Fig.13.45A ).Onhistologicexamination,thesetumorsrangefromwell-differentiatedsquamouscellneoplasmsshowingkeratinpearls(see
Fig.13.45B )andintercellularbridgestopoorlydifferentiatedneoplasmsexhibitingonlyminimalsquamouscellfeatures.
Large cell carcinomas areundifferentiatedmalignantepithelialtumorsthatlackthecytologicfeaturesofneuroendocrinecarcinomaandshownoevidenceofglandularorsquamousdifferentiation.Thecellstypicallyhavelargenuclei,prominentnucleoli,andmoderateamountsofcytoplasm.
Small cell lung carcinomas (SCLCs)generallyappearaspalegray,centrally located masses thatextendintothelungparenchyma.Thesecancersarecomposedofrelativelysmalltumorcellswitharoundtofusiformshape,scantcytoplasm,andfinelygranularchromatinwithasaltandpepperappearance.Numerousmitoticfiguresarepresent(
Fig.13.46 ).Necrosisisinvariablypresentandmaybeextensive.Thetumorcellsarefragileandoftenshowfragmentationand“crushartifact”insmallbiopsyspecimens.Anotherfeature,bestappreciatedincytologicspecimens,isnuclearmoldingresultingfromcloseappositionoftumorcellsthathavescantcytoplasm.Thesetumorsexpressavarietyofneuroendocrinemarkers( http://ebooksmedicine.net
Fig. 13.43 Adenocarcinomaandassociatedlesions.(A)Atypicaladenomatoushyperplasiawithcuboidalepitheliumandmildinterstitialfibrosis.(B)Adenocarcinomainsitu,mucinoussubtype,withcharacteristicgrowthalongpreexistingalveolarsepta,withoutinvasion.(C)Gland-formingadenocarcinoma;insetshowsthyroidtranscriptionfactor1(TTF-1)positivity,whichisseeninamajorityofpulmonaryadenocarcinomas.
13.7 )andmaysecreteahostofpolypeptidehormonesthatmayresultinparaneoplasticsyndromes(seelater).Bythetimeofdiagnosis,mostwillhavemetastasizedtohilarandmediastinallymphnodes.Inthe2015WHOClassification,SCLCisgroupedtogetherwithlargecellneuroendocrinecarcinoma,anotherveryaggressivetumorthatexhibitsneuroendocrinemorphologyandexpressesneuroendocrinemarkers(synaptophysin,chromogranin,andCD56).Mixed patterns (e.g.,adenosquamouscarcinoma,mixedadenocarcinoma,smallcellcarcinoma)areseenin10%orlessoflungcarcinomas.