病理學(xué)：Chapter 5 Tumor,Neoplasm

1、Chapter 5 Tumor, Neoplasm pathologyTumor (腫瘤): benign and malignantCancer（癌）: malignant tumor（clinical)Carcinoma（癌）: malignant tumor of epithelia Cancer Incidence-common disease1. There are about 1,800,000 （180萬(wàn)）new cancer cases in China.2. There are about 1,300,000 （130萬(wàn)） new cancer cases in Americ

2、a. 3. There are about 9,000,000 （900萬(wàn)） new cancer cases in all over the worldTumor-?diseasemalignant tumors- severely damaged human health1. The death of malignant tumors ： About 7,000,000 (700萬(wàn)) in the world About 1,000,000 (100萬(wàn)) in the ChinaCancer deaths accounting for all deaths: In western coun

3、tries: second cause. In china: first (in city) or third cause (in countryside).The incidence & death rate of cancer in 1996 Respiratory tract: lung cancer nasopharyngeal cancer Gastrointestinal tract: esophageal cancer gastric cancer, liver cancer, large intestine cancer. Female genital: breast canc

4、er, ovary cancer Lymphoid tissue: lymphomas Hematologic system: leukemia The ten commonest malignant tumors in China:More in persons of maturity age Difficulty Many related factors Unknown pathogenesis Lack of effective treatment and prevention Section 1. Conception of Tumor（腫瘤的概念）Abnormal prolifera

5、tion of cells An abnormal mass 一.Definition of tumor or neoplasm:(neoplastic proliferation）Special pathological hyperplasia Environmental oncogenic agents genetic factors Local tissue cells Abnormal proliferation Neoplasm (most of them are mass tumors) 1. Change in quality: (morphology, function, me

6、tabolism, biological behavior) Anaplasia（間變): also called un(de)differentiation. This means the different characters on growth morphology, function, metabolism and biological behaviors, between the tumor cells and normal cell.Features of abnormality in cellsAtypia (異型增生): formerly known as Dysplasia

7、 (不典型增生): It has some properties of anaplasia, but is light, reversible, and few become malignantdivided into three degrees (mild, moderate and severe).severe ones should be treated as carcinoma in situ.Dysplasia-precancerous lesion, Anaplasia（間變): 2.Autonomy（自律性） uncontrol, no limitation, incoordin

8、ate Different from physiological proliferation, general pathological proliferation,regeneration（再生）, metaplasia（化生）3.“Heredity” of tumor cells（遺傳性） properties of anaplasiaprogeny cells (characteristics of generations)4. “Heterogeneity” of tumor cells（異質(zhì)性）在腫瘤性增生中，間變是腫瘤存在的根本，自律性是腫瘤生長(zhǎng)的動(dòng)力，遺傳性是瘤體形成的基礎(chǔ)，異質(zhì)

9、性給腫瘤發(fā)展以機(jī)會(huì)。在腫瘤性增生中，間變是腫瘤存在的根本，自律性是腫瘤生長(zhǎng)的動(dòng)力，遺傳性是瘤體形成的基礎(chǔ)，異質(zhì)性給腫瘤發(fā)展以機(jī)會(huì)。生長(zhǎng)信號(hào)的自給自足，使腫瘤細(xì)胞生長(zhǎng)具有自律性和不可調(diào)節(jié)性對(duì)控制非腫瘤性增生的增生抑制信號(hào)不敏感細(xì)胞對(duì)凋亡的逃避腫瘤細(xì)胞獲得無(wú)限生長(zhǎng)的潛能（永生化）產(chǎn)生腫瘤血管以維持腫瘤細(xì)胞生長(zhǎng)侵襲和轉(zhuǎn)移能力的獲得-“Heterogeneity”重組特殊的代謝途徑獲得逃避免疫攻擊的能力“Heterogeneity”neoplastic hyperplasia has the following characteristics:Section 3. Basic pathological

