病理學(xué)教學(xué)課件：Diseases of Respiratory System 呼吸系統(tǒng)疾病

DiseasesofRespiratorySystem呼吸系統(tǒng)疾病AnatomyandFunctionUpperrespiratorytract

nasopharynx(鼻咽),larynx(喉)Lowerrespiratorytract

trachea(氣管),bronchi(支氣管) Rightbronchusdivergingatalesser angle,foreignmaterialmorefrequently aspirated

Lobar,segmental,lobular

1. Bronchialtree(通氣）

conductingportion

frommainbronchitoterminalbronchioles2. Terminallungunit(gasexchange)

respiratoryportion

fromrespiratorybronchioletoalveoliBronchialtree1. Mucosa

pseudostratifiedciliatedcolumncell gobletcell,producingmucus basalcell-stemcell smallgranulescell highlyspecializedbronchialliningcells, containingneurosecretorygranules2. Submucosalgland

serousandmucus3. Wallsmoothmusclecontractile

elasticfibers,provideflexibility cartilageplate,forsupportBronchioles

Φ<1mm

1. Mucosa

ciliatedepithelialcell Claracell(non-ciliatedsecretorycell)2. Wall

smoothmusclenoglandnocartilageRespiratorymembrane

? AlveolitypeIcells

95%ofthesurfacegaspermeable? AlveolitypeIIcells 5%ofthesurface producingsurfactant,loweringthesurfacetension

Involvedintherepairofalveolarepithelium? Capillarynetwork 85%~95%ofthesurface

ArrangedideallyforgasexchangePulmonaryvasculatureDoublebloodsupply,protectingfromischemia

Pulmonarycirculation:functional Bronchialsystem:nutrientPulmonarylymphcirculationDeepandsuperficialnetwork

drainingtothehilumlymphnodesNolymphaticsinmostalveolarwallsLocationHostDefenseMechanismUpperAirwaysNasopharynxOropharynxNasalhairTurbinatesMucociliaryapparatusIgAsecretionSalivaSloughingofepithelialcellsLocalcomplementproductionInterferencefromresidentfloraDefensemechanismsConducingAirwaysTrachea,bronchiLowerRespiratoryTractTerminalairways,alveoliCough,epiglotticreflexesSharp-angledbranchingofairwaysMucociliaryapparatusImmunoglobulinproduction(IgG,IgM,IgA)Alveolarliningfluid(surfactant,immunoglobulin,complement,fibronectin)Cytokines(IL-1,TNF)AlveolarmacrophagesPolymorphonuclearleukocytesCell-mediatedimmunityLungdefensemechanismsRemarks

1. Respiratorysystemiscommunicatingwithexternalenviroment,fromwhichpathogens,noxiousgasorparticles,soitissusceptibletothediseases.2. Allbloodfromthebodywillpassthroughthelungandthebiologicalpathogens(e.gbacterial,neoplasmic)embolusetc.canbetrappedinthelung.

Remarks3.Thelungiscloselyrelatedtotheheart,notonlybytheirlocationbutalsobythepulmonarycirculation.4.Damageanddisturbancetothespecializedstructuresandfunctionofthelungwillleadtothedevelopmentofthediseasesspecifictothelung.(e.gdamagetothewallofbronchialtree,obstructionofbronchiolesanddisintegrationofalveolar/capillarymembrane)

silicosisI.Pneumonia肺炎Pulmonaryinfections1/6ofalldeathsintheU.S.ACausesEpithelialsurfaceexposedtocontaminatedairNasopharyngealfloraaspiratedduringsleepLungparenchymavulnerabletovirulentorganismsDefectsininnateimmunityandhumoralimmunodeficiencyCell-mediatedimmunedefectsLifestylefactors(eg.cigarettesmoke,alcohol)causedFacilitatinginfectionsPneumoniacanbeverybroadlydefinedasanyinfectioninthelungAcute,fulminantorchronicHistologicspectrum

