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CYTOPATHOLOGY Volume 40 Number 11 ISSN 1091-8620 (print) ISSN 2167-2210 (online) © ASCP October 2012 129 ® If you wish to obtain an MOC self-assessment module (SAM) credit for this exercise, please log in to www.ascp.org. 129 CYTOPATHOLOGY NO. CY 12-11 (CY-461) Nalini Gupta, MD, DNB Associate Professor Department of Cytology and Gynaecological Pathology Satyawati Mohindra, MS Associate Professor Department of Otolaryngology Arvind Rajwanshi, MD, FRCPath Professor and Head Department of Cytology and Gynaecological Pathology Postgraduate Institute of Medical Education and Research, Chandigarh, India

CYTOPATHOLOGY - Amazon S3 · • include appropriate entities in the differential diagnosis based on results of ... polymerase chain reaction, to make a proper diagnosis on FNAC

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cytopathology

Volume 40

Number 11

ISSN 1091-8620 (print)

ISSN 2167-2210 (online)

© aScp October 2012

129

®

If you wish to obtain an MOC self-assessment module (SAM) credit for this exercise, please log in to www.ascp.org.

129

CYTOPATHOLOGY NO. CY 12-11 (CY-461)

Nalini Gupta, MD, DNB Associate Professor Department of Cytology and Gynaecological Pathology

Satyawati Mohindra, MS Associate ProfessorDepartment of Otolaryngology

Arvind Rajwanshi, MD, FRCPath Professor and Head Department of Cytology and Gynaecological Pathology

Postgraduate Institute of Medical Education and Research, Chandigarh, India

LEARNING OBJECTIVES

On completion of this exercise, the participant should be able to

• choosefromdifferentapproachestoperformingfine-needleaspirationcytology(FNAC)insinonasalregions.

• triagecasesforotherancillarytechniquesormicrobiologicstudiesbeforeFNACtoensurethatadequatematerialisobtained.

• includeappropriateentitiesinthedifferentialdiagnosisbasedonresultsofFNACinsinonasallesions.

• identifythemajorpitfallsintheroutinecytomorphologicanalysisofvarioussinonasallesions.

• applyancillarytechniques,suchasimmunochemistry,flowcytometry,orpolymerasechainreaction,tomakeaproperdiagnosisonFNAC.

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Copyright©2012bytheAmericanSocietyforClinicalPathology.Allrightsreserved.CopyrightlawallowsformultiplecopyduplicationoftheCheckSampleexercisesandcolorimages(printedordigital)forclassroomuseandforin-servicecontinuingeducationbynonprofitgroups.Writtenpermissionisnotrequiredinthesecasesaslongascopiesmadedonotexceedthenumberofstudentsorparticipantsandcopiesarenotchargedfor.Allotheruses includingreproduction, storage ina retrieval system,or transmission inany formorbyanymeans(includingelectronic,mechanical,photocopying,orrecording)requirepriorwrittenpermissionoftheAmericanSocietyforClinicalPathology,[email protected]®isaregisteredtrademarkoftheAmericanSocietyforClinicalPathology.

The American Society for Clinical Pathology (ASCP) is accredited by the AccreditationCouncil for ContinuingMedicalEducationtoprovidecontinuingmedicaleducation(CME)forphysicians.

TheASCPdesignatesthiseducationalactivityfor1AMA PRA Category 1 CreditTM.Physiciansshouldonlyclaimcreditcommensuratewiththeextentoftheirparticipationintheactivity.

TheseactivitiesmeettheAmericanBoardofPathology’sMaintenanceofCertificationProgramPartIILifelongLearningrequirements.

SelectASCPcontinuingeducationactivitiesareacceptedbyCalifornia,Florida,andmanyotherstatesforrelicensureof clinical laboratorypersonnel.ASCPdesignates these activities for the indicatednumberofContinuingMedicalLaboratoryEducation(CMLE)credits.ASCPCMLEcreditsareacceptabletomeetthecontinuingeducationrequire-mentsfortheASCPBoardofRegistryCertificationMaintenanceProgram.AllASCPCMLEprogramsareconductedatintermediatetoadvancedlevelsoflearning.

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Materialswillbereplacedwithoutcharge,worldwide, if thepublisherreceivesarequestwithin90daysofthemailingdate.

