Pap Smear: A Bird's Eye View from a Cytopathologist

Role of Pap Smear as a screening test for cancer

1. PAP SMEAR: BIRD’S EYE VIEW FROM
CYTOPATHOLOGIST
-Dr. Shubhi Saxena
(Dept. of Pathology)

2. What is PAP smear ?
•Screening is a public health intervention on population at risk or
target population.
•The Pap test is the most cost-effective cancer reduction program
ever devised. Credit for its conception and development goes to
Dr George N. Papanicolaou.
•PAP smear is a screening test to identify premalignant and
malignant lesions of cervix so that they can be treated, thereby
reducing Ca Cx rates in the population.
•So far most efficient screening test

4. NewGuidelines:
Targetgroup-Allwomenaged18-70yrswho
haveeverhadsex.
TimingofInitialScreening-
Initialscreeningatageof21yearsor
within3yearsofsexualactivity
PAPSMEARASASCREENINGMETHOD

5. Pap smear: Guidelines
Screening interval
-Yearly till the age of 30 then 3 yearly
When to End Screening
-After 70 yrs
-Post Hysterectomy
-Previous 3 normal PAP reports
-Confirmed complete removal of cervical epithelium

7. PAPSmears-Limitations
Low sensitivity 51%
False negative rates are due to faulty
sampling, improper fixation or
interpretation problems
No consensus regarding testing

8. Test Requisition
•Under the supervision and guidance of
the physician, a laboratory requisition
must be legibly and accurately filled out
before obtaining the cellular sample.
•The laboratory requisition is the main
communication link between the
physician and the laboratory.

9. •Patient’sname(anynamechangeinthepast5yearsshouldbe
noted.)
•Ageanddateofbirth.
•Menstrualstatus(LMP,hysterectomy,pregnant,postpartum,
hormonetherapy)
•Previousabnormalcervicalcytologyresult,previoustreatment,
biopsyorsurgicalprocedure.
•Patient’sriskstatusfordevelopingcervicalcancer,e.g.“high
risk”.Theclinicianshouldexpectthatthelaboratorywouldrely
upontheinformationprovidedonthecurrentrequisitionin
arrivingatanassessmentofriskstatus.
•Sourceofspecimene.g.cervical,vaginal.
•Hormone/contraceptiveuse.
•Relevantclinicalfindings(abnormalbleeding,grosslyvisible
lesionetc.)

10. TRANSFORMATION ZONE
•Cervixdevelopsfrom2embryonicsites:
*fromMullerianduct-linedbycolumnarepithelium
*fromurogenitalplate-linedbystratifiedsquamous
epithelium
•Pointatwhichcolumnarandsquamousepitheliummeetiscalledas
originalsquamo-columnarjunction.
•ExposureofTZtocarcinogensbeginstheprocessofintraepithelial
neoplasia
•Whileexactroleofcarcinogensinthisprocessremainspoorlyunderstood,
itisclearthatHPVandcigarettesmokingcancausedysplasiaattheTZ
•95%ofcervicalcancersdevelopinTZ.
•ImportanttotakesamplefromTZ.

11. Thelocationofthesquamo-columnar
junction(8mmto13mmproximal
totheexternalcervicalOS)inmost
womenvarieswiththeageand
fertility.

13. Fixation
Fixativeisanagentusedtoprepare
cytologicspecimenforthepurposeof
preservingandmaintainingtheexisting
formandstructureofallconstituent
elements.

14. Spray with Fixative
•Within10-15seconds
•Allowtofullydry
beforepackaging
•CytologicFixative
(hairsprayworks
acceptablyalso)

15. Fixation of smear
Fixationisdoneimmediatelywithfixativelike95%alcoholor
cytofixspraytoavoidairdrying
Sprayshouldbekeptat10inches,toavoiddestructionofcells
bypropellentinthespray
Smearshouldmonolayerforproperpenetrationofcellsurfaceby
fixative

18. FIXATIVES
•95%Ethanol.
•95%RectifiedSpirit.
•100%Methanol.
•80%IsopropanolorPropanol.
•Ether/95%Ethanol(1:1).
•Sprayfixativescontainsisopropanol
•Propyleneglycol.

