结节性硬化症的发病机制与特征性表现
|
摘要
结节性硬化症是一种罕见的常染色体显性遗传病,其临床表现非常独特,可出现脑、皮肤、心脏、肺和肾等器官的多发良性肿瘤,以及广泛的中枢神经系统功能异常。掌握结节性硬化症的发病机制,有助于理解其临床表现的多样性。对结节性硬化症患者做出准确的临床诊断,依赖于对其特征性表现的全面评估。本文就结节性硬化症的发病机制与特征性表现的最新研究情况进行一综述。
Tuberous sclerosis complex is a rare autosomal dominant disorder with clinical manifestations that are unique. The disease can cause multiple benign tumors of the brain, skin, heart, lungs and kidneys, as well as a wide range of central nervous system dysfunction. Mastering the pathogenesis of tuberous sclerosis complex helps to understand the diversity of clinical manifestations.Accurate clinical diagnosis of patients with tuberous sclerosis complex relies on a comprehensive assessment of its characteristic manifestations. This article reviews the recent research on the pathogenesis and characteristic manifestations of tuberous sclerosis complex.
Tuberous sclerosis complex is a rare autosomal dominant disorder with clinical manifestations that are unique. The disease can cause multiple benign tumors of the brain, skin, heart, lungs and kidneys, as well as a wide range of central nervous system dysfunction. Mastering the pathogenesis of tuberous sclerosis complex helps to understand the diversity of clinical manifestations.Accurate clinical diagnosis of patients with tuberous sclerosis complex relies on a comprehensive assessment of its characteristic manifestations. This article reviews the recent research on the pathogenesis and characteristic manifestations of tuberous sclerosis complex.
引文
[1]Laguna MP.Re:everolimus for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis(EXIST-2):a multicentre,randomised,double-blind,placebo-controlled trial[J].JUrol,2014,191(3):626-7.
[2]Dibble CC,Cantley LC.Regulation of mTORC1 by PI3K signaling[J].Trends Cell Biol,2015,25(9):545-55.
[3]Kim YC,Guan KL.mTOR:a pharmacologic target for autophagy regulation[J].J Clin Invest,2015,125(1):25-32.
[4]Li J,Kim SG,Blenis J.Rapamycin:one drug,many effects[J].Cell Metab,2014,19(3):373-9.
[5]Henske EP,Neumann HP,Scheithauer BW,Herbst EW,Short MP,Kwiatkowski DJ.Loss of heterozygosity in the tuberous sclerosis(TSC2)region of chromosome band 16p13 occurs in sporadic as well as TSC-associated renal angiomyolipomas[J].Genes Chromosomes Cancer,1995,13(4):295-8.
[6]Tyburczy ME,Dies KA,Glass J,et al.Mosaic and Intronic Mutations in TSC1/TSC2 Explain the Majority of TSC Patients with No Mutation Identified by Conventional Testing[J].PLoS Genet,2015,11(11):e1005637.
[7]Crino PB,Henske EP.New developments in the neurobiology of the tuberous sclerosis complex[J].Neurology,1999,53(7):1384-90.
[8]Tworetzky W,McElhinney DB,Margossian R,et al.Association between cardiac tumors and tuberous sclerosis in the fetus and neonate[J].Am JCardiol,2003,92(4):487-9.
[9]Kwiatkowski DJ.Tuberous sclerosis:from tubers to mTOR[J].Ann Hum Genet,2003,67(Pt 1):87-96.
[10]Webb DW,Fryer AE,Osborne JP.Morbidity associated with tuberous sclerosis:a population study[J].Dev Med Child Neurol,1996,38(2):146-55.
[11]Curatolo P,Verdecchia M,Bombardieri R.Tuberous sclerosis complex:a review of neurological aspects[J].Eur J Paediatr Neurol,2002,6(1):15-23.
