病理学课件：绪论

1、Chapter IIntroduction to Pathology1Definition of pathologyDevelopment of pathologyObjective of researchResearch methodsLearning of pathologyDefinition of Pathology Pathology Literally：pathos（suffering）logos（study） To study diseases by scientific methods. Disease may be defined as an abnormal alterat

2、ion of structure or function in any part of the body.Pathology: a bridge connecting basic science to clinic Etiology: Cause of disease. Knowledge of etiology remains the backbone: Pathogenesis: Mechanisms of development of disease. Understanding the nature of diseases Morphology: The structural alte

3、rations induced in cell and tissues. Disease diagnosis Functional consequences: symptoms, singes Functional consequences of the morphologic changes as observed clinically. Treatment of diseases.Pathology: still golden standard in diagnosis of diseasePathology A bridge between: Evidence and practice

4、Advances and applicability Benchside and bedside “Guiding the Surgeons Hand” (Juan Rosai)Doctors doctor患者患者临床医生临床医生胸外科医师胸外科医师内镜医师内镜医师收集组织标本收集组织标本病理科医生病理科医生疾病诊断疾病诊断实验操作及结果分析实验操作及结果分析实验室人员实验室人员报告结果给临床医生报告结果给临床医生-肿瘤科医生肿瘤科医生-放疗科医生放疗科医生-呼吸科医生呼吸科医生肺癌目前是全世界癌症死因的第一名肺癌目前是全世界癌症死因的第一名70%肺癌发现确诊时已属晚期肺癌发现确诊时已属晚期肺

5、癌发生于支气管粘膜上皮亦称支气管肺癌肺癌发生于支气管粘膜上皮亦称支气管肺癌基本类型基本类型 小细胞肺癌小细胞肺癌SCLC非小细胞肺癌（非小细胞肺癌（NSCLC)，约，约85%腺癌腺癌NOS腺腺鳞鳞癌癌鳞癌鳞癌大细胞癌大细胞癌肺癌肺癌Genetic alterations in lung cancerAdenocarcinomaSquamous-cell carcinomaLarge cell carcinoma组织分型 Current Standard of NSCLC CareNon-squamousNSCLC 分型现状SquamousEGFR WTEGFR MuSquamousEGFR M

6、uKRAS MuALK+Other non-squamous WTSquamous2012NCCN2014NCCNEGFR MuALK+KRAS MuOther non-squamous WTSquamousROS1+2010NCCNNCCN Guidelines, NSCLC, Version 4. 2014Horn L, et al. Clin Oncol. 2009驱动基因分型 早期NSCLC肿瘤驱动基因肿瘤驱动基因-分子类型分子类型Development of PathologyOrgan pathologyautopsy and macropathologic analysis on

7、 organs 1616thth - 18 - 18thth century century P r a c t i c e d b y b e d s i d e P r a c t i c e d b y b e d s i d e clinicians working part-timeclinicians working part-time For better understand the For better understand the b a s i s o f t h e p a t i e n tb a s i s o f t h e p a t i e n t s s s

8、ymptoms and signs, and the symptoms and signs, and the cause of their deathscause of their deaths The most famous early gross pathologist was Giovanni Morgagni (1682-1771). modern autopsy process derives from the anatomists of the Renaissance. Giovanni Morgagni (16821771), celebrated as the father o

9、f anatomical pathology Histopathology1919thth century: century: f following the invention ollowing the invention of the compound microscopeof the compound microscope Rudolf Virchow （1821-1902, father of modern pathology）& his many enlightened pupils : Histopathology: a hallmark of modern patholo

10、gy A student of Virchows, Julius Cohnheim(1839-1884): inflammation, frozen section The great 19th-century medical researcher Rudolf Virchow, in r e s p o n s e t o a l a c k o f standardization of autopsy procedures, established and published specific autopsy protocols Modern pathology 20th century

11、Formation of modern pathology Surgeons examining specimens for their patients, using microscope Academic researchModern pathologyModern pathology Organ pathology: Autopsy Macromorphology Histopathology: light microscope: HE staining Histochemical pathology: chemical staining for lipid, protein, DNA,

