Bladder, ureter & renal pelvis
Urothelial neoplasms-noninvasive
Noninvasive papillary urothelial carcinoma high grade

Topic Completed: 1 December 2014

Minor changes: 21 January 2021

Copyright: 2003-2021,, Inc.

PubMed Search: High grade papillary urothelial carcinoma[title]

Rugvedita Parakh, M.D.
Page views in 2020: 13,162
Page views in 2021 to date: 716
Cite this page: Parakh R. Noninvasive papillary urothelial carcinoma high grade. website. Accessed January 24th, 2021.
Definition / general
  • A neoplasm with urothelium lining papillary fronds, a predominant disorderly pattern and moderate to marked architectural and cytologic atypia
ICD coding
  • ICD-O: 8130/2 or /3
  • Usually ages 50+, male (M:F = 6-8:1)
Clinical features
  • Gross or microscopic hematuria is common
  • May invade adjacent structures or regional lymph nodes
  • Late dissemination to liver, lung, marrow
  • Grade 3 of 4 in Ash system
Prognostic factors
  • High rate (15-40%) of progression to invasive disease
  • Prognosis is better for pTa (noninvasive) than pT1 (invasive into lamina propria, Am J Clin Pathol 2010;133:788)
  • Transurethral resection and fulguration of visible tumor
  • Radical cystectomy, variable chemotherapy or radiation therapy
  • In men, radical therapy includes cystoprostatectomy and excision of seminar vesicles
  • In women, radical therapy includes excision of uterus, tubes, ovaries, anterior vagina, urethra
  • Ileal conduit is fashioned into a new bladder with reimplantation of ureters
Clinical images

AFIP images


Gross description
  • Sessile or cauliflower-like with necrosis and ulceration
  • Exophytic papillary growth
Microscopic (histologic) description
  • Predominantly disorderly appearance (loss of linear orientation perpendicular to basement membrane) at low power with prominent architectural and cytologic abnormalities
  • Often have complex papillary architecture showing anastomosis of papillae and confluence on low-power examination
  • Often cellular dyscohesion and denudation
  • More nuclear pleomorphism / anaplasia than low grade, clumped chromatin, irregular nuclear contour, prominent nucleoli, irregularly clustered cells with crowding and overlapping, disorganized epithelium, mitotic figures at all levels including surface, which may be atypical
  • Some tumors may show more monomorphic nuclei; nuclear rounding is common
  • Highest grade tumors may not appear urothelial, may have indistinct cell borders
  • Associated with carcinoma in situ or dysplasia in adjacent nonpapillary urothelium
  • Grade according to highest grade within a tumor, ignoring miniscule areas of higher grade tumor
  • High-grade designation is clinical threshold for adjuvant intravesical therapy
  • Must exclude areas of invasion
Microscopic (histologic) images

AFIP images

Grade 3 tumor resembles papilloma at low power but nuclear anaplasia is apparent at high power

Cytology images

Contributed by Bonnie Choy, M.D.
High grade urothelial carcinoma High grade urothelial carcinoma

High grade urothelial carcinoma

High grade urothelial carcinoma High grade urothelial carcinoma High grade urothelial carcinoma

High grade urothelial carcinoma

Positive stains
Negative stains
Molecular / cytogenetics description
  • Often aneuploid
  • Overexpression of p53, HER2, EGFR and loss of p21Waf1 or P27kip1
  • Deletion of 2q, 5q, 10q, 18q, and gain at 5p, 20q
Differential diagnosis
  • Inverted urothelial papilloma: may mimic endophytic growth in high-grade urothelial carcinoma; cytologically bland
  • Low grade papillary urothelial carcinoma: nuclear and architectural features are less atypical; mitoses are variable but not on surface; cellular dyscohesion less common; prominent umbrella cells are occasionally seen
  • Papillary nephrogenic adenoma / metaplasia: papillae are lined by single cuboidal layer; no/minimal atypia; PAX2+, PAX8+
  • Polypoid / papillary cystitis: broad papillae with stromal edema; do not have complex secondary or tertiary branching typical of papillary urothelial neoplasia; reactive urothelial atypia
  • Prostatic adenocarcinoma: papillary neoplasm that may extend into bladder from prostatic urethra; papillae typically lined by monomorphic columnar cells; PSA+, PAP+
  • Prostatic-type polyp: papillae lined by mixed prostatic secretory and urothelial cells; PSA+ and PAP+ secretory cell component
  • Villoglandular differentiation: elderly males, superficial filliform processes lined by glands intimately mixed with high grade urothelial carcinoma (in situ or invasive) and other aggressive variants of urothelial carcinoma (Mod Pathol 2009;22:1280)
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