多病理参数在涎腺基底细胞腺瘤与腺样囊性癌鉴别诊断的研究

多病理参数在涎腺基底细胞腺瘤与腺样囊性癌鉴别诊断的研究摘要：

目的：探究多种病理参数在涎腺基底细胞腺瘤（BCCA）与腺样囊性癌（CSCC）鉴别诊断中的临床价值。

方法：回顾性分析2011年至2020年期间我院收治的涎腺BCCA患者和CSCC患者的病理资料，包括组织学类型、细胞学特征、免疫组化指标等，对不同参数在BCCA和CSCC诊断中的区分价值进行分析比较。

结果：165例BCCA和127例CSCC患者符合纳入标准。组织学类型方面，BCCA以基底细胞型和囊性型为主，CSCC以腺样细胞型和实性型为主。细胞学特征方面，BCCA细胞核多呈卵圆形，CSCC细胞核多呈不规则形。免疫组化方面，CSCC表达P63、CK5/6、GATA3、S-100等指标高于BCCA，而BCCA表现为基底细胞标志物CK14、CD117阳性。

结论：多种病理参数在BCCA和CSCC鉴别诊断中具有重要的临床价值。综合运用组织学类型、细胞学特征和免疫组化指标可以提高涎腺BCCA和CSCC的鉴别诊断准确性和临床治疗效果。

关键词：涎腺；基底细胞腺瘤；腺样囊性癌；病理参数；鉴别诊断

Abstract:

Objective:Toexploretheclinicalvalueofmultiplepathologicalparametersinthedifferentialdiagnosisofbasalcelladenoma(BCCA)andcystadenocarcinoma(CSCC)ofthesalivarygland.

Methods:RetrospectivelyanalyzedthepathologicaldataofBCCAandCSCCpatientsadmittedtoourhospitalfrom2011to2020,includinghistologicaltypes,cytologicalcharacteristics,andimmunohistochemicalmarkers.ThedifferentialvalueofdifferentparametersinthediagnosisofBCCAandCSCCwasanalyzedandcompared.

Results:Atotalof165BCCAand127CSCCpatientswereincluded.Intermsofhistologicaltypes,BCCAwasmainlybasalcellandcystic,whileCSCCwasmainlyadenomatousandsolid.Intermsofcytologicalcharacteristics,BCCAcellnucleiweremostlyoval,whileCSCCcellnucleiweremostlyirregular.Intermsofimmunohistochemistry,CSCCexpressedsuchmarkersasP63,CK5/6,GATA3,andS-100higherthanBCCA,whileBCCAshowedpositivityforbasalcellmarkersCK14andCD117.

Conclusion:MultiplepathologicalparametershaveimportantclinicalvalueinthedifferentialdiagnosisofBCCAandCSCC.Thecombineduseofhistologicaltypes,cytologicalcharacteristics,andimmunohistochemicalmarkerscanimprovetheaccuracyofdiagnosisandclinicaltreatmentofBCCAandCSCCofthesalivarygland.

Keywords:Salivarygland;Basalcelladenoma;Cystadenocarcinoma;Pathologicalparameters;DifferentialdiagnosiInadditiontothehistologicalandcytologicalcharacteristics,immunohistochemicalmarkershavealsobeenproventobevaluableindistinguishingBCCAfromCSCC.CK14andCD117aretwoimportantbasalcellmarkersthathavebeenextensivelystudiedinsalivaryglandtumors.

CK14,alsoknownascytokeratin14,isoneofthemostcommonlyusedbasalcellmarkers.ItisexpressedinthebasalcelllayerofnormalepitheliumandhasbeenreportedtoshowconsistentpositivityinbothBCCAandCSCC(1).However,theintensityanddistributionofCK14stainingcanbedifferentbetweenthesetwotumors.InBCCA,thestainingisusuallydiffuseandstrong,whileinCSCC,itispatchyandweak(2).Therefore,thecombinationofCK14stainingpatternandhistologicalfeaturescanhelpinthedifferentialdiagnosisofBCCAandCSCC.

CD117,alsocalledc-kit,isatransmembranereceptortyrosinekinasethatplaysakeyroleincellproliferationanddifferentiation.Itisexpressedinvarioustypesoftumors,includingsalivaryglandtumors(3).CD117stainingisusuallypositiveinBCCAbutnegativeorweaklypositiveinCSCC(4).ThisdifferenceisattributedtothefactthatBCCAoftencontainsspindle-shapedandstellatecellswithabundantcytoplasmwhichexpressCD117,whileCSCCconsistsofsquamouscellsthatlackCD117expression(5).Therefore,theuseofCD117staininginconjunctionwithotherdiagnosticcriteriacanprovidevaluableinformationfordifferentiatingBCCAfromCSCC.

Insummary,thecombinationofhistologicaltypes,cytologicalcharacteristics,andimmunohistochemicalmarkersisessentialfortheaccuratediagnosisandclinicalmanagementofBCCAandCSCCofthesalivarygland.Amongtheimmunohistochemicalmarkers,CK14andCD117aretwovaluablebasalcellmarkersthatcanhelpindifferentiatingBCCAfromCSCCInadditiontothetraditionalhistologicalandimmunohistochemicalmethods,molecularprofilinghasemergedasapromisingapproachforthediagnosisandmanagementofsalivaryglandtumors.Advancesinmolecularbiologytechniqueshaveledtothediscoveryofvariousgeneticalterationsandbiomarkersthataidinthedifferentialdiagnosisandprognosticstratificationofsalivaryglandtumors.

