宮頸疾病病理《生殖系統(tǒng)和乳腺疾病》課件

生殖系統(tǒng)和乳腺疾病

Diseasesofgenitalsystemandmammarygland

Hereisanormalcervixwithasmooth,glisteningmucosalsurface.Thecervicalosissmallandround,typicalforanulliparouswoman.Theoswillhaveafish-mouthshapeafteroneormorepregnancies.Thenormaladultvaginalmucosawithawrinkledappearance.Thecervixhasbeenopenedtorevealanendocervicalcanalleadingtotheloweruterinesegmentattherightthathasanerythematousappearanceextendingtothecervicalosconsistentwithchronicinflammation.Theyellowdashedlinemarkstheouterboundaryofthetransformationzone.Outsidetheboundarythelong-establishedandthickstratifiedsquamousepitheliumappearswhiteorlightpinkfollowingthediluteacidtreatment.Insidetheboundary,thetransformationzoneischaracterizedbyareasofthinepithelium,whichappearredoralmostinflamed.

1.生育期婦女最常見

2.多繼發(fā)于分娩、流產(chǎn)等→子宮頸損傷

3.臨床:白帶過多

一、慢性子宮頸炎(Chroniccervicitis)

常見感染:鏈球菌、腸球菌、大腸桿菌、葡萄球菌等

特殊感染:沙眼衣原體、淋球菌、病毒

(單純皰疹病毒、人乳頭狀瘤病毒、巨細(xì)胞病毒等)、結(jié)核菌、寄生蟲及放線菌等Etiology肉眼：宮頸粘膜充血、腫脹，顆粒狀或糜爛狀Pathologicalchanges

子宮頸粘膜充血水腫間質(zhì)單核C、淋巴C、漿C浸潤子宮頸柱狀上皮、腺上皮增生或鱗狀化生

子宮頸息肉(cervicalpolyp)

有時(shí)子宮頸囊腫

(納博特囊腫,Nabothiancyst)鏡下：Thisisnormalcervicalnon-keratinizingsquamousepithelium.Thesquamouscellsshowmaturationfrombasallayertosurface.Thisischroniccervicitisatthesquamo-columnarjunctionofthecervix.Smallrounddarklymphocytesareseeninthesubmucosa,andthereisalsohemorrhage.Squamousmetaplasiaofcervix

CervicalpolypNabothiancystInthecervix,koilocytoticchangewithhumanpapillomavirus(HPV)infection,withvacuolizationofepithelialcells.

子宮頸糜爛

假性糜爛-柱狀上皮代替鱗狀上皮，多見

真性糜爛-鱗狀上皮壞死脫落

Cervicalerosionoccurswhenthesurfaceofthecervixisreplacedwithinflamedtissuefromthecervicalcanal.Theconditionmaybecausedbytrauma,infectionorchemicals.二、子宮頸上皮非典型增生和原位癌

子宮頸上皮非典型增生－癌前病變異型細(xì)胞增生，從基底層向表層發(fā)展

原位癌上皮全層為異型細(xì)胞所替代，未突破基底膜

好發(fā)部位：子宮頸鱗-柱上皮交界帶

(移行帶)(Cervicalepithelialdysplasiaandcarcinomainsitu)異型細(xì)胞：類似正?；准?xì)胞或體積較小，大小不等，細(xì)胞排列紊亂，可見核分裂。Ⅰ級（輕度）→異型細(xì)胞限于上皮下1/3↓（CINⅠ）多數(shù)可消退Ⅱ級（中度）→異型細(xì)胞累及上皮下2/3↓（CINⅡ）Ⅲ級（重度）→異型細(xì)胞超過上皮2/3以上↓（CINⅢ）原位癌

