《病理学》英文课件：10 生殖系统疾病

The diseases of Genital SystemThe diseases of Genital System(生殖系统疾病）生殖系统疾病）刘国元刘国元Pathology Department,School of Basic Medical Sciences,Fudan UniversityFemale Genital SystemFemale Genital SystemThe common diseasesChronic Cervicitis (慢性宫颈炎）慢性宫颈炎）Carcinoma of the Cervix (宫颈癌）宫颈癌）Gestational Trophoblastic Tumors (绒毛膜滋养细胞肿瘤）绒毛膜滋养细胞肿瘤）Carcinoma of the Breast (乳腺癌乳腺癌)Nodular hyperplasia of the Prostate (前列腺结节状增生前列腺结节状增生)Carcinoma of the Prostate (前列腺癌）前列腺癌）一、一、Diseases of CervixnChronic cervicitisnTumors Normal cervixNormal cervixNormal cervixSchematic of the development of the cervical transformation zone宫颈移行区宫颈移行区Chronic CervicitisChronic CervicitisnEtiology and Types of chronic cervicitis1.Specific:tuberculosis,gonorrhea(淋病淋病),HSV2.Nonspecific:many types of germs and viruses3.Some degree of cervical inflammation may be found in virtually all multiparous and in many nulliparous adult women with little clinical consequence.Pathological classifications n糜烂型糜烂型：最常见：最常见 复层鳞状上皮脱落为单复层鳞状上皮脱落为单 层柱状上皮增生下移所取代层柱状上皮增生下移所取代n颗粒型：真性糜烂颗粒型：真性糜烂n增生型：腺体腺瘤样增生增生型：腺体腺瘤样增生n囊泡型囊泡型：Nabothian囊肿（纳博特囊肿）囊肿（纳博特囊肿）n肥厚型：子宫脱垂肥厚型：子宫脱垂 肥厚增大肥厚增大2-3倍倍 鳞状上皮和纤维结缔组织增生鳞状上皮和纤维结缔组织增生伴有：宫颈管上皮和腺体伴有：宫颈管上皮和腺体鳞状化生鳞状化生 宫颈息肉宫颈息肉Chronic Cervicitis Erosive ecto and endo cervicitis due to HSV infectionpInflammatory infiltrate:polymorphonuclear leukocytes and mononuclear cells.pIf severe,the loss of the epithelial lining(erosion or ulceration)and epithelial repair(reparative atypia or dysplasia of repair).Microscopy Nabothian Cyst (纳博特囊肿，粘液潴留性囊肿）纳博特囊肿，粘液潴留性囊肿）Overgrowth of the regenerating squamous epithelium blocks the orifices of endocervical glands leading to cystic dilation of these glands 增生的鳞状上皮覆盖或阻塞子宫颈管腺体开口，使粘液潴留，腺体扩大呈囊，形成子宫颈囊肿Cervical polyp (宫颈息肉）宫颈息肉）usually occur in endocervical canal with proliferation of mucosa epithelium to form fingerlike inflammatory polyp宫颈粘膜、腺体和间质结缔组织局限性增生形成宫颈粘膜、腺体和间质结缔组织局限性增生形成PolypusIn squamous metaplasia,the nuclei may be larger and more immature appearing and the cytoplasm more dense.Squamous metaplasia鳞状上皮化生鳞状上皮化生宫颈管内膜的柱状上皮为成熟的复层鳞状上皮替代宫颈管内膜的柱状上皮为成熟的复层鳞状上皮替代Squamous metaplasia at the transition zone.Mature squamous epitheliumSquamous metaplasiaCurablePersisted chronic inflammationColumnarSquamous metaplasia Dysplasia Cervical Carcinomaconsequence?Cervical Carcinoma(宫颈癌宫颈癌)Tumors of the CervicalTumors of the Cervicalthe 2nd commonest female malignancy nCIN cervical intraepithelial neoplasianInvasive carcinomaEpidemiologyPeak age CIN-30y Invasive carcinoma-45yTransformation zoneuSquamous Ca.（75%）uadenocarcinoma(20%)uNeuroendocrine Ca.(less than 5%)Risk Factors:MajornEarly age at first intercoursenMultiple sexual partnersnA male partner with multiple previous sexual partnersnpersistent infection by“high-risk”papillomavirusesMinornSmoking nLower social class nImmunosuppression e.g.HIV,post-transplant nSlight increase in risk with use of combined oral contraceptive nNon-attendance at cervical screening program(Pap smear).HPV infectionHPV infectionCondyloma(尖锐湿疣尖锐湿疣)CINLow riskHPV-6 HPV-11HPV-42HPV-44HPV infectionsHigh riskHPV-16HPV-18HPV-31HPV-33HPV-35Encode