如何定义恶性潜能未定的甲状腺滤泡性病变？

如何定义恶性潜能未定的甲状腺滤泡性病变？刘志艳[e-mail]山东大学齐鲁医院病理科2015/10/23*目录CONTENTS甲状腺滤泡上皮性肿瘤诊断现状FTT争论的焦点之一：PTC-NFTT争论的焦点之二：有无浸润展望*Ⅰ.甲状腺滤泡上皮性肿瘤诊断现状Follicularcelloriginatedthyroidtumor（FTT）良性：滤泡腺瘤1.乳头状癌（PTC）2.滤泡癌（FTC）3.低分化癌（PDC）4.未分化癌（UDC）恶性：Noprecursorlesion!!!IsthereBorderlinerumor???非典型腺瘤？？？NoprecursorlesionofFollicularthyroidtumor!!!IsthereBorderlinelesioninthyroid???Atypicalfollicularadenoma非典型腺瘤？？？Differentcriteriaindifferentorgans?恶性嗜铬细胞瘤诊断标准：I.体积大II.肿瘤性坏死III.局灶性浸润和/或血管浸润任何单一组织学特征，都不能直接作为诊断恶性的依据。普遍认为恶性嗜铬细胞瘤必须有转移！胰腺高分化内分泌肿瘤，恶性行为未定（WDT-UMP)诊断标准？有下列条件之一者:1.2cm,2.核分裂像2-10/10HPF,3.MIB-12%,4.脉管或神经浸润即使有血管和神经浸润，也不足以诊断恶性，而是交界性肿瘤恶性最可靠的证据是：转移到邻近淋巴结或肝脏；或者肉眼上浸润到邻近器官形态学依然是诊断PTC的“金标准”！Strictcriteriashouldbeappliedinthediagnosisofencapsulatedfollicularvariantofpapillarythyroidcarcinoma.ChanJK:AmJClinPathol117:16-18,2002.ChanJK甲状腺孤立性滤泡性病变细胞学评价乳头状癌，滤泡亚型评价结构及其周围包膜或血管侵犯?滤泡性癌滤泡性腺瘤细胞密度低;大滤泡;乳头状增生;与周围甲状腺相似胶样结节有无细胞密度低;大滤泡;乳头状增生;与周围甲状腺相似*Ⅱ.甲状腺肿瘤争论的焦点之一：PTC-N①.Encapsulatedfollicularvariantpapillarythyroidcarcinoma(EnFVPTC)2keypoints:Follicularvariantpapillarythyroidcarcinoma(FVPTC)•FirstdescribedbyLindsay(1960)•PopularizedbyChen&Rosai(1977)•Athyroidcarcinomashowingnuclearfeaturesofclassicalpapillarycarcinoma,butgrowinginapurefollicularpattern(lackingpapillae)ChanJKChanJKLiuJ,etal.Follicularvariantofpapillarythyroidcarcinoma:aclinicopathologicstudyofaproblematicentity.Cancer2006;15;107(6):1255-64.该例是癌吗！13374:71-y-o,female:WDT-UMP=NIFTP15116:40-y-o,male.HyperplasticNodulewithincompletePTC-N15116:40-y-o,male,HyperplasticNodulewithincompletePTC-N12473:59y,male：FA+focalPTC-NKi67:notincreasedMalignantdiagnosis(FVPTC)shouldnotbeusedtononinvasiveencapsulatedfollicularpatternlesionswithequivocalPTC-Nuntiluncertaintyaboutthenatureofthislesionissettled.Weproposedtocallitaswelldifferentiatedtumorofuncertainbehavior(WDT-UB)asaborderlinelesion.KKakudo,BaiY,LiuZ,OzakiT,PathologyInternational62:155-160,2012.神户KumaHospital（隈病院）是日本最大的甲状腺专科医院。隈病院院长KanjiKuma在实践中发现，包裹性非浸润性甲状腺滤泡性病变，即便是单纯切除后，肿瘤生物学行为也几近良性——他因之对病理医生的诊断产生了怀疑。HistoryofDiagnosticCriteriaforEnFVPTC1996年，Kuma教授组织7名甲状腺病理专家对100例包裹性甲状腺肿瘤进行评估，结果存在较大的不一致性。ReviewersRates(%)ofmalignancyamong100casesyearsafterboardcertifiedyearsyearsyearsyearsyearsyearsyears病理医生如何评价甲状腺乳头状癌细胞核特点（PTC-N）Case1(70yearsoldfemale)美国病理工作者(benign:malignant=1:2)FollicularadenomaPapillarycarcinomaFollicularvariantofpapillarycarcinoma日本病理工作者(benign:malignant=3:0)Follicularadenoma(atypicaladenoma)AtypicaladenomaFollicularadenomaEndocrPathol,2002Hirokawa和Kakudo教授组织四名USA-P4名J-P对21例甲状腺滤泡性肿瘤进行评判。