外科病理學(xué)實(shí)踐：診斷過程的初學(xué)者指南第10章胰

外科病理學(xué)實(shí)踐：診斷過程的初學(xué)者指南第10章胰第10章胰（Pancreas）Whipple手術(shù)(TheWhippleProcedure)TheWhippleprocedureis,atminimum,apancreaticoduodenectomy,whichmayormaynotalsoincludepylorusofthestomachandthegallbladder.Inthepylorus-preservingWhippleprocedure,thesimplestversion,youreceivethesegmentofduodenumfromjustpastthepylorustoabout20cmbeyondtheampullaofVater.Theheadofthepancreasisnestledinthecurveoftheduodenumneartheampulla;thepancreasisshapedlikeaJ,andtheheadisthebaseoftheJ,withtheuncinateprocessasthehook.Thedistalcommonbileductrunsthroughthepancreasandenterstheampulla,whereitisjoinedbythemainpancreaticduct(Figure10.1).Usuallyitisonlytheheadofpancreasthatcomesout;ifthetailisalsoinvolved,youmaygetthetotalpancreasandspleen.Whipple手術(shù)至少是胰十二指腸切除術(shù)，可能包括或不包括胃幽門和膽囊。在保留幽門的Whipple手術(shù)中，最簡單的術(shù)式是從剛過幽門到Vater壺腹外約20厘米的十二指腸段。胰頭位于壺腹附近的十二指腸彎曲處；胰腺呈J形，胰頭為J形的基部，鉤突為彎鉤處。遠(yuǎn)端膽總管穿過胰腺進(jìn)入壺腹，在壺腹與主胰管相連（圖10.1）。通常只有胰頭露在外面；如果胰尾也受累，你可能會得到整個(gè)胰腺和脾。Figure10.1.DiagramofspecimenobtainduringaWhippleprocedure.Theheadofthepancreascomesoutattachedtoasegmentofduodenum.Themainpancreaticductisvisibleatthepancreaticneckmargin(asurgicalmargin).Thecommonbileductentersthepancreastojointhepancreaticduct(alsoasurgicalmargin).Theuncinateprocessisthetipofthepancreas,anditsedgeabutsmajorvessels(asofttissuemargin).圖10.1.Whipple手術(shù)標(biāo)本示意圖。露在外面的胰頭與一段十二指腸相連。主胰管在胰頸切緣（手術(shù)切緣）可見。膽總管（也是一個(gè)外科切緣）進(jìn)入胰腺與胰管相連。鉤突在胰腺的一端，其切緣鄰接大血管（軟組織切緣）。圖中文字：proximalmargin，近端切緣ampulla，壺腹distalmargin，遠(yuǎn)端切緣duodenum，十二指腸pancreaticneckandduct，胰頸和胰管commonbileduct，膽總管uncinate，鉤突inkededge，墨染切緣Therearefiveprincipalmarginsthatareusuallysampledonfrozensection(seeFigure10.1).Thefirstisthepancreaticmargin,orthepancreaticneck(wheretheJistransected).Thisisusuallytakenasashavemargin,samplingtheentirecrosssectionofpancreas,andcanceranywhereontheslideisapositivemargin.Thereisnoneckmarginonatotalpancreatectomy.冰凍切片通常要取5個(gè)主要切緣（見圖10.1）。第一個(gè)是胰腺切緣或胰頸切緣（J形被切斷的地方）。這里通常削取切緣，取胰腺的整個(gè)橫截面，切片上任何位置有癌都視為陽性切緣。全胰腺切除術(shù)沒有胰頸切緣。Thesecondmarginisthecommonbileductmargin,whichisashaveofthebileductstump.Thisensuresthatcancerisnottrackingupthebileducttowardtheliver.第二個(gè)切緣是膽總管切緣，這是膽管殘端，也是幻燈片。這確保癌不會沿著膽管向肝轉(zhuǎn)移。Thethirdistheuncinatemargin.ThisisthetipoftheshortendoftheJ,anditrepresentstheplacewherethepancreassitsagainstthemajorvessels.Fortheuncinate,youshouldtakeonerepresentativeperpendicularmargin,andtheedgeofthetissueisinked.Cancerontheslideisokay,aslongasitdoesnottouchink.Asthistissueabutsmajorvessels,thesurgeonoftencannotresectadditionaltissueanyway.