肺结节指南与临床实践

肺结节最新指南与临床实践Fleischner2017guidelineforpulmonarynodules

byOnnoMetsandRobinSmithuis

theAcademicalMedicalCentre,AmsterdamandtheAlrijneHospital,Leiderdorp,theNetherlands2017年费莱舍尔学会：肺结节指南Introduction

FleischnerGuideline2017

Introduction介绍

Solidnodules

实性结节Subsolidnodules

亚实性结节Riskfactors

危险因素Notes

注意点PulmonaryNoduleMeasurements

肺结节的测量

Perifissuralnodules叶间裂旁结节

PublicationdateJuly1,2017PulmonarynodulesarefrequentlyencounteredincidentallyonchestCT.

Theroleoftheradiologististoseparatebetweenbenignandpossiblymalignantlesions,andadviseonfollow-upimagingoradditionalinvasiveimagingtechniques.Thisarticlesummarizesthebasicsofindeterminatepulmonarynodules,andpresentsthenewestmanagementrecommendationsoftheFleischnerSociety.2017年7月1日文章：肺结节是偶然胸部CT检查中频繁遇到的。放射学家的角色就是在良性灶或恶性灶二者间做出鉴别诊断，并提出影像学的随访或附加另外的有创性的介入技术。该文章概括了不能定性的肺结节的基本概念，介绍了由费舍尔学会推荐的最新的管理方法。Pulmonarynodulescanbedividedintosolidlesionsandsubsolidlesions,whichcanbefurthersubdividedintopart-solidandpuregroundglassnodules.Heresomedefinitions:Subsolidnodule(SSN)

ApulmonarynodulewithatleastpartialgroundglassappearanceGroundglass

Opacificationwithahigherdensitythanthesurroundingtissue,notobscuringunderlyingbronchovascularstructures肺结节分为实性病灶和亚实性病变。再进一步分为部分实性和纯磨玻璃结节。也有做如下的定义：

*亚实性结节（SSN）：肺结节至少有一部分呈磨玻璃的表现。*磨玻璃：相比周围组织为不透明性的高密度，但不遮挡支气管血管结构。肺结节亚实性（SSN）实性部分实性（PSN）纯磨玻璃（PGGN）中放2015年4月49卷4期（放射学分会心胸组专家共识）FleischnerGuideline2017IntroductionIn2017theupdatedFleischnerSocietyguidelinewaspublished[1].

Thesereplacetherecommendationsforsolid(2005)[2]andsubsolidpulmonarynodules(2013)[3].

Thesenewguidelinesshouldreducethenumberofunnecessaryfollow-upexaminationsandprovideclearmanagementdecisions.Nodulecharacterizationshouldbeperformedonthin-sliceCTimages≤1.5mm,sinceasmallsolidnodulemayappeartohavegroundglassdensityonathicksliceduetopartial-volumeeffect.费舍尔学会：2017年指南更新过的“2017年费舍尔学会肺结节指南”

已经发布。它替换了以往推荐的实性结节（2005年）和亚实性肺结节（2013年）新的指南将减少不必要的随访检查并提供了明确的管理决策。结节特征的评价需要薄层CT成像，即层厚要≤1.5mm,理由：小的实性结节在较厚的图像上因部分容积效应可以类似于磨玻璃密度。SolidnodulesSolidpulmonarynodulescanrepresentvariousetiologies:benigngranulomasfocalscarintrapulmonarylymphnodesprimarymalignanciesmetastaticdisease.Perifissuralnodulesareaseparateentity,sincetheyusuallyrepresentintrapulmonarylymphnodes,whicharebenignandneednofollowup.

Theyarediscussedinthelastchapter.

