precancerous lesions

1. BETHESDA SYSTEM
Winner Of Shan S Ratnam Young Gynaecologist Award- Asia Oceania 2017
Winner Of FOGSI- Dr. Shanti Yadav Award In Infertility 2019
Fogsi-Dr. Prabhavati R. Dixit Scholarship For Overseas Study 2019-20
Winner Of Prestigious FOGSI Kamini Rao YUVA Orator 2016-17 Award
Winner Of Pravin Mehta Fellowship Award For Laparoscopy 2016
Winner Of Nimish Shelat Award For Endocrinology Best Paper 2016
Winner Of IMA CT Thakkar National Award 2014, Winner Of Dr Kumud P. Tamaskar Award 2014,
Winner Of FOGSI CORION Award '13, Winner Of IMA Dr DS Munagekar National Award '13
Winner Of FOGSI GSK Oncology Award '13
Winner Of Travelling Fellowship Award'13
Dr Indranil Dutta 9831476666
Prof.DrIndranilDutta
MBBS, M.S (OBG), PGDHHM,PGDMLS, FIAOG,F.A.G.E, FIAMS
Dip. Advanced Laparoscopic Surgery (Kiel, Germany)
Dip. Cosmetic Gynaecology (American Aesthetic Asso.)
Fel.USG, Fel. Endo.Surg, Fel. Infertility
Fel. Gynae Oncology. (CNCI, Kol), Trained in IVF/ICSI/ Embryology
Professor,MedicalCollege,IQCity& NH,Durgapur(WB)
Immediate Past President, KOGS (FOGSI), Exc Member YTP CommitteeFOGSI
Past East Zone Coordinator (2020-21)under FOGSI President
IMA Standing Committee Memberfor Anti Microbial Resistance (2018-2022)
• Published 40 Articles in various Indexed Journals
• Articles of Repute included in PUBMED Database and Cochrane Database
• Contributed Chapters in 20 FOGSI books including one International Book “Jefcoatte’s Gynaecology”
• Editor – Two Books including FOGSI Focus on Drugs Update
• Organized 5 FOGSI Conferences in Kolkata and 10 other CME/ Local Body Conferences
• Member of FOGSI, IMA, SAFOG, ISAR, IAGE and ASPIRE (Asia Pacific Initiative on Reproduction)

2. THE BETHESDA SYSTEM
It is a system of reporting cervical or vaginal cytology (used
for reporting Pap smear results).
The Papanicolaou test (also called Pap smear, pap test,
cervical smear or smear test) is a screening test used to detect
potentially pre-cancerous and cancerous process in the cervix.

3. History of the Bethesda system:
In December 1988, a small group of individuals with expertise in
cytopathology, histopathology, and patient management met at the
National Institutes of Health in Bethesda, Maryland
This meeting was the first Bethesda workshop chaired by Robert Kurman
Objective: To establish terminology that would provide clear-cut
thresholds for management and decrease interobserver variability in
reporting of cervical cytology.
Subsequent Bethesda workshops were convened in 1991 and 2001 and
2014.

4. Noteworthy Points from the 2001
Bethesda Update Included the Following
1.The terms ‘interpretation' or ‘result' were recommended instead
of ‘diagnosis' in the heading of the cervical cytology report, because
cervical cytology is primarily a ‘screening test, which serve as a
medical consultation by providing an interpretation that contributes
to a diagnosis.
2.Specimens from other sites in the lower anogenital tract, such as
the vagina and anus, could also be reported using this terminology
3.Between 1991 and 2001, liquid-based cytology, automation,
computer-assisted imaging, and HPV testing were introduced and
increasingly utilized in laboratories that offered cervical cytology
testing. It addressed all of these considerations
4.Print atlas published and an educational Bethesda website was
established

5. Bethesda 2014: Why?
Increased use of liquid-based preparations; the addition of co-testing
(Pap and hrHPV testing) and, more recently, primary hrHPV testing as
additional screening options
Management guidelines for abnormal cervical cytology results were
updated in 2006 and 2012, with increased incorporation of hrHPV and
genotyping for triage and follow-up.
On the basis of all of these changes, 2014 was an appropriate time
for a review and update of the 2001 Bethesda System terminology,
refinements of morphologic criteria, and incorporation of revisions
and additional new information

6. Cervical screening:
Patient preparation:
1)Women should be tested 2 weeks after the first day of their last
menstrual period.
2)Women should not use any vaginal medication, contraception during the
48 hrs prior to sample collection.
3)Sexual relationship is not recommended the night before the test.

