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Squamous Lesions (SIL)

including HPV and cancer Terminology

 BSCC (UK) current terminology


 BSCC (UK) proposed new terminology
 Bethesda 2001 terminology
 ECTP (European terminology)

Dr. M. Desai
Head of Cytopathology Service/Clinical Lead for Gynaecological Cytology/Consultant
Cytology/Consultant Cytopathologist
& Training School Director
Manchester Cytology Centre
U.K.

BSCC 1986 BSCC Bethesda system 2001 ECTP Terminology


Comparison of BSCC (UK), Bethesda (USA) and ECTP (European) Terminology Proposed new
Terminology
BSCC 1986 BSCC Bethesda system 2001 ECTP Terminology
Proposed new
Terminology
Mild dyskaryosis Low grade dyskaryosis LSIL Mild dysplasia
Negative Negative Negative for Within normal limits (includes all cases of Includes koilocytosis (CIN1)
intraepithelial lesion or koilocytosis provided that
malignancy no high grade dyskaryosis
is present)
Inadequate Inadequate Unsatisfactory for Unsatisfactory due to …
evaluation Moderate dyskaryosis High grade dyskaryosis HSIL Moderate dysplasia
(CIN2).
Borderline nuclear change 1. Borderline change, 1. Atypical 1. Koilocytes (without
Include squamous, but not squamous cells of changes Severe dyskaryosis HSIL 1. Severe dysplasia
otherwise specified. suggestive of (CIN3)
(ASC-
(ASC-US)
intraepithelial
undetermined
neoplasia)
2. Carcinoma in situ
2. Borderline change, high significance (CIN3)
grade dyskaryosis not
excluded. 2. Squamous cell Severe dyskaryosis Severe dyskaryosis ? Squamous cell 1. Severe dysplasia
2. ASC-
ASC-H (cannot changes (not Invasive carcinoma ? Invasive.
? Invasive
exclude HSIL) definitely
3. Borderline change in 2. Invasive
endocervical cells. neoplastic but
merit early squamous cell
3. Atypical
repeat). carcinoma
endocervical /
endometrial / ? Glandular neoplasia ? Glandular neoplasia 1. Endocervical Adenocarcinoma
glandular cells: 3. Atypical glandular carcinoma in situ
NOS or favour cells (qualify).
Endocervical AIS
neoplastic. Non cervical 2. Adenocarcinoma Endocervical
Endocervical Endometrial
From: Revised BSCC terminology : cytopathology Vol19 no.3 June 2008 P.137-157
Endometrial Extrauterine
Extrauterine NOS
NOS

Definition of Dyskaryosis Normal Chromatin Pattern


(SIL) smooth with equal
distribution of nuclear chromatin
 Abnormal chromatin pattern is the essential
requirement.
 Finely speckled, punctate or coarsely clumped chromatin
 Abnormal size,spacing and distribution of chromatin
granules
 Hyper or Hypochromasia
 Irregular nuclear outline + or –
 Minor changes in nuclear outline e.g.single or multiple
folds,wrinkling or serration occur with inflammation and
degeneration.
 Large bulbous protrusions,scalloping or deep notches not
associated with linear folds occur in dyskaryosis.
 Raised nuclear : cytoplasmic ratio

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Abnormal Chromatin Pattern - Abnormal Chromatin Pattern -
Finely Speckled Finely Speckled and Punctate Chromatin

Abnormal Chromatin Pattern - Densely Definition of Dyskaryosis


Hyperchromatic with Clumped Chromatin (SIL)
 Abnormal chromatin pattern is the essential
requirement.
 Finely speckled, punctate or coarsely clumped chromatin
 Abnormal size,spacing and distribution of chromatin
granules
 Hyper or Hypochromasia
 Irregular nuclear outline + or –
 Minor changes in nuclear outline e.g.single or multiple
folds,wrinkling or serration occur with inflammation and
degeneration.
 Large bulbous protrusions,scalloping or deep notches not
associated with linear folds occur in dyskaryosis.
 raised nuclear : cytoplasmic ratio