E6 E7 proteinHPV infectionsTP53Growth inhibitorsTP53RB hyperphosphorylatedRB hypophosphorylatedRBPathogenesis：nPredilection site:Transformation ZonenHPVs infect immature basal cells of the squamous epithelium in areas of epithelial breaks,or immature metaplastic squamous cells present at the squamocolumnar junction.nSequence of events:HPV infection-precancerous lesion(CIN)-invasive carcinomaCervical intraepithelial neoplasia(宫颈上皮内肿瘤，宫颈上皮内肿瘤，CIN)定义：宫颈上皮部分被不同程度的异形性细胞取代。定义：宫颈上皮部分被不同程度的异形性细胞取代。Precancerous lesion of cervical carcinoma pCIN I:Mild dysplasiapCIN II:Moderate dysplasiapCIN III:Severe dysplasia and carcinoma in situLatent periodLatent period：As long as 20yrsAs long as 20yrsPap smear screening:Cytologic examinationPap smear screening:Cytologic examinationCervical intraepithelial neoplasia(宫颈上皮内肿瘤，宫颈上皮内肿瘤，CIN)MicroscopyCIN I:limited in the lower 1/3 layers of the epitheliumCIN II:limited in the lower 2/3 layers of the epitheliumCIN III:all layers of the epithelium,no invasionNormalCIN ICIN IICIN IIILow grade,LSILSquamous intraepithelial lesion High grade,HSILCervical intraepithelial neoplasiaKoilocyte(凹空细胞凹空细胞):A squamous cell with HPV virus.The nuclei are hyperchromatic(dark)and raisinoid,crinkly;(see arrows),with a surrounding clear halo in the cytoplasm.细胞核深染，皱缩，核周胞质有空晕细胞核深染，皱缩，核周胞质有空晕Low-grade squamous intraepithelial lesion,LSIL低级别上皮内肿瘤低级别上皮内肿瘤KoilocytesCIN I，扁平湿疣，扁平湿疣The nuclei are hyperchromatic and may have slightly irregular nuclear outlines,but the most striking feature at low power is the high nuclear/cytoplasmic ratios present from top to bottom.High-grade squamous intraepithelial lesion,HSILCIN II&IIIGross morphology1.Carcinoma in situ is very difficult to be distinguished from chronic cervicitis2.Schillers Test碘溶液涂抹实验：癌细碘溶液涂抹实验：癌细胞内缺乏糖原，不显红胞内缺乏糖原，不显红棕色。棕色。Cytologic examination:Pap smear巴氏涂片巴氏涂片-用于宫颈癌的筛查与预防。取宫颈外口鳞用于宫颈癌的筛查与预防。取宫颈外口鳞柱上皮交界处的细胞标本涂在玻片上，经巴氏染色柱上皮交界处的细胞标本涂在玻片上，经巴氏染色后在显微镜下观察。后在显微镜下观察。50%-60%regression逆转逆转 30%persistence 20%CIN III 1%-5%invasive carcinoma(20 years)33%regression 6%-74%progression Condyloma hundreds of thousands/yr CIN million/yr Higher-grade CIN 300,000/yr Invasive cancer 15,000/yr Metastasis 5000/yr CIN I NormalCINbasilar membraneCervical intraepithelial neoplasiaGross morphology3 types:cauliflower-like(菜花型)ulcer(溃疡型)diffusely invasive(弥漫浸润型)spread to the pelvisStage 0carcinoma in situStage IThe lesion is limited in the cervix Iainvasive lesion 5mm，no spread to the cervical around tissueStage IItumor spread to the cervical around tissue,but has not to the pelvis.Spread to the vagina,but has not to the lower 1/3.Stage IIItumor spread to the lower 1/3 vagina tissue or to the pelvis.Stage IVtumor spreads to the tissue outside the pelvis,or infiltrates bladder or rectum.5 Stages 分期分期Invasive carcinoma of the cervixlimited to the cervix(stage I)0 stage：carcinoma in situIa：invasive lesion 5mmBroad fronts of cells push into the stroma of the cervix,and at the leading edge there is a ragged border with individual infiltrating cells(arrowhead).Occasional huge and pleomorphic cells are visible(arrow).AdenocarcinomaAdenocarcinoma