7. Collection of sample:
Sample collection :
Optimal sample include cells from the ectocervix and endocervix.
Squamo-columnar junction (Most likely site of dysplasia).

8. American cancer society recommendation
for cervical screening
Screening should begin no later than age 21.
Screening should begin earlier than age 21 if the patient is sexually
active. In this case, it should start 3years after initiation of vaginal
intercourse.
Once initiated, screening should be performed annually.
After age 30, for women who have had 3 consecutive normal pap
smears, screening frequency may be reduced to every two to three
years.
Women who are HIV positive, immunocompromised should continue
annual screening.
Patient tested positive for HPV, should continue to be screened
indefinitely.
May stop after age 70. if patient is low risk and has had three normal
pap smears over the last 10 years.

9. THE 2014 BETHESDA SYSTEM
(TBS)
 SPECIMEN TYPE
 SPECIMEN ADEQUACY
 GENERAL CATEGORIZATION (optional)
 INTERPRETATION / RESULT
 ANCILLARY TESTING
 AUTOMATED REVIEW
 EDUCATIONAL NOTES AND SUGGESTIONS(optional)

10. The 2014 BETHESDA SYSTEM FOR
REPORTING CERVICAL CYTOLOGY
1)SPECIMEN TYPE:
Indicate conventional smear (Pap smear) vs. liquid-based preparation vs. other
2)SPECIMEN ADEQUACY :
•Satisfactory for evaluation ( describe presence or absence of
endocervical/transformation zone component and any other quality indicators,
e.g., partially obscuring blood, inflammation, etc. )
• Unsatisfactory for evaluation ( specify reason )
– Specimen rejected/not processed ( specify reason )
–Specimen processed and examined, but unsatisfactory for evaluation of
epithelial abnormality because of ( specify reason )

11. 3)GENERAL CATEGORIZATION ( optional )
• Negative for Intraepithelial Lesion or Malignancy
• Other: See Interpretation/Result ( e.g., endometrial cells in a woman ≥45
years of age )
•Epithelial Cell Abnormality: See Interpretation/Result ( specify ‘squamous’ or
‘glandular’ as appropriate )
4)INTERPRETATION/RESULT
I)NEGATIVE FOR INTRAEPITHELIAL LESION OR MALIGNANCY:
When there is no cellular evidence of neoplasia, state this in the General
Categorization above and/or in the Interpretation/Result section of the report
-- whether or not there are organisms or other non-neoplastic findings

12. A)NON-NEOPLASTIC FINDINGS ( optional to report; list not inclusive )
• Non-neoplastic cellular variations
– Squamous metaplasia
– Keratotic changes
– Tubal metaplasia
– Atrophy
– Pregnancy-associated changes
• Reactive cellular changes associated with:
– Inflammation (includes typical repair)
- Lymphocytic (follicular) cervicitis
– Radiation
– Intrauterine contraceptive device (IUD)
• Glandular cells status post hysterectomy

13. B)ORGANISMS
• Trichomonas vaginalis
• Fungal organisms morphologically consistent with Candida spp.
• Shift in flora suggestive of bacterial vaginosis
• Bacteria morphologically consistent with Actinomyces spp.
• Cellular changes consistent with herpes simplex virus
• Cellular changes consistent with cytomegalovirus
C)OTHER
• Endometrial cells ( in a woman ≥45 years of age ) ( Specify if “negative
for squamous intraepithelial lesion” )

14. II)EPITHELIAL CELLABNORMALITIES
SQUAMOUS CELL
• Atypical squamous cells – of undetermined significance (ASC-US)
– cannot exclude HSIL (ASC-H)
•Low-grade squamous intraepithelial lesion (LSIL) ( encompassing: HPV/mild
dysplasia/CIN 1 )
•High-grade squamous intraepithelial lesion (HSIL) ( encompassing: moderate and
severe dysplasia, CIS; CIN 2 and CIN 3 ) – with features suspicious for invasion ( if
invasion is suspected )
• Squamous cell carcinoma
GLANDULAR CELL
• Atypical
– endocervical cells (NOS or specify in comments )
– endometrial cells (NOS or specify in comments )
– glandular cells (NOS or specify in comments )
• Atypical
– endocervical cells, favor neoplastic
– glandular cells, favor neoplastic

