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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5186_Библиотеки_им_академика_М_И_Перельмана.pdf
can be unsatisfactory for a variety of reasons, and this should be indicated on the report.
Somespecimensarerejectedandnotprocessed;theseareusuallytheresultofabrokenslide
or empty collection vial. Others are found to be unsatisfactory after processing and
examinationoftheslide.AcommoncauseofunsatisfactoryThinPrepspecimensistheuseof
lubricantscontainingcarbomersorcarbopolpolymerswhenobtainingthesample.Cytychas
distributedanonexhaustivelistoflubricantsthatarelesslikelytointerferewithprocessing
(Table 6.3). Another common cause of unsatisfactory specimens is obscuring blood.
Althoughliquid-based systemscanremove bloodfrom the sample,the ThinPrepsystemis
abletohandlelessbloodthantheSurePathFicollgradient.
SquamousCellAbnormalities
LSIL in cervical cytology specimens is characterized by enlarged, dark nuclei (more than
three times the size of an intermediate cell nucleus), with irregular, thickened nuclear
membranes.Whenthecellsarebinucleatedandsurroundedbyasharplydefined,irregularly
shapedhalo witha peripheralrim ofthickened cytoplasm,thecellisknown asa koilocyte
(Fig.6.6).AlthoughkoilocytesarepathognomonicforadiagnosisofLSIL,theyarenot
required.LSILcanbediagnosedbasedoncellswithenlarged,dark,irregularnucleiandno
cytoplasmic halo. Koilocytes can be mimicked by prominent glycogen vacuoles or
inflammatoryhalos(Fig.6.7).Inthesecases,theareaofperinuclearclearingisnotsharply
demarcated,andtendstoberoundandregularwiththenucleuscentrallylocated.Whenthe
findings fall short of LSIL, the diagnosis of atypical squamous cells of undetermined
significance(ASC-US)isused(Fig.6.8).Usually,thisisbecauseoneofthenuclearfeatures
islacking:thenucleimaybenotquitelargeenough(2.5to3timesthesizeofanintermediate
cellnucleus),darkenough,orirregularenough.
Table6.3LubricantsLessLikelytoInterferewithThinPrepSamples
Brand Company
KYJelly Johnson&Johnson
Surgilube E.Fougera&Co.
Astroglide Biofilm,Inc.
Crystelle DeltexPharmaceuticals
Figure6.6 Low-gradesquamousintraepitheliallesion.Koilocyteshavesharplydelineated,
irregularhalosandmultipledarknucleiwithirregularnuclearborders.(Papanicolaoustain)
Figure 6.7 Inflammatory halos. Perinuclear clearing with a centrally located nucleus and
hazyedgescanbeseenwithinfections(e.g.,trichomonas)andcanbemistakenforkoilocytes.
(Papanicolaoustain)
Figure6.8 Atypicalsquamouscellsofundeterminedsignificance(ASC-US).Thenucleus
is2.5timesthesizeoftheintermediatecellnucleus,andthenuclearmembranesaresmooth.
(Papanicolaoustain)
HSILischaracterizedbycellswithdarknuclei,irregularnuclearmembranes,andhigh
nuclear-to-cytoplasmicratios(Fig.6.9).Thedysplasticcellscanoccursingly,insheets,or
assyncytialaggregates.Thechromatinmayrangefromcoarse tobland,and thecytoplasm
fromdelicateto dense. The nuclei vary in size and are frequently smaller than those seen
with LSIL. With liquid-based preparations, dispersed abnormal single cells are more
common than aggregates. In addition, with ThinPrep, the nuclei may not be dark; the
diagnosisreliesonfindingsinglecellswithirregularnuclearmembranesandhighnuclear-tocytoplasmicratios.
Figure 6.9 High-grade squamous intraepithelial lesion. The dysplastic cells have dark
nuclei with focal nuclear membrane irregularities and high nuclear-to-cytoplasmic ratios.
(Papanicolaoustain)
Figure6.10Atrophy.Atrophicvaginitis is characterizedbysheetsofparabasalcells andan
inflammatorybackgroundthatcanmimicsquamouscellcarcinoma.(Papanicolaoustain)
Mimics of HSIL include squamous metaplasia, atrophy, repair, endometrial cells,
histiocytes,andendocervicalcells.Atrophyandsquamousmetaplasiacanbeespecially
difficult to distinguish from HSIL. With atrophic changes, the basal and parabasal cells
havehighnuclear-to-cytoplasmicratioswithenlarged,darknuclei,andthebackgroundcan
resemble tumor diathesis (Fig. 6.10). The distinction from HSILrelies on finding smooth
nuclear membranes, flat monolayer sheets, and lack of variability in the nuclear size and
shape. Squamous metaplastic cells have high nuclear-to-cytoplasmic ratios and dense
cytoplasm, but smooth nuclear membranes. If the cytologic features fall short of a
diagnosis of HSIL, the diagnosis of “atypical squamous cells–cannot exclude HSIL
(ASC-H)”shouldbeused.Ifdysplasticcellsareclearlypresentbutdonotquitemeet
criteriafor HSIL, thenthechangesshould be characterized as “LSILcannotexclude
HSIL.”