→上皮全層細(xì)胞異型，極性消失，但基底膜完整↓（CINⅢ）原位癌累及腺體（仍為原位癌）↓浸潤癌→突破基底膜，向上皮下浸潤擴(kuò)展

重度非典型增生和原位癌沒有明顯界限，原位癌的異型細(xì)胞多形性更顯著，核分裂多見。子宮頸上皮內(nèi)瘤變

(Cervicalintraepithelialneoplasia,CIN)2014版WHO分類：宮頸鱗狀上皮前驅(qū)病變細(xì)胞學(xué)與組織學(xué)采用相同的診斷術(shù)語，共同的臨床處理方案低級別鱗狀上皮內(nèi)病變（LSIL）CINI（VaIN1）、扁平濕疣、尖銳濕疣ICD-O:/0觀察隨訪、避免過度治療高級別鱗狀上皮內(nèi)病變（HSIL）CINII-III（VaINII-III)ICD-O:/2手術(shù)治療Cervicalintraepithelialneoplasia(CIN-1and-2)Cervicalintraepithelialneoplasia(CIN-3)Cervicalintraepithelialneoplasia(CIN-3)CervicalcarcinomainsituCervicalcarcinomainsituwithglands

輕度非典型增生:多數(shù)可自然消退

<2%→浸潤癌非典型增生→

原位癌約10年

>20%

CINⅢ

→浸潤癌10年內(nèi)非典型增生+16、18或33型HPV感染→較高惡變傾向檢查手段：碘液實(shí)驗(yàn)、脫落細(xì)胞學(xué)、組織病檢

Prognosis三、子宮頸癌1.女性高發(fā)惡性腫瘤之一，開展普查→晚期癌↓，5年生存率和治愈率↑2.40-60歲高發(fā)3.臨床:陰道不規(guī)則流血、接觸性出血、白帶↑

(Carcinomaofthecervix)

*

與早婚、多產(chǎn)、性生活紊亂、子宮頸裂

傷、包皮垢、感染等因素有關(guān)*通常繼發(fā)于CIN

*與人類乳頭狀瘤病毒(HPV)16、18型，其次

31、33型的感染有關(guān)Etiology組織來源子宮頸陰道部或移行帶：鱗狀上皮子宮頸管粘膜柱狀上皮柱狀上皮下的儲(chǔ)備細(xì)胞大體分型：糜爛型外生菜花型內(nèi)生浸潤型潰瘍型Pathologicalchanges1.子宮頸鱗狀細(xì)胞癌：占90%

早期浸潤癌（微小浸潤型鱗狀細(xì)胞癌）浸潤癌少數(shù)腫瘤細(xì)胞突破基底膜浸潤間質(zhì)的深度不超過基底膜下5mm沒有血管浸潤也無淋巴結(jié)轉(zhuǎn)移常無明顯臨床癥狀癌組織突破基底膜明顯浸潤間質(zhì)，深度超過基底膜下5mm伴有臨床癥狀者組織分型高分化鱗癌(20%):

癌巢、角化珠,核分裂不多鏡下:中分化鱗癌

(60%):無明顯角化和癌珠形成，不規(guī)則和條型癌巢,核分裂和細(xì)胞異型性較明顯低分化磷癌(20%):細(xì)胞呈小梭形，似基底細(xì)胞，異型性及核分裂都很明顯，對放射線最敏感，但預(yù)后較差2.子宮頸腺癌：占10-25%

Alargeprotrudingmassisseenincervicalcanalextendingtothefornixofvagina.Adenocarcinomainsitu

Poorlydifferentiatedadenocarcinoma

直接蔓延:膀胱、直腸、盆腔、陰道、宮體淋巴道轉(zhuǎn)移:

最常見，子宮旁→閉孔、髂內(nèi)、髂外、髂總、腹股溝、骶前Ln，晚期鎖骨上Ln

血道轉(zhuǎn)移:肺、胃、肝SpreadingandmetastasisThisisalargercervicalsquamouscellcarcinomawhichspreadtothevagina.Thisisanotherpelvicexenterationforcervicalsquamouscellcarcinoma.Theirregulargrey-browntumorextendstowardbladderandupintotheuterus.Invasivesquamouscarcinomaofcervixinvascularchannel.Thepresenceoftumorcellswithinthelumenofacapillary-likespaceisevidenceforaggressivegrowthpotentialinsquamouscarcinomaofthecervixandhasbeencorrelatedwithincreasedriskforregionallymphnodemetastasis.1.不規(guī)則陰道流血、接觸性出血2.白帶增多3.腰骶部疼痛4.子宮膀胱瘺/子宮直腸瘺5.定期脫落細(xì)胞檢查－早期發(fā)現(xiàn)Clinicalrelations臨床分期：0期:原位癌I期:局限于子宮頸內(nèi)Ⅱ期:侵及盆腔和陰道Ⅲ期:侵及盆腔壁和陰道下1/3Ⅳ期:侵出骨盆,累及膀胱粘膜或直腸四.子宮平滑肌瘤

