PagetdiseaseofthenippleiscausedbytheextensionofDCISupthelactiferousductsandintothecontiguousskinofthenipple,producingaunilateralcrustingexudateoverthenippleandareolarskin.UnlikePagetdiseaseofthevulva(describedearlier),Pagetdiseaseofthenipplestemsfrominsituextensionofanunderlyingcarcinoma.TheprognosisofthecarcinomaoforiginisaffectedbythepresenceofPagetdiseaseandisdeterminedbyotherfactors(discussedunderClinicalFeatures).
LCIShasauniformappearance.Thecellsaremonomorphic,havebland,roundnuclei,andarefoundinlooselycohesiveclusterswithinthelobules(
Fig.19.28A ).LCISisvirtuallyalwaysanincidentalfindingbecause,unlikeDCIS,itisonlyrarelyassociatedwithcalcifications.Therefore,theincidenceofLCIShasremainedunchangedinmammographicallyscreenedpopulations.Approximatelyone-thirdofwomenwithLCISeventuallydevelopinvasivecarcinoma.UnlikeDCIS,invasivecarcinomasfollowingadiagnosisofLCISmayariseineitherbreast—2 13 inthecontralateralbreast.Thus,LCISisbothamarkerofanincreasedriskofcarcinomainbothbreastsandadirectprecursorofsomecancers.Currenttreatmentoptionsincludecloseclinicalandradiologicfollow-up,chemopreventionwithtamoxifenor,lesscommonly,bilateralprophylacticmastectomy.
Thedistinctivehistologicpatternsofthesubtypesofinvasivecarcinomaaredescribedfirst,followedbygrading,whichisusedforall.
Invasiveductalcarcinomaisatermusedforallcarcinomasthatcannotbesubclassifiedintooneofthespecializedtypesdescribedbelow.Amajority(70%–80%)ofcancersfallsintothisgroup.ThistypeofcancerusuallyisassociatedwithDCIS.Themicroscopicappearancevaries,rangingfromtumorswithwell-developedtubulesandlow-gradenuclei(
Fig.19.29A )totumorsconsistingofsheetsofanaplasticcells.Mostinvasiveductalcarcinomasproduceadesmoplasticresponse,whichreplacesnormalbreastfat(resultinginamammographicdensity;
Fig.19.29B )andeventuallyleadstotheappearanceofahard,palpableirregularmass.About50%to65%ofductalcarcinomasareERpositive,20%areHER2positive,and15%arenegativeforbothERandHER2(
Table19.7
InvasivelobularcarcinomaconsistsofinfiltratingcellsthataremorphologicallysimilartothetumorcellsseeninLCIS;indeed,two-thirdsofthecasesareassociatedwithLCIS.Thesetumorscomprise10%to15%ofallbreastcarcinomas.Thecellsinvadestromaindividuallyandoftenarealignedin“single-file”(
Fig.19.29C ).Althoughmostmanifestaspalpablemassesormammographicdensities,asignificantsubgroupinvadewithoutproducingadesmoplasticresponse;suchtumorsmaybeclinicallyoccultanddifficulttodetectbyimaging(
Fig.19.29D ).Thepatternofmetastasisoflobularcarcinomaisuniqueamongbreastcancers,astheyfrequentlyspreadtocerebrospinalfluid,serosalsurfaces,gastrointestinaltract,ovary,uterus,andbonemarrow.Almostalllobularcarcinomasexpresshormonereceptors,whereasHER2overexpressionisrare.
Carcinomaswithmedullaryfeaturesareaspecialtypeoftriple-negativecancercomprisingabout5%ofallbreastcancers.Thesecarcinomastypicallygrowasroundedmassesthatcanbedifficulttodistinguishfrombenigntumorsonimaging(