Fibrinopurulentalveolarexudate acutebacterialpneumonias

Mononuclearinterstitialinfiltrates viralandotheratypicalpneumonias Granulomasandcavitation chronicpneumoniasAcuteBacterialPneumoniasLobarpneumonia

ConsolidationofanentirelobeLobularpneumonia(Bronchopneumonia)

ScatteredsolidfociinthesameorseverallobesLobarPneumoniaContiguousairspacesofpartorallofalobearehomogeneouslyfilledwithanexudatethatcanbevisulizedonradiographsasalobarorsegmentalconsolidation.AdiseaseofacuteexudativeinflammationPathogenesisHealthyadultHostdefensesdepressedNormalinhabitantsoftheoropharynxandNasopharynx,Pneumococcus AspirationofpharyngealfloraLowerlobesortherightmiddlelobemostfrequentlyinvolvedPathologyandclinicalfeaturesAratherclearcut4stagedbattleintheaffectedlunginaperiodabout7-8daysAcompleteandunsloppyrecovery

Fourstagesa.Congestionb.Redhepatizationc.Grayhepatizationd.ResolutionCongestion(1-2d)

Gross Heavy,red,boggyLM VascularcongestionProteinaceousfluidcontainingnumerouspneumococcifillingthealveoliScatteredneutrophilsClinicalfeature

Acute,fever,chillCrepitation,moistraleChestradiographdim,uniformshadowRedhepatization(3-4d)Gross Aliver-likeconsistency AfibrinousorfibrinopurulentexudateofpleuraLM Intra-alveolarhemorrhage Massiveneutrophils

Fibrinpackingwithinalveolarspaces NumeruspneumococcidetectedClinicalfeature

Hemoptysis(rusty) Chestradiograph:asolidappearanceextending toentirelobesorsegments Dyspnea,debility,chestpain

Grayhepatization(4-6d)

“Aturningpoint”Gross Dry,gray,firm,granularLM Redcellslysed Fibrinousexudatepersistingwithinalveoli NopneumococcidetectedClinicalfeatureResolutionGross Pleuralresolvedororganized fibrousthickeningorpermanent

adhesionsLM Exudateswithinalveoli enzymaticallydigested eitherresorbedorexpectoratedClinicalfeatures recoveryComplications

NotcommonDeathrate:3-5% Carnification (肺肉化,organizingpneumonia)PulmonaryabscessandpyothoraxSepticemia

ToxicpneumoniaLobularpneumonia(Bronchopneumonia)Resultingfromaninitialinfectionofthebronchi andbronchioleswithextensionintotheadjacentalveoliApurulentinflammationApatchydistributionofinflammationthatgenerallyinvolvesmorethanonelobeMostfrequentlybilateralandbasalPathogenesisOrganismsRelativelyavirulent Pneumococcus,staphylococcus,and streptococcus,etc.“Opportunisticinfection”O(jiān)ftenasecondarydisease Terminallyillpatients,infantsandtakingimmunosuppressivedrugs,etc.Acommoncauseofdeath “terminalpneumonia”Aspirationpneumonia

PathologyandclinicalfeaturesGrossInthelowerandposteriorportions Becauseofthetendencyforsecretionstogravitateintothelowerlobes

Ф3-4cm,graytoyellow Confluenceoffoci theappearanceofalobarconsolidation Hyperemicandedematous—surroundingareasScatteredirregularfociofpneumoniaarecenteredonterminalbronchiolesandrespiratorybronchiolesLM

Focalsuppurativeexudatefillingthebrochi,bronchiolesandadjacentalveolarspaces

clinicalfeatures

ComplicationsCommonPoorinprognosis“terminalpneumonia” Abscessformation Empyema Meningitis,arthritis,infectiveendocarditis Respiratoryinsufficient CardiacinsufficientComparisonbetweenlobarandlobularpneumonialobarlobularPrimaryAdefinitediseaseentitySecondaryNotadefiniteentityPrimaryorsecondaryAgedistributionAdiseaseofhealthyadultsOfteninfantsandtheelderlyCausativeorganismsMostlypneumococcusAtleast20differentagents,oftencommensalsorrelativelyavirulentPrognosis&recoveryAcompleterecoveryPoorinprognosis,“terminalpneumonia”MultiplecomplicationslobarlobularPathologicfeaturesAnacuteexudativeinflammationApurulentinflammationFrequentlybilateralandbasalLowerlobesortherightmiddlelobeGrossLiver-like,orgray,dry,firm,granularApachydistributionLMAfibrinousexudate

