Rationale of The Paris System for Reporting Urinary Cytopathology: The NEW paradigm

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Rationale of The Paris System for Reporting Urinary Cytopathology: The NEW paradigm Eva M. Wojcik, MD Professor and Chair of Pathology Professor of Urology Loyola University, Chicago, Il

Why to standardize reporting? Reproducibility Improvement of communication If information in multiple locations is to be searched, shared, and synthesized when needed, we will need common vocabularies for personal, clinical and public health information Agency for Healthcare Research and Quality, Prospects for Care Coordination Measurement Using Electronic Data Sources, AHRQPub No. 12-0014-EF, March 2012

Why to standardize reporting of urinary cytology?

Why to standardize reporting of urinary cytology? Range of atypia 2% -30%

System has to be build based on: Consensus Evidence Inclusion Acceptance Understanding Surgeons misunderstood pathologists reports 30% of the time. Urothelial Carcinoma Powsner, SM. Costa J, Homer RJ. Clinicians are from Mars and pathologists are from Venus. Clinician Interpretation of Pathology Reports. Arch Pathol Lab Med 2000. 124:1040 1046

Papillary Pathway 80% Normal Urothelium Non-Papillary Pathway 20% 9p-, 9qp16 Genetically Stable FGFR3 (~85%) Hyperplasia Genetically Unstable p53 (~60%) Dysplasia <10% RAS (?) Low Grade Carcinoma High Grade Carcinoma Carcinoma in situ Recurrence Recurrence Invasive Carcinoma

Cheng L, Zhang S, Maclennan GT, Williamson SR, Lopez-Beltran A, Montironi R. Bladder cancer: translating molecular genetic insights into clinical practice. Hum Pathol 2011;42:455 81.

Bladder cancer more then one disease? ~ 75 % Non-Muscle- Invasive (Ta/T1) Good prognosis Recurrence 10%-15% progression (LG Ta -<1%)* ~ 25 % Muscle-Invasive (>T2) >60% overall survival *Nielsen ME et al. Trends in Stage-Specific Incidence Rates for Urothelial Carcinoma of the Bladder In the United States: 1998-2006. Cancer 2014:120:86

Question. Carcinoma? GU GI

Question. Carcinoma? CARCINOMA ADENOMA

Classifications WHO 1973 Papilloma Grade I Grade II Grade III Papilloma PUNLMP Low Grade High Grade WHO/ISUP 2004 ~ 10-20% ~ 50-60% ~ 80-90% URINE CYTOLOGY SENSITIVITY Very high probability that we are going to be wrong 11

What really matters? High Grade Urothelial Carcinoma

Diagnostic Categories Hope HGUC Everything else Reality Positive Atypical/Suspicious Negative

Why Paris? 18 th International Congress of Cytology, Paris, May, 2013 Paris Group all participants of two Urine Cytology Symposia Outline of the Paris System for Reporting Urinary Cytopathology that is based on consensus, wide participation and evidences Ultimate goal detection of HGUC Sponsorship by the ASC and IAC Contract with Springer Numerous face-to-face meetings

Orlando, November 2013 Paris, May 2013 USCAP 2014 ASC 2014 European Congress of Cytology, Geneva, 2014

Subgroups to define. I. Adequacy II. Negative III. Atypical urothelial cells IV. Suspicious V. High Grade Urothelial Carcinoma VI. Low grade urothelial carcinoma VII. Other malignancies, both primary and secondary VIII. Ancillary Studies IX. Clinical management X. Preparatory techniques relative to Urinary Tract samples

Chapters in the Book I. Adequacy II. Negative for High Grade Urothelial Carcinoma III. Atypical Urothelial Cells IV. Suspicious for High Grade Urothelial Carcinoma V. High Grade Urothelial Carcinoma VI. Low Grade Urothelial Neoplasm VII. Other malignancies, both primary and secondary VIII. Ancillary Studies IX. Clinical management X. Preparatory techniques relative to Urinary Tract samples

NEW paradigm It is all about High Grade Urothelial Carcinoma Negative for High Grade Urothelial Carcinoma AUC SHGUC HGUC based on quantity LGUN Low Grade Urothelial Neoplasm

What about these? LGUC?

Is a consistent cytologic diagnosis of low-grade urothelial carcinoma in instrumented urinary tract cytologic specimens possible? A comparison between cytomorphologic features of low-grade urothelial carcinoma and non-neoplastic changes shows extensive overlap, making a reliable diagnosis impossible. McCroskey Z, Kliethermes S, Bahar B, Barkan GA, Pambuccian SE, Wojcik EM Journal of American Society of Cytopathology. 2014;4:90-97. The majority of the features described previously as diagnostic for LGPUC were observed almost equally in patients with or without biopsy-proven LGPUC, regardless of whether the specimens were from the upper or the lower urinary tract Mild nuclear membrane irregularity was present in 48% of LGPUC and 47.2% of negative controls (p=0.93); mild nuclear enlargement was observed in 42.9% of LGPUC patients and 49.1% negative controls (p=0.26)

Low Grade Urothelial Neoplasm - LGUN LGUN -combined cytologic term for low grade papillary urothelial neoplasms (LGPUN)(which include urothelial papilloma, PUNLMP and LGPUC) and flat, low grade intraurothelial neoplasia

LGUC LGUN

Cytologic Criteria of Low Grade Urothelial Neoplasia (LGUN) (regardless of the specimen type: voided or instrumented): Three-dimensional cellular papillary clusters (defined as clusters of cells with nuclear overlapping, forming "papillae") with fibrovascular cores with capillaries

LGUNmay be considered in correlation with cystoscopic or biopsy findings Diagnosis -NHGUC Three-dimensional cellular clusters without fibrovascular cores Increased numbers of monotonous single (nonumbrella) cells

Cytologic Criteria of Low Grade Urothelial Neoplasia (LGUN) (regardless of the specimen type: voided or instrumented): Cell Block

Urine Cytology State of Mind and