第三個(gè)是鉤突切緣。這是J形短端的尖端，代表胰腺靠著大血管的位置。對于鉤突，切取一個(gè)有代表性的垂直切緣，并且組織切緣已涂抹墨水。切片上有癌是可以的，只要它不接觸墨水。由于該組織毗鄰大血管，外科醫(yī)生通常無法切除更多的其他組織。Thefourthandfifthmarginsaretheproximalanddistalduodenalmargins.Itisrareforthesesectionstocontaintumor.第四和第五個(gè)切緣是十二指腸近端和遠(yuǎn)端切緣。這些切片很少含有腫瘤。MostWhippleproceduresareperformedforapancreaticmassseenradiologically.Althoughitispossibletogetacancerdiagnosisbyfine-needleaspiration,thisisnotalwaysperformed,andfalse-negativeresultsarenotuncommon.Therefore,oftenourfirstlookatthetumorisduringtheWhippleprocedure.大多數(shù)Whipple手術(shù)是針對放射學(xué)看到的胰腺腫塊。雖然可以通過細(xì)針穿刺獲得癌診斷，但并不總是這樣，假陰性結(jié)果并不少見。因此，我們通常在Whipple手術(shù)標(biāo)本第一次看到腫瘤。（譯注：補(bǔ)充胰腺解剖示意圖如下）正常胰腺（TheNormalPancreas）Thenormalpancreasisalargemixedexocrineandendocrinegland,withacinarcellsarrangedaroundductsinlobularunits.Theacinarcellssecretedigestiveenzymesinprecursorforms,whichtraveltotheduodenumviatheducts.Normalductsarelowcuboidalepithelium,andtheacinarcellsarewedge-shapedgranularpinkandpurplecells(Figure10.2).ScatteredamongthemaretheneuroendocrineisletsofLangerhans,whichshowtypicalneuroendocrinecytologyandarearrangedinlittlenests.正常胰腺是一個(gè)巨大的外分泌和內(nèi)分泌混合腺，腺泡細(xì)胞排列在導(dǎo)管周圍，形成小葉單位。腺泡細(xì)胞分泌消化酶前體，通過導(dǎo)管進(jìn)入十二指腸。正常導(dǎo)管為低立方上皮，腺泡細(xì)胞為楔形顆粒性粉紅色和紫色細(xì)胞（圖10.2）。其中散布著Langerhans神經(jīng)內(nèi)分泌小島（譯注：即胰島），顯示出典型的神經(jīng)內(nèi)分泌細(xì)胞學(xué)，排列成小巢狀。Figure10.2.Normalpancreaticacinus.Theductisseenatthecenter(arrowhead),withsurroundingaciniofsecretorycells(arrow).圖10.2.正常胰腺腺泡。導(dǎo)管位于中心（箭頭），周圍有分泌細(xì)胞的腺泡（箭號）。慢性胰腺炎與導(dǎo)管腺癌(ChronicPancreatitisVersusDuctalAdenocarcinoma)Chronicpancreatitisisnotanuncommonfindinginaresectedpancreas.Thedamagedonetothepancreasbychronicobstruction,aswithamass,causesdiffusefibrosis,atrophyoftheacinarunits,reactivechanges,anddisruptionofthenormalarchitecture,allofwhichcanmimiccarcinoma.Oneofthehardesttasks(especiallyonfrozensection)isdifferentiatingreactivepancreaticductsfromwell-differentiatedinfiltratingadenocarcinoma,themostcommonpancreaticmalignancy.Sometipsincludethefollowing:慢性胰腺炎在切除的胰腺中并不少見。慢性阻塞（如腫塊）對胰腺造成的損害，會導(dǎo)致彌漫性纖維化、腺泡單位萎縮、反應(yīng)性改變和正常結(jié)構(gòu)破壞，所有這些都可能貌似癌。最困難的任務(wù)之一（尤其是冰凍切片）是區(qū)分反應(yīng)性胰腺導(dǎo)管和高分化浸潤性腺癌，后者是最常見的胰腺惡性腫瘤。一些提示包括：有用但主觀（Helpfulbutsubjective）Onlowpower,chronicpancreatitishasalobulararchitecture,withlargecentralductssurroundedbysmallerperipheralones.Cancerishaphazard,withrandomandirregulardistributionofglands(Figure10.3).低倍鏡下，慢性胰腺炎具有小葉結(jié)構(gòu)，大的中央導(dǎo)管圍繞著小的外周導(dǎo)管。癌是雜亂的，腺體隨機(jī)地不規(guī)則分布（圖10.3）。Figure10.3.Chronicpancreatitisversuscancer,lowpower.