19. What is liquid based cytology?
Collectionofcellularmaterialintoa
vialofpreservativefluid.

20. How LBC Different
•Easiermethod for smear takers
•Technology diminishes blood,
mucus & polymorphs
•Thin layer preparation
•Smaller area of the slide to screen

21. LBC
•LBCforgynaecologicalcytologyhasbeenintroducedinBelgium
•Liquid-basedcytologytechniques:
FDAapproved:
ThinPrep®
Filtrationandcollectionofvacuum-packedcellsonamembraneandtransferring
totheglassslide.
Surepath®
Centrifugationandsedimentationthroughadensitygradient
NotFDAapproved:
Cytoscreen®
Turbitec®
Cellslide®
Papspin®
Centrifugationandsedimentationbymanualtechniques

22. ThinPrep
®
Process
1. Dispersion 2. Cell Collection 3. Cell Transfer

23. SUREpath Method

26. The prepared slide with the new
ThinPrep
Conventional smear

27. What we see under the
microscope. Notice the clean back
ground and how well the cells are
dispersed rendering easier to

28. TechniqueAdvantages Disadvantages
Conventional
Pap test
•Gold standard for 50 years
•Comfortable with the method
•Ready for staining when arrives in lab
•Inexpensive
•>80% of materials lost
•More cells to screen
•Uneven distribution of cells,
fixation artifacts
Liquid based
cytology
•Minimal loss of collected material
•Ease of use for smear taken
•Limited obscuring material—fewer
unsatisfactory slides
•Even distribution of cells, cleaner
backgrounds
•Fewer but well-preserved cells to
examine—reduction of screening time
•Residual materials for additional
studies
•Enable automated screening
•Training required
•Increased workload in prep
lab
•Increased costs

30. Howtostainthesmear
•Pap stain is a multichromaticstaining cytological technique
developed by George Papanicolaou, the father of cytopathology.
•The classic form of pap stain involves five dyes in 3 solutions:
–Hematoxylin
–Orangestaining solution: orange G
–Polychromic staining solutions: Eosin G, Light green SF,
Bismarck brown

32. Reporting of smears
•WhatisTHEBETHESDASYSTEM?
–TBSisarecommendedsystemofreporting
cervical/vaginalsmears.
–TBSprovidesacommonlanguage,auniform
terminologytodescribefindings,sothatitis
understooduniformlybyoneandall,leadingtobetter
management.

33. THE 2014 BETHESDA SYSTEM
SPECIMENTYPE
SPECIMENADEQUACY
GENERALCATEGORISATION(OPTIONAL)
INTERPRETATION/RESULT
ANCILLARYTESTING
AUTOMATEDREVIEW
EDUCATIONALNOTESANDSUGGESTIONS(OPTIONAL)

34. SPECIMEN TYPE
Indicateconventionalsmear(Pap
smear)vs.liquidbased
preparation

35. Specimen Adequacy
•Adequate smear:
–An adequate pap smear is one that includes a
sampling from the exocervix, endocervix and
transformation zone.
–An adequate cytologic sample contains more than
300 squamous cells, including at least two
clusters of 5 cells each of endocervical or
metaplastic cells with mucus material.

36. Estimatednumberofsquamouscells
Liquidbased:5,000
Conventional:8,000–12,000

37. Thisspecimenisunsatisfactoryduetoscantsquamouscellularityseenat10X

39. Criteria for specimen
adequacy
“Satisfactoryforevaluation”
–Appropriatelabellingandidentifyinginformation.
–Whenevenlyspreadwillnormallycoveratleastone
thirdoftheclearglasspartoftheslide.
–Relevantclinicalinformation.
–Adequatenumbersofwellpreservedandwell
visualizedsquamousepithelialcells.
–Anadequateendocervicaltransformationzone
component.

41. Unsatisfactory for evaluation…
•Lackofpatientidentificationonspecimen.
•Theclinicianindicatesthatthecervixwaspoorlyvisualised
•Slidethatisbrokenandcannotberepaired,orcellularmaterial
thatisinadequatelypreserved.
•Scantsquamousepithelialcomponent(wellpreservedand
wellvisualizedsquamousepithelialcellscovering<10%ofthe
slidesurface)
•Obscuring(blood,inflammatorycells,lubricant,thickclumps
ofcells,air-dryingartefactorpoorlyfixedcells,spermatozoa,
menstrualdebris,bacteria)thatprecludesinterpretationof
approximately>75%ofepithelialcells.