15. • Endocervical adenocarcinoma in situ
• Adenocarcinoma
– endocervical
– endometrial
– extrauterine
– not otherwise specified (NOS)
OTHER MALIGNANT NEOPLASMS: (specify)
5)ADJUNCTIVE TESTING: Provide a brief description of the test method(s) and
report the result so that it is easily understood by the clinician.
6)COMPUTER-ASSISTED INTERPRETATION OF CERVICAL CYTOLOGY: If case
examined by an automated device, specify device and result.
7)EDUCATIONAL NOTES AND COMMENTS APPENDED TO CYTOLOGYREPORTS
(optional): Suggestions should be concise and consistent with clinical follow-up
guidelines published by professional organizations (references to relevant
publications may be included)

16. The Bethesda
system
1)SPECIMEN TYPE
Indicate Conventional smear (Pap smear)
vs. liquid-based preparation
vs. other.

17. Conventional
Pap
In a conventional Pap smear , samples are smeared directly onto slide after
collection.
Liquid based cytology
The sample of (epithelial) cells is taken from the Transitional Zone
Liquid-based cytology uses an arrow-shaped brush
The cells taken are suspended in a bottle of preservative & transported to the
laboratory .

20. 2)SPECIMEN ADEQUACY
I)Satisfactory for evaluation
describe presence or absence of endocervical/ transformation
zone component and any other quality indicators, e.g.,
partially obscuring blood, inflammation, etc., as appropriate
II)Unsatisfactory
indicate whether or not the laboratory has processed/ evaluated
the slide. Suggested wording:
A.Rejected specimen: Specimen rejected (not processed)
because (specimen not labeled, slide broken, etc.)
B. Fully evaluated, unsatisfactory specimen: Specimen processed
and examined but unsatisfactory for evaluation of epithelial
abnormality because of (obscuring blood, etc.)
Additional comments/recommendations, as appropriate

21. Minimum squamous cellularity criteria
:
5000 well visualized / well preserved squamous cells in liquid based
preparation .
8000 – 12000 cells in conventional preparation .
Endocervical / Transformation Zone component :
Presence of transformation zone sampling is not necessary for an adequate
specimen – only squamous cellularity is necessary.
However, lab should report the presence or absence of a transformation zone
component as it may be a useful quality assurance measure.
Adequate transformation zone sample: 10 well preserved endocervical /
squamous metaplastic cells singly / in clusters

22. 3)GENERAL CATEGORIZATION (optional)
Negative for Intraepithelial Lesion or malignancy (NILM).
Other :See Interpretation/result
(e.g., endometrial cells in a woman >= 45years of
age).
Epithelial Cell Abnormality: See Interpretation/result (specify ‘squamous’ or
‘glandular’ as appropriate)

23. 4)INTERPRETATION / RESULT
i)Negative For Intraepithelial Lesion Or Malignancy
 Specimens for which no epithelial abnormality is
identified are reported as “negative for intraepithelial
lesion or malignancy” (NILM). If optional non-neoplastic
findings are reported, NILM should still be included as the
primary interpretation or as the General Categorization to
avoid ambiguity.

24. Negative For Intraepithelial Lesion Or
Malignancy
1) Normal Cellular Elements
Squamous cells
Endocervical cells
Endometrial cells
Lower uterine segment cells
2)Non neoplastic findings
Non Neoplastic cellular variations
Reactive cellular changes
Glandular cell changes post hysterectomy
3)Organisms :
Trichomonas , Candida , Bacterial vaginosis ,
Actinomyces, HSV ,CMV

25. • Superficial squamous cell :
• Mature, polygonal
• Derived from outermost layer of cervical epithelium
• Seen in proliferative phase of menstrual cycle and in presence of
irritation
• Cytoplasm: abundant and eosinophilic
• Nucleus :pyknotic and cross- sectional area of 10-15µm2

26. • Intermediate squamous cell :
• Generally present in the middle or intermediate layer of squamous
epithelium
• Prominent in pregnancy and with use of progestationalagents.
• Cytoplasm –Cyanophilic
• Nucleus - non pyknotic ,vesicular nucleus, larger than that of superficialcell
i.e. cross-sectional area 35µ2;Fine granular chromatin pattern; elongate with
longitudinal nuclear groove.
• The intermediate cell nucleus serves as the basic size reference for other
cells in cervical cytology specimens

