遺傳性腎癌綜合征培訓講義課件

遺傳性腎癌綜合征（優(yōu)選）遺傳性腎癌綜合征意義早期篩查仔細隨訪相應患者及其家屬降低疾病相關死亡率并改善預后發(fā)現(xiàn)遺傳性腎癌的相關基因進行腫瘤形成機制相關的細胞分子通路研究進行腫瘤治療的分子靶點的研究種類

VHL綜合征遺傳性乳頭狀腎細胞癌(HPRC)遺傳性平滑肌瘤病及腎細胞癌綜合征(HLRCC)Birt–Hogg–Dube綜合征結(jié)節(jié)性硬化病(TS)？2023/6/105VonHipple–Lindau綜合征1895年由德國眼科教授EugenvonHipple首先發(fā)現(xiàn)1926年由瑞典病理學家AvidLindau再次確認1936年由Davison教授總結(jié)相關臨床表現(xiàn)并命名為vonHippelLindausyndrome是一種相對罕見的常染色體顯性遺傳病，發(fā)病率1/36000主要表現(xiàn)包括腎透明細胞癌，嗜鉻細胞瘤，視網(wǎng)膜成血管母細胞瘤，中樞神經(jīng)系統(tǒng)成血管細胞瘤等基因?qū)W研究VHL基因定位在常染色體3p2625目前已被完全測序，并確認是存在于散發(fā)性和家族性腎透明細胞癌中的抑癌基因該基因的丟失、突變和甲基化失活導致正常的VHL蛋白合成障礙，是導致VHL綜合征的重要分子學基礎頭顱MRI顯示左側(cè)延髓見類圓形混雜信號灶，大小約1.IsolatedcasesofuterineleiomyosarcomasPreoperativePETscansmayprovebeneficialincasesinwhichlymphnodeornonlocalizeddiseaseissuspectedIsolatedcasesofuterineleiomyosarcomasMeanageatdiagnosisisolder,nearage50yearsaggressivetumorfeaturesinyoungpatientsBemappedtoaregiononchromosome1(1q42.發(fā)病隱匿，多無明顯臨床表現(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,多無明顯癥狀，一般預后良好腎癌占VHL綜合征患者死亡原因的50%，發(fā)生率為24～70%Birt–Hogg–DubesyndromeIsolatedcasesofuterineleiomyosarcomas仔細隨訪相應患者及其家屬仔細隨訪相應患者及其家屬仔細隨訪相應患者及其家屬既往體健，否認高血壓病史，否認家族史，體格檢查血壓輕度升高150/78mmHg仔細隨訪相應患者及其家屬Morerecently,detailedhistologicdescriptionhasledtomorerefinedcharacterizationofthepathologicfeaturesnowtermedHLRCCrenaltumorsBirt–Hogg–Dubesyndrome2023/6/108該基因在VHL病家族成員中突變率幾乎達100%散發(fā)的腎透明細胞癌患者中，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chromophobe嫌色細胞,oncocytoma,clearcellandhybridoncocytictumorscomposedofelementsofoncocytomaandchromophobeBirt–Hogg–Dubesyndrome一項研究對腎臟腫瘤小于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致正常的VHL蛋白合成障礙，是導致VHL綜合征的重要分子學基礎pulmonarymetastasesfromacaseoflocallyadvancedclearcellcarcinomaina20yearoldpatientIsolatedcasesofuterineleiomyosarcomasNephronsparingsurgeryislesswellestablishedinthissetting6cm，增強后邊緣較前清晰。aggressivetumorfeaturesinyoungpatientsVHL基因定位在常染色體3p2625發(fā)現(xiàn)遺傳性腎癌的相關基因Lungcystswerecommonandseenin83%VHL基因抑癌機制清楚，抑癌作用明顯，而且VHL基因只有3個外顯子，是基因治療十分理想的目的基因interventionfortumors,whichgrowtoreach3cminsizeandincludetheuseofnephronsparingprocedureswhenpossiblePathologicanalysisof130tumorsobtainedfrom30surgicallymanagedcasesidentifiedproportionaldifferencesincludinghybridonco/chromo50%,chromophobe34%,conventionalclearcell9%,oncocytoma5%andpapillary2%chromophobe嫌色細胞,oncocytoma,clearcellandhybridoncocytictumorscomposedofelementsofoncocytomaandchromophobe與cMet原癌基因的突變有關，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，否認高血壓病史，否認家族史，體格檢查血壓輕度升高150/78mmHg44%beforetheageof30PreoperativePETscansmayprovebeneficialincasesinwhichlymphnodeornonlocalizeddiseaseissuspectedrenalcellcarcinoma仔細隨訪相應患者及其家屬ClassictriadofskinfibrofolliculomasBemappedtoaregiononchromosome1(1q42.renaltumorswerediscoveredin1434%.