遺傳性腎癌綜合征遺傳性腎癌綜合征1（優(yōu)選）遺傳性腎癌綜合征（優(yōu)選）遺傳性腎癌綜合征2意義早期篩查仔細(xì)隨訪相應(yīng)患者及其家屬降低疾病相關(guān)死亡率并改善預(yù)后發(fā)現(xiàn)遺傳性腎癌的相關(guān)基因進(jìn)行腫瘤形成機(jī)制相關(guān)的細(xì)胞分子通路研究進(jìn)行腫瘤治療的分子靶點(diǎn)的研究意義早期篩查3種類

VHL綜合征遺傳性乳頭狀腎細(xì)胞癌(HPRC)遺傳性平滑肌瘤病及腎細(xì)胞癌綜合征(HLRCC)Birt–Hogg–Dube綜合征結(jié)節(jié)性硬化病(TS)？種類VHL綜合征42022/12/1852022/12/145VonHipple–Lindau綜合征1895年由德國(guó)眼科教授EugenvonHipple首先發(fā)現(xiàn)1926年由瑞典病理學(xué)家AvidLindau再次確認(rèn)1936年由Davison教授總結(jié)相關(guān)臨床表現(xiàn)并命名為vonHippelLindausyndrome是一種相對(duì)罕見(jiàn)的常染色體顯性遺傳病，發(fā)病率1/36000主要表現(xiàn)包括腎透明細(xì)胞癌，嗜鉻細(xì)胞瘤，視網(wǎng)膜成血管母細(xì)胞瘤，中樞神經(jīng)系統(tǒng)成血管細(xì)胞瘤等VonHipple–Lindau綜合征1895年由德6基因?qū)W研究VHL基因定位在常染色體3p2625目前已被完全測(cè)序，并確認(rèn)是存在于散發(fā)性和家族性腎透明細(xì)胞癌中的抑癌基因該基因的丟失、突變和甲基化失活導(dǎo)致正常的VHL蛋白合成障礙，是導(dǎo)致VHL綜合征的重要分子學(xué)基礎(chǔ)基因?qū)W研究VHL基因定位在常染色體3p26257頭顱MRI顯示左側(cè)延髓見(jiàn)類圓形混雜信號(hào)灶，大小約1.IsolatedcasesofuterineleiomyosarcomasPreoperativePETscansmayprovebeneficialincasesinwhichlymphnodeornonlocalizeddiseaseissuspectedIsolatedcasesofuterineleiomyosarcomasMeanageatdiagnosisisolder,nearage50yearsaggressivetumorfeaturesinyoungpatientsBemappedtoaregiononchromosome1(1q42.發(fā)病隱匿，多無(wú)明顯臨床表現(xiàn)其他病變?nèi)缫认倌夷[、附睪或闊韌帶乳頭狀囊腺瘤、腎囊腫,多無(wú)明顯癥狀，一般預(yù)后良好腎癌占VHL綜合征患者死亡原因的50%，發(fā)生率為24～70%Birt–Hogg–DubesyndromeIsolatedcasesofuterineleiomyosarcomas仔細(xì)隨訪相應(yīng)患者及其家屬仔細(xì)隨訪相應(yīng)患者及其家屬仔細(xì)隨訪相應(yīng)患者及其家屬既往體健，否認(rèn)高血壓病史，否認(rèn)家族史，體格檢查血壓輕度升高150/78mmHg仔細(xì)隨訪相應(yīng)患者及其家屬M(fèi)orerecently,detailedhistologicdescriptionhasledtomorerefinedcharacterizationofthepathologicfeaturesnowtermedHLRCCrenaltumorsBirt–Hogg–Dubesyndrome2022/12/188頭顱MRI顯示左側(cè)延髓見(jiàn)類圓形混雜信號(hào)灶，大小約1.2022該基因在VHL病家族成員中突變率幾乎達(dá)100%散發(fā)的腎透明細(xì)胞癌患者中，VHL基因突變率為46%～70%腎臟其他病理類型腫瘤未發(fā)現(xiàn)VHL基因突變?cè)摶蛟赩HL病家族成員中突變率幾乎達(dá)100%9chromophobe嫌色細(xì)胞,oncocytoma,clearcellandhybridoncocytictumorscomposedofelementsofoncocytomaandchromophobeBirt–Hogg–Dubesyndrome一項(xiàng)研究對(duì)腎臟腫瘤小于3cm的108例VHL綜合征患者與腫瘤大于3cm的73例患者做比較該基因的丟失、突變和甲基化失活導(dǎo)致正常的VHL蛋白合成障礙，是導(dǎo)致VHL綜合征的重要分子學(xué)基礎(chǔ)pulmonarymetastasesfromacaseoflocallyadvancedclearcellcarcinomaina20yearoldpatientIsolatedcasesofuterineleiomyosarcomasNephronsparingsurgeryislesswellestablishedinthissetting6cm，增強(qiáng)后邊緣較前清晰。aggressivetumorfeaturesinyoungpatientsVHL基因定位在常染色體3p2625發(fā)現(xiàn)遺傳性腎癌的相關(guān)基因Lungcystswerecommonandseenin83%VHL基因抑癌機(jī)制清楚，抑癌作用明顯，而且VHL基因只有3個(gè)外顯子，是基因治療十分理想的目的基因interventionfortumors,whichgrowtoreach3cminsizeandincludetheuseofnephronsparingprocedureswhenpossiblePathologicanalysisof130tumorsobtainedfrom30surgicallymanagedcasesidentifiedproportionaldifferencesincludinghybridonco/chromo50%,chromophobe34%,conventionalclearcell9%,oncocytoma5%andpapillary2%chromophobe嫌色細(xì)胞,oncocytoma,clearcellandhybridoncocytictumorscomposedofelementsofoncocytomaandchromophobe與cMet原癌基因的突變有關(guān)，定位于染色體7q31pulmonarycysts陰囊B超提示雙側(cè)附睪頭囊腫，左側(cè)0.既往體健，否認(rèn)高血壓病史，否認(rèn)家族史，體格檢查血壓輕度升高150/78mmHg44%beforetheageof30PreoperativePETscansmayprovebeneficialincasesinwhichlymphnodeornonlocalizeddiseaseissuspectedrenalcellcarcinoma仔細(xì)隨訪相應(yīng)患者及其家屬ClassictriadofskinfibrofolliculomasBemappedtoaregiononchromosome1(1q42.renaltumorswerediscoveredin1434%.仔細(xì)隨訪相應(yīng)患者及其家屬One39yearoldpatientwithBHDandmixedrenaltumor,includingclearcellcomponentsdevelopeddistantprogressionanddeathBirt–Hogg–Dubesyndrome結(jié)節(jié)性硬化病(TS)？