42. •Ifitisentirelycomposedofseparatedsuperficial
squamouscellssuggestingavaginalratherthan
cervicalorigin.
•Ifthecellularsmearissothicklyspread.
•Ifitisentirelycomposedofendocervicalcells,
unlesstheonlyobjectofthetestwastosamplethe
endocervicalmucosa.

43. •Anyepithelialabnormalityisof
paramountimportanceandmustbe
reportedregardlessofcompromised
specimenadequacy.
•Ifabnormalcellsaredetected,the
specimenisnevercategorisedas
“UNSATISFACTORY”

44. CytomorphologicCriteria:Over75%ofcellsareobscuredbyinflammationandblood

49. Making of Pap Smear
•Asthinaspossible
•Properlylabeled

50. Interpretation/Result
1.Negativeforintraepitheliallesionor
malignancy(NILM)
2.Epithelialcellabnormalities
3.Othermalignantneoplasms(specify)

51. 1. NEGATIVE FOR INTRAEPITHELIAL LESION OR MALIGNANCY (NILM)
1. ORGANISMS:
-Trichomonasvaginalis
-Fungal organisms morphologically consistent with candidaspecies
-Shift in flora suggestive of bacterial vaginosis
-Bacteria morphologically consistent with Actinomycesspecies
-Cellular changes consistent with Herpes simplex virus
2. OTHER NONNEOPLASTIC FINDINGS:
* Reactive cellular changes associated with
-Inflammation
-Radiation
-Intrauterine contraceptive device
* Glandular cells status posthysterectscopy
* Atrophy
Interpretation/Result

52. NILM
•Specimensforwhichnoepithelial
abnormalityisidentifiedarereportedas
NILM.
•Ifnon-neoplasticfindingsarereported,
NILMshouldstillbeincludedasan
interpretationorasthegeneral
categorizationtoavoidambiguity.

53. What to see in a PAP smear?
Adequacyofmaterial
Arrangementofcells
Celltypes
Cellshape
Cellsize
Typeofcytoplasm
Nuclearfeatures:-Size,shape,number
-N/Cratio
-Nuclearcontour
-Chromasia
-Chromatintexture
-Nucleolarfeatures
Organisms
Noncellularmaterial-smearbackground

55. The Normal PAP
•Squamouscells
•Theectocervixislinedbyastratifiedsquamousepitheliumthatmaturesunder
theinfluenceofestrogen.
•Superficialsquamouscells:Theyhaveasmall,pyknoticnucleusthatis5–6
μmindiameter.
•Intermediatesquamouscells:havealargernucleusmeasuring8μmin
diameter,whichisnotpyknoticbutinsteadhasafinelygranulartexture.
Bothsuperficialandintermediatecellsarelargepolygonalcellswith
transparentpinkorgreencytoplasm.

57. •Immaturesquamouscellsarecalledparabasalcellsand
basalcells.
•Parabasalcells:areroundorovalratherthanpolygonal
andhaveavariablysizednucleusthatisusuallylarger
thanthatofanintermediatecell.
•Basalcells:areevensmallerandhaveveryscant
cytoplasm.

58. Different types of squamous cells:
A. Superficial (arrow) B. Intermediate
C. Parabasal D. Metaplastic

59. Transformation zone componentEndocervical cells demonstrating both picket
fence and honeycomb arrangements compose a transformation zone component.
20X

60. ESTROGEN PHASE

61. OVULATORY SMEAR

62. PROGESTERONE PHASE

63. Endometrial cells
•Exfoliated endometrial cells occur in ball-like clusters and rarely
singly
•Nuclei are small, round and similar to the area of normal
intermediate cell nucleus
•Occur in 3D clusters so chromatin pattern is difficult to identify
•Nucleoli are inconspicuous
•Cytoplasm is scant, basophilic and occasionally vacuolated
•Cell borders are ill defined
•During first half of menstrual cycle, double contoured clusters of
endometrial cells (exodus pattern) may be seen

65. LACTOBACILLI
•Lactobacilli are observed in
about 50% of normal healthy
adult female
population.
•These bacilli release
enzymes causing extensive
cytolysis of glycogen
containing cells.
•Mainly affect intermediate
and superficial cells.
•Parabasal cells are
generally spared.

