Unified global reporting of

cervical cytology and histology

Dr J H F Smith Royal Hallamshire Hospital, Sheffield

North of England Pathology & Screening Education Centre

Dr J H F Smith Royal Hallamshire Hospital, Sheffield

North of England Pathology & Screening Education Centre

ECC 2016

Papanicolaou classification

Class I Negative Absence of atypical or abnormal

cells

Class II Negative Atypical cells present but without

abnormal features

Class III Suspicious Cells with abnormal features

suggestive but not conclusive for

malignancy

Class IV Positive Cells and cell clusters fairly

conclusive for malignancy

Class V Positive Cells and cell clusters conclusive

for malignancy

WHO classification: Dysplasia

In mild dysplasia the cells are usually of superficial

or intermediate cell type. Chromatin pattern is

uniform; there may be numerous small

chromocentres

In moderate dysplasia there is a group of cellular

patterns intermediate between mild and severe

dysplasia

In severe dysplasia the cells are mainly of

parabasal and small intermediate type. The

chromatin is dense and uniform, with many darkly

stained, slightly enlarged chromocentres

Dyskaryosis

Dys =

Karyon =

Abnormal

Nucleus

Dyskaryosis

Disproportionate nuclear enlargement

Irregularity in form and outline

Hyperchromasia

Multinucleation

Irregular chromatin distribution - stippled, clumped or stranded with condensation beneath the nuclear membrane

Abnormalities of the number, size and form of nucleoli

Papanicolaou 1954

Grading dyskaryosis 1986-2013

Mild

dyskaryosis

Abnormal nucleus

occupies less than half the

area of the cell CIN 1

Moderate

dyskaryosis

Abnormal nucleus

occupies one half to two

thirds of the area of the cell CIN 2

Severe

dyskaryosis

Abnormal nucleus

practically fills the cell or at

least two thirds of its area CIN 3

CIN 1 CIN 2 CIN 3

MILD

DYSKARYOSIS

MODERATE

DYSKARYOSIS

SEVERE

DYSKARYOSIS

Grading dyskaryosis. Have we

been doing what we think we’ve

been doing?

No

Proposed Sheffield quantitative criteria in cervical cytology to

assist in grading of squamous cell dyskaryosis as the British

Society for Clinical Cytology definitions require amendment.

D N Slater, S Rice, R Stewart, S E Melling, E M Hewer, J H F Smith

Cytopathology 2005; 16: 179-192

Morphometry identifies mild, moderate and

severe dyskaryosis as separate

populations statistically but high degree of

overlap

Moving to two-tier system gives practical

separation between the groups

Diameter ratio of 50% separates high

and low grade dyskaryosis

Works for LBC and conventional

Similar NC area ratios for borderline

changes associated with HPV and mild

dyskaryosis support combining these as

low grade dyskaryosis

Reporting and classification of

cervical cytology

Definition of dyskaryosis

The primary requirement for identification

of dyskaryosis is an abnormal chromatin

pattern

Denton et al. Cytopathology 2008; 19: 137-157

BSCC terminology

1986

BSCC terminology 2008 Result

code

Borderline change Borderline change in squamous cells 8

Borderline change in endocervical cells 9

Mild dyskaryosis

Borderline change with koilocytosis

Low-grade dyskaryosis 3

Moderate dyskaryosis High-grade dyskaryosis (moderate) 7

Severe dyskaryosis High-grade dyskaryosis (severe) 4

Severe dyskaryosis?

invasive

High-grade dyskaryosis ?invasive squamous

carcinoma

5

?Glandular neoplasia ?Glandular neoplasia of endocervical type 6

?Glandular neoplasia (non-cervical) 0

Cytopathology 2008; 19: 137-157

Cytopathology 2008; 19: 137-157

Reporting and classification of

cervical cytology

Grading squamous dyskaryosis

Low-grade dyskaryosis

– Dyskaryotic cells with a nuclear:cytoplasmic

diameter ratio of <50 %.

Slater et al. Cytopathology 2005; 16: 179-162

Reporting and classification of

cervical cytology

Grading squamous dyskaryosis

Low-grade dyskaryosis

– Borderline nuclear change with koilocytosis

Low grade dyskaryosis

Reporting and classification of

cervical cytology

Grading squamous dyskaryosis

High-grade dyskaryosis

– Dyskaryotic cells with a nuclear:cytoplasmic

(N:C) diameter ratio of >50 %.

– If the N:C diameter ratio is <75 %, report as high-grade

dyskaryosis (moderate)

– If the N:C diameter ratio is >75 %, report as high-grade

dyskaryosis (severe)

Reporting and classification of

cervical cytology

Grading squamous dyskaryosis

High-grade dyskaryosis

– Dyskaryotic cells with a nuclear:cytoplasmic

(N:C) diameter ratio of >50 %.

MODERATE SEVERE

Why two tiers rather than three?

Clinical management uses two tier system

Most cases CIN 2 and CIN 3 have

integrated HPV DNA and therefore persist

with risk of progression

Mirrors the distinction between LSIL and

HSIL in the Bethesda System

Why two tiers rather than three?

Clinical management uses two tier system

Most cases CIN 2 and CIN 3 have

integrated HPV DNA and therefore persist

with risk of progression

Mirrors the distinction between LSIL and

HSIL in the Bethesda System

CIN 2 Ranking Unvaccinated Point Est (95% CI)

1 hpv16 62.8 (57.8, 67.6) 2 hpv33 15.6 (12.3, 19.7) 3 hpv31 14.8 (11.6, 18.8) 4 hpv52 10.5 (7.8, 14) 5 hpv51 7.5 (5.3, 10.7) Vaccinated 1 hpv16 41 (27.1, 56.6)

2= hpv 31,33,56 15.4 (7.2, 29.7) 3= hpv 52, 58 and 82 10.3 (4.1, 23.6) 4= hpv 11, 51, 53 7.7 (2.7, 20.3) 5= hpv 39,42,45,73 5.1 (1.4, 16.9)

CIN 3 Ranking Unvaccinated

1 hpv16 78.2 (73.8, 82.1) 2 hpv31 15.1 (11.9, 19.1) 3 hpv33 14.3 (11.1, 18.2) 4 hpv52 8.2 (5.9, 11.4) 5 hpv18 7.4 (5.2, 10.5) Vaccinated 1 hpv 16 55 (39.8, 69.3) 2 hpv 33 17.5 (8.7, 31.9) 3 hpv 31 15 (7.1, 19.1) 4 hpv 82 12.5 (5.5, 26.1)

5= hpv 58, 66 10 (4, 23.1)

Ranking of most common HPV types in CIN2 & 3 by immunisation status

Why two tiers rather than three?

Clinical management uses two tier system

‘CIN 2 is likely to be a mixed category containing

some productive infection (LSIL) that show

greater nuclear abnormality and less

cytoplasmic maturation; and some transforming

infections (HSIL) that show greater cytoplasmic

maturation and less nuclear abnormality’

Mirrors the distinction between LSIL and

HSIL in the Bethesda System

Castle. Am J Clin Pathol 2007; 127: 805

Herrington. Cytopathology 2015: 26: 346

A Global Terminology

Low grade

High grade Favour CIN 2

Favour CIN 3