病理學英文課件：neoplasm(part I)

1、1 腫腫 瘤瘤 (1) 2 Malignant tumors! 1981-2015 Pancreatic neuroendocrine tumor 胰腺神經(jīng)內(nèi)分泌腫瘤胰腺神經(jīng)內(nèi)分泌腫瘤 Breast cancer 乳腺癌乳腺癌 3 56%64% in developing countries 4 Cancer Statistics in US, 2014 CA CANCER J CLIN 2014; 64(1): 9-29 新發(fā)病例（新發(fā)病例（1,665,540） 5 CA CANCER J CLIN 2014; 64(1): 9-29 Cancer Statistics in US, 201

2、4 死亡病例（死亡病例（585,720） 6 Trends in cancer incidence and death rates by sex, united states, 1975-2010 CA CANCER J CLIN 2014; 64(1): 9-29 7 Six person are Dx of Cancer in one minute pMorbidity (發(fā)病率發(fā)病率) nEstimated new cases 3,120,000 pMortality (死亡率死亡率) nEstimated deaths 2,700,000 Lung Stomach Colorectum

3、 Liver Breast Esophagus Cervix Prostate Ovary uterus Top10 Cancers in Chinese cities morbiditymortality Cancer Statistics in China, 2012 No.1 cause of human death in China 8 Lung cancer 肺癌 9 Hepatocellular carcinoma 肝細胞癌 10 Colorectal cancer 結(jié)直腸癌 11 Esophageal cancer 食管癌 12 stomach Cancer? Ulcer? 13

4、 Inflammation? Cancer? Pathologic diagnosis! 14 pPathologic evaluation is still the in tumor diagnosis pTumor pathology is the starting point for understanding of tumor 15 pDefinition * pCharacteristics of neoplasm * pClinical features of neoplasm pDiagnosis of tumor * pThe molecular basis of cancer

5、 pEtiology of cancer pCommon tumors * 16 Definition pA neoplasm is an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the normal tissues and persist the same excessive manner after cessation of the stimuli which evoke the change p腫瘤是機體在各種腫瘤是機體在各種致瘤因素致瘤因素(oncoge

6、nic factor)的作的作 用下，局部組織的用下，局部組織的細胞細胞在基因水平上失掉了對其在基因水平上失掉了對其 生長的正常調(diào)控，導(dǎo)致生長的正常調(diào)控，導(dǎo)致異常增生異常增生而形成的而形成的新生物新生物 (neoplasm)，通常形成腫塊，通常形成腫塊(mass) 17 Glossary pNeoplasia (new growth in Greek, 腫瘤形成腫瘤形成) nThe process of abnormal and uncontrolled growth of cells in a tissue or organ, usually forming a distinct mass

7、pTumor (腫瘤腫瘤): swelling in Latin, a synonym of neoplasm pCancer: malignant neoplasm (惡性腫瘤惡性腫瘤), carcinos or crab in Greek) 18 Glossary pOncology (腫瘤學腫瘤學): the study of neoplasms pCarcinogenesis (Tumorigenesis, 癌發(fā)生癌發(fā)生): mechanism of neoplasia pTransformation (轉(zhuǎn)化轉(zhuǎn)化): cancers induced in experiment pImm

8、ortalization (永生化永生化): unlimited cell growth, induced in experiment, incomplete transformation 19 Categories of tumors 20 pBenign tumors nCell type from which the tumor arises + -oma pFibroma (纖維瘤纖維瘤) pLipoma (脂肪瘤脂肪瘤) pLeiomyoma (平滑肌瘤平滑肌瘤) nGrowth pattern + -oma pPapilloma (乳頭狀瘤乳頭狀瘤) nCell type + gr

9、owth pattern + -oma pPapillary cystadenoma (乳頭狀囊腺瘤乳頭狀囊腺瘤) pTubular adenoma (管狀腺瘤管狀腺瘤) 21 Benign tumors 良性腫瘤 22 p Malignant tumor (Cancer, 癌癥癌癥) nCarcinoma 癌癌 deriving from epithelia p Squamous cell carcinoma, adenocarcinoma nSarcoma 肉瘤肉瘤 deriving from mesenchyma p Fibrosarcoma, liposarcoma Essential