[12]Cuccia V,Zuccaro G,Sosa F,Monges J,Lubienieky F,Taratuto AL.Subependymal giant cell astrocytoma in children with tuberous sclerosis[J].Childs Nerv Syst,2003,19(4):232-43.
[13]Kalantari BN,Salamon N.Neuroimaging of tuberous sclerosis:spectrum of pathologic findings and frontiers in imaging[J].AJR Am JRoentgenol,2008,190(5):W304-9.
[14]Umeoka S,Koyama T,Miki Y,et al.Pictorial review of tuberous sclerosis in various organs[J].Radiographics,2008,28(7):e32.
[15]Józwiak S,Schwartz RA,Janniger CK,et al.Usefulness of diagnostic criteria of tuberous sclerosis complex in pediatric patients[J].J Child Neurol,2000,15(10):652-9.
[16]Roach ES,Gomez MR,Northrup H.Tuberous sclerosis complex consensus conference:revised clinical diagnostic criteria[J].J Child Neurol,1998,13(12):624-8.
[17]Fitzpatrick TB.History and significance of white macules,earliest visible sign of tuberous sclerosis[J].Ann N Y Acad Sci,1991,615:26-35.
[18]Tilgen W.Ultrastructure of white leaf-shaped macules in tuberous sclerosis(author’s transl)[J].Arch Dermatol Forsch,1973,248(1):13-27.
[19]Jó?wiak S,Schwartz RA,Janniger CK,Micha?owicz R,Chmielik J.Skin lesions in children with tuberous sclerosis complex:their prevalence,natural course,and diagnostic significance[J].Int J Dermatol,1998,37(12):911-7.
[20]Webb DW,Clarke A,Fryer A,Osborne JP.The cutaneous features of tuberous sclerosis:a population study[J].Br J Dermatol,1996,135(1):1-5.
[21]Lagos JC,Gomez MR.Tuberous sclerosis:reappraisal of a clinical entity[J].Mayo Clin Proc,1967,42(1):26-49.
[22]Kim H,Kerr A,Morehouse H.The association between tuberous sclerosis and insulinoma[J].AJNR Am J Neuroradiol,1995,16(7):1543-4.
[23]Ilgren EB,Westmoreland D.Tuberous sclerosis:unusual associations in four cases[J].J Clin Pathol,1984,37(3):272-8.
[24]WERMER P.Genetic aspects of adenomatosis of endocrine glands[J].Am JMed,1954,16(3):363-71.
[25]Kobayasi T,Wolf-Jürgensen P,Danielsen L.Ultrastructure of shagreen patch[J].Acta Derm Venereol,1973,53(4):275-8.
[26]NICKEL WR,REED WB.Tuberous sclerosis.Special reference to the microscopic alterations in the cutaneous hamartomas[J].Arch Dermatol,1962,85:209-26.
[27]Ward PE,McCarthy DJ.Periungual fibroma[J].Cutis,1990,46(2):118-24.
[28]Sampson JR,Attwood D,al Mughery AS,Reid JS.Pitted enamel hypoplasia in tuberous sclerosis[J].Clin Genet,1992,42(1):50-2.
[29]Curatolo P,Maria BL.Tuberous sclerosis[J].Handb Clin Neurol,2013,111:323-31.
[30]Northrup H,Krueger DA,International Tuberous Sclerosis Complex Consensus Group.Tuberous sclerosis complex diagnostic criteria update:recommendations of the 2012 Iinternational Tuberous Sclerosis Complex Consensus Conference[J].Pediatr Neurol,2013,49(4):243-54.
[31]Flanagan N,O’Connor WJ,McCartan B,et al.Developmental enamel defects in tuberous sclerosis:a clinical genetic marker[J].J Med Genet,1997,34(8):637-9.
[32]Lygidakis NA,Lindenbaum RH.Oral fibromatosis in tuberous sclerosis[J].Oral Surg Oral Med Oral Pathol,1989,68(6):725-8.
