《病理学》课件:04 肿瘤

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1、Chapter5Tumor,NeoplasmSchool of Basic Medical SciencesSchool of Basic Medical Sciences,Fudan Fudan UniversityUniversity改错改错P82下行癌(下行癌(carcinoma,cancer)P86下行浸润癌(下行浸润癌(infiltratingcarcinoma)invasionCancerIncidence-commondisease1.Thereareabout1,800,000(180万)万)newcancercasesinChina.2.Thereareabout1,300,

2、000(130万)万)newcancercasesinAmerica.3.Thereareabout9,000,000(900万)万)newcancercasesinallovertheworldTumor-?diseasemalignanttumors-severelydamagedhumanhealth1.Thedeathofmalignanttumors:About7,000,000(700万万)intheworldAbout1,000,000(100万万)intheChina2.Cancerdeathsaccountingforalldeaths:Inwesterncountries:

3、secondcause.Inchina:first(incity)orthirdcause(incountryside).Theincidence&deathrateofcancerin1996MoreinmaturityagepersonsDifficultyManyrelatedfactorsUnknownpathogenesisLackofeffectivetreatmentandpreventionRespiratorytract:lungcancernasopharyngealcancerGastrointestinaltract:esophagealcancerstomachcan

4、cer,livercancer,largeintestinecancer.Femalegenital:breastcancer,ovarycancerLymphoidtissue:lymphomasHematologicsystem:leukemiaThetencommonestmalignanttumorsinChina:SectionI. ConceptionofTumor(肿瘤的概念)瘤的概念)AbnormalproliferationofcellAnabnormalmass 一一.Definitionoftumororneoplasm:(肿瘤性增生)肿瘤性增生)特殊的病理性增生特殊的病

5、理性增生EnvironmentaloncogenicagentsgeneticfactorsLocaltissuecellsAbnormalproliferationNeoplasm(mostofthemaremasstumors)1.Changeinquality:(morphology,function,metabolism,biologicalbehavior)Anaplasia(间变(间变):alsocalledundifferentiation.Thismeansthedifferentcharactersongrowthmorphology,function,metabolisma

6、ndbiologicalbehaviors,betweenthetumorcellsandnormalcell.FeaturesofcellabnormalityAtypia(异形增生异形增生):Usuallyreferredastocellmorphologicabnormalitycausedbyinflammationandtumor.Dysplasia(不典型增生不典型增生):referredastosomebenignneoplasticlesionhassomecharactersofmalignancy,buthasnotreachthecriterionsofmalignanc

7、y.ldividedintothreedegrees(Mild,moderateandsevere).severeonesshouldbetreatedascarcinomainsitu.Dysplasiaprecancerouslesion,Dysplasiamalignantlesion,butitcanalsobereversedtonormalcellafterthecassationofthestimuliwhichevokedthechange.Anaplasia(间变(间变): 2.Autonomy(自律性)(自律性)uncontrol,nolimitation,incoordi

8、nateDifferentfromphysiologicalproliferation,generalpathologicalproliferation,regeneration(再生)(再生),metaplasia(化生)(化生)3. “Heredity”oftumorcells(遗传性)(遗传性)间变特性子代细胞,传代的特性为间变特性子代细胞,传代的特性为4. “Heterogeneity”oftumorcells(异质性)(异质性)在肿瘤性增生中,间变是肿瘤存在的根本,自律性在肿瘤性增生中,间变是肿瘤存在的根本,自律性是肿瘤生长的动力,遗传性是瘤体形成的基础,异质性是肿瘤生长的动力,遗传

9、性是瘤体形成的基础,异质性给肿瘤发展以机会。给肿瘤发展以机会。Tumor(肿瘤肿瘤):benignandmalignantbenignandmalignantCancer(癌)(癌):malignanttumormalignanttumor(clinical)clinical)CarcinomaCarcinoma(癌)(癌): malignanttumorofepitheliamalignanttumorofepitheliaSection. BasicpathologicalchangesofTumor(肿瘤的基本病瘤的基本病变)1.Appearance (Contour)-Generalm

10、orphology (Grossly)Shape:various Accordingtotumoritself,location,modeofgrowth,tissue,etc一一. MorphologyandStructureofTumor:PolypoidPapillomatousNodularmulticysticMulti-nodularcauliflower-likeUlcerativeInvasivetumor图图肿瘤的外形和生长方式模式图肿瘤的外形和生长方式模式图息肉状息肉状 乳头状乳头状 结节状结节状 多囊状多囊状多结节型多结节型 菜花型菜花型 溃疡型溃疡型 浸润型浸润型 Co

11、lor:Determinedbythecharacteristicoftumor, blood supply, interstitial tissue, withorwithoutgrayishwhite:benigntumorsorcarcinomagrayishred:sarcomayellows:lipomared:hemangiomablack:melanomaSize:accordingtobehavior,time,location,effectonhost,medicalcare(0.8mm,30cm)Number: In most cases, tumor is singleo

12、ne. singlemonoclonal“multipletumors”twokind1.Tumorsarefromdifferenttissuewithdifferentorsamecharacteristicsinsametime.2.Tumorsarefromsametissuewithsamecharacteritics,insameordifferenttime.lipoma,neurofibroma,myelomaHardness:firm: more stroma, calcification or carcinomasoft: less stroma, necrosis obv

13、iously; or sarcoma纤维瘤病纤维瘤病vParenchyma-tumorcells(1) Main component: just one kind in most tumor (2) Determine tumors character, growth partner, shape, structure, and nomenclature (命名).(3) Differentiation refers to the extent to which tumor cells resemble their origin normal cells. Well (poor, lack)

14、differentiation2. Basic tumor tissue structure-twobasiccomponentsvStroma:connectivetissue(fiber,matrix),bloodvessel,nerve,immunecells(lymphocytes)(1) Connective tissue, blood vessel: support and nutrition tumor parenchyma(2) Immune cells: anti tumor immune reaction(3) Myofibrils: limit tumor spread

15、2. Basic tumor tissue structure-twobasiccomponents *Different tumors have their own specific parenchyma, but their stroma are almost the same. 1.Classification organtumorofstomachtissuefibroma,lipoma behavior tumor, carcinoma (orsarcoma)Forexample:leftbreastinvasiveadenocarcinoma二二.Classificationand