(A)Inchronicpancreatitis,thelargeductsmayshowmarkedreactivechanges,appearingblueandprominent,buttheyshouldstillbelocatedbetweenlobulesofacini(arrow).Theacinishowmarkedatrophyandfibrosissuchthatonlythesmallductsremainandappearinfiltrative;however,thelobulesretainacircumscribedoutline(blackline).(B)Inadenocarcinoma,large,prominent,irregularlyshapedductsarescatteredthroughout,withoutrespecttonormalarchitecture(1).Largeductsnexttovessels(2)ornerves(3)arediagnosticofcancer.圖10.3.慢性胰腺炎與癌，低倍。（A）在慢性胰腺炎中，大導(dǎo)管可能顯示明顯的反應(yīng)性改變，呈藍(lán)色且明顯，但仍應(yīng)位于腺泡小葉之間（箭號）。腺泡顯示明顯萎縮和纖維化，只有小導(dǎo)管殘留，像是浸潤性；然而，小葉保留一個(gè)邊界清楚的輪廓（黑線）。（B）在腺癌中，大的、顯著的、不規(guī)則形狀的導(dǎo)管散在遍布，與正常結(jié)構(gòu)無關(guān)（1）?？拷埽?）或神經(jīng)（3）的大導(dǎo)管對癌有診斷意義。Incompletelumina,inwhichtheluminalspacesarenotsymmetricallysurroundedbynuclei,andluminalnecrosisbothpointtoadiagnosisofpancreaticcancer(Figure10.4).腺腔不完整，腺腔周圍的細(xì)胞核不對稱地分布；以及腺腔壞死，二者對癌均有診斷意義（圖10.4）。Figure10.4.Adenocarcinoma.Onhighpower,theinfiltrativeglandsshowincompletelumens(arrow),cribriformgrowthpattern(arrowhead),andperineuralinvasion(N).Inset:Markedvariationinnuclearsizeisdiagnosticofcancer.Notethelargenucleuswithprominentnucleolus(arrowhead)acrosstheglandfromnucleilessthanonefourthofitssize.圖10.4.腺癌。高倍鏡下，浸潤腺體顯示腺腔不完整（箭號）、篩狀生長模式（箭頭）和神經(jīng)周圍浸潤（N）。插圖：細(xì)胞核大小的顯著變化對癌有診斷意義。注意大核有顯著核仁（箭頭），大核穿過腺體中較小的核，小核不到大核的1/4。Notecellularpleomorphism.Ingeneral,cancertendstohavehyperchromaticandirregularlyshapednuclei,mitoses,andnecrosis(seeFigure10.4).Youwillhearofthe“4:1rule,”whichstatesthatif,inonegland,onenucleusisfourtimesthesize(area)ofanother,itiscancer.However,chronicpancreatitiscanleadtosomemoresubtleatypia,anditdoestakesomeexperiencetotellthedifferencebetweena4:1ratioanda3:1ratio.Also,youwillsometimesseewell-differentiatedpancreaticcarcinomawithuniformnuclei.注意細(xì)胞多形性。一般來說，癌往往有核深染和核不規(guī)則、核分裂和壞死（見圖10.4）。你會聽到“4:1規(guī)則”，即，如果一個(gè)腺體中的一個(gè)核的大?。娣e）是另一個(gè)核的四倍，那就是癌。然而，慢性胰腺炎可能會導(dǎo)致某些更微妙的非典型性，要區(qū)分4:1和3:1的比例確實(shí)需要一些經(jīng)驗(yàn)。此外，你有時(shí)會看到分化良好的胰腺癌，細(xì)胞核均勻。無用（Nothelpful）Thefibrosisofchronicpancreatitiscanlookmuchlikeadesmoplasticstromalresponse.However,thepaleedematousfibrosiscanaccentuatethelobulararchitectureofchronicpancreatitis,whichishelpful.慢性胰腺炎的纖維化可能貌似促結(jié)締組織增生性間質(zhì)反應(yīng)。然而，淡染水腫性纖維化可能使得慢性胰腺炎的小葉結(jié)構(gòu)更明顯，有助于區(qū)分。EveryinterndotsallthebenignisletsofLangerhansonapancreaticneck,usuallymissingthesneakyinvasivestuff.Islets,inchronicpancreatitis,areessentiallyallthatremainsofthewitheredparenchyma,andthereforetheylookcrowded,infiltrative,andhaphazard(Figure10.5).Asistrueforanyendocrinecell,thesecellscanhavesomepleomorphism,andinsomecasestheycaninvolveperineuralspaces.Fortunately,thechromatinstilllooksneuroendocrine,sotrytoignorethemeventhoughtheyreallydolookalittlelikelobularbreastcarcinoma.