10、 changes of Tumor（腫瘤的基本病變） 1. Appearance (Contour) - General morphology (Grossly) Shape: various According to tumor itself, location, mode of growth, tissue, etc一. Morphology and Structure of Tumor: Polypoid Papillomatous Nodular multicystic Multi-nodular cauliflower-like Ulcerative Invasive tumor圖

11、腫瘤的外形和生長(zhǎng)方式模式圖息肉狀 乳頭狀 結(jié)節(jié)狀 多囊狀多結(jié)節(jié)型 菜花型 潰瘍型 浸潤(rùn)型 Color: Determined by the characteristic of tumor, blood supply, interstitial tissue (with or without) grayish white: benign tumors or carcinoma grayish red: sarcoma yellows: lipoma red: hemangioma black: melanoma Size: according to behavior, time, locatio

12、n, effect on host, medical care (0.8mm, 30cm)Number: In most cases, tumor is single one. single monoclonal “multiple tumors”two kind 1. Tumors are from different tissue with different or same characteristics in same time. 2. Tumors are from same tissue with same characteritics, in same or different

13、time. lipoma, neurofibroma, myelomaHardness:firm: more stroma, calcification or carcinomasoft: less stroma, necrosis obviously; or sarcoma纖維瘤病Parenchyma-tumor cells Main component: just one kind in most tumor (2) Determine tumors character, growth partner, shape, structure, and nomenclature (命名).(3)

14、 Differentiation refers to the extent to which tumor cells resemble their origin normal cells. Well (poor, lack) differentiation2. Basic tumor tissue structure- two basic componentsStroma: connective tissue (fiber, matrix), blood vessel, nerve, immune cells (lymphocytes)(1) Connective tissue, blood

15、vessel: support and nutrition tumor parenchyma(2) Immune cells: anti tumor immune reaction(3) Myofibrils (肌原纖維）: limit tumor spread 2. Basic tumor tissue structure- two basic components *Different tumors have their own specific parenchyma, but their stroma are almost the same. 1.Classification organ

16、tumor of stomachtissuefibroma, lipomabehaviortumor, carcinoma (or sarcoma)For example: left breast invasive adenocarcinoma二. Classification and Nomenclature 2.Nomenclature - according to Parenchyma (tumor cell) All tumors (benign and malignant) have two basic components. 2. Nomenclature Benign Chine

17、se：來(lái)源的組織名+瘤； English： Name of arised tissue + “oma” adeno-(aden-) adenoma(腺瘤), lipo-, lipoma（脂肪瘤） More detail: cyst-, papillary- except: aneurysm (動(dòng)脈瘤), atheroma (粥樣瘤）, hematoma (血腫), granuloma (肉芽腫)Malignant tumor = cancer -carcinoma(癌):malignant tumors arise in epithelial tissues such as: squamous

18、 cell carcinoma, adenocarcinoma, basal cell carcinoma -sarcoma (肉瘤): malignant tumors arised in mesenchymal tissues lymphohematopoietic-no non-lymphohematopoietic such as: fibro- -fibrosarcoma (纖維肉瘤) lipo- leiomyo- chondro- osteo-Difference between Carcinoma & Sarcoma Carcinoma SarcomaTissue epithel

19、ia mesenthymeAge 45 youngerHistology nest, layer more cells, rounded by interstitial Growthinfiltration, like crab feet on cut surfacemargination, but infiltration earlier under microscopeMetastasis lymphatic vessels blood vessels Special kinds carcinosarcoma (癌肉瘤) Both epithelial and mesenchymal ti

20、ssues are malignant. blastoma（母細(xì)胞瘤，部分為成母-）：Tumors arised in fetal tissues. 間葉良性; 上皮和神經(jīng) 惡性 neuro-, medullo-, nephro-, hepato-, leiomyo-, osteo-, chondro-, etc. customary leukemia, Hodgkins disease, Ewings tumor, melanoma, etc. “+malignant” - germ layer unkown: such as: menigioma（腦膜瘤）, malignant menig