10、ly follows that of benign tumors, with certain additions and exceptions 23 pExceptions n-blastoma: Neuroblastoma (神經(jīng)母細胞瘤神經(jīng)母細胞瘤), retinoblastoma (視網(wǎng)視網(wǎng) 膜母細胞瘤膜母細胞瘤), hepatoblastoma ( (肝母細胞瘤肝母細胞瘤) ) pNotice! osteoblastoma (骨母細胞瘤骨母細胞瘤), chondroblastoma (軟骨母軟骨母 細胞瘤細胞瘤) are benign n-oma: Melanoma (黑色素瘤黑色素瘤

11、), Seminoma (精原細胞瘤精原細胞瘤) , Myeloma (骨髓瘤骨髓瘤), lymphoma (淋巴瘤淋巴瘤) n-emia: Leukemia (白血病白血病) nBe named after sb.: Hodgkin disease (霍奇金病霍奇金病), Bowen disease (鮑文病鮑文病), Ewing sarcoma (尤文肉瘤尤文肉瘤) , etc. 24 pBorderline tumor (交界性腫瘤交界性腫瘤): nMalignant, but low grade pCarcinosarcoma (癌肉瘤癌肉瘤): 2 in 1 pConfusing t

12、erminology pHamartoma (錯構(gòu)瘤錯構(gòu)瘤): a non-neoplastic, malformation of disorganized tissue indigenous to the particular site pChoristoma (迷離瘤迷離瘤): heterotopic rest of cells 25 pDefinition * pCharacteristics of neoplasm * pClinical features of neoplasm pThe molecular basis of cancer pEtiology of cancer pD

13、iagnosis of tumor * pCommon tumors * 26TBCa 27 NeoplasiaReactive hyperplasia Growth autonomy, unlimited response, limited Cellsmonoclonalpolyclonal Geneticmutationno Functionnorepair, protection Host damage or deathno or little damage Neoplasia vs reactive hyperplasia 28 Characteristics of neoplasm

14、pMorphology nGross appearances nHistopathologic features pBiologic behavior nRate of growth nProgression and heterogenesis nSpread 29 Gross appearances 30 31 Familial adenomatous polyposis (FAP) 大腸家族性腺瘤性息肉病大腸家族性腺瘤性息肉病 32 pInfluencing factors nStage nLocation nNature (benign or maligant) p Diagnostic

15、 marker p Prognostic marker 33 34 Lung carcinoma LipomaHemangioma MelanomaChloromaRenal cell carcinoma 35 36 37 38 39 pMost of the benign tumors remain localized nEncapsulated or well demarcated nException：e.g. hemangioma pRelatively easy to remove pRarely recur 40 Invasive growth pattern nInvade an

16、d destroy surrounding tissues nRadical surgery must be performed nSurgical margin must be carefully examined 41 42 Exophytic growth pBenign or malignant 43 Benign vs malignant in gross CharateristicsBenignmalignant Well defined Slow growth necrosis ulcerative Growth pattern expansiveinfiltrative 44

17、Histopathologic features pArchitecture nParenchyma (實質(zhì)實質(zhì)) Determine the nature of the tumor Benign/malignant; histogenesis; differentiation nStroma (間質(zhì)間質(zhì)) Supportive tissues Blood vessels, lymphatics, connective tissues, etc. 45 pParenchyma and stroma CarcinomaSarcoma $%#&*! 46 47 p Differentiation

18、(分化分化) nThe maturation of parenchyma, the extent to which tumor cells resemble comparable normal cells nDegree of differentiation, generally relates to its biological behavior Benign tumors: well-differentiated Malignant tumors: loss of differentiation with varying degree Well (高分化高分化) low grade (低級

19、別低級別) Moderately (中分化中分化) low grade (低級別低級別) Poorly (低分化低分化) high grade (高級別高級別) 48 nThe differences between the tumor and tissue from which it originated both cytologically and structurally nAccompanies failure of differentiation Architecture: disorganized, disordered growth pattern Cytology: nucle

20、ar atypia (or pleomorphic) 49 pAnaplasia (間變間變) nliterally means “to form backward” nIt implies dedifferentiation, or loss of the structural and functional differentiation of normal cells pPleomorphism (多形性多形性) 50 nWell-dif. nModerately-dif. nPoorly-dif. nDe- or Un-dif. nNo- or mild atypia nProminen

