病理学与病理生理学：NEOPLASIA

1、柳叶刀：柳叶刀：2013年中国各地区死因调查年中国各地区死因调查1. 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 hyperplasia to form neoplasm Definition and morphology of tumor Neoplastic Non-neoplastic Monoclonality Polyclo

2、nality Abnormal morphology Normal and function Abnormal differentiation Matured differentiationPersistent LimitedHarmful BeneficialMacropathology1. Number and Size : various2. Shape : various3. Color and Consistency: 4. firmness:5. Capsule: benign with intact capsuleNumber and SizeShapeColor and Con

3、sistencyCapsulefirmnessballballnodeinfiltration cauliflowerulcerationCyst formationCystoadenomas (ovary) number is vary Size is vary1. Parenchyma Major component of tumor :neoplastic cell Determine the biologic feature and specificity2. Stroma: Made up of CT and BV support the tumor Growth speed dep

4、end on the stroma blood supply LC infiltration immune reaction to tumor高分化管状腺癌高分化管状腺癌Parenchyma Stroma Atypia: Neoplastic tissue has various extent of differences with its originated normal tissue, both cell morphologically and tissue architecturally. Differentiation: Refer to the extent to which ne

5、oplastic cells resemble comparable its originated normal cells, both morphologically and functionally. Well - differentiation Poorly - differentiation Anaplasia: Lack of differentiation of malignant neoplastic cell, with obviously atypia. Anaplastic tumor: composed of undifferentiated cell. Pleomorp

6、hism: obvious variation in size and shape, obviously atypiaAnaplastic tumorPleomorphism1. Refers to difference between neoplastic tissue and its originated normal tissue on arrangement of neoplastic tissue polarization, organ-like structure, the relationship with stromaIntestinal adenomaAdenocarcino

7、maNormal structureAdenocarcinomaAdenocarcinomaSquamous cell carcnomaAtypia of neoplastic cells(a) Pleomorphism of neoplastic cells1. Variation in size and shape2. Generally larger than normal cells tumor giant cellsAtypia of neoplastic cells1. Increased nucleus: The nuclear- to - cytoplasmic ratio m

8、ay approach 1:1 instead of the normal 1:4-6. 2. Variation in size, color and shape: 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

9、chromatin is coarsely clumped and distributed along the nuclear membrane.ii) Increased mitotic figures : atypical, bizarre mitotic figures sometimes producing tripolar, quadripolar, or multipolar spindles. 1. Cytoplasm: Basophilic nucleoprotein increased2. Abnormal products or secretion: Mucus, glyc

10、ogen , lipid helpful to determine histogenesis of tumorMucoid carcinomaMelanoma of the skin Organelles : signs of histogenesis Neuroendocrine granules neuroendocrine tumorTonofilament and desmosomes squamous cell carcinomaMyofilament and dense body SMCBiology of tumor growth1. Monoclonality: Tumor i

11、s 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.3. The multiple factors that influence t

12、umor growth are considered under three headings:(1) kinetics of tumor cell growth(2) Tumor angiogenesis(3) Tumor progression and heterogeneity 1. Doubling time of tumor cells: In reality, cell cycle time for many tumors equal to or longer than that of corresponding normal cells. So the growth of tum

13、or is not associated with a shortening of cell doubling time.2. 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 continu

14、e to grow cell leave the replicative pool by differentiating and by reversion to Go in rapidly growing tumors approximately 20%3. Tumor cell production and loss : Growth of tumors are determined by the excess of cell production over cell loss. 4. Tumor stem cell The rate of tumor growth depends on :

15、 Growth fraction Degree of imbalance between cell production and cell lossHigh 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 (ca. of colon) no susceptibility to chem

16、otherapy1. Angiogenesis is a necessary biologic correlate of malignancy :tumors cannot enlarge beyond 1 to 2 mm in diameter or thickness unless they are vascularized. 2. Angiogenesis is requisite not only for continued tumor growth, but also for metastasis. 3. Neovascularization has dual effects :(1

17、) Perfusion supplies nutrients and oxygen(2) Newly formed endothelial cell secreting polypeptides such as insulin-like GF, PDGF stimulate the growth of tumor cell 1. Tumor progression: Malignant tumor become more aggressive in the process of growth including accelerated growth; local invasion; dista

18、nt metastasis. In the process of growth, monoclonal tumor cells generate subclones with different characteristics, such as Invasiveness , rate of growth hormonal responsiveness susceptibility to antineoplastic drugs. 3. Mechanism: Mutant additional genes damage(a) Growth pattern of tumor1. Expansive

