中国医科大学病理学英文9课件

1、Chapter 5. NeoplasiaXu HT 病 例，女，21岁主诉：近半年左下肢膝关节附近疼痛，活动后 加重，一个月前发现左股骨下端局部隆 起，逐渐长大，疼痛难忍，来诊。查体：左股骨下端局部肿物，压痛（）处置：1. 左股骨下端X线正侧位像2. 胸部X线正侧位像3. 左股骨下端肿物穿刺活检检查结果 1.左股骨下端X线正位像： 左股骨下端占位病变， 骨皮质破坏,骨膜反应。2.胸部X线正侧位像： 未见明显异常临床诊断：恶性骨肿瘤？ 活检病理诊断：骨肉瘤 1.什么是肿瘤？具有哪些特性？2.肿瘤有哪些种类、各自特点？3.肿瘤生物学行为如何？对机体有何影响？4.肿瘤的结局如何？5.肿瘤是如何发生发

2、展的？如何防治？思 考 题 Chapter 5. NeoplasiaTumors is common diseases. Bad news: Malignant tumor (cancer) is the second leading cause of death in some countries. (The first leading cause is cardiovascular diseases.)According to American Cancer Society estimates, in 2003, about 23% of all deaths in the United

3、States (1500 cancer deaths per day).Section 1. Definition and morphologyTwo question:What is tumor? DefinitionWhat are tumors look like? MorphologyDefinitionNeoplasia literally means the process of “new growth” and a new growth is called a neoplasm.tumor was originally applied to the swelling caused

4、 by inflammation. Oncology is the study of tumors or neoplasms. Cancer is the common term for all malignant tumors. NeoplasiaIn 1953, The eminent British oncologist Willis had given neoplasia a famous definition: “A neoplasm is an abnormal mass of tissue, the growth of which exceeds and is uncoordin

5、ated with that of the normal tissues and persists in the same excessive manner after cessation of the stimuli which evoked the change.” A more scientific difinition: “Neoplasia is genetic disease, in which the growth of tumors is loss of responsiveness to normal growth control, and shows an excessiv

6、e hyperplasia with abnormal differentiation.”Tumor (neoplasm): under the stimulation of tumorgenic agents a single cell of local tissue loss the controlling to its growth at the gene level excessive proliferation to form neoplasmDistinguish between neoplastic and non-neoplastic hyperplasia Neoplasti

7、c Non-neoplastic Monoclonality Polyclonality Abnormal morphology Normal morphology and function and function Abnormal differentiation Matured differentiationPersistent, autonomous LimitedHarmful BeneficialMorphology and structure Number and Size: variousShape: sessile, papillary, nodular, lobular, c

8、ystic, fungating, ulcerated, and infiltratingColor: dependent on histogenesis and secondary changes (hemorrhage, necrosis)Consistency: Parenchyma-stroma ratio, Secondary changesCapsule: benign with intact capsuleSecondary changes: hemorrhage, necrosisMacropathology: The gross appearance of tumors is

9、 varied, reflecting the nature of the tumor to some extent.papillarypolypousShape: relate to histogenesis, site and biologic behaviorPapillomaPolypous adenomaBenignNodular or lobularcysticLipoma FibroadenomaMucinous cystadenoma BenignColor: The color of a benign tumor resembles that of the normal ti

10、ssue from which it derived. The color of the cut surface of a malignant tumor may be gray-white, and often varied due to secondary changes (hemorrhage, degeneration and necrosis).CapsuleThe benign tumor is usually circumscribed by a clearly defined border and often encapsulated by thin fibrous capsu

11、le.The malignant tumor is invasive and poorly circumscribed.FibromaCarcinoma of stomach Consistency Resembles the normal tissue it derived fromTumors are usually firmer than surrounding tissuesProportion of parenchyma and stromaSecondary changesAdipose tissue Lipoma: softCartilage Chondroma: hardSci

12、rrhous carcinomaConsistencyParenchyma-stroma ratio stromaParenchyma hardMedullary carcinomaConsistencyParenchymaStroma softSecondary changesNecrosisHemorrhageParenchyma StromaStromal BVFibrosarcoma Take home question:What is neoplasia? (The definition)How to describe the gross appearance of a tumor?