27. • Parabasal / Basal squamous cells :
• small , oval,round immature
• predominate in postmenopausal and postpartum states.
• Cytoplasm -cyanophilic / eosinophilic
• Nucleus –oval; larger than in intermediate cells with an area of
50μm2; fine chromatin
• The cytoplasmic area is smaller and the nuclear to cytoplasmic
ratio is higher than in intermediate or superficial cells; and the
cytoplasmic texture is more granular and dense

28. • Endocervical cells:
 Columnar in shape & contain mucin
 In cervical smears endocervical cells
arranged singly, in layers & in sheets
forming a palisade .
 Honey comb / picket fence appearance .
 Nucleus: large, rounded, placed at
basal portion ;granular evenly
distributed chromatin
 Cytoplasm:eosinophilic / basophilic

29. • Endometrial cells :
 in smears appear asrounded
clusters
typically smaller than endocervical
cells
nuclear area equal to or slightly
smaller than an intermediate cell
nucleus (35 μm2 ) and have a higher
nuclear to cytoplasmic ratio
 Cytoplasm: scanty , vacuolated
 cell border: ill defined

30. NILM - NON NEOPLASTIC FINDINGS
1) Non neoplastic cellular variations.
A)Squamous Metaplasia.
Nucleus- round to oval
Evenly distributed chromatin
The mean nuclear area is larger than that of the intermediate cell and
similar to the parabasal cell at 50µm2
Cells having spindled cytoplasmic projections (“spider cells”) are often
seen in conventional preparations due to disruption of the cohesion of
cellular attachments by the force of the smearing procedure

32. NILM- NON NEOPLASTICFINDINGS
• Nonneoplastic cellular variations
2)Keratotic cellular changes :
Normally, the cervix is a nonkeratinizing, stratified squamous epithelium. Keratotic
changes usually occur as a protective reactive phenomenon or in association with
human papillomavirus (HPV)-induced cell changes. Both of these processes lead to
hypermaturation of the native squamous epithelium, more closely approximating
the normal appearance of skin.
 Keratosis
 Hyperkeratosis
 Parakeratosis
 Dyskeratosis

33. KERATOHYALINEGRANULES
• After metaplastic conversion, continued trauma may lead to formation
of cytoplasmic keratohyaline granules.
• Picture showing Intermediate squamous cells showing prominent
cytoplasmic keratohyaline granules, a precursor to full keratinization

34. PARAKERATOSIS:
• Squamous cells with dense orangeophilic or eosinophilic
cytoplasm .
• Cells- isolated /in sheets/ in whorls
• Cell shape – round / polygonal / spindle shaped
• Nuclei are small and dense (pyknotic).
• Nucleus - pyknotic

35. HYPERKERATOSIS:
• Anucleate but otherwise unremarkable mature polygonal squamous
cells
• Empty spaces or “ghost nuclei” may be noted

36. NILM- NON NEOPLASTICFINDINGS
Non-neoplastic cellular changes:
• 3)TUBALMETAPLASIA:
• metaplastic phenomenon in which the normal
endocervical epithelium is replaced by an
epithelium that recapitulates that of the
normal fallopian tube
• Criteia
 columnar ciliated / pseudostratified
 Nucleus: round-oval , enlarged,
pleomorphic , hyperchromatic
 N:C ratio high
 Cytoplasm: vacuoles / goblet cell
change

37. NILM- NON NEOPLASTICFINDINGS
• Non-neoplastic cellular changes :
4)ATROPHY
CRITERIA:
 Flat monolayer sheets of parabasal-like cells
 Nuclear enlargement , N:C ratio, regular
contour
 Abundant inflammatory exudate,basophilic
granular debris in background.
 Globular collections of basophilic amorphous
material (blue blobs) reflect either
degenerated parabasal cells or inspissated
mucus.

38. NILM- NON NEOPLASTICFINDINGS
Non neoplastic cellular changes:
5)Pregnancy related cellular changes
 Navicular cells- boat shaped
intermediate cells(prominent
glycogen with a flattened
“boatlike” appearance)
 Abundant basophilic clear
cytoplasm
 Nucleus- vesicular , delicate
chromatin

39. NILM- OTHER NON NEOPLASTICFINDINGS
• 2.Reactive cellularchanges:
1. Inflammation :
Nuclear enlargement of a variable degree
Nuclei:nonoverlapping.
Occasional binucleation or multinucleation
Nuclear outlines:smooth, round, and uniform.
Chromatin structure and distribution remain
uniformly finely granular.
Prominent single or multiple nucleoli.
Cytoplasmic boundaries are well defined.
Cytoplasm may show polychromasia,
vacuolization, or perinuclear halos but without
peripheral thickening

40. NILM- NON NEOPLASTICFINDINGS
Reactive cellular changes :
2. Lymphocytic (Follicular) cervicitis:
Polymorphous population of lymphocytes with or without tingible body
macrophages.

