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The Language of Cytopathology

The Journey from Bethesda to

Paris and Beyond

Syed Z. Ali, MD, FIAC, FRCPath

Professor of Pathology and Radiology

The Johns Hopkins Hospital

Baltimore, Maryland

USA

Scientific Language or Terminology

< aka Nomenclature >

“As ideas are preserved and communicated by means

of words, it necessarily follows that we cannot improve

the language of any science, without at the same time

improving the science itself; neither can we, on the

other hand, improve a science without improving the

language or nomenclature which belongs to it”

Antoine-Laurent Lavoisier (1743-1794), French chemist

On Reporting Terminology -

“an accurate cytologic diagnosis of disease is

both possible and desirable: therefore, the

reports should be expressed in simple

language that can be readily understood by the

clinician.”

Leo Koss – Diagnostic Cytology and its Histopathologic Bases, 1st ed, 1961

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“The history of cytology is like a winding road, with many

obstacles, detours and sudden turns. The roadside

ravines are filled with discarded, once believed,

obsolescent tools, ideas and personnel. Despite many

roadblocks and potholes the traveler may find long

stretches of neatly landscaped road with brightly

illuminated directional signs and clearly visible names”

Steve I. Hajdu

Reporting Terminology Follows

the History of Cytology

Papanicolaou Classification

For Cervical Cytology

Class I – Absence of atypical or abnormal cells

Class II – Atypical cytology but no evidence of

malignancy

Class III – Cytology suggestive of, but not diagnostic

for, malignancy

Class IV – Cytology strongly suggestive of malignancy

Class V – Cytology conclusive of malignancy

It all started from

BethesdaMaryland, USA

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“The Architect”

Diane Solomon

1988

National Institute of

Health

Bethesda,

Maryland

1994(1988, 1991)

2004(2001)

2015(2014)

The Bethesda System for

Reporting Cervical Cytology

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154 registrants

Pathologists

Surgeons

Endocrinologists

Radiologists Andrea Abati

2007

2006-2007 – “Terminology Committee” prepared a draft document

2007 – Three online discussion periods

2007 – October 22-23 “Bethesda” Live Conference

2008 – Documents published in 2 journals

2010 – Monograph published

TBSRTC - History and Timeline

NCI Thyroid FNA State of the Science Conference

General agreement on need for defined categories

• Clarity of communication

• Exchange of data across institutions

Discussion focused on number of categories and names

Succinct, unambiguous, clinically relevant

Endorsed by all in the multidisciplinary team

Probabilistic approach

Robust and reproducible morphologic criteria

Well-defined clinical management algorithms

Thyroid FNA Terminology< Prerequisites and Goals >

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TBSRTC 2010 - Probabilistic

Approach andRelationship to

Clinical Algorithms

ROM (%) Management

Nondiagnostic 1-4 Repeat FNA with US

Benign 0-3 Follow-up

AUS/FLUS 10-15 Repeat FNA

SFN/FN 15-30 Lobectomy

SFM 60-75 Lobectomy or total

thyroidectomy

Malignant 97-99 Total thyroidectomy

Digital Image Atlas –

http://www.papsociety.org

Over 35k copies sold (English ed)

Andrea Abati

John Abele

Jacki Abrams

Pedro de Agustin

Erik Alexander

Sylvia Asa

Zubair Baloch

Carol Benson

Douglas Clark

Beatrix Cochand-Priollet

R. Mac DeMay

Gerard Doherty

Dan Duick

Tarik El Sheikh

Doug Evans

Bill Faquin

Armando Filie

William Frable

Hossein Gharib

Kim Geisinger

Frank

Greenspan

Jill Langer

Lester Layfield

Virginia Livolsi

Britt-Marie Ljung

Sanjay Logani

Susan Mandel

Ernest

Mazzaferri

Maria Merino

Claire Michael

Bill Middleton

Ted Miller

Yuri Nikiforov

Martha Pitman

Celeste Powers

Yolanda Oertel

Steve Raab

Greg Randolph

Juan Rosai

Leslie Scoutt

Mary Sidawy

Philippe Vielh

Jerry Waisman

Helen Wang

Sam Wells

Matt White

The Bethesda System for Reporting Thyroid

Cytopathology: Past, Present and Future

(ICC, Yokohama May-June, 2016)

Moderators – Syed Z. Ali, Philippe Vielh, (Ed Cibas)

Group Leaders - William C. Faquin, Marc Pusztaszeri, Diana Rossi

Contributors - Erik K. Alexander, Manon Auger, Zubair W. Baloch,

Justin A. Bishop, Massimo Bongiovanni, Ashish Chandra,

Béatrix Cochand-Priollet, David S. Cooper, Barbara A. Crothers,

Tarik M. Elsheikh, Guido Fadda, William C. Faquin, Armando C. Filie, Pinar Firat, Mary C. Frates, Hossein Gharib, Michael R.