Bemappedtoaregiononchromosome1(1q42.chromophobe嫌色細(xì)胞,oncocytoma,clearcellandhybridoncocytictumorscomposedofelementsofoncocytomaandchromophobe對(duì)最大徑超過(guò)3cm的腫瘤行腎部分切除術(shù)，這樣可以減低腫瘤的轉(zhuǎn)移的風(fēng)險(xiǎn)而且保留腎臟的功能指的是病人易于罹患腎乳頭狀細(xì)胞癌的狀態(tài)therelativeheterogeneityoftumorsubtypesCutaneousleiomyomasarecommonamongaffectedindividuals,thoughmaybedifficulttoidentifyrenaltumorsVHL綜合征臨床表現(xiàn)2022/12/1810chromophobe嫌色細(xì)胞,oncocytoma,cVHL綜合征診斷標(biāo)準(zhǔn)（1）中樞神經(jīng)系統(tǒng)或視網(wǎng)膜成血管細(xì)胞瘤家族病史，有一種成血管細(xì)胞瘤或內(nèi)臟病變（如腎腫瘤、胰腺腫瘤或囊腫、嗜鉻細(xì)胞瘤、附睪乳頭狀囊腺瘤等）（2）對(duì)于無(wú)明確家族遺傳史的孤立病例，若患有兩種或兩種以上成血管母細(xì)胞瘤,或一種成血管母細(xì)胞瘤和一種內(nèi)臟病變VHL綜合征診斷標(biāo)準(zhǔn)（1）中樞神經(jīng)系統(tǒng)或視網(wǎng)膜成血管細(xì)胞瘤11類型I型不表現(xiàn)為腎上腺嗜鉻細(xì)胞瘤，病變可累及中樞神經(jīng)系統(tǒng)、腎臟、胰腺等Ⅱ型伴發(fā)腎上腺嗜鉻細(xì)胞瘤ⅡA型，不伴有腎癌ⅡB型，伴有腎癌ⅡC型，僅有腎上腺嗜鉻細(xì)胞瘤表現(xiàn)類型I型不表現(xiàn)為腎上腺嗜鉻細(xì)胞瘤，病變可累及中樞神經(jīng)系統(tǒng)、12chromophobe嫌色細(xì)胞,oncocytoma,clearcellandhybridoncocytictumorscomposedofelementsofoncocytomaandchromophobeMeanageatdiagnosisisolder,nearage50years但是復(fù)雜的囊腫有可能包含腫瘤組織而逐漸生長(zhǎng)，需要定期監(jiān)測(cè)renaltumorswerediscoveredin1434%.目前已被完全測(cè)序，并確認(rèn)是存在于散發(fā)性和家族性腎透明細(xì)胞癌中的抑癌基因與散發(fā)的腎癌相比并無(wú)特異性遺傳性平滑肌瘤病及腎細(xì)胞癌Spontaneouspneumothoracesoccurredin23%:mostcommoninyoungerfamilymembers(<40years)renaltumorswerediscoveredin1434%.其他病變?nèi)缫认倌夷[、附睪或闊韌帶乳頭狀囊腺瘤、腎囊腫,多無(wú)明顯癥狀，一般預(yù)后良好降低疾病相關(guān)死亡率并改善預(yù)后44%beforetheageof30Pathologicanalysisof130tumorsobtainedfrom30surgicallymanagedcasesidentifiedproportionaldifferencesincludinghybridonco/chromo50%,chromophobe34%,conventionalclearcell9%,oncocytoma5%andpapillary2%對(duì)最大徑超過(guò)3cm的腫瘤行腎部分切除術(shù)，這樣可以減低腫瘤的轉(zhuǎn)移的風(fēng)險(xiǎn)而且保留腎臟的功能1895年由德國(guó)眼科教授EugenvonHipple首先發(fā)現(xiàn)Lungcystswerecommonandseenin83%仔細(xì)隨訪相應(yīng)患者及其家屬IsolatedcasesofuterineleiomyosarcomasPreoperativePETscansmayprovebeneficialincasesinwhichlymphnodeornonlocalizeddiseaseissuspectedinterventionfortumors,whichgrowtoreach3cminsizeandincludetheuseofnephronsparingprocedureswhenpossible影像學(xué)表現(xiàn)為乏血供的腫瘤，CT增強(qiáng)僅表現(xiàn)為輕度強(qiáng)化（增加1030HU），MRI增強(qiáng)僅15%影像學(xué)表現(xiàn)為乏血供的腫瘤，CT增強(qiáng)僅表現(xiàn)為輕度強(qiáng)化（增加1030HU），MRI增強(qiáng)僅15%6cm，增強(qiáng)后邊緣較前清晰。臨床特點(diǎn)一般情況下，病變是視網(wǎng)膜成血管母細(xì)胞瘤最早出現(xiàn)，然后是中樞神經(jīng)系統(tǒng)血管母細(xì)胞瘤，而腎癌出現(xiàn)較晚中樞神經(jīng)系統(tǒng)血管母細(xì)胞瘤和腎臟透明細(xì)胞癌為該病最常見(jiàn)的致死原因嗜鉻細(xì)胞瘤，臨床上多因出現(xiàn)高血壓癥狀而發(fā)現(xiàn)其他病變?nèi)缫认倌夷[、附睪或闊韌帶乳頭狀囊腺瘤、腎囊腫,多無(wú)明顯癥狀，一般預(yù)后良好chromophobe嫌色細(xì)胞,oncocytoma,c13VHL綜合征是遺傳性腎癌最常見(jiàn)的原因腎癌也是VHL綜合征主要的惡性腫瘤與散發(fā)的腎癌相比并無(wú)特異性腎癌占VHL綜合征患者死亡原因的50%，發(fā)生率為24～70%加上腎囊腫，VHL綜合征患者中腎臟病變的發(fā)生率可達(dá)到60%腎臟病變的平均年齡為39歲(16～67)體積較小的腎臟腫瘤（<3cm）惡性度低VHL綜合征腎臟病變?yōu)槎嘣钚訴HL綜合征是遺傳性腎癌最常見(jiàn)的原因14Walther等對(duì)VHL綜合征患者的腎臟標(biāo)本進(jìn)行研究，顯微鏡下觀察，發(fā)現(xiàn)有的標(biāo)本中存在600個(gè)腫瘤病灶和1100個(gè)囊腫病灶隨訪研究表明由單純囊腫變?yōu)槟I癌的可能性很小所以VHL綜合征的單純腎囊腫若沒(méi)有癥狀一般無(wú)需特殊治療但是復(fù)雜的囊腫有可能包含腫瘤組織而逐漸生長(zhǎng)，需要定期監(jiān)測(cè)Walther等對(duì)VHL綜合征患者的腎臟標(biāo)本進(jìn)行研究，顯微鏡15散發(fā)的腎癌一樣，VHL綜合征腎癌缺乏早期臨床癥狀，通常在很長(zhǎng)時(shí)間內(nèi)都沒(méi)有任何表現(xiàn)腎癌進(jìn)展的病例可以表現(xiàn)為血尿，疼痛或腫塊腎癌病理類型基本是透明細(xì)胞癌亞型，腫瘤體積越小傾向惡性程度越低與非VHL綜合征腎癌相比，VHL綜合征腎癌的發(fā)病年齡較早，通常表現(xiàn)為雙側(cè)多中心的實(shí)性和囊性的病變散發(fā)的腎癌一樣，VHL綜合征腎癌缺乏早期臨床癥狀，通常在很長(zhǎng)16治療VHL綜合征患者腎癌的預(yù)后與腫瘤的大小密切相關(guān)對(duì)最大徑超過(guò)3cm的腫瘤行腎部分切除術(shù)，這樣可以減低腫瘤的轉(zhuǎn)移的風(fēng)險(xiǎn)而且保留腎臟的功能對(duì)于直徑較小的腫瘤（≤3cm）可以選擇密切觀察治療VHL綜合征患者腎癌的預(yù)后與腫瘤的大小密切相關(guān)17一項(xiàng)研究對(duì)腎臟腫瘤小于3cm的108例VHL綜合征患者與腫瘤大于3cm的73例患者做比較中位時(shí)間超過(guò)5年隨訪結(jié)果顯示腫瘤小于3cm患者中無(wú)病例發(fā)生轉(zhuǎn)移，而腫瘤大于3cm組73例患者中有20例發(fā)生轉(zhuǎn)移（27%）VHL綜合征腎癌常為雙側(cè)多發(fā)，腫瘤生長(zhǎng)較慢，轉(zhuǎn)移較晚，腎臟腫瘤平均每年增長(zhǎng)0.5cm一般不建議對(duì)VHL綜合征行腎根治性切除術(shù)，即使為單側(cè)腎癌，也應(yīng)盡量行保留腎單位的腫瘤切除手術(shù)，因?yàn)閷?duì)側(cè)腎臟也有再發(fā)生腎癌的可能一項(xiàng)研究對(duì)腎臟腫瘤小于3cm的108例VHL綜合征患者與腫瘤18如果無(wú)法保留腎臟，可選擇進(jìn)行雙側(cè)腎根治性切除術(shù)，再透析或行腎移植術(shù)加服免疫抑制劑當(dāng)VHL患者接受腎移植以后，移植腎無(wú)發(fā)展為腎囊腫或腎癌的傾向但長(zhǎng)期服用免疫抑制劑是否增加VHL綜合征其他系統(tǒng)腫瘤的發(fā)病率？