16、Nomenclature 2.Nomenclature-accordingtoParenchyma(tumorcell) All tumors (benign and malignant) have two basic components. 2.Nomenclature Benign中文:组织来源中文:组织来源+瘤;瘤;英文:英文: tissue+“oma”adeno-(aden-)adenoma(腺瘤腺瘤),lipo-,lipoma(脂肪瘤)(脂肪瘤)More detail: cyst-,papillary-except:aneurysm(动动脉脉瘤瘤),atheroma(粥粥样样瘤瘤),

17、hematoma(血肿血肿),granuloma(肉芽肿肉芽肿) Malignanttumor=cancer -carcinoma(癌癌):malignanttumorsariseinepithelialtissuessuchas:squamouscellcarcinoma,adenocarcinoma,basalcellcarcinoma,transitionalcellcarcinoma-sarcoma(肉瘤肉瘤):malignanttumorsariseinmesenchymaltissueslymphohematopoietic-nonon-lymphohematopoieticsuc

18、has:fibro-fibrosarcoma(纤维肉瘤纤维肉瘤)lipo-leiomyo-chondro-osteo-DifferencebetweenCarcinoma&SarcomaCarcinomaSarcomaTissueepitheliamesenthymeAge45youngerHistologynest,layermorecells,roundedbyinterstitial Growthinfiltration,crabfeetlikeoncutsurfacemargination,butinfiltrationearlierundermicroscopeMetastasisl

19、ymphaticvesselsbloodvesselsSpecialkindsucarcinosarcoma(癌肉瘤癌肉瘤)Bothepithelialandmesenchymaltissuesaremalignant.ublastoma(母细胞瘤)(母细胞瘤):Tumorsariseinfetaltissues. 间叶良性间叶良性;上皮和神经上皮和神经恶性恶性neuro-,medullo-,nephro-,hepato-,leiomyo-,osteo-,chondro-,etc.ucustomaryleukemia, Hodgkins disease, Ewings tumor, melan

20、oma,etc.u“malignant”-germlayerunkown:suchas: menigioma(脑膜瘤)(脑膜瘤),malignantmenigioma(恶性脑膜瘤)恶性脑膜瘤)-multigermlayers: Tumorscontainmorethanonegerm-celllayer. suchas:teratoma(畸胎瘤)(畸胎瘤),malignantteratoma(恶性畸胎瘤)恶性畸胎瘤)-singlegermlayer:Tumorscontainmorethanonekindofelements,butalltheelementsariseinasinglelay

21、ersuchas:polymorphism-mixedtumor(混合瘤)(混合瘤)malignantmixedtumor(恶性混合瘤)(恶性混合瘤)SpecialkindsPolymorphicadenoma(mixedtumor)teratoma多形性腺瘤uGrading: accordingtodifferentiationandmitosisBroders(1922):squamouscellcarcinoma(75%),Stout(1975-):welldifferentiationmediumdifferentiationundifferentiation三三.Gradingand

22、StaginguStaging肿瘤的范围和播散肿瘤的范围和播散Twomethodsofstagingarecurrentlyinuse:1.TNMsystem(T,primarytumor;N,regionallymphnodeinvolvement;M,metastasis)by国际抗癌联盟国际抗癌联盟2.AJCsystem:肿瘤波及范围肿瘤波及范围by美国癌肿分期联合委员会美国癌肿分期联合委员会(AmericanJointCommittee)StagingaccordingtoextentandspreadUICCTNMseriesTNM1-40-30-1AJCS0insituinorga

23、noutoforganinvasionneighbourorganmetastasis胃活检是低分化癌,该病人的肿瘤分期是晚期癌这话对吗?SectionII. BenignandMalignanttumors(Howtodistinguishbenignandmalignanttumors)accordingtoharmfulness Benignborderlinemalignantrelatedtotreatmentandprognosis1.Differentiation(分化)(分化):Benign:highlydifferentiated;Malignant:poorlydiffer

24、entiated. “Tumoristhedisturbanceofcelldifferentiation.”2.Mode of growthBenign:Expansivehaveenvelope. marginated,capsulated,effectivetreatmentMalignant:Infiltrativenoenvelop radical operation needed chemical and radiationtreatmentadded3.Speed of growthBenign:Slow,growthstopped,degeneration,mightbemal

25、ignantchangeMalignant:Fast,necrosis,bleeding4.Mitosis(核分裂象)(核分裂象)Benign:few,normalchrysanthemum,equatorialMalignant:more,abnormalmultipolar,unsymmetrical,abortive“菊花”状“赤道板”状NormalmitosisAnormalmitosisnon- symmetry, tripolar, quadripolar, multipolar spindles and abortion types pathologic mitoses.5. S

26、pread of tumors Invasion(侵袭侵袭),infiltration(浸润浸润),metastasis(转移转移) Metastasis:是鉴别良、恶性肿瘤的重要依据是鉴别良、恶性肿瘤的重要依据DetachmentTransportationFormationPrimarytumor,Secondary(Metastatic)tumor 6.Effects on hostB.&M.tumors:pressure,obstruction,functional,psychologicalB.tumors:hormoneM. tumors: bleeding, pain, feve

27、r, infection, metastasis,cachexia(恶恶病病质质),paraneoplasmsyndrome(肿肿瘤瘤伴伴随随综综合合征征。15%晚晚期期-异异位位激激素素或或生生物物活活性性物物质质分分泌泌内内分分泌泌症症状状和和其其他他),spreadtodistantsitestocausedeath. 7. Result of treatment and prognosisB.tumors:norecurrenceafterresection,canbecuredM.tumors:mightberecurrentafterresectionradicaloperatio

28、nneeded,early-good,butComparisonsbetweenbenignandmalignanttumors Benign Malignant DifferentiationWellPoororlackMitosesFewnopathologicmitosesAlways,havepathologicmitosesGrowthrateSlowRapidSecondarychangesLessbleedingandnecrosisCommon in bleeding andnecrosisComparisonsbetweenbenignandmalignanttumors B

29、enignMalignantGrowthpatternExpansiveorexotexichaveenvelopeInvasive or exotexic noenvelopMetastasisNoOftenRecurrenceRareAlwaysAffectionMainly local oppress andobstructionGreat,destruction,bleeding,infection,pain,cachexiaRelativityofB.&M.tumors:hemangioma,basalcellcarcinoma,tumorinbrain,mesotheliomain