CentrallylocatedbronchioleswhichareintenselyinflammedandfilledwithpusInterstitialpneumonia

Atypicalpneumonia

Modestsputumproduction Nophysicalfindingsofconsolidation WhitecellcountmoderatelyelevatedMononuclearinflammatoryinfiltrationin pulmonaryinterstitiumPathogenesisMycoplasmathemostcommoncauseViruses,ChlamydiaeandRickettsiae,etc.Aprimarilyupperrespiratorytractinfectionwith coryza,pharyngitis,laryngitisandtracheobronchitis

AttachmentoftheorganismstotherespiratoryepitheliumNecrosisandaninflammatoryresponseInterstitialinflammation

Damageto/denudationoftheepitheliumChildren&youngadultsfrequentlyattackedSporadicallyoraslocalepidemicsViralinfections—atanyageInfluenzavirusesAandB—adultscoldagglutinationtest

-Mucociliaryclearance+

SecondarybacterialinfectionsPathologyGross Patchy,involvingwholelobesbilaterallyor unilaterally Red-yellow,congestedandsubcrepitantLM Inflammatoryreactionlargelyconfinedwithinthe wallsofalveoli Septawidenedandedematous

Amononuclearinflammatoryinfiltrate

Freeofcellularexudate Full-blowndiffusealveolardamagewithhyaline membranesinseverecases Amixedhistologicpicturewithsecondary infection

ClinicalcourseExtremelyvaried asevereupperrespiratorytractinfection chestradiographs transient,ill-definedpatchesmainlyinthelowerlobes physicalfindingscharacteristicallyminimal

Prognosis

good,completerecovery Mostseriousinfectionscomplicatedbybacterialsuperinfection

poorinprognosisSARS(Severeacuterespiratorysyndrome)FirstidentifiedinNovember2002inChinaSARScoronavirus

Laboratorydiagnosticcriteria—Serologicaltestofanti-SARSCoVClinicalfeatures

Fulminant,fever,contagious RapidlyprogressingtoseverrespiratorysyndromePathologicalfeatureSevereatypicalpneumoniaAtelectasis(肺不張/肺萎陷）LossoflungvolumecausedbyinadequateexpansionofairspacesCategories:

ResorptionAtelectasis

Amucousormucopurulentplug,foreignbody,tumors,enlargedlymphnodes,vascularaneurysms,etc.CompressionAtelectasis

Accumulationoffluid,blood,orairwithinthepleuralcavityElevatedpositionofdiaphragmMicroatelectasis

Lossofsurfactant,postsurgicalatelectasisConstrictionAtelectasis

LocalorgeneralizedfibroticchangesinthelungorpleuraAtelectasis(肺不張/肺萎陷）ⅡAcuteRespiratoryDistressSyndrome

(ARDS)BriefintroductionDiffusealveolardamage

Injuryofalveolarepithelial,basementmembraneandcapillaryendothelialcells(therespiratorymembrane)Developingrapidlyprogressiverespiratoryfailure

AccompaniedbyDecreasedlungcomplianceHypoxemia(cyanosis)Extensiveradiologicalopacitiesinbothlungs (“white-out”)PathogenesisinducedbyalargevarietyofinsultsPulmonary Respiratorytractinfections,aspirationofgastriccontents, inhalationoftoxicgases,near-drowning,radiationpneumonitis, alargeassortmentofdrugsandotherchemicalsOutofpulmonarySepsis,shock,DIC,etc.