21、ioma (惡性腦膜瘤） mesothelioma (間皮瘤) - multi germ layers: Tumors contain more than one germ-cell layer. such as: teratoma （畸胎瘤）, malignant teratoma (惡性畸胎瘤） - single germ layer: Tumors contain more than one kind of elements, but all the elements arise in a single layer such as: polymorphism-mixed tumor（混合

22、瘤） malignant mixed tumor（惡性混合瘤）Special kindsPolymorphic adenoma (mixed tumor)teratoma多形性腺瘤 Grading: according to differentiation and mitosis Broders (1922): squamous cell carcinoma （75%）, , , Stout (1975-): well differentiation medium differentiation undifferentiation三. Grading and StagingStaging Th

23、e extent of tumor invasion and metastasesTwo methods of staging are currently in use: 1. TNM system (T, primary tumor; N, regional lymph node involvement; M, metastasis) by UICC 國(guó)際抗癌聯(lián)盟2. AJC system ： by American Cancer Joint Committee (美國(guó)癌腫分期聯(lián)合委員會(huì)) Staging according to extent and spread UICCTNM seri

24、esT N M 1- 4 0-3 0-1AJCS 0 in situ in organ out of organ invasion neighbour organ metastasis胃活檢是低分化癌，該病人的腫瘤分期是晚期癌這話對(duì)嗎？Section 2. Benign and Malignant tumors(How to distinguish benign and malignant tumors) according to harmfulness Benign borderline malignant related to treatment and prognosisDifferen

25、tiation（分化）: Parenchyma-tumor cells Benign: highly differentiated; Malignant: poorly differentiated. “Tumor is the disturbance of cell differentiation.”2. Mode of growth Benign: Expansive or periphery have envelope. marginated, capsulated, effective treatment Malignant:Infiltrative or periphery have

26、 no envelope. after radical operation need chemical and radiation treatment added 3. Speed of growth Benign: Slow, growth stopped, degeneration, might change to malignant one Malignant: Fast, necrosis, bleeding 4. Mitosis（核分裂） Benign: few, normal chrysanthemum (菊花）, equatorial（赤道） Malignant: more, a

27、bnormal multipolar, unsymmetrical（不對(duì)稱）, abortive（流產(chǎn)的）“菊花”狀“赤道板”狀Normal mitosisAnormal mitosisnon- symmetry, tripolar, quadripolar, multipolar spindles and abortion types pathologic mitoses.Normal mitosisAnormal mitosis5. Spread of tumors Invasion (侵襲), infiltration (浸潤(rùn)), metastasis (轉(zhuǎn)移) Metastasis：I

28、ts an important basis for identifying benign and malignant tumors Detachment TransportationFormation Primary tumor, Secondary (Metastatic) tumor 6. Effects on host B.&M. tumors: pressure, obstruction, functional, psychological B. tumors: hormone M. tumors: bleeding, pain, fever, infection, metastasi

29、s, cachexia（惡病質(zhì)）, paraneoplasm syndrome（腫瘤伴隨綜合征。15%晚期-異位激素或生物活性物質(zhì)分泌內(nèi)分泌癥狀和其他), spread to distant sites to cause death. 7. Result of treatment and prognosis B. tumors: no recurrence after resection, can be cured M. tumors: might be recurrent after resection radical operation needed, early-good, but Co

30、mparisons between benign and malignant tumors Benign Malignant DifferentiationWellPoor or lackMitoses Few， no pathologic mitosesAlways, have pathologic mitosesGrowth rateSlow Rapid Secondary changesLess bleeding and necrosisCommon in bleeding and necrosisComparisons between benign and malignant tumo

31、rs BenignMalignantGrowth patternExpansive or periphery (exterio) have envelopeInvasive or periphery (exterio) no envelopMetastasis No Often Recurrence Rare Always Affection Mainly local oppress and obstructionGreat, destruction, bleeding, infection, pain, cachexia Relativity of B. & M. tumors: heman