Inanotherarticlewepresentedsomefeaturesthatcanhelptodifferentiatebetweenbenignandmalignantlesions(clickhere)Unfortunately,thereisconsiderableoverlapandoftennodefinitiveanswercanbegivenbasedonimagingmorphology.Follow-upisthereforeacommonlyusedstrategy.实性结节实性肺结节可有多种病因学：良性肉芽肿、局灶瘢痕、肺内的淋巴结、原发性恶性肿瘤、转移性病变。叶间裂周围的结节是一单独的小体，因为它通常代表肺内的淋巴结而作为良性灶，不需随访（见后述）在另外的文章中我们提出一些影像学特点目的是用于帮助良恶病变间的鉴别，但遗憾的是有相当大的重叠，故而不能根据影像形态学做出更明确的结论，因此随访仍是常用的策略。实性大小随访低风险低、高低风险低风险低风险高风险高风险高风险高风险多发单发多发多发单发不常规随访3-6个月CT，然后18-24个月CT不常规随访考虑3个月CT，PET-CT或活检6-12个月CT，然后18-24个月CT选择性的1年复查CT选择性的1年复查CT6-12个月CT，然后考虑18-24个月CT3-6个月CT，然后考虑18-24个月CT3-6个月CT，然后考虑18-24个月CT3-6个月CT，然后18-24个月CT低风险高风险单发SubsolidnodulesMostsubsolidnodulesaretransientandtheresultofinfectionorhemorrhage.

However,persistentsubsolidnodulesoftenrepresentpathologyintheadenocarcinomatousspectrum.Noreliabledistinctioncanbemaderadiologically,althoughstudiessuggestthatlargersizeandasolidcomponentareassociatedwithmoreinvasivebehaviour.

Comparedtosolidlesions,persistentsubsolidnoduleshaveamuchslowergrowthrate,butcarryamuchhigherriskofmalignancy.

InastudybyHenschkeetal,part-solidnodulesweremalignantin63%,puregroundglassSSNsin18%andsolidnodulesonlyin7%[4].亚实性结节大部分的亚实性结节是一过性的并作为感染或出血的结果。然而，持续性的亚实性结节其病理学上多为肺腺癌之谱线。在放射学上，尽管一些研究提示：在较大的结节灶并伴实性成分及侵润征象等，仍没有更可靠的鉴别特征。与实性结节对比，持久性的亚实性结节尽管具有较缓慢的生长速度，但其更多见于恶性肿瘤。在Henschkeetal的研究中，恶性肿瘤的分别是：部分实性成分者为63%；纯磨玻璃结节（SSNs）则为18%；实性结节仅7%。磨玻璃6-12月复查CT,若持续，则3、5年CT随后的处理主要基于可疑结节随访单发亚实性结节无需随访部分实性多发性无需随访3-6月复查CT,若持续，则5年内年度CT3-6月复查CT,若稳定，则2年、4年CT3-6月复查CTSubsolidnodulesintheadenocarcinomatousspectrumwereformerlyknownasbronchoalveolarcarcinomaorBAC.

Thisterminologyshouldnolongerbeused.Anewpathology-basedclassificationforadenocarcinomawasintroducedin2011andthiscurrentclassificationmakesdistinctionbetween:Adenocacinomainsitu.Minimallyinvasiveadenocarcinoma.Invasiveadenocarcinoma.Transientsubsolidnodulesusuallyrepresentinfectionoralveolarhemorrhage.

Todifferentiatebetweentransientorpersistentsubsolidnodulesafollow-upCTshouldbeobtained.

Previously,itwasrecommendedtorepeatimagingafter3months,however,thisintervalhasbeenincreasedto12months.

Becauseoftheslowergrowthrate,thetotalfollow-upperiodforpersistentsubsolidnoduleshasbeenincreasedto5years.Theimagesshowa7mmpuregroundglasssubsolidnoduleintherightupperlobe.

Onfollow-upCTthisprovedtobeatransientsubsolidnodule.在肺腺癌中的亚实性结节即旧称的支气管肺泡癌或BAC。腺癌的新的病理学分类已在2011年公布：1、原位腺癌2、微侵润腺癌3、侵润性腺癌见左上图短暂性的亚实性结节通常代表感染或肺泡出血。为了区分短暂性或持久性亚实性结节，需要CT随访证实。在以前，这种病灶推荐3个月复查。而现在复查间隔增加到12个月。处于较缓慢增长的原因，对恒定的亚实性结节的整个的随访时期，增加到5年。左下图显示：右上叶7mm纯磨玻璃亚实性结节。随访CT证实为短暂性亚实性结节。Theseimagesshowapuregroundglasssubsolidnoduleintherightlowerlobe.

Thislesiondemonstratedgrowthinatwoyearintervalandprovedtobemalignantafterresection.RiskfactorsDefininghigh-orlow-riskiscurrentlymoredifficultthanitwasintheoldguideline.