InjuriesofrespiratorymembraneOxygenradicalsHydrolyticenzymesCytokinesActivationofthecomplementsystemSequestrationofneutrophilsandmacrophageDamagetothecapillaryendotheliumDamagetotheepithelialjunctionsExudationoffluidandproteinsfromtheinterstitiumintothealveolarspacesPathologyGrossEarlystage Wine,liver-like,large,heavy Cutsurfaceconsolidation,dim fluid 1weeklater-Diffusegray, lustering3phasesExudativephase(1-3d)Edema,exudationofplasmaproteinsHyperemia,hemorrhageAccumulationofinflammatorycellsHyalinemembranes

DamagetobothendothelialcellsandtypeIpneumocytesSloughingoftypeIcells&appearanceofdenudedbasementmembranesFibrinthrombiincapillariesandarteriolesProliferativephase(3-10d)ProliferationoftypeIIpneumocytesandfibroblastsAlveolarseptathickenedFibroticphaseDiffuseinterstitialfibrosis“Honeycomblung”Multiplecyst-likespacesthroughoutthelungRemodelingofthelungarchitectureClinicalfeatureTachypnea,dyspnea,cyanotic,etc.Radiologicallybilateraldiffuseshadow

PrognosisPoor,progressive,50%diedinacutephaseScarredlungs,respiratorydysfunction, pulmonaryhypertension,etc.Recoveringnormalpulmonaryfunction4~6monthslaterIdiopathicpulmonaryfibrosis

characteristics:patchyfibroblastexpansiontissueremodelingexcessiveaccumulationoftheextracellularmatrix

classficationusualinterstitialpneumoniaDesquamativeInterstitialPneumoniaRespiratoryBronchiolitisInterstialLungDiseaseAcuteInterstitialPneumoniaNonspecificInterstitialPneumoniaⅢChronicObstructivePulmonaryDiseases(COPD)慢性阻塞性肺部疾病ConceptionAgroupofdiseasesinwhichfundamentaldisorderistheincreaseresistancetorespiratoryairflowcausedbydiseasesaffectingtheconductingairwayand/orlungparenchymaIncluding

ChronicbronchitisEmphysemaBronchiectasisAsthmaAirflowcanbereducedintwoways

Byincreasingtheresistancetoairflow Narrowedairways-chronicbronchitisorasthma Byreducingtheoutflowpressure Lossofelasticrecoil-emphysema

Smallairwaydisease

ObstructionofsmallbronchiolesФ<2mm

narrowchannel thinwall lackofcartilage lessciliatedcellsChronicbronchitis

ChronicinflammationofbronchiandbronchiolesDefinedclinicallyasthepresenceofapersistent productivecoughwithoutadiscerniblecauseforatleast3consecutivemonthsinatleast2consecutiveyearsPathogenesisPhysicalandchemicalfactors

cold,humid primarilyadiseaseofcigarettesmoking,airpollution(SO2,NO2,Cl2,etc.)

InfectionsBacteria,virus

inflammation

Mucousepitheliuminjured Destructionofciliatedcolumnarcell,interferingofcilia movement,MetaplasiaofthebronchialepitheliumInflammationextendingdeeplyintothewall Hypersecretionofthebronchialmucousglands,hypertrophyofmucousglands,smoothmuscleandelasticfibersinjuredinvolvementofbronchioles Mucusplugging,thickeningofthewall resultinginnarrowingandobstructionofthelumenincapabilityofIgAsynthesisorphagocytosisPathology

GrossMucousmembraneduskyred(hyperemic) andswollenbyedemafluidLumenfilledwithmucusandpusDilatedbronchialglandducts“Pits”onthesurfaceofthebronchialepitheliumLMEpithelialdamage

Alternationofcilia Epithelialcell-degenerative,proliferative Increasednumberofgobletcells Squamousmetaplasia

Hypertrophyofmucinousglands

“Thereidindex” Ameasureoftheincreaseinthesizeofthemucousglandsinflammationinthewall

Infiltrationoflymphocytesandmacrophage Destructionofsmoothmuscle(hypertrophy,hyperplasia) Destructionofelasticfibers FibrosisDestructionofcartilage

Atrophy,degenerationExpiratoryoutflowobstructionClinicalcourseAprominentcoughandtheproductionofsputumMoresevereinthewintermonthsFromhibernaltoperennialAccompaniedbyhypercapnia,hypoxemia,cyanosisandemphysemaComplicatedbypulmonaryhypertension&cardiacfailure(corpulmonale)RecurrentinfectionsandrespiratoryfailureTreatments

Stopingsmoking,promptantibiotictreatment,administrationofbronchodilatordrugs,etc.