[33]Jaiarj N.Drug-induced gingival overgrowth[J].J Mass Dent Soc,2003,52(3):16-20.
[34]Gutierrez GC,Smalley SL,Tanguay PE.Autism in tuberous sclerosis complex[J].J Autism Dev Disord,1998,28(2):97-103.
[35]Holley DG,Martin GR,Brenner JI,et al.Diagnosis and management of fet al cardiac tumors:a multicenter experience and review of published reports[J].J Am Coll Cardiol,1995,26(2):516-20.
[36]Jó?wiak S,Kotulska K,Kasprzyk-Obara J,et al.Clinical and genotype studies of cardiac tumors in 154 patients with tuberous sclerosis complex[J].Pediatrics,2006,118(4):e1146-51.
[37]Nir A,Tajik AJ,Freeman WK,et al.Tuberous sclerosis and cardiac rhabdomyoma[J].Am J Cardiol,1995,76(5):419-21.
[38]Fesslova V,Villa L,Rizzuti T,Mastrangelo M,Mosca F.Natural history and long-term outcome of cardiac rhabdomyomas detected prenatally[J].Prenat Diagn,2004,24(4):241-8.
[39]Bader RS,Chitayat D,Kelly E,et al.Fet al rhabdomyoma:prenatal diagnosis,clinical outcome,and incidence of associated tuberous sclerosis complex[J].JPediatr,2003,143(5):620-4.
[40]Pipitone S,MongiovìM,Grillo R,et al.Cardiac rhabdomyoma in intrauterine life:clinical features and natural history.A case series and review of published reports[J].Ital Heart J,2002,3(1):48-52.
[41]Smythe JF,Dyck JD,Smallhorn JF,et al.Natural history of cardiac rhabdomyoma in infancy and childhood[J].Am J Cardiol,1990,66(17):1247-9.
[42]Bosi G,Lintermans JP,Pellegrino PA,et al.The natural history of cardiac rhabdomyoma with and without tuberous sclerosis[J].Acta Paediatr,1996,85(8):928-31.
[43]Jó?wiak S,Kotulska K.Are all prenatally diagnosed multiple cardiac rhabdomyomas a sign of tuberous sclerosis[J].Prenat Diagn,2006,26(9):867-9.
[44]Khanna PC,Godinho S,Pungavkar SA,Patkar DP.Ultrafast MRI in the prenatal diagnosis of Bourneville’s tuberous sclerosis[J].Neurol India,2005,53(3):349-50.
[45]Chen CP,Liu YP,Huang JK,et al.Contribution of ultrafast magnetic resonance imaging in prenatal diagnosis of sonographically undetected cerebral tuberous sclerosis associated with cardiac rhabdomyomas[J].Prenat Diagn,2005,25(6):523-4.
[46]Henske EP,McCormack FX.Lymphangioleiomyomatosis-a wolf in sheep’s clothing[J].J Clin Invest,2012,122(11):3807-16.
[47]Adriaensen ME,Schaefer-Prokop CM,Duyndam DA,Zonnenberg BA,Prokop M.Radiological evidence of lymphangioleiomyomatosis in female and male patients with tuberous sclerosis complex[J].Clin Radiol,2011,66(7):625-8.
[48]Aubry MC,Myers JL,Ryu JH,et al.Pulmonary lymphangioleiomyomatosis in a man[J].Am J Respir Crit Care Med,2000,162(2 Pt 1):749-52.
[49]Franz DN,Brody A,Meyer C,et al.Mutational and radiographic analysis of pulmonary disease consistent with lymphangioleiomyomatosis and micronodular pneumocyte hyperplasia in women with tuberous sclerosis[J].Am J Respir Crit Care Med,2001,164(4):661-8.
[50]Strizheva GD,Carsillo T,Kruger WD,et al.Sullivan EJ,Ryu JH,Henske EP.The spectrum of mutations in TSC1 and TSC2 in women with tuberous sclerosis and lymphangiomyomatosis[J].Am J Respir Crit Care Med,2001,163(1):253-8.