66. ORGANISMS
TRICHOMONAS VAGINALIS
Criteria:
–Pearshaped,oval,orroundcyanophilicorganism
–15to30µminsize
–Eosinophiliccytoplasmicgranulesareoftenevident
–Flagellaareusuallynotseen
–Nucleusispale,vesicularandeccentricallylocated

69. Trichomonas
vaginalis

70. Candida species
Criteria:
–Buddingyeast(3-7µm);pseudohyphaeareeosinophilicto
gray-brownonpapstain
–Pseudohyphae,formedbyelongatedbudding,show
constrictionsalongtheirlength
–Fragmentedleukocytenucleiandrouleaxformationof
squamouscells“speared”byhyphaemaybeseen

71. Liquid-basedpreparation:
–“Spearing”ofepithelialcellsismorecommonin
LBPsandcanbeseenatlowpowerevenifthe
pseudohyphaearenotprominent(“sheeshkebab
effect”)
–Candida(Torulopsis)glabrataconsistofsmall,
uniform,roundbuddingyeastformssurroundedby
clearhalosonpapstain.Unlikeothercandida
species,itdoesnotformpseudohyphaeinvivoorin
culture

75. ThefigureaboveshowsfungalorganismmorphologicallyconsistentwithCandidaglabrata.
Candidaglabrataconsistsofsmall,uniform,roundformsurroundedbyclearhalo

76. Shift in flora suggestive of bacterial vaginosis
Criteria:
–Filmybackgroundofsmallcoccobacilliisevident
–Individualsquamouscellsmaybecoveredbyalayerofbacteria
thatobscurethecellmembrane,formingso-calledClueCells
–Thereisaconspicuousabsenceoflactobacilli
Liquid-basedpreparation:
–Squamouscellsarecoveredwithcoccobacilliincleanbackground

78. BACTERIAL VAGINOSIS

79. Actinomyces
Criteria:
–Tangled clumps of filamantous organisms, with acute angle
branching, are recognizable as “cotton ball” clusters on low
power
–Filaments sometimes have radial distribution or have an
irregular “wolly body” appearance.
–Masses of leukocytes adherent to microcolonies of the
organisms, with swollen filaments or “clubs” at the periphery,
may be identified.
–An acute inflammatory response with polymorphs is often +nt.

81. Herpes simplex virus
Criteria:
–Nucleihave“groundglass”appearanceduetointranuclear
viralparticlesandenhancementofnuclearenvelopecaused
byperipheralMarginationofchromatin.
–Denseeosinophilicintranuclearinclusionssurroundedby
ahaloorclearzoneare+nt.
–LargeMultinucleatedepithelialcellswithMolded
nucleiarecharacteristicbutnotalwayspresent;
mononucleatecellswiththenuclearfeaturesmaybethe
onlyfinding.

82. Ground glass appearance of nuclei due to accumulation of viral particles

83. HPV (human papilloma virus)
Large squamous
cell with
enlarged
hyperchromatic
nucleus & large
sharply
demarcated
perinuclear
clear
zone

84. PSEUDOKOILOCYTES
•Glycogenin squamous
cells can give the
appearance of
"pseudokoilocytosis“
•Nuclear abnormalities
required for an
interpretation of ASC-
US/LSIL are absent.

85. Other Non-Neoplastic Findings
Reactivecellularchanges:
–Reactivecellularchangesthatarebenigninnature,
associatedwithinflammation,radiation,anIUDor
othernonspecificcauses.

