Bladder, ureter & renal pelvis

Urothelial neoplasms - noninvasive

Noninvasive papillary urothelial carcinoma low grade


Editorial Board Member: Maria Tretiakova, M.D., Ph.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Yan Hong Shirley Yu, M.D.
Michelle R. Downes, M.D.

Topic Completed: 26 April 2021

Minor changes: 26 April 2021

Copyright: 2002-2021, PathologyOutlines.com, Inc.

PubMed Search: Low grade papillary urothelial carcinoma [TIAB] pathology

Yan Hong Shirley Yu, M.D.
Michelle R. Downes, M.D.
Page views in 2020: 22,929
Page views in 2021 to date: 26,739
Cite this page: Yu YHS, Downes MR. Noninvasive papillary urothelial carcinoma low grade. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/bladderLGpap.html. Accessed October 21st, 2021.
Definition / general
  • Neoplastic proliferation of the urothelium in a papillary configuration, with no invasion through the basement membrane
  • Low grade architectural and cytologic abnormality, absence of high grade features, such as irregular nuclei with frequent, prominent nucleoli and mitoses, pleomorphism
Essential features
  • Noninvasive papillary urothelial neoplasm with low grade cytoarchitectural abnormality
  • Loss of polarity, rare mitoses, subtle variation in nuclear size but no significant pleomorphism
  • Immunohistochemistry not helpful for diagnosis
  • Hematuria common presentation
  • Disease related death and progression is rare but recurrence common
Terminology
  • Grade 1 and subset of grade 2 carcinomas from 1973 WHO classification
ICD coding
  • ICD-O: 8130/2 - papillary transitional cell carcinoma, noninvasive
Epidemiology
Sites
  • Most commonly found in posterior and lateral walls of bladder
  • 85% of urothelial neoplasms of renal pelvis are papillary but only 34% of them are low grade (Mod Pathol 2005;18:11)
  • Anywhere with urothelium
Pathophysiology
  • Normal urothelium, through loss of chromosome 9, becomes hyperplasia
  • Followed by further genetic alterations, such as mutations in FGFR3, which activates mitogen activated protein (MAP) kinase pathway, leading to development of low grade noninvasive papillary urothelial carcinoma (Int J Clin Oncol 2008;13:287)
  • Other genetic alterations: PIK3CA, loss of 11p or CCND1
Etiology
Clinical features
  • Most common presentation: painless hematuria (gross or microscopic)
  • Disease associated death and progression is rare (< 5%)
  • Recurrence common (48 - 71%)
Diagnosis
  • Cystoscopy: exophytic lesion, solitary or multiple, with varying size
  • CT urography or ultrasound
  • Urine cytology
Radiology description
  • CT urography shows hydronephrosis and filling defects (Abdom Radiol (NY) 2018;43:663)
  • Ultrasound can detect hydronephrosis and any intraluminal bladder masses
Prognostic factors
Case reports
Treatment
  • Surgical: transurethral resection
  • Adjuvant: usually not indicated for low grade
  • Mitomycin C
Gross description
  • Exophytic papillary lesions, single or multiple; can vary greatly in size
Frozen section description
Microscopic (histologic) description
  • Neoplastic urothelium lining fibrovascular cores
  • Long, slender papillae with minimal fusing or branching
  • Orderly architecture at low magnification, some loss of polarity and mild pleomorphism at medium magnification
  • Cells generally uniform in size, may have slight variation but no significant nuclear pleomorphism or nucleomegaly, occasional slight irregularities in nuclear contour
  • Mitoses may be present but not atypical and usually confined to lower half of urothelium
  • Inverted growth pattern (exophytic and endophytic components) may be present
Microscopic (histologic) images

Contributed by Michelle R. Downes, M.D.
Low grade, noninvasive papillary urothelium carcinoma

Low grade,
noninvasive
papillary urothelium
carcinoma

Renal pelvis

Noninvasive papillary,
low grade urothelial
carcinoma of
renal pelvis

Papillary architecture

Papillary architecture

Architectural features

Architectural features


Endophytic growth pattern

Endophytic growth pattern

GATA3

GATA3

p53 staining

p53

Ki67

Ki67



Contributed by Nicole K. Andeen, M.D. and Maria Tretiakova, M.D.
Noninvasive papillary urothelial carcinoma, low grade (pTa) Noninvasive papillary urothelial carcinoma, low grade (pTa) Noninvasive papillary urothelial carcinoma, low grade (pTa)

Noninvasive papillary urothelial carcinoma, low grade (pTa)

Papillary urothelial<br>carcinoma, muscularis<br>is absent

Papillary urothelial
carcinoma, muscularis
is absent

Cytology description
Cytology images

Contributed by Zeina Ghorab M.D. and Bonnie Choy, M.D.
Cytology of non high grade lesion

Cytology of
non high grade lesion

Low grade urothelial neoplasia

Low grade urothelial neoplasia

Negative stains
Electron microscopy description
  • Subset with urothelial eddies show microvillous projections and increased intercellular space (Int J Clin Exp Pathol 2013;6:1458)
  • Low grade papillary urothelial carcinoma has zonula occludens (tight junctions) and well developed macula adherens (desmosomes), with fewer surface vesicles than normal epithelium
Molecular / cytogenetics description
  • Activating mutations in FGFR3
  • Somatic mutations in TERT promoter in 50% of low grade papillary noninvasive urothelial carcinomas; more commonly associated with FGFR3 mutated tumors (Histopathology 2018;72:795)
  • Inactivating mutations in cohesion complex gene STAG2 in 32 - 36% noninvasive urothelial carcinomas; associated with low histologic grade and low tumor stage (Ann Surg Oncol 2017;24:4059)
  • PIK3CA (25% cases) TSC1, HRAS, APC
  • Epigenetic silencing of tumor suppressor genes through promoter hypermethylation: RUNX3, CDKN2A, MLH1, MGMT, VHL, DAPK, TBX2, TBX3, GATA2, ZIC4, GSTP1, CDH1 (Eur Urol 2012;61:1245, Nat Rev Urol 2013;10:327)
  • MicroRNA alterations (J Pak Med Assoc 2018;68:759)
  • Loss of chromosome 9 (9q and 9p in low grade)
Videos

Urothelial carcinoma, papillary and invasive

Sample pathology report
  • Bladder, lesion, transurethral resection:
    • Noninvasive papillary urothelial carcinoma, low grade
    • Muscularis propria is present
Differential diagnosis
Board review style question #1

A transurethral resection of bladder was performed on a 62 year old man. Histological examination showed a noninvasive papillary lesion. Which of the following is true about the lesion depicted above?

  1. Immunohistochemistry is helpful for diagnosis
  2. Mitoses are rare and usually confined to lower half of urothelium
  3. Nuclear pleomorphism is marked
  4. Progression to invasive disease is common
Board review style answer #1
B. Mitoses are rare and usually confined to lower half of urothelium. Diagnosis: low grade noninvasive papillary urothelial carcinoma.

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Reference: Noninvasive papillary urothelial carcinoma low grade
Board review style question #2

Which of the following is the correct diagnosis?

  1. High grade noninvasive papillary urothelial carcinoma
  2. Invasive papillary urothelial carcinoma
  3. Inverted papilloma
  4. Low grade noninvasive papillary urothelial carcinoma
  5. Urothelial papilloma
Board review style answer #2
D. Low grade noninvasive papillary urothelial carcinoma

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Reference: Noninvasive papillary urothelial carcinoma low grade
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