MORPHOLOGYCarcinomasofthelungbeginassmalllesionsthattypicallyarefirmandgray-white.Theymayariseasintraluminalmasses,invadethebronchialmucosa,orformlargebulkymassespushingintoadjacentlungparenchyma.Adenocarcinomas areusuallyperipherally located, butalsomayoccurclosertothehilum.Ingeneral,adenocarcinomasgrowslowlyandformsmallermassesthandotheothersubtypes,buttheytendtometastasizewidelyatanearlystage.Theymayassumeavarietyofgrowthpatterns,includingacinar (gland-forming) (Fig.13.43C );papillary; mucinous whichisoftenmultifocalandmaymanifestaspneumonia-likeconsolidation);andsolid types. Thesolidvariantoftenrequiresdemonstrationofintracellularmucinbyspecialstainstoestablishitsadenocarcinomatousdifferentiation.
Fig.13.43A ),whichisthoughttoprogressinastepwisefashiontoadenocarcinomainsitu,minimallyinvasiveadenocarcinoma(<3cmindiameterwithaninvasivecomponentof<5mm),andinvasiveadenocarcinoma(atumorofanysizewithanareaofinvasion>5mm).AAHappearsasawell-demarcatedfocusofepithelialproliferation(withadiameterof5mmorless)composedofcuboidaltolow-columnarcellsthatdemonstratenuclearhyperchromasia,pleomorphism,andprominentnucleoli.GeneticanalyseshaveshownthatAAHismonoclonalandsharesmanymolecularaberrationswithadenocarcinomas(e.g.,KRAS mutations).
Adenocarcinoma in situ (AIS)(formerlybronchioloalveolarcarcinoma),ofteninvolvesperipheralpartsofthelungasasinglenodule.ThekeyfeaturesofAISarediameterof3cmorless,growthalongpreexistingstructures,andpreservationofalveolararchitecture(see
Fig.13.43B ).Thetumorcells,whichmaybenonmucinous,mucinous,ormixed,growinamonolayeralongthealveolarsepta,whichserveasascaffold.Bydefinition,AISdoesnotdemonstratedestructionofalveolararchitectureorstromalinvasionwithdesmoplasia,featuresthatwouldmeritthediagnosisofinvasiveadenocarcinoma.
Squamous cell carcinomas aremorecommoninmenthaninwomenandarecloselycorrelatedwithasmokinghistory;theytendtoarise centrally in major bronchi andeventuallyspreadtolocalhilarnodes,buttheydisseminateoutsidethethoraxlaterthandootherhistologictypes.Largelesionsmayundergocentralnecrosis,givingrisetocavitation. Thepreneoplasticlesionsthatantedate,andusuallyaccompany,invasivesquamouscellcarcinomaarewellcharacterized.Squamouscellcarcinomasoftenareprecededbythedevelopment,overyears,ofsquamous metaplasia or dysplasia inthebronchialepithelium,whichthentransformstocarcinoma in situ, aphasethatmaylastforseveralyears(
Fig.13.44 ).Bythistime,atypicalcellsmaybeidentifiedincytologicsmearsofsputumorinbronchiallavagefluidsorbrushings,althoughthelesionisasymptomaticandundetectableonradiographs.Eventually,thesmallneoplasmreachesasymptomaticstage,whenawell-definedtumormassbeginstoobstructthelumenofamajorbronchus,oftenproducingdistalatelectasisandinfection.Simultaneously,thelesioninvadessurroundingpulmonarysubstance(