86. Reactive cellular changes associated with Inflammation(includes typical
repair)
Criteria:
–Nuclearenlargement(oneandone-halftotwotimesthearea
ofanormalintermediatecellnucleusormore)
–Endocervicalcellsmayshowgreaternuclearenlargement
–Nuclearoutlinesaresmooth,roundanduniform

87. -Mildhyperchromasiamaybepresent
–Prominentsingleormultiplenucleolimaybepresent
–Cytoplasmmayshowpolychromasia,vacuolization,or
perinuclearhalosbutwithoutperipheralthickening
–Similarchangesmaybeseeninsquamousmetaplastic
cells,cytoplasmicprocesses(spidercells)mayalsobe
seen

88. Reparative
process with
inflammatory
changes. The
cells are
arranged in
monolayers
and contain
enlarged
nucleoli.

89. NILM: Reactive cellular changes, Repair
Mild nuclear enlargement
without significant chromatin
abnormality

90. Reactive cellular changes associated with Radiation
Criteria:
–CellsizeismarkedlyincreasedwithoutincreaseinN:Cratio
–Bizarrecellshapemayoccur
–Enlargednucleimayshowdegenerativechangeslikenuclearpallor,
wrinklingorsmudgingofchromatin,andnuclearvacuolization
–Binucleation or multinucleation is common
–Cytoplasmic vacuolization and/or cytoplasmic polychromatic staining
may be seen

91. Cellswithenlargednuclei,abundantvacuolatedpolychromaticcytoplasm,
mildnuclearhyperchromasiaandprominentnucleoli

93. Reactive cellular changes associated with IUD
Criteria
–Glandularcellsmaybepresentsinglyorinclusters
of5to15cellsinacleanbackground
–Theamountofcytoplasmvaries,andlargevacuole
maydisplacethenucleus,creatingasignetring
appearance

94. –Nucleardegenerationisevident
–Nucleolimaybeprominent
–Calcificationresemblingpsammoma
bodiesarevariably+nt

95. Smallclusters
ofglandular
cellswith
cytoplasmic
vacuoles
displacing
nuclei

97. Atrophywith/without inflammation
Criteria:
–Flat,monolayersheetsofparabasal-likecellswithpreservednuclear
polarity
–Dispersedparabasallikecellsmaypredominate
–Generalisednuclearenlargementupto3to5timestheareaofnormal
intermediatecellnucleuswithslightincreaseinN:Cratio
–Chromatinisuniformlydistributed
–Autolysismayresultinnakednuclei

98. –Intermediatecellsarenormochromicbutparabasalcellsshow
mildhyperchromasiaandhavemoreelongatednuclei
–Anabundantinflammatoryexudateandbasophilicgranular
backgroundthatresemblestumordiathesismaybe+nt
–Globularcollectionofbasophilicamorphousmaterial(blue
blobs)+nteitherduetodegeneratedparabasalcellsor
inspissatedmucus
–Degeneratedorangeophilicoreosinophilicparabasalcellswith
nuclearpyknosisresembling“parakeratotic”cellsmaybe+nt.
–Histiocytesmaybeseenwithvaryingsizeandshape.

99. Granular debris in background,
degenerating parabasal cells
Multinucleated histiocytic giant cells,
often seen in postmenopausal and
postpartum specimens
Degenerated parabasal cells in a clean
background
Granular debris is clumped and
adheres to cell clusters

103. Epithelial cell abnormalities
(1) Squamous cell
•Atypical squamous cells
–of undetermined significance (ASC-US)
–cannot exclude HSIL (ASC-H)
•Low grade squamous intraepithelial lesion (LSIL)
(HPV /mild dysplasia/CIN 1)
•High grade squamous intraepithelial lesion (HSIL)
(moderate and severe dysplasia, CIS, CIN 2 and CIN 3)
With features suspicious for invasion (if invasion is suspected)
•Squamous cell carcinoma

104. (2)Glandularcell
•ATYPICAL
oEndocervicalcells(NOSorspecifyincomments)
oEndometrialcells(NOSorspecifyincomments)
oGlandularcells(NOSorspecifyincomments)
•ATYPICAL
oEndocervicalcells,favorneoplastic
oGlandularcells,favorneoplastic
•ENDOCERVICALADENOCARCINOMAINSITU(AIS)
•ADENOCARCINOMA
-Endocervical
-Endometrial
-Extrauterine
-NOS
3.OtherMalignantneoplasms(specify)

105. Squamous cell
Atypicalsquamouscells
–ofundeterminedsignificance(ASC-US)
–cannotexcludeHSIL(ASC-H)
ASC:
CytologicchangessuggestiveofSIL,whichqualitativelyor
quantitativelyinsufficientfordefinitiveinterpretation.
•3essentialfeatures:
1.Squamousdifferentiation
2.HighN:Cratio
3.Multinucleation,irregularity,minimalnuclearhyperchromasia,
chromatinclumping,smuding

