病理学英文课件9.ppt

Chapter 5. Neoplasia,Xu HT,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,病 例，女，21岁,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,检查结果,病理学英文课件9,病理学英文课件9,1.什么是肿瘤？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.肿瘤是如何发生发展的？如何防治？,思 考 题,1.什么是肿瘤？具有哪些特性？思 考 题,Chapter 5. Neoplasia,Tumors 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 States (1500 cancer deaths per day).,Chapter 5. NeoplasiaTumors,Good news: The rapid progress has been made in understanding the molecular basis and biological behavior of cancer and cancer therapy. Many cancers can be cure or arrested. For example: breast cancer, cervical cancerBut many problems still need to be solved!,Good news:,Section 1. Definition and morphology,Two question:What is tumor? DefinitionWhat are tumors look like? Morphology,Section 1. Definition and mor,Definition,Neoplasia literally means the process of “new growth” and a new growth is called a neoplasm.tumor was originally applied to the swelling caused by inflammation. Oncology is the study of tumors or neoplasms. Cancer is the common term for all malignant tumors.,DefinitionNeoplasia literally,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 uncoordinated 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 excessive hyperplasia with abnormal differentiation.”,Neoplasia,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 neoplasm,Tumor (neoplasm):,Distinguish between neoplastic and non-neoplastic hyperplasia,Neoplastic Non-neoplastic Monoclonality Polyclonality Abnormal morphology Normal morphology and function and function Abnormal differentiation Matured differentiationPersistent, autonomous LimitedHarmful Beneficial,Distinguish between neoplastic,Morphology and structure,Number and Size: variousShape: sessile, papillary, nodular, lobular, cystic, fungating, ulcerated, and infiltratingColor: dependent on histogenesis and secondary changes (hemorrhage, necrosis)Consistency: Parenchyma-stroma ratio, Secondary changesCapsule: benign with intact capsuleSecondary changes: hemorrhage, necrosis,Macropathology: The gross appearance of tumors is varied, reflecting the nature of the tumor to some extent.,Morphology and structure Numb,Number and size:various,Fibroadenoma,Polypous adenoma,Number and size:FibroadenomaPo,papillary,polypous,Shape: relate to histogenesis, site and biologic behavior,Papilloma,Polypous adenoma,Benign,papillarypolypousShape: relate,Nodular or lobular,cystic,Lipoma Fibroadenoma,Mucinous cystadenoma,Benign,Nodular or lobularcysticLipoma,Fungating Ulcerated Infiltrative,Malignant,Fungating,Color: The color of a benign tumor resembles that of the normal tissue 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).,Color:,CapsuleThe benign tumor is usually circumscribed by a clearly defined border and often encapsulated by thin fibrous capsule.The malignant tumor is invasive and poorly circumscribed.,Fibroma,Carcinoma of stomach,CapsuleFibromaCarcinoma of sto,Consistency,Resembles the normal tissue it derived fromTumors are usually firmer than surrounding tissuesProportion of parenchyma and stromaSecondary changes,Adipose tissue Lipoma: soft,Cartilage Chondroma: hard,Consistency Resembles,Scirrhous carcinoma,Consistency,Parenchyma-stroma ratio stromaParenchyma hard,Scirrhous ConsistencyParenchym,Medullary carcinoma,Consistency,ParenchymaStroma soft,Medullary carcinomaConsistency,Secondary changes,Necrosis,Hemorrhage,Secondary changesNecrosisHemor,Histological structure,All tumors have basic two components:1. Parenchyma Major component of tumor: neoplastic cellDetermine the biologic nature and specificity2. StromaComposed of CT and BV support the tumorGrowth speed depend on the stroma blood supplyLC infiltration immune reaction to tumor,Histological structureAll tumo,Parenchyma Stroma,Parenchyma Stroma,Stromal BV,Fibrosarcoma,Stromal BVFibrosarcoma,NO stromal BV,NO stromal BV,Take home question:What is neoplasia? (The definition)How to describe the gross appearance of a tumor? (Number, size, shape, color, consistency, capsule,secondary changes),Take home question:,What is neoplastic atypia?The atypia of tissue architectureThe