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Urothelial neoplasms-noninvasive

High grade papillary urothelial carcinoma

Reviewer: Rugvedita Parakh, M.D. (see Reviewers page)
Revised: 9 February 2013, last major update May 2010
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.


● A neoplasm with urothelium lining papillary fronds, a predominant disorderly pattern and moderate to marked architectural and cytologic atypia
● 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


Gross description

● Sessile or cauliflower-like with necrosis and ulceration
● Exophytic papillary growth

Gross images

Multifocal papillary tumor

Micro 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

Micro images

Series of high grade tumors

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

Highly pleomorphic cells with voluminous cytoplasm

Architectural disorganization and cytologic atypia

Enlarged nuclei and increased chromatin content

Pronounced polymorphism and loss of polarity

Pleomorphism and loss of polarity

H&E, loss of CD44, diffusely CK20+

Fig G-I: H&E, Survivin, Ki-67

Positive stains

● CK20 (Mod Pathol 2000;13:1315)
● Also Ki-67 and survivin (Arch Pathol Lab Med 2008;132:224), p53 (Arch Pathol Lab Med 2001;125:646)
● Overexpression of p16(INK4a, Am J Clin Pathol 2009;132:776)
● Beta hCG in 1/3 of urothelial carcinomas, particularly high grade or high stage tumors (Hum Pathol 1998;29:377)
● Estrogen receptor in 14% (Arch Pathol Lab Med 2005;129:194)

Negative stains

● Blood group antigens
● No/weak expression of E-cadherin (Hum Pathol 1995;26:940)

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)

End of Bladder > Urothelial neoplasms-noninvasive > High grade papillary urothelial carcinoma

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