病理学教学课件：neoplasm(part I)

1Neoplasm/Tumor肿瘤(1)2Malignanttumors!1981-2015Pancreaticneuroendocrinetumor胰腺神经内分泌肿瘤Breastcancer乳腺癌3

GlobalCancerStatistics

56%64%indevelopingcountries4CancerStatisticsinUS,2014CACANCERJCLIN2014;64(1):9-29

新发病例（1,665,540）5CACANCERJCLIN2014;64(1):9-29

CancerStatisticsinUS,2014死亡病例（585,720）6Trendsincancerincidenceanddeathratesbysex,unitedstates,1975-2010CACANCERJCLIN2014;64(1):9-297SixpersonareDxofCancerinoneminuteMorbidity(发病率)

Estimatednewcases3,120,000Mortality(死亡率)Estimateddeaths2,700,000LungStomachColorectumLiverBreastEsophagusCervixProstateOvaryuterusTop10CancersinChinesecitiesmorbiditymortalityCancerStatisticsinChina,2012No.1causeofhumandeathinChina8Lungcancer肺癌9Hepatocellularcarcinoma肝细胞癌10Colorectalcancer结直肠癌11Esophagealcancer食管癌12stomachCancer?Ulcer?13Inflammation?Cancer?

Pathologicdiagnosis!14PleaserememberPathologicevaluationisstillthegoldstandardintumordiagnosisTumorpathologyisthestartingpointforunderstandingoftumor15Definition**Characteristicsofneoplasm**ClinicalfeaturesofneoplasmDiagnosisoftumor*ThemolecularbasisofcancerEtiologyofcancerCommontumors*Outlines16DefinitionAneoplasmisanabnormalmassoftissue,thegrowthofwhichexceedsandisuncoordinatedwiththatofthenormaltissuesandpersistthesameexcessivemanneraftercessationofthestimuliwhichevokethechange肿瘤是机体在各种致瘤因素(oncogenicfactor)的作用下，局部组织的细胞在基因水平上失掉了对其生长的正常调控，导致异常增生而形成的新生物(neoplasm)，通常形成肿块(mass)17Glossary

Neoplasia(newgrowth

inGreek,肿瘤形成)Theprocessofabnormalanduncontrolledgrowthofcellsinatissueororgan,usuallyformingadistinctmassTumor(肿瘤):

swelling

inLatin,

asynonymofneoplasmCancer:

malignantneoplasm(恶性肿瘤),

carcinos

orcrab

inGreek)18GlossaryOncology(肿瘤学):thestudyofneoplasmsCarcinogenesis(Tumorigenesis,癌发生):mechanismofneoplasiaTransformation(转化):cancersinducedinexperimentImmortalization

(永生化):unlimitedcellgrowth,inducedinexperiment,incompletetransformation19BenigntumorMalignanttumorCategoriesoftumors20NomenclatureBenigntumorsCelltypefromwhichthetumorarises

+-omaFibroma(纤维瘤)Lipoma(脂肪瘤)Leiomyoma(平滑肌瘤)Growthpattern+

-omaPapilloma(乳头状瘤)Celltype+

growthpattern+

-omaPapillarycystadenoma(乳头状囊腺瘤)Tubularadenoma(管状腺瘤)21Benigntumors良性肿瘤22NomenclatureMalignanttumor(Cancer,癌症)Carcinoma癌——

derivingfromepitheliaSquamouscellcarcinoma,adenocarcinomaSarcoma肉瘤

——derivingfrommesenchymaFibrosarcoma,liposarcomaEssentiallyfollowsthatofbenigntumors,withcertainadditionsandexceptions23Exceptions-blastoma:Neuroblastoma(神经母细胞瘤),retinoblastoma(视网膜母细胞瘤),hepatoblastoma(肝母细胞瘤)Notice!osteoblastoma(骨母细胞瘤),chondroblastoma(软骨母细胞瘤)arebenign-oma:Melanoma(黑色素瘤),