19、 growth:-The mode of most benign tumorNodular; Intact capsule.(1) Sites: surface of body , body cavities or tract organs.(2) Shape: papillary, polypoid, cauliflower(3) Growth pattern both benign and malignant tumor(also grow by infiltrating)2. Exophytic growth:E Exophytic growth-The mode of most mal

20、ignant tumorabsence of capsule, infiltrate and destroy surrounding tissue 3. Infiltrating growthSpreading of neoplasms1. Direct spread: Malignant tumor Cinfiltrate tissue, lymphatic, BV, N2. Metastasis: Malignant cells from primary site invade into lymphatics, BVs and body cavities and reach remote

21、site continue 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 (1) Lymphatic metastasis:Left supraclavicular LNLymphatic metastasisLymphatic meta

22、stasisLymphatic 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 (Ca. of Prostate/thyroid) Common sites:lung(most),liver,bone Features of metastatic

23、tumor: Clear border, scattered in distribution, multiple , close to surface of organ. Carcinoma umbilicus: Metastatic tumor located surface of the organ form umbilication because of central hemorrhage and necrosisMetastatic tumor in lung(3) Transcoelomic metastasis Definition: Malignant tumor of org

24、an in body cavity penetrate into the surface of the organ, tumor cells drop to seed in the surface of the organs of body cavity and form majority of metastatic tumor.Transcoelomic metastasis Krukenberg tumor: Gastric carcinoma destroy gastric wall and tumor cells seed in the ovaries to form metastat

25、ic tumor. Sites peritoneal cavity (most common) pleural, pericardial, subarachnoid, joint space Surgical instruments : an artificial mode of dissemination (1) Detachment of the tumor cells from each other : Down-regulation of E-cadherin expression(2) Degradation of extracellular matrix: Tumor cell s

26、ecrete proteolytic enzymes induce host cell to elaborate proteases(3) Attachment to matrix components: Integrin(epithelium) binding to laminin(BM)(4) Migration of tumor cells: Mediated by Tumor cell derived motility factors Cleavage products of matrix components Mechanism of local invasionBCVascular

27、 dissemination and homing of tumor cellsTumor cells are destroyed by NKCFormation of platelet-tumor aggregateEnhance the survival and implantabilityTumor embli involve adhesion to EC Egress through the BM (1) Tumor cell express the adhesion molecules whose ligand are expressed on the EC of the targe

28、t 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 . Vascular dissemination 1. No single metastasis gene has been found. 2. The gene that encode E-cadherin, inhibitors of metallop

29、roteinases is considered matastasis suppressor genes. 3. SNAIL and TWIST are transcriptional repressors that promote EMT by down-regulating E-cadherin expression.1. Grading of tumor: According to degree of differentiation atypia and the number of mitoses: Grade : well-differentiated Grade : moderate

30、 Grade : poorly-differentiated Well-differentiatedModerate-differentiatedPoorly-differentiated Based on the size of the primary lesion, infiltritive depth , its extent of spread to LNand distant metastases: TNM staging system T: primary tumor, T1T4 enlarge N: LN involved, N0no involved; N1-N3 M: dis

31、tant metastases, M0 no; M1-M2Benign tumor: less effects Local oppression and obstruction: Relate to site and secondary change Important organs: intestinal, brain Tumor of endocrine glands: systemic symptoms Acidophilic adenoma: gigantism or acromegaly Adenoma of pancreatic islets: fatal hypoglycemia

32、1. Local oppress + obstruction + pain 2. Constitutional symptoms: Fever, weight loss, night sweat3. Cachexia: Refer to the state of progressive loss of weight, anemia, weakness and systemic failure . 4. Ectopic endocrine syndrome: Some non-endocrine tumors elaborate hormones or hormone-like substanc

33、e ( ACTH, PTH, ADH, insulin) give rise to endocrine disorder and show homologous symptoms. Neoplastic product (ectopic hormones) Abnormal immune reaction ( cross immune autoimmune, IC ) Other unclear causes lead to lesions of endocrine, nervous, digestive system and so on Section 5. Difference betwe

34、en benign and malignant tumorDifference between benign and malignant tumor Degree of well poor differentiation unobvious atypia obvious atypiaMitotic figure no or rarely increased no pathologic mitotic pathologic mitoticGrowth speed slow rapidGrowth pattern expansive infiltrative exophytic exophytic