The cytologic diagnosis of squamous cell carcinoma implies invasive carcinoma, because
carcinomainsituisencompassedwithinthecategoryofHSIL.Keratinizingsquamouscell
carcinoma has single cells with dense, dark nuclei and dense, orangeophilic (i.e., orangecolored)cytoplasm.Nonkeratinizingsquamous cellcarcinomahassyncytialaggregatesand
singlecells with coarse chromatinandpoorly defined cell borderswith delicate basophilic
(i.e., blue-colored) cytoplasm. Macronucleoli and tumor diathesis (i.e., necrosis,
degenerating blood, inflammation) can be seen with both, but more frequently with
nonkeratinizing squamous cell carcinoma. With liquid-based preparations, tumor
diathesis is seen as necrotic material clinging to the edges of cell groups and is less
apparentthanonconventionalsmears whereit is spreadacrossthebackground (Fig.
6.11).SquamouscellcarcinomacanbedifficulttodistinguishfromHSIL,becausethere
isasignificant morphologicoverlapbetweenthesetwo entities.Becausekeratinizationcan
be seen with both, the findings of macronucleoli and tumor diathesis are more reliable
indicatorsofsquamouscell carcinomabutarenotalwayspresent.ForHSILandsquamous
cellcarcinoma,thenextstepiscolposcopywithbiopsy,whichwillprovidematerialformore
definitiveassessmentofinvasivecarcinoma.
GlandularCellAbnormalities
Thediagnosis of“atypicalglandularcells”accounts forless than1%of allPaptests.
Significantdiseaseispresentin9–38%ofcases,withHSILthemostcommonabnormal
finding(11).Otherfindingsincludeendocervicaladenocarcinomainsitu(AIS),endocervical
adenocarcinoma, endometrial pathology including carcinoma, and extrauterine carcinoma.
Postmenopausal women have a higher rate of abnormality, with a significant cervical or
endometrialabnormalityfoundinmorethan30%ofcases.
Endocervical AIS is characterized by enlarged, elongated nuclei, with irregular nuclear
membranes and coarse chromatin arranged radially as rosettes or in strips as crowded
palisades(Fig.6.12). When the cytoplasm is partially stripped away,the palisading nuclei
canresembleanarrayoffeathers.Thisfeatureisreferredtoasfeatheringandisconsidered
characteristicofAIS.Mitoticfiguresarecommonlypresent.
Figure 6.11 Squamous cell carcinoma. Necrosis in liquid-based preparations is
characterizedbygranulardebristhatclingstotheedgesoftumorcellclusters.(Papanicolaou
stain)
EndocervicalAIScanbecloselymimickedbytubalmetaplasia,directsamplingofthe
endometrium, and HSIL involving endocervical glands. Tubal metaplasia is
distinguishedbythelackofnuclearcrowdingandsmoothnuclearmembranes.Thepresence
ofciliaischaracteristicbutnotalwaysseen.Directsamplingoftheendometriumcanyield
stripsandsheetsofatypicalglandularcellswithfeathering,rosetteformation,andfrequent
mitoticfigures.Identifyingsmall,tightlycohesiveendometrialstromalcellscanhelpinthe
distinction from AIS. Sampling of endometrial glands can occur as the result of cervical
endometriosis,orinadvertentsamplingof the lower uterine segment or endometrial cavity
(Fig. 6.13). The latter occurs more frequently in patients who have a shortened cervix
because of previous LEEP or cone biopsy. The presence of glands embedded in stroma
should raise the possibility of direct endometrial sampling. HSIL involving endocervical
glandscanbedistinguishedfromAISbythelackofpalisading,presenceofsinglecellswith
high nuclear-to-cytoplasmic ratios and irregular nuclear membranes, or evidence of
keratinization. AIS and HSIL can coexist. If the features fall short of a diagnosis of AIS,
dependingonthe degreeof atypiapresent,thefollowingBethesda diagnosesmaybeused:
“Atypicalendocervicalcells,nototherwisespecified(NOS)”or“Atypicalendocervicalcells,
favor neoplastic.” The latter diagnosis is associated with a higher likelihood of finding a
clinicallysignificantlesiononbiopsy.
Figure6.12Endocervicaladenocarcinomainsitu. Palisadingnucleistrippedof cytoplasm
(“feathering”) is a characteristic feature. The nuclei are enlarged and elongated with coarse
chromatin.(Papanicolaoustain)
Figure6.13Endometriosis.Directsamplingofendometrial glandsincervicalendometriosis
canmimicendocervicaladenocarcinoma insitu.Thesmooth nuclear membranesandlackof
nuclearcrowdingsupportabenignprocess.(Papanicolaoustain)
Adenocarcinomasmostcommonlyoriginatefromtheendocervixorendometrium,but
malignant glandular cells on cervical cytology may represent spread from an
extrauterine source (e.g., ovary,breast, stomach, colon, kidney,or bladder). Invasive
endocervicaladenocarcinomasresembleAISbutaredistinguishedbythepresenceofatumor
diathesis in the background. Endometrial carcinoma is characterized by three-dimensional
groups or papillary clusters of cells with enlarged nuclei, and often vacuolated cytoplasm
(Fig. 6.14). Intracytoplasmic neutrophils are common. When the tumor cells have large
cytoplasmicvacuolesandareassociatedwithpsammomabodies,thefindingsaresuggestive
of a serous carcinoma. Adenocarcinoma cells in a clean background or with unusual
morphologythatisnottypicalofauterineprimaryraisethepossibilityofmetastaticdisease
(Fig.6.15).
The diagnosis of atypical endometrial cells is used when endometrial cell clusters show
mildnuclearenlargement,vacuolatedcytoplasm,orcytoplasmicneutrophils.Ifitcannotbe
determinedwhethertheatypicalcellsareendocervicalorendometrialinorigin,thediagnosis
of atypical glandular cells (NOS) or atypical glandular cells, favor neoplastic can be
used.