30、heartMalignantchangeofB.tumors:adenomaofcolonReverseofmalignanttumors:neuroblastoma,trophoblastoma(绒癌)Borderlinetumors:PapillomaofbladderBenignmorphologyandmalignantbehavior:polymorphicadenomaofsalivaryglandMalignanttumorandbenignbehavior:juvenilemelanomainadultsNoteSectionIV. BiologicalCharacterist

31、icsofTumor1.MorphologyDetectingHEstainedsectioninlightmicroscope.Benigntumor:celldifferentiationMalignanttumor:bizzare(6)a.pleomorphism:markedvariationinsizeandshape.b.losenormalpolarity.c.thenuclear-cytoplasmicratiomayapproach1:1(1:51:1)d.nucleiareextremelyhyperchromaticandlarge.e.mitosesareoftennu

32、merousanddistinctlyatypicalf.withabasophilic(嗜碱染色的) cytoplasm.一一.BiologicalCharacteristicsofTumorCellsBizzare cellAtypical mitosisspecialkinds:smallcellcarcinoma,clearcellcarcinoma,giantcellcarcinomaEM:Nospecificfinding,butcanhelptodeterminethetumorderiving.Lessdifferentiation,simplerorganelleDiffer

33、entialdiagnosis:desmosome(桥粒桥粒)tonofilaments(张力丝张力丝)microvilli(微绒毛微绒毛)granule(颗粒)myofibrils(肌原纤维肌原纤维)Byelectronmicroscopy,featuresofacarcinomacanbeseen.Thisadenocarcinomademonstratesseveralfeaturestypicalofaneoplasmofepithelialorigin,includingthejunctionalcomplex(tightjunctionattheasteriskandthedesm

34、osomesatcrosses).Themucingranule(M)andlumenalmicrovilliattheupperrightarealsotypicalforanadenocarcinoma.Featuresofacarcinomaareseeninthiselectronmicrograph.Thissquamouscellcarcinomademonstratesmanydesmosomes,alongwithcytoplasmictonofilamentsstreamingtotheleft.Chromosome Benign tumor: haploid,diploid

35、,2346Malignanttumor:multiploid,aneuploid(非整倍体)非整倍体)69,9241,96broken,lost,translocation,ringformation,reformation22q9qPhiladelphiachromosomeCGL(90%慢粒慢粒)(费城染色体,费城染色体,Ph小体)小体)8q 14q90%Burkitt淋巴瘤淋巴瘤8q 21qAGL(急粒急粒)FlowCytometry. Red 8q24 C-myc Cyan - Centromere 8 Green - Centromere 14FISH染色体片段移位染色体片段移位19

36、59年年NowellP在在美国费城美国费城研究慢性粒细胞白血病研究慢性粒细胞白血病(CML)时发现时发现了了Ph染色体。染色体。这是染色体异常与肿瘤关系的第一个例证。这是染色体异常与肿瘤关系的第一个例证。RedChr.9GreenChr.22多色多色FISHM-FISH技术技术荧光原位杂交荧光原位杂交急性髓细胞白血病(AML)病例,患儿的主要染色体易位为t(10;11).这用传统的细胞生成的方法是不能觉察的.此种易位可用于特异性诊断AML ,预后较差。 淋巴瘤细胞核型分析结果不同颜色代表着不同号数的染色体,图中有些染色体出现了不只一种颜色,箭号标示处为发生染色体易位之位置Histochemis

37、tryDNA,RNA,fat,bilirubin,r-GT,DOPAreactionImmunohistochemistry,ISHAFP(甲胎蛋白甲胎蛋白)CK,Des,Vim,LN,FN,collagenAntigenofvirusHBV,HCV,HPV,Oncogene,tumorsuppressorgeneandtheirproteinproducts毛玻璃肝细胞Hereisanexampleofc-erb-B2positivityinabreastcarcinoma. 名称: 赫赛汀 通用名: 注射用曲妥珠单抗 英文名: TrastuzumabThisisanexampleofbcl

38、-2positivityinalymphoma. 2.PhysiologySecretion&function insulin(胰岛素)(胰岛素),bilirubin(胆红素)(胆红素),myofibrilabnormalsubstancesBence-Jonesprotein(多发性骨髓瘤)(多发性骨髓瘤)ectopichormones(ACTH,ADH,PTH)Lostcontactinhibition(接触抑制接触抑制)Tumorangiogenesis(血管形成血管形成)SignaltransductionTumorcellsculturedinvitroTransplantation

39、onimmunodeficiencyanimals3.BiochemistryIntumorcells,transportationofcarbohydrateandpolypeptideincrease,andnormalconnectionofcellsloss.Cellmembraneanion,Ca2+viscosityofcells(粘性)(粘性).CrabtreeeffectinsteadofPasteureffectCrabtreeeffect:在有氧条件下的糖酵解在有氧条件下的糖酵解.Improvementofsyntheticmetabolism,RNADNAReceptor

40、sofplantcoagulatorsofexternalorigin(i.e,ConA).Enzymenospecialenzymesfordiagnosis,moresynthesizeenzymesassociatedenzymesfordiagnosisAKP,ACP(酸和碱性磷酸酶酸和碱性磷酸酶)(如骨肉瘤和肝细胞癌中的(如骨肉瘤和肝细胞癌中的AKP等)。等)。Human tumor antigens: TSA (肿瘤特异性抗原), TAA (肿瘤相关抗原) 1.Antigensresultingfrommutationalchangeinproteins.(Suchas:mutat

41、edp53)2.Over-expressedoncogenes,HER2/neu.3.Someviralantigens.(E6,E7proteinsinHPV)4.Oncofetalantigens(胚胎蛋白抗原)(胚胎蛋白抗原):alpha-fetoprotein(甲胎蛋白)(甲胎蛋白),carcinoembryonicantigen(CEA)注:甲胎蛋白:注:甲胎蛋白:90%肝癌升高,如肝癌升高,如ng/ml(非常高几乎一定是癌)(非常高几乎一定是癌)5.Tissuespecificantigens(分化抗原)(分化抗原):PSA(前列腺特异抗原)(前列腺特异抗原)4.Immunolog

42、y:肿瘤免疫主要为细胞免疫肿瘤免疫主要为细胞免疫Antitumor Mechanisms: 1.CytotoxicTlymphocytes:2.NKcells:inducingNon-MHCrestrictedcytotoxicity.3.Macrophages:inducingsomeselectivecytotoxicity4.Immunology:肿瘤免疫主要为细胞免疫肿瘤免疫主要为细胞免疫Spreadoftumors:invasion(侵袭)(侵袭)metastasis(转移)(转移)thecharacteristicsofmalignantsolidtumors二二.Spreadof