Emphysema(肺氣腫)DefinedasastateofpathologicallyincreasedinflationofterminallungunitPermanentenlargementoftheacinuswithdestructionoftheirwallsbutwithoutfibrosisOverinflationwithoutdestructionofwallAclearassociationbetweenheavycigarettesmokingandemphysema

Typesandpathology

AccordingtoitsdistributioninthelobuleandacinusAcinus Distaltotheterminalbronchiole including:therespiratorybronchiole,alveolarducts,alveoliAlobule Aclusterofthreetofiveacinithreetypes

centriacinar panacinar distalacinarCentriacinartypeCentralorproximalpartsoftheaciniaffectedwhiledistalalveolisparedMorecommonandsevereintheupperlobes,particularlyintheapicalsegmentsSeverecases:DistalacinusalsoinvolvedAconsequenceofcigarettesmoking

PanacinartypeEntireAcinienlargedfromtherespiratorybronchioletotheterminalblindalveoliMorecommonlyinthelowerlungzonesPaleandvoluminouslungsoftenobscuringtheheartinautopsy1-antitrypsindeficiencyDistalacinar(paraseptal)typeDistalpartoftheacinusdominantlyinvolvedDistributionalongthelobularsepta AtthemarginsofthelobulesandadjacenttothepleuraAdjacenttoareasoffibrosis,scarring,oratelectasisMoresevereintheupperhalfofthelungsCharacteristicfindings

multiple,contiguous,enlargedairspacesthatrangeindiameterfrom<0.5mmto>2.0cm,sometimesformingcystlikestructures(bullae),CauseofthecasesofspontaneouspneumothoraxinyoungadultsLMThinninganddestructionofalveolarwallsMarkedenlargementofairspacesFibrosisofrespiratorybronchiolesCollapsingduringexpirationPathogenesis

Incompleteobstructionornarrowofbronchiole chronicbronchiolitis obstructionofthelumen destructionofthewallandtheadjacentalveoli

increasingtheresistancetotheexpiratoryairflowInjuryofalveolarwall

Theprotease-antiproteaseimbalance

—Ageneticdeficiencyofα1-antitrypsin

—Neutrophilsandmacrophagesreleasingprotease-containinggranulesElastictissuedestruction—Destructiveeffectofhighproteaseactivityinsubjectswithlowantiproteaseacitivity

Normallypresentinserum,tissuefluids,andmacrophages,amajorinhibitorofproteases(particularlyelastase)secretedbyneutrophilsduringinflammationClinicalfeaturesDyspnea:theusualfirstsymptomRespiratoryacidosisBarrel-chestProlongedexpiration,hyperventilationAchronicbronchitisCyanotic,corpulmonale,edema, secondarypulmonaryhypertension

Bronchiectasis(支氣管擴(kuò)張癥)DefinitionThepermanentdilationofbronchiandbronchiolescausedbydestructionofthemuscleandelasticsupportingtissue,resultingfromorassociatedwithchronicnecrotizinginfections.