每個(gè)實(shí)習(xí)生都會在胰頸畫出所有良性胰島，卻通常會漏掉那些鬼鬼祟祟的浸潤性東西。在慢性胰腺炎中，胰島基本上是萎縮的胰腺實(shí)質(zhì)的全部殘余，因此它們看起來擁擠、浸潤且雜亂分布（圖10.5）。正如任何內(nèi)分泌細(xì)胞一樣，這些細(xì)胞可能具有某些多形性，在某些病例中，它們可能累及神經(jīng)周圍間隙。幸運(yùn)的是，染色質(zhì)看起來仍然是神經(jīng)內(nèi)分泌的，所以盡量忽略它們，即使它們看起來確實(shí)有點(diǎn)像乳腺小葉癌。Figure10.5.ResidualisletsofLangerhans.Neuroendocrinecellsareamongthelasttogoinchronicpancreatitisandappeartoinfiltratethroughthefibroticstroma(arrowheads).However,theirsmall,round,dense,regularnucleidonotresemblepancreaticadenocarcinoma.圖10.5.殘留的胰島。神經(jīng)內(nèi)分泌細(xì)胞是慢性胰腺炎最后剩余的細(xì)胞之一，似乎通過纖維化間質(zhì)浸潤（箭頭）。然而，它們的核小、圓、致密、規(guī)則分布，與胰腺癌不同。免費(fèi)贈(zèng)品（即使是初學(xué)者也能解釋）（Freebies(eventhebeginnercaninterpretthem)）Glandsinanerve,orperineuralinvasion,alwaysindicatecancer.神經(jīng)中的腺體，或神經(jīng)周圍浸潤，總是提示癌。Largeductsrunningnexttoalargemuscularvesselalmostalwaysindicatecancer(Figure10.6).靠近肌性大血管的大導(dǎo)管，幾乎總是提示癌（圖10.6）。Ductsleavingthepancreastoinfiltratetheduodenumalwaysindicatecancer.離開胰腺的導(dǎo)管浸潤十二指腸，總是提示癌。Figure10.6.Adenocarcinomanexttoavessel.Largeduct-likestructures(arrow)nexttoalarge-calibervessel(V)arealmostcertainlycancer,evenifdeceptivelywelldifferentiated.圖10.6.血管旁邊的腺癌。大口徑血管（V）旁邊的大導(dǎo)管狀結(jié)構(gòu)（箭號）幾乎肯定是癌，即使貌似溫良。胰腺中的異型增生（DysplasiainthePancreas）Thepancreasisnotanorganthatcanbeevaluatedwithserialbiopsies,andthusthenaturalhistoryandmalignantpotentialofdysplasiaarenotwellunderstood.However,therearerecognizedgradesofdysplasiawithintheductsystem,calledpancreaticintraepithelialneoplasia(PanIN).ThisrangesfromPanIN1,whichmayoverlapwithhyperplasticorreactivechanges,toPanIN3,whichiscarcinomainsitu.Alesionshouldalwaysbegradedbythehighestlevelofdysplasiaseen.胰腺不能通過連續(xù)活檢來評估，因此異型增生的自然史和惡性潛能還不清楚。然而，導(dǎo)管系統(tǒng)內(nèi)存在公認(rèn)的異型增生分級，稱為胰腺上皮內(nèi)腫瘤（PanIN）。其范圍從可能與增生性或反應(yīng)性改變重疊的PanIN1到PanIN3（原位癌）。始終按所見的最高異型增生程度進(jìn)行分級。PanIN1Ahasaflatlayeroftallcolumnarcellswithbasalnucleiandapicalmucinandnoatypia.Thecellsaresimilartonormalendocervicalglands(Figure10.7).PanIN1BisthesameasPanIN1Abutwithapapillaryorundulatingappearance.Panin1A有一層平坦的高柱狀細(xì)胞，有基底核和頂端黏液，無非典型性。這些細(xì)胞類似正常的宮頸腺（圖10.7）。PanIN1B與PanIN1A相同，但有乳頭狀或起伏的結(jié)構(gòu)。Figure10.7.Thegradesofpancreaticintraepithelialneoplasia(PanIN).(A)PanIN1showstallmucinouscellsresemblingendocervix.(B)PanIN2showsincreasingnuclearcrowding,enlargement,andatypia,suggestiveofatubularadenomaofcolon.