12、 organelles Ultrastructural pathology: electron microscope Immunohistochemical pathology: antigen-antibody reaction: protein staining Molecular pathology: DNA, RNA analysis: hybridization, PCR, microarray, flowcytometry, etcMolecular pathologyModern pathologyAcademic pathology: Department of patholo

13、gy in medical school academic researchClinical pathology: Department of pathology in hospital Surgical pathologist in diagnosis Autopsy Resection Biopsy Cytology Molecules: proteins, DNA, RNA, etc Experimental studies: In vitro: tissue culture organ culture cell culture In vivo: Experimental animals

14、Analytic objectives Macroscopic observation Microscopic observation (H&E) Electron Microscope (EM) Immunohistochemistry (IHC) Molecular analysis: In Situ Hybridization PCR Flow Cytometry Microarray Sequencing: NGSPathology methods21Autopsy The Anatomy Lesson of Dr. Nicolaes Tulp Surgical resecti

15、onBiopsyn Open resection:Open resection:n Needle biopsy:Needle biopsy:24LCNB: 14-gaugeVAB: 8-gaugeneedle 11-gauge needle vacuum assisted biopsy probeFrozen section25Cervical Pap SmearCervical Pap Smear26CytologyNormalLSILHSILcarcinoma27UltrapathologyElectron MicroscopyImmunohistochemistry28For Diagn

16、osis+-For Treatment- HER-2/neu in breast carcinomaImmunohistochemistry30In-situ HybridizationEBER in Nasopharyngeal carcinoma11111818MALT Lymphoma t(11;18): BCL-10 11q22 (Spectrum Green): YAC 906c5 & 921f3 18q22 (Spectrum Red): YAC 949b6FISH原理原理31Fluorescence in situ hybridization analysis for H

17、ER2/neu in breast carcinomaAnalysis of IgH PCR Products33polyclonalmonoclonal 1 2 3 4 5 100bp10% polyacrylamide gelGene ScanFr3-JHFr3-JHFlow cytometry34n DNA Ploidyn Growth Fragmentn Surface Receptorsn Immunophenotyping of Lymphohematopoitic Cellsn Sorting of Viable CellsMicroarrays35cDNA Microarray

18、 - Diffuse large B cell lymphoma NEJM 2002;346:1937-47高通量测序类型高通量测序类型 Nude mice Knock-out mice，Transgene mice37Experimental studiesThe flowchart of computerized image analysis for prognosis based on H&E histopathology images The system (a) acquires a digitized image via microscope-mounted digital

19、 camera or whole slide image scanner, (b1) preprocesses the image via color normalized and automatically detects the region of interest (ROI), (b2) automatically detects and segments the objects, (b3) extracts pixel-level, object-level, and spatial-arrangement-level features based on the segmentatio

20、n results, and (c) builds the computer-aided prognosis (CAP) system on top of these features. DR: dimensionality reduction.Tumor diagnosisOrigin:Biologic behavior: benign or malignantSubtypes:Prognosis:Treatment: molecular targetingA 12-year-old boy presented with a short history of pain in his thig

21、hSolitary Bone Cyst (SBC)The x-ray picture of GCT usually shows a large, eccentric, oval, radioluscent destructive lesion centered in the epiphysis, producing cortical erosion and thinning, and expanding the bone contours without a border of periosteal reactive new-bone formation and sclerosis.Giant

22、 cell tumor (GCT)composed of plump, spindly, and oval stromal cells and multinucleated tumor giant cellsOsteosarcomaNeuroendocrine tumorNeuroendocrine granules in cytoplasm of tumor cellBreast carcinomaMorphology in carcinogenesisBronchial: from normal to squamous carcinoma正常上皮正常上皮轻度异型轻度异型Adenoepithelial cell preneoplasia and genetic alterationsK-rasp53LOH: 3p, 9p, 17phTERTLung nodule Histologic progression of atypic