Forsubscriptioninformation,addresscorrections,ornotificationofdamagedshipments,contacttheASCP.For instructions on submitting your answers, please visit http://www.ascp.org/checksampleinstructions.Credit for 2012 Check Sample exercises may be earned through December 31, 2014.

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HISTORIES

Case AA22-year-oldwomanwitha2-yearhistoryofnasalobstructionandagraduallyincreasingswellingovertherightsideanddorsumofthenoseunderwenttestinginanoutpatientotolaryngologyclinic.Computedtomography(CT)revealedaheterogeneouslyenhancingsoft-tissuelesioninthemedialaspectoftherightorbit,rightethmoidaircells,andthesuperioraspectoftherightnasalcavity(Image 1A).Therewasintraorbitalextraconalextensionofthesofttissue,andtherightglobewasdisplacedsuperiorlybythelesion.Thepatienthadnohistoryofcorticosteroidintakeorimmunocompromisedstatus.

Aspecimenfromtheswellingovertherightdorsumofthenosewasobtainedviatranscutaneousfine-needleaspirationcytology(FNAC).Theaspiratewasthickandparticulate.Air-driedsmearswerestainedwithMay-GrünwaldGiemsa(MGG)(Image1Band1C),andwet-fixedsmearswerestainedwithH&E(Image1D)andperiodicacid–Schiff(Image 1E).Theleftoveraspiratedmaterialwassenttothemicrobiologydepartmentforfungalculture.

Case BA42-year-oldwomansoughttreatmentfora7-monthhistoryofintermittent,severepainintherightcheek,nasalobstruction,andnasalbleeding.Examinationrevealeda3×2–cmdiffuse,tender,softswellingovertherightcheekandrightsideofthenose.Contrast-enhancedCTshoweduniformandmoderatecontrastenhancementofahomogeneoussoft-tissuemedium-densitymassinvolvingbilateralmaxillary,ethmoid,frontal,andsphenoidsinuses,andextendingtothenasopharynx(Image 2A).Thelesionwascausinglocaltissuedestruction.

TranscutaneousFNACwasperformedontherightnasalswelling.Theaspiratewasthickwithparticulatematter.Air-driedandwet-fixedsmearsandacellblockwereprepared.Theair-driedsmearswerestainedwithMay-GrünwaldGiemsa(Images 2B,2C,and2D),andwet-fixedsmearswerestainedwithH&E(Image 2E).Immunochemicalanalysiswasdoneonthecellblock(Images 2F, 2G,and 2H).

Case CA34-year-oldmanhadahistoryofright-sidednasalblockagethatbegan2yearspreviously;9monthsaftertheblockagebegan,hebegantoexperienceleft-sidednasalblockageassociatedwithdirty-whitenasaldischargeandoccasionalnasalbleeding.Onexamination,therewasafoulsmellingmassintherightnasalcavity.Contrast-enhancedCTrevealedapolypoid,homogenouslyenhancingmedium-densitymassinvolvingtherightmaxillaryantrumandbilateralnasalcavity,withthepolypoidcomponentofthesofttissueprojectingintothenasopharynx(Image 3A).Radiologicfindingssuggestedanasopharyngealcarcinoma(NPC).

AnFNACspecimenwasobtainedfromtherightnasalswelling.Basedonclinicoradiologicfindings,acellblockwasprepared,andtheaspiratewassubmittedforancillarystudies,includingflowcytometrybecauseofsuspicionofnon-Hodgkin

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lymphoma,andpolymerasechainreactionforEpstein-Barrvirus(EBV),owingtoitsassociationwithNPC(Images 3B-3F).

Case DA33-year-oldmancomplainedofswellingontherightsideofhishardpalatethatstartedonemonthpreviously.Onexamination,therewasanintraoralswellingmeasuringabout3cmindiameter,withmissingteethonthesameside(Image 4A).Theoverlyingmucosawascongested.Contrast-enhancedCTrevealedalarge,lyticlesionoccupyingtherightmaxillaryregion.Therewasdestructionofbonymarginsandexpansionintoadjacentsofttissues.IntraoralFNACwasperformed,andair-driedandwet-fixedsmearswereprepared(Images4B-4F).Acellblockwasalsoprepared(Image 4G).