41. NILM- NON NEOPLASTICFINDINGS
Reactive cellular changes :
3. Radiation :
cell size, bizarre shape, nuclear degeneration & ballooning
nucleus size / Binucleation / Multinucleation
cytoplasm –vacuolated, polychromatic.

42. NILM- NON NEOPLASTICFINDINGS
Reactive cellular changes :
4.IUCD :
Endometrial or endocervical columnar cells exfoliated as a result of
chronic irritation by the device.
Glandular cells -singly / clusters in clean background
Large vacuoles displace nucleus-signet ring appearance

43. NILM- NON NEOPLASTICFINDINGS
3)Glandular cell changes Post hysterectomy :
Benign-appearing endocervical-type glandular cells

44. NILM - ORGANISMS
1. Trichomonas vaginalis : Parasitic
infection
• Pear shaped, oval or roundcyanophilic
organism
• Nucleus: pale ,vesicular ,eccentrically
placed
• Cytoplasm : eosinophilic granules
• Flagella and leptothrix association may
be seen
• Background changes: mature
squamous cells with perinuclear halos
(trich change) and 3-D clusters of
neutrophils (polyballs)

45. NILM - ORGANISMS
2. Candida : Fungal infection
• Budding yeast & pseudo hyphae.
• Fragmented leukocyte nuclei and groups of squamous epithelial
cells “speared” by pseudohyphae and held together in a rouleaux
are often seen: “shish kebab” effect

46. NILM- ORGANISMS
3. Bacterial vaginosis :
Individual squamous cells are covered by a layer of coccobacilli that
obscure the cell membrane, forming the so-called clue cells
Clue cells – hallmark for presence of Gardnerella vaginalis

47. NILM- ORGANISMS
4.Bacteria Morphologically Consistent withActinomyces
• Tangled clumps of filamentous organisms, with acute angle branching
• “cotton ball” clusters on low power
• Caused by :Actinomyces israeli

48. NILM- ORGANISMS
5.Cellular Changes Consistent with
Herpes Simplex Virus
 Herpes cytopathic effect shows 3 “Ms” –
multinucleation, molding, and
margination of chromatin.
 Nuclei :“ground-glass” appearance due
to intranuclear viral particles
 Dense eosinophilic intranuclear
(Cowdry) inclusions surrounded by a
halo.
 Large multinucleated epithelial cells
with molded nuclei are characteristic
but may not always be present

49. NILM- ORGANISMS
6.Cellular Changes Consistent with Cytomegalovirus
 Endocervical glandular cells affected
 cells & nucleus –enlarged
 Large eosinophilic intranuclear viral inclusions with prominent halo

50. OTHERS:
Endometrial cells( in a woman >45 years of age)
(Specify if negative for squamous intraepithelial
lesion)
Exfoliated endometrial cells-Criteria:
 Cells are arranged in three dimensional
clusters.
 Nuclei are small and similar in size to an
intermediate squamous cell nucleus.
 Nucleoli are inconspicuous.
 Cytoplasm is scant, and cell borders are
indistinct
 Mitoses are absent.
 Double-contoured clusters of endometrial
cells may be seen

51. INTERPRETATION/RESULT
Epithelial cell abnormalities:
1) Squamous cell
 Atypical squamous cells (ASC)
- of undetermined significance (ASC-US)
- cannot exclude HSIL (ASC-H)
 Low grade squamous intraepithelial lesion (LSIL)
(encompassing: HPV /mild dysplasia/ CIN 1)
 High grade squamous intraepithelial lesion (HSIL)
(encompassing: moderate and severe dysplasia, CIS,
CIN II and CIN III)

52. Atypical Squamous Cells
ASC refers to cytologic changes suggestive of SIL, but which are
qualitatively or quantitatively insufficient for a definitive interpretation
as such
Requires 3 essential features:
(1) squamous differentiation
(2) increased nuclear to cytoplasmic ratio
(3) minimal nuclear changes which may include hyperchromasia,
chromatin clumping, irregularity, smudging, and/or multinucleation.
Abnormal-appearing nuclei are a prerequisite for the interpretation of
ASC.