如果無(wú)法保留腎臟，可選擇進(jìn)行雙側(cè)腎根治性切除術(shù)，再透析或行腎19VHL基因抑癌機(jī)制清楚，抑癌作用明顯，而且VHL基因只有3個(gè)外顯子，是基因治療十分理想的目的基因目前VHL基因治療還處在體外研究動(dòng)物實(shí)驗(yàn)階段VHL基因治療將為VHL綜合征治療開(kāi)辟一個(gè)新的方向VHL基因抑癌機(jī)制清楚，抑癌作用明顯，而且VHL基因只有3個(gè)20隨訪VHL綜合征合并腎癌的患者應(yīng)每年復(fù)查一次CT或MRI如果最大腫瘤直徑超過(guò)3cm，就應(yīng)對(duì)所有腫瘤行腫瘤剜除術(shù)或腎部分切除術(shù)有VHL家族病史的人，也應(yīng)該每年復(fù)查一次CT對(duì)于無(wú)腫瘤的單純囊腫，不推薦手術(shù)切除隨訪VHL綜合征合并腎癌的患者應(yīng)每年復(fù)查一次CT或MRI21遺傳性腎癌綜合征培訓(xùn)講義課件22遺傳性乳頭狀腎細(xì)胞癌指的是病人易于罹患腎乳頭狀細(xì)胞癌的狀態(tài)與cMet原癌基因的突變有關(guān)，定位于染色體7q31常染色體顯性遺傳遺傳性乳頭狀腎細(xì)胞癌指的是病人易于罹患腎乳頭狀細(xì)胞癌的狀態(tài)23臨床表現(xiàn)發(fā)病隱匿，多無(wú)明顯臨床表現(xiàn)多為多灶性，雙側(cè)發(fā)病影像學(xué)表現(xiàn)為乏血供的腫瘤，CT增強(qiáng)僅表現(xiàn)為輕度強(qiáng)化（增加1030HU），MRI增強(qiáng)僅15%臨床表現(xiàn)發(fā)病隱匿，多無(wú)明顯臨床表現(xiàn)242022/12/18252022/12/1425治療通常選擇腎部分切除術(shù)術(shù)中仔細(xì)檢查，防止遺漏病灶治療通常選擇腎部分切除術(shù)26遺傳性平滑肌瘤病及腎細(xì)胞癌Arelativelynew,rareandaggressiveformofHRCsyndromecutaneousleiomyomasuterineleiomyomasrenalcellcarcinomafumaratehydratase,aKrebscycleenzyme遺傳性平滑肌瘤病及腎細(xì)胞癌Arelativelynew,27GeneticsBemappedtoaregiononchromosome1(1q42.343)encodesfortheHLRCCgeneproduct,fumaratehydrataseanautosomaldominantpatternthetumorsuppressorfunctionofthegeneGeneticsBemappedtoaregion28Clinicalfeaturesthefindingofseverelysymptomaticuterinefibroidsamongaffectedwomenwithinfamiliesoftenrequiringearlyhysterectomyduetodifficultiesfrommenometrorrhagia89%ofaffectedwomenunderwenthysterectomy44%beforetheageof30Clinicalfeaturesthefindingo29Clinicalfeatures89%ofaffectedwomenunderwenthysterectomypotentiallymisclassifiedascollectingducttumors1926年由瑞典病理學(xué)家AvidLindau再次確認(rèn)Lungcystswerecommonandseenin83%遺傳性乳頭狀腎細(xì)胞癌(HPRC)Pathologicanalysisof130tumorsobtainedfrom30surgicallymanagedcasesidentifiedproportionaldifferencesincludinghybridonco/chromo50%,chromophobe34%,conventionalclearcell9%,oncocytoma5%andpapillary2%thefindingofseverelysymptomaticuterinefibroidsamongaffectedwomenwithinfamiliesIsolatedcasesofuterineleiomyosarcomasBirt–Hogg–Dubesyndromepotentiallymisclassifiedascollectingducttumors散發(fā)的腎透明細(xì)胞癌患者中，VHL基因突變率為46%～70%但長(zhǎng)期服用免疫抑制劑是否增加VHL綜合征其他系統(tǒng)腫瘤的發(fā)病率？cutaneousleiomyomasthetumorsuppressorfunctionofthegene6cm，增強(qiáng)后邊緣較前清晰。頭顱MRI顯示左側(cè)延髓見(jiàn)類圓形混雜信號(hào)灶，大小約1.腎癌占VHL綜合征患者死亡原因的50%，發(fā)生率為24～70%IsolatedcasesofuterineleiomyosarcomasCutaneousleiomyomasarecommonamongaffectedindividuals,thoughmaybedifficulttoidentifyClinicalfeaturesIsolatedcase30Renalcancerswithaprevalenceestimatedbetween2and21%papillarytype2tumorspotentiallymisclassifiedascollectingducttumorsMorerecently,detailedhistologicdescriptionhasledtomorerefinedcharacterizationofthepathologicfeaturesnowtermedHLRCCrenaltumorsRenalcancerswithaprevalenc31ManagementRadiographicappearanceofHLRCCtumorsmayappearpartlycysticandpoorlydefinedNephronsparingsurgeryislesswellestablishedinthissettingSurgicalinterventionmustbeperformedwithcaretoensureminimalhandlingofthetumorandcompletewideresection,includinglymphnodedissectionPreoperativePETscansmayprovebeneficialincasesinwhichlymphnodeornonlocalizeddiseaseissuspectedManagementRadiographicappeara32Birt–Hogg–DubesyndromeThefamilialassociationofperifolliculardermatosisinvolvingthefaceandtrunkamongthreefirstdegreerelativeswasfirstdescribedbyHornsteinandKnickenbergin1975Twoyearslater,DrsBirt,HoggandDubedescribedclinicaldermatologicfindingsinvolving15familymemberswithsimilarskinnodulesdescribedasfibrofolliculomas纖維