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Recent changes in Urothelial Cancers

The Paris System for Reporting Urinary Cytology 2022

The Paris System for Reporting Urinary Cytology (TPSRUC, The Paris System [TPS] 1.0-2016

OLDER VERSION

The Paris System for Reporting Urinary Cytology (TPSRUC, The Paris System [TPS] 2.0-2022

NEWER VERSION

Risk of Malignancy (ROM) vs Risk of high-grade Malignancy (ROHM)

Clinical Management

ROM (%)

(TPS 1.0)

ROHM (%)

(TPS 2.0)


I)non-diagnostic

I)non-diagnostic

<5-10

0-16

Identify cause, repeat sample depending on the risk of malignancy

II)Negative for high grade urothelial carcinoma (NHGUC)

II)Negative for high grade urothelial carcinoma (NHGUC)

0-10

8-24

Continue the routine surveillance at intervals as per the risk of recurrence

III)Atypical urothelial cells (AUC)

III)Atypical urothelial cells (AUC)

8-35

24-53

Individualized workup based on the risk

IV) Suspicious for high-grade urothelial carcinoma (SHGUC)

IV) Suspicious for high-grade urothelial carcinoma (SHGUC)

50-90

59-94

Active investigation to identify the source of the suspicious or positive cells - for both lower and upper tracts in form of CPE and cross sectional imaging for upper tract either as CT or MRI 

VI)Low-grade urothelial neoplasm (LGUN)

Categorized under Negative for high grade UC




V)High grade urothelial carcinoma (HGUC)

V)High grade urothelial carcinoma (HGUC)

>90

76-100

Active investigation to identify the source of the suspicious or positive cells


Novel Molecular Classification of Muscle Invasive Bladder Cancer

Subtypes

Luminal papillary (LumP)

Luminal non-specified (LumNS)

Luminal unstable (LumU)

Stroma-rich

Basal/squamous (Ba/Sq)

Neuroendocrine-like (NE-Like)

Differentiation Type

Luminal

Luminal

Luminal

Luminal and Basal

Basal and Squamous

Neuroendocrine

Expression of Genes

PPARγ 

GATA3 FOXA1 UPK1A 

UPK2 

KRT20 

ESR2

PPARγ

 GATA3 FOXA1 UPK1A 

UPK2 

KRT20

ESR2

PPARγ GATA3 FOXA1 UPK1A UPK2 KRT20 ESR2

Markers of smooth muscle, endothelium, fibroblasts, myofibroblasts

KRT5 

KRT6A

KRT14 

CD44

TGM1 

DSC3 

PI3

Synaptophysin CGA

NSE/CD56

Alternation of Genomic 

-FGFR3 Alternation (Over expression Amplification or FGFR3-TAC3 Fusions)

-KDM6A Mutations

-CDKN2A Deletions

-ELF3 Mutations

-Amplification or Fusion of PPARγ

-PPARγ Mutation

-Over-expression of E2F3 and SOX4, 

-Mutation affecting nucleotide-excision repair pathway,

ERCC2 

TP53 Mutation


TP53

or

RB1

Inactivation/Mutation/Deletion of TP53 

or

RB1

Infiltration

Not seen

-Stromal Cells i.e. Fibroblasts,

-Immune cells i.e. Lymphocytes B and T

Not seen

Stromal and Immune cells (T and B- Cells)

Immune Cells- Cytotoxic Lymphocytes and NK cells

Not Seen

Prognosis

The Best

Poor

Intermediate

Intermediate

Poor

The Worst

Compiled by Dr Siddharth Verma, VMMC & SJH, New Delhi

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