Seminoma(精原细胞瘤),Myeloma

(骨髓瘤),lymphoma(淋巴瘤)-emia:Leukemia(白血病)Benamedaftersb.:Hodgkindisease(霍奇金病),

Bowendisease(鲍文病),Ewingsarcoma(尤文肉瘤),

etc.24Borderlinetumor(交界性肿瘤):Malignant,butlowgradeCarcinosarcoma(癌肉瘤):2in1Confusingterminology

Hamartoma(错构瘤):anon-neoplastic,malformationofdisorganizedtissueindigenoustotheparticularsite

Choristoma(迷离瘤):heterotopicrestofcells

Nomenclature25Definition**Characteristicsofneoplasm**ClinicalfeaturesofneoplasmThemolecularbasisofcancerEtiologyofcancerDiagnosisoftumor*Commontumors*Outlines26TBCa27NeoplasiaReactivehyperplasiaGrowthautonomy,unlimitedresponse,limitedCellsmonoclonalpolyclonalGeneticmutationnoFunctionnorepair,protectionHostdamageordeathnoorlittledamageNeoplasiavsreactivehyperplasia28CharacteristicsofneoplasmMorphologyGrossappearancesHistopathologicfeaturesBiologicbehaviorRateofgrowthProgressionandheterogenesisSpread29GrossappearancesNumber:singlevsmultipleSize：minute>>>hugeShapeColorConsistencyGrowthpattern30Number31Familialadenomatouspolyposis(FAP)大肠家族性腺瘤性息肉病32SizeInfluencingfactorsStageLocationNature(benignormaligant)DiagnosticmarkerPrognosticmarker33Shape34colorLungcarcinomaLipomaHemangiomaMelanomaChloromaRenalcellcarcinomaColor35ConsistencyInfluencingfactorsHistologictypesSecondarychanges36ConsistencySecendarychanges

Cysticchange,necrosis,calcification,ossificationetc.37GrowthpatternExpansivegrowthpattern膨胀性生长Invasivegrowthpattern浸润性生长Exophyticgrowthpattern外生性生长3839ExpansivegrowthpatternMostofthebenigntumorsremainlocalizedEncapsulatedorwelldemarcatedException：e.g.hemangiomaRelativelyeasytoremoveRarelyrecur40InvasivegrowthpatternCommonlyseeninmalignanttumorsInvadeanddestroysurroundingtissuesRadicalsurgerymustbeperformedSurgicalmarginmustbecarefullyexaminedAredflagformalignanttumor41乳腺癌42ExophyticgrowthBenignormalignant43BenignvsmalignantingrossCharateristicsBenignmalignantWelldefined×Slowgrowth×necrosis×ulcerative×Growthpatternexpansiveinfiltrative44HistopathologicfeaturesArchitectureParenchyma(实质)DeterminethenatureofthetumorBenign/malignant;histogenesis;differentiationStroma(间质)SupportivetissuesBloodvessels,lymphatics,connectivetissues,etc.45ParenchymaandstromaCarcinomaSarcoma$※%#&@*!46CarcinomaSarcomaReticulinstain(网织纤维染色)47Differentiation

(分化)Thematurationofparenchyma,theextenttowhichtumorcellsresemblecomparablenormalcellsDegreeofdifferentiation,generallyrelatestoitsbiologicalbehaviorBenigntumors:well-differentiatedMalignanttumors:lossofdifferentiationwithvaryingdegreeWell~(高分化)——lowgrade(低级别)Moderately~(中分化)——lowgrade(低级别)Poorly~(低分化)——highgrade(高级别)48Atypia(异型性，非典型性)ThedifferencesbetweenthetumorandtissuefromwhichitoriginatedbothcytologicallyandstructurallyAccompaniesfailureofdifferentiationArchitecture:disorganized,disorderedgrowthpatternCytology:nuclearatypia(orpleomorphic)49Anaplasia(间变)literallymeans“toformbackward”Itimpliesdedifferentiation,orlossofthestructuralandfunctionaldifferentiationofnormalcellsPleomorphism(多形性)50Well-dif.Moderately-dif.Poorly-dif.De-orUn-dif.No-ormildatypiaProminentatypiaAnaplasia(间变)Pleomorphic(多形性)orprimitive(原始的)differentiationatypia51coloniccryptsadenomaadenocarcinoma52skinpapillomasquamouscellCa53Adiposetissuelipomaliposarcoma54Smoothmuscleleiomyomaleiomyosarcoma55CellularatypiaVaryinginshapeandsizeSizelargerthannormalcellssmallprimitivetumorcells,similartolymphocytesShape:irregularityTumorgiantcells(瘤巨细胞)Bizarretumorcells(奇异型瘤细胞)Increasedratioofnucleustocytoplasm↑56benignmalignantmalignant57Pleomorphicsarcoma5859EwingSarcomaUndifferentiatedorprimitivetumor60