Cytologic FindingsCase A Thesmearswerecellularandpredominantlyshowednecrosis,withoccasionalepithelioidcellcollectionsandmanymultinucleatedgiantcellsinabackgroundofmixedinflammatoryinfiltrate.Manynarrowseptatefungalprofileswithacute-anglebranchingwerenotedinthenecroticbackgroundaswellasinthegiantcells(Images1B-1D).ThemorphologicfeatureswereconsistentwiththoseofAspergillus.Periodicacid–Schiffhighlightedfungusinthesmearbackgroundandwithinthegiantcells(Image1E).FungalcultureconfirmedthepresenceofAspergillus flavus.

Case B Onmicroscopicevaluation,thesmearswerehighlycellularandcomprisedadispersedpopulationofmalignantsmallblueroundcells.Pericapillaryarrangementoftumorcells,looseclusters,prominenteosinophilicfibrillarymaterialinthebackground,androsetteswithtumorcellsarrangedaroundthefibrillarymaterialwereseen.Thetumorcellshadroundtoovalnuclei,highnuclear-cytoplasmicratio,finegranularchromatin,andinconspicuousnucleoli(Images2B-2D).Thecellblockshowedsimilarfindings(Image2E).

Thedifferentialdiagnosisincludedolfactoryneuroblastoma/esthesioneuroblastoma(ENB),sinonasalneuroendocrinecarcinoma,embryonalrhabdomyosarcoma,sinonasalundifferentiatedcarcinoma,andlymphoma.Toestablishadiagnosis,apanelofimmunostainswasperformed,includingvimentin,chromogranin,desmin,cytokeratin,HMB45,leukocytecommonantigen(LCA),andmyc-2protein.Thetumorshowedcytoplasmicpositivityforvimentinandchromogranin(Images2Fand2G).Tumorcellswerenegativefordesmin(Image2H),cytokeratin,HMB45,LCA,andmyc-2.Theoverallfeatureswerethoseofolfactoryneuroblastoma/ENB.

Case CThesmearswerecellularandshowedamonomorphicpopulationofatypicallymphoidcellswithprominentcapillarychannels.Thecellswere2to3timesthesizeofmaturelymphocytes,withahighnuclear-cytoplasmicratio,openchromatin,1to2conspicuousnucleoli,andscantycytoplasm(Images3B,3C,and3D).Thebackgroundshowednumerouslymphoglandularbodies,nucleardebris,apoptoticbodies,andscatteredmaturelymphocytes.

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Thecellblockwaspreparedforimmunochemicalanalysis,andflowcytometricimmunophenotypingwasperformedforapanelofantibodies.Oncellblock,thecellsshowedstrongmembranouspositivityforCD20andnegativityforCD3andcytokeratin(Images3Eand3F).Onflowcytometry,thecellsshowedpositivityforCD19,CD20,CD79a,andκlightchain.CD3wasnegative.Basedonflowcytometricimmunophenotypingandimmunochemistry,adiagnosisofdiffuselargeB-celllymphoma(DLBCL)wasmade.

Case D Thesmearswerecellular,comprisinglargetissuefragmentsandscatteredtumorcells.Thetumorcellswereplasmacytoidtopolygonaltospindleshaped,hadmarkednuclearpleomorphism,coarsechromatin,prominentnucleoli,andmoderatetoabundantgranularcytoplasm(Image4B).Numerousosteoclasticgiantcellswerealsoseen(Image4C).Thetumorcellswerecloselyassociatedwithbrightlymetachromaticmatrixmaterialrepresentingosteoid(Images4Dand4E).Thedifferentialdiagnosisincludedgiantcelltumorandpleomorphicsoft-tissuesarcoma.Markednuclearpleomorphismandlackofspatialarrangementofgiantcellswithspindlecellsfavoredthepossibilityofosteosarcomaovergiantcelltumor.Thecellblockrevealedosteoiddepositedbythetumorcells(Image4G),confirmingthediagnosisofosteosarcoma.