43、Tumors: 1.Invasion(侵袭)(侵袭)oftumorcellsTheabilityoftumorcellstoinfiltratethearoundtissues(interstitialtissue,lymph-vessel,bloodvessel).是肿瘤转移的前奏是肿瘤转移的前奏a.ill-definedandnon-encapsuledb.Theparticulargrowthpatternofmalignanttumorsc.Besurgicallyenucleateddifficultly infiltratingInvasive growth patternThes

44、tepsandmechanismofinvasioni. Cancerous cells attaching basement membrane Cancerous cells have more receptors of lamina and fibronectin (纤维连接蛋白) ii. Local proteolysis iii. Locomotion 移动Schematicillustrationofthesequenceofeventsintheinvasionofepithelialbasementmembranesbytumorcells.Tumorcellsdetachfro

45、meachotherbecauseofreducedadhesiveness,thenattachtothebasementmembraneviathelamininreceptorsandsecreteproteolyticenzymes,includingtypecollagenaseandplasminogenactivator.Degradationofthebasementmembraneandtumorcellmigrationfollow.Tumor cells detach (loosening of intercellular junctions)Attach to the

46、basement membraneDegradation of the basement membraneTumor cell migration follow .Metastasis(转移转移):Definition:metastasis connotes the development of secondary implants discontinuous with the primary tumor, possibly in remote tissue. IncludeThreesteps:1.detachment(脱离)(脱离): Tumorcellsinvasionintothelo

47、callymphvessel,bloodvessel,orotherspace.2.transportation(转运)(转运): Becarriedtootherplacethroughthespace.3.formation(生成)(生成): Growthesamekindtumorintheremoteplaceasthatintheoriginalplace.1.Localbiochemicalcircumstancesthyroid,pancreas,cartilage软骨(抗侵袭因子和内皮细胞生长抑制因子)2.Tissuestructureandfunctionspleen,str

48、iatedmuscle3.Immunityofhost,immunefactorsinlocalplace,NKcellsInfluenceoflocalcircumstancestotumormetastasis Influenceoftumorcelltotumormetastasis1.Tumorcellssurface,mobility,viscosity,receptors2.Highmetastaticcelllines 3.Genesandotherfactors:ras,c-erbB2,nm23,WDNM2,TIMP,adhesivemolecules,MMP “种子和土壤学说

49、”Lymphaticmetastasis:isthetypicalofcarcinomas.Especiallyfortheearlystagemetastasis.VirchowsLymphnodes(左左锁骨上淋巴骨上淋巴结)晚期胃癌晚期胃癌三三.ThreePathwaysofMetastasis*晚期肺癌右锁骨上淋巴结晚期肺癌右锁骨上淋巴结Lymphaticmetastasis Lymphatic metastasisHematogenousmetastasis:Allformsofcancermaydisseminatethrougheitherorbothpathways.metas

50、tatictumormultiple,balllike,marginoforgan,demarcated,umbilicated(类似肚脐样)(类似肚脐样)肠道原发瘤肠道原发瘤门脉中的瘤细胞栓子门脉中的瘤细胞栓子肝转移瘤肝转移瘤胃胃肠肠道道肿肿瘤瘤经经门门脉脉系系统统转转移移至至肝肝Hematogenousmetastasis:Blood metastasisHematogenousmetastasis:a.Thispathwayistypicalofsarcoma,butisalsousedbycarcinomainadvancedstageb.Process:tumorcellssmall

51、bloodvesselstumorembolidistantpartsadherestotheendotheliumofthevesselinvasivethewallofthevesselproliferateintheadjacenttissueestablishanewmetastatictumor.Hematogenousmetastasis:c.liver,lung?d.Somecancershavepreferentialsitesformetastases.lungcancerfrequentlymetastasizetothebrain,bones,andadrenalglan

52、ds.Prostatecancerfrequentlymetastasizetothebones.Seedingmetastasis(种植性转移)(种植性转移)a. Tumor cells seed the surface of body cavitiesb. Most often involved is the peritoneal cavityc. But also may affected pleural, pericardial, subarachnoid, and joint space.转移到浆膜腔后果:转移到浆膜腔后果:bloody,mucoid,adhesion转移易到处:转移

53、易到处:costophrenic(肋隔角)(肋隔角),rectocystic(直肠膀胱陷窝)(直肠膀胱陷窝),rectouterus(膀胱子宫陷窝)(膀胱子宫陷窝) spaces Seedingmetastasis(种植性转移)(种植性转移)Krkenbergstumor(克氏瘤)(克氏瘤)precancerouslesion(pp92)andcarcinomainsitu(pp86)1.Precancerouslesion(癌前病变)(癌前病变):akindofbenignlesionthatcandeveloptomalignantlesion,butitcanalsobereversed

54、tonormalcellafterthecessationofthestimuliwhichevokedthechange.2.Carcinomainsitu(原位癌)原位癌):carcinomalimitedinepidermisormucosa,andhasnotpenetratebasementmembrane.i.e.Stage=0,noninvasioncarcinomawellprognosisafterresectionCarcinomainsituDysplasiaThecommonprecancerouslesion1.Fibrocysticadenosis(纤维囊性乳腺病纤

55、维囊性乳腺病):withdysplasia2.Familialadenomatouspolyposisofthecolon(家族性结肠腺瘤性息家族性结肠腺瘤性息肉病肉病)3.Leukoplakia(粘膜白斑粘膜白斑)4.Chroniculcer(慢性溃疡慢性溃疡)5.Dysplasia6.Chronicatrophicgastritis(慢性萎缩性胃炎慢性萎缩性胃炎)7.Chroniccholecystitisandchelolithiasis(慢性胆囊炎胆石症慢性胆囊炎胆石症)8.Chroniccervicitis(慢性宫颈炎慢性宫颈炎)9.Cirrhosis(结节性肝硬化结节性肝硬化)10

56、.Cryptorchidism(未降睾丸未降睾丸)上皮内肿瘤上皮内肿瘤FinalDiagnosis!-bonetumor*Authorityandimportanceofpathologicaldiagnosischeckingdiagnosisdefiningtissue,character,expandingdeterminingtreatment-radiation,chemicalunderstandingrecurrenceandestimateprognosisexperimentonanimalsSectionV. PathologicalDiagnosisofTumors一一.