DYSKARYOTIC CELL (SIL) Abnormal Chromatin distribution


Coarse chromatin with unequal
distribution

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Definition of Dyskaryosis
 Abnormal chromatin pattern is the essential
requirement.
 Finely speckled, punctate or coarsely clumped chromatin
Fine,Speckled and coarse granularity but even distribution of  Abnormal size,spacing and distribution of chromatin
chromatin in NON-DYSKARYOTIC nuclei granules
 Hyper or Hypochromasia
 Irregular nuclear outline + or –
 Minor changes in nuclear outline e.g.single or multiple
folds,wrinkling or serration occur with inflammation and
degeneration.
 Large bulbous protrusions,scalloping or deep notches not
associated with linear folds occur in dyskaryosis.
Fine,speckled and coarse but irregularly distributed  Raised nuclear : cytoplasmic ratio
chromatin of DYSKARYOTIC (SIL) nuclei

Spot the Difference

Chromasia Definition of Dyskaryosis (SIL)


 Abnormal chromatin pattern is the essential
requirement.
 Finely speckled, punctate or coarsely clumped chromatin
 Hyperchromasia  Abnormal size,spacing and distribution of chromatin
granules
 Hyper or Hypochromasia
 Irregular nuclear outline + or –
 Minor changes in nuclear outline e.g.single or multiple
folds,wrinkling or serration occur with inflammation and
degeneration.
 Large bulbous protrusions,scalloping or deep notches not
 Hypochromasia associated with linear folds occur in dyskaryosis.
 Raised nuclear : cytoplasmic ratio

Minor changes in nuclear outline


in Inflammation
Nuclear folds in
normal cell

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Abnormal Nuclear membrane
In Dyskaryosis (SIL)
(Bulbous Protrusion)

Smooth nuclear membrane In


Dyskaryosis (SIL)

Spot the Difference Spot the Difference

Nuclear wrinkling and folding of Nuclear membrane protrusion


and deep notches in
NON DYSKARYOTIC cell
DYSKARYOTIC (SIL) cell

Definition of Dyskaryosis (SIL) Raised Nuclear:Cytoplasmic Ratio


 Abnormal chromatin pattern is the essential
requirement.  Used for grading of dyskaryosis (SIL)
 Finely speckled, punctate or coarsely clumped chromatin  Nucleus occupies more than 50% of area of
 Abnormal size,spacing and distribution of chromatin
granules cytoplasm in High Grade Dyskaryosis (HSIL)
 Pale vs. Hyperchromatic  High Grade dyskaryosis (HSIL) is found in less
 Irregular nuclear outline + or – mature cells
 Minor changes in nuclear outline e.g.single or multiple
folds,wrinkling or serration occur with inflammation and  Moderate dyskaryosis is seen in larger and
degeneration. intermediate size parabasal squamous cells
 Large bulbous protrusions,scalloping or deep notches not
associated with linear folds occur in dyskaryosis.  Severe dyskaryosis is seen in small parabasal
 Raised nuclear : cytoplasmic ratio and basal squamous cells

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Pitfalls (false positive) - high
nuclear:cytoplasmic ratio with:

Endocervical cells
Immature squamous metaplastic
cells
Endometrial cells
Moderate Dyskaryosis Severe Dyskaryosis
HSIL HSIL Lymphocytes

Immature metaplastics Endometrials


Mild Dyskaryosis (LSIL)
Back to Basics
 Cells occur singly and in sheets
 Nuclear changes in mature superficial or
intermediate cells
 Nuclear enlargement
 mild dyskaryotic (LSIL) nuclei at least x3 size
of intermediate nucleus
 Chromatin irregularity
 Irregularity of nuclear membrane + or -
– Notches
– Protrusions
– Spurs
– Not just folds or wavy outline
Follicular cervicitis Endocervicals

Mild Dyskaryosis (LSIL)


Back To Basics
 Dyskaryotic nucleus
 Enlarged nucleus <50% of cell area
 Bi and multinucleation often seen
 Polygonal cytoplasm of mature
squamous cells, individual cell
borders
 Strong association with ASCUS or LSIL? LSIL or HSIL?
koilocytosis Spot the difference

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Dyskaryosis (SIL)
? Grade

Borderline(ASCUS) Mild to Moderate Dyskaryosis


TO (LSIL TO HSIL)
Mild Dyskaryosis (LSIL)