106. ASC-US
Criteria:
•Nucleus:
–Size-increased (two and half to three times)
–Slight increased N:C ratio
–Minimal nuclear hyperchromasia
–Irregular chromatin distribution
–Irregular nuclear shape
•Cytoplasm:
–Dense orangeophilic (“Atypical Parakeratosis”)

107. Plaqueofcells
withdense
orangeophilic
cytoplasmand
minimally
irregular,
hyperchromatic
nuclei

108. ASC-H
•ASC-H cells are usually sparse and seen in pattern.
•Small cells with high N:C ratios: “Atypical (immature)
Metaplasia”
Criteria:
–Cell arrangement: single, small fragment of <10 cells, stream
in mucus (occasionally)
–Cell size: that of metaplastic cells
–Nuclear size: 1&1/2 to 2&1/2 times larger than normal
–N:C ratio: slightly increased

109. CellswithmetaplasticcytoplasmshowingvariationInshape,sizeandhigh
N:Cratio

110. Interpretation:
ASC-H
Cytomorphologic
Criteria:
Thickaggregateof
looselycohesive,
overlappingcells
containingenlarged
nucleiwitheven
chromatin,variation
insizeandshape
andobscuredcell
boundaries.

111. LSIL
SquamouscellchangesassociatedwithHPVinfection
encompass“MildDysplasia”and“CIN1”.
Criteria:
–Singlyorinsheets
–Superficialsquamouscells
–Cellsize:Largecells
–Abundantmaturewell-definedcytoplasm
–Nucleienlarged:>3timeswithslightincreasedN:C
ratio

112. –Variable degree of nuclear hyperchromasia
–Variation in nuclear size, shape and number
–Binucleation and multinucleation
–Uniform chromatin distribution, but coarsely granular,
smudged or densely opaque
–Nucleoli –nt
–Nuclear membrane: slightly irregular or may be smooth
–Perinuclear cavitation (“koilocytosis”)

113. Nucler enlargement and
hyperchromasia
Large cell size, smudged nuclear
chromatin, well defined cytoplasm,
multinucleation

116. HSIL
Criteria:
•Singly,insheetsorinsyncytiallikeaggregates
•Lessmaturecells
•Variablecellsize
•Nuclearhyperchromasia
•Degreeofnuclearenlargementismorevariable
•MarkedincreasedinN:Cratio
•Evenlydistributedchromatin,fineorcoarselygranular
•Nuclearmembraneisquiteirregular,prominentindention
orgrooves-frequently

117. •Nucleoli –nt, but may be seen when HSIL extends into
endocervical gland spaces
•Variable appearance of cytoplasm: immature, lacy, delicate,
densley metaplastic, occasionally mature and densely
keratinized

118. Dysplastic cells in syncytial
clusters

121. Variation in nuclear size
and shape and delicate
cytoplasm
Metaplastic or dense
cytoplasm

123. SCC
Malignantinvasivetumorshowing
differentiontowardsquamous
cells.

124. Keratinizing SCC
Criteria:
•Markedvariationincellsizeandshape---caudateandspindle
cells
•Denseorangeophiliccytoplasm
•Markedvariationinnuclearsize
•Numerousdenseopaquenuclei
•Irregularlydistributedchromatin,coarselygranularwith
parachromatinclearing
•Macronucleoli
•Hyperkeratosisorpleomorphicparakeratosis
•Tumordiathesis

125. Marked pleomorphismof cell size and shape, cytoplasmic
keratinizationand tumordiathesis in background

126. SCC: Tumor Diathesis

127. Non-Keratinizing SCC
Criteria:
•Cellsoccursinglyorinsyncytialaggregateswith
poorlydefinedcellborders
•CellsaresmallerthanHSILcellsbutdisplay
mostofthefeaturesofHSIL
•Coarselyclumpedirregularlydistributed
chromatin
•Tumordiathesisoften+nt