57、ExcisionBiopsyThemostreliablediagnosismethod:1.Frozensection:itisareferencefordeterminingtheextentofoperation.Itisnotthefinaldiagnosis.2.Permanentsection:Finaldiagnosis.Requirementofexcisionspecimen1.Tumormarginwithgoodbloodsupply.2.Representativetissue3.Preventingtissuecrash.4.Fixtissueimmediatelyo

58、rsendtothedepartmentofpathologyforfixingatonce.5.Fillallthepartsofthepathologicapplyingform.病理申请单的填写病理申请单的填写1.姓名:医院纠纷的相当大部分。姓名:医院纠纷的相当大部分。2.性别:可能与病理诊断发生重要关系。性别:可能与病理诊断发生重要关系。3.年龄:诊断的最要参考依据。年龄:诊断的最要参考依据。4.出生地:与某些肿瘤的流行有关。出生地:与某些肿瘤的流行有关。5.有关经历(包括病史):有关经历(包括病史):6.临床发现及临检发现:临床发现及临检发现:3.Fine-needleaspirat

59、ionandaspirationbiopsyoftumorsAdvantage:obviatesurgeryanditsattendantrisks.Inexperiencedhands,itcanbeextremelyreliable,rapidanduseful.Disadvantage:smallsamplesizeandsamplingerror.lsimple,convenient,repeated,usinginmassscreeningsecretion,storagefluidlHE,Papanicoloausstain(巴氏)(巴氏)二二.Exfoliativecytolog

60、y(脱落细胞学脱落细胞学)andCytologicsmearsCytologicdiagnosisisonlyareferencediagnosis.theanaplasticcellswerefound,histologicdiagnosisshouldbemakeforgettingthefinaldiagnosis.肺癌可以宫颈涂片痰涂片三三.Othertechniquesforpathologicdiagnosis1.EM:canbeusedtohelptodeterminethederiveoftumor2.Histochemistry:SudanIIIforfatstain,PAS

61、.3.immunohistochemistry:Itisgettingmoreandmoreimportantintumorpathologicdiagnosis.4.InstrumentsICM,FCMnucleustype,cellsindifferentstages5.Hybridization:FISH,PCRDNA,RNA,virus,oncogene,tumorsuppressorgenesDNAmicroarrayanalysis,tissuearray.Section9(pp101)TumorandHostTumoreffectsonhost(pp104,80)B.&M.tum

62、ors:pressure,obstruction,pain,psychologicaldisturbanceB.tumors:hormone,malignantchangeM.tumors:bleeding,necrosis,infection,fever,spread,recurrence(pp104)Cachexia(恶病质):(恶病质):氧化过程减弱,代谢物质堆积体重减氧化过程减弱,代谢物质堆积体重减轻,贫血,软弱,明显衰竭的状态轻,贫血,软弱,明显衰竭的状态癌性恶病质:癌性恶病质:(pp104) Paraneoplasticsyndrome(肿瘤伴随综合征):肿瘤伴随综合征):ecto

63、pichormone(APUD,non-APUD)otherbiologicalactivators导致病人内分泌,皮肤,骨关节,神经肌肉等病变和症状功能性肿瘤:恶病质恶病质Cachexia: extremely thin, anemia, and weak. Tumor tissue may synthesize tumor proteins.Theeffectsofhostontumor:1.Hormonetopromotethegrowthoftumor:forexample,Breastcarcinoma,prostatecarcinoma,2.Tumorimmunity-seePPT

64、543.Angiogenesisoftumor(血管形成血管形成)血管生成因子:血管生成因子:VEGF,bFGF(碱性成纤维细胞生长因子)(碱性成纤维细胞生长因子)血管生成抑制因子血管生成抑制因子:Thrombospondin(血小板反应蛋白(血小板反应蛋白)tp53Angiostatin(血管抑素)(血管抑素),Endostatin(内皮细胞抑素),(内皮细胞抑素),Vasculostatin(脉管抑素脉管抑素)血管生成因子血管生成因子血管生成抑制因子血管生成抑制因子Section7(pp91,93-97)Etiology(aetiology,病因学)病因学)A.Externalfactor

65、sChemicalCarcinogenicAgents:1775Pott1915Yamajiva&Ichikawa煤焦油,兔耳煤焦油,兔耳动物实验多种,与人恶性肿瘤有关多种动物实验多种,与人恶性肿瘤有关多种(1)Direct-actingagents(直接致癌剂)(直接致癌剂):烷化剂:二甲基硫化物烷化剂:二甲基硫化物(2)Indirect-actingagents(间接致癌剂)(间接致癌剂) :Referstochemicalsthatrequiremetabolicconversionbeforetheybecomeactive.Theyarepotentcarcinogens.一一.Et

66、iology(pp93)indirect-actingagents1.Polycyclicandheterocyclicaromatic(多环和异环芳香碳氢化合物)(多环和异环芳香碳氢化合物)hydrocarbons:,-苯并芘苯并芘和和,-苯并蒽苯并蒽为煤焦油成分为煤焦油成分2.Aromaticamines,azodyes(芳香胺和偶氮染料)(芳香胺和偶氮染料)在印染厂和橡胶厂,膀胱癌萘胺有关(吸收后羟化),染料染黄油使肝癌增多在印染厂和橡胶厂,膀胱癌萘胺有关(吸收后羟化),染料染黄油使肝癌增多3.Naturalplantandmicrobialproducts:AflatoxinB1(黄曲

67、霉素)大鼠肝癌(黄曲霉素)大鼠肝癌(细胞内质网内形成环氧化物有关)细胞内质网内形成环氧化物有关),Betelnuts(槟榔)人类口腔癌(东南亚)(槟榔)人类口腔癌(东南亚)4.Others:Nitrosamine(亚硝胺)(亚硝胺),Insecticides(杀虫剂)(杀虫剂)Asbestos(石绵)(石绵),Arsenic(砷)(砷)Biologicalcarcinogencarcinogen(1)VirusTumorvirusinanimals(600oncogenicviruses)but,onlyafewviruseshavebeenlinkedwithhumancancer(HTLV

68、-1人细胞白血病病毒,人细胞白血病病毒,HPV,EBV,HBV,HCV.)RNA-virusDNAvirusHumanTumorsandVirusHTLV1:TcellleukemiaorlymphomaHSV,HPV16,18:cancerofcervixEBV:Nasopharyngealcarcinoma,BurkittlymphomaHBV,HCV:hepatocellularcarcinomaHSV:人单纯疱疹:人单纯疱疹型病毒型病毒HumanTumorsandVirusThemechanismofviralcarcinogenesisisnorclearexceptHPV.HPVc