毛囊瘤,trichodiscomas毛盤狀瘤acrochordons軟垂疣Birt–Hogg–DubesyndromeThefam33GeneticsautosomaldominantpatternsofinheritancechromosomeThegeneproduct,folliculin,isthoughttobeinvolvedinregulationofthemammaliantargetofrapamycin(mTOR)pathwaybyactingthroughfolliculininteractingprotein(FNIP1)and50AMPactivatedproteinkinaseGeneticsautosomaldominantpat34ClinicalfeaturesClassictriadofskinfibrofolliculomaspulmonarycystsrenaltumorsClinicalfeaturesClassictriad35renaltumorswerediscoveredin1434%.Spontaneouspneumothoracesoccurredin23%:mostcommoninyoungerfamilymembers(<40years)Lungcystswerecommonandseenin83%Skinlesionsin90%renaltumorswerediscoveredi36therelativeheterogeneityoftumorsubtypesindolentformsofdiseasechromophobe嫌色細(xì)胞,oncocytoma,clearcellandhybridoncocytictumorscomposedofelementsofoncocytomaandchromophobeMeanageatdiagnosisisolder,nearage50yearstherelativeheterogeneityof37Pathologicanalysisof130tumorsobtainedfrom30surgicallymanagedcasesidentifiedproportionaldifferencesincludinghybridonco/chromo50%,chromophobe34%,conventionalclearcell9%,oncocytoma5%andpapillary2%Pathologicanalysisof130tum38lessaggressivetumorhistologiesnotbeconsideredanindolentdiseaseprocessaggressivetumorfeaturesinyoungpatientspulmonarymetastasesfromacaseoflocallyadvancedclearcellcarcinomaina20yearoldpatientOne39yearoldpatientwithBHDandmixedrenaltumor,includingclearcellcomponentsdevelopeddistantprogressionanddeathlessaggressivetumorhistolog39既往體健，否認(rèn)高血壓病史，否認(rèn)家族史，體格檢查血壓輕度升高150/78mmHgVHL基因抑癌機(jī)制清楚，抑癌作用明顯，而且VHL基因只有3個(gè)外顯子，是基因治療十分理想的目的基因Thegeneproduct,folliculin,isthoughttobeinvolvedinregulationofthemammaliantargetofrapamycin(mTOR)pathwaybyactingthroughfolliculininteractingprotein(FNIP1)and50AMPactivatedproteinkinase與cMet原癌基因的突變有關(guān)，定位于染色體7q31Meanageatdiagnosisisolder,nearage50yearsPathologicanalysisof130tumorsobtainedfrom30surgicallymanagedcasesidentifiedproportionaldifferencesincludinghybridonco/chromo50%,chromophobe34%,conventionalclearcell9%,oncocytoma5%andpapillary2%6cm，增強(qiáng)后邊緣較前清晰。一般情況下，病變是視網(wǎng)膜成血管母細(xì)胞瘤最早出現(xiàn)，然后是中樞神經(jīng)系統(tǒng)血管母細(xì)胞瘤，而腎癌出現(xiàn)較晚發(fā)現(xiàn)遺傳性腎癌的相關(guān)基因PreoperativePETscansmayprovebeneficialincasesinwhichlymphnodeornonlocalizeddiseaseissuspected仔細(xì)隨訪相應(yīng)患者及其家屬1895年由德國(guó)眼科教授EugenvonHipple首先發(fā)現(xiàn)結(jié)合上述臨床表現(xiàn)診斷為VHL綜合征。影像學(xué)表現(xiàn)為乏血供的腫瘤，CT增強(qiáng)僅表現(xiàn)為輕度強(qiáng)化（增加1030HU），MRI增強(qiáng)僅15%與cMet原癌基因的突變有關(guān)，定位于染色體7q31Birt–Hogg–Dubesyndrome但是復(fù)雜的囊腫有可能包含腫瘤組織而逐漸生長(zhǎng)，需要定期監(jiān)測(cè)降低疾病相關(guān)死亡率并改善預(yù)后2022/12/1840既往體健，否認(rèn)高血壓病史，否認(rèn)家族史，體格檢查血壓輕度升高12022/12/18412022/12/14412022/12/18422022/12/14422022/12/18432022/12/1443Managementinterventionfortumors,whichgrowtoreach3cminsizeandincludetheuseofnephronsparingprocedureswhenpossibleManagementinterventionfortum44該基因的丟失、突變和甲基化失活導(dǎo)致正常的VHL蛋白合成障礙，是導(dǎo)致VHL綜合征的重要分子學(xué)基礎(chǔ)該基因在VHL病家族成員中突變率幾乎達(dá)100%VHL綜合征診斷標(biāo)準(zhǔn)autosomaldominantpatternsofinheritancechromosome嗜鉻細(xì)胞瘤，臨床上多因出現(xiàn)高血壓癥狀而發(fā)現(xiàn)renalcellcarcinomaPathologicanalysisof130tumorsobtainedfrom30surgicallymanagedcasesidentifiedproportionaldifferencesincludinghybridonco/chromo50%,chromophobe34%,conventionalclearcell9%,oncocytoma5%andpapillary2%Pathologicanalysisof130tumorsobtainedfrom30surgicallymanagedcasesidentifiedproportionaldifferencesincludinghybridonco/chromo50%,chromophobe34%,conventionalclearcell9%,oncocytoma5%andpapillary2%加上腎囊腫，VHL綜合征患者中腎臟病變的發(fā)生率可達(dá)到60%Renalcancerswithaprevalenceestimatedbetween2and21%One39yearoldpatientwithBHDandmixedrenaltumor,includingclearcellcomponentsdevelopeddistantprogressionanddeath腎臟其他病理類型腫瘤未發(fā)現(xiàn)VHL基因突變chromophobe嫌色細(xì)胞,oncocytoma,clearcellandhybridoncocytictumorscomposedofelementsofoncocytomaandchromophobeBirt–Hogg–DubesyndromeBirt–Hogg–DubesyndromePreoperativePETscansmayprovebeneficialincasesinwhichlymphnodeornonlocalizeddiseaseissuspected但長(zhǎng)期服用免疫抑制劑是否增加VHL綜合征其他系統(tǒng)腫瘤的發(fā)病率？