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FINE-NEEDLE ASPIRATION CYTOLOGY OF LESIONS OF THE NOSE, NASAL CAVITY, AND PARANASAL SINUSES

FNACcanactasanimportantdiagnostictechniqueinsinonasallesions,especiallywheninterpretedwithclinicoradiologicdata.1ManysinonasallesionsmaynotbeamenabletoFNACinearlystages;thecomplexanatomyofthenoseandparanasalsinusesisanimportantcauseofsamplingerrorinFNACofthissite.Anadequatesamplecanbeobtainedbyvariousmeans,suchasatranscutaneous,intraoral,orintranasalapproach,ultrasound-guidedFNAC,orendoscopy-guidedFNAC,dependingonthelocationofthelesion. Whenthereisclinicoradiologicevidencesuggestinganinfectiouscause,theaspiratedmaterialshouldbesenttothemicrobiologydepartmentforbacterialandfungalcultures.

Whenamalignantneoplasmissuspected,acellblockshouldbepreparedforfurtherimmunochemicalstudyand,ifnon-Hodgkinlymphomaissuspected,theaspiratedmaterialshouldundergoflowcytometricimmunophenotypingandimmunochemicalstudyoncellblocks.

Awidevarietyofnonneoplasticaswellasneoplasticlesionscaninvolvethesinonasalregion.1Fungalinfections,especiallyAspergillusinfectionofthesinonasalregion,arecommon.Aspergillosisoftheparanasalairsinusescanbeinvasiveornoninvasive.2Invasivefungalsinusitiscanbeclassifiedinto3categories:acutefulminantinvasivefungalsinusitis,chronicinvasivefungalsinusitis,andinvasivegranulomatousfungalsinusitis.3-5Aspergillusisthemostcommonfungusaffectingthesinonasalregion,followedbyfungioftheorderMucorales,whichcausemucormycosis(zygomycosis).Uncommonly,Pseudallescheria boydii,Paecilomyces,Alternaria,Cladosporium trichoides,andFusarium causesinonasalinfection.Morphologically,hyphaeinAspergillusarenarrow,withregularseptationsandacute-anglebranching.AspergillosisisusuallyassociatedwithanexcessofeosinophilinfiltrationandCharcot-Leydencrystals.Hyphaeinmucormycosisarebroad,ribbonlike,delicate,andnonseptate,foldingonthemselveswithright-anglebranching.Mucormycosisisusuallyassociatedwithnecrosis.Inaspirate,fungalhyphaeshouldbesoughtinthenecroticbackgroundaswellasinthecytoplasmofmultinucleatedgiantcells.Periodicacid–SchiffandGomorimethenaminesilverstainscanbeusedtohighlightthefungalprofiles.Therecanbevariableimmunologicresponsetothefungalinfection,includinggranulomatousreaction,necrotizinginflammation,andnonspecificinflammationwithanexcessofeosinophils.Treatmentincludessurgicaldebridementandappropriatesystemicantifungaltherapy.

Themostcommonlocationformalignantsinonasaltumorsisthemaxillarysinus,followedbythenasalcavityandtheethmoidsinus.Fortypercentto50%ofthesetumorsaresquamouscellcarcinomas.1

Olfactoryneuroblastoma/ENB accountsforabout5%ofsinonasaltumorsandusuallyarisesinthesuperiornasalcavity.Itoccursinpersonsaged3to79years,withamedianageofapproximately50years.Itaffectsmalesandfemales,andthemainclinicalmanifestationisnasalobstructionthatisfollowedbyepistaxis.Kadishetalproposeda3-stageclassificationforENB6:groupA,tumorslimitedtothenasal

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fossa;groupB,tumorsthatextendtotheparanasalsinuses;andgroupC,tumorsthatextendbeyondthenasalcavityandparanasalsinuses.

Onmicroscopy,theappearanceofthetumorissimilartothatofchildhoodneuroblastoma.Smearsareusuallyhypercellularandcomposedofaproliferationofrelativelyuniformsmallroundcellswithscantcytoplasm.Thecellsmaybearrangedinlooselycohesiveclusters,withfibrillarymaterialinbetween.Onhistologicexamination,similartumorcellsareseeninnestsorsheetsseparatedbyfibrovascularseptae.Truerosettes(Flexner-Wintersteinerrosettes)aswellaspseudorosettes(HomerWrightrosettes)maybenoted.Truerosetteshavetumorcellsarrangedringlikearoundacentralroundorovalclearspace.Apseudorosetteisaloosearrangementoftumorcellsaroundfibrillarymaterial.ItisusuallydifficulttodistinguishtruerosettesfrompseudorosettesonFNAC.