13、 (Number, size, shape, color, consistency, capsule,secondary changes)What is neoplastic atypia?The atypia of tissue architectureThe atypia of neoplasic cellsSection 2. Neoplastic atypiaWhat is atypia? Atypia: Neoplastic tissue has various extent of differences with its originated normal tissue, both

14、 cell morphologically and tissue architecturally. Differentiation: The degree to which a neoplasic cells resembles its originated normal mature cells, both morphologically and functionally.Anaplasia: Lack of differentiation of malignant neoplastic cell, with obviously atypia.Anaplastic tumor: compos

15、ed of undifferentiated cell.Pleomorphism: obvious variation in size, shape obviously atypiaAtypia of tissue architectureRefers to difference between neoplastictissue and its originated normal tissueThe arrangement of neoplastic tissue The polarization of neoplastic tissue the relationship with strom

16、aIntestinal adenomaAdenocarcinomaSquamous cell carcinomaAtypia of neoplastic cellsPleomorphism of neoplastic cells1. Variation in size and shape2. Generally larger than normal cells tumor giant cells Pleomorphism of nucleus1. Increased nucleus: The nuclear- to - cytoplasmic ratio may approach 1:1 in

17、stead of the normal 1:4 - 6. 2. Variation in size, color and shape of nucleus: Size: Huge, two or more nuclei, bizarre nuclei, large nucleoli are usually present. Color: The nuclei contain an abundance of DNA and are extremely dark staining Shape :i) The shape is usually extremely variable, the chro

18、matin is coarsely clumped ii) Increased mitotic figures : Atypical, bizarre mitotic figures producing tripolar, quadripolar, or multipolar spindles. Normal structureAdenocarcinoma Changes of cytoplasm1. Cytoplasm: Basophilic nucleoprotein increased2. Abnormal products or secretion: Mucus, glycogen,

19、lipid helpful to determine histogenesis of tumorMucoid carcinomaSquamous cell carcinomaMelanoma of the skin Ultrastructural changes (electron microscope)Organelles : signs of histogenesis Neuroendocrine granules neuroendocrine tumorTonofilament and desmosomes squamous cell carcinomaMyofilament and d

20、ense body SMC Take home questions:What is atypia? (The definition)What is atypia include? The atypia of tissue architectureThe atypia of neoplasic cellsCell nucleusCytoplasmUltrastructureSection 3. Growth and spread of tumorGrowth pattern of tumorBiology of tumor growthSpread of neoplasms (Invasion

21、and metastasis)Mechanisms of invasion and metastasisGrading and staging of tumor1. The growth of tumorI. Growth pattern of tumorExpansive growthExophytic growthInfiltrating growth Growth pattern of tumor 1. Expansive growth:The mode of most benign tumornodularintact capsuleLeiomyoma (1) Sites: surfa

22、ce of body, body cavities or tract organs.(2) Shape: papillary, polypoid, cauliflower(3) Growth pattern of both benign (has a pedicle) and malignant tumor (also grow by infiltrating)2. Exophytic growth:Exophytic growth The mode of most malignant tumorabsence of capsule, infiltrate and destroy surrou

23、nding tissue 3. Infiltrating growthII. Biology of tumor growth1. Monoclonality: Tumor is formed by a transformed cell proliferation 2. The natural history of most malignant tumors can be divided into four phases:(1) Malignant transformation in the target cell(2) Clonal growth of the transformed cell

24、s(3) Local invasion(4) Distant metastasis3. The multiple factors that influence tumor growth are considered under three headings:(1) kinetics of tumor cell growth(2) Tumor angiogenesis(3) Tumor progression and heterogeneity Kinetics of tumor cell growthDoubling time of tumor cellsGrowth fractionTumo

25、r cell production and lossDoubling time of tumor cells: In reality, cell cycle time for many tumors equal to or longer than that of corresponding normal cells growth of tumor is not associated with a shortening of cell doubling timeGrowth fraction: the proportion of cells within the tumor population

26、 that are in the proliferative pool ( S + G2 phase ). Early stage vast majority of transformed cell are in the proliferative pool high growth fraction As tumors continue to grow cell leave the replicative pool by differentiating and by reversion to Go in rapidly growing tumors approximately 20%Tumor