35、 intact capsule no capsule Benign malignantSecondary rare common changes ( hemorrhage, necrosis, ulcer) Metastasis no common Recurrence rarely commonEffects compression compression, obstructionon host obstruction secondary changes, infection cachexia, metastasis, Benign malignantDifference between b

36、enign and malignant tumor Section 6. Nomenclature and classification 1. Benign tumor:(1) Histogenesis + “oma” Fibroma, adenoma, fibroadenoma(2) Cells of origin + morphologic feature Adenoma cystadenoma papillary cystadenoma Non neoplastic “oma”: Granuloma , tuberculoma, hamartoma(1) Carcinoma: Arisi

37、ng in epithelial cell Squamous cell carcinoma, Adenocarcinoma (2) Sarcoma: Arising in mesenchymal tissue Fibrosarcoma, liposarcoma, Leiomyosarcoma, rhabdomyosarcoma(3) Carcinosarcoma: Carcinoma + sarcoma(1) Arising in totipotential cells: Teratoma (benign, malignant):Made up of a variety parenchymal

38、 cell type of more than one germ layer (2) -blastoma: Neuroblastoma, medulloblastoma, (3) Malignant-: Malignant melanoma/meningioma(4) Custom: Leukemia, seminoma(5) Name: Ewings sarcoma, Hodgkins lymphoma(6) cell morphology: Clear cell sarcoma, oat cell carcinoma(7) -omatosis: Neurofibromatosis, lip

39、omatosis, angiomatosis3 . Others:二二. Classification Tissue of origin Benign Malignant一. Epithelial tumorsStratified squamous squamous cell squamous cell or palilloma epidermoid carcinoma Basal cells of skin or adnexa basal cell carcinomaEpithelial lining of Glands or ducts adenoma adenocarcinoma pap

40、illoma papillary carcinoma cystadenoma cystadenocarcinoma pleomorphic adenoma malignant mixed tumor (mixed tumor of salivary origin) of salivary gland originUrinary tract epithelium Transitional cell Transitional cell (transitional) papilloma carcinoma二. Mesenchymal tumorsConnective tissue fibroma f

41、ibrosarcoma lipoma liposarcomaSmooth muscle leiomyoma leiomyosarcomaStriated muscle rhabdomyoma rhabdomyosarcomaBlood vessels hemangioma angiosarcomaLymph vessels lymphangioma lymphangiosarcoma osteoma osteogenic sarcoma chondroma chondrosarcomaSynovium synovil sarcomaMesothelium mesothelioma malign

42、ant mesotheliomaTissue of origin Benign MalignantLymphoid tissue malignant lymphomasHematopoietic cells leukemiasBrain coverings meningioma invasive meningiomaMelenin cell nevus malignant melanomaPlacental epithelium Hydatidiform mole choriocarcinoma(trophoblast) Testicular epithelium seminoma(germ

43、cells) embryonalcarcinomaTotipotential cells in gonads mature teratoma immature teratoma or in embryonic rests dermoid cystteratocarcinomaTissue of origin Benign MalignantSection 7. Introduction of common tumorsBenign epithelial tumor 1. Papilloma (1) Origin: squamous, transitional cell (2) Site: sk

44、in, vulva, urinary tract (3) Gross: papillary mass(exophytic) with pedicel (4) LM papillary epithelium connective tissue core Canceration: papilloma of auricle tract, penisFinger-like structurePapilloma of skin 2. Adenoma(1) Origin epithelium of glands or ducts secretive epithelium (2) Site: thyroid

45、 gland,ovary,breast, intestines(3) Gross: polypus, papillary, nodular(4) LM: glands various in size, and abnormity(1)Cystadenoma Commonly in ovary/thyroid gland/pancreas Serous papillary cystadenoma: liable to cancerationSerous papillary cystadenoma Mucinous cystadenomaMucinous cystadenoma of ovary(

46、2) Fibroadenoma:commonly in breast(3) Pleomorphic adenoma: Origin: glandular epithelial cells and myoepithelial cells Sites: salivary gland, most commonly in parotid Lesion epithelial tissue mucoid tissue cartilage-like tissue Character liable to recurrence minority:canceriationPleomorphic adenoma o

47、f parotid(4) Polypous adenoma Site: commonly in rectum , colon Character: multiple ( liable to canceration)Malignant epithelial tumor 1. Squamous cell carcinoma(1) Sites skin, oral cavity , esophagus, larynx , cervix of uterus , vulva(2) Gross:cauliflower (3) LM: Well - differentiated Keratin pearl