54. Atypical Squamous Cells –
Undetermined Significance (ASC-US)
Criteria :
 Nuclei:approx 21/2 to 3 times the area of the nucleus of a normal
intermediate squamous cell or twice the size of a squamous metaplastic cell
nucleus
 increased N/C ratio
 Minimal nuclear hyperchromasia and irregularity in chromatin distribution or
nuclear shape.
 Nuclear abnormalities associated with dense orangeophilic cytoplasm
(“atypical parakeratosis”), cytoplasmic changes that suggest HPV cytopathic
effect (incomplete koilocytosis) – including poorly defined cytoplasmic halos
or cytoplasmic vacuoles resembling koilocytes but with absent or minimal
concurrent nuclear changes

56. • Atypical squamous cel cannot exclude –HSIL (ASC – H )
Cell resemble basal or parabasal in configuration
Nuclei – hyperchromatic , uneven chromatin pattern
Nuclear membrane – thick and uneven

57. Encompasses the cellular changes
associated with the older terms of
koilocytosis, mild dysplasia, and
CIN1
Criteria:
 Cell:singles/clusters/ sheets
 Overall cell size is large, with
fairly abundant “mature” well-
defined cytoplasm.
 Nucleus: enlarged,hyperchromatic,
anisonucleosis
is coarsely
to smudgy
- chromatin
granular
- binucleated
/multinucleated
Low-Grade Squamous Intraepithelial Lesion (LSIL)

58. LSIL

59. High-Grade Squamous Intraepithelial Lesion
(HSIL)
Encompasses more clinically
significant lesions previously termed
moderate and severe dysplasia, CIN 2,
CIN 3, and carcinoma in situ.
Criteria:
 Cells:smallerandshowlesscytoplasmic
maturity than LSIL
singly/ sheets/ syncytialaggregate
hyperchromatic crowdedgroup
 Nucleus:Enlarged ,High N:Cratio than
LSIL
Chromatin may be fine or coarsely
granular and is evenly distributed
Irregular nuclear membrane

60. Invasive epithelial tumor composed of
squamous cells of varying degrees of
differentiation
SCC – Keratinizing SCC
Non keratinizingSCC
 Keratinizing SCC:
 Cells:variablesizes& shapes,
keratinized tadpole cells
 Nucleus:vesicularto pyknotic
 Cytoplasm–deeply eosinophilic /cyanophilic
background
 Tumordiathesismaybepresent
Squamous Cell Carcinoma

61. Squamous Cell Carcinoma
 Non Keratinizing SCC :
Cells: singly / syncytial
aggregates with poorly defined
cell borders
Cells smaller than HSILbut
features similar to HSIL
Nucleus: irregular , coarsely
clumped chromatin
nucleoli prominent,
hyperchromasia
Back ground – tumor diathesis

62. Epithelial cell anormality
2)GLANDULAR CELL
 Atypical
– endocervical cells (NOS or specify in comments )
– endometrial cells (NOS or specify in comments )
– glandular cells (NOS or specify in comments )
 Atypical
– endocervical cells, favor neoplastic
– glandular cells, favor neoplastic
 Endocervical adenocarcinoma in situ
 Adenocarcinoma
– endocervical
– endometrial
– extrauterine
– not otherwise specifi ed (NOS)

63. Atypical Endocervical Cells
• Nuclear atypia that exceeds
reactive or reparative changes
but lack unequivocal features
of endocervical
adenocarcinoma in situ or
invasive adenocarcinoma
• Atypical Endocervicalcells:NOS
• Cells:sheets,cell crowding
Distinct cell borders
• Nucleus: overlapping , nuclear
enlargement,enlargednucleoli,
increased N:Cratio

64. • Atypical Endocervical cels ,favour
Neoplastic
• Cells:sheets,strips,rosettes/ feather ,
pseudostratification
• ill-defined border
• Nucleus : crowding ,overlap, enlarged and
elongated with some hyperchromasia
• Coarse chromatin with heterogeneity.
• Occasional mitoses and/or apoptotic
debris.
• Nuclear to cytoplasmic ratios are
increased.

