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Bladder

Urothelial neoplasms-noninvasive

Low grade papillary urothelial carcinoma


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

Definition
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● 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

Terminology
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● 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

Epidemiology
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● Incidence: 5 per 100,000 individuals per year
● Mean age 70 years
● 75% male

Sites
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● Commonly on posterior bladder wall
● Lateral wall close to ureteral orifices is another common site

Etiology
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● 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
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● 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)

Treatment
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● 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
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● More solid cores with firmer consistency than papillomas, usually solitary
● Wide variation in size

Micro description
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● 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
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Papillary fronds lined by thickened urothelium


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


Various levels of magnification


H&E, CD44, CK20

Orderly growth pattern

Low malignant potential (A/B) vs. low grade papillary (C/D)

Thickened urothelium in papillary fronds

Non invasive tumor

8+ cell layers with small dysplastic changes
Minimal variation in nuclear size from one cell to another Lesion composed of papillary fronds lined by thickened urothelium
Distinct nucleoli is more atypia than in tumor of low malignant potential The covering of papillary urothelial tumor is thickened considerably
Papillary tumor with uniformly distributed, densely packed nuclei; more irregular than in most low grade urothelial carcinomas Resembles PUNLMP, but too much cytologic atypia

Cytology description
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● 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
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Neoplastic cells with high N/C ratio, marked nuclear eccentricity, irregular nuclear borders and characteristic chromatin pattern


Tumor cells in center with normal cell at lower left

Positive stains
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● Blood group antigens, p53 (Urol J 2007;4:230)

Negative stains
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● Usually survivin negative, compared to high grade lesions (Arch Pathol Lab Med 2008;132:224)

Molecular description
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● Usually diploid

Differential diagnosis
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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

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


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