Subjectivity Still Persist : Not a full proof Science

Spot The Spot The


Difference Difference

Mild Dyskaryosis (LSIL)

Borderline changes (ASCUS)

Features of high-
high-grade dyskaryosis
(HSIL)
Back To Basics
 Increased depth of focus
 Irregularity of nuclear membrane (walnut)
 Increase in single, isolated and small abnormal
cells
 Few abnormal cells
 Isolated abnormal cells present in empty spaces
between cell clusters
 Rounding up of cells resulting in smaller size and
higher N:C ratio
 Cleaner background

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Features of high-
high-grade dyskaryosis
(HSIL)
Back To Basics
 Increased depth of focus
 Irregularity of nuclear membrane (walnut)
 Increase in single, isolated and small abnormal
cells
 Few abnormal cells
 Isolated abnormal cells present in empty spaces
between cell clusters
 Rounding up of cells resulting in smaller size and
higher N:C ratio
 Cleaner background

Features of high-
high-grade dyskaryosis
(HSIL)
 Increased depth of focus
 Irregularity of nuclear membrane (walnut)
 Increase in single, isolated and small
abnormal cells
 Few abnormal cells
 Isolated abnormal cells present in empty spaces
between cell clusters
 Rounding up of cells resulting in smaller size and
higher N:C ratio
 Cleaner background

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Features of high-
high-grade dyskaryosis
(HSIL)
 Increased depth of focus
 Irregularity of nuclear membrane (walnut)
 Increase in single, isolated and small abnormal
cells
 Few abnormal cells
 Isolated abnormal cells present in empty spaces
between cell clusters
 Rounding up of cells resulting in smaller size and
higher N:C ratio
 Cleaner background

Features of high-
high-grade dyskaryosis
(HSIL)
 Increased depth of focus
 Irregularity of nuclear membrane (walnut)
 Increase in single, isolated and small abnormal
cells
 Few abnormal cells
 Isolated abnormal cells present in empty
spaces between cell clusters in LBC and in
streaks in conventional smears
 Rounding up of cells resulting in smaller size and
higher N:C ratio
 Cleaner background

Features of high-
high-grade dyskaryosis
(HSIL)
 Increased depth of focus
 Irregularity of nuclear membrane (walnut)
 Increase in single, isolated and small abnormal
cells
 Few abnormal cells
 Isolated abnormal cells present in empty spaces
between cell clusters
 Rounding up of cells resulting in smaller size
and higher N:C ratio
 Cleaner background

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Features of high-
high-grade dyskaryosis
(HSIL)
 Increased depth of focus
 Irregularity of nuclear membrane (walnut)
 Increase in single, isolated and small abnormal
cells
 Few abnormal cells
 Isolated abnormal cells present in empty spaces
between cell clusters
 Rounding up of cells resulting in smaller size and
higher N:C ratio
 Cleaner background in LBC

Grade the Dyskaryosis (SIL) ?


Grading of dyskaryosis (SIL)
Useful Tips
 Higher N:C ratios / areas / diameter with
increasing grade of dyskaryosis (SIL).
 HSIL (Moderate between ½ to 2/3
Severe > 2/3)
 Mild (LSIL) in superficial and Intermediate cells
 HSIL( Moderate in Large and intermediate size
parabasal and Severe in Small parabasal and
basal cells.)
 Dyskaryosis (SIL) in immature squamous cells
most likely represents high-
high-grade dyskaryosis
(HSIL)

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Grade the Dyskaryosis (SIL) ?
Grade the Dyskaryosis (SIL)

Moderate and Severe


Dyskaryosis
(HSIL)

Mild and Moderate


Dyskaryosis
(LSIL AND HSIL)

Grade the Dyskaryosis (SIL)

Grade the Dyskaryosis (SIL)

Mild Dyskaryosis/LSIL

Grade the Dyskaryosis (SIL)


Grade the Dyskaryosis (SIL)

Moderate Dyskaryosis/HSIL

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Grade the Dyskaryosis (SIL)
Grade the Dyskaryosis (SIL)

Severe Dyskaryosis/HSIL

Grade the Dyskaryosis (SIL)


Low grade or High Grade?