(C)PanIN3showshighgradenucleiwithlossofpolarity,frequentmitoses,andlossofmucinousdifferentiation.圖10.7.胰腺上皮內(nèi)腫瘤（PanIN）的分級。（A）PanIN1顯示類似子宮頸內(nèi)膜的高柱狀黏液細(xì)胞。（B）PanIN2顯示核擁擠、核增大和異型性增加，類似結(jié)腸管狀腺瘤。（C）PanIN3顯示高級別細(xì)胞核，極性喪失，核分裂頻繁，黏液分化喪失。PanIN2isflatorpapillarybutwithnuclearabnormalities,includingnuclearcrowdingandenlargement,stratification,hyperchromasia,andsometimesbasalmitoses.Thisepitheliumshouldremindyouofatubularadenomaorwhatwouldbecalledlow-gradedysplasiainthegastrointestinaltract(seeFigure10.7).PanIN2呈平坦或乳頭狀，但有核異常，包括核擁擠和增大、復(fù)層化、深染，有時(shí)有基底部核分裂。這種上皮讓你想起管狀腺瘤或胃腸道的低度異型增生（見圖10.7）。PanIN3iscarcinomainsitu.Youmayseeacribiforming,papillary,ormicropapillaryarchitectureornecrosis.Cytologicfeaturesincludelargeuglynucleiwithprominentnucleoli,totallossofpolarity,atypicalmitoses,malorientedgobletcells(upsidedown)—essentiallythesamecriteriayouwoulduseforhigh-gradedysplasiainothergastrointestinalepithelia(seeFigure10.7).PANIN3是原位癌?？赡軙吹胶Y狀、乳頭狀或微乳頭狀結(jié)構(gòu)或壞死。細(xì)胞學(xué)特征包括丑陋的大核，核仁顯著，極性完全喪失，非典型核分裂象，方向錯(cuò)亂的杯狀細(xì)胞（倒置）—基本上與其他胃腸道上皮高度異型增生的標(biāo)準(zhǔn)相同（見圖10.7）。InvasivecarcinomaarisingoutofPanIN3iswelldocumented.However,rememberthatPanINisacommonincidentalfindinginapancreas.Itisnotvisibleradiologically,itdoesnotmakeamass,anditdoesnotcauseobstruction.Ifyouhaveaclinicalmass,youshouldbethinkinginsteadofaninvasivecarcinomaorintraductalpapillarymucinousneoplasm(IPMN;seenextsection).Also,donotworrytoomuchaboutthePanINs.WiththeexceptionofPanIN3,theyareofnoprovenclinicalsignificance;marginswithPanIN1orPanIN2lesionscansafelybecallednegative.起源于PanIN3的浸潤性癌已有大量的文獻(xiàn)報(bào)道。然而，請記住，PanIN是胰腺中常見的偶然發(fā)現(xiàn)。放射學(xué)上看不見，不形成腫塊，也不造成阻塞。如果有臨床腫塊，應(yīng)該考慮的浸潤性癌或?qū)Ч軆?nèi)乳頭狀黏液性腫瘤（IPMN；見下一節(jié)）。另外，不要太擔(dān)心PanIN。除PanIN3外，它們沒有已證實(shí)的臨床意義；PanIN1或PanIN2病變的切緣可以安全地稱為陰性。導(dǎo)管內(nèi)乳頭狀黏液性腫瘤（IntraductalPapillaryMucinousNeoplasm）AnIPMNisdefinedasamucin-producingneoplasmarisingineitherthemainpancreaticductorasecondary(side-branch)duct.Theductsareusuallydilatedbecausetheyarefullofapapillaryproliferationandabundantmucin.Themainlesiontoconsiderinthedifferentialdiagnosisisthemucinouscysticneoplasm(discussedlater).Ifyouhaveamucin-producingcysticneoplasminthepancreas,alwaysprobethemainducttoseeifthecystsareconnectedtoit(anIPMN)ornot(amucinouscysticneoplasm).Essentiallyitisagrossdiagnosisandmayevenbeanendoscopicone;ifmucinwasseencomingoutoftheampulla,thecystsmustbeconnectedtothepancreaticductsandthelesionismorelikelytobeanIPMN.However,onceyouhaveidentifiedanIPMNgrossly,youmustlookmicroscopicallytoevaluatethelevelofatypiaandruleoutaninvasivecarcinoma.Intraductalpapillarymucinousneoplasmsaredividedintothreecategories:IPMN的定義是一種產(chǎn)生黏液的腫瘤，發(fā)生在主胰管或副胰管（側(cè)支）。