Themaindifferentialdiagnosisonmorphologicevaluationincludessinonasalneuroendocrinecarcinomaandsinonasalundifferentiatedcarcinoma(SNUC).Sinonasalneuroendocrinecarcinomausuallyarisesinthelarynx;thetumorsrangefromwell-topoorlydifferentiated.Itischaracterizedbyhypercellularsmearscomposedofamonotonouspopulationofdispersedtumorcells.Thecellsusuallyhaveeccentricallyplacednuclei,salt-and-pepperchromatin,andanampleamountofeosinophilicgranularcytoplasm.Thesetumorsdonothaverosettesoraneurofibrillarybackground.High-gradeENBshouldbedifferentiatedfromSNUC.SNUCusuallyhaslooselycohesiveclustersandadispersedpopulationofhighlypleomorphictumorcellswithmoreamplecytoplasm.SNUCisadiagnosisofexclusion,ENBshouldalsobedistinguishedfromothermalignantsmallroundcelltumors,suchasEwingsarcoma,lymphoma,rhabdomyosarcoma,andmelanoma.Toestablishadiagnosis,apanelofimmunostains,includingS-100protein,synaptophysin,chromogranin,cytokeratin,desmin,actin,HMB-45,LCA,andmyc-2protein,isneeded.ENBshowsscatteredandperipheralS-100positivityandcanshowpositivityforneuroendocrinemarkers,suchaschromograninandsynaptophysin.AllothermarkersareusuallynegativeinENB.ApositiveneuroendocrinemarkerinconjunctionwithanegativecytokeratininENBdifferentiatesitfromSNUC,whichispositiveforcytokeratin,andsinonasalneuroendocrinecarcinoma,whichispositiveforcytokeratinandneuroendocrinemarkers.Densecoreneurosecretorygranules,neuronalprocessescontainingmicrotubules,andneurofilamentsareseenonelectronmicroscopyinENB.Thetreatmentofchoiceiscompletesurgicalresectionofthetumorfollowedbyradiotherapy.

Non-Hodgkinlymphomaaccountsforabout14%ofallmalignantsinonasaltumors.7

SinonasallymphomasaremorecommoninpersonsofAsiandescentthaninpersonsofEuropeandescent.ThesetumorscanbeofB-cellorT-cell/naturalkillercelltypes,andarecategorizedasextranodallymphomas.8B-cellphenotypesinonasallymphomainvolvestheparanasalsinusesandismorelikelythanT-cellsinonasallymphomatoextendtotheorbit.T-cell/naturalkillercelltypeismorecommoninpersonsofAsiandescentthaninpersonsofEuropeandescent.FNACisausefultechniqueforestablishinganinitialdiagnosis;immunophenotypingoftheaspiratecanhelpwithpropersubtyping.InitialtriagingoftheaspiratedmaterialisimportanttoavoidrepeatingFNACforancillarystudiessuchasflowcytometricimmunophenotypingorimmunochemistry.Thedifferentialdiagnosisofnon-Hodgkinlymphomaincludes

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NPC(WorldHealthOrganization[WHO]classIII;lymphoepithelioma),SNUC,andothermalignantsmallroundbluecelltumors,suchasEwingsarcoma/primitiveneuroectodermaltumor(EWS/PNET).FNACsmearsinDLBCLusuallyshowadispersedpopulationofatypicalcellswithroundorcleavedvesicularnucleihavingirregularnuclearmembranesand1ormultiplesmallnucleoli.Thebackgroundcharacteristicallyshowslymphoglandularbodies;however,thesameareseeninlymphnodeaspiratesfrompatientswithmetastaticcarcinoma.NPC,WHOclassIII,isanundifferentiatedcarcinomawithlarge,syncytialcells,withahighnuclear-cytoplasmicratio,vesicularnuclei,andlargeamphophilicnucleoli.Thesecellscanbecloselyadmixedwithlymphocyticinfiltrate.SNUCisadiagnosisofexclusionandisusuallycharacterizedbysmallorlargetumorcellswithcoarsechromatin,prominentnucleoli,andmoderatetoabundantcytoplasm.Thesefeaturesmaybeaccompaniedbynumerousmitoticfeaturesandnecrosis.