Previouslyahigh-risksubjectwasidentifiedbasedonahistoryofheavysmoking,historyoflungcancerinafirst-degreerelativeorexposuretoasbestos,radonoruranium.Now,itisaimedfortoseparatehigh-risklesionsfromlow-riskonesbyconsideringmoreparametersthansubjectcharacteristicsalone(SeeTable).左图显示右下叶纯磨玻璃亚实性结节。该病变随访两年期间增大。手术证实为恶性。

危险因素定义高或低风险，目前要比旧的指南更困难。先前，被定义为高风险的因素是基于严重吸烟史，直系亲属肺癌史，接触石棉、氡、铀。而今，它是以区分高风险或低风险病灶为目的，则要考虑更多的参数而不是仅靠单一的某些因素。危险因素严重吸烟史暴露于石棉、氡、铀肺癌家族史老龄性别（女多于男）种族（黑人、土著人、夏威夷人多于白种人）边境投机商上叶部位多重性（结节少于5个，恶性几率增加）肺气肿和肺纤维化（特别是IPF）Sincetheseriskfactorsarenumerousandhavedifferenteffectsonthemalignancyrisk,itisproposedtoassessfinalriskcategoriesconcerningtheprobabilityofmalignancy[8](Table).NotesTheguidelinerecommendsfollow-upfornoduleswithanestimatedlungcancerriskofaround1%orgreater,whichisanarbitrarycut-off.Thelikelihoodofmalignancyisdifferentforanincidentallyfoundpulmonarynoduleinthelowerlobeofarelativelyyoungpatientcomparedtoanoduleintheupperlobeofahigh-riskheavysmoker,orinapatientwithaknownorsuspectedmalignancy.

ForthisreasontheFleischnerguidelineforthemanagementofpulmonarynodulesseparateshigh-andlow-risk,anddoesnotapplytosubjectsyoungerthan35years,immunocompromisedpatientsorpatientswithcancer[1].恶性肿瘤的可能性评估低概率（＜5%）年轻不吸烟无先前癌结节小边缘规则结节非上叶中概率（5-65%）具有高与低混合特征高概率（>65%）年老严重吸烟有先前癌结节大边缘不规则结节位于上叶使用2017年费舍尔学会肺结节指南的注意点仅用于35岁及以上者不适用免疫功能低下者，或已患有确诊性癌症者使用薄层（低剂量）CT成像重组图描述其特征和进行肺结节随访。结节的手工测量是基于结节的长轴和短轴径线；选择性地使用结节灶的容积测量，需保证随访期间的成像技术和软件的恒定性。新的指南的风险分级是两方面的综合，即病人高危因素、肺结节的特征。而不同于单一分析低或高危因素的往年的文献。PulmonaryNoduleMeasurementsIntheFleischnerguidelinesnoduledimensionscanbeobtainedusingeither2Dcalipermeasurementsor3Dnodulevolumetry.

Manual2Dcalipermeasurementsshouldbebasedontheaverageofthelong-andshort-axisdiametersofthenodule.

Theseshouldbeobtainedonthesametransverse,coronalorsagittalreconstructedimage,whicheverplanerevealsthegreatestdimensions[1].

Thisisnewcomparedtothepriorguideline,inwhichdimensionswereaverageddiametersintheaxialplaneonly[2].

Manual2Dcalipermeasurementsshouldberoundedtothenearestwholemillimeter.

Inpart-solidsubsolidnodulesboththetotalnoduleaswellasthesolidcomponentdimensionsshouldbemeasuredseparately,bothusingtheabovementionedaveragingtechnique.肺结节测量费舍尔指南中，对肺结节的大小可以通过2D卡尺测量，或者3D结节容积测量获得。手动的2D卡尺测量应是以结节的最大长轴和短轴之和除以2，而获得结节的平均大小。随访对比，应以同样的轴位、冠状、矢状重组图，选择层面内的最大径。在对部分实性的亚实性结节测量，要对其实性及磨玻璃成分要分别测量。同先前的指南比较，结节的大小只是由轴位层面上的平均直径表示。而新的2D手工卡尺测量应该是更接近实际的整体大小（mm）Alesionwhichmeasures8×5mmhasanaverageof(8+5):2=6.5mm-roundedupto7mm最终测量：7mmPerifissuralnodules(PFN)Perifissuralnodulesareaseparateentity,andlikelyrepresentintrapulmonarylymphnodes.