Subjectivity persist

Grade the Dyskaryosis (SIL)

Grade the Dyskaryosis (SIL)


Low Grade or High Grade?
Patterns of Dyskaryosis (SIL)
Pattern recognition and experience

Subjectivity persist

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Patterns of dyskaryosis (SIL) Ungraded Dyskaryosis
 Ungraded Dyskaryosis (SIL)
(SIL)
 Large cell non-
non-keratinising (Syncitial
(Syncitial))  Dyskaryotic bare nuclei
 Keratinising  Loss of cytoplasm due to cytolysis or atrophy
 Mixed  Loss of cell boundaries
 Scanty dyskaryosis (SIL)
 Small cell dyskaryosis (SIL)
 CIN microbiopsies (HCGs
(HCGs))
 Flag cells
 Pale cell dyskaryosis (SIL)
 Bland cell dyskaryosis (SIL) In Thinprep
 Grade as High grade dyskaryosis (HSIL)

Large cell non-


non-keratinising (syncitial
(syncitial))
High Grade Dyskaryosis with High gradeDyskaryosis (HSIL)
bare nulcei
 Loose syncytial groupings
 Nuclei four to six times diameter of
polymorphs
 Nuclei rounded and pale staining
 Finely speckled chromatin
 Cytoplasm relatively abundant, delicate and
indistinct
 N/C ratio difficult to assess, usually less than
half, misinterpreted as mild diskaryosis (LSIL)
Ungraded Dyskaryosis  Misinterpreted as CGIN when in continuity
with endocervical cells

Large cell non-keratinising severe dyskaryosis


Keratinising High grade
Dyskaryosis (HSIL)

 Cytologically indistinguishable from


keratinising squamous cell carcinoma

Syncytial variety

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Small Cell Dyskaryosis
(HSIL)
 Monotonous cell population
 Abnormal chromatin pattern
 Nuclear diameter less than twice of
polymorphs or lymphocyte
 High nuclear:cytoplasmic ratio
 Can have regular nuclear membrane
 D/D immature metaplastic
cell,EM,Histiocyte,Follicular
cervicitis,atrophic EC and atrophic parabasal
squamous cells

Small cell dyskaryosis


Screening and Interpretation Error
Small cell dyskaryosis
Misinterpreted as
 Normal endometrial cell

 Immature metaplastic cells

 Lymphocyte

 Follicular cervicitis

 Normal Histiocyte

 Atrophic endocervical cells

 Normal parabasal squamous cell

HISTIOCYTES,
Small cell severe dyskaryosis

Sparse (Scanty) dyskaryosis (SIL)

 Litigation cell
 Easily overlooked in routine screening
 More difficult to recognise if pale,small and
FOLLICULAR CERVICITIS
single

LYMPHOCYTES ENDOMETRIALS

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Scanty dyskaryosis

Scanty Dyskaryosis (SIL): overlapping of the Litigation cell


fields is essential in screening

Scanty Dyskaryosis (SIL) Flag Cell

 Small keratinised cell with pyknotic,


India ink nucleus
 On its own should not be reported as
High grade dyskaryosis
 Search for High grade dyskaryosis in
other areas

Flag cell Associated High grade dyskaryosis

Flag cells : Search for High grade dyskaryosis


(HSIL) or invasive features

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Pale cell Dyskaryosis (SIL)
Pale cell Dyskaryosis (SIL)
 Hypo chromatic nuclei
 May be a staining artefact
 Identified by abnormal chromatin
pattern
 Can be seen in all grades of
dyskaryosis (SIL) and types of cells
 Often present mixed with some
“normal”
normal” staining cells
 Nuclear membrane irregularity + or -

Pale dyskaryosis /SIL Pale dyskaryosis/SIL

Pale dyskaryosis/SIL

Bland Dyskaryosis/SIL:
A New Pitfall in Liquid Based
Cytology (ThinPrep)
Dr. D.N.Rana,Dr.K.Denton,
D.N.Rana,Dr.K.Denton,
Dr. M. Desai & Dr. M. Lynch
Cytopathology May-
May-June 2008,
19(3) P162-
P162- 166