Notaprimarydiseasebutsecondarytopersistinginfectionorobstruction

AcharacteristicsymptomcomplexdominatedbycoughandexpectorationofcopiousamountsofpurulentsputumCommoninolderchildrenandyoungadultsPathogenesisBronchialobstruction Tumors,foreignbodies,impactionofmucus

LocalizedtotheobstructedlungsegmentCongenitalorhereditaryconditions

Cysticfibrosis,immunoglobulindeficiencies, KartagenersyndromeNecrotizingorsuppurativepneumonia

Childhoodpneumoniasthatcomplicated

measles, whoopingcoughandinfluenzaPathologyGross

UsuallythelowerlobesbilaterallyDiffuseorsegmental

SomesharplylocalizedtoasinglesegmentTumorsoraspirationofforeignbodies

AirwaysdilatedextendingalmosttothepleuraBronchialmembraneroughed,redandcoveredwithmucopusFociofcollapse,fibrosisoremphysema

Dilation Uniformthroughout-cylindricaltype Localwidening-fusiformorsacculartypeLMVariedwiththeactivityandchronicityofthediseaseEpithelium

Atrophic,proliferativeorsquamousmetaplasia Desquamation,necrosisandulcerationinacutephaseSubmucosa

InfiltrationofmononuclearcellsWall

Destructionofelasticfibers,musclesandevencartilageFibrosis,peribronchiolarfibrosisAbnormaldilationandscarringLungabscessClinic-pathologicalcorrelationSevere,persistentcoughwithexpectorationofmucopurulent IrritatedbyaccumulationofpusanddrainageofcollectedpoolsofpusintotheunaffectedportionofbronchiHemoptysis-Damageofthewallofbloodvesselsorruptureofbloodvesselduringcough

Constitutionalmanifestation,suchasfever,weightlossandmalaise-infectionandintoxication

ⅣSilicosis(肺硅沉著病,硅肺)BriefintroductionInhalationofcrystallinesilicaPathologicallycharacterizedby

formingnumerousminutesilicoticfibroticnodulesanddiffusefibrosisinthelungandeventuallyleadstorespiratoryinsufficiencyPersonsworkinginmine,sandblastingandstonecuttingwithoutprotectionareattheriskofdevelopingsilicosis.Ittakesatleastmorethan10years,usually20-30yearstodevelopsilicosis.AslowprogressivecourseTheseveritydirectlyproportionaltothedurationtoexposureandtheamountoftheinhaledparticlesPathogenesis

Smallerthan5umreachingtheterminalairways Approximately1umtoberetainedandtocause fibrosis

EngulfmentoftheparticlebythemacrophageIncorporationofphagocytosedparticlewithlysosomeandformationofphagolysosomeDisruptionofphagolysosomewithreleaseof lysosomeenzymeDeathofmacrophagebylysisandsilicaparticlesreleaseFreeparticlere-ingestedbyanothermacrophageMacrophagemigratestothelymphaticandaccumulatesinrespiratorybronchioleandlymphnodecellularaggregationofthemacrophageformedandlatelybecomescollagenousnodulesSilicacidLysozymeMechanicalstimulationOxygenfreeradicalandproteaseChemokineFibrogenesisfactorderivedfrommacrophageImmunologicmechanism

Pathology

TwocharacteristicfeaturesSilicoticnoduleGross Tiny,barelypalpable,discrete,pale-to blackenednodulesLM Concentricallyarrangedhyalinized collagenfiberssurroudingacentralbloodvessel Weaklybirefringentsilicaparticles primarilyinthecenterbypolarized microscopically Expansionandcoalescence,

Hard, collagenousscarsPathology

Twocharacteristicfeatures

Diffusefibrosis

PulmonarymassivefibrosisFibrosisalsointhehilarlymphnodesandpleuraCalcificationStagesandclinico-pathologicalcorrelationsStageISmallnodulesscatteringinthehilarlymphnodesandcentralzonesofmiddleandlowerlobesLessfibrosis,withoutsymptomStageII

Largernodules,coalescing,scatteringalloverthelung,pleurathickening,emphysematouschangeStageIIINodulescoalescingintolargefibrousmass,centralareanecrotic,calcifiedorwithcavityformation,pulmonarymassivefibrosisPleurathickeningandadhesionirregularemphysemaandbullaeformationComplicationsCorpulmonale chronichypoxia-inducedvasoconstriction andparenchymaldestructionTuberculosis—mostcommon adepressionofcell-mediatedimmunity Silicotuberculosis