27、 cell production and loss: Growth of tumors are determined by the excess of cell production over cell loss. The rate of tumor growth depends on: Growth fraction Degree of imbalance between cell production and cell lossHigh grow fraction: Clinical course is rapid (lymphoma) susceptibility to chemothe

28、rapyLow grow fraction (cell production exceeds cell loss by only about 10%): Grow at a much slower pace (car. of colon) no susceptibility to chemotherapy Tumor angiogenesisAngiogenesis is a necessary biologic correlate of malignancy: tumors cannot enlarge beyond 1 to 2 mm in diameter or thickness un

29、less they are vascularized.Angiogenesis is requisite not only for continued tumor growth, but also for metastasis. Neovascularization has dual effect: Perfusion supplies nutrients and oxygen Newly formed endothelial cell secreting polypeptides such as insulin-like GF, PDGF stimulate the growth of tu

30、mor cell How do growing tumors develop a blood supply? Tumor associated angiogenesis factors produced by tumor cells infiltrated inflammatory cells VEGF, FGF, PDGF Tumor induce antiangiogenesis molecules: WP53 induce thrombospondin 1 inhibit formation of BV P53 gene mutation thrombospondin 1BVPlasmi

31、nogen, collagen, transthyretin proteolytic cleavage angiostatin, endostatin, vasculostatin, potent angiogenesis inhibitors Tumor progression and heterogeneity 1. Tumor progression Malignant tumor become more aggressive in the process of growth accelerated growthlocal invasiondistant metastasis 2. Tu

32、mor heterogeneity In the process of growth, monoclonal tumor cells generate subclones with different characteristics 3. Mechanism: Mutant additional genes damageInvasiveness, rate of growthhormonal responsivenesssusceptibility to antineoplastic drugs2. Spread of neoplasmsLocal invasion (direct sprea

33、d)MetastasisLymphatic metastasisHematogeneous metastasisTranscoelomic metastasis (Metastasis in body cavities) (seeding) Spread of neoplasms1. Direct spread Malignant tumor C infiltrate tissue, lymphatic, BV, nervous tissue 2. Metastasis Malignant cells from primary site invade into lymphatics, BVs

34、and body cavities and reach distant site continues growth to form the same type tumor with primary tumor The most common pathway for the initial dissemination of carcinoma Sarcoma may also use this route The most common site: Lung Gastrointestinal tract Arm pit, groin, cervical glands(1) Lymphatic m

35、etastasis:Left supraclavicular LNAfferent lymphaticsTumor emboliSubcapsular sinusEfferent lymphaticsRetrograde metastasisPrimary tumorLymphatic nodule Lymphatic metastasisLymphatic metastasis(2) Hematogeneous metastasis The favored pathway of sarcoma. Metastatic pathway: Caval blood lung Portal bloo

36、d liver Pulmonary v(cap) brain, bone, kidney Vertebral vein paravertebral plexus brain ( Prostate, thyroid) Common sites: lung (most), liver, bone Features of hematogeneous metastatic tumor: multiple, rounded nodules with clear border, scattered in distribution, close to surface of organ.Choriocarci

37、noma Carcinoma umbilicus Hematogeneous metastatic tumor located surface of the organ forms umbilication because of central hemorrhage and necrosis(3) Transcoelomic metastasis (Metastasis in body cavities or Seeding) Definition: Malignant tumor cell of an organ in body cavity penetrate into the surfa

38、ce of the organ and break off to seed in the surface of the organs of body cavity and form metastatic tumor.Transcoelomic metastasisColloid carcinoma of stomachseed in the surface of intestine krukenberg tumor: Gastric carcinoma destroy gastric wall and tumor cell seed in the ovaries to form metasta

39、tic tumor Sites peritoneal cavity (most common) pleural, pericardial, subarachnoid, joint space Surgical instruments: rare an artificial mode of dissemination The mechanisms of invasion and metastasisThe mechanism of local invasionVascular dissemination and homing of tumor cellsMolecular genetics of

40、 metastasis The mechanism of local invasion(1) Detachment of the tumor cells from each other : Down-regulation of E-cadherin (CAM) expression(2) Attachment to matrix components: Integrin (epithelium) binding to laminin (BM)(3) Degradation of extracellular matrix: Tumor cell secrete proteolytic enzym