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BLAND CELL DYSKARYOSIS (SIL)
Bland Dyskaryosis (SIL) •Chaotic group
• Mimicking endocervicals
 Dyskaryotic/SIL cells appear deceptively bland
on low - power examination

 Misinterpreted as squamous metaplastic cells


or endocervical cells

 Seen in groups

 Disorganised architecture within the group

Bland Dyskaryosis (SIL)


 Variation in cell size

 Raised nuclear:cytoplasmic ratio

 Speckled / punctate chromatin pattern

 Chromatin may be evenly distributed


Bland cell dyskaryosis (SIL)
 Smooth nuclear outlines Overcrowding
• Speckled chromatin pattern
• Smooth nuclear membranes

CIN Microbiopsies (HCGs


(HCGs))
 3D groups
 Nuclear crowding
 Disorderly chaotic architecture
 Steep relief at edge of group
 Evaluate the cells at edge
 Abnormal nuclear chromatin
 Hyperchromatic nuclei
 Nuclear membrane irregularities less pronounced
 Increased mitotic activity
 Nucleoli more visible

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ALL of the following cells are
normal !

ALL of the following cells are


abnormal !

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High-
High-grade dyskaryosis (HSIL)
Pitfalls
 Metaplastic cells
 Endometrial cells
 Histiocytes
 Atrophy
 Blue blobs
 IUCD cells
 Reactive inflammatory sheets
 Glandular neoplasia (cervical type)

Invasive Squamous
Carcinoma

Different types of Invasive


Squamous Cell Carcinoma Microinvasive

 Micro invasive
* Can not be diagnosed reliably
 Keratinising
* Indistinguishable from severe
 Non keratinising large cell
dyskaryosis
 Non keratinising small cell
* Macronucleoli in syncitial
 Verrucous carcinoma
aggregates of severe dyskaryosis
* Irregular chromatin distribution

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Invasive Squamous cell Invasive squamous cell
Carcinoma: carcinoma :
Architectural features Cellular features

* Tumour diathesis
* Large numbers of dyskaryotic cells
(severe dyskaryosis)
* Very bizarre cell shapes
* Single cells, loose aggregate
* Fibre and tadpole cells
* Sheets of undifferentiated cells
HCCG * Cell embracement ( cell into cell
pattern)

Invasive Squamous cell Tumour Diathesis


Carcinoma:
Nuclear features *Grey/blue granular material
• Marked pleomorphism clinging to malignant cells
( Different size & shape) * Blood fresh and old (haemosiderine
(haemosiderine))
* Fibrin and protein
• Irregular Nuclear Membrane
* Cell necrosis and debris
• Coarse, granular chromatin pattern * Nuclear and cytoplasmic fragment
• Hyperchromasia with windowing * polys ,inflammatory dirty background
(parachromatin clearing) Diathesis is rare, reflects ulceration of surface mucosa and
associated with late stage disease
• Angulated chromatin Absent in microinvasive and verrucous carcinoma
• Mitotic figure
• irregular macronucleoli

Benign Diathesis
Benign Diathesis

*Inflammatory,dirty background
*Absence of Malignant cells
*Severe infection e.g.Trichomonas Tumour Diathesis
*Severe atrophy
*Abscess
*Necrotic,ulcerated polyp

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Abnormal nucleoli Nucleoli

 These can be single or multiple


 If single, they are usually large and
abnormal with windowing
 If multiple the nucleoli vary in size and
shape
 They may be red staining

Nucleoli Nucleoli
Malignant Reactive

Small Cell Non-


Non-keratinizing Differential Diagnosis of Small Cell
Squamous Carcinoma Squamous cell carcinoma

*Tumour cells occur singly or in small


* Normal and abnormal endometrial cells
discohesive syncitial like groups. * Lymphoid lesions
* Cells small, cuboidal or round * Small cell severe dyskaryosis
* Scanty cytoplasm * Reserve cell hyperplasia
* High N/C ratio
* No keratinization
* Nuclei large, round to oval
* Hyperchromatic, coarsley granulated chromatin
* Nucleoli small, may be obscured