NuclearatypiaAbnormalnuclearmorphology(异常核形态)Abnormalmitoses(异常核分裂像)

Lossofpolarity(极性丢失)61NuclearatypiaAbnormalnuclearmorphology(异常核形态)LargenucleiandvariationinshapeandsizeHyperchromaticnuclei染色质深染ChromatinaggregatedundernuclearmembraneProminentnucleoli大核仁62NuclearatypiaAbnormalmitosesIncreasedmitoticfiguresPathologicmitosis(病理性核分裂像)63Interphase间期Prometaphase前中期Metaphase中期Anaphase后期Telaphase末期

64Squamouscellcarcinoma6566PathologicmitosisAsymmetricTripolarQuardripolarAbortive67Structureandfunctionofcentrosomes68Abnormalmitosescausedbyamplifiedcentrosomes,andtheconsequentialdestabilizationofchromosomes6970NuclearatypiaNuclearcrowding,stratificationandlossofpolarity71CytoplasmicchangesBasophilicIncreasedribosomeLossinsecretedproductsortoomuchabnormalproducts72Ultrastructuralchanges:Non-diagnostic73Benigntumors:mildatypia

Malignanttumors:moderatetosevereatypiaArchitecture:disorganizedCytologyleiomyomanormal74Benignvsmalignantneoplasms75CarcinomavssarcomacarcinomasarcomaoriginepitheliummesenchymaIncidencecommonlesscommonAge

adultschildren,adolescentsGrossfeaturesfirm,grey-white,drysoft,reddish,moistureHistologicfeaturestumorcellsformingnestsorcords,usuallywellseparatedfromstroma

TumorcellsusuallymixedwithstromalcellsReticulinstainreticularfiberssurroundcellnestsreticularfiberssurroundeachcellsmetastsislymphaticchannelsbloodvessels76CharacteristicsofneoplasmMorphologykeywords:atypiaBiologiccharactersRateofgrowthProgressionandheterogenesisSpread77

RateofgrowthCorrelatesingeneralwithtumordifferentiationBenigntumors:growslowlyMalignanttumors:usuallygrowrapidly

Proliferativeindex

(增殖指数)IHCMarkers:Ki67,PCNA,PHH3Flowcytometry7879ThebalancebetweencellproliferationandcelllostProliferation＞Death→TumorgrowthDeath：necrosis,apoptosis,aging,autophagy80Gastrointestinalstromaltumor81Cancerstemcells

(CSC,肿瘤干细胞)InanalogytotissuestemcellsHavethecapacityofself-renewalInitiateandsustainthetumorConstitute0.1-2%ofthecellsintumorHaveimportantimplicationsforcancertreatment82CSC：生长速度、侵袭能力、对生长信号的反应、对抗癌药物的敏感性等等的不同83Progression

andheterogeneityBecomesmoreaggressiveAccelerationofgrowthInvadesadjacenttissuesMetastasisHeterogeneityMonoclone→multiplesubclonePrecancerouslesionCarcinomainsitumetastasisLocalspreadEarlyinvasion84Precancerouslesions(癌前病变)SomeepitheliallesionswithpredispositionstodevelopmentofmalignantneoplasmChronicatrophicgastritisChroniculcerativecolitisAdenomaofthecolon:familialadenomatouspolyposisDysplasiaoftheepithelia:cervix,esophagus,endometriumMalignantchange恶变

Cancerarisingfromprecancerouslesionsorbenigntumor85Dysplasia

(异型增生)

