Bladder, ureter & renal pelvis

Urothelial neoplasms - noninvasive

Papillary urothelial neoplasm of low malignant potential


Editorial Board Member: Bonnie Choy, M.D.
Deputy Editor-in-Chief: Maria Tretiakova, M.D., Ph.D.
Daniel Athanazio, M.D., Ph.D.

Last author update: 6 September 2022
Last staff update: 16 September 2022

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PubMed Search: Papillary urothelial neoplasm of low malignant potential

Daniel Athanazio, M.D., Ph.D.
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Cite this page: Athanazio D. Papillary urothelial neoplasm of low malignant potential. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/bladderPUNLMP.html. Accessed December 1st, 2022.
Definition / general
  • Neoplastic proliferation of the urothelium in a papillary configuration, with no invasion through the basement membrane
  • Thickened urothelium or increased cellularity, without marked cytological atypia
Essential features
  • Epithelial lining of fibrovascular cores is thicker than normal urothelium
  • No nuclear atypia or hyperchromatic nuclei in neoplastic urothelial cells
  • Maybe exophytic papillary or endophytic papillary (inverted)
  • Exclusion criteria is prior history of urothelial carcinoma
Terminology
ICD coding
  • ICD-O: 8130/1 - papillary transitional cell neoplasm of low malignant potential
  • ICD-11: 2F78 & XH5UU5 - neoplasms of uncertain behavior of urinary organs & papillary urothelial neoplasm of low malignant potential
Epidemiology
Sites
  • Most diagnosed in the bladder
  • Occurs anywhere along urinary mucosae
Pathophysiology
Etiology
Clinical features
  • Gross or microscopic hematuria
  • Urine cytology is negative in most cases
Diagnosis
  • Cystoscopy: exophytic lesion with varying sizes (no specific cut off) but usually a small and single lesion
Radiology description
  • Bladder mass with polypoid configuration and papillary / exophytic surface
  • Inverted tumor shows a polypoid shape with a nonpapillary surface
Radiology images

Images hosted on other servers:

Exophytic lesion with internal vascularity

Prognostic factors
  • This diagnostic category is justified because the recurrence and progression rates of papillary urothelial neoplasm of low malignant potential (PUNLMP) are expected to be higher than urothelial papilloma and lower than low grade noninvasive urothelial carcinoma
  • Recurrence rate: 18 - 20% (Am J Clin Pathol 2010;133:788, Diagn Pathol 2015;10:3)
  • Progression rate: 1.9 - 11.1%, mainly to low grade noninvasive papillary urothelial carcinoma (Am J Clin Pathol 2010;133:788, Diagn Pathol 2015;10:3)
  • ~1% progress to invasive urothelial carcinoma (Diagn Pathol 2015;10:3)
  • Limited data on recurrence of inverted PUNLMP but it seems to be rare (Diagn Pathol 2015;10:3)
  • In a population based study from Sweden, 5 year recurrence rates of PUNLMP and noninvasive low grade papillary urothelial carcinoma were 21% and 42%, respectively; progression rates were 0.7% and 4%, respectively (Scand J Urol 2022;56:14)
  • Not all series show differences in recurrence and progression between PUNLMP and low grade noninvasive urothelial carcinoma:
    • 5 year recurrence rate is 51% for PUNLMP versus 48% for low grade papillary urothelial carcinoma
    • Progression to muscle invasive disease is 3.9% for PUNLMP versus 2.6% for low grade papillary urothelial carcinoma (Urol Oncol 2020;38:440)
Case reports
Treatment
  • Surgical: transurethral resection with no need of further topical treatments
Clinical images

Images hosted on other servers:

Exophytic papillary - recurrent PUNLMP

Cystoscopy: exophytic papillary

Gross description
  • Variable size but most tumors are single and regular polypoid masses measuring < 2 cm
Gross images

Contributed by Daniel Athanazio, M.D., Ph.D.

Fresh specimen

Formalin fixed specimen

Microscopic (histologic) description
  • Noninvasive papillary urothelial neoplasm with exophytic or endophytic (inverted) configuration; a cut off of > 80% is proposed by the Genitourinary Pathology Society to designate a urothelial neoplasm of inverted type (Adv Anat Pathol 2021;28:179)
  • Epithelial lining of fibrovascular cores is thicker than normal urothelium: urothelial cells show monotonous appearance and slight cytoplasmic and nuclear enlargement
  • No variation in nuclear size, shape or chromatin pattern
  • Preserved polarity of urothelial cells
  • Mitoses are rare and basally located
  • No hyperchromatic nuclei in urothelial cells in intermediate layers of neoplastic epithelium
Microscopic (histologic) images

Contributed by Daniel Athanazio, M.D., Ph.D. and Luciana Schultz, M.D., Ph.D. (source: Instituto de Anatomia Patológica)
Exophytic intraluminal urothelial papillary neoplasm Exophytic intraluminal urothelial papillary neoplasm