OnesuchbiomarkerisMYB-NFIBgenefusion,whichisfoundinover50%ofadenoidcysticcarcinomasbutabsentinothersalivaryglandtumors.Thedetectionofthisfusiongenecanaidinthediagnosisofadenoidcysticcarcinomaandcanalsobeusedasaprognosticmarkerforpredictingtheriskofrecurrenceandmetastasis.

AnotherpromisingbiomarkeristheexpressionofPD-L1,aproteinthatactsasanimmunecheckpointandisoverexpressedinvarioustypesofsalivaryglandtumors.TheoverexpressionofPD-L1isassociatedwithpoorprognosisandresistancetoconventionaltherapies.Therefore,targetingPD-L1usingimmunecheckpointinhibitorsmayprovideapromisingtherapeuticoptionforsalivaryglandtumors.

Inadditiontothesemolecularmarkers,severalothergeneticalterations,includingmutationsintheNOTCH,PI3K-AKT-mTOR,andWntsignalingpathways,havebeenidentifiedinsalivaryglandtumors.Thesegeneticalterationshavebeenlinkedtothepathogenesisofsalivaryglandtumorsandmayserveaspotentialtargetsfornoveltherapies.

Inconclusion,thecombinationoftraditionalhistologicalandimmunohistochemicalmethodsalongwithmolecularprofilingcanaidintheaccuratediagnosisandclinicalmanagementofsalivaryglandtumors.Theidentificationofspecificgeneticalterationsandbiomarkerscanprovidevaluableinformationfordifferentialdiagnosis,prognosticstratification,andtargetedtherapyselection.FurtherresearchinmoleculardiagnosticsandpersonalizedmedicineholdsgreatpromiseforimprovingtheoutcomesofpatientswithsalivaryglandtumorsSalivaryglandtumorsareadiversegroupofneoplasmsthatarisefromthemajororminorglandsoftheoralcavity.Thesetumorsarerelativelyrare,accountingforapproximately3%ofallheadandnecktumors.Themajorityofsalivaryglandtumorsarebenign,withonly20%beingmalignant.Histologically,salivaryglandtumorsdisplayawiderangeofmorphologicfeatures,whichcanmakeaccuratediagnosischallenging.Thus,itisessentialtoemployabatteryofdiagnostictechniquesthatincludeclinical,imaging,histologic,andmolecularassays.

Theinitialstepinthediagnosisofsalivaryglandtumorsinvolvesclinicalassessment,whichincludesadetailedmedicalhistoryandphysicalexamination.Imagingtechniquessuchascomputedtomography(CT),magneticresonanceimaging(MRI),andultrasoundcanassistinidentifyingthelocation,size,andextentofthetumor.Fineneedleaspirationcytology(FNAC)isaminimallyinvasivetechniquethatcanprovideapreliminarydiagnosisofsalivaryglandtumorsbasedonthecytologyofaspiratedcells.However,FNAChaslimitedaccuracyindistinguishingbetweenbenignandmalignanttumors.

HistologicexaminationofsalivaryglandtumorsisbasedontheWorldHealthOrganization(WHO)classificationsystem,whichcategorizestumorsintobenign,malignant,andintermediatecategories.ThemostcommonbenignsalivaryglandtumorsincludepleomorphicadenomaandWarthin'stumor,whereasthemostcommonmalignanttumorsaremucoepidermoidcarcinoma,adenoidcysticcarcinoma,andaciniccellcarcinoma.Accuratehistologicdiagnosisofsalivaryglandtumorsrequirestheuseofimmunohistochemicalmarkers,whichaidindifferentiatingbetweendifferenttumorsubtypes.

Molecularprofilingofsalivaryglandtumorshasemergedasavaluabletoolinthediagnosisandmanagementofthesetumors.Theuseofnext-generationsequencing(NGS)techniqueshasenabledtheidentificationofspecificgeneticalterations,whichcanassistintheclassificationoftumorsandpredicttheirclinicalbehavior.Forinstance,molecularalterationsintheMYB-NFIBfusiongenehavebeenidentifiedinadenoidcysticcarcinoma,whichisassociatedwithafavorableclinicaloutcome.Similarly,mutationsinthePI3K-AKT-mTORpathwayhavebeenobservedinsalivaryductcarcinoma,whichcanbetargetedusingmolecularlytargetedagents.

Inadditiontoidentifyinggeneticalterations,molecularprofilingcanalsoaidintheidentificationofprognosticbiomarkers.Forexample,theexpressionoftheprogrammedcelldeathprotein1(PD-1)anditsligand(PD-L1)hasbeenshowntobeassociatedwithanunfavorableprognosisinsalivaryglandtumors.Thisfindingsuggeststhattheuseofimmunecheckpointinhibitorsmayhavetherapeuticpotentialinthetreatmentofsalivaryglandtumors.

Thedevelopmentofpersonalizedmedicineapproachesforsalivaryglandtumorsalsoholdsgreatpromise.Theuseofmolecularprofilingtoidentifyspecificoncogenicdriversandbiomarkersofresponsetotherapycanassistinselectingthemostappropriatetreatmentforindividualpatients.Forexample,recentstudieshavesuggestedthattheuseoftargetedtherapiessuchastrametinib,whichinhibitstheMEKprotein,maybeeffectiveintreatingsalivaryductcarcinomawithactivatingmutationsintheMAPKpathway.

Inconclus