atypia of neoplasic cells,Section 2. Neoplastic atypia,What is neoplastic atypia?Sect,What is atypia?,Atypia: Neoplastic tissue has various extent of differences with its originated normal tissue, both cell morphologically and tissue architecturally. Differentiation: The degree to which a neoplasic cells resembles its originated normal mature cells, both morphologically and functionally.,What is atypia? Atypia: Neopl,Anaplasia: Lack of differentiation of malignant neoplastic cell, with obviously atypia.Anaplastic tumor: composed of undifferentiated cell.Pleomorphism: obvious variation in size, shape obviously atypia,Anaplasia: Lack of differentia,Atypia of tissue architecture,Refers to difference between neoplastictissue and its originated normal tissueThe arrangement of neoplastic tissue The polarization of neoplastic tissue the relationship with stroma,Atypia of tissue architectureR,Intestinal adenoma,Adenocarcinoma,Intestinal adenomaAdenocarcino,病理学英文课件9,Squamous cell carcinoma,Squamous cell carcinoma,Atypia of neoplastic cellsPleomorphism of neoplastic cells1. Variation in size and shape2. Generally larger than normal cells tumor giant cells,Atypia of neoplastic cells, Pleomorphism of nucleus,1. Increased nucleus: The nuclear- to - cytoplasmic ratio may approach 1:1 instead of the normal 1:4 - 6., Pleomorphism of nucleus1. I,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,2. Variation in size, color an, Shape :i) The shape is usually extremely variable, the chromatin is coarsely clumped, Shape :,ii) Increased mitotic figures : Atypical, bizarre mitotic figures producing tripolar, quadripolar, or multipolar spindles.,ii) Increased mitotic figu,病理学英文课件9,Normal structure,Adenocarcinoma,Normal structureAdenocarcinoma, Changes of cytoplasm,1. Cytoplasm: Basophilic nucleoprotein increased2. Abnormal products or secretion: Mucus, glycogen, lipid helpful to determine histogenesis of tumor, Changes of cytopla,Mucoid carcinoma,Mucoid carcinoma,Squamous cell carcinoma,Squamous cell carcinoma,Melanoma of the skin,Melanoma of the skin,病理学英文课件9,Ultrastructural changes (electron microscope),Organelles : signs of histogenesis Neuroendocrine granules neuroendocrine tumorTonofilament and desmosomes squamous cell carcinomaMyofilament and dense body SMC,Ultrastructural changes (elect,Take home questions:,What is atypia? (The definition)What is atypia include? The atypia of tissue architectureThe atypia of neoplasic cellsCell nucleusCytoplasmUltrastructure,Take home questions:What i,Section 3. Growth and spread of tumor,Growth pattern of tumorBiology of tumor growthSpread of neoplasms (Invasion and metastasis)Mechanisms of invasion and metastasisGrading and staging of tumor,Section 3. Growth and spread o,1. The growth of tumor,I. Growth pattern of tumorExpansive growthExophytic growthInfiltrating growth,1. The growth of tumorI. Growt, Growth pattern of tumor,1. Expansive growth:The mode of most benign tumornodularintact capsule,Leiomyoma, Growth pattern of tumor 1. E,(1) Sites: surface 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:,(1) Sites: surface of body, b,Exophytic growth,Exophytic growth,The mode of most malignant tumorabsence of capsule, infiltrate and destroy surrounding tissue,3. Infiltrating growth,The mode of most malignant tu,II. Biology of tumor growth,1. 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 cells(3) Local invasion(4) Distant metastasis,II. Biology of tumor growth1.,3. 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,3. The multiple factors that, Kinetics of tumor cell growth,Doubling time of tumor cellsGrowth fractionTumor cell production and loss, Kinetics of tumor cell growt,Doubling 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 time,Doubling time of tumor cells:,Growth fraction: the proportion of cells within the tumor population 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%,Growth fraction: the proportio,Tumor 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 loss,Tumor cell production and loss,High grow fraction: Clinical course is rapid (lymphoma) susceptibility to chemotherapyLow grow fraction (cell production exceeds