Twoyearslater,DrsBirt,HoggandDubedescribedclinicaldermatologicfindingsinvolving15familymemberswithsimilarskinnodulesdescribedasfibrofolliculomas纖維毛囊瘤,trichodiscomas毛盤狀瘤acrochordons軟垂疣VHL綜合征腎癌常為雙側(cè)多發(fā)，腫瘤生長(zhǎng)較慢，轉(zhuǎn)移較晚，腎臟腫瘤平均每年增長(zhǎng)0.interventionfortumors,whichgrowtoreach3cminsizeandincludetheuseofnephronsparingprocedureswhenpossible一般不建議對(duì)VHL綜合征行腎根治性切除術(shù)，即使為單側(cè)腎癌，也應(yīng)盡量行保留腎單位的腫瘤切除手術(shù)，因?yàn)閷?duì)側(cè)腎臟也有再發(fā)生腎癌的可能Surgicalinterventionmustbeperformedwithcaretoensureminimalhandlingofthetumorandcompletewideresection,includinglymphnodedissection總結(jié)中、青年居多，有/無(wú)家族史腎腫瘤多為雙側(cè)、多發(fā)合并其它臟器病變?nèi)旧w和基因異常治療腎腫瘤直徑小于3cm者觀察等待，當(dāng)腎腫瘤直徑大于3cm時(shí)可手術(shù)，以NSS首選該基因的丟失、突變和甲基化失活導(dǎo)致正常的VHL蛋白合成障礙，45病例男性，21歲體檢B超發(fā)現(xiàn)雙腎占位，胰腺占位3周就診患者無(wú)明顯的癥狀，無(wú)血尿、心悸、出汗、頭痛。既往體健，否認(rèn)高血壓病史，否認(rèn)家族史，體格檢查血壓輕度升高150/78mmHg病例男性，21歲46腹部CT顯示雙腎多個(gè)大小不等低密度影，部分邊緣欠清晰，增強(qiáng)后，右腎上極及左腎門處見(jiàn)不均勻性強(qiáng)化，分別為3.3×3.6cm，2.6×3.4cm。內(nèi)未見(jiàn)脂肪密度。雙腎內(nèi)亦可見(jiàn)多個(gè)不強(qiáng)化低密度影，最大者于右腎實(shí)質(zhì)內(nèi)，大小2.5×2.6cm，增強(qiáng)后邊緣較前清晰。左腎上腺區(qū)類圓形軟組織腫塊影，密度均勻，邊緣光滑，大小1.5×1.6cm，增強(qiáng)后見(jiàn)明顯均勻強(qiáng)化。胰頸部、尾部見(jiàn)斑片狀低密度影，增強(qiáng)后有輕度強(qiáng)化。CT影像表現(xiàn)提示雙腎多發(fā)腫瘤、多發(fā)囊腫，左腎上腺腫瘤，胰腺囊腺瘤2022/12/1847腹部CT顯示雙腎多個(gè)大小不等低密度影，部分邊緣欠清晰，增強(qiáng)后頭顱MRI顯示左側(cè)延髓見(jiàn)類圓形混雜信號(hào)灶，大小約1.5×1.4mm，增強(qiáng)掃描明顯強(qiáng)化，符合血管母細(xì)胞瘤行眼底熒光血管造影提示雙眼視網(wǎng)膜大動(dòng)脈血管母細(xì)胞瘤陰囊B超提示雙側(cè)附睪頭囊腫，左側(cè)0.5×0.3cm，右側(cè)0.3×0.2cm，精液囊腫可能結(jié)合上述臨床表現(xiàn)診斷為VHL綜合征。術(shù)前檢查患者血清兒茶酚胺水平位于正常范圍內(nèi)頭顱MRI顯示左側(cè)延髓見(jiàn)類圓形混雜信號(hào)灶，大小約1.5×1.48遺傳性腎癌綜合征培訓(xùn)講義課件49Meanageatdiagnosisisolder,nearage50years6cm，增強(qiáng)后邊緣較前清晰。chromophobe嫌色細(xì)胞,oncocytoma,clearcellandhybridoncocytictumorscomposedofelementsofoncocytomaandchromophobe對(duì)最大徑超過(guò)3cm的腫瘤行腎部分切除術(shù)，這樣可以減低腫瘤的轉(zhuǎn)移的風(fēng)險(xiǎn)而且保留腎臟的功能6cm，增強(qiáng)后邊緣較前清晰。renaltumors1936年由Davison教授總結(jié)相關(guān)臨床表現(xiàn)并命名為vonHippelLindausyndrome行眼底熒光血管造影提示雙眼視網(wǎng)膜大動(dòng)脈血管母細(xì)胞瘤（2）對(duì)于無(wú)明確家族遺傳史的孤立病例，若患有兩種或兩種以上成血管母細(xì)胞瘤,或一種成血管母細(xì)胞瘤和一種內(nèi)臟病變影像學(xué)表現(xiàn)為乏血供的腫瘤，CT增強(qiáng)僅表現(xiàn)為輕度強(qiáng)化（增加1030HU），MRI增強(qiáng)僅15%Isolatedcasesofuterineleiomyosarcomas結(jié)合上述臨床表現(xiàn)診斷為VHL綜合征。interventionfortumors,whichgrowtoreach3cminsizeandincludetheuseofnephronsparingprocedureswhenpossiblepotentiallymisclassifiedascollectingducttumors但是復(fù)雜的囊腫有可能包含腫瘤組織而逐漸生長(zhǎng)，需要定期監(jiān)測(cè)potentiallymisclassifiedascollectingducttumorsCT影像表現(xiàn)提示雙腎多發(fā)腫瘤、多發(fā)囊腫，左腎上腺腫瘤，胰腺囊腺瘤治療腎腫瘤直徑小于3cm者觀察等待，當(dāng)腎腫瘤直徑大于3cm時(shí)可手術(shù)，以NSS首選進(jìn)行腫瘤形成機(jī)制相關(guān)的細(xì)胞分子通路研究腎癌病理類型基本是透明細(xì)胞癌亞型，腫瘤體積越小傾向惡性程度越低Pathologicanalysisof130tumorsobtainedfrom30surgicallymanagedcasesidentifiedproportionaldifferencesincludinghybridonco/chromo50%,chromophobe34%,conventionalclearcell9%,oncocytoma5%andpapillary2%VHL基因抑癌機(jī)制清楚，抑癌作用明顯，而且VHL基因只有3個(gè)外顯子，是基因治療十分理想的目的基因pulmonarycystsI型不表現(xiàn)為腎上腺嗜鉻細(xì)胞瘤，病變可累及中樞神經(jīng)系統(tǒng)、腎臟、胰腺等既往體健，否認(rèn)高血壓病史，否認(rèn)家族史，體格檢查血壓輕度升高150/78mmHg仔細(xì)隨訪相應(yīng)患者及其家屬（2）對(duì)于無(wú)明確家族遺傳史的孤立病例，若患有兩種或兩種以上成血管母細(xì)胞瘤,或一種成血管母細(xì)胞瘤和一種內(nèi)臟病變IsolatedcasesofuterineleiomyosarcomasencodesfortheHLRCCgeneproduct,fumaratehydratase是一種相對(duì)罕見(jiàn)的常染色體顯性遺傳病，發(fā)病率1/360006cm，增強(qiáng)后邊緣較前清晰。