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、巨細胞病毒等)、結核菌、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－癌前病變異型細胞增生，從基底層向表層發(fā)展

原位癌上皮全層為異型細胞所替代，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)異型細胞：類似正?；准毎蝮w積較小，大小不等，細胞排列紊亂，可見核分裂。Ⅰ級（輕度）→異型細胞限于上皮下1/3↓（CINⅠ）多數(shù)可消退Ⅱ級（中度）→異型細胞累及上皮下2/3↓（CINⅡ）Ⅲ級（重度）→異型細胞超過上皮2/3以上↓（CINⅢ）原位癌

→上皮全層細胞異型，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，原位癌的異型細胞多形性更顯著，核分裂多見。子宮頸上皮內瘤變

(Cervicalintraepithelialneoplasia,CIN)2014版WHO分類：宮頸鱗狀上皮前驅病變細胞學與組織學采用相同的診斷術語，共同的臨床處理方案低級別鱗狀上皮內病變（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病變（HSIL）CINII-III（VaINII-III)ICD-O:/2手術治療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：碘液實驗、脫落細胞學、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、性生活紊亂、子宮頸裂

傷、包皮垢、感染等因素有關*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備細胞大體分型：糜爛型外生菜花型內生浸潤型潰瘍型Pathologicalchanges1.子宮頸鱗狀細胞癌：占90%

早期浸潤癌（微小浸潤型鱗狀細胞癌）浸潤癌少數(shù)腫瘤細胞突破基底膜浸潤間質的深度不超過基底膜下5mm沒有血管浸潤也無淋巴結轉移常無明顯臨床癥狀癌組織突破基底膜明顯浸潤間質，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,核分裂和細胞異型性較明顯低分化磷癌(20%):細胞呈小梭形，似基底細胞，異型性及核分裂都很明顯，對放射線最敏感，但預后較差2.子宮頸腺癌：占10-25%

Alargeprotrudingmassisseenincervicalcanalextendingtothefornixofvagina.Adenocarcinomainsitu

Poorlydifferentiatedadenocarcinoma

直接蔓延:膀胱、直腸、盆腔、陰道、宮體淋巴道轉移:

最常見，子宮旁→閉孔、髂內、髂外、髂總、腹股溝、骶前Ln，晚期鎖骨上Ln

血道轉移: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，絕經后萎縮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膜下單發(fā)或多發(fā)：多者達數(shù)十個大小懸殊：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胞相似瘤細胞-

核排列較密集束狀或編織狀排列核長桿狀，兩端鈍圓，染色質纖細

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

良、惡性之間的區(qū)別取決于三個標準：

分裂像

細胞異型性壞死腫瘤核分裂像10個/10HP，有細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(子宮內膜腺癌)

（Endometrialadenocarcinoma）1.發(fā)病率上升2.絕經期、絕經后婦女，50-59歲3不規(guī)則陰道流血4.生長緩慢,轉移較晚5.一般與雌激素長期作用有關肉眼：局部型：多見，多位于子宮底或子宮角，息肉狀、乳頭狀彌漫型：內膜彌漫性增厚，灰白質脆，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：實體片狀，無腺樣結構，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、腹膜和大網膜淋巴道：

宮底－腹主動脈旁Ln

子宮角－腹股溝Ln

宮頸－宮旁、髂內外、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，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脆組織，顯微鏡下腺體排列擁擠、紊亂，細胞有明顯異型性。病理診斷：?

Casediscuss子宮內膜腺癌

乳腺癌

Carcinomaofbreast

Anormalductcells

Bbasementmembrane

Clumen(centerofduct)導管雙層上皮內腺上皮，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>中央區(qū)>內上象限

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

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

浸潤性癌導管內原位癌小葉原位癌粉刺癌非粉刺導管內癌Paget病浸潤性導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

沒有突破導管和腺泡的基底膜分類:導管內原位癌

小葉原位癌

一、非浸潤性癌1．導管內原位癌

（Intraductalcarcinomainsitu）

起于乳腺小葉的終末導管限于導管內,基膜完整檢出率↑，5%－15%－30%

組織學: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%位于乳腺中央部質硬、腫塊明顯，易觸診查出導管擴張，內含壞死物質擠壓導管,壞死物質會像粉刺一樣被擠出

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

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

debris.Theneoplasticcellsexhibitnuclearpleomorphismandhyperchromasia.Thebasementmembraneisintact(2)非粉刺型導管內癌（Noncomedointraductalcarcinoma）實性、乳頭狀、篩狀排列，輕微壞死癌細胞小，較規(guī)則導管周間質纖維組織增生較輕2.小葉原位癌（Lobularcarcinomainsitu）

來自小葉的終末導管及腺泡

癌細胞局限于管泡內，未穿破其基底膜，小葉結構存在

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

AnormallobularcellsBlobularcancercellsCbasementmembraneLobularcarcinomainsituconsistsofaneoplasticproliferationofcellsintheterminalbreastductsandacini.Thecellsaresmallandround.Thereisa30%riskfordevelopmentofinvasivecarcinomainthesameortheoppositebreast.導管內癌－－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：瘤細胞孤立散在、成簇分布

大而異型，胞質透明3.佩吉特?。≒agetdisease)癌細胞穿破乳腺導管或腺泡的基底膜而侵入間質占乳腺癌>85%分類：浸潤性導管癌和浸潤性小葉癌兩種類型可并存，占10%，浸潤性小葉癌的預后較差

二、浸潤性癌導管內癌細胞突破管壁基底膜向間質浸潤最常見（70%）1.浸潤性導管癌（Invasiveductalcarcinoma）

AnormalductcellsBductalcancercellsbreakingthroughthebasementmembraneCbasementmembrane大體：色灰白，質硬，無包膜界不清，活動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、團索狀、腺樣，可見導管內原位癌癌細胞異型明顯，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%，老年婦女多見癌細胞突破基底膜向間質浸潤約20%可累及雙側乳房，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*

轉移特殊性：腦脊液、漿膜面、卵巢、子宮、骨髓肉眼：

串珠狀、細條索或環(huán)形排列正常導管周圍癌細胞小、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、鱗狀細胞癌、炎性癌

直接浸潤：乳腺實質、乳頭、皮膚、筋膜、胸肌及胸壁

淋巴結轉移：

外上、外下象限和中心區(qū)→同側腋窩淋巴結

內上、內下象限→乳內動脈旁淋巴結

血行轉移：遠處任何器官

轉移途徑135影響預后的因素

早期不易發(fā)現(xiàn)，發(fā)現(xiàn)時約50%病例已有局部淋巴結轉移

原發(fā)灶大?。?lt;1cm、無LN轉移者預后好

淋巴結轉移：無LV轉移者5年生存率70-80%

組織學類型：

組織學分級：腺管的分化程度、細胞異型性、核分裂

ER和PR：內分泌治療、預后

HER-2：靶向藥物Herceptin、預后

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歲多見單個或多個，單側或雙側發(fā)生界清，切片灰白、質韌、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，以末梢導管、腺泡擴張，間質纖維組織和上皮不同程度增生為特點25-45