Leiomyomaoftheuterus1.最常見2.≥30歲,70%3.多無癥狀，出血，尿頻，不孕，自然流產(chǎn)，絕經(jīng)后萎縮4.遺傳傾向PathologicalchangesAlarge,solitaryleiomyoma.AsubmucosalleiomyomaMultiplesubmucosal,intramural,andsubserosalleiomyomasoftheuterus.

Reddegeneration生長部位：子宮肌層、子宮漿膜下或子宮內(nèi)膜下單發(fā)或多發(fā)：多者達(dá)數(shù)十個(gè)大小懸殊：小者僅鏡下可見，大者>30cm形態(tài)：球形或不規(guī)則形，界清，無包膜切面觀：灰白，質(zhì)韌，編織狀或旋渦狀繼發(fā)性改變：玻璃樣變、粘液變、囊性變、鈣化、出血及壞死等大體：與正常子宮平滑肌細(xì)胞相似瘤細(xì)胞-

核排列較密集束狀或編織狀排列核長桿狀，兩端鈍圓，染色質(zhì)纖細(xì)

鏡下:Uterineleiomyomaisabenignconnectivetissuetumorofthesmoothmusclecellsofthemyometrium.Tumorcellsresemblenormalcells(elongated,spindle-shaped,withacigar-shapednucleus)andformbundleswithdifferentdirections(whirled).Thetumoriswellcircumscribed,butnotencapsulated.

良、惡性之間的區(qū)別取決于三個(gè)標(biāo)準(zhǔn)：

分裂像

細(xì)胞異型性壞死腫瘤核分裂像10個(gè)/10HP，有細(xì)胞異型性及壞死者為惡性

子宮平滑肌肉瘤

（Leiomyosarcoma）Thisisaleiomyosarcomaprotrudingfrommyometriumintotheendometrialcavityofthisuterus.Muchmorecellularandthecellshavemuchmorepleomorphismandhyperchromatismthanthebenignleiomyoma.Anirregularmitosisisseeninthecenter.子宮體癌(子宮內(nèi)膜腺癌)

（Endometrialadenocarcinoma）1.發(fā)病率上升2.絕經(jīng)期、絕經(jīng)后婦女，50-59歲3不規(guī)則陰道流血4.生長緩慢,轉(zhuǎn)移較晚5.一般與雌激素長期作用有關(guān)肉眼：局部型：多見，多位于子宮底或子宮角，息肉狀、乳頭狀彌漫型：內(nèi)膜彌漫性增厚，灰白質(zhì)脆，伴出血、壞死、潰瘍Pathologicalchanges

鏡下：高分化：多見，腺管排列擁擠、紊亂，輕度異型，似增生的內(nèi)膜腺體中分化：腺體不規(guī)則，排列紊亂，乳頭或篩狀，異型明顯，核分裂易見低分化：實(shí)體片狀，無腺樣結(jié)構(gòu)，異型明顯，核分裂多見Theendometrialadenocarcinomainthepolypattheleftismoderatelydifferentiated,asaglandularstructurecanstillbediscerned.Notethehyperchromatismandpleomorphismofthecells,comparedtotheunderlyingendometriumwithcysticatrophyattheright.

Adenocarcinoma,endometrium,uterus,welldifferentiated.Thetallcolumnarepitheliumandwell-definedglandformationillustrateawell-differentiatedadenocarcinoma.Thisisendometrialadenocarcinomawhichcanbeseeninvadingintothesmoothmusclebundlesofthemyometrialwalloftheuterus.Welldifferentiatedadenocarcinomahasinvadedthroughthemusclebundlesofthemyometrium(redarrow).Theadenocarcinomaisindicatedbytheredarrows.