PreoperativePETscansmayprovebeneficialincasesinwhichlymphnodeornonlocalizeddiseaseissuspected但長(zhǎng)期服用免疫抑制劑是否增加VHL綜合征其他系統(tǒng)腫瘤的發(fā)病率？中、青年居多，有/無(wú)家族史發(fā)現(xiàn)遺傳性腎癌的相關(guān)基因ClassictriadofskinfibrofolliculomasBemappedtoaregiononchromosome1(1q42.IsolatedcasesofuterineleiomyosarcomasVHL綜合征患者腎癌的預(yù)后與腫瘤的大小密切相關(guān)腎臟其他病理類型腫瘤未發(fā)現(xiàn)VHL基因突變散發(fā)的腎透明細(xì)胞癌患者中，VHL基因突變率為46%～70%加上腎囊腫，VHL綜合征患者中腎臟病變的發(fā)生率可達(dá)到60%PreoperativePETscansmayprovebeneficialincasesinwhichlymphnodeornonlocalizeddiseaseissuspected加上腎囊腫，VHL綜合征患者中腎臟病變的發(fā)生率可達(dá)到60%PreoperativePETscansmayprovebeneficialincasesinwhichlymphnodeornonlocalizeddiseaseissuspected該基因的丟失、突變和甲基化失活導(dǎo)致正常的VHL蛋白合成障礙，是導(dǎo)致VHL綜合征的重要分子學(xué)基礎(chǔ)Isolatedcasesofuterineleiomyosarcomas結(jié)合上述臨床表現(xiàn)診斷為VHL綜合征。chromophobe嫌色細(xì)胞,oncocytoma,clearcellandhybridoncocytictumorscomposedofelementsofoncocytomaandchromophobeRenalcancerswithaprevalenceestimatedbetween2and21%chromophobe嫌色細(xì)胞,oncocytoma,clearcellandhybridoncocytictumorscomposedofelementsofoncocytomaandchromophobe（優(yōu)選）遺傳性腎癌綜合征VHL綜合征腎癌常為雙側(cè)多發(fā)，腫瘤生長(zhǎng)較慢，轉(zhuǎn)移較晚，腎臟腫瘤平均每年增長(zhǎng)0.Lungcystswerecommonandseenin83%Birt–Hogg–Dubesyndrome其他病變?nèi)缫认倌夷[、附睪或闊韌帶乳頭狀囊腺瘤、腎囊腫,多無(wú)明顯癥狀，一般預(yù)后良好Thegeneproduct,folliculin,isthoughttobeinvolvedinregulationofthemammaliantargetofrapamycin(mTOR)pathwaybyactingthroughfolliculininteractingprotein(FNIP1)and50AMPactivatedproteinkinaseVHL基因定位在常染色體3p2625potentiallymisclassifiedascollectingducttumors腎癌占VHL綜合征患者死亡原因的50%，發(fā)生率為24～70%加上腎囊腫，VHL綜合征患者中腎臟病變的發(fā)生率可達(dá)到60%Bemappedtoaregiononchromosome1(1q42.1926年由瑞典病理學(xué)家AvidLindau再次確認(rèn)Twoyearslater,DrsBirt,HoggandDubedescribedclinicaldermatologicfindingsinvolving15familymemberswithsimilarskinnodulesdescribedasfibrofolliculomas纖維毛囊瘤,trichodiscomas毛盤狀瘤acrochordons軟垂疣Cutaneousleiomyomasarecommonamongaffectedindividuals,thoughmaybedifficulttoidentify但是復(fù)雜的囊腫有可能包含腫瘤組織而逐漸生長(zhǎng)，需要定期監(jiān)測(cè)interventionfortumors,whichgrowtoreach3cminsizeandincludetheuseofnephronsparingprocedureswhenpossible嗜鉻細(xì)胞瘤，臨床上多因出現(xiàn)高血壓癥狀而發(fā)現(xiàn)6cm，增強(qiáng)后邊緣較前清晰。仔細(xì)隨訪相應(yīng)患者及其家屬對(duì)最大徑超過(guò)3cm的腫瘤行腎部分切除術(shù)，這樣可以減低腫瘤的轉(zhuǎn)移的風(fēng)險(xiǎn)而且保留腎臟的功能Meanageatdiagnosisisolder,nearage50yearschromophobe嫌色細(xì)胞,oncocytoma,clearcellandhybridoncocytictumorscomposedofelementsofoncocytomaandchromophobe（優(yōu)選）遺傳性腎癌綜合征遺傳性平滑肌瘤病及腎細(xì)胞癌interventionfortumors,whichgrowtoreach3cminsizeandincludetheuseofnephronsparingprocedureswhenpossible（1）中樞神經(jīng)系統(tǒng)或視網(wǎng)膜成血管細(xì)胞瘤家族病史，有一種成血管細(xì)胞瘤或內(nèi)臟病變（如腎腫瘤、胰腺腫瘤或囊腫、嗜鉻細(xì)胞瘤、附睪乳頭狀囊腺瘤等）PreoperativePETscansmayprovebeneficialincasesinwhichlymphnodeornonlocalizeddiseaseissuspectedClassictriadofskinfibrofolliculomas治療腎腫瘤直徑小于3cm者觀察等待，當(dāng)腎腫瘤直徑大于3cm時(shí)可手術(shù)，以NSS首選Birt–Hogg–Dubesyndromepotentiallymisclassifiedascollectingducttumors1926年由瑞典病理學(xué)家AvidLindau再次確認(rèn)PreoperativePETscansmayprovebeneficialincasesinwhichlymphnodeornonlocalizeddiseaseissuspectedClassictriadofskinfibrofolliculomas患者無(wú)明顯的癥狀，無(wú)血尿、心悸、出汗、頭痛。中、青年居多，有/無(wú)家族史患者實(shí)施雙腎部分切除術(shù)，左腎上腺切除術(shù)。行眼底熒光血管造影提示雙眼視網(wǎng)膜大動(dòng)脈血管母細(xì)胞瘤與散發(fā)的腎癌相比并無(wú)特異性結(jié)合上述臨床表現(xiàn)診斷為VHL綜合征。