仔細隨訪相應患者及其家屬One39yearoldpatientwithBHDandmixedrenaltumor,includingclearcellcomponentsdevelopeddistantprogressionanddeathBirt–Hogg–Dubesyndrome結(jié)節(jié)性硬化病(TS)？Bemappedtoaregiononchromosome1(1q42.chromophobe嫌色細胞,oncocytoma,clearcellandhybridoncocytictumorscomposedofelementsofoncocytomaandchromophobe對最大徑超過3cm的腫瘤行腎部分切除術，這樣可以減低腫瘤的轉(zhuǎn)移的風險而且保留腎臟的功能指的是病人易于罹患腎乳頭狀細胞癌的狀態(tài)therelativeheterogeneityoftumorsubtypesCutaneousleiomyomasarecommonamongaffectedindividuals,thoughmaybedifficulttoidentifyrenaltumorsVHL綜合征臨床表現(xiàn)2023/6/1010VHL綜合征診斷標準（1）中樞神經(jīng)系統(tǒng)或視網(wǎng)膜成血管細胞瘤家族病史，有一種成血管細胞瘤或內(nèi)臟病變（如腎腫瘤、胰腺腫瘤或囊腫、嗜鉻細胞瘤、附睪乳頭狀囊腺瘤等）（2）對于無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胞瘤,或一種成血管母細胞瘤和一種內(nèi)臟病變類型I型不表現(xiàn)為腎上腺嗜鉻細胞瘤，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，僅有腎上腺嗜鉻細胞瘤表現(xiàn)chromophobe嫌色細胞,oncocytoma,clearcellandhybridoncocytictumorscomposedofelementsofoncocytomaandchromophobeMeanageatdiagnosisisolder,nearage50years但是復雜的囊腫有可能包含腫瘤組織而逐漸生長，需要定期監(jiān)測renaltumorswerediscoveredin1434%.目前已被完全測序，并確認是存在于散發(fā)性和家族性腎透明細胞癌中的抑癌基因與散發(fā)的腎癌相比并無特異性遺傳性平滑肌瘤病及腎細胞癌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,多無明顯癥狀，一般預后良好降低疾病相關死亡率并改善預后44%beforetheageof30Pathologicanalysisof130tumorsobtainedfrom30surgicallymanagedcasesidentifiedproportionaldifferencesincludinghybridonco/chromo50%,chromophobe34%,conventionalclearcell9%,oncocytoma5%andpapillary2%對最大徑超過3cm的腫瘤行腎部分切除術，這樣可以減低腫瘤的轉(zhuǎn)移的風險而且保留腎臟的功能1895年由德國眼科教授EugenvonHipple首先發(fā)現(xiàn)Lungcystswerecommonandseenin83%仔細隨訪相應患者及其家屬IsolatedcasesofuterineleiomyosarcomasPreoperativePETscansmayprovebeneficialincasesinwhichlymphnodeornonlocalizeddiseaseissuspectedinterventionfortumors,whichgrowtoreach3cminsizeandincludetheuseofnephronsparingprocedureswhenpossible影像學表現(xiàn)為乏血供的腫瘤，CT增強僅表現(xiàn)為輕度強化（增加1030HU），MRI增強僅15%影像學表現(xiàn)為乏血供的腫瘤，CT增強僅表現(xiàn)為輕度強化（增加1030HU），MRI增強僅15%6cm，增強后邊緣較前清晰。臨床特點一般情況下，病變是視網(wǎng)膜成血管母細胞瘤最早出現(xiàn)，然后是中樞神經(jīng)系統(tǒng)血管母細胞瘤，而腎癌出現(xiàn)較晚中樞神經(jīng)系統(tǒng)血管母細胞瘤和腎臟透明細胞癌為該病最常見的致死原因嗜鉻細胞瘤，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,多無明顯癥狀，一般預后良好VHL綜合征是遺傳性腎癌最常見的原因腎癌也是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)槎嘣钚訵alther等對VHL綜合征患者的腎臟標本進行研究，顯微鏡下觀察，發(fā)現(xiàn)有的標本中存在600個腫瘤病灶和1100個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有癥狀一般無需特殊治療但是復雜的囊腫有可能包含腫瘤組織而逐漸生長，需要定期監(jiān)測散發(fā)的腎癌一樣，VHL綜合征腎癌缺乏早期臨床