ImmunochemistryDLBCLshowspositivityforLCAandmembranouspositivityforCD20.MostDLBCLsarepositiveforbcl-6.AberrantcoexpressionofCD43inabout20%ofcasesorofCD5in5%to10%ofcasesmaybenoted.CD10andbcl-2mayalsobepositive.ImmunostainingforcytokeratinmayhighlightNPCWHOclassIII,andtheendemicformofNPCisassociatedwithEBV;therefore,polymerasechainreactionforEBVmaybehelpful.AlthoughSNUCalsoexpressesepithelialmarkers,itisusuallyadiagnosisofexclusion.EWS/PNETshowspositivityforneuroendocrinemarkers,andEWSispositiveformyc-2.EWSisalsoassociatedwithEWS-FLI1fusionresultingfromthespecificchromosomaltranslocationt(11;22)(q24;q12).

Sarcomasarisingfromthesofttissueandbonecanbeseeninthesinonasalregion.Osteosarcoma isamalignantbonetumorcharacterizedbytheformationofdisorganizedimmaturewovenboneorosteoid.9Itaccountsfor15%to35%ofallprimarybonetumors.Osteosarcomaofthejawbonesisrare,representing4%to8%ofallosteosarcomas.10Peakincidenceforjawosteosarcomaoccursinpersonsintheir20sand30s.11Osteosarcomaofthejawhasapredilectionforthemandible,althoughinvolvementofthemaxillaisnotrare.Maxillarylesionsusuallyinvolvethealveolarridge,sinusfloor,andpalate.11Histologically,itiscategorizedintoosteoblastic,chondroblastic,telangiectatic,fibroblastic,fibrohistiocytic,androundcelltypes.Owingtothedestructivenatureofthetumor,FNACcanprovideinitialdiagnosis.Smearsareusuallyhypercellularwithhyperchromaticpleomorphicspindletoepithelioidstromalcells,someofwhichproducemetachromaticmatrixmaterialconsistentwithosteoid.12OsteoidisbetterseeninRomanowsky-stainedsmears,whereitformslacelikematerialordensedepositsofbrightlyeosinophilicmatrixmaterial.Avariablenumberofgiantcellsisfrequentlypresent.Cytopathologistsshouldbeawareoftelangiectatic,chondroblastic,roundcell,andgiantcell–richvariantsofosteosarcoma.Thetumorcellsinosteosarcomaareusuallypositiveforvimentin,osteocalcin,osteonectin,andS-100.Themainstayoftreatmentissurgeryandadjuvantchemotherapy.Prognosisdependsmainlyonthetumorstage.

SummaryFNACcanbesafelyperformedinthesinonasalregion.Cytopathologistsshouldbeawareofthewidevarietyofnonneoplasticandneoplasticlesionsthatcanbeseen

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8. JaffeES,HarrisNL,SteinH,VardimanJW,eds.World Health Organization Classification of Tumours:Pathology and Genetics: Tumours of Haematopoietic and Lymphoid Tissues.4thedition.Lyon,France:IARC;2008.

9. FernandesR,NikitakisNG,PazokiA,OrdRA.Osteogenicsarcomaofthejaws:a10-yearexperience.J Oral Maxillofac Surg.2007;65:1286-1291.

10. WarnockG.Malignantneoplasmsofthegnathicbones.In:ThompsonLD,GoldblumJR,eds.Head & Neck Pathology.1sted.Philadelphia,PA:Elsevier;2006:492-497.

11. AngelaC.Bonepathology.In:NevilleBW,DammDD,AllenCM,BouquotJE,eds.Oral & Maxillofacial Pathology.3rded.Philadelphia,PA:Saunders;2009:660-664.

12. WoldLE,UnniKK,SimFH,etal.Atlas of Orthopedic Pathology.3rded.Philadelphia,PA:W.B.SaundersCompany;2008.

inthisregion.Themainreasonforfalse-negativeresultsissamplingerror;therefore,radiologicguidanceinFNACmaybehelpfulindifficultcases.AplannedapproachtoFNACwithpropertriagingoftheaspiratedmaterialcanavoidrepeatedFNACandfalse-negativeresults.