128. Pleomorphic cell shapes, dysplastic cells

129. ATYPICAL GLANDULAR
CELLS

130. Atypical endocervicalcells: NOS
Criteria:
–Cells in sheets and strips with some cell crowding and
nuclear overlap
–Nuclei enlarged 3 to 5 times
–Some variation in nuclear size and shape
–Mild hyperchromasia
–Nucleoli +nt
–Mitotic figure are rare
–Abundant cytoplasm but high N:C ratio
–Distinct cell borders are often discernible

131. Sheet of cells with nuclear enlargement, prominent nucleoli

132. Atypical endocervical cells, favor Neoplastic
Definition:
cellmorphology,qualitativelyorquantitatively,fallsjust
shortofaninterpretationofendocervical
adenocarcinomainsituorinvasiveadenocarcinoma.

133. Criteria:
–Abnormalcellsinsheetsandstripswithnuclear
crowdingandoverlap
–Rarecellgroupsmayshowrosettingorfeathering
–Nuclei:enlargedwithsomehyperchromasia
–Occasionalmitosis
–N:Cratioincreased
–Quantityofcytoplasmdiminished
–Cellbordersilldefined

134. Sheet of crowded cells with high
N:C ratio, featheringat the
edges of the sheet
Pseudostratified strip of endocervical
cells with enlarged, elongated
nuclei,some chromatin granularity

135. Atypical endometrial cells
Criteria:
–Smallgroups:5to10cellspergroup
–Nuclei:slightlyenlarged
–Mildhyperchromasia
–Smallnucleoli
–Scantyvacuolatedcytoplasm
–Illdefinedcellborders

136. Three dimensional groups of small cells with mildly
hyperchromatic nuclei, small nucleoli,

137. Endocervical adenocarcinoma in situ
Definition:
highgradeendocervicalglandularlesionc/bnuclearenlargement,
hyperchromasiaandmitoticactivitybutwithoutinvasion.
Criteria:
–Cellsinsheets,clusters,strips,androsetteswithnuclearcrowdingand
overlap,lossofhoneycombpattern.
–Somecellhavedefinitecolumnarappearance
–Cellclustershavepalisadingnucleararrangementwithnucleiand
cytoplasmictagsprotrudingfromperiphery(feathering)

138. –Nuclei:enlarged,variablesized,ovalorelongatedinshape&stratified
–Nuclearhyperchromasiawithevenlydispersed,coarselygranular
chromatin
–Nucleoli:smallorinconspicuous
–Mitosesandapoptoticbodiesseen
–N:Cratiohigh
–Cleanbackground
–Abnormalsquamouscellsmaybepresent

139. Oval nuclei are crowded with
nuclear overlapping and
hyperchromasia, evenly
distributed coarsely granular
chromatin
Three dimensional cluster
with feathering

140. Endocervical adenocarcinoma
•CytologiccriteriaoverlapthoseforAIS,butmayshow
featuresofinvasion.
•Criteria:
–Abundantabnormalcellswithcolumnarconfiguration
–Singlecells,sheets,clusters,syncytialaggregates
–Nuclei:enlarged,pleomorphic,irregularchromatindistribution,
parachromatinclearing,nuclearmembraneirregularities
–Macronucleoli
–Cytoplasm:finelyvacuolated

141. Adenocarcinoma,
Endocervical
Cytomorphologic Criteria:
Cluster of cells enlarged
nuclei, macronucleoliand
some nuclear membrane
irregularities; poorly defined,
finely vacuolated cytoplasm;
ghost of RBC's and cell debris
noted at the edge of the cluster
("clinging diathesis").

142. Other malignant neoplasms
•Uncommon primary tumors of cervix and uterine corpus:
•CARCINOMAS
–Spindle squamous cell carcinoma
–Poorly differentiated squamous cell carcinoma with small cells
–Small cell undifferentiated carcinoma
–Carcinoid tumors
–Malignant mixed mesodermal tumor or carcinosarcoma
•SARCOMAS

143. •Other primary tumors:
–Primary cervical germ cell tumors including choriocarcinoma,
yolk sac tumor and teratomas
–Lymphoma and malignant malanoma are rare primary tumor of
the cervix

144. •Secondary or metastatic tumors:
–3 routes
1.Direct extension
2.Lymphatic and/or hematogenous spread
3.Through fallopian tube
Malignant melanoma from vulva or vagina