[51]Logginidou H,Ao X,Russo I,Henske EP.Frequent estrogen and progesterone receptor immunoreactivity in renal angiomyolipomas from women with pulmonary lymphangioleiomyomatosis[J].Chest,2000,117(1):25-30.
[52]Knudson AG.Hereditary cancer:two hits revisited[J].J Cancer Res Clin Oncol,1996,122(3):135-40.
[53]Hayashi T,Kumasaka T,Mitani K,Yao T,Suda K,Seyama K.Loss of heterozygosity on tuberous sclerosis complex genes in multifocal micronodular pneumocyte hyperplasia[J].Mod Pathol,2010,23(9):1251-60.
[54]Song MG,Park KB,Lee ES.Resurfacing of facial angiofibromas in tuberous sclerosis patients using CO2 laser with flashscanner[J].Dermatol Surg,1999,25(12):970-3.
[55]Fischer K,Blain B,Zhang F,Richards L,Lineaweaver WC.Treatment of facial angiofibromas of tuberous sclerosis by shave excision and dermabrasion in a dark-skinned patient[J].Ann Plast Surg,2001,46(3):332-5.
[56]Ewalt DH,Sheffield E,Sparagana SP,Delgado MR,Roach ES.Renal lesion growth in children with tuberous sclerosis complex[J].J Urol,1998,160(1):141-5.
[57]Henske EP,Wessner LL,Golden J,et al.Loss of tuberin in both subependymal giant cell astrocytomas and angiomyolipomas supports a two-hit model for the pathogenesis of tuberous sclerosis tumors[J].Am JPathol,1997,151(6):1639-47.
[58]Robb VA,Karbowniczek M,Klein-Szanto AJ,Henske EP.Activation of the mTOR signaling pathway in renal clear cell carcinoma[J].J Urol,2007,177(1):346-52.
[59]Karbowniczek M,Yu J,Henske EP.Renal angiomyolipomas from patients with sporadic lymphangiomyomatosis contain both neoplastic and nonneoplastic vascular structures[J].Am J Pathol,2003,162(2):491-500.
[60]Manoukian SB,Kowal DJ.Comprehensive imaging manifestations of tuberous sclerosis[J].AJR Am J Roentgenol,2015,204(5):933-43.
[61]Evans JC,Curtis J.The radiological appearances of tuberous sclerosis[J].Br JRadiol,2000,73(865):91-8.
[62]Martignoni G,Bonetti F,Pea M,Tardanico R,Brunelli M,Eble JN.Renal disease in adults with TSC2/PKD1 contiguous gene syndrome[J].Am J Surg Pathol,2002,26(2):198-205.
[63]Sampson JR,Maheshwar MM,Aspinwall R,et al.Renal cystic disease in tuberous sclerosis:role of the polycystic kidney disease 1 gene[J].Am J Hum Genet,1997,61(4):843-51.
[64]Brook-Carter PT,Peral B,Ward CJ,et al.Deletion of the TSC2 and PKD1genes associated with severe infantile polycystic kidney disease--a contiguous gene syndrome[J].Nat Genet,1994,8(4):328-32.
[65]Guo J,Tretiakova MS,Troxell ML,et al.Tuberous sclerosis-associated renal cell carcinoma:a clinicopathologic study of 57 separate carcinomas in 18patients[J].Am J Surg Pathol,2014,38(11):1457-67.
[66]De Waele L,Lagae L,Mekahli D.Tuberous sclerosis complex:the past and the future[J].Pediatr Nephrol,2015,30(10):1771-80.
[67]Muglia VF,Prando A.Renal cell carcinoma:histological classification and correlation with imaging findings[J].Radiol Bras,2015,48(3):166-74.
[68]Crino PB,Nathanson KL,Henske EP.The tuberous sclerosis complex[J].NEngl J Med,2006,355(13):1345-56.