Henry, SoonWon Hong, Jeffrey F. Krane, Kennichi Kakudo,

Lester J. Layfield, Virginia A. LiVolsi, Claire W. Michael, Ritu

Nayar, Michiya Nishino, Martha B. Pitman, Celeste N. Powers,

Gregory W. Randolph, Andrew A. Renshaw, Miguel A. Sanchez,

Fernando Schmitt, Vinod Shidham, Mary K. Sidawy,

Gregg A. Staerkel, Edward B. Stelow, Paul A. VanderLaan, William H. Westra, Grace C. H. Yang, Matthew A. Zarka

TBSRTC 2017

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TBSRTC 2017 - Probabilistic Approach

and Relationship to Clinical Algorithms

ROM (%) Management

Nondiagnostic (1-4) 5-10 Repeat FNA with U/S

Benign (0-3) 0-3 Follow-up

AUS/FLUS (10-15) ~10-30 Repeat FNA, molec

testing or lobectomy

SFN/FN (15-30) 25-40 Molec testing, lobectomy

SFM (60-75) 50-75 Near-total thyroidectomy

or lobectomy

Malignant (97-99) 97-99 Near-total thyroidectomy

or lobectomy*

The Journey from Bethesda to

Paris and Beyond

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Three Hopkins Articles

18th International Congress of Cytology - Paris

American Society of Cytopathology - Orlando

“The Paris System for Reporting Urinary Tract Cytology”

2013 - Year of Urinary Tract

Cytopathology

A review of reporting systems and terminology for urine cytology. Owens CL, Vandenbussche CJ, Burroughs FH, Rosenthal DL.

Cancer Cytopathol. 2013 Jan;121(1):9-14

The Johns Hopkins Hospital template for urologic cytology samples: part I -creating the template. Rosenthal DL, Vandenbussche CJ, Burroughs FH,

Sathiyamoorthy S, Guan H, Owens C. Cancer Cytopathol. 2013 Jan;121(1):15-20

The Johns Hopkins Hospital template for urologic cytology samples: parts II and III: improving the predictability of indeterm inate

results in urinary cytologic samples: an outcomes and cytomorphologic study. VandenBussche CJ, Sathiyamoorthy S,

Owens CL, Burroughs FH, Rosenthal DL, Guan H. Cancer Cytopathol. 2013 Jan;121(1):21-8

Dotty L. Rosenthal Philippe Vielh

The Johns Hopkins

Template for Urothelial

Cytodiagnostic Categories

No urothelial atypia/malignancy (NUAM)

Urothelial carcinoma (specify)

High grade (HGUC)

Low grade (LGUC)

Atypical urothelial cells of uncertain significance (AUC-US)

Atypical urothelial cells, cannot exclude high grade urothelial carcinoma (AUC-H)

Other________________________

• 18th International Congress of Cytology, Paris, May, 2013• “Paris Group” – All participants of two Urine Cytology Symposia

• Outline of the Paris System for Reporting Urinary Cytology that is based on consensus, wide participation and evidence

• Ultimate goal – detection of HGUC

• Sponsorship by the ASC and IAC

• Numerous face-to-face meetings

Orlando, November 2013

ASC, 61st Annual Meeting

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Create a Urinary Cytology Diagnostic/Reporting System

that is -

Highly reliable as a non-invasive tool to determine those

patients who need immediate cystoscopy vs. those who can

be followed at an interval based upon risk stratification of

their diagnostic category

Evidence-based involving cytopathologists, urologists,

clinical scientists, biostatisticians

Based on the assumption that the target of urinary cytology

is high grade urothelial carcinoma (HGUC)