AmJSurgPathol,2002.这些病例中有25%被美国病理工作者诊断为PTC，远高于日本病理工作者的4%。USA开始关注：DrLloyd对MayoClinic的87例FVPTC进行了回顾性研究，证实在FVPTC的诊断中存在较大的不一致性。Pleasenote,thereviewerNo.9madethehighestrateofbenigndiagnosisamong10reviewers,isKennichiKakudo.StricklandKCetal:TheImpactofNon-InvasiveFollicularVariantofPapillaryThyroidCarcinomaonRatesofMalignancyforFineNeedleAspirationDiagnosticCategories.Thyroid25:987-992,2015.Theircohortof655FNAswithsubsequentresectionspecimensincluded53(8.1%)non-diagnostic,167(25.5%)benign,97(14.8%)AUS/FLUS,88(13.4%)suspiciousforfollicularneoplasm,94(14.4%)suspiciousformalignancy,and156(23.8%)malignantcases.Surgicalresectionsdemonstratedbenignfindingsin309(47.2%)andmalignanttumorsin346(52.8.0%),including85NIFTPsaccountingfor24.6%ofmalignancies.OurfindingsdemonstratethatifterminologyweretochangeandNIFTPswerenotconsideredcarcinomas,thiswouldsubstantiallydecreasetherateofmalignancyforFNAdiagnosticcategories.NIFTPsoccupied25%ofallmalignancy.Risksofmalignancydroppedsignificantly,ifNIFTPisnolongeracarcinoma.AUS:21.6%（45%decrease）FN:37.8%（18%decrease）Suspicious:45.7%（48%decrease）Therewere2648thyroidsamplesexaminedattheDepartmentofHumanPathology,WakayamaMedicalUniversitybetween1990and2009.Thereareonly2casesofnon-invasiveEnFVPTCand501casesofconventionalandothervariantsofPTCinthatperiod.IncidenceofEFVPTCinOurPracticeTheincidenceofnon-invasiveEnFVPTCwasonly0.4%(2/503)inourpracticeandtheincidenceofcombinedEnFVPTCandWDT-UMP(EnFVPTCinUSA)was6.0%.30additionalcasesofWDT-UMPwereidentifiedfrombenigndiagnoses.Minorfully-developedPTC-Nin12casesanddiffusequestionablePTC-Nin18cases.2010年04月28日本病理学会2011年2月28美国100thUSCAP*Ⅲ.甲状腺滤泡性肿瘤争论的焦点之二：有无浸润②.CapsularinvasiononlyFollicularThyroidCarcinomaandFolliculartumorwithUncertaincapsularinvasion2keypoints:FTAFTCWhatisyourdiagnosis?滤泡性腺瘤还是滤泡性癌?•区分滤泡性癌与滤泡性腺瘤的唯一标准是:–血管侵犯或–包膜侵犯•不能仅通过细胞密度高，复杂的结构或细胞异型诊断滤泡性癌•滤泡性癌的诊断必须应用严格的标准ChanJKC:Tumorsofthethyroidandparathyroidglands.In:FletcherCDM,editor.DiagnosticHistopathologyofTumors.3rded.London,England:ChurchillLivingston;2007.p.997–1078.那么，有包膜侵犯足以诊断FTC吗？Pseudoinvasion?Whatistrueinvasion?可疑包膜浸润的滤泡癌应该退一步诊断，因仅有包膜浸润的FTC癌死亡率为0。VanHeerdenJA:Follicularthyroidcarcinomawithcapsularinvasionalone:Nonthreateningmalignancy.Surgery112:1130-1136,1992.如果包膜浸润不足以诊断恶性(?)那么是良性病变么?PianaSetal:Encapsulatedwell-differentiatedfollicular-patternedthyroidcarcinomadonotplayasignificantroleinthefatalityratefromthyroidcarcinoma.AmJSurgPathol,34:868-872,2010.Pianaetalreviewed67casesthatdiedofthyroidcarcinomainacohortof1