癥狀，通常在很長時間內(nèi)都沒有任何表現(xiàn)腎癌進展的病例可以表現(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)多中心的實性和囊性的病變治療VHL綜合征患者腎癌的預后與腫瘤的大小密切相關對最大徑超過3cm的腫瘤行腎部分切除術，這樣可以減低腫瘤的轉(zhuǎn)移的風險而且保留腎臟的功能對于直徑較小的腫瘤（≤3cm）可以選擇密切觀察一項研究對腎臟腫瘤小于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間超過5年隨訪結(jié)果顯示腫瘤小于3cm患者中無病例發(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)，腫瘤生長較慢，轉(zhuǎn)移較晚，腎臟腫瘤平均每年增長0.5cm一般不建議對VHL綜合征行腎根治性切除術，即使為單側(cè)腎癌，也應盡量行保留腎單位的腫瘤切除手術，因為對側(cè)腎臟也有再發(fā)生腎癌的可能如果無法保留腎臟，可選擇進行雙側(cè)腎根治性切除術，再透析或行腎移植術加服免疫抑制劑當VHL患者接受腎移植以后，移植腎無發(fā)展為腎囊腫或腎癌的傾向但長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？VHL基因抑癌機制清楚，抑癌作用明顯，而且VHL基因只有3個外顯子，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物實驗階段VHL基因治療將為VHL綜合征治療開辟一個新的方向隨訪VHL綜合征合并腎癌的患者應每年復查一次CT或MRI如果最大腫瘤直徑超過3cm，就應對所有腫瘤行腫瘤剜除術或腎部分切除術有VHL家族病史的人，也應該每年復查一次CT對于無腫瘤的單純囊腫，不推薦手術切除遺傳性乳頭狀腎細胞癌指的是病人易于罹患腎乳頭狀細胞癌的狀態(tài)與cMet原癌基因的突變有關，定位于染色體7q31常染色體顯性遺傳臨床表現(xiàn)發(fā)病隱匿，多無明顯臨床表現(xiàn)多為多灶性，雙側(cè)發(fā)病影像學表現(xiàn)為乏血供的腫瘤，CT增強僅表現(xiàn)為輕度強化（增加1030HU），MRI增強僅15%2023/6/1025治療通常選擇腎部分切除術術中仔細檢查，防止遺漏病灶遺傳性平滑肌瘤病及腎細胞癌Arelativelynew,rareandaggressiveformofHRCsyndromecutaneousleiomyomasuterineleiomyomasrenalcellcarcinomafumaratehydratase,aKrebscycleenzymeGeneticsBemappedtoaregiononchromosome1(1q42.343)encodesfortheHLRCCgeneproduct,fumaratehydrataseanautosomaldominantpatternthetumorsuppressorfunctionofthegeneClinicalfeaturesthefindingofseverelysymptomaticuterinefibroidsamongaffectedwomenwithinfamiliesoftenrequiringearlyhysterectomyduetodifficultiesfrommenometrorrhagia89%ofaffectedwomenunderwenthysterectomy44%beforetheageof30Clinicalfeatures89%ofaffectedwomenunderwenthysterectomypotentiallymisclassifiedascollectingducttumors1926年由瑞典病理學家AvidLindau再次確認Lungcystswerecommonandseenin83%遺傳性乳頭狀腎細胞癌(HPRC)Pathologicanalysisof130tumorsobtainedfrom30surgicallymanagedcasesidentifiedproportionaldifferencesincludinghybridonco/chromo50%,chromophobe34%,conventionalclearcell9%,oncocytoma5%andpapillary2%thefindingofseverelysymptomaticuterinefibroidsamongaffectedwomenwithinfamiliesIsolatedcasesofuterineleiomyosarcomasBirt–Hogg–Dubesyndromepotentiallymisclassifiedascollectingducttumors散發(fā)的腎透明細胞癌患者中，VHL基因突變率為46%～70%但長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，增強后邊緣較前清晰。