41、es induce host cell to elaborate proteases(4) Migration of tumor cells: Mediated by Tumor cell derived motility factors Cleavage products of matrix components Vascular dissemination and homing of tumor cellsSingle tumor cell is destroyed by nature killer cell (NKC)Formation of platelet-tumor aggrega

42、teEnhance the survival and implantabilityTumor emboli involve adhesion to endothelium cells (EC) Egress through the basement membrane (BM) prostate to bone lung to adrenal, brain breast to lung, liver, bone(1) Tumor cell express the adhesion molecules whose ligands are expressed on the EC of the tar

43、get organs.(2) Some target organs may liberate chemoattractants to recruit tumor cell to the site.(3) Some organs may be an unfavorable soil for the growth of tumor seeding: such as spleen, heart, skeletal muscleOrgan tropism Molecular genetics of metastasis No single metastasis gene has been found.

44、The gene that encode E-cadherin, inhibitors of metalloproteinases, nm23, etc. is considered metastasis suppressor genes.III. Grading and staging of tumor Grading of tumor: According to degree of differentiation and the number of mitoses: Grade : well-differentiated Grade : moderately-differentiated

45、Grade : poorly-differentiated Grade : undifferentiated Well-differentiatedModerately-differentiatedPoorly-differentiatedUndifferentiated Staging of tumor: Based on size of the primary lesion, its extent of spread to LN distant metastasis: UICC (international union against cancer) TNM classification

46、of malignant tumours T: primary tumor, T1T4 increasing size N: Regional LN involved, N0no involved; N1-N3 M: distant metastasis, M0no; M1-M2Take home question:How tumor growth? (growth pattern)How neoplasms Spread? (Invasion and metastasis)The concepts of metastasis, carcinoma umbilicus and transcoe

47、lomic metastasis, tumor progression and heterogeneity?Try to explain The process of tumor cells local invasionSection 4. Effects of tumor on hostBenign tumor: less effects Local oppression and obstruction: Relate to site and secondary changeImportant organs: intestinal, brainherniaTumor of endocrine

48、 glands: systemic symptomsAcidophilic adenoma of hypophysis cerebri: gigantism or acromegalyAdenoma of pancreatic islets: fatal hypoglycemia Malignant tumor1. Local compression + obstruction + pain 2. Constitutional symptoms: Fever, infection, night sweat3. Cachexia: Refer to the state of progressiv

49、e loss of weight, anemia, weakness and systemic failure.4. Paraneoplastic syndrome ( PNS ) Neoplastic product (ectopic hormones) Abnormal immune reaction (cross immune, autoimmune, immune complex ) Other unclear causes Lead to lesions of endocrine, nervous, digestive system and so on (1) Ectopic end

50、ocrine syndrome: Some non-endocrine tumors elaborate hormones or hormone-like substance cause endocrine disorder. Hypercalcemia: parathormone -like substance elaborated by carcinoma of lung, kidney Hypoglycemia: elaboration of insulin-like substance by fibrosarcoma, mesothelioma(2) Hypertrophic oste

51、oarthropathy: Formation of bone, arthritis of the adjacent joint and clubbing of the digits.(3) Vascular and hematologic syndrome: Migratory thrombophlebitis, endocarditisSection 6. Differences between Benign and malignant tumor Degree of well poorlydifferentiation structure is typical obvious atypi

52、aMitotic figure rare and normal increased no pathologic mitotic pathologic mitoticRate of growth slow rapidGrowth pattern expansive infiltrative exophytic exophytic well demarcated poorly demarcated Benign malignant Difference between benign and malignant tumor(Part I)Secondary rare common changes (

53、 hemorrhage, necrosis) Local invasive noninvasive locally invasive Metastasis absent common Recurrence rare commonEffects compression cachexia on host obstruction metastasisBenign malignant Difference between benign and malignant tumor (Part II)Section 3. Nomenclature and classification Nomenclature

54、 Benign tumor:(1) Cells of origin + “oma” Fibroma, adenoma, fibroadenoma(2) Cells of origin + morphologic feature Adenoma + cystic cystadenoma + papillary papillary cystadenoma Malignant tumor(1) Carcinoma: Arising in epithelial cell Squamous cell carcimnoma Adenocarcinoma Transitional cell carcinoma(2) Sarcoma: Arising in mesenchymal tissue Cells of origin + “sarcoma” Fibrosarcoma, liposar