Urothelial neoplasms-noninvasive
Low grade papillary urothelial carcinoma

Author: Rugvedita Parakh, M.D. (see Authors page)

Revised: 12 July 2016, last major update December 2014

Copyright: (c) 2003-2016,, Inc.

PubMed Search: Low grade papillary urothelial carcinoma[title]
Cite this page: Low grade papillary urothelial carcinoma. website. Accessed October 25th, 2016.
Definition / General
  • Papillary urothelial neoplasm with some degree of cytoarchitectural disorder and distinct but low grade cytologic abnormality
  • No high-grade cytologic features (no pleomorphism, no mitoses toward surface, no nucleoli throughout)
  • ICD-O: 8130/1 or /2
  • Grade 2 of 4 in Ash system (old grading system)
  • Categories do not translate between nomenclature systems; low grade papillary urothelial carcinoma is not synonymous with WHO 1973 grade 1
  • Incidence: 5 per 100,000 individuals per year
  • Mean age 70 years
  • 75% male
  • Commonly on posterior bladder wall
  • Lateral wall close to ureteral orifices is another common site
  • Theories of multicentricity are (a) field effect: carcinogenic agents cause malignant transformation of multiple urothelial cells or (b) intramucosal spreading of tumor
  • In one study, low grade, noninvasive urothelial carcinomas were monoclonal, and multifocal lesions had identical clonal origin, supporting the intramucosal spreading hypothesis (Hum Pathol 1999;30:1197)
  • May represent a continuous spectrum with high grade tumors (Hum Pathol 2003;34:893)
Clinical Features
  • Gross or microscopic hematuria is common
  • Cystoscopy shows exophytic fronds of tumor
  • Solitary or multiple lesions
  • Represent 12-25% of urothelial neoplasms
  • 48-71% recur, low risk of recurrence (<5%) as high grade lesions, which may lead to invasion and death
  • In one study, no difference in cumulative incidence of progression or cancer-specific mortality between pTa (noninvasive) and pT1 (invasive into lamina propria) low grade papillary urothelial carcinomas (Am J Clin Pathol 2010;133:788)
  • Transurethral resection of bladder tumor (TURBT)
  • Surveillance cystoscopy at 6 month intervals with outpatient fulguration (J Urol 2007;178:1201)
  • Intravesical therapy not generally used for low grade carcinoma
Gross Description
  • More solid cores with firmer consistency than papillomas, usually solitary
  • Wide variation in size
Micro Description
  • Papillary with central fibrovascular cores; orderly with recognizable variation of cytologic and architectural features, even at scanning magnification
  • Loss of cellular polarity, random distribution of cells in urothelium
  • Loss of linear perpendicular orientation to basement membrane
  • Only assess papillary fronds cut perpendicular to long axis of papillary frond (i.e. longitudinal sections)
  • Rare to numerous mitotic figures, usually distributed randomly
  • Compared to papilloma and low malignant potential, have distinctly neoplastic cells with more crowding and layering, more hyperchromasia and mitoses
  • May be associated with denuding urothelium (Am J Surg Pathol 2007;31:298)

Definite cytologic atypia is present:
  • Cells are relatively uniform in size without significant nuclear pleomorphism or nucleomegaly
  • Subtle variation in nuclear size may be present
  • Nuclei are often rounded with occasional irregularities of nuclear contour
  • Relatively fine to slightly abnormal chromatin distribution
  • Nucleoli may be present, but are inconspicuous

  • Atypia in superficial umbrella cells should be discounted
  • Distinguishing low grade papillary urothelial carcinoma from high grade is important, because therapy is different (intravesical therapy for high grade)
Micro Images

Images hosted on Pathout server:

Densely packed but evenly distributed nuclei with high N/C ratios

Papillary tumor with uniformly distributed, densely packed nuclei; more irregular than in most low grade urothelial carcinomas

Images hosted on other servers:
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Non invasive tumor

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8+ cell layers with small dysplastic changes

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The covering of papillary urothelial tumor is thickened considerably

Cytology Description
  • May be cellular with loose clusters with high N/C ratios, irregular nuclear borders
  • Cytoplasm may surround only a portion of the nucleus
Cytology Images

Images hosted on Pathout server:

Neoplastic cells with high N/C ratio

Tumor cells

Positive Stains
Negative Stains
Molecular / Cytogenetics Description
  • Usually diploid
Differential Diagnosis
    High grade papillary urothelial carcinoma:
  • Wide morphologic spectrum
  • High-grade features may be diffuse, focal or patchy
  • Even focal high-grade features warrants a high grade designation
  • Marked nucleomegaly common
  • Also marked variation in size and shape of nuclei
  • Irregularly clumped nuclear chromatin
  • Irregular nuclear membranes
  • Mitotic figures may be easily identified
  • May be associated with invasive carcinoma

    Papillary nephrogenic adenoma:
  • Papillae lined by single cuboidal epithelial layer
  • Underlying tubular, cystic, or diffuse pattern may be present

    Papillary-polypoid cystitis:
  • Exophytic papillary excrescences on low power
  • Edematous or fibrotic papillary cores
  • No significant branching architecture
  • No anastomosing epithelial growth
  • Broad base of excrescences may taper to slender papillae toward lumen
  • May have associated reactive atypia (Am J Surg Pathol 2008;32:758)

    Papillary urothelial neoplasm of low malignant potential:
  • Similar to low grade papillary urothelial carcinoma at low and intermediate magnification
  • Lacks distinct nuclear abnormalities
  • No variation in nuclear shape or size
  • Maintains normal perpendicular polarity to basement membrane (order)
  • No nucleoli, no mitotic figures