REFERENCES

1. GuptaN,KaurJ,MohindraS,etal.FNACinthelesionsofnose,nasalcavityandparanasalsinuses.Acta Cytol.2011;55(2):135-141.

2. SanghviV,BokilK,KelkarR.Aspergillosisoftheparanasalairsinuses(casereportsandreviewofliterature).Indian J Cancer.1992;29:7-13.

3. deShazoRD,O’BrienM,ChapinK,etal.Anewclassificationanddiagnosticcriteriaforinvasivefungalsinusitis.Arch Otolaryngol Head Neck Surg.1997;123(11):1181-1188.

4. deShazoRD.Fungalsinusitis.Am J Med Sci.1998;316(1):39-45.

5. StringerSP,RyanMW.Chronicinvasivefungalrhinosinusitis.Otolaryngol Clin North Am.2000;33(2):375-387.

6. KadishS,GoodmanM,WangCC.Olfactoryneuroblastoma:aclinicalanalysisof17cases.Cancer. 1976;37(3):1571-1576.

7. HarboG,GrauC,BundgaardT,etal.Cancerofthenasalcavityandparanasalsinuses:aclinico-pathologicalstudyof227patients.Acta Oncol.1997;36:45-50.

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CME DOCUMENTATION QUESTIONS

1. ThecytomorphologicfeaturesofAspergilluscanbebestdescribedas

A. broaddelicatehyphaewithregularseptationsandacute-anglebranching.B. narrowhyphaewithregularseptationsandacute-anglebranching.C. broad,delicate,aseptatehyphaewithright-anglebranching.D. narrowaseptatehyphaewithright-anglebranching.

2. A37-year-oldmanhada3-monthhistoryofepistaxisandnasalobstruction.Fine-needleaspirationcytology(FNAC)fromthenasallesionshowssheetsofmalignantsmallblueroundcellswithfocalrosettelikestructureswithafibrillarybackground.Themostusefulpanelofimmunomarkerstomakeacorrectdiagnosisincludes

A. cytokeratin,myc-2protein,CA-125,myogenin,leukocytecommonantigen(LCA),andcarcinoembryonicantigen.

B. S-100protein,chromogranin,desmin,cytokeratin,HMB45,LCA,andmyc-2protein.

C. Myo-D1,pancytokeratin,vimentin,CK5/6,p63,HMB-45,CD15,andcalretinin.

D. S-100protein,HMB-45,CD3,CD20,thyroidtranscriptionfactor1,inhibin,andWT-1.

3. WhattypeofsinonasallymphomaiscommoninAsianpopulations?

A. FollicularlymphomaB. PrecursorB-lymphoblasticlymphomaC. BurkittlymphomaD. T-cell/naturalkiller–celltypelymphoma

4. A36-year-oldwomanhasasoft-tissuemassinvolvingbilateralnasalcavitiesandextendingintothenasopharynx.FNACisperformedontherightnasallesion.OnFNAC,thedifferentialdiagnosisisnarroweddowntonasopharyngealcarcinoma,WorldHealthOrganizationclassificationIII,lymphoepitheliomatype,andnon-Hodgkinlymphoma.Whatisthemostusefulpanelofimmunomarkerstoreachaproperdiagnosis?

A. LCA,CD20,CD3,andcytokeratinB. LCA,cytokeratin,thyroidtranscriptionfactor1,andmelan-AC. Cytokeratin,MIC-2,calretinin,andS-100D. Cytokeratin,carcinoembryonicantigen,andp63

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Note:ToreceiveCMEorSAMScredit,pleasesubmityouranswersonline.

5. A39-year-oldmanhadamaxillaryswellingforthepast2months.FNACisperformedontheswelling,andthesmearsarecellular.Thereareclustersofplasmacytoidtospindlecellswitheosinophilicgranularcytoplasm.Eosinophilicmatrixmaterialisnoted,closelyassociatedwiththetumorcells.Thecellblockisadequate,andtumorcellsformingosteoidaredemonstrated.Thecytologicimpressioninlightoftheradiologicdataisthatofanosteogenicsarcoma.Whatshouldbethenextapproach?

A. BiopsyandhistopathologicexaminationB. LocalradiotherapyC. NeoadjuvantchemotherapyandcompletesurgicalexcisionD. Immunotherapy

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®

View and download digital versions of these images at:https://www.ascp.org/services/MyMaterials.aspx

Image 1A. Case A. Computed tomographic scan showing a soft-tissue mass in the right anterior ethmoid sinus extending into the right orbit, with destruction of intervening lamina papyracea.