導(dǎo)管通常擴(kuò)張，因?yàn)槌錆M乳頭狀增殖和豐富的黏液。主要鑒別診斷是黏液性囊性腫瘤（稍后討論）。如果在胰腺發(fā)現(xiàn)分泌黏液的囊性腫瘤，一定要探測主導(dǎo)管，看看囊腫與之相連（IPMN），或不相連（黏液性囊性腫瘤）。本質(zhì)上，這是一個(gè)大體診斷，甚至可能是一個(gè)內(nèi)窺鏡診斷；如果看到壺腹流出黏液，囊腫必然與胰管相連，病變更可能是IPMN。然而，一旦你大體上確定了IPMN，你必須在顯微鏡下觀察以評估非典型性水平并排除浸潤性癌。導(dǎo)管內(nèi)乳頭狀黏液性腫瘤分為三類：Withlow-gradedysplasia:Theseneoplasmsarecytologicallyblandandhavethesame

criteriaasPanIN1.伴低度異型增生：這些腫瘤的細(xì)胞形態(tài)學(xué)溫和，其標(biāo)準(zhǔn)與PanIN1相同。Withmoderatedysplasia(formerlyknownasborderline):TheseneoplasmscytologicallyshowincreasingnuclearabnormalitiesandhavethesamecriteriaasPanIN2.中度異型增生（以前稱為交界性）：這些腫瘤細(xì)胞學(xué)顯示核異常增加，其標(biāo)準(zhǔn)與PanIN2相同。Withhigh-gradedysplasia:Theseneoplasmsarecytologicallymalignant(seePanIN3criteria,discussedearlier).AnyIPMNwithhigh-gradedysplasiamustbecarefullyscrutinizedforinvasivecarcinomaslippingoutoftheduct.伴高度異型增生：這些腫瘤細(xì)胞學(xué)呈惡性（參見前面討論的PanIN3標(biāo)準(zhǔn)）。任何伴有高度異型增生的IPMN都必須仔細(xì)檢查是否有浸潤性癌超出導(dǎo)管范圍。Acommonquestionis,howcanItellPanINinalargishductfromIPMNinasmallishsidebranchduct?FeaturesthatfavoranIPMNincludethefollowing:一個(gè)常見的問題是，如何區(qū)分大導(dǎo)管中的PanIN和較小側(cè)支管管道中的IPMN？傾向IPMN的特點(diǎn)包括：Longpapillae,orfinger-likeprojectionswithfibrovascularcores(Figure10.8)長乳頭，或指狀突起，有纖維血管軸心（圖10.8）Figure10.8.Papillaryprojections,intraductalpapillarymucinousneoplasmwithmoderatedysplasia.Thesetallpapillaryfrondsarecoveredwithmucinouscellsshowingmoderatedysplasia,similartoPanIN2.圖10.8.乳頭狀突起，導(dǎo)管內(nèi)乳頭狀黏液性腫瘤伴中度異型增生。這些高高的乳頭結(jié)構(gòu)被覆黏液細(xì)胞，顯示中度異型增生，類似于PanIN2。Bluemucininthelumenoftheduct導(dǎo)管腔中的藍(lán)色黏液Continuitywithoneofthemainpancreaticducts與其中一條主胰管相連Grosslyorradiologicallyvisible肉眼可見或放射學(xué)上可見Whenitcomesrightdowntoit,identifyingthegradeofdysplasiacorrectlyrightismuchmoreimportantthandistinguishingbetweenanIPMNandaPanIN.歸根結(jié)底，正確識別異型增生的等級比區(qū)分IPMN和PanIN更重要。浸潤性導(dǎo)管腺癌（InvasiveAdenocarcinoma(Ductal)）Themostcommonformofinfiltratingadenocarcinomainthepancreasisductal.Itusuallyarisesintheheadandofteninvadesadjacentstructuresbeforecomingtoclinicalattention.Thehistologicfeaturesofductaladenocarcinomahavebeendescribedearlier.Onceyouhaveestablishedcarcinoma,lookcarefullyatallsectionsofduodenumandextrapancreaticbileducttoseeifthecarcinomainvadesthosestructures(inincreaseinstage).Thebileductandampullaryregionhavenumerousbenignglandsbranchingoffofthem,butrememberthatthebenignglandswillhavealobularandsymmetriclookatlowpower.Variantsofductaladenocarcinomaincludeadenosquamous,colloid(mucinous),hepatoid,medullary,signetringcell,undifferentiated(anaplastic),andundifferentiatedcarcinomawithosteoclast-likegiantcells.