in situ.This field shows some residual normal endocervical glands(arrowhead)adjacent to a very abnormal population with dark,elongated,crowded,and stratified nuclei representing adenocarcinoma in situ.Invasive adenocarcinomaClinical Pathologic conference(CPC,临床与病理联系临床与病理联系)nCIN:No clinical manifestation or the manifestation of chronic cervicitisnInvasive carcinoma:bleeding after touch.nIn advanced cases:unscheduled vaginal bleeding,leukorrhea（白带）（白带）,painful coitus,dysuria（排尿困难）（排尿困难）,secondary infection,fistula between rectum and vagina,or bladder and vagina,remote metastasis.nSign:In early-stage,examination can be relatively normal.white or red patches on the cervix.Rectal examination:a mass or bleeding due to erosion.Bimanual palpation:pelvic bulkiness/masses due to pelvic spread.Leg edema may develop due to lymphatic or vascular obstruction.Hepatomegaly may develop in the case of liver metastases.Prognosis (预后预后)Precancerous lesions can be diagnosed and treated with Pap smear screening.nInvasive cancers are removed by surgical excision,with adjunctive radiation therapy and chemotherapy.nA new aspect is an HPV vaccination program,approved by the US Food and Drug Administration(FDA)for preventing HPV infection.nHPV vaccines are also being evaluated for effectiveness as a therapeutic tool in cervical precancersTreatment&Prevention(治疗治疗&预防预防)(绒毛膜滋养细胞肿瘤绒毛膜滋养细胞肿瘤)Hydatidiform Mole(水泡状胎块水泡状胎块)Invasive Mole（恶性水泡状胎块）（恶性水泡状胎块）Choriocarcinoma(绒毛膜上皮细胞癌绒毛膜上皮细胞癌)Level of HCG（绒毛膜促性腺激素）in urine and blood：choriocarcinomainvasive molehydatidiform mole51绒毛：胎盘的组成单位绒毛：胎盘的组成单位 表面主要由两种细胞覆盖：细胞滋养层细胞表面主要由两种细胞覆盖：细胞滋养层细胞 合体滋养层细胞合体滋养层细胞功能：吸收营养和生成激素（如功能：吸收营养和生成激素（如HCG),间质的血管：连接母体和胎儿血液循环的桥梁间质的血管：连接母体和胎儿血液循环的桥梁异常：胎儿异常：胎儿 母体母体 正常绒毛正常绒毛 Pathogenesis：Uncertain Abnormal fertilization胚胎发育不正常胎儿死亡滋养层细胞继续增生绒毛间质血管关闭水泡状胎块吸收水分Hydatidiform mole(水泡状胎块水泡状胎块,俗称葡萄胎俗称葡萄胎)Incidence:1-1.5/2000 pregnanciesComplete hydatiform molePartial hydatiform moleFeatures of Complete versus Partial Hydatidiform MoleFeature Complete MolePartial MoleKaryotypeDiploid(46,xx/46,xy)Triploid(69,xxy)Villous edema All villi Some VilliTrophoblastDiffuse;Focal;slight proliferation circumferential Atypia Often presentAbsentSerum hCGElevatedLess elevatedhCG in tussue+Behavior2%choriocarcinomarareMorphology(病理变化病理变化)Gross:n the uterine cavity is fill with a delicate,friable mass of thin walled,translucent cystic structures.n Fetal parts are not seen in complete moles but are rare in partial moles.Complete hydatidiform mole子宫腔充满大小不一的水泡，状如葡萄Partial hydatidiform moleThree characters:1.hydropic swelling of chorionic villi,with myxomatous edematous stroma.2.most of blood vessels in the interstitial tissue disappeared.3.proliferation of chorionic epithelium both cytotrophoblast and syncytiotrophoblastn绒毛间质疏松，呈粘液性性水肿绒毛间质疏松，呈粘液性性水肿n绒毛间质血管消失绒毛间质血管消失n绒毛滋养细胞显著增生绒毛滋养细胞显著增生 Normal villi hydatidiform moleClinico-pathologic relations(临床与病理联系临床与病理联系)uOccur during 12-14 weeks of gestationuUterus grow faster than that in the normal pregnancy（超过正常妊娠子宫）uUnpainful vaginal bleedinguIncreased hCG in urine and blooduNo fetal heart