48、, intercullular bridgeSquamous cell carcinoma of skin2. Basal cell carcinoma(1)Sites: commonly in the face of old man, such as eyelid , nosewing (2) Gross: ulcer, growth slowly(3) LM: cancerous cells like basal cells cancerous nests(4) Character less metastasis sensitivity to radiotherapyBasal cell

49、carcinoma3. Transitional cell carcinoma (1) Sites: bladder , ureter , renal pelvis(2) Lesion: papillary 4. Adenocarcinoma Origin: Gland , duct or secretive epithelium Types Well-differentiated Tuburlar Papillary Poorly- differentiated Solid Mucoid(1) Tuburlar adenocarcinoma Sites: gastrointestinal t

50、ract , thyroid gland , gallbladder, uterus body LM: Arranged in the form of glandsAdenocarcinoma of intestinesTubular adenocarcinoma of intestinePoorly differentiated adenocarcinoma Sites: Thyroid gland , ovary Lesion : papillary structure 不正常的 Sites Breast(common) Thyroid gland , stomach Lesion: Ar

51、ranged in solid nest or cord (4) Mucoid (colloid) carcinoma: Sites:Stomach, large intestine , Lesion: signet-ring cell or floated in mucus lake Mucoid carcinomasignet-ring cell carcinoma1. Precancerous lesions(1) Concept: certain benign lesions possess the possibility of cancerization , which progre

52、ss to cancinoma with duration.(2) Classification Heredity Acquired Precancerous lesions, dysplasia and carcinoma in situ Leukoplakia :oral cavity,vulva,cervix,penis Chronic cervicitis and cervical erosion Proliferative fibrocystic change of the breast Polypous adenoma of colon and rectum Chronic atr

53、ophic gastritis and gastric ulcer Chronic ulcerative colitis Chronic skin ulcer Cirrhosis of the liver :HBVPolypous adenoma(1) Concept: The morphological changes of precancerous lesions, possess a certain atypia of proliferative epithlia, manifested by a loss of normal orientation and cell pleomorph

54、ism and enlarged, deeply stained nulei, increased mitotic figure.(2) Commonly arises in squamous epithelium, also in gland epithelium(3) Intraepithelial Neoplasia, INNormalCIN CIN CIN 3. Carcinoma in situ: A focus of severe dysplasia totally involved to the mucosa or epidermis without penetration of

55、 the basement membrane. 1. Fibroma(1) Origin: connective tissue (2) Sites: Subcutis of extremities and trunk(3) Gross: intact capsule, nodular, gray, pliable and tough (4) LM: well-differentiated tumor cells are spindle shape and arrange in a crisscross pattern Mesenchymal tumorsBenign mesenchymal t

56、umorsFibroma 2. Lipoma： (1) Origin: adipose tissue (2) Sites: Subcutais of extremities , trunkLipoma3. Hemangioma Sites: skin of head in children , liver Gross: infiltrative growth erythema or nodular LM capillary hemangioma cavernous hemangioma mixed hemangioma Capillary hemangiomaHemangioma of ven

57、trical wallCavernous hemangioma of liver 4. Leiomyoma(1) Sites: uterus, gastrointestinal tract(2) Gross: nodular, intact capsule, gray, firm(3) LM Fascicles of spindle cells arranging in a crisscross pattern or in fences. Blunt-ended elongated nucleiLeiomyoma of uterus Carcinoma Sarcoma Origin epith

58、elium mesenchymalIncidence common, 40 yearsless, young soft, gray-red, wet, fleshy Grossbrittle, gray-white, dry Histologycell nestDifference between carcinoma and sarcoma diffuse arrangmentMalignant mesenchymal tumorsDifference between carcinoma and sarcoma Carcinoma SarcomaReticulum fiberabscence(

59、intercellular)presence(intercellular)hematogenousMetastasislymphaticEpithelial marker CK(+)ImmunohistochemistryMesenchymal markervimentine (+)Reticulum fiberSarcomaCarcinoma 1. Fibrosarcoma (1) Origin: connective tissue (fibroblast) (2) Sites : subcutis of extremities (3) Gross: soft, fish-flesh, wi

60、th hemorrhage and necrosis (4) LM: spindle shape arranged in herringbone pattern FibrosarcomaFibrosarcoma2. Liposarcoma(1) Origin: original mesenchymal tissue (2) Sites retroperitoneum deep soft tissue of extremities(3) Gross: nodular, lobular, yellow and red (4) LM poorly-differentiated, fatty diff