胰腺中最常見的浸潤性腺癌是導(dǎo)管腺癌。它通常發(fā)生在胰頭，并在引起臨床注意之前侵入鄰近結(jié)構(gòu)。導(dǎo)管腺癌的組織學(xué)特征已在前面描述過。一旦確定了癌，仔細(xì)觀察十二指腸和胰外膽管的所有部分，看看癌是否侵入這些結(jié)構(gòu)（分期升級）。膽管和壺腹區(qū)有許多良性腺體從中分支出來，但要記住，良性腺體在低倍鏡下呈小葉狀和對稱外觀。導(dǎo)管腺癌的變異型包括腺鱗癌、膠樣癌（黏液癌）、肝樣癌、髓樣癌、印戒細(xì)胞癌、未分化癌（間變性癌），和具有破骨細(xì)胞樣巨細(xì)胞的未分化癌。胰腺其他囊性病變(OtherCysticLesionsofthePancreas)黏液囊性腫瘤(MucinousCysticNeoplasm)Themucinouscysticneoplasmoccursalmostalwaysinmiddle-agedwomen,usuallyinthetailofthepancreas.Thismucinousneoplasmproducesmultilocularcyststhatdonotcommunicatewiththemainductsystem.Theyhave,bydefinition,arimofovarianstroma(Figure10.9),sothinkofthemasmucinousovariantumorsheterotopicintothepancreas.Asintheovary,theyhavethreegrades,andthesegradesconvenientlyparallelthethreegradesoftheIPMN:黏液囊性腫瘤幾乎總是發(fā)生在中年女性，通常發(fā)生在胰尾。該腫瘤產(chǎn)生多房囊腫，與主導(dǎo)管系統(tǒng)不相連。根據(jù)定義，它們有一圈卵巢型間質(zhì)（圖10.9），因此可以視為異位進(jìn)入胰腺的黏液性卵巢腫瘤。與卵巢一樣分三級，與IPMN的三個(gè)等級平行：Figure10.9.Mucinouscysticneoplasm.Thecystliningiscomposedofmucinouscells,benigninthisexample,andunderlyingbluespindlyovarian-typestroma(arrow).圖10.9.黏液囊性腫瘤。囊腫被覆黏液細(xì)胞，本例為良性，下面為藍(lán)色梭形卵巢型間質(zhì)（箭號）。Withlow-gradedysplasia:noatypia,likePanIN1低伴度異型增生：無非典型性，如PanIN1Withmoderatedysplasia:increasingnuclearatypiaand/orarchitecturalcomplexity,likePanIN2伴中度異型增生：核異型性和/或結(jié)構(gòu)復(fù)雜性增加，如PanIN2Withhigh-gradedysplasia:carcinomainsitu,likePanIN3伴高度異型增生：原位癌，如PanIN3Approximatelyonethirdofmucinouscysticneoplasmshaveanassociatedinvasivecarcinoma,whichwouldbecalledinfiltratingmoderatelydifferentiatedadenocarcinomaarisinginassociationwithamucinousneoplasmwithhigh-gradedysplasia.大約1/3黏液囊性腫瘤伴有浸潤性癌，稱為浸潤性中分化腺癌起源于并發(fā)的黏液性腫瘤伴高度異型增生。漿液性囊腺瘤(SerousCystadenoma)Serouscystadenomasofthepancreas,unliketheserouscystadenomasoftheovary,arealmostalwaysmicrocystic.Grossly,theyhaveacentralscarandradiatingsmallclear-fluid-filledcysts,likethecrosssectionofalime.Microscopically,thecystsarelinedbycuboidalcellswithclearcytoplasm(glycogen)andsmall,uniform,roundnuclei(Figure10.10).Areasofmoresolidortrabeculargrowthmaylookmuchlikemetastaticrenalcellcarcinoma,whichisinfactinthedifferential.Serouscystadenocarcinomasexistbutareextremelyrare.與卵巢漿液性囊腺瘤不同，胰腺漿液性囊腺瘤幾乎都是微囊。大體上，有一個(gè)中心瘢痕和放射狀分布的充滿透明液體的小囊腫，像酸橙的橫截面。顯微鏡下，囊腫被覆立方形細(xì)胞，胞質(zhì)透明（糖原），核小、圓而均勻（圖10.10）。更加實(shí)性或小梁生長的區(qū)域可能貌似轉(zhuǎn)移性腎細(xì)胞癌，確實(shí)需要鑒別。也存在漿液性囊腺癌，但極為罕見。Figure10.10.Serouscystadenoma,highpower.Thecellsliningthemultilocularcystaresmall,withdenseroundnucleiandclearcytoplasm(arrow).