beating in ultrasound detectionUltrasound;elevated HCG levels;absence of fetal parts and fetal heart soundsprognosisComplete moles:n80%-90%benignn10%complete invasiven Asia and Africa 2.Age:uncommon30 years 3.Genetics and family history:5-10%related to specific inherited mutation1st malignant neoplasm in women Etiology and PathogenesisPathogenesis:(1)Genetic Changes:mutations of BRCA1,BRCA2;mutations of RB and TP53 genes;Overexpression of HER2/neu (2)Hormonal Influences:prolonged exposure to estrogens(3)Others:radiotherapy,obesity,fat diet,excessive drinking,fibrocystic changesCompositionLocation of the Tumors within the BreastUpper outer quadrant50%Central portion20%Lower outer quadrant10%Upper inner quadrant10%Lower inner quadrant10%All the carcinoma of the breast derive from the TDLU(terminal duct-lobular unit)终末导管小叶单位终末导管小叶单位Classifications:Breast carcinomas are divided into two groups:Noninvasive 1.Ductal carcinoma in situ(DCIS)The most common subtype is comedo,and cribriform.2.Lobular carninoma in situ(LCIS)Invasive 1.invasive ductal carcinoma(70-80%)(70-80%)2.invasive lobular carcinoma 3.medullar carcinoma 4.colloid carcinoma 5.tubular carcinoma 6.Other types:inflammatoryNoninvasivelobular carcinoma in situNoninvasive ductal carcinoma in situ粉刺癌粉刺癌 导管内癌管腔内灰黄色软膏样坏死物质，导管内癌管腔内灰黄色软膏样坏死物质，挤压时由导管溢出，如皮肤粉刺挤压时由导管溢出，如皮肤粉刺Noninvasive ductal carcinoma in situ实性实性筛孔状筛孔状Paget disease佩吉特病，佩吉特病，导管内癌沿导导管内癌沿导管生长累及乳头皮肤。出管生长累及乳头皮肤。出现渗出和浅表溃疡，又称现渗出和浅表溃疡，又称湿疹样癌。湿疹样癌。肿瘤细胞体积大，胞质透肿瘤细胞体积大，胞质透明呈空泡状明呈空泡状1.1.浸润性导管癌浸润性导管癌 (70-80%)(70-80%)2.2.浸润性小叶癌浸润性小叶癌 3.3.髓样癌髓样癌4.4.胶样癌胶样癌5.5.管状癌管状癌 6.6.其他类型其他类型:炎性乳癌炎性乳癌乳房浸润癌乳房浸润癌94Invasive Carcinoma of the BreastInvasive Carcinoma of the BreastGross morphology肿瘤内纤维组织增生收缩使乳头下陷局部淋巴转移，淋巴回流障碍，局部皮肤增厚，呈橘皮状。Carcinoma of the breast1.Invasive ductal carcinoma2.Invasive lobular carcinoma （几乎都表达几乎都表达ERER和和PRPR，无，无HER2HER2过过表达）表达）3.Medullary carcinoma(约约2%2%，不表达，不表达ERER和和PRPR，无，无HER2HER2过过表达表达)髓样癌，癌细胞大，间质少，髓样癌，癌细胞大，间质少，排列呈片状，间质淋巴细胞排列呈片状，间质淋巴细胞浸润浸润4.Colloid(mucinous)carcinoma （绝大多数表达绝大多数表达ERER和和PRPR，少数，少数HER2HER2过表达过表达）胶样癌，粘液癌。细胞外大量粘液。胶样癌，粘液癌。细胞外大量粘液。5.Tubular carcinoma管状癌，少见，排列良好管状癌，少见，排列良好的腺管状结构，细胞无明的腺管状结构，细胞无明显异形，无基膜。显异形，无基膜。Clinical Pathologic conference无痛性肿块 2-3cm 可被推动，约半数淋巴转移晚期累积肌肉和胸壁深筋膜，不易推动乳头下陷、皮肤橘皮样改变炎性乳癌炎性乳癌（inflammatory carcinoma)：肿瘤生长迅速，引起急性炎症样反应，出现红、肿、触痛。见于妊娠妇女。Grading,Staging and Metastasis 1.Grading is not very commonly used in the breast carcinoma.nNoninvasive carcinoma is a curable lesion;nMedullar,colloid,tubular carcinoma have relatively better prognosis;nInvasive ductal and lobular carcinoma are high grade malignant tumors.2.Staging:The most commonly used is AJC system.Including stage 0stage.3.Metastasis:nThe outer quadrant and centrally located lesions typically spread to the auxillary nodes.（外上象限外上象限和中央区肿瘤转移至腋窝淋巴结）和中央区肿瘤转移至腋窝淋巴结）nThe inner quadrants often involve the lymph node along the internal mammary arteries.