelial carcinoma
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