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Large Cell
Non-
Non-Keratinizing Differential Diagnosis of Large cell, Non-
Non-
Squamous cell carcinoma keratinizing Squamous cell carcinoma

* Numerous single cells and discohesive * Repair cells


syncitial groups of cells * Endocervical Adenocarcinoma
* Cellular and nuclear pleomorphism is
less than keratinizing SCC
* High N/C ratio
* Nuclear overlapping

Repair Cells

* Cohesive, flat, monolayered sheets of polygonal


squamous cells
* Distinct cytoplasmic boundaries
* Frequent cytoplasmic projectious (pseudopodia)
* Tumour diathesis ABSENT
cont……

Differential Diagnosis of
Repair Cells Repair Cells vs Non-keratinizing SCC

Features Favour Repair

* Inflammatory benign diathesis * Flat sheet arrangement of cells rather than


* Cytoplasm delicate, cyanophilic, no keratinization syncitia or three dimensional clusters
* Cytoplasmic vacuoles containing neutrophils and nuclear * Lack of nuclear overlapping
debris * Lack or rarity of single cells
* Nuclei enlarged * Lack of tumour diathesis
* N/C ratio is only slightly or moderately Increased * Fine Chromatin
* Nuclear chromatin finely granular and evenly distributed
* One or several prominent eosinophlilic nucleoli
* Mitotic figures may be present

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Quiz Time

Invasive Carcinoma

Atypical repair

Keratinizing Differential Diagnosis


Squamous Cell Carcinoma of Keratinizing SCC

* Highly discohesive cells


* Spindle keratinized cells Atypical parakeratosis/ dyskeratosis
* Keratinised cells with bizarre cytoplasmic - individual cell may look malignant but are
forms too small
* Tadpole and caudate Cells - can occur in Sq.cell ca, inflammation,
* Nuclei hyperchromatic with coarsely clumped, condyloma (wart) and keratinizing CIN
irregularly distributed chromatin
* Indistinct nucleoli
* Tumour diathesis maybe absent

Keratinizing SCC
Verrucous
False negative result Carcinoma
*Rare tumour
*Infected,ulcerated tumour *Slow growing, exophytic tumour,
*rarely metastasize
*Scanty malignant cells
*Cytology misleading
*Verrucous carcinoma *Hyperkeratosis and parakeratosis
*Scanty dyskaryotic cells
*Absence of Malignant nuclei

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Acknowledgement
My special thanks to
Dr. Rana,Dr.
Rana,Dr. Denton & Dr. Bijal Shah
From UK
&
Mr.Andrew Evered
From Wales Training School
For
Producing images and drawings
and
Writing some of the texts

I have also used Hologic Cytyc Thinprep Images, BD


Surepath Images Images from NHSCSP atlas and images
and the tables from arts and Science of cytology book from
Prof. DeMay for this presentation

Koilocytes
Cytology of HPV  Koilo = Hollow or cavity
 Cytopathic effect of HPV infection
Two Pathognomic cell pattern  Intermediate or superficial squamous cells
containing large perinuclear cavity with
 Koilocyte sharply cut borders
 Dyskeratocyte  Dense eosinophilic or cyanophilic cytoplasm
Other Non-
Non- specific cell patterns peripheral to the cavity
 Enlarged abnormal nucleus
 Cells – Macrocytes , Kites, balloons
 Chromatin varies from degenerate (smudged
 Cytoplasm – Polka dots, cracks pyknotic,
pyknotic, fragmented) to normal or slight
 Nuclei – Bi and multinucleation,
multinucleation, spindling, coarsening
smudging  Nuclear membrane NOT apparent
 Inconspicuous nucleoli
 No inclusion bodies
 Bi and Multinucleation is common

Koilocytotic Atypia Group of Koilocytes


Back To Basics
 Clear well defined area around
nucleus
 Thickened edge, sharply
demarcated border
 Some nuclear atypia

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Koilocyte Simulation
Diagnostic Dilemmas
Koilocyte Simulation (Pseudokoilocyte
(Pseudokoilocyte)) Figure 162 Figure 163 Figure 164

 Non HPV changes


 Rolling edge of cytoplasm (common with LBC)
 Intracytoplasmic glycogen lacking yellow-
yellow-brown
staining
 Non HPV inflammation
Terminology Figure 165 Figure 166