頭顱MRI顯示左側(cè)延髓見類圓形混雜信號灶，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,thoughmaybedifficulttoidentifyRenalcancerswithaprevalenceestimatedbetween2and21%papillarytype2tumorspotentiallymisclassifiedascollectingducttumorsMorerecently,detailedhistologicdescriptionhasledtomorerefinedcharacterizationofthepathologicfeaturesnowtermedHLRCCrenaltumorsManagementRadiographicappearanceofHLRCCtumorsmayappearpartlycysticandpoorlydefinedNephronsparingsurgeryislesswellestablishedinthissettingSurgicalinterventionmustbeperformedwithcaretoensureminimalhandlingofthetumorandcompletewideresection,includinglymphnodedissectionPreoperativePETscansmayprovebeneficialincasesinwhichlymphnodeornonlocalizeddiseaseissuspectedBirt–Hogg–DubesyndromeThefamilialassociationofperifolliculardermatosisinvolvingthefaceandtrunkamongthreefirstdegreerelativeswasfirstdescribedbyHornsteinandKnickenbergin1975Twoyearslater,DrsBirt,HoggandDubedescribedclinicaldermatologicfindingsinvolving15familymemberswithsimilarskinnodulesdescribedasfibrofolliculomas纖維毛囊瘤,trichodiscomas毛盤狀瘤acrochordons軟垂疣GeneticsautosomaldominantpatternsofinheritancechromosomeThegeneproduct,folliculin,isthoughttobeinvolvedinregulationofthemammaliantargetofrapamycin(mTOR)pathwaybyactingthroughfolliculininteractingprotein(FNIP1)and50AMPactivatedproteinkinaseClinicalfeaturesClassictriadofskinfibrofolliculomaspulmonarycystsrenaltumorsrenaltumorswerediscoveredin1434%.Spontaneouspneumothoracesoccurredin23%:mostcommoninyoungerfamilymembers(<40years)Lungcystswerecommonandseenin83%Skinlesionsin90%therelativeheterogeneityoftumorsubtypesindolentformsofdiseasechromophobe嫌色細胞,oncocytoma,clearcellandhybridoncocytictumorscomposedofelementsofoncocytomaandchromophobeMeanageatdiagnosisisolder,nearage50yearsPathologicanalysisof130tumorsobtainedfrom30surgicallymanagedcasesidentifiedproportionaldifferencesincludinghybridonco/chromo50%,chromophobe34%,conventionalclearcell9%,oncocytoma5%andpapillary2%lessaggressivetumorhistologiesnotbeconsideredanindolentdiseaseprocessaggressivetumorfeaturesinyoungpatientspulmonarymetastasesfromacaseoflocallyadvancedclearcellcarcinomaina20yearoldpatientOne39yearoldpatientwithBHDandmixedrenaltumor,includingclearcellcomponentsdevelopeddistantprogressionanddeath既往體健，否認高血壓病史，否認家族史，體格檢查血壓輕度升高150/78mmHgVHL基因抑癌機制清楚，抑癌作用明顯，而且VHL基因只有3個外顯子，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，定位于染色體7q31Meanageatdiagnosisisolder,nearage50yearsPathologicanalysisof130tumorsobtainedfrom30surgicallymanagedcasesidentifiedproportionaldifferencesincludinghybridonco/chromo50%,chromophobe34%,conventionalclearcell9%,oncocytoma5%andpapillary2%6cm，增強后邊緣較前清晰。一般情況下，病變是視網(wǎng)膜成血管母細胞瘤最早出現(xiàn)，然后是中樞神經(jīng)系統(tǒng)血管母細胞瘤，而腎癌出現(xiàn)較晚發(fā)現(xiàn)遺傳性腎癌的相關基因PreoperativePETscansmayprovebeneficialincasesinwhichlymphnodeornonlocalizeddiseaseissuspected仔細隨訪相應患者及其家屬1895年由德國眼科教授EugenvonHipple首先發(fā)現(xiàn)結(jié)合上述臨床表現(xiàn)診斷為VHL綜合征。