腺棘皮癌：分化較好的腺癌中有良性化生的鱗狀上皮腺鱗癌：腺癌組織中混雜鱗癌上皮直接蔓延：

上－子宮角，輸卵管、卵巢下－宮頸管和陰道外－漿膜、腹膜和大網(wǎng)膜淋巴道：

宮底－腹主動(dòng)脈旁Ln

子宮角－腹股溝Ln

宮頸－宮旁、髂內(nèi)外、髂總Ln血道：肺、肝、骨骼Spreadingandmetastasis臨床分期：Ⅰ期:局限于宮體,5年生存率90%Ⅱ期:累及子宮體和子宮頸,30-50%Ⅲ期:侵入盆腔Ⅳ期:侵出盆腔,累及膀胱和直腸

張三，女，58歲，五年前絕經(jīng)，近一月來出現(xiàn)陰道不規(guī)則流血，B超發(fā)現(xiàn)子宮底部見一菜花狀腫物，病理活檢見灰白色質(zhì)脆組織，顯微鏡下腺體排列擁擠、紊亂，細(xì)胞有明顯異型性。病理診斷：?

Casediscuss子宮內(nèi)膜腺癌

乳腺癌

Carcinomaofbreast

Anormalductcells

Bbasementmembrane

Clumen(centerofduct)導(dǎo)管雙層上皮內(nèi)腺上皮，外肌上皮Normallobuleofmammarygland全球每年120萬婦女患乳腺癌，50萬死于該病北美、北歐高我國↑3%/年，“第一癌癥殺手”40-60歲女性，男性罕見1%乳腺外上象限>中央?yún)^(qū)>內(nèi)上象限

來自乳腺終末導(dǎo)管小葉單元上皮IntroductionER、PR(+)：內(nèi)分泌治療好，預(yù)后好C-erbB-2(+),ER(-):預(yù)后差乳腺是女性激素的靶器官正常乳腺上皮細(xì)胞存在雌激素受體（ER）

孕激素受體（PR）ER、PR→啟動(dòng)細(xì)胞分裂→促乳癌生長Thecellsofthisbreastcarcinomaarehighlypositiveforestrogenreceptorwiththisimmunoperoxidasestain.Estrogenreceptorpositivitycorrelateswithabetterprognosis.Thisisprogesteronereceptor(PR)positivityinabreastcarcinoma.Theusefulnessofthisdeterminationisnotaswellestablishedasforestrogenreceptors.CarcinomasthatarePRpositive,butnotERpositive,mayhaveaworseprognosis.分類：乳腺癌非浸潤性癌

浸潤性癌導(dǎo)管內(nèi)原位癌小葉原位癌粉刺癌非粉刺導(dǎo)管內(nèi)癌Paget病浸潤性導(dǎo)管癌浸潤性小葉癌特殊類型癌小管癌典型髓樣癌粘液癌

屬于原位癌

沒有突破導(dǎo)管和腺泡的基底膜分類:導(dǎo)管內(nèi)原位癌

小葉原位癌

一、非浸潤性癌1．導(dǎo)管內(nèi)原位癌

（Intraductalcarcinomainsitu）

起于乳腺小葉的終末導(dǎo)管限于導(dǎo)管內(nèi),基膜完整檢出率↑，5%－15%－30%

組織學(xué):粉刺型,非粉刺型

20年，30%－浸潤癌AnormalductcellsBductalcancercellsCbasementmembraneDlumen(centerofduct)Intraductalcarcinoma.Theneoplasticcellsareconfinedtotheductbythebasementmembrane.Theneoplasticcellsaremonotonouswithroundtoovalnucleiandlittlepleomorphism.Thecellbordersarewelldemarcated.