腎癌病理類型基本是透明細(xì)胞癌亞型，腫瘤體積越小傾向惡性程度越低遺傳性平滑肌瘤病及腎細(xì)胞癌綜合征(HLRCC)仔細(xì)隨訪相應(yīng)患者及其家屬chromophobe嫌色細(xì)胞,oncocytoma,clearcellandhybridoncocytictumorscomposedofelementsofoncocytomaandchromophobeBemappedtoaregiononchromosome1(1q42.CT影像表現(xiàn)提示雙腎多發(fā)腫瘤、多發(fā)囊腫，左腎上腺腫瘤，胰腺囊腺瘤PreoperativePETscansmayprovebeneficialincasesinwhichlymphnodeornonlocalizeddiseaseissuspected有VHL家族病史的人，也應(yīng)該每年復(fù)查一次CTTwoyearslater,DrsBirt,HoggandDubedescribedclinicaldermatologicfindingsinvolving15familymemberswithsimilarskinnodulesdescribedasfibrofolliculomas纖維毛囊瘤,trichodiscomas毛盤狀瘤acrochordons軟垂疣該基因的丟失、突變和甲基化失活導(dǎo)致正常的VHL蛋白合成障礙，是導(dǎo)致VHL綜合征的重要分子學(xué)基礎(chǔ)（優(yōu)選）遺傳性腎癌綜合征notbeconsideredanindolentdiseaseprocessLungcystswerecommonandseenin83%VHL綜合征合并腎癌的患者應(yīng)每年復(fù)查一次CT或MRI腎臟其他病理類型腫瘤未發(fā)現(xiàn)VHL基因突變VHL綜合征腎癌常為雙側(cè)多發(fā)，腫瘤生長(zhǎng)較慢，轉(zhuǎn)移較晚，腎臟腫瘤平均每年增長(zhǎng)0.但是復(fù)雜的囊腫有可能包含腫瘤組織而逐漸生長(zhǎng)，需要定期監(jiān)測(cè)胰頸部、尾部見(jiàn)斑片狀低密度影，增強(qiáng)后有輕度強(qiáng)化。chromophobe嫌色細(xì)胞,oncocytoma,clearcellandhybridoncocytictumorscomposedofelementsofoncocytomaandchromophobe發(fā)現(xiàn)遺傳性腎癌的相關(guān)基因VHL基因定位在常染色體3p2625lessaggressivetumorhistologiesSurgicalinterventionmustbeperformedwithcaretoensureminimalhandlingofthetumorandcompletewideresection,includinglymphnodedissection1926年由瑞典病理學(xué)家AvidLindau再次確認(rèn)NephronsparingsurgeryislesswellestablishedinthissettingMeanageatdiagnosisisolder,nearage50yearsVHL綜合征腎癌常為雙側(cè)多發(fā)，腫瘤生長(zhǎng)較慢，轉(zhuǎn)移較晚，腎臟腫瘤平均每年增長(zhǎng)0.VHL基因定位在常染色體3p2625interventionfortumors,whichgrowtoreach3cminsizeandincludetheuseofnephronsparingprocedureswhenpossible對(duì)于無(wú)腫瘤的單純囊腫，不推薦手術(shù)切除發(fā)現(xiàn)遺傳性腎癌的相關(guān)基因VHL綜合征腎癌常為雙側(cè)多發(fā)，腫瘤生長(zhǎng)較慢，轉(zhuǎn)移較晚，腎臟腫瘤平均每年增長(zhǎng)0.VHL綜合征診斷標(biāo)準(zhǔn)Meanageatdiagnosisisolder,nearage50years加上腎囊腫，VHL綜合征患者中腎臟病變的發(fā)生率可達(dá)到60%患者實(shí)施雙腎部分切除術(shù)，左腎上腺切除術(shù)。胰腺病變考慮良性腫瘤可能性大，另外同期手術(shù)創(chuàng)傷大，故未一期同時(shí)處理Meanageatdiagnosisisolder50遺傳性腎癌綜合征遺傳性腎癌綜合征51（優(yōu)選）遺傳性腎癌綜合征（優(yōu)選）遺傳性腎癌綜合征52意義早期篩查仔細(xì)隨訪相應(yīng)患者及其家屬降低疾病相關(guān)死亡率并改善預(yù)后發(fā)現(xiàn)遺傳性腎癌的相關(guān)基因進(jìn)行腫瘤形成機(jī)制相關(guān)的細(xì)胞分子通路研究進(jìn)行腫瘤治療的分子靶點(diǎn)的研究意義早期篩查53種類

VHL綜合征遺傳性乳頭狀腎細(xì)胞癌(HPRC)遺傳性平滑肌瘤病及腎細(xì)胞癌綜合征(HLRCC)Birt–Hogg–Dube綜合征結(jié)節(jié)性硬化病(TS)？種類VHL綜合征542022/12/18552022/12/145VonHipple–Lindau綜合征1895年由德國(guó)眼科教授EugenvonHipple首先發(fā)現(xiàn)1926年由瑞典病理學(xué)家AvidLindau再次確認(rèn)1936年由Davison教授總結(jié)相關(guān)臨床表現(xiàn)并命名為vonHippelLindausyndrome是一種相對(duì)罕見(jiàn)的常染色體顯性遺傳病，發(fā)病率1/36000主要表現(xiàn)包括腎透明細(xì)胞癌，嗜鉻細(xì)胞瘤，視網(wǎng)膜成血管母細(xì)胞瘤，中樞神經(jīng)系統(tǒng)成血管細(xì)胞瘤等VonHipple–Lindau綜合征1895年由德56基因?qū)W研究VHL基因定位在常染色體3p2625目前已被完全測(cè)序，并確認(rèn)是存在于散發(fā)性和家族性腎透明細(xì)胞癌中的抑癌基因該基因的丟失、突變和甲基化失活導(dǎo)致正常的VHL蛋白合成障礙，是導(dǎo)致VHL綜合征的重要分子學(xué)基礎(chǔ)基因?qū)W研究VHL基因定位在常染色體3p262557頭顱MRI顯示左側(cè)延髓見(jiàn)類圓形混雜信號(hào)灶，大小約1.IsolatedcasesofuterineleiomyosarcomasPreoperativePETscansmayprovebeneficialincasesinwhichlymphnodeornonlocalizeddiseaseissuspectedIsolatedcasesofuterineleiomyosarcomasMeanageatdiagnosisisolder,nearage50yearsaggressivetumorfeaturesinyoungpatientsBemappedtoaregiononchromosome1(1q42.發(fā)病隱匿，多無(wú)明顯臨床表現(xiàn)其他病變?nèi)缫认倌夷[、附睪或闊韌帶乳頭狀囊腺瘤、腎囊腫,多無(wú)明顯癥狀，一般預(yù)后良好腎癌占VHL綜合征患者死亡原因的50%，發(fā)生率為24～70%Birt–Hogg–DubesyndromeIsolatedcasesofuterineleiomyosarcomas仔細(xì)隨訪相應(yīng)患者及其家屬仔細(xì)隨訪相應(yīng)患者及其家屬仔細(xì)隨訪相應(yīng)患者及其家屬既往體健，否認(rèn)高血壓病史，否認(rèn)家族史，體格檢查血壓輕度升高150/78mmHg仔細(xì)隨訪相應(yīng)患者及其家屬M(fèi)orerecently,detailedhistologicdescriptionhasledtomorerefinedcharacterizationofthepathologicfeaturesnowtermedHLRCCrenaltumorsBirt–Hogg–Dubesyndrome2022/12/1858頭顱MRI顯示左側(cè)延髓見(jiàn)類圓形混雜信號(hào)灶，大小約1.2022該基因在VHL病家族成員中突變率幾乎達(dá)100%散發(fā)的腎透明細(xì)胞癌患者中，VHL基因突變率為46%～70%腎臟其他病理類型腫瘤未發(fā)現(xiàn)VHL基因突變?cè)摶蛟赩HL病家族成員中突變率幾乎達(dá)100%59chromophobe嫌色細(xì)胞,oncocytoma,clearcellandhybridoncocytictumorscomposedofelementsofoncocytomaandchromophobeBirt–Hogg–Dubesyndrome一項(xiàng)研究對(duì)腎臟腫瘤小于3cm的108例VHL綜合征患者與腫瘤大于3cm的73例患者做比較該基因的丟失、突變和甲基化失活導(dǎo)致正常的VHL蛋白合成障礙，是導(dǎo)致VHL綜合征的重要分子學(xué)基礎(chǔ)pulmonarymetastasesfromacaseoflocallyadvancedclearcellcarcinomaina20yearoldpatientIsolatedcasesofuterineleiomyosarcomasNephronsparingsurgeryislesswellestablishedinthissetting6cm，增強(qiáng)后邊緣較前清晰。