69、ausestumorbyE6andE7(病毒基因)(病毒基因)throughthepathwayofblockingp53andRBgenesproductsactivity.E7蛋白:阻抑蛋白:阻抑RB并替代由并替代由RB基因封闭的基因封闭的E2F转录因子转录因子,也抑制,也抑制CDKIs,p21,p27等等E6蛋白:蛋白:blockingp53介导介导BCL2家族的细胞凋亡前成员家族的细胞凋亡前成员BAX的的降解,及激活端粒酶等降解,及激活端粒酶等RB:视网膜母细胞瘤蛋白视网膜母细胞瘤蛋白(2)BacteriaHelicobacterpylori(HP,幽幽门门螺螺杆杆菌菌):gastri

70、clymphoma,gastriccancer(3)ParasitesClonorchissinensis(支睾吸虫)(支睾吸虫):cholangiocarcinoma(胆管)(胆管)Schistosomiasisjaponica(日本血吸虫)(日本血吸虫):carcinomaofcolonSchistosomiasishaematobia(埃及血吸虫)(埃及血吸虫):carcinomaofbladderPhysicalX-ray,isotopes(同位素)(同位素),extravioletlongtermofpathogenesis,lowincidence,effectiveprevent

71、ionActionofEnvironmentalandGeneticinCarcinogenesisMortalityofTumorPatientsTumorJapaneseNiseiAmericansStomach1003817Colon100290490Pancreas(胰)(胰)100170270Lung100170320Leukemia100150270B.InternalfactorsHeredity.Inheritedcancersyndromesfamilyretinoblastoma(视视网网膜膜母母细细胞胞瘤瘤),familypolyposisofcolon,.Familia

72、lcancersbreastcancer,ovarycancer,cancerofcolon.DefectiveDNArepairxerodermapigmentosum(着着色色性性干干皮皮病病),ataxia-telangiectasia(毛毛细血管扩张性共济失调症)细血管扩张性共济失调症),Bloomssyndrome,FanconisanemiaAgechildrenacuteleukemia,-blastomayoungpersonosteosarcoma,rhabdomyosarcoma,seniorcancerEndocrinebreastcarcinomaImmunityTce

73、lls,BcellsinseniorpersonsimmunodeficiencyexperimentaltumorsMolecularBasisofcarcinogenesispp97-1.Nonlethal(非致死的非致死的)geneticdamageliesattheheartofcarcinogenesisSuchgeneticdamagemaybeacquiredbychemicals,radiation,orviruses2.Tumormassderivedfromsinglecell,monocloneThePrincipaltargetsofgeneticdamageincar

74、cinogenesis1.Growth-promotingprotooncogenes(原癌基因)(原癌基因)ras,myc,jun,fos,bcl-2.2.Growth-inhibitingtumorsuppressorgenesorantioncogenesRb,TP53,p16,p213.Genesthatregulateapoptosisbax,bad,TP53促凋亡促凋亡bcl-2抑制凋亡抑制凋亡.DNArepairgenesAcquired (environmental)DNAdamagingagents:ChemicalsRadiationvirusesNormalcellDNA

75、DamageMutations in the genomeofsomaticcellsActivation of growth-promotingoncogenesAlterations of genesthatregulateapoptosisInactivation of cancersuppressorgenesExpressionofalteredgeneproductsandlossofregulatorygeneproductsMalignantneoplasmSuccessful DNA repair Failure of DNA repair Inherited mutatio

76、ns in:GenesaffectingDNArepairClonal expansionAdditional mutations (progression)HeterogeneityOncogene(癌基因)(癌基因)istheactivatedprotooncogene.OncogenewasfoundbyVarmusandBishopatfirst.1.Whatisthefunctionof oncogeneproducts?2.Howcanprotooncogenebeactivated?细胞增生过程细胞增生过程生长因子细胞膜特殊受体生长因子细胞膜特殊受体激活细胞膜上激活细胞膜上信号转

77、导蛋白信号转导蛋白信号通过第二信使信号通过第二信使从细胞质转入核从细胞质转入核核调节因子启动转录和细胞周期进程核调节因子启动转录和细胞周期进程细胞分裂细胞分裂Theclassesofoncogenes1.Growthfactors:,2.GrowthfactorReceptors:EGFrfamilyoverexpression,amplification,pointmutation(erbb1-80%肺鳞癌;肺鳞癌;erbb-0%乳癌,肺癌和卵巢癌)乳癌,肺癌和卵巢癌)3.Signal-transducingproteins:pointmutation,translocation.(ras)

78、4.Nuclearregulatoryproteins:myc,myb,jun,fospointmutation,translocation.5.Cellcycleregulators(周期素和周期素依赖激酶)(周期素和周期素依赖激酶):overexpression,amplification,pointmutation(增生调节因子)GTPGDPGTPaseGAPsRas(Signal-transducingproteins)为例说明为例说明周期素和周期素依赖激酶酶周期素和周期素依赖激酶酶Howaretheprotooncogenesactivited?1.Pointmutation2.Am

79、plification:a.amplificationofhomogeneous-stainingregion(同源染色区扩大(同源染色区扩大)b.formationofdoubleminutes(双粒小体形成)(双粒小体形成)3.ChromosomalTranslocation(染色体转位染色体转位)(均染区)(均染区)慢粒白血病慢粒白血病CancersuppressorgenesThebrakeofcellproliferationGenerallyspeaking,bothofthenormalallelesofthesamecancersuppressorgenemustbeinact

80、ivated(homozygousloss)forthedevelopmentofcancercancer suppressor genes Molecules that regulated nuclear transcription and cell cycleRb gene: 13q14, G1 SP53 gene: 17p13.1, related to 50% of human tumorsBRCA- l gene: 17q12-21,BRCA-2 gene: 13q12-13Two famouscancer suppressor genes Molecules that regula

81、ted signal transductionNF-1 gene: 17q11.2; APC gene: 5q21 Cell surface receptorsSMAD2 gene, SMAD4 gene: DCC gene: 18q21 Other tumor suppressor genes NF- 2 gene,VHL gene: 3p; PTEN gene: 10q23, WT- 1 gene: 11p13(转录因子)(转录因子)RBp53基因基因Inhibit apoptosis: bc1- 2 gene (18q21), bc1-XlFavor apoptosis: bax, ba