32、gioma, basal cell carcinoma, tumor in brain, mesothelioma in heart Malignant change of B. tumors: adenoma of colon Reverse of malignant tumors: neuroblastoma, trophoblastoma (絨癌) Borderline tumors: Papilloma of bladder Benign morphology and malignant behavior: polymorphic adenoma of salivary gland M

33、alignant tumor and benign behavior: juvenile melanoma in adultsNoteSection 4. Biological Characteristics of Tumor1. MorphologyDetecting HE stained section in light microscope. Benign tumor: cell differentiation Malignant tumor: bizzare (6) a. pleomorphism: marked variation in size and shape. b. lose

34、 normal polarity. c. the nuclear-cytoplasmic ratio may approach 1:1 (1:5 1:1) d. nuclei are extremely hyperchromatic and large. e. mitoses are often numerous and distinctly atypical f. with a basophilic (嗜堿染色的) cytoplasm.一. Biological Characteristics of Tumor CellsBizzare cellAtypical mitosisspecial

35、 kinds: small cell carcinoma, clear cell carcinoma, giant cell carcinoma EM: No specific finding, but can help to determine the tumor deriving. Less differentiation, simpler organelle Differential diagnosis: desmosome (橋粒) tonofilaments (張力絲) microvilli (微絨毛) granule (顆粒) myofibrils (肌原纖維)By electro

36、n microscopy, features of a carcinoma can be seen. This adenocarcinoma demonstrates several features typical of a neoplasm of epithelial origin, including the junctional complex (tight junction at the asterisk and the desmosomes at crosses). The mucin granule (M) and lumenal microvilli at the upper

37、right are also typical for an adenocarcinoma.Features of a carcinoma are seen in this electron micrograph. This squamous cell carcinoma demonstrates many desmosomes, along with cytoplasmic tonofilaments streaming to the left. Chromosome Benign tumor: haploid, diploid, 23 46 Malignant tumor: multiplo

38、id, aneuploid（非整倍體） 69, 92 41, 96 broken, lost, translocation, ring formation, reformation 22 q 9q Philadelphia chromosome CGL (90%慢粒) （ 費(fèi)城染色體，Ph小體） 8 q 14q 90%Burkitt淋巴瘤 8 q 21q AGL (急粒)Flow Cytometry. Red 8q24 C-myc Cyan - Centromere 8 Green - Centromere 14FISH染色體片段移位1959年Nowell P在美國(guó)費(fèi)城研究慢性粒細(xì)胞白血病(C

39、ML)時(shí)發(fā)現(xiàn)了Ph染色體。這是染色體異常與腫瘤關(guān)系的第一個(gè)例證。Red Chr. 9 Green Chr. 22多色FISHM-FISH技術(shù)熒光原位雜交急性髓細(xì)胞白血病(AML)病例，患兒的主要染色體易位為t(10;11).這用傳統(tǒng)的細(xì)胞生成的方法是不能覺(jué)察的.此種易位可用于特異性診斷AML ,預(yù)后較差。 淋巴瘤細(xì)胞核型分析結(jié)果不同顏色代表著不同號(hào)數(shù)的染色體，圖中有些染色體出現(xiàn)了不只一種顏色，箭號(hào)標(biāo)示處為發(fā)生染色體易位之位置 Histochemistry DNA, RNA, fat, bilirubin, r-GT, DOPA reaction Immunohistochemistry, IS

40、H AFP(甲胎蛋白) CK, Des, Vim, LN, FN, collagen Antigen of virusHBV, HCV, HPV, Oncogene, tumor suppressor gene and their protein productsHere is an example of c-erb-B2 positivity in a breast carcinoma. 名稱： 赫賽汀 通用名： 注射用曲妥珠單抗 英文名： Trastuzumab This is an example of bcl-2 positivity in a lymphoma. 2. Physiol