aggressivetumorfeaturesinyoungpatientsVHL基因定位在常染色體3p2625發(fā)現(xiàn)遺傳性腎癌的相關(guān)基因Lungcystswerecommonandseenin83%VHL基因抑癌機(jī)制清楚，抑癌作用明顯，而且VHL基因只有3個(gè)外顯子，是基因治療十分理想的目的基因interventionfortumors,whichgrowtoreach3cminsizeandincludetheuseofnephronsparingprocedureswhenpossiblePathologicanalysisof130tumorsobtainedfrom30surgicallymanagedcasesidentifiedproportionaldifferencesincludinghybridonco/chromo50%,chromophobe34%,conventionalclearcell9%,oncocytoma5%andpapillary2%chromophobe嫌色細(xì)胞,oncocytoma,clearcellandhybridoncocytictumorscomposedofelementsofoncocytomaandchromophobe與cMet原癌基因的突變有關(guān)，定位于染色體7q31pulmonarycysts陰囊B超提示雙側(cè)附睪頭囊腫，左側(cè)0.既往體健，否認(rèn)高血壓病史，否認(rèn)家族史，體格檢查血壓輕度升高150/78mmHg44%beforetheageof30PreoperativePETscansmayprovebeneficialincasesinwhichlymphnodeornonlocalizeddiseaseissuspectedrenalcellcarcinoma仔細(xì)隨訪相應(yīng)患者及其家屬ClassictriadofskinfibrofolliculomasBemappedtoaregiononchromosome1(1q42.renaltumorswerediscoveredin1434%.仔細(xì)隨訪相應(yīng)患者及其家屬One39yearoldpatientwithBHDandmixedrenaltumor,includingclearcellcomponentsdevelopeddistantprogressionanddeathBirt–Hogg–Dubesyndrome結(jié)節(jié)性硬化病(TS)？Bemappedtoaregiononchromosome1(1q42.chromophobe嫌色細(xì)胞,oncocytoma,clearcellandhybridoncocytictumorscomposedofelementsofoncocytomaandchromophobe對(duì)最大徑超過(guò)3cm的腫瘤行腎部分切除術(shù)，這樣可以減低腫瘤的轉(zhuǎn)移的風(fēng)險(xiǎn)而且保留腎臟的功能指的是病人易于罹患腎乳頭狀細(xì)胞癌的狀態(tài)therelativeheterogeneityoftumorsubtypesCutaneousleiomyomasarecommonamongaffectedindividuals,thoughmaybedifficulttoidentifyrenaltumorsVHL綜合征臨床表現(xiàn)2022/12/1860chromophobe嫌色細(xì)胞,oncocytoma,cVHL綜合征診斷標(biāo)準(zhǔn)（1）中樞神經(jīng)系統(tǒng)或視網(wǎng)膜成血管細(xì)胞瘤家族病史，有一種成血管細(xì)胞瘤或內(nèi)臟病變（如腎腫瘤、胰腺腫瘤或囊腫、嗜鉻細(xì)胞瘤、附睪乳頭狀囊腺瘤等）（2）對(duì)于無(wú)明確家族遺傳史的孤立病例，若患有兩種或兩種以上成血管母細(xì)胞瘤,或一種成血管母細(xì)胞瘤和一種內(nèi)臟病變VHL綜合征診斷標(biāo)準(zhǔn)（1）中樞神經(jīng)系統(tǒng)或視網(wǎng)膜成血管細(xì)胞瘤61類型I型不表現(xiàn)為腎上腺嗜鉻細(xì)胞瘤，病變可累及中樞神經(jīng)系統(tǒng)、腎臟、胰腺等Ⅱ型伴發(fā)腎上腺嗜鉻細(xì)胞瘤ⅡA型，不伴有腎癌ⅡB型，伴有腎癌ⅡC型，僅有腎上腺嗜鉻細(xì)胞瘤表現(xiàn)類型I型不表現(xiàn)為腎上腺嗜鉻細(xì)胞瘤，病變可累及中樞神經(jīng)系統(tǒng)、62chromophobe嫌色細(xì)胞,oncocytoma,clearcellandhybridoncocytictumorscomposedofelementsofoncocytomaandchromophobeMeanageatdiagnosisisolder,nearage50years但是復(fù)雜的囊腫有可能包含腫瘤組織而逐漸生長(zhǎng)，需要定期監(jiān)測(cè)renaltumorswerediscoveredin1434%.目前已被完全測(cè)序，并確認(rèn)是存在于散發(fā)性和家族性腎透明細(xì)胞癌中的抑癌基因與散發(fā)的腎癌相比并無(wú)特異性遺傳性平滑肌瘤病及腎細(xì)胞癌Spontaneouspneumothoracesoccurredin23%:mostcommoninyoungerfamilymembers(<40years)renaltumorswerediscoveredin1434%.其他病變?nèi)缫认倌夷[、附睪或闊韌帶乳頭狀囊腺瘤、腎囊腫,多無(wú)明顯癥狀，一般預(yù)后良好降低疾病相關(guān)死亡率并改善預(yù)后44%beforetheageof30Pathologicanalysisof130tumorsobtainedfrom30surgicallymanagedcasesidentifiedproportionaldifferencesincludinghybridonco/chromo50%,chromophobe34%,conventionalclearcell9%,oncocytoma5%andpapillary2%對(duì)最大徑超過(guò)3cm的腫瘤行腎部分切除術(shù)，這樣可以減低腫瘤的轉(zhuǎn)移的風(fēng)險(xiǎn)而且保留腎臟的功能1895年由德國(guó)眼科教授EugenvonHipple首先發(fā)現(xiàn)Lungcystswerecommonandseenin83%仔細(xì)隨訪相應(yīng)患者及其家屬IsolatedcasesofuterineleiomyosarcomasPreoperativePETscansmayprovebeneficialincasesinwhichlymphnodeornonlocalizeddiseaseissuspectedinterventionfortumors,whichgrowtoreach3cminsizeandincludetheuseofnephronsparingprocedureswhenpossible影像學(xué)表現(xiàn)為乏血供的腫瘤，CT增強(qiáng)僅表現(xiàn)為輕度強(qiáng)化（增加1030HU），MRI增強(qiáng)僅15%影像學(xué)表現(xiàn)為乏血供的腫