82、d, bc1-xSGenesthatregulateapoptosisTelomere(染色体端粒):真核细胞线性染色体末端序列的多个重复 人类:5TTAGGG3作用:保护和稳定染色体末端,使细胞维持生长作用:保护和稳定染色体末端,使细胞维持生长Telomerase (端粒酶):核糖核蛋白酶85-95%人类恶性肿瘤有端粒酶上调telomerase activity increased in most human tumors.CarcinogenesisisamultistepprocessatboththephenotypicandthegeneticlevelsSection10(pp10

83、5)CommonTumorslBenignPapillomaAdenoma:Breast,Thyroid,Colon,OvarylMalignantSquamouscellcarcinomaBasalcellcarcinomaTransitionalcellcarcinomaAdenocarcinomaUndifferentiatedcarcinomaCarcinoidtumor 一一.EpithelialtumorsA.BenignTumors DerivedinEpithelium:(Papilloma-P26;Adenoma-P28)(1)Papilloma Origin: covera

84、ge epithelium Shape: finger-like projections into the lumen or on the surface of skin Site: commonly in skin or bladder.Papilloma(2)AdenomaOrigin: adenocytesTypes: Typical adenoma Cystadenoma: having single or multiple cysts containing watery secretion. Commonly in ovaryAdenomaofcolonAdenomaofcolonC

85、ystadenomaofovary Fibroademoma: both adenocytes and fibrous are parenchymal compositions commonly in breast Plesmorphic adenoma: having gland, mucoid, and cartilage-like tissues. Commonly in salivary gland. Polypous adenoma: single or multiple commonly in gastrointestinal track. Fibroadenomaofbreast

86、Polypous adenomaB.MalignantTumorsDerivedinEpithelium:CarcinomaCarcinimaisthemostcommonmalignanttumor.Theincidenceofcarcinomaisatleast9timeshigherthanthatofsarcoma.(1)SquamouscellcarcinomaOrigin: squamous cell Morphology: grossly: cauliflower-like, polyp, mushroom-like, ulceration. Histological: Well

87、- differentiated type are similar to normal squamous epithelial cells, with intercellular bridges and nets of keratin pearls (carcinoma pearls). But poor-differentiated type are pleomorphism, no intercellular bridges and keratin pearls.SquamouscellcarcinomaSquamouscellcarcinoma(2)Basalcellcarcinoma

88、Origin: basal cells of skin Features: locally invasive growth, almost never metastasis commonly in face of ololster.Basalcellcarcinoma色素性基底细胞癌色素性基底细胞癌鳞状基底细胞癌鳞状基底细胞癌特点:形态上恶性程度高,但生长慢,很少转移对放射线敏感,早期治疗预后好 Basal cell carcinomaLeft, Gross appearance. Offered by Dr. Pan Jian-Kai. Right, Histological 鼻基底细胞癌鼻

89、基底细胞癌 左:大体左:大体 右:镜下右:镜下Basalcellcarcinoma(3)Transitionalcellcarcinoma Origin: transitional cells Features: exoteric, finger-like, commonly in bladder, renal pelvis.特点:多见于膀胱和肾盂常呈乳头状生长早期发生浸润和转移(Papillary)trasitionalcellcarcinoma(4)Adenocarcinoma Origin: adenocytes large quantities of type: Typical ade

90、nocarcinoma Mucoid carcinoma or colloid Signet-ring cell and carcinoma mucin Solid carcinoma or carcinoma simplex Poor defferentiation adenoma carcinoma, and the tumor cells arrange in solid columns, or masses. Adenocarcinoma:单纯:单纯,囊,囊 乳头状囊 ,黏液 ,Signet-ring cell carcinoma Adenocarcinomaofbreast(carc

91、inoma simplex)Types:a. Sclerous carcinoma: dense stromab. Medullary carcinoma encephaloid carcinoma: Little stroma, and large masses of tumor cells.c. Carcinoma simplex: Poor defferentiation adenocarcinoma with equal quantities of tumor cells and stroma. Undifferentiatedcarcinoma:分化差,组织来源难鉴别的恶性肿瘤分化差

92、,组织来源难鉴别的恶性肿瘤特点:多见于肺,可见于胃,食道,鼻咽等多见于肺,可见于胃,食道,鼻咽等网状纤维染色用于鉴别诊断网状纤维染色用于鉴别诊断恶性程度高,常发生血道转移恶性程度高,常发生血道转移对放射线和化疗药较敏感对放射线和化疗药较敏感Carcinoid(类癌)(类癌)argentaffincarcinoma来源:神经嵴的嗜银细胞来源:神经嵴的嗜银细胞好发部位:胃肠道与支气管,阑尾多好发部位:胃肠道与支气管,阑尾多生长慢,生长慢,cm很少转移很少转移组织学特点:细胞小,大小和形态较一致核圆分裂少;组织学特点:细胞小,大小和形态较一致核圆分裂少;细胞质少,细胞质少,嗜银染色嗜银染色young

93、erperson,B.M.tumorsrelativity,changeoftissue(moreforms,complicatedelements)fibro-,lipo-,leiomyo-,rhabdomyo-,hemagio-,lymphangio-,osteo-,chondro二二.Mesenchymaltissue(nonlymphohematopoietic)2.Tumorsofsofttissues(1)tumorsoffibro-tissuea.fibromab.fibrosarcoma(2)tumorsoffattissuea.lipoma(2)tumorsoffattiss

94、ueb.liposarcoma()TumorsofmuscleLeiomyoma部位:多见子宫和肠壁(子宫奇异型)部位:多见子宫和肠壁(子宫奇异型)大体:界清,球形,硬大体:界清,球形,硬镜下:瘤细胞与正常平滑肌细胞相似镜下:瘤细胞与正常平滑肌细胞相似,栅状排,栅状排列,核分裂象很少列,核分裂象很少Leiomyosarcoma部位:多见子宫和肠壁部位:多见子宫和肠壁大体:鱼肉状大体:鱼肉状镜下:瘤细胞索状排列或不规则,核分裂象多镜下:瘤细胞索状排列或不规则,核分裂象多个个/高倍高倍()TumorsofmuscleleiomyomaleiomyosarcomaMasson三色:胶原纤维:绿色;肌

