粘表-腺樣囊性癌-腺泡細(xì)胞癌-上皮肌上皮癌

粘液表皮樣癌、腺樣囊性癌，腺泡細(xì)胞癌和上皮-肌上皮癌陳國璋MucoepidermoidcarcinomaAciniccellcarcinomaAdenoidcysticcarcinoma黏液表皮樣癌癌細(xì)胞引人注目的特征：-鱗狀細(xì)胞-粘液細(xì)胞-不確定型細(xì)胞（中間細(xì)胞）無痛性緩慢增長，實(shí)性腫塊黏液表皮樣癌大體觀邊界不清的腫塊（可有囊性變）質(zhì)地韌或硬囊腫常見囊腫內(nèi)可有黏液黏液表皮樣癌組織學(xué)浸潤性多個(gè)不規(guī)則腫瘤細(xì)胞巢纖維性/促結(jié)締組織增生性間質(zhì)伴有炎癥細(xì)胞浸潤上皮細(xì)胞巢實(shí)性或囊性（充滿分泌物）粘液外滲黏液表皮樣癌的細(xì)胞類型1、粘液分泌細(xì)胞（柱狀或杯狀狀）2、表皮樣細(xì)胞

-多邊形，胞漿呈淡嗜酸性-幾乎看不到細(xì)胞間橋或角化-幾乎沒有明確鱗化！3、中間型細(xì)胞細(xì)胞形態(tài)更小鑲嵌狀排列在黏液細(xì)胞下

黏液表皮樣癌的細(xì)胞發(fā)生涎腺導(dǎo)管儲(chǔ)備細(xì)胞中間型細(xì)胞表皮樣細(xì)胞SquamouscellMucouscellClearcellP63免疫組化常常陽性！黏液表皮樣癌：變型透明細(xì)胞（含有豐富的糖原）嗜酸性細(xì)胞梭形細(xì)胞生長硬化型透明細(xì)胞嗜酸性細(xì)胞梭形細(xì)胞硬化黏液表皮樣癌黏液進(jìn)入囊內(nèi)，形成微囊或大囊黏液滲出慢性炎癥反應(yīng)纖維化高級(jí)別腫瘤不突出!!黏液滲出粘液表皮樣癌：傳統(tǒng)的三層分級(jí)系統(tǒng)低級(jí)別中級(jí)別高級(jí)別許多微囊和大囊一些囊少數(shù)囊許多黏液細(xì)胞混合性細(xì)胞少量黏液細(xì)胞很少核分裂核分裂不常見很多核分裂溫和的細(xì)胞形態(tài)有一定的異型性細(xì)胞多形性LGHGHGPASDLGIG黏液表皮樣癌的過度診斷Warthin瘤鱗化和/或黏液上皮化生(如果一個(gè)溫和的腫瘤有很多的鱗狀表現(xiàn)，它就不是一個(gè)黏液表皮樣癌)囊腺瘤（非浸潤性和單型細(xì)胞）壞死性涎腺化生Warthin瘤伴鱗化多形性腺瘤多形性腺瘤壞死性涎腺化生黏液表皮樣癌診斷不足缺乏腫瘤細(xì)胞島和黏液外滲，誤診為黏液囊腫溫和的細(xì)胞，誤診為良性腫瘤囊性變占大部分的腫瘤（誤為囊腺瘤）硬化和炎癥占主要部分(誤診為炎癥性病變)大涎腺不明原因的黏液池伴炎癥黏液表皮樣癌，除非被證實(shí)為其它黏液表皮樣癌

診斷檢查表浸潤性邊界硬化性間質(zhì)(常見)慢性炎癥細(xì)胞浸潤(常見)特征性上皮島/巢如果有明顯的鱗狀上皮或角化，大概就不是黏液表皮樣癌了。腺泡細(xì)胞癌定義：上皮性腫瘤顯示向細(xì)胞腺泡細(xì)胞分化主要發(fā)生在腮腺極少發(fā)生在小涎腺慢性生長的腫瘤，有或無痛可能是雙側(cè)性的（常見）腺泡細(xì)胞癌：

病理常常是局限性的，偶爾是多結(jié)性的或浸潤性的實(shí)性或囊性通常是混合生長模式通常混合細(xì)胞形態(tài)(核分裂少見)間質(zhì)通常不明顯可能有突出的淋巴細(xì)胞聚集腺泡細(xì)胞癌：