Morphologicallythesearesolid,homogeneousnoduleswithasmoothmargin,andareovalorrounded,lentiformortriangularinshape.

Theirlocationiswithin15mmofthefissureorthepleura.Theymayormaynothavecontactwithaninterlobarseptum.

ThelatterdifferentiatesbetweenatypicalandatypicalPFN(seeFigure).

PFNscanshowsignificantgrowthratesonserialimaging,sometimescomparabletomalignantnodules.

Thisisnotatypicalsignofmalignancy,butmerelyaresultoftheirpresumedlymphaticorigin.典型的PFN不典型的PFN非PFN叶间裂周围的结节叶间裂周围的结节是单独的实体，很可能是肺内的淋巴结。在形态上，这些结节为实性、密度均匀，边缘光滑，呈椭圆形或圆形、或凸透镜状或三角形。在PFN的位置上，胸膜或叶间裂位于其内占据15mm。或伴/不伴随与小叶间隔的接触。多个PFN在系列成像上可能显示其明显的增长率，有时候酷似恶性结节。这并非典型的恶性特征，只不过提示为淋巴源性。Inscreeningsettingithasbeenshownthatnoneofthe919typicalandatypicalPFNswerefoundtobemalignantina5.5yearfollow-up[5].

ThisconfirmedpriorresultsofAhnetal.[6].

Itisassumedthatthisbenignetiologycanbeextrapolatedtoclinicalsubjects,whichissupportedbyyetunpublisheddatainroutine-careclinicalCTimaging[7].Thecurrentlyavailableguidelinesrecommendthatwhensmallnoduleshaveaperifissuralorotherjuxtapleurallocationandamorphologyconsistentwithanintrapulmonarylymphnode,follow-upCTisnotrecommended,eveniftheaveragedimensionexceeds6mm.Perifissurallylocatednodulesthatdonotconformtothemorphologiccharacteristicsshouldberegardedasnon-PFNnodules(Figure)anddoesrequirefollow-up.处于叶间裂旁的结节，它不符合PFN的形态特点，应被列为非PFN结节（左下图）并需要随访。作者的919个典型的或不典型的PFNs在随访5.5年后没有一个发现是恶性的病灶。这也证实之前Ahnetal的研究结果。假如该良性病因如果为临床学科所接受，那么将是对至今还没有出版的临床CT成像常规护理一书的支持。Incidentalperifissuralnodulesonroutinechestcomputedtomography:lungcancerornot?

byMetsetal.

[Unpublisheddata.Submitted]当前的能查到的多数指南中建议：当叶间裂周围或邻近胸膜部位发现小结节并且其形态与肺内淋巴结一致时，即使平均大小超过6mm,也不推荐对其做CT随访。GuidelinesforManagementofIncidentalPulmonaryNodulesDetectedonCTImages:FromtheFleischnerSociety2017July2017Volume284,Issue1Publishedin:HeberMacMahon;DavidP.Naidich;JinMoGoo;KyungSooLee;AnnN.C.Leung;JohnR.Mayo;AtulC.Mehta;YoshiharuOhno;CharlesA.Powell;MathiasProkop;GeoffreyD.Rubin;CorneliaM.Schaefer-Prokop;WilliamD.Travis;PaulE.VanSchil;AlexanderA.Bankier;Radiology