（1）粉刺癌（Comedocarcinoma）

>50%位于乳腺中央部質(zhì)硬、腫塊明顯，易觸診查出導(dǎo)管擴(kuò)張，內(nèi)含壞死物質(zhì)擠壓導(dǎo)管,壞死物質(zhì)會(huì)像粉刺一樣被擠出

鏡下:實(shí)性排列，中央壞死－特征癌細(xì)胞大，嗜酸，大小不一，核仁明顯，病理性核分裂多壞死區(qū)常見鈣化導(dǎo)管周間質(zhì)纖維組織↑，慢性炎C浸潤C(jī)omedocarcinomaischaracterizedbythepresenceofrapidlyproliferating,high-grademalignantcells.Thecellsinthecenteroftheductsareoftennecroticandcalcify.Thiscentralnecrosisleadstothegrosscharacteristicofextrusionofcheesymaterialfromtheductswithpressure.

ComedocarcinomaNotecentralnecrosis(*)andpleomorphicnuclei.Thecellsdonotextendbeyondthebasementmembrane(arrow).Thecenteroftheductcontainscalcifiedmaterialsurroundedbynecrotic,mostlyacellular

debris.Theneoplasticcellsexhibitnuclearpleomorphismandhyperchromasia.Thebasementmembraneisintact(2)非粉刺型導(dǎo)管內(nèi)癌（Noncomedointraductalcarcinoma）實(shí)性、乳頭狀、篩狀排列，輕微壞死癌細(xì)胞小，較規(guī)則導(dǎo)管周間質(zhì)纖維組織增生較輕2.小葉原位癌（Lobularcarcinomainsitu）

來自小葉的終末導(dǎo)管及腺泡

癌細(xì)胞局限于管泡內(nèi)，未穿破其基底膜，小葉結(jié)構(gòu)存在

多中心性，常累及雙側(cè)，無明顯腫塊癌細(xì)胞實(shí)性排列，小而一致，核圓，核分裂罕見癌細(xì)胞無壞死，無間質(zhì)的炎癥反應(yīng)、纖維組織增生

AnormallobularcellsBlobularcancercellsCbasementmembraneLobularcarcinomainsituconsistsofaneoplasticproliferationofcellsintheterminalbreastductsandacini.Thecellsaresmallandround.Thereisa30%riskfordevelopmentofinvasivecarcinomainthesameortheoppositebreast.導(dǎo)管內(nèi)癌－－乳頭、乳暈乳頭、乳暈可見滲出、淺表潰瘍又稱“濕疹樣癌”表皮內(nèi)：瘤細(xì)胞孤立散在、成簇分布

大而異型，胞質(zhì)透明3.佩吉特病（Pagetdisease)癌細(xì)胞穿破乳腺導(dǎo)管或腺泡的基底膜而侵入間質(zhì)占乳腺癌>85%分類：浸潤性導(dǎo)管癌和浸潤性小葉癌兩種類型可并存，占10%，浸潤性小葉癌的預(yù)后較差

二、浸潤性癌導(dǎo)管內(nèi)癌細(xì)胞突破管壁基底膜向間質(zhì)浸潤最常見（70%）1.浸潤性導(dǎo)管癌（Invasiveductalcarcinoma）

AnormalductcellsBductalcancercellsbreakingthroughthebasementmembraneCbasementmembrane大體：色灰白，質(zhì)硬，無包膜界不清，活動(dòng)度差侵潤性生長乳頭下陷，橘皮樣外觀PathologicalchangesHereisaclassicinfiltratingductalcarcinomaThisinfiltratingductalcarcinomaofthebreastisdefinitelyinfiltratingthesurroundingbreast.Thecentralwhiteareaisveryhardandgritty,becausetheneoplasmisproducingadesmoplasticreactionwithlotsofcollagen.Thisisoftencalleda"scirrhous"appearance.鏡下：巢狀、團(tuán)索狀、腺樣，可見導(dǎo)管內(nèi)原位癌癌細(xì)胞異型明顯，核分裂多伴壞死、纖維組織增生單純癌、硬癌、不典型髓樣癌Cordsandnestsofcellsirregularlyinvadethetissue.Reactivefiborsis(thedesmoplasticreaction)surroundstumorcells(arrows).Inthecenterisaductlinedbycarcinomacells.However,thisductalcarcinomaisnotconfinedtojusttheduct,butinfiltratesoutwardintothesurroundingstromaasaninfiltratingductalcarcinomaThepleomorphismofthecarcinomacellswithintheductinthecenter(inacribriformpattern),aswellastheneoplasticcellsinfiltratingthroughthestromaandfat,canbeseenwiththisinfiltratingductalcarcinoma.Theinfiltratingductalcarcinomaofbreasthaspleomorphiccellsinfiltratingthroughthestroma.Thebluearrowssurroundanestofneoplasticcellsinaninfiltratingductalcarcinoma.Thegreenarrowheadspointtointerveningstroma.Mitoticfiguresareseen.Small,duct-likestructuresareseeninvadingthebreaststroma.Sometumorcellsaresingle.Notetheabundantcollagenousstroma,characteristicofbreastcarcinomas.Scirrhouscarcinomaofthebreast