 USA-
USA-Bethesda – LSIL
 UK – BL vs. Mild dysk
 ECTP-
ECTP-European-
European-Separate category

Diagnostic Dilemma
Terminology
Koilocyte Terminology
U Turn
Theories of pathogenesis
 Koilocyte is cellular changes of HPV infection Bethesda Explanatory Notes
that mimics dysplasia but is not genuine  Koilocytic nuclear changes that fall short of
dysplasia a definitive SIL interpretation may be
 Koilocyte is precursor to dysplasia categorised as ASC-
ASC-US
 Koilocyte is dysplasia Revised BSCC (UK) Terminology
Current Terminologies  In koilocytosis,
koilocytosis, it is difficult to achieve
 USA-
USA- Bethesda-
Bethesda-Koilocyte is dysplasia = LSIL consistency in the differentiation of nuclear
changes between BNC and Mild Dyskaryosis,
Dyskaryosis,
 UK-
UK- Koilocyte is precursor to dysplasia = therefore combine them as Low- Low-grade
BNC or mild dyskaryosis dependent squamous dyskaryosis
on nuclear abnormality
 ECTP – koilocyte is cellular changes of
infection=
infection= separate entity

T
E Spot The
R Difference
M
I
N
O
L
O
G
BNC vs. Mild dysk ASCUS vs. LSIL
Y

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Dyskeratocytes
HPV Cytology In The Absence Of HPV
Dyskeratocytes Infection
 Small keratinized pearls, rafts or spikes
 Abnormal Keratinization
 Cells arranged in orderly pattern
 Keratinized squamous cells staining
 Small,uniform,widely spaced nuclei that
brilliant orange with OG-
OG-6 of pap stain
flattens towards the edge to lie along the
( Pink with Surepath LBC ) long axis of the group
 Single or in thick, 3D clusters  No nuclear abnormality
 Clusters without discernible polarity
 Nuclear enlargement with condensed or
granular chromatin details

Other Non-
Non-specific cell
patters

Macrocyte Kite Cells

Dyskeratotic cells Dyskeratotic cells


Without HPV With HPV

Balloon Cells Polka Dot

Cytology of HPV infection


Incidence of HPV Infection
After HPV Test
 Incidence 4 % by cytology diagnosis  Cytology Negative / HPV positive
and 20-
20-30% by molecular diagnosis  Cytology BNC with Koilocyte (LSIL) /
 Koilocytes are covered by dyskeratotic cells HPV positive
and not shedding in many cases of HPV
infection  Cytology BNC without koilocyte
(ASCUS) / HPV positive
 Cytology Dyskaryosis (LSIL OR HSIL)/
Cytology severely underestimates the true HPV positive
incidence of HPV infection

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Cytology reporting HPV reporting
after HPV Test Cytology vs Molecular test
Should we be reporting Koilocyte Should we be replacing cytology
in cytology? with HPV Molecular Test?

 Koilocyte demonstrates complete Dilemma of Cytology negative BUT HPV positive Molecular
Test
infective viral particles  Epithelial cells are not producing virus particles
 Patient is likely to be in immunologic equilibrium with
 Pathognomic of HPV infection the virus
 Virus will eventually disappear
 Koilocyte with HPV test neg. is  Transmission of virus to sexual partner (s) at this stage
is doubtful
confusing for pt  Eventual outcome of the infection is not known
 Require long term follow-
follow-up study to establish long
 UK decided not to report koilycyte in term FU protocol
cytology report at sentinel sites for HPV ARTISTIC Trial is extended for further 6 years
triage with low grade abnormality

Modern Koilocyte is
Moving The End
To
The Molecular LBC Smears
with HPV Test

AND
NOT Retiring Yet!

Acknowledgement
My special thanks to
Dr. Rana,Dr.
Rana,Dr. Denton & Dr. Bijal Shah
From UK
&
Mr.Andrew Evered
From Wales Training School
For
Producing images and drawings
and
Writing some of the texts

I have also used Hologic Cytyc Thinprep Images, BD


Surepath Images and
Images from NHSCSP atlas
For this presentation

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