28 Gynecologic : Squamous Abnormalities and Mimics condensation. is noperipheralcytoplasmic halo. Unlikekoilocytes,there be centrallylocatedwithinthe clear, andthenucleustendsto halos aresmall,notoptically overgrowth. Thesereactive secondary toCandidast ſt fromreactivechanges image st. seen inthelowerpartof irregularities. Koilocytesare hyperchromasia, andcontour including enlargement, but withnuclearfeatures, koilocytic cytoplasmicclearing shows cellsſtwithoutthe lesion (LSIL)onThinPrep squamous intraepithelial the biopsy. are seenintheupper1/2stof cervical epithelium.Koilocytes limited tothelower1/3of crowding andirregularityſt characterized bynuclear intraepithelial lesiongrade1, shows LSIL/cervical (Left) Cervicalbiopsysection the halos. not centrallylocatedwithin irregularities. Thenucleiare hyperchromasia, andcontour nuclear enlargement, an opticallyclearhaloand and bi-nuclearkoilocyteswith demonstrates agroupofuni- (Left) ThisThinPrepPaptest • CYTOPATHOLOGY • • • CLINICAL ISSUES • • ETIOLOGY/ • • TERMINOLOGY Mature celltypes(i.e.,superficialorintermediate) independent event intraepithelial lesion(HSIL),whichisbiologically Persistence isindicatorforcoexistenthigh-gradesquamous Often regressesspontaneouslyoverperiodof1-2years Asymptomatic; presentsasabnormalPapsmear/test HPV-16 dominatesinHR-HPV(+)group Grade TriageStudy);othersduetolow-risktypes6and11 due tohigh-riskHPV(HR-HPV)types(85%perASC-USLow- Most low-gradesquamousintraepitheliallesions(LSILs)are lesion grade1(CIN1) Includes koilocytosis,milddysplasia/cervicalintraepithelial Squamous cellchangesassociatedwithHPVinfection

(Right) Low-grade

(Right) Tighthalos Low-Grade SquamousIntraepithelialLesionandMimics LSIL, KoilocytesonThinPrep Cervical BiopsyWithLSIL KEY FACTS • • • • • • • • • early herpesviralchanges,tighthalosofreactivechanges Interpretive trapsincludenavicularcells,radiationchanges, anogenital squamousterminologyconferencein2012 Terminology forcytologyandhistologyunifiedafterlower not qualifyforadiagnosisofLSIL Perinuclear halosinabsenceofnuclearabnormalitiesdo Cytoplasm maybedenselykeratinized(orangeophilic) not requirementfordiagnosis of denselystainedcytoplasm(koilocyte)ischaracteristicbut Sharply delineatedperinuclearclearingwithperipheralrim Nuclear contoursaresmoothorslightlyirregular opaque andsmudged Coarsely granularanduniformlydistributedordensely (binucleated andmultinucleated) Variable hyperchromasia,size,shape,andnumber nucleus withmildincreaseinnucleus:cytoplasmratio Nuclear enlargement>3xsize(area)ofintermediatecell Tight Halos,NotLSIL LSIL Gynecologic Cytopathology: Squamous Cell Abnormalities and Mimics 29 (Right)

(Left) LSIL on SurePath Pap shows nuclear enlargement, hyperchromasia, smudged chromatin ﬈, nuclear contour irregularities, and ↑ nucleus:cytoplasm ratio but no cytoplasmic clearing. Pap smear shows navicular cells with yellow-tinged coloration ﬈ to the cytoplasmic clearing. Nuclear changes of LSIL are absent in this mimic. Utilize p16 to further clarify issue on Utilize p16 to further = LSIL/CIN 1 Lack of block staining features True koilocytes have clear halo and nuclear Nayar R et al: The for Reporting Cervical Cytology: Nayar R et al: The Bethesda System for Reporting Cervical York: Springer- Definitions, Criteria, and Explanatory Notes. 3nd ed. New Verlag, 2015 Nuclear changes of LSIL are not seen contours Slight nuclear enlargement (< 3x) and smooth cytopathic effect Early may lack characteristic viral altered Nuclear enlargement, chromatinic smudging, shapes Cytoplasm may be densely keratinized (orangeophilic) may be densely keratinized Cytoplasm do nuclear abnormalities halos in absence of Perinuclear for a diagnosis of LSIL not qualify mild or CIN 1) LSIL on biopsy (a.k.a. and histology unified after lower Terminology for cytology terminology conference in 2012 anogenital squamous 2 possible Some overlap with CIN ○ ○ be useful for triage in certain age HR-HPV testing may (per ASCCP guidelines) groups and clinical scenarios Yellow-tinged, large halo due to glycogen ○ SELECTED REFERENCES ANCILLARY TESTS DIFFERENTIAL DIAGNOSIS Hyperkeratosis • Tight Halos Due to / • Herpes Viral Infection • Radiation Effect • 1. • • Correlation Cytology-Histology • • • PCR • Navicular Cells • LSIL Mimic, Navicular Cells Low-Grade Squamous Intraepithelial Lesion and Mimics and Lesion Intraepithelial Squamous Low-Grade LSIL on SurePath Cases with LSIL and rare cells suggestive of HSIL can be Cases with LSIL and rare cells suggestive of LSIL; cannot reported as LSIL and ASC-H or just ASC-H or not sanction rule out HSIL (LSIL-H); Bethesda 2014 does new category of LSIL-H due to potential confusion Sharply delineated perinuclear clearing with peripheral rim Sharply delineated perinuclear clearing with characteristic but of densely stained cytoplasm (koilocyte) is not requirement for diagnosis Nuclear enlargement > 3x size (area) of intermediate cell Nuclear enlargement > 3x size (area) of intermediate ratio nucleus with mild increase in nucleus:cytoplasm number Variable hyperchromasia, size, shape, and (binucleated and multinucleated) or densely Coarsely granular and uniformly distributed opaque and smudged Smooth or slightly irregular nuclear contours Nucleoli usually absent or inconspicuous Mature cell types (i.e., superficial or intermediate cells) Mature cell types (i.e., superficial or intermediate Variable cellularity with cells in clumps, small groups, or Variable cellularity with cells in clumps, small single in clean or inflammatory background ○ Often regresses spontaneously over period of 1-2 years Often regresses spontaneously management guidelines are Country-/continent-specific available surveys range from 1.1-6.2% on Reporting rates per CAP and 0.0-4.3% for conventional liquid-based cytology cytology is 2.7% smears; median for liquid-based Low-grade squamous intraepithelial lesion (LSIL) squamous intraepithelial Low-grade CYTOPATHOLOGY CLINICAL ISSUES TERMINOLOGY Cytoplasmic Details • • • • • • • Nuclear Details Cells • Cellularity, Pattern, and Background • • • Presentation, Treatment, and Prognosis Presentation, Treatment, Abbreviations •