病理學教學課件：Chapter I Introduction to Pathology

1ChapterIIntroductiontoPathology2SectionA：DefinitionofPathologySectionB：DevelopmentofPathologySectionC：ObjectivesofResearchSectionD：ResearchMethodsSectionE:LearningofPathology

3DefinitionofPathologyPathologyLiterally：pathos（suffering）＋logos（study）Tostudydiseasesbyscientificmethods.Diseasemaybedefinedasanabnormalalterationofstructureorfunctioninanypartofthebody.SectionA4AcquiredIntrinsicorgeneticOneetiologicagent/single－gene→onedisease.同病不同癥，同癥不同??；病同癥不同，癥同病不同。Severaletiologicagents→onediseaseOneetiologicagent→severaldiseasesKnowledgeofetiologyremainsthebackboneonwhichAdiseasecanbeunderstoodAdiagnosiscanbemadeAtreatmentdevelopedWhy?ETIOLOGYCauseofdiseasePathologymainlyfocusesonfouraspectsofdiseasesnolongersufficientModernPathology5Adenomatouspolyposisincolons(inteens)and100%malignanttransformation(

40ys)APCloci,5q21,theproteinlocatesincytoplasm,severalpartners,eg.

-catenin(enterthenucleus

activategrowth-promotinggenes)Causingdegradationof

-catenin

maintaininglowlevelof

-catenininthecytoplasmAdenomatousPolyposisColi(APC)6DetectionofAPCDNAinFeces7HOW?ThecoreofthescienceofpathologyInitialstimulus→ultimateexpressionofthediseaseMolecularrevolutionLinkspecificabnormalitiestodiseasemanifestationTodesigntherapeuticapproachesMoreexcitingscientificallyormorerelevanttomedicinePATHOGENESISMechanismsofdevelopmentofdiseaseETIOLOGYCauseofdiseasePathologymainlyfocusesonfouraspectsofdiseases8GIST（gastrointestinalstromaltumor）CD1179ETIOLOGYCauseofdiseasePATHOGENESISMechanismsofdevelopmentofdiseaseWhat’sthealteration？MORPHOLOGYThestructuralalterationsinducedincellsandtissuesRemainsattheheartofdiagnosticpathologyCharacteristicofthediseaseanddiagnosticoftheetiologicprocessesLimitations:morphologicallyidenticallesionsmayhavewidelydifferentcourses,therapeuticresponsesandprognosis.ExpandedtoencompassmolecularbiologicandimmunologicapproachesPathologymainlyfocusesonfouraspectsofdiseases10ETIOLOGYCauseofdiseasePATHOGENESISMechanismsofdevelopmentofdiseaseMORPHOLOGYThestructuralalterationsinducedincellsandtissuesPathologymainlyfocusesonfouraspectsofdiseasesFUNCTIONALCONSEQUENCESandCLINICALMANIFESTATIONSClinicalfeatures(symptomsandsigns),courses,andprognosisofthediseaseStartwithMolecularorstructuralalterationsTissueandorganinjuryClinicalpatternsCelltocellinteractionsCell-matrixinteractions11FUNCTIONALCONSEQUENCES

&CLINICALMANIFESTATIONSETIOLOGYPATHOGENESISMORPHOLOGYPathologyWithouttheconceptofsurgicaltreatment,oneisnotagoodphysician.Withouttheconceptofclinicaltreatment,oneisnotagoodpathologist.Withouttheknowledgeofpathology,oneisnotagooddoctor.Asisourpathology,soisourmedicine.-WilliamOsler病理為醫(yī)之本12

DevelopmentofPathologySectionB

OrganpathologyCellpathologyMolecularpathology13Apathologistwas…16th-18thcenturyFollowingtheinventionofthecompoundmicroscopePracticedbybedsidecliniciansworkingpart-timeForbetterunderstandthebasisofthepatient’ssymptomsandsigns,andthecauseoftheirdeaths

14Apathologistwas…19thcenturyRudolfVirchow（fatherofmodernpathology）&hismanyenlightenedpupils

Full-timeautopsypathologistsBearersofscientificmedicinethrough,mainly,autopsystudiesThe“academicpathologists”becamelessandlessclinicallyanddiagnosticallyoriented15Apathologistwas…Early20thcenturyBeginningofmodernsurgicalpathologySurgeonsexaminingspecimensfortheirpatients,usingmicroscopeIntroductionandperfectionoffrozensectiontechniques“Academicpathologists”fadedawayasnotbeingabletodeliver16Apathologistis…Firstandforemost:AclinicianAbridgebetween:EvidenceandpracticeAdvancesandapplicabilityBenchsideandbedside“GuidingtheSurgeon’sHand”(JuanRosai)Doctor‘sdoctor17SectionCOBJECTIVESOFRESEARCHAutopsyBiopsyCytologyExperimentalstudiesInvitro:Tissueculture；Organculture；CellcultureInvivo:Experimentalanimals，eg.nudemice；knock－outmice；18necrosisnormalmargin46/F,shortofbreathforoneday,comafor12hrs.Autopsy（orNecropsy,Postmortem）

19CheckthemesenteryvesselsPhlebitisFinalDiagnosisThrombosisinmesentery,splenicandportalveinsinducedbyphlebitis.InfarctionofsmallintestineAcutesuppurativeperitonitisDiedofshock.20BiopsyClinicalinformationMacroscopicobservationMicroscopicobservationAccessoryexaminations21FrozenSection

BenignormalignantClearmarginandmetastasisPitfallsUnsuitableconditions

22CytologyNormalLSILHSILcarcinomaCervicalPapSmear23ExperimentalstudiesNudemiceKnock-outmice，Transgenemice24ResearchmethodsSectionDMacroscopicobservationMicroscopicobservation(H&E)ElectronMicroscope(EM)Immunohistochemistry(IHC)InSituHybridizationPCRFlowCytometryMicroarray25ElectronMicroscopy26In-situHybridizationEBERinNasopharyngealcarcinoma11111818MALTLymphomat(11;18):BCL-10

11q22(SpectrumGreen):YAC906c5&921f318q22(SpectrumRed):YAC949b627ImmunohistochemistryForDiagnosis++++++-ForTreatment-HER-2/neuinbreastcarcinoma28AnalysisofIgHPCRProductspolyclonalmonoclonal12345100bp10%polyacrylamidegelGeneScanFr3-JHFr3-JHPCR29ConcurrentGastricandIntestinalMALTLymphomasCase1GGGCCTTGCAAAGTATAGCAGCTCGTCCCTTGACTCC

S---------------G-T-C--------------A-Case2GGCAGAAATGAACGAGGGCTGGTTCGACCCC

S----T----GC-------------------Case3GCGACAATATGGTGCGACCTATCCGGTATGGTTCGACCCC

S---------------------------------------Case4GGATCTCAACTATGGGGGGGGCCACTTTGACTAC

S---------------------------------Case5GCGCAATCAGTGGCCGGAAGGGGGTTGGATC

S------------------------------Case6GGCGCTTGTTAGTGGGAGCTACGTCATTGACTAC

S---------------------------------Case7GCTAGGTCTCGGGGACTTACTCAACTTTGACTTTGACTACS---------------------------------------CDR3Sequence311bp249bp+-GSI100bp+-GSI+-GSIFr1-JHFr2-JHFr3-JH30Fusiongenesinsarcomassynovialsarcoma-SYT-SSXFusiongeneinsynovialsarcomaTRANSACTIVATIONRDRDSYT(18q11.2)SSX(Xp11.2)SYT-SSXFUSION

HighlyprevalentinagivensarcomaHighlyspecificto