41、ogy Secretion & function insulin（胰島素）, bilirubin（膽紅素）, myofibril abnormal substancesBence-Jones protein（多發(fā)性骨髓瘤） ectopic hormones (ACTH, ADH, PTH) Lost contact inhibition (接觸抑制) Tumor angiogenesis (血管形成) Signal transduction Tumor cells cultured in vitro Transplantation on immunodeficiency animals3. B

42、iochemistry In tumor cells, transportation of carbohydrate and polypeptide increase, and normal connection of cells loss. Cell membrane anion , Ca2+ viscosity of cells （粘性）. Crabtree effect instead of Pasteur effect Crabtree effect: 在有氧條件下的糖酵解. Improvement of synthetic metabolism, RNA DNA. Enzyme no

43、 special enzymes for diagnosis, more synthesize enzymes associated enzymes for diagnosis AKP, ACP( 酸和堿性磷酸酶)（如骨肉瘤和肝細(xì)胞癌中的AKP等）。Human tumor antigens: 以前：TSA (腫瘤特異性抗原）, TAA (腫瘤相關(guān)抗原）；現(xiàn)結(jié)構(gòu)和來(lái)源： 1. Antigens resulting from mutational change in proteins. (Such as: mutated p53) 2. Over-expressed oncogenes, HER2

44、/neu . 3. Some viral antigens. (E6, E7 proteins in HPV) 4. Oncofetal antigens（胚胎蛋白抗原）: alpha-fetoprotein（甲胎蛋白）, carcinoembryonic antigen (CEA )注：甲胎蛋白：90%肝癌升高，如ng/ml（非常高幾乎一定是癌） 5. Tissue specific antigens（分化抗原）: PSA（前列腺特異抗原）4. Immunology: 腫瘤免疫主要為細(xì)胞免疫Antitumor Mechanisms: 1. Cytotoxic T lymphocytes: 2

45、. NK cells: inducing Non-MHC restricted cytotoxicity. 3. Macrophages: inducing some selective cytotoxicity4. Immunology: 腫瘤免疫主要為細(xì)胞免疫 Spread of tumors ： invasion（侵襲）metastasis（轉(zhuǎn)移） the characteristics of malignant solid tumors 二.Spread of Tumors: 1. Invasion（侵襲） of （malignant） tumor cells The ability

46、of tumor cells to infiltrate the around tissues (interstitial tissue, lymph-vessel, blood vessel). 是腫瘤轉(zhuǎn)移的前奏 a. ill-defined and non-encapsuled b. The particular growth pattern of malignant tumors c. Be surgically enucleated difficultly infiltratingInvasive growth patternThe steps and mechanism of inv

47、asioni. Cancerous cells attaching basement membrane Cancerous cells have more receptors of lamina and fibronectin (纖維連接蛋白) ii. Local proteolysis (蛋白水解) iii. Locomotion 移動(dòng)Tumor cells detach (loosening of intercellular junctions)Attach to the basement membraneDegradation of the basement membraneTumor

48、cell migration follow 自身的運(yùn)動(dòng)因子，阿米巴楊運(yùn)動(dòng). Metastasis (轉(zhuǎn)移)： Definition: metastasis connotes the development of secondary implants discontinuous with the primary tumor, possibly in remote tissue. Include Three steps: 1. detachment（脫離）: Tumor cells invasion into the local lymph vessel, blood vessel , or ot

49、her space. 2. transportation（轉(zhuǎn)運(yùn)）: Be carried to other place through the space. 3. formation（生成）: Grow the same kind tumor in the remote place as that in the original place.Local biochemical circumstances thyroid, pancreas, cartilage軟骨（抗侵襲因子和內(nèi)皮細(xì)胞生長(zhǎng)抑制因子）2. Tissue structure and function spleen, striate

50、d muscle3. Immunity of host, immune factors in local place, NK cellsInfluence of local circumstances to tumor metastasis Influence of tumor cell to tumor metastasis1. Tumor cells surface, mobility, viscosity, receptors 2. High metastatic cell lines 3. Genes and other factors: ras, c-erb B2, nm 23, W