cell loss by only about 10%): Grow at a much slower pace (car. of colon) no susceptibility to chemotherapy,High grow fraction:, Tumor angiogenesis,Angiogenesis is a necessary biologic correlate of malignancy: tumors cannot enlarge beyond 1 to 2 mm in diameter or thickness unless they are vascularized.Angiogenesis is requisite not only for continued tumor growth, but also for metastasis., Tumor angiogenesisAngiogene,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 tumor cell,Neovascularization has dual e,How do growing tumors develop a blood supply?, Tumor associated angiogenesis factors produced by tumor cells infiltrated inflammatory cells VEGF, FGF, PDGF,How do growing tumors develop, Tumor induce antiangiogenesis molecules: WP53 induce thrombospondin 1 inhibit formation of BV P53 gene mutation thrombospondin 1BVPlasminogen, collagen, transthyretin proteolytic cleavage angiostatin, endostatin, vasculostatin, potent angiogenesis inhibitors, Tumor induce antiangiogenesi, Tumor progression and heterogeneity,1. Tumor progression Malignant tumor become more aggressive in the process of growth,accelerated growthlocal invasiondistant metastasis, Tumor progression and hetero,2. Tumor heterogeneity,In the process of growth, monoclonal tumor cells generate subclones with different characteristics 3. Mechanism: Mutant additional genes damage,Invasiveness, rate of growthhormonal responsivenesssusceptibility to antineoplastic drugs,2. Tumor heterogeneity In,2. Spread of neoplasms,Local invasion (direct spread)MetastasisLymphatic metastasisHematogeneous metastasisTranscoelomic metastasis (Metastasis in body cavities) (seeding),2. Spread of neoplasmsLocal in,Spread of neoplasms,1. Direct spread Malignant tumor C infiltrate tissue, lymphatic, BV, nervous tissue 2. Metastasis Malignant cells from primary site invade into lymphatics, BVs and body cavities and reach distant site continues growth to form the same type tumor with primary tumor,Spread of neoplasms1. Direct, 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 metastasis:,Left supraclavicular LN, The most common pathway for,Afferent lymphatics,Tumor emboli,Subcapsular sinus,Efferent lymphatics,Retrograde metastasis,Primary tumor,Lymphatic nodule,Afferent lymphaticsTumor embol,Lymphatic metastasis,Lymphatic metastasis,Lymphatic metastasis,Lymphatic metastasis,(2) Hematogeneous metastasis, The favored pathway of sarcoma. Metastatic pathway: Caval blood lung Portal blood liver Pulmonary v(cap) brain, bone, kidney Vertebral vein paravertebral plexus brain ( Prostate, thyroid) Common sites: lung (most), liver, bone,(2) Hematogeneous metastasis, Features of hematogeneous metastatic tumor: multiple, rounded nodules with clear border, scattered in distribution, close to surface of organ.,Choriocarcinoma, Features of hematogeneous, Carcinoma umbilicus Hematogeneous metastatic tumor located surface of the organ forms umbilication because of central hemorrhage and necrosis, Carcinoma umbilicus,(3) Transcoelomic metastasis (Metastasis in body cavities or Seeding) Definition: Malignant tumor cell of an organ in body cavity penetrate into the surface of the organ and break off to seed in the surface of the organs of body cavity and form metastatic tumor.,(3) Transcoelomic metastasis,Transcoelomic metastasis,Colloid carcinoma of stomach,seed in the surface of intestine,Transcoelomic metastasisColl, krukenberg tumor: Gastric carcinoma destroy gastric wall and tumor cell seed in the ovaries to form metastatic tumor Sites peritoneal cavity (most common) pleural, pericardial, subarachnoid, joint space Surgical instruments: rare an artificial mode of dissemination, krukenberg tumor:,The mechanisms of invasion and metastasis,The mechanism of local invasionVascular dissemination and homing of tumor cellsMolecular genetics of metastasis,The mechanisms of invasion an, 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 enzymes induce host cell to elaborate proteases(4) Migration of tumor cells: Mediated by Tumor cell derived motility factors Cleavage products of matrix components, The mechanism of local invas,病理学英文课件9, Vascular dissemination and