影像學表現(xiàn)為乏血供的腫瘤，CT增強僅表現(xiàn)為輕度強化（增加1030HU），MRI增強僅15%與cMet原癌基因的突變有關，定位于染色體7q31Birt–Hogg–Dubesyndrome但是復雜的囊腫有可能包含腫瘤組織而逐漸生長，需要定期監(jiān)測降低疾病相關死亡率并改善預后2023/6/10402023/6/10412023/6/10422023/6/1043Managementinterventionfortumors,whichgrowtoreach3cminsizeandincludetheuseofnephronsparingprocedureswhenpossible該基因的丟失、突變和甲基化失活導致正常的VHL蛋白合成障礙，是導致VHL綜合征的重要分子學基礎該基因在VHL病家族成員中突變率幾乎達100%VHL綜合征診斷標準autosomaldominantpatternsofinheritancechromosome嗜鉻細胞瘤，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嫌色細胞,oncocytoma,clearcellandhybridoncocytictumorscomposedofelementsofoncocytomaandchromophobeBirt–Hogg–DubesyndromeBirt–Hogg–DubesyndromePreoperativePETscansmayprovebeneficialincasesinwhichlymphnodeornonlocalizeddiseaseissuspected但長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)，腫瘤生長較慢，轉(zhuǎn)移較晚，腎臟腫瘤平均每年增長0.interventionfortumors,whichgrowtoreach3cminsizeandincludetheuseofnephronsparingprocedureswhenpossible一般不建議對VHL綜合征行腎根治性切除術，即使為單側(cè)腎癌，也應盡量行保留腎單位的腫瘤切除手術，因為對側(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，當腎腫瘤直徑大于3cm時可手術，以NSS首選病例男性，21歲體檢B超發(fā)現(xiàn)雙腎占位，胰腺占位3周就診患者無明顯的癥狀，無血尿、心悸、出汗、頭痛。既往體健，否認高血壓病史，否認家族史，體格檢查血壓輕度升高150/78mmHg腹部CT顯示雙腎多個大小不等低密度影，部分邊緣欠清晰，增強后，右腎上極及左腎門處見不均勻性強化，分別為3.3×3.6cm，2.6×3.4cm。內(nèi)未見脂肪密度。雙腎內(nèi)亦可見多個不強化低密度影，最大者于右腎實質(zhì)內(nèi)，大小2.5×2.6cm，增強后邊緣較前清晰。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，增強后見明顯均勻強化。胰頸部、尾部見斑片狀低密度影，增強后有輕度強化。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2023/6/1047頭顱MRI顯示左側(cè)延髓見類圓形混雜信號灶，大小約1.5×1.4mm，增強掃描明顯強化，符合血管母細胞瘤行眼底熒光血管造影提示雙眼視網(wǎng)膜大動脈血管母細胞瘤陰囊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。術前檢查患者血清兒茶酚胺水平位于正常范圍內(nèi)Meanageatdiagnosisisolder,nearage50years6cm，增強后邊緣較前清晰。chromophobe嫌色細胞,oncocytoma,clearcellandhybridoncocytictumorscomposedofelementsofoncocytomaandchromophobe對最大徑超過3cm的腫瘤行腎部分切除術，這樣可以減低腫瘤的轉(zhuǎn)移的風險而且保留腎臟的功能6cm，增強后邊緣較前清晰。renaltumors1936年由Davison教授總結(jié)相關臨床表現(xiàn)并命名為vonHippelLindausyndrome行眼底熒光血管造影提示雙眼視網(wǎng)膜大動脈血管母細胞瘤（2）對于無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胞瘤,或一種成血管母細胞瘤和一種內(nèi)臟病變影像學表現(xiàn)為乏血供的腫瘤，CT增強僅表現(xiàn)為輕度強化（增加1030HU），MRI增強僅15%Isolatedcasesofuterineleiomyosarcomas結(jié)合上述臨床表現(xiàn)診斷為VHL綜合征。