21、t atypia nAnaplasia (間變間變) nPleomorphic (多形性多形性) or primitive (原始的原始的) differentiation atypia 51 colonic crypts adenoma adenocarcinoma 52 skin papilloma squamous cell Ca 53 Adipose tissue lipoma liposarcoma 54 Smooth muscle leiomyoma leiomyosarcoma 55 Cellular atypia pVarying in shape and size nSize

22、 larger than normal cells small primitive tumor cells, similar to lymphocytes nShape: irregularity Tumor giant cells (瘤巨細胞瘤巨細胞) Bizarre tumor cells (奇異型瘤細胞奇異型瘤細胞) pIncreased ratio of nucleus to cytoplasm 56 benign malignant malignant 57 Pleomorphic sarcoma 58 59 Ewing Sarcoma 60 Nuclear atypia pAbno

23、rmal nuclear morphology (異常核形態(tài)異常核形態(tài)) pAbnormal mitoses (異常核分裂像異常核分裂像) pLoss of polarity (極性丟失極性丟失) 61 Nuclear atypia pAbnormal nuclear morphology (異常核形態(tài)異常核形態(tài)) nLarge nuclei and variation in shape and size nHyperchromatic nuclei 染色質(zhì)深染染色質(zhì)深染 nChromatin aggregated under nuclear membrane nProminent nucle

24、oli 大核仁大核仁 62 Nuclear atypia pAbnormal mitoses nIncreased mitotic figures nPathologic mitosis (病理性核分裂像病理性核分裂像) 63 Interphase 間期間期Prometaphase 前中期前中期Metaphase 中期中期 Anaphase 后期后期Telaphase 末期末期 64 65 66 AsymmetricTripolarQuardripolar Abortive 67 68 Abnormal mitoses caused by amplified centrosomes, and

25、the consequential destabilization of chromosomes 69 70 Nuclear atypia pNuclear crowding, stratification and loss of polarity 71 Cytoplasmic changes pBasophilic nIncreased ribosome pLoss in secreted products or too much abnormal products 72 Non-diagnostic 73 : mild atypia : moderate to severe atypia

26、pArchitecture: disorganized pCytology leiomyomanormal 74 75 carcinomasarcoma originepitheliummesenchyma Incidencecommonless common Age adultschildren, adolescents Gross features firm, grey-white, drysoft, reddish, moisture Histologic features tumor cells forming nests or cords, usually well separate

27、d from stroma Tumor cells usually mixed with stromal cells Reticulin stain reticular fibers surround cell nests reticular fibers surround each cells metastsislymphatic channelsblood vessels 76 Characteristics of neoplasm pMorphology nkey words: atypia pBiologic characters nRate of growth nProgressio

28、n and heterogenesis nSpread 77 pCorrelates in general with tumor differentiation nBenign tumors: grow slowly nMalignant tumors: usually grow rapidly p Proliferative index (增殖指數(shù)增殖指數(shù)) nIHC Markers: Ki67, PCNA, PHH3 nFlow cytometry 78 79 pThe balance between cell proliferation and cell lost nProliferat

29、ion Death Tumor growth nDeath：necrosis, apoptosis, aging, autophagy 80 Gastrointestinal stromal tumor 81 Cancer stem cells (CSC, 腫瘤干細胞腫瘤干細胞) pIn analogy to tissue stem cells pHave the capacity of self-renewal pInitiate and sustain the tumor pConstitute 0.1- 2% of the cells in tumor pHave important i

30、mplications for cancer treatment 82 CSC：生長速度、侵襲能力、對生長信號的反應(yīng)、對抗癌藥物的敏感性等等的不同：生長速度、侵襲能力、對生長信號的反應(yīng)、對抗癌藥物的敏感性等等的不同 83 Precancerous lesion Carcinoma in situ metastasis Local spread Early invasion 84 Precancerous lesions (癌前病變癌前病變) pSome epithelial lesions with predispositions to development of malignant neo