（硅肺結(jié)核病）Spontaneouspneumothorax(自發(fā)性氣胸)Ⅴ.Corpulmonale(肺源性心臟病)DefinitionRightventricularhypertrophy,dilation,andpotentiallyfailuresecondarytopersistedpulmonaryhypertensioncausedbydisordersofthelungsorpulmonaryvasculatureCausesandpathogenesis

PrimarydiseaseswithinthelungCOPD,Silicosis,TuberculosisPrimarydiseasesofpulmonaryarteriesAcutePulmonaryembolismPrimarydisordersofthoraciccageChronicPulmonaryhypertensionthemostcommoncause-COPD

Pathology

Changesoftheheart Increaseweightoftheheart Hypertrophyofrightheart Apexformedbytherightheartisblunt BulgingofcornuspulmonalePulmonaryencephalopathy

Clinico-pathologicalcorrelationsRight-sidedheartfailure

Tachycardia,cyanosis,swellingoflowerextremityRespiratoryinsufficiencyHeadache,convulsion,coma

ⅥTumorsofrespiratorysystem呼吸系統(tǒng)腫瘤

Nasopharyngealcarcinoma>40years,men>womensmokingPathogenesisEBvirusPathology

Pearlygray,ulcerating,fungating Squamouscellcarcinoma95% AdenocarcinomasrareClinicalcoursepalpableneckmass,headache,nasalobstruction,hearingloss,dysphagiaTreatmentResectionand/orradiotherapyPrimarylungcancer

Bronchogeniccarcinomas Arisingfromthebronchialepithelium95% USA1/3ofcancerdeathsinmentheleadingcauseofcancerdeathsinwomen Peakincidence50~59years Male:female=1.5:1Amiscellaneousgroup5%EtiologyandpathogenesisCigarettesmokingEnvironmentalinsultsAstepwiseaccumulationofamultitudeofgeneticabnormalitiesTransformationofbenignprogenitorintoneoplastictissueHereditary(genetic)factorsP-450monooxygenaseenzymesystemP-450genesInactivationoftheputativetumorsuppressorgeneslocatedon3p,

TP53

mutations,KRASactivation,EGFRmutations,EML4-ALKtyrosinekinasefusiongenesandc-METtyrosinekinasegeneamplications.Thetop20censusgenemutationsinCOSMIC(catalogueofsomaticmutationsincancer)databaseandthemutationpercentage(%)ofthreesubtypesoflungcancer.(a)ADC;(b)SCC;(c)SCLC.TP53ishighestfrequentmutatedgene(about40%)inallthethreesubtypesoflungcancer.OtherfrequentgenemutationsincludeKRAS,EGFRandSTK11inADC;PI3KCA,KMT2andCDKN2AinSCC;RB1,GRIN2AandEP300inSCLC.Thesedatashowedthedifferentgeneticvariationsinlungcancersubtype.Lancet.2015Sep5;386(9997):957-63.MorphologyGrossSmallmucosallesions Firm,gray-white

Intraluminalmasses Invadingthebronchialmucosa Forminglargebulkymassespushingintoadjacentlungparenchyma Cavitation-centralnecrosis Focalhemorrhage

Tumorsarisingfromlargebronchus InCentralzoneoflungorinthehilarregion Aglobusshape,non-capsulated,andistinctirregularboundaryTumorsarisingfromsmallerbronchiorbronchiole

InperipheralregionoflungSmall,solitary,withoutcapsule,lobularincontour,hazyedgeCutsurface:GreyishwhiteGlisteningwhencontainingmucouselement

Diffusetype

Fourmajorhistologicaltypes AdenocarcinomaSquamouscellcarcinomaLargecellcarcinoma SmallcellcarcinomaAcombinationofhistologicpatternsAdenocarcinomas36.8～46.5%,morecommoninwomenArisingfrombasalcellorgobletcelllineoflargeorsmallbronchusGrowingslowly,formingsmallermasses,tendingtometastasizewidelyatanearlystageGross

moreperipherallylocated,manywithacentralscarLM

Acinar(glandforming),orpapillary,ormucinous,o