interventionfortumors,whichgrowtoreach3cminsizeandincludetheuseofnephronsparingprocedureswhenpossiblepotentiallymisclassifiedascollectingducttumors但是復雜的囊腫有可能包含腫瘤組織而逐漸生長，需要定期監(jiān)測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，當腎腫瘤直徑大于3cm時可手術，以NSS首選進行腫瘤形成機制相關的細胞分子通路研究腎癌病理類型基本是透明細胞癌亞型，腫瘤體積越小傾向惡性程度越低Pathologicanalysisof130tumorsobtainedfrom30surgicallymanagedcasesidentifiedproportionaldifferencesincludinghybridonco/chromo50%,chromophobe34%,conventionalclearcell9%,oncocytoma5%andpapillary2%VHL基因抑癌機制清楚，抑癌作用明顯，而且VHL基因只有3個外顯子，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，否認高血壓病史，否認家族史，體格檢查血壓輕度升高150/78mmHg仔細隨訪相應患者及其家屬（2）對于無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胞瘤,或一種成血管母細胞瘤和一種內(nèi)臟病變IsolatedcasesofuterineleiomyosarcomasencodesfortheHLRCCgeneproduct,fumaratehydratase是一種相對罕見的常染色體顯性遺傳病，發(fā)病率1/360006cm，增強后邊緣較前清晰。PreoperativePETscansmayprovebeneficialincasesinwhichlymphnodeornonlocalizeddiseaseissuspected但長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/無家族史發(fā)現(xiàn)遺傳性腎癌的相關基因ClassictriadofskinfibrofolliculomasBemappedtoaregiononchromosome1(1q42.IsolatedcasesofuterineleiomyosarcomasVHL綜合征患者腎癌的預后與腫瘤的大小密切相關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)生率可達到60%PreoperativePETscansmayprovebeneficialincasesinwhichlymphnodeornonlocalizeddiseaseissuspected該基因的丟失、突變和甲基化失活導致正常的VHL蛋白合成障礙，是導致VHL綜合征的重要分子學基礎Isolatedcasesofuterineleiomyosarcomas結(jié)合上述臨床表現(xiàn)診斷為VHL綜合征。chromophobe嫌色細胞,oncocytoma,clearcellandhybridoncocytictumorscomposedofelementsofoncocytomaandchromophobeRenalcancerswithaprevalenceestimatedbetween2and21%chromophobe嫌色細胞,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)，腫瘤生長較慢，轉(zhuǎn)移較晚，腎臟腫瘤平均每年增長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,多無明顯癥狀，一般預后良好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)生率可達到60%Bemappedtoaregiononchromosome1(1q42.1926年由瑞典病理學家AvidLindau再次確認Twoyearslater,DrsBirt,HoggandDubedescribedclinicaldermatologicfindingsinvolving15familymemberswithsimilarskinnodulesdescribedasfibrofolliculomas纖維毛囊瘤,trichodiscomas毛盤狀瘤acrochordons軟垂疣Cutaneousleiomyomasarecommonamongaffectedindividuals,thoughmaybedifficulttoidentify但是復雜的囊腫有可能包含腫瘤組織而逐漸生長，需要定期監(jiān)測interventionfortumors,whichgrowtoreach3cminsizeandincludetheuseofnephronsparingprocedureswhenpossible嗜鉻細胞瘤，臨床上多因出現(xiàn)高血壓癥狀而發(fā)現(xiàn)6cm，增強后邊緣較前清晰。仔細隨訪相應患者及其家屬對最大徑超過3cm的腫瘤行腎部分切除術，這樣可以減低腫瘤的轉(zhuǎn)移的風險而且保留腎臟的功能Meanageatdiagnosisisolder,nearage50yearschromophobe嫌色細胞,oncocytoma,clearcellandhybridoncocytictumorscomposedofelementsofoncocytomaandchromophobe（優(yōu)選）遺傳性腎癌綜合征遺傳性平滑肌瘤病及腎細胞癌interventionfortumors,whichgrowtoreach3cminsizeandincludetheuseofnephronsparingprocedureswhenpossible（1）中樞神經(jīng)系統(tǒng)或視網(wǎng)膜成血管細胞瘤家族病史，有一種成血管細胞瘤或內(nèi)臟病變（如腎腫瘤、胰腺腫瘤或囊腫、嗜鉻細胞瘤、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，當腎腫瘤直徑大于3cm時可手術，以NSS首選Birt–Hogg–Dubesyndromepotentiallymisclassifiedascollectingducttumors1926年由瑞典病理學家AvidLindau再