Exophytic intraluminal urothelial papillary neoplasm

Preserved polarity and no atypia Preserved polarity and no atypia

Preserved polarity and no atypia

Thickened urothelium and hypercellularity

Thickened urothelium and hypercellularity

Thickened urothelium / no atypia

Thickened urothelium / no atypia


Papillary exophytic neoplasm

Papillary exophytic neoplasm

Preserved polarity and hypercellularity

Preserved polarity and hypercellularity

Basally located mitosis

Basally located mitosis

Transition zone between normal ureteral urothelium and a shoulder lesion Transition zone between normal ureteral urothelium and a shoulder lesion

Transition zone between normal ureteral urothelium and a shoulder lesion


Endophytic / inverted growth Endophytic / inverted growth

Endophytic / inverted growth

Exophytic and endophytic growth

Exophytic and endophytic growth

Preserved polarity

Preserved polarity

Thickened epithelium / no atypia

Thickened epithelium / no atypia

Thickened epithelium / inverted growth

Thickened epithelium / inverted growth


Thickened epithelium / inverted growth

Thickened epithelium / inverted growth

Preserved polarity

Preserved polarity

Inverted PUNLMP

Inverted PUNLMP

Inverted PUNLMP – anastomosing cords

Inverted PUNLMP - anastomosing cords

Thickened epithelium

Thickened epithelium

Thickened epithelium / no atypia

Thickened epithelium / no atypia


Inverted PUNLMP

Inverted PUNLMP

Inverted PUNLMP - no atypia

Inverted PUNLMP - no atypia

Papillary exophytic

Papillary exophytic

Thickened  epithelium

Thickened epithelium

No atypia No atypia

No atypia


Papillary exophytic

Papillary exophytic

Hypercellular monotonous urothelial lining Hypercellular monotonous urothelial lining Hypercellular monotonous urothelial lining

Hypercellular monotonous urothelial lining

No atypia

No atypia

Preserved polarity

Preserved polarity


GATA3

GATA3

Cytokeratin 5

CK5

p16

p16

Virtual slides

Images hosted on other servers:

H&E

GATA3

CK5

p16

Cytology description
  • Usually not detected in urinary cytology, unless entire papillary formations are seen (then a diagnosis of low grade urothelial neoplasm, including both PUNLMP and low grade noninvasive papillary urothelial carcinoma, may be suggested as a comment within the diagnosis of “negative for high grade urothelial carcinoma”)
  • The Paris System states that, in most cases, urinary cytology is unable to detected low grade urothelial neoplasms, including PUNLMP (J Am Soc Cytopathol 2016;5:177, J Am Soc Cytopathol 2022;11:62)
Positive stains
  • Markers of urothelial differentiation (not helpful in the differential diagnosis)
Negative stains
  • Not helpful
Molecular / cytogenetics description
Videos

Differential diagnosis of noninvasive endophytic urothelial neoplasms

PUNLMP at cytology

Sample pathology report
  • Bladder, lesion, transurethral resection:
    • Low grade urothelial neoplasm of low malignant potential (see comment)
    • Muscularis propria is present
    • Comment: The sample shows urothelial neoplasia with thickened epithelial lining and no atypia. There are no invasive foci. The findings are consistent with the diagnosis of urothelial neoplasm of low malignant potential (PUNLMP), an indolent tumor expected to have lower rates of recurrence and progression when compared to noninvasive low grade papillary urothelial carcinoma. For a sample of an incompletely resected multifocal or larger tumor, complete excision of all visible lesions for pathologic analysis is recommended. The diagnosis of PUNLMP requires exclusion of prior history of urothelial carcinoma. In cases involving a prior history of carcinoma, the present tumor should be considered a recurrence of the original neoplasia.
Differential diagnosis
Board review style question #1

A transurethral resection of bladder was performed on a 60 year old man. Histological examination showed a noninvasive papillary lesion with fibrovascular cores lined by thickened urothelium with cells with monotonous appearance and no nuclear atypia. Which of the following additional information would exclude the diagnosis of urothelial neoplasm of low malignant potential?

  1. Multicentric disease
  2. Prior history of prostate adenocarcinoma
  3. Prior history of urothelial carcinoma
  4. Size larger than 3 cm
Board review style answer #1
C. Prior history of urothelial carcinoma

Comment Here

Reference: Papillary urothelial neoplasm of low malignant potential
Board review style question #2
The differential diagnosis between urothelial neoplasm of low malignant potential and noninvasive low grade papillary urothelial carcinoma usually shows poor reproducibility in different studies. Which of the following is the most important criterion favoring the diagnosis of urothelial carcinoma?

  1. EGFR3 mutation
  2. Scattered hyperchromatic nuclei among intermediate neoplastic urothelial cells
  3. TERT promoter mutation
  4. TP53 mutation
Board review style answer #2
B. Scattered hyperchromatic nuclei among intermediate neoplastic urothelial cells

Comment Here

Reference: Papillary urothelial neoplasm of low malignant potential
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