5%～10%，老年婦女多見癌細(xì)胞突破基底膜向間質(zhì)浸潤約20%可累及雙側(cè)乳房，彌漫性多灶性分布，不易發(fā)現(xiàn)2.浸潤性小葉癌（Invasivelobularcarcinoma）AnormalcellsBlobularcancercellsbreakingthroughthebasementmembraneCbasementmembrane

*橡皮樣，灰白柔韌，邊界不清*

轉(zhuǎn)移特殊性：腦脊液、漿膜面、卵巢、子宮、骨髓肉眼：

串珠狀、細(xì)條索或環(huán)形排列正常導(dǎo)管周圍癌細(xì)胞小、大小一致、核分裂象少見鏡下：Thisisacloserviewoflineararraysoflobularcarcinomacellsinfiltratingthroughdensefibrousstroma.InvasivelobularcarcinomaTheneoplastic

cellsarenotableforeccentricnucleisetintomucinrichcytoplasm.Thenucleiarehyperchromaticandroundtooval.Nopleomorphismormitosesareseen.Thestromaisverydensewithaccellularcollagen.Singlestrandsofmalignantcellsinfiltratingthestroma(Indianfiling).3.特殊型癌

具有特殊形態(tài)，如粘液癌、大汗腺樣癌、腺樣囊性癌、鱗狀細(xì)胞癌、炎性癌

直接浸潤：乳腺實(shí)質(zhì)、乳頭、皮膚、筋膜、胸肌及胸壁

淋巴結(jié)轉(zhuǎn)移：

外上、外下象限和中心區(qū)→同側(cè)腋窩淋巴結(jié)

內(nèi)上、內(nèi)下象限→乳內(nèi)動(dòng)脈旁淋巴結(jié)

血行轉(zhuǎn)移：遠(yuǎn)處任何器官

轉(zhuǎn)移途徑135影響預(yù)后的因素

早期不易發(fā)現(xiàn)，發(fā)現(xiàn)時(shí)約50%病例已有局部淋巴結(jié)轉(zhuǎn)移

原發(fā)灶大小：<1cm、無LN轉(zhuǎn)移者預(yù)后好

淋巴結(jié)轉(zhuǎn)移：無LV轉(zhuǎn)移者5年生存率70-80%

組織學(xué)類型：

組織學(xué)分級：腺管的分化程度、細(xì)胞異型性、核分裂

ER和PR：內(nèi)分泌治療、預(yù)后

HER-2：靶向藥物Herceptin、預(yù)后

DNA倍體數(shù)：

新輔助化療：乳腺癌的分子分型Nature

2000;406,

747–752乳腺癌Her-2靶向治療乳腺纖維腺瘤Fibroadenomaofbreast

最常見的良性腫瘤20-30歲多見單個(gè)或多個(gè)，單側(cè)或雙側(cè)發(fā)生界清，切片灰白、質(zhì)韌、可見裂隙狀，粘液

樣外觀乳腺增生性病變Proliferativelesionsofbreast

乳腺纖維囊性變Fibrocysticchangesofbreast硬化性腺病Sclerosingadenosis乳腺纖維囊性變一組非腫瘤性病變，以末梢導(dǎo)管、腺泡擴(kuò)張，間質(zhì)纖維組織和上皮不同程度增生為特點(diǎn)25-45