(Atypicalhyperplasia，非典型性增生)DisorderedgrowthofepithelialcellsLossintheuniformityofepithelialcellsLossinnormalarchitecturalorientationVariationinshapeandsizeofcellsHyperchromaticnucleiMoremitoticfiguresMaybereversibletoacertainpointwithstimulusremoved86Intraepithelialneoplasm(上皮内瘤变)Milddysplasia:lower1/3Moderatedysplasia:mid1/3Severedysplasia/Cainsitu:upper1/3~wholelayer87Cervicalintraepithelialneoplasia(CIN)

88Esophagealprecancerouslesion——上皮内肿瘤Intraepithelialneoplasm8990Dysplasticcolumnarepithelium91Definition:Thewholelayerofepitheliumisinvolved,but

withoutinvasion

(withintactbasementmembrane)Representsa

veryearlystage

ofmalignancyOften

completelycurativeExamplesbreastductalorlobularcarcinomainsituskinsquamouscellcarcinomainsituCarcinomainsitu

(原位癌)

92Carcinomainsitu.Theentirethicknessoftheepitheliumisreplacedbyatypicaldysplasticcells.93CarcinomainsituInvasivecarcinoma94Tumorspread(肿瘤播散)Directextension直接蔓延Cancersgrowbyprogressiveinfiltration,invasion,destruction,andpenetrationofthesurroundingtissueMetastasis转移9596MetastasisThedevelopmentofsecondaryimplants(metastases)Discontinuouswiththeprimarytumor

FromRobbinsBasicPathologyTumorspreadInvasivenessandmetastasis,moreunequivocallyidentifyaneoplasmasmalignant97TumorspreadLymphaticmetastasis(淋巴道转移)MoretypicalofcarcinomasDependsprincipallyonthenaturalpathwaysoflymphaticdrainageofthesiteskipmetastasesmaybepresent9899100Sentinellymphnode(前哨淋巴结)TheinitialnodesencounteredbythewanderingcancercellsAnimportantaidinassessingwhetheratumorhasmetastasizedviathelymphaticsystem101TumorspreadHematogenousmetastasis(血道转移)FavoredbysarcomasCarcinomasuseitaswellTheliverandlungsarethemostfrequentlyinvolvedsites102Metastasisoflivercarcinomatothelung103Metastasisofmelanomatothebrain104MetastasisofChoriocarcinomatotheliver105Livermetastasisofcoloncarcinoma106TumorspreadSpreadbyseeding(种植性转移)OccurswhenneoplasmsinvadeanaturalbodycavityPeritonealcavity(腹腔),Pleuralcavity(胸腔),occasionallypericardialcavity(心包腔),jointspace(关节腔)andsubarachnoidspace(蛛网膜下腔)Mayprovoketheformationoffluid(e.g.,ascites,pleuralfluid)107108Krukenberg瘤109GradingandstagingofcancersTopredictclinicalbehaviorandtoestablishcritieriafortherapy

Grading:reflectstheorganizationandcytologyofthetumorsStaging:referstotheextendofspread110GradingBasedon:

ThedegreeofanaplasiaThenumberofproliferatingcellsGradeLowgrade–well/moderatelydifferentiatedHighgrade–Poorlydifferentiated111Adenocarcinoma(well,moderately,poorlydifferentiated)112Squamouscellcarcinoma(well,moderately,poorlydifferentiated)113Neuroendocrinetumors(grade1,grade2,grade3)114StagingInternationalTNMstagingsystemT:basedontumorsizeand/orextentoflocalspreadN:lymphnodemetastasesM:distantmetastases115115TNMstagingand5-yrsurvivalrateStageTNM0TisN0M0IT1-2N0M0IIAT3N0M0IIBT4aN0M0IICT4bN0M0IIIAT1-2T1N1N2aM0IIIBT3-T4aT2-3T1-2N1N2aN2bM0IIICT4aT3-4aT4bN2aN2bN1-2M0IVAnyTAnyNM1116Definition**Characteristicsofneoplasm**Clinicalfeaturesofneoplasm

ThemolecularbasisofcancerEtiologyofcancerDiagnosisoftumor*Commontumors*Outlines117Clinicalfeaturesofneo