95、纤维:红色;红细胞:橘红色胶原纤维:绿色;肌纤维:红色;红细胞:橘红色Rhabdomyosarcoma部位:部位:多见四肢深部的横纹肌多见四肢深部的横纹肌大体:大体:软,紫红色,伴出血坏死软,紫红色,伴出血坏死镜下:镜下:瘤细胞极不一致(球拍形,蝌蚪形,带状瘤细胞极不一致(球拍形,蝌蚪形,带状等),胞质红和可见纹,核分裂象多等),胞质红和可见纹,核分裂象多恶性度高,早期血道转移恶性度高,早期血道转移磷钨酸苏木素()染色:磷钨酸苏木素()染色:横纹肌:兰色;胶原纤维:黄红色横纹肌:兰色;胶原纤维:黄红色rhabdomyosarcoma肉瘤有多的核分裂象肉瘤有多的核分裂象(4)Angiomaa.H

96、emangioma(头颈皮下和肝脾;紫红色,界不清)(头颈皮下和肝脾;紫红色,界不清)b.Lymphangioma(颈,口腔等)(颈,口腔等)左:毛细血管瘤左:毛细血管瘤 右:海绵状血管瘤右:海绵状血管瘤三三.TumorsofBone1.Osteochondroma(骨软骨瘤骨软骨瘤),osteoma(骨瘤骨瘤)2.Chondroma(软骨瘤软骨瘤),3.Osteosarcoma(骨肉瘤骨肉瘤)4.Giantcelltumor(巨细胞瘤巨细胞瘤)orOsteolastoma(破骨细胞瘤破骨细胞瘤)1.osteoma(骨瘤骨瘤)(儿童,青年)(儿童,青年)部位:长骨(股骨下端,胫骨上端多见)部位

97、:长骨(股骨下端,胫骨上端多见)骨瘤骨瘤Benign osteoma. 2.Chondroma(软骨瘤软骨瘤)小骨的软骨瘤:术后不易复发小骨的软骨瘤:术后不易复发长骨及扁骨的软骨瘤:术后易复发长骨及扁骨的软骨瘤:术后易复发软骨瘤软骨肉瘤软骨瘤软骨肉瘤中心部Osteochondroma. Left, The tumor seen on X-ray. Right, The histologic appearance of the tumor. The cartilagenous component forms a cap at the top of the bone 软骨瘤软骨瘤3.Osteosa

98、rcoma(骨肉瘤骨肉瘤)(青年,男多于女,有外伤史)(青年,男多于女,有外伤史)部位:部位:长骨干端,股骨下端胫骨上端和肱骨上端长骨干端,股骨下端胫骨上端和肱骨上端大体:大体:镜下:瘤细胞丰富,镜下:瘤细胞丰富,恶性度高,早期血道转移病理性骨折恶性度高,早期血道转移病理性骨折截肢外加化疗截肢外加化疗A highly malignant tumor of bore Infiltrative growth manner both into the marrows and outwards into the surrounding soft tissue. Formatting tumor ost

99、eoid by the tumor cells. Say characteristics: “sunburst” appearance codmans triangleOsteosarcomacodmans trianglesunburstOsteosarcoma瘤细胞内多量碱性磷酸酶Osteoclastoma(giantcelltumorofbone)部位:长骨骨部,股骨下端胫骨上端和挠骨上端部位:长骨骨部,股骨下端胫骨上端和挠骨上端大体:大体:膨胀性生长,膨胀性生长,“蛋壳蛋壳”,紫红色,紫红色镜下:单核基质及多核巨细胞镜下:单核基质及多核巨细胞良性,预后好良性,预后好Osteoclast

100、oma(giantcelltumorofbone)TumorsofHematopoieticandLymphoidSystem(Mesenchymaltissue): chapter10Allthetumorsofhematopoieticandlymphoidsystemaremalignanttumors.LeukemiaLymphoma:Non-HodgkinlymphomaandHodgkinlymphomaMyeloma(骨随瘤)(骨随瘤)LymphomaHodgkinlymphomaHodgkinlymphomaHodgkinlymphoma白血病肝白血病肝Tumorsofnerv

101、oussystem1.Thecentralnervoustumors(1) Glioma Astrocytoma Oligodendroglioma Ependymoma(2) Medulloblastoma (3) Meningioma 成人脑瘤成人脑瘤以胶质细胞以胶质细胞瘤多,多位于大脑;瘤多,多位于大脑;儿童脑瘤儿童脑瘤以胶质细胞以胶质细胞瘤和髓母细胞瘤多,瘤和髓母细胞瘤多,多位于小脑;多位于小脑;2.Peripheralnervoustumors (1) Neurofibroma (2) Neurilemmoma3.RetinoblastomaNeurilemmomaRetinobla

102、stomaRetinoblastomaOthersNevus(Nevi):先天性畸形,非真性肿瘤先天性畸形,非真性肿瘤来源:皮内黑色素母细胞及皮神经鞘膜细胞来源:皮内黑色素母细胞及皮神经鞘膜细胞a.DermalNevi(表皮内痣表皮内痣)b.JunctionalNevi(交界痣交界痣):恶变多恶变多c.CompoundNevi(复合痣复合痣)Others(1)Pigmentednevus Most authorities agree that the melanocytes are derived from neuro-ectoderm, and migrate to the basal la

103、yer of the skin in early intrauterine life A nevus or more implies a benign pigmented tumor containing nevus cells.melanoma(黑色素瘤)(黑色素瘤)Highgrademalignanttumor. Most from junctional nevi 大体:边不规则,棕黑色镜下:核仁明显诊断:反应阳性,染色预后:极差早期淋巴道转移放射线不敏感易转移到肝,肺和脑Pleomorphicadenoma(多形性腺瘤)(多形性腺瘤)Itisalsoreferredasmixedtumo

104、r.Thisisaborderlinetumor. 来源:闰管上皮成分多样术后复发率高,多次复发可癌变Teratoma(畸胎瘤)(畸胎瘤)Teratomaiscomposedofatleasttwogerm-celllayers.Generally,thecystictumorisbenign,whilethesolidoneismalignant.部位:性腺和躯干正中线良,恶(卵巢多良性;睾丸多恶性)水泡状胎块水泡状胎块(hydatidiformmole)水泡状胎块水泡状胎块1.Definitionoftumororneoplasm,andFeaturesoftumorcellabnormality.2.Whatmeans“Precarcinomalesion”?Listfourcommonexample.3.Whatmeans“Carcinomain situ”?“Protooncogenes”?“Oncogene”?4.Brieflystatethedifferencesbetweencarcinomaandsarcoma.病例分析病例分析Thanks!

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