圖10.10.漿液性囊腺瘤，高倍。多房囊腫的被覆細(xì)胞小，有致密的圓核和透明胞質(zhì)（箭頭）。實(shí)性假乳頭狀腫瘤(Solid-PseudopapillaryNeoplasm)Solid-pseudopapillaryneoplasmsareunusualanddistinctivetumorsinthedifferentialdiagnosisofcysticlesionsinyoungwomen.Theyaremalignantbutextremelyindolent.Thecelloforiginisnotknown,andsotheneoplasmisnamedbasedonitsappearance.Theseneoplasmsstartoutsolidbutundergocysticdegenerationandthereforemaypresentasacyst(despitethename).Thecellsarecharacteristicallynoncohesive,andsotheremainingsolidareasshowapseudopapillarygrowthpattern(meaningthereissolidgrowthalongfibrovascularsepta,withadropoutofthelooselycohesivecellsinbetweenseptaandaresultingpapillarylook).Thenucleiaresmall,oval,bland,andgrooved(Figure10.11).在年輕女性囊性病變的鑒別診斷中，實(shí)性假乳頭狀腫瘤是一種少見的獨(dú)特腫瘤。它們是惡性的，但極其惰性。起源細(xì)胞未知，因此根據(jù)其形態(tài)學(xué)命名。這些腫瘤開始是實(shí)性，但會發(fā)生囊性變，因此可能表現(xiàn)為囊性（盡管名稱不同）。細(xì)胞的特征是無黏附性，因此其余的實(shí)性區(qū)域顯示假乳頭狀生長模式（意思是沿著纖維血管間隔呈實(shí)性生長，間隔之間的細(xì)胞呈松散黏附并脫落，因此看似假乳頭結(jié)構(gòu)）。細(xì)胞核小，橢圓形，形態(tài)溫和，有核溝（圖10.11）。Figure10.11.Solidpseudopapillarytumor.Thesmallplasmacytoidcellswithneuroendocrine-typechromatincouldbemistakenforisletcelltumororacinarcellcarcinoma.However,thisgrowthpattern,withrosette-likegrowtharoundfibrovascularcores(arrows)anddropoutoftheinterveningcells,istypicalofthesolidpseudopapillarytumor.圖10.11.實(shí)性假乳頭狀腫瘤。漿細(xì)胞樣小細(xì)胞伴神經(jīng)內(nèi)分泌型染色質(zhì)，可能誤診為胰島細(xì)胞瘤或腺泡細(xì)胞癌。然而，這種生長模式（圍繞纖維血管軸心（箭號）的菊形團(tuán)樣生長，介于其間的細(xì)胞脫落）是實(shí)性假乳頭狀腫瘤的典型表現(xiàn)。Thedifferentialdiagnosisforthisneoplasmincludeswell-differentiatedpancreaticendocrineneoplasmandacinarcellcarcinoma,bothofwhicharediscussedlater.Immunohistochemicallabelingisveryhelpful,assolid-pseudopapillaryneoplasmsareCD10positiveandshownuclearlabelingforβ-catenin.該腫瘤的鑒別診斷包括高分化胰腺內(nèi)分泌腫瘤和腺泡細(xì)胞癌（下文討論）。免疫組化非常有用，因?yàn)樵撃[瘤呈CD10陽性，并且核表達(dá)β-catenin。假囊腫(Pseudocyst)Thedefinitionofapseudocystis“l(fā)ackinganepitheliallining.”Thisisawalled-offareaoffatnecrosisandgranulationtissuecontaininghighlevelsofpancreaticenzymesthatisnotusuallymistakenforamalignancy,clinicallyormicroscopically.Rememberthatmostpseudocystsareactuallyextrapancreatic.假囊腫的定義是“缺乏被覆上皮”。這是由脂肪壞死和肉芽組織構(gòu)成的封閉區(qū)域，含有高水平的胰酶，在臨床或顯微鏡下通常不會被誤認(rèn)為惡性腫瘤。記住，大多數(shù)假囊腫實(shí)際上是胰腺外的。胰腺其他實(shí)性腫瘤(OtherSolidTumorsinthePancreas)Thereareonlytwopancreaticcelltypesnotyetdiscussed(notcountingsofttissueelementssuchasvesselsandnerves):theacinarcells(exocrinesecretory)andtheisletcells(endocrine).Neoplasmscomposedofthesecellsareimportanttorememberbecausetheycanreleaseenzymesorhormones,causingdramaticclinicalpresentations.These