31、plasm nChronic atrophic gastritis nChronic ulcerative colitis nAdenoma of the colon: familial adenomatous polyposis nDysplasia of the epithelia: cervix, esophagus, endometrium Cancer arising from precancerous lesions or benign tumor 85 p Disordered growth of epithelial cells nLoss in the uniformity

32、of epithelial cells nLoss in normal architectural orientation nVariation in shape and size of cells nHyperchromatic nuclei nMore mitotic figures p May be reversible to a certain point with stimulus removed 86 Intraepithelial neoplasm (上皮內(nèi)瘤變上皮內(nèi)瘤變) pMild dysplasia: lower 1/3 pModerate dysplasia: mid 1

33、/3 pSevere dysplasia/ Ca in situ: upper 1/3 whole layer 87 88 Esophageal precancerous lesion上皮內(nèi)腫瘤上皮內(nèi)腫瘤 Intraepithelial neoplasm 89 90 91 pDefinition: The whole layer of epithelium is involved, but without invasion (with intact basement membrane) pRepresents a very early stage of malignancy pOften co

34、mpletely curative pExamples nbreast ductal or lobular carcinoma in situ nskin squamous cell carcinoma in situ Carcinoma in situ 92 Carcinoma in situ. The entire thickness of the epithelium is replaced by atypical dysplastic cells. 93 Carcinoma in situ Invasive carcinoma 94 Tumor spread (腫瘤播散腫瘤播散) pD

35、irect extension 直接蔓延直接蔓延 nCancers grow by progressive infiltration, invasion, destruction, and penetration of the surrounding tissue pMetastasis 轉(zhuǎn)移轉(zhuǎn)移 95 96 pMetastasis nThe development of secondary implants (metastases) nDiscontinuous with the primary tumor From Robbins Basic Pathology Tumor spread

36、Invasiveness and metastasis, more unequivocally identify a neoplasm as malignant 97 nMore typical of carcinomas nDepends principally on the natural pathways of lymphatic drainage of the site nskip metastases maybe present 98 99 100 Sentinel lymph node (前哨淋巴結(jié)) pThe initial nodes encountered by the wa

37、ndering cancer cells pAn important aid in assessing whether a tumor has metastasized via the lymphatic system 10 1 nFavored by sarcomas nCarcinomas use it as well nThe liver and lungs are the most frequently involved sites 102Metastasis of liver carcinoma to the lung 103Metastasis of melanoma to the

38、 brain 104Metastasis of Choriocarcinoma to the liver 105Liver metastasis of colon carcinoma 106 nOccurs when neoplasms invade a natural body cavity nPeritoneal cavity(腹腔腹腔), Pleural cavity (胸腔胸腔), occasionally pericardial cavity (心包腔心包腔), joint space (關(guān)節(jié)腔關(guān)節(jié)腔) and subarachnoid space (蛛網(wǎng)膜蛛網(wǎng)膜 下腔下腔) 107

39、 10 8 Krukenberg瘤瘤 109 pTo predict clinical behavior and to establish critieria for therapy nGrading: reflects the organization and cytology of the tumors nStaging: refers to the extend of spread 110 Grading pBased on: nThe degree of anaplasia nThe number of proliferating cells pGrade nLow grade wel

40、l/moderately differentiated nHigh grade Poorly differentiated 111 Adenocarcinoma (well, moderately, poorly differentiated) 112 Squamous cell carcinoma (well, moderately, poorly differentiated) 113 Neuroendocrine tumors (grade 1, grade 2, grade3) 114 Staging pInternational TNM staging system nT: base

41、d on tumor size and/or extent of local spread nN: lymph node metastases nM: distant metastases 115 11 5 StageTNM 0TisN0M0 IT1-2N0M0 IIAT3N0M0 IIBT4aN0M0 IICT4bN0M0 IIIAT1-2 T1 N1 N2a M0 IIIBT3-T4a T2-3 T1-2 N1 N2a N2b M0 IIICT4a T3-4a T4b N2a N2b N1-2 M0 IVAny TAny NM1 116 pDefinition * pCharacteris

42、tics of neoplasm * pClinical features of neoplasm pThe molecular basis of cancer pEtiology of cancer pDiagnosis of tumor * pCommon tumors * 117 Clinical features of neoplasm pLocal effects: caused either by the primary tumor or by its metastases nLocation and impingement on adjacent structures nUlceration,