65. Atypical Endometrial Cells
• Cells occur in small groups,
usually 5–10 cells per group
• Nuclei are slightly enlarged
compared to normal
endometrial cells.
• Mild hyperchromasia.
• Chromatin heterogeneity.

66. Endocervical Adenocarcinoma in situ (AIS) :
Cells: Sheets, clusters, pseudostratified strips, and
rosettes with nuclear crowding and overlap and loss
of a well-defined honeycomb pattern
Cell clusters have palisading nuclear arrangement
with nuclei and cytoplasmic tags protruding from the
periphery (“feathering”)
Nucleus: Enlarged,oval orelongated,
hyperchromatic, increased N:C Ratio
coarsely granular chromatin
mitoses ,apoptotic bodies are commom
Cytoplasm:less
Background:clean

67. • Adenocarcinoma:
1)Endocervical
Adenocarcinoma 2)Endometrial
Adenocarcinoma 3)Extrauterine
Adenocarcinoma

68. Adenocarcinoma:
Endocervical Adenocarcinoma
•Abundantabnormalcellstypically
withcolumnarconfiguration
•Cells:Singlecells,sheets,clusters,
syncytialaggregates
•Nucleus: Enlarged,pleomorphic,
irregularchromatin,nuclear
membraneirregularities.
macronucleoli
• Cytoplasm: finelyvacuolated,
• Background: necrotictumor
diathesis

69. •Adenocarcinoma:
Endometrial Adenocarcinoma:
•Cells: singles or in smal tightclusters
round inshape
•Nucleus :enlarged ,hyperchromasia,
irregular chromatin, prominentnucleoli
•Cytoplasm:vacuolated ,scanty,
cyanophilic
•Background: finely granular or watery
Tumordiathesis

70. • Adenocarcinoma :
Extrauterine Adenocarcinoma:
When cells diagnostic of adenocarcinoma
occur in association with a clean (no
diathesis) background or with morphology
unusual for tumors of the uterus or cervix,
an extrauterine neoplasm should be
considered
Papillary clusters
from ovarian
carcinoma

71. Cytological distinction between endocervical, endometrial
and extrauterine
Features Endocervical Ca Endometrial Ca Extrauterine Ca
Cellularity Hypercellular Low cellularity
usually
Rare cells
Pattern Strips, rosettes, sheets
with feathering, single
malignant cells
Small clusters
rarely papillae
Varies depending
upon primary and
mode of spread
Diathesis Visible, type varies by
preparation
Variable Usually absent
Cell shapes Oval, columnar,
pleomorphic
Round, irregular in
high grade
Variable
Nuclei Oval, elongated vesicular Round, irregular in
high grade
Variable
High –risk
HPV
Positive in most Negative Negative
P16 Block positive Patchy/focal
except in serous /
high grade
Variable, depends
on types

72. Adjunctive Testing
Adjunctive testing is now commonly used in association with cervical
cytology.
1.Adjunctive HPV Testing:
As of 2014, there are four hrHPV tests that are FDA approved for
performance in association with cervical cytology. Three are DNA based
and one is RNA based.
Description of Test Method and Results:
• The test method(s) should be briefly described (e.g., hybrid capture,
polymerase chain reaction, RNA amplification, etc.)
• Results reported in a clear and concise manner to the ordering clinician.
• For HPV testing, the specific types detected by the assay should be
reported.

73. 2.Immunochemical Assays
Best-studied biomarkers are p16, ProExC, and Ki67.
p16 and ProExC are biomarkers of an aberrant cell cycle which has been
affected by the oncogenic effects of HPV.
Ki67 is a marker of cellular proliferation.
p16 stains both the nucleus and cytoplasm; ProExC and Ki67 stain the
nucleus
Reporting of Molecular/Immunochemical and Cytologic Results
Cytology and adjunctive test results to be reported concurrently to
facilitate communication and record keeping.

74. Educational Notes and Comments
Appended to Cytology Reports
1. Educational notes and comments should be concise and relevant.
2. Suggestions for additional clinical follow-up should be evidence
based and consistent with guidelines published by professional
organizations.
3. Reference to relevant publications may be included.

76. Limitation of TBS
The limitation of the Bethesda system is mainly in the
category of low grade squamous intraepithelial lesion
(LSIL).
Despite the fact that 60% of LSIL cases will regress all
such cases must be followed up since it’s impossible to
predict their outcome.
Follow up require a lot of understanding and co-
operation on the part of the patient without frightening
her with the diagnosis.

77. Thank You