(内测象限肿瘤内测象限肿瘤转移至内乳淋巴结转移至内乳淋巴结).nDistant dissemination eventually involves almost any organ or tissue in the body.Favored locations are the lungs,skeleton,liver,and adrenals.Major factors Minor factors 1.Tumor size2.Lymph node metastases4.Distant metastases5.Locally advanced disease6.Inflammatory carcinoma1.Histologic subtypes 2.Lymphovascular invasion 3.Tumor grade4.Estrogen and progesterone receptors5.HER2/neu6.Proliferative rate7.DNA contentPrognosis(预后预后)nWith no axillary lymph node involvement,5 years survival rate is close to 90%.nLymphatic Metastasis is important fact for poor prognosis.1.Lymph node involvement and metastasesnGrading is not very commonly used in the breast carcinoma.Usually,the noninvasive carcinoma is a curable lesion;medullary,colloid,tubular carcinoma have relatively better prognosis.nInvasive ductal and lobular carcinomas are high grade malignant tumors with poor prognosis.3.The presence of estrogen receptor or progesterone receptorn The presence of hormone receptors confers a slightly better prognosis.n The highest rate of response(80%）to anti-estrogen therapy is seen in women whose tumors with positive of estrogen receptor or progesterone receptor.n ER or PR of tumor can be detected by immunohisto-chemistry method.nOver expression of this membrane-bound protein is associated with a poorer prognosis.nHowever,the significance of evaluating HER2/neu is to predict response to a monoclonal antibody(Hereceptin)to the gene product,and improve the prognosis of patients.4.Overexpression of HER2/neu乳腺癌分子分型乳腺癌分子分型(基底细胞标志:CK5/6,CK14)注：2000年，Perou等进行乳腺癌基因表达的研究，Nature:Molecular Portraits of human breast110（曲妥珠单抗）（曲妥珠单抗）ER(-)/HER-2(+)111112四、四、Tumors of the ovary23,000 new case/y the 5th most common cancer in US women serous Tu teratoma fibroma mucinous Tu dysgerminoma granulosa-theca cell endometrioid Tu endodermal sinus sertoli-leydig cell clear cell Tu choriocarcinoma Brenner Tu cystadenofibroma Frequency65-70%15-20%5-10%malignance 90%3-5%2-3%Surface epithelial cellGerm cellSex cord-stromaClassification Serous tumors浆液性肿瘤浆液性肿瘤 Cystadenomas/cystadenocarcinomas卵巢内最常见肿瘤卵巢内最常见肿瘤 30-40 years 60%benign;15%low malignant;25%malignantMorphology:Gross:small 5-10cm to large 30-40cmMicroscope:a single layer of tall columnar epithelium psammoma bodies瘤瘤癌癌交界交界瘤瘤serous Cystadenoma良性囊腺瘤，囊腔由单层立方上皮、或矮柱状上良性囊腺瘤，囊腔由单层立方上皮、或矮柱状上皮覆盖，具有纤毛，类似输卵管上皮。皮覆盖，具有纤毛，类似输卵管上皮。Borderline serous tumor上皮层次增加，形成乳头状上皮层次增加，形成乳头状突起。无间质或包膜浸润突起。无间质或包膜浸润serous cystadenocarcinoma psammomma bodies分层同心圆状钙化小体分层同心圆状钙化小体serous carcinoma.Mucinous tumorsCystadenomas/cystadenocarcinomas粘液性囊腺瘤粘液性囊腺瘤 80%benign;10%low malignant;10%malignantMorphology:Gross:larger,multilocular,mucinous nature 肿瘤由多个囊腔组成，腔内充满富含糖蛋白的粘稠液体肿瘤由多个囊腔组成，腔内充满富含糖蛋白的粘稠液体Microscope:mucin-secreting cellsMucinous cytoadenomaBorderline mucinous tumor.间质微小浸润，细胞层次增加间质微小浸润，细胞层次增加Mucinous cytoadenocarcinoma乳头状结构，层次增加，深染乳头状结构，层次增加，深染Teratomas 畸胎瘤畸胎瘤Mature/immature90%benignGerm-cell originThe younger,the greater likelihood of malignancy Mature Immature Nodular Hyperplasia of the Prostate 前列腺结节性增生前列腺结节性增生Carcinoma of the Prostate前列腺癌前列腺癌前列腺结节性增生前列腺结节性增生前列腺结节性增生前列腺结节性增生腺体增生，淀粉样小体腺体增生，淀粉样小体前列腺癌前列腺癌前列腺癌前列腺癌Question 1.What is cervical intraepithelial neoplasia(CIN)?2.Try to explain the relationship between CIN and squamous cell carcinoma of cervix.