生長模式微囊型**

腺泡群或簇實(shí)性（常呈器官樣）乳頭狀囊性（常富含空泡、鞋釘、閏管及非特異性腺細(xì)胞）濾泡（類似甲狀腺濾泡）腺泡細(xì)胞癌：

細(xì)胞類型腺泡細(xì)胞（偏位的暗的核，嗜堿性胞漿）閏管樣細(xì)胞（小立方形細(xì)胞；中位核；粉紅色細(xì)胞質(zhì)）–可占主導(dǎo)地位空泡細(xì)胞（大小類似于腺泡細(xì)胞；單個(gè)或多個(gè)空泡）非特異性腺細(xì)胞（通常是模糊的細(xì)胞邊界；中位核）透明細(xì)胞(不常見，糖原陰性)沒有肌上皮/基底細(xì)胞，P63陰性正常的腺泡和閏管CKSomepeculiarfeaturesof

aciniccellcarcinomaSelf-destructivequalityinsome:ischemiaandnecrosis--->SolitaryorloculatedcystswithpapillaeandhydropicclearcellsLipogranulomatousreactionInfarctafterFNABUnderdiagnosisofaciniccellcarcinomaSomeaciniccellcarcinomasarepredominantlycystic--canbemistakenforbenignsalivarycystAciniccellcarcinoma:behaviorLowgrade,indolentmalignancyGradingorhistologicvarianthasnoprognosticsignificanceRecurrence35%(maybedelayedto30yr)Metastasis16-19%(oftendelayedaftermanyyears)LymphnodeDistant(lungs,bone)Survival:5-yr90%;20-yr56%Aciniccellcarcinoma:

unfavorableprognosticfactorsGrossinvasionHighstagediseaseDesmoplasiaSignificantcellularatypiaIncreasedmitoticactivityorMIB1index(>5%:62%unfavorableoutcome)JPathol1994;173:13-21DedifferentiatedaciniccellcarcinomaAtypiaDedifferentiatedaciniccellCAAciniccellcarcinoma:

favorableprognosticfactorsSmallsize(<3cm)RichinlymphoidstromaHumPathol1997;28:595-600Adequateinitialexcision**(recurrence11%,versus>90%forincompleteexcision)Aciniccellcarcinoma:

essenceofdiagnosisIdentificationofaciniccelldifferentiationinthetumorcells(whichisoftenfocal)Canbehelpedby:PAS-diastasestain(intracytoplasmicgranules)Amylaseimmunohistochemistry(notreadilyavailable)Onlyluminalcell,butnotabluminalcell,differentiationADENOIDCYSTICCARCINOMAAninfiltrativecarcinomahavingvariousfeaturesofthreegrowthpatterns:glandular(cribriform),tubularorsolidTwocelltype:ductal-liningcellsmyoepithelial/basaltypecellsUsuallyaslow-growingtumorBoneinvasionmayoccurwithoutradiologicalevidenceAdenoidcysticcarcinoma:pathologyGross:Invasiveborders;solidappearanceTubules,cribriformstructures,solidmassesVariableamountsofhyalinizedstroma(sometimes“drowning”thetumor)Mayhavelattice-likepattern,andabundantstromalmucin/hyalinematerialPerineuralinvasionischaracteristic(butnotessentialfordiagnosis)Adenoidcysticcarcinoma:

celltypesDuctalepitheliumCuboidalSurroundsdistinctsmalllumina(oftenwitheosinophilicsecretion)Eosinophiliccytoplasm;vesicularnucleiCanbedifficulttoappreciateSmallbasaloidcells(modifiedmyoepithelium)OftenpredominantHyperchromaticnucleiIndistinctcellbordersOftenassociatedwithbasementmembranematerial,hyalinematerialorstromalmucinPseudocysts/stromalinclusionsc-kitp63SMAAdenoidcysticcarcinoma:geneticsAdistinctivechromosomaltranslocationrecentlyrecognizedinadenoidcysticcarcinoma:t(6;9)(q22-23;p23-24),resultinginMYB-NFIBfusionThisisfoundin50-86%ofallcases,butnotinothersalivaryglandtumorsInfuture,detectionofthemolecularalterationmayaidinthediagnosisofthistumortypeAdenoidcysticcarcinoma:grading