The Paris System For Reporting Urinary Tract Cytology

<Goals and Objectives>

The Paris System For Reporting

Urinary Tract Cytology

Negative for High Grade Urothelial Carcinoma

Atypical Urothelial Cells (AUC)

Suspicious for High Grade Urothelial Carcinoma

High Grade Urothelial Carcinoma

Other Malignancies

Nondiagnostic/Inadequate

Clinical Management

Category Risk of Malignancy

HGUC

Management

Nondiagnostic/Unsatisfactory 0-5% Repeat cytology, cystoscopy in 3 months if high clinical suspicion

Negative for HGUC 0-5% Clinical follow up as needed

Atypical Urothelial Cells (AUC) 8-20% Clinical follow up as needed? TBD

Suspicious for HGUC 50-70% More aggressive follow up, cystoscopy, biopsy

Low Grade Urothelial NeoplasmLGUN

10% Need biopsy to further evaluate grade and stage

High Grade UC >90% More aggressive follow up, cystoscopy, biopsy, staging

Other malignancy >90% More aggressive follow up, cystoscopy, biopsy, staging

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The Milan System for Reporting

Salivary Gland Cytopathology

Sponsored by the ASC and the IAC

Practical classification system, user-friendly and internationally

accepted

Evidence-based, providing a useful & uniform format for clinicians

treating salivary gland disease

The classification system and ROM for the diagnostic categories

will be further refined as more data is available in the literature

The Milan System for Reporting

Salivary Gland Cytopathology

Non-diagnostic

Insufficient material (quantitatively/qualitatively)

Non-mucinous cyst contents, Benign elements only

10% cutoff

Non-neoplastic

Inflammatory, metaplastic, reactive

Sialadenitis, sialadenosis, oncocytosis, etc, reactive LN

Clinicoradiologic correlation is important

Atypia of Undetermined Significance (AUS)

Heterogeneous category, mostly compromised specimens

Majority will be reactive atypia

10% cutoff

Neoplasm

Benign

SUMP (Neoplasm but specific entity cannot be named)

Suspicious for Malignancy

Malignant

(LG or HG, Primary or Metastatic)

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ROM (%) Management

Non-diagnostic 25 Clinical/radiographic correlation

Repeat FNA

Non-neoplastic 10 Clinical f/u and radiologic

correlation

AUS 20 Repeat FNA or surgery

Neoplasm – a) Benign

b) SUMP

< 5

35

Conservative surgery or clinical

f/u

Conservative surgery

Suspicious for Malignancy

(Low grade vs. High grade)

60 Surgery

Correlate LG vs. HG

Malignant

(Low grade vs. High grade)

90 Surgery

Correlate LG vs. HG

The Milan System for Reporting

Salivary Gland Cytopathology

No numerics, just bullets

TMS “AUS”

Adenoid Cystic Carcinoma

Basal Cell AdenomaC-kit, MYB

TMS - “NEOPLASM, SUMP (Basaloid)”

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The IAC-Yokohama System for

Reporting Breast FNAB

Cytopathology

Insufficient/Inadequate

Benign

Atypical

Suspicious For Malignancy

Malignant

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Porto

Madrid

The Porto-Madrid System for

Reporting Serous Effusions and

Body Cavity WashingsAn IAC-ASC Initiative (Feb-June 2018)

The International System for

Reporting Serous Fluid

Cytopathology

Non-diagnostic (ND)

Negative For Malignancy (NFM)

Atypia Of Uncertain Significance (AUS)

Suspicious For Malignancy (SFM)

Malignant (M) – Primary and Secondary

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“IAC Sydney” Lymph Node FNA

“International System” Lung Cytology

Offer a common global language regardless of geographic

boundaries and nationalities

Enhance and improve communication and clarity amongst

health care professionals, their patients and administrative

staff

Allows us the ability to describe with adequate precision,

regardless of patient demographics, the exact disease type

and extent of an illness or condition and permits rational

clinical management plans to be developed and implemented

REMEMBER, an early and accurate diagnosis which is

effectively communicated using a standard terminology

would save some poor patient’s life

Advantages of Nomenclature and

Terminologies

Ali SZ and Leteurtre E. The official nomenclature and terminologies in diagnostic cytopathology:

History, evolution, applicability and future. Ann Pathol. 2012 Dec;32(6):e3-7