2017,284,228-243.DOI:10.1148/radiol.20171616592017bytheRadiologicalSocietyofNorthAmerica,Inc./doi/abs/10.1148/radiol.2017161659Apictureisworthathousandwords一幅图胜千言接下来就以近期刊在Radiology上的一篇文献中的13个病例的26幅图为例，学习一下偶然发现的肺结节影像学特点及对待原则。Figure1:(a)Lungwindowand(b)soft-tissuewindow1-mmtransverseCTsectionsshowasmoothlymarginatedsolidnodule(arrow)withinternalfatandcalcification,consistentwithahamartoma.NofurtherCTfollow-upisrecommendedforsuchfindings.这样的结节不推荐CT随访含钙化、脂肪：肺错构瘤Figure2:(a)CTimageshowsasmoothlymarginatedsolidnodulewithcentralcalcification,typicalofahealedgranuloma.NofurtherCTfollow-upisrecommendedforsuchnodules.(b)CTimageshowsasmoothlymarginatedsolidnodulewithlaminarcalcification,typicalofahealedgranuloma.NofurtherCTfollow-upisrecommendedforsuchfindings.这两例结节不推荐CT随访中央钙化、层状钙化：为愈合后的肉芽肿Figure3:(a)Transverse5-mmCTsectionshowsanapparentlypureground-glassnoduleintheleftlowerlobe(arrow).(b)Transverse1-mmCTsectionatthesamelevelasarevealsthatthisisasuspiciouspart-solidnodulewithcysticcomponents(arrow).轴位5mm层厚显示左下肺病变似乎为纯磨玻璃结节同水平的轴位1mmCT如图，可疑为部分实性结节伴囊性成分。Figure4:(a)Transverse1-mmCTsectionshowsanodularopacityadjacenttotheminorfissure(arrow).(b)CoronalreconstructedCTimageshowsthattheopacityisabenignlinearscarorlymphoidtissue(arrow).轴位1mm层厚CT显示结节密度紧邻于小裂。冠状重组CT图显示该密度为良性线样瘢痕或淋巴样组织。Figure6:Transverse1-mmCTsectionthroughtheleftupperlobeshowsasuspicioussolidspiculatednodule(arrow).Surgeryrevealedinvasiveadenocarcinoma.Figure5:CTimageshowsasolidtriangularsubpleuralnodule(arrow)withalinearextensiontothepleuralsurface,typicalofanintrapulmonarylymphnode.NoCTfollow-upisrecommendedforsuchfindings.轴位1mm层厚显示左上肺一周边针状结节，手术证实侵润性腺癌。实性三角形胸膜下结节并线样延伸至胸膜表面，此为典型的肺内淋巴结。这种表现不推荐做CT随访。Figure7:Transverse1-mmCTsectionsobtained10monthsapartshowahighlysuspiciouspatternofprogressivethickeninginthewallofarightlowerlobecyst(arrow).Resectionrevealedinvasiveadenocarcinoma.轴位1mm层厚的图像，间隔10个月后显示右下叶囊壁明显增厚。手术及病理为侵润性腺癌。必须重视这样的特殊肺癌（囊性肺癌）Figure8:CTimageshowsmultiplesolidnodulesofvaryingsizewithlowerzonepredominance(arrows)secondarytometastaticthyroidcarcinoma.Figure9:Transverse1-mmCTsectionsthroughtherightlowerlobe.(a)Awell-defined6-mmground-glassnodule(arrow)canbeseen.(b)Imageobtainedmorethan2yearsafterashowsasubtleincreaseinthesizeofthenodule(arrow).Thisfindingwasconfirmedbynotingtheslightlyalteredrelationshiptoadjacentvascularstructures.Suchsubtleprogressioncanbedetectedonlybyusing1-mmcontiguoussections.Findingsareconsistentwithadenocarcinomainsituorminimallyinvasiveadenocarcinoma,andcontinuedyearlyfollow-upisrecommended.CT图显示下叶多发性结节，源自甲状腺癌的转移瘤。1、轴位1mmCT图见右肺下叶。左图：6mm磨玻璃结节。右图：2年

后显示轻度增大。2、这种增大，可通过结节与邻近血管的关系得到验证。3、这种轻度的进展只能通过1mm的连续层面才能观察到。4、这些表现符合肺腺癌（原位癌或微浸润腺癌），并且推荐对

其做年度随访。Figure10:(a)A1-mmtransverseCTimagethroughtherightmidlungshowsa10-mmpureground-glassnodule(arrow).(b)CTimageinthesamelocationasaat15-monthfollow-upshowsonlyaverysubtleincreaseinopacity.(c)CTimageinthesamelocationasaandbafurther10monthsafterbshowsthenodulehasevolvedintoalargerpart-solidnodule.Surgicalresectionrevealedstage1Ainvasivelepidicpredominantadenocarcinoma.图A）右中肺1mm轴位图显示一10mm纯磨玻璃结节。图B）15个月后，同层面轴位图显示该结节仅仅轻微的密度上的增高。图C）又10个月后，同层轴位图显示该结节发展有较大的部分实性结节。手术及病理：1A期浸润性鳞状上皮癌Figure11:(a)Transverse1-mmCTsectionthroughtheleftupperlobeshowsanindeterminate10-mmground-glassnodule(arrow).(b)Follow-upCTimageafter4monthsshowsintervalresolutionwithouttreatment,consistentwithabenignca