(M.D.Anderson)Grade1Grade2Grade3Tubularandcribriform,withnosolidareasPurecribriformormixedbutwith<30%solid>30%solidareas;necrosiscommon;morecellularatypiaUsuallysmallandamendabletototalsurgicalexcision.Protractedcourse.IntermediatebehaviorLargertumors.Frequentlyrecur(early).Oftenkillingwithin4yrs.15-yrsurvival39%26%5%Adenoidcysticcarcinoma:behaviorLocalinvasionMayextendforlongdistancealongnervesUsuallyslowlyprogressivecourse(dependingongrade)FrequentrecurrenceMetastasis30-40%(LN,lungs,bone)MajorityofpatientseventuallysuccumbtodiseaseafterprolongedclinicalcourseAdenoidcysticcarcinoma:

prognosticfactorsSize(betterif<2cm)Histologicgrade/presenceofsolidcomponentStageofdiseaseBoneinvasion(unfavorable)CompletenessofexcisionPresenceofdedifferentiation(worsenedprognosis)p63Adenoidcysticcarcinoma:checklistfordiagnosisInvasivebordersTwo-celltype(ductalepitheliummaybedifficulttofind)VariableamountsofbasementmembraneandhyalinematerialCribriformstructuresoftenpresentClearcellsveryrareProblemsindiagnosisof

adenoidcysticcarcinomaMorphologicoverlapwithotherentitieswithdual-celltypearchitecture:Pleomorphicadenoma,basalcelladenomaEpithelial-myoepithelialcarcinomaBasalcelladenocarcinomaSolidareasmaynotbediagnostic:needtosearchforinterspersedtubulesMarkedstromalhyalinizationrendersrecognitiondifficultAdenoidcysticcarcinomaBasalcell/pleomorphicadenomaBordersInfiltrativeCircumscribedCribriformpatternVerycommonRare(butcanoccur)ChondroidmatrixAbsentCommoninpleomorphicadenomaSpindlystromafocallyAbsentDiagnosticofbasalcellorpleomorphicadenoma“Melting”intostromaAbsent(buthyalinizationmaymimic“melting”)DiagnosticofpleomorphicadenomaPleomorphicadenomaS100BasalcelladenomaAdenoidcysticcarcinomaOthersalivarytumorsCD43/L60clone(Woo,2006)100%7%PLGA12%MonomorphicadenomaCD43/MT1clone(Seethala,2004)48%0%CD43Adenoidcysticcarcinoma:DiagnosisDon’t

makeadiagnosisofadenoidcysticcarcinomaifthereisnoinvasion!EPITHELIAL-MYOEPITHELIALCARCINOMACalled“clearcelladenoma”inthepastDefinition:Variableproportionsoftwocelltypeswhichtypicallyformductalstructures:innerlayerofductalcellsandouterlayerofclear(myoepithelial)cellsMostcommoninparotidEpithelial-myoepithelialcarcinoma:histologyUsuallymultinodularorpartlyencapsulatedInvadesinbroadfrontsDuctalepithelium:pinkcytoplasm;lumenmaycontaineosinophilicsecretion;mayformbranchingluminaOuterlayerofmyoepitheliumhasclearcytoplasm(Glycogen+;S100protein+;Actin+;Myosin+;p63+);oftenassociatedwiththickB.M.orhyalinematerialEpithelial-myoepithelialcarcinoma:histologyBiphasicpatternmaynotbeobviousinsomecases:anastomosingislandsandlargesheetsofclearcells(whichcanevenbecomespindly,withfasciculargrowth),onlyoccasionalinterspersedtubulesVariableamountsofhyalinizedstromaPerineuralandvascularinvasionsometimesseenPASPASDCD117p63SMAEpithelial-myoepithelialcarcinoma:behaviorLowgrade,indolenttumorMayevolvetoamyoepithelialcarcinomaRecurrence30-40%(canberepeated)CervicalLNmetastasis10-20%Distantmetastasis9%Tumormortality9%Epithelial-myoepithelialcarcinoma:D.Dx.AdenoidcysticCAMorepermeativebordersAbluminalcellsmuchsmaller(“basaloid”)ClearcellsrareFrequentcribriformstructureswithbasophilicmucinBranchinglumensrarePle