51、DNM2, TIMP, adhesive molecules, MMP4. Extracellular matrix (ECM,細(xì)胞外基質(zhì)） “種子和土壤學(xué)說(shuō)”Lymphatic metastasis : is the typical of carcinomas. Especially for the early stage metastasis. Virchows Lymph nodes (左鎖骨上淋巴結(jié))晚期胃癌三. Three Pathways of Metastasis*晚期肺癌右鎖骨上淋巴結(jié)Lymphatic metastasis Lymphatic metastasisHemato

52、genous metastasis: All forms of cancer may disseminate through either or both pathways. metastatic tumormultiple, ball like, margin of organ, demarcated, umbilicated（類似肚臍樣）腸道原發(fā)瘤門(mén)脈中的瘤細(xì)胞栓子肝轉(zhuǎn)移瘤胃腸道腫瘤經(jīng)門(mén)脈系統(tǒng)轉(zhuǎn)移至肝Hematogenous metastasis: Blood metastasisHematogenous metastasis: a. This pathway is typical of

53、sarcoma, but is also used by carcinoma in advanced stage b. Process: tumor cells small blood vessels tumor emboli distant parts adheres to the endothelium of the vessel invasive the wall of the vessel proliferate in the adjacent tissue establish a new metastatic tumor.Hematogenous metastasis: c. liv

54、er, lung？Some cancers have preferential sites for metastases. lung cancer frequently metastasize to the brain, bones, and adrenal glands. Prostate cancer frequently metastasize to the bones.Seeding metastasis（種植性轉(zhuǎn)移） a. Tumor cells seed the surface of body cavitiesb. Most often involved is the perito

55、neal cavityc. But also may affected pleural, pericardial, subarachnoid, and joint space.轉(zhuǎn)移到漿膜腔后果：bloody, mucoid，adhesion轉(zhuǎn)移易到處：costophrenic（肋隔角）, rectocystic（直腸膀胱陷窩）, rectouterus （膀胱子宮陷窩） spaces Seeding metastasis（種植性轉(zhuǎn)移） Krkenbergs tumor（克氏瘤） precancerous lesion (pp93)and carcinoma in situ(pp86)Preca

56、ncerous lesion（癌前病變）：a kind of benign lesion that can develop to malignant lesion, but it can also be reversed to normal cell after the cessation of the stimuli which evoked the change.2. Carcinoma in situ (原位癌）: carcinoma limited in epidermis or mucosa, and has not penetrate basement membrane. i. e

57、. Stage = 0, non invasion carcinoma well prognosis after resectionDysplasiaIntraepithelial neoplasm -high grade: dysplasiaIII -low grade: dysplasia I and IICarcinoma in situInfiltrating carcinomaThe common precancerous lesion1. Fibrocystic adenosis (纖維囊性乳腺病): with dysplasia2. Familial adenomatous po

58、lyposis of the colon (家族性結(jié)腸腺瘤性息肉病)3. Leukoplakia (粘膜白斑)4. Chronic ulcer (慢性潰瘍)5. Dysplasia 6. Chronic atrophic gastritis (慢性萎縮性胃炎)7. Chronic cholecystitis and chelolithiasis (慢性膽囊炎膽石癥)8. Chronic cervicitis (慢性宮頸炎)-HPV9. Cirrhosis (結(jié)節(jié)性肝硬化)10. Cryptorchidism (未降睪丸)Section 5. Diagnosis of TumorsFinal D

59、iagnosis!-bone tumor* Authority and importance of pathological diagnosis checking diagnosis defining tissue, character, expanding determining treatment-radiation, chemical understanding recurrence and estimate prognosis experiment on animals一. Pathological Diagnosis of Tumors(一)Excision Biopsy（切下） T

60、he most reliable diagnosis method:1. Resection biopsy: Final diagnosis2. Frozen section: it is a reference for determining the extent of operation. It is not the final diagnosis.Requirement of resection biopy1. Tumor margin with good blood supply. 2. Representative tissue3. Preventing tissue crash.4