Image 1B. Case A. Necrotic material with degenerated inflammatory cells and fragmented hyphae (May-Grünwald Giemsa, original magnification ×40).

Image 1C. Case A. Multinucleated giant cells with narrow septate fungal hyphae in the cytoplasm (May-Grünwald Giemsa, original magnification ×40).

Image 1D. Case A. An ill-defined epithelioid cell collection and a multinucleated giant cell (H&E, original magnification ×40).

Image 1E. Case A. Fungal hyphae with acute-angle branching (periodic acid–Schiff, original magnification ×100).

Image 2A. Case B. Computed tomographic scan showing a homogenous medium-density mass in the ethmoid and sphenoid sinuses, causing their expansion and bone destruction. The lesion extends into the extraconal space in the right orbit.

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®

View and download digital versions of these images at:https://www.ascp.org/services/MyMaterials.aspx

Image 2B. Case B. Loosely cohesive clusters and dispersed population of small blue round cells in a fibrillary background (May-Grünwald Giemsa, original magnification ×20).

Image 2C. Case B. Malignant small blue round cells with focal rosettelike structures (May-Grünwald Giemsa, original magnification ×40).

Image 2D. Case B. Malignant small round cells with high nuclear-cytoplasmic ratio and scanty cytoplasm (May-Grünwald Giemsa, original magnification ×100).

Image 2E. Case B. Cell block showing small blue round cells (H&E, original magnification ×100).

Image 2F. Case B. Tumor cells show cytoplasmic positivity for vimentin on cell block (immunostain, original magnification ×100).

Image 2G. Case B. Tumor cells show cytoplasmic positivity for chromogranin on cell block (immunostain, original magnification ×100).

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Image 2H. Case B. Tumor cells show negativity for desmin on cell block (immunostain, original magnification ×100).

Image 3A. Case C. Contrast-enhanced computed tomographic scan showing a moderate homogenously enhancing soft-tissue medium-density mass almost completely obliterating the nasal cavities and right maxillary sinus, extending posteriorly into the nasopharynx. An air fluid level is seen in the left maxillary sinus, due to retained secretions caused by blockage of the ostium.

Image 3B. Case C. Sheets of atypical lymphoid cells, naked nuclei, with many lymphoglandular bodies in the background (May-Grünwald Giemsa, original magnification ×40).

Image 3C. Case C. Dispersed population of atypical lymphoid cells, apoptotic bodies, and lymphoglandular bodies (May-Grünwald Giemsa, original magnification ×100).

Image 3D. Case C. Atypical lymphoid cells with round nuclei having irregular nuclear membranes, 1 or multiple small nucleoli, and few cells showing cytoplasmic vacuolation (May-Grünwald Giemsa, original magnification ×100).

Image 3E. Case C. Atypical lymphoid cells showing membranous positivity for CD20 (original magnification ×100).

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Image 3F. Case C. Atypical lymphoid cells, negative for CD3 (original magnification ×100).

Image 4A. Case D. Clinical picture shows a right-sided intraoral lesion involving the upper alveolar ridge of the maxilla, with missing teeth on the same side.

Image 4B. Case D. Smear showing polygonal to spindle-shaped tumor cells exhibiting marked nuclear pleomorphism associated with eosinophilic matrix material (May-Grünwald Giemsa, original magnification ×20). Inset: Dense eosinophilic aggregate representing osteoid material (May-Grünwald Giemsa, original magnification ×20).

Image 4C. Case D. Tumor cells with eosinophilic granular cytoplasm closely admixed with multinucleated giant cells (May-Grünwald Giemsa, original magnification ×40).

Image 4D. Case D. Pleomorphic tumor cells with cytoplasmic vacuolation with evidence of osteoid production (May-Grünwald Giemsa, original magnification ×100).

Image 4E. Case D. Tumor cells with intracytoplasmic eosinophilic material representing osteoid (May-Grünwald Giemsa, original magnification ×100).

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Image 4F. Case D. Tumor cells showing moderate nuclear pleomorphism (H&E, original magnification ×40).

Image 4G. Case D. Cell block, showing osteoid material deposited by the tumor cells (H&E, original magnification ×40).