[69]Robertson DM.Ophthalmic manifestations of tuberous sclerosis[J].Ann NY Acad Sci,1991,615:17-25.
[70]Rowley SA,O’Callaghan FJ,Osborne JP.Ophthalmic manifestations of tuberous sclerosis:a population based study[J].Br J Ophthalmol,2001,85(4):420-3.
[71]Braun RA,Milito CF,Goldman SM,et al.Ivory vertebra:imaging findings in different diagnoses[J].Radiol Bras,2016,49(2):117-21.
[72]Andrade Neto F,Teixeira MJ,et al.Knee bone tumors:findings on conventional radiology[J].Radiol Bras,2016,49(3):182-9.
[73]Lima Júnior FV,Savarese LG,Monsignore LM,et al.Computed tomography findings of paracoccidiodomycosis in musculoskelet al system[J].Radiol Bras,2015,48(1):1-6.
[74]Petrilli M,Senerchia AA,Petrilli AS,et al.Computed tomography-guided percutaneous trephine removal of the nidus in osteoid osteoma patients:experience of a single center in Brazil[J].Radiol Bras,2015,48(4):211-5.
[2]Dibble CC,Cantley LC.Regulation of mTORC1 by PI3K signaling[J].Trends Cell Biol,2015,25(9):545-55.
[3]Kim YC,Guan KL.mTOR:a pharmacologic target for autophagy regulation[J].J Clin Invest,2015,125(1):25-32.
[4]Li J,Kim SG,Blenis J.Rapamycin:one drug,many effects[J].Cell Metab,2014,19(3):373-9.
[5]Henske EP,Neumann HP,Scheithauer BW,Herbst EW,Short MP,Kwiatkowski DJ.Loss of heterozygosity in the tuberous sclerosis(TSC2)region of chromosome band 16p13 occurs in sporadic as well as TSC-associated renal angiomyolipomas[J].Genes Chromosomes Cancer,1995,13(4):295-8.
[6]Tyburczy ME,Dies KA,Glass J,et al.Mosaic and Intronic Mutations in TSC1/TSC2 Explain the Majority of TSC Patients with No Mutation Identified by Conventional Testing[J].PLoS Genet,2015,11(11):e1005637.
[7]Crino PB,Henske EP.New developments in the neurobiology of the tuberous sclerosis complex[J].Neurology,1999,53(7):1384-90.
[8]Tworetzky W,McElhinney DB,Margossian R,et al.Association between cardiac tumors and tuberous sclerosis in the fetus and neonate[J].Am JCardiol,2003,92(4):487-9.
[9]Kwiatkowski DJ.Tuberous sclerosis:from tubers to mTOR[J].Ann Hum Genet,2003,67(Pt 1):87-96.
[10]Webb DW,Fryer AE,Osborne JP.Morbidity associated with tuberous sclerosis:a population study[J].Dev Med Child Neurol,1996,38(2):146-55.
[11]Curatolo P,Verdecchia M,Bombardieri R.Tuberous sclerosis complex:a review of neurological aspects[J].Eur J Paediatr Neurol,2002,6(1):15-23.
[12]Cuccia V,Zuccaro G,Sosa F,Monges J,Lubienieky F,Taratuto AL.Subependymal giant cell astrocytoma in children with tuberous sclerosis[J].Childs Nerv Syst,2003,19(4):232-43.
[13]Kalantari BN,Salamon N.Neuroimaging of tuberous sclerosis:spectrum of pathologic findings and frontiers in imaging[J].AJR Am JRoentgenol,2008,190(5):W304-9.
[14]Umeoka S,Koyama T,Miki Y,et al.Pictorial review of tuberous sclerosis in various organs[J].Radiographics,2008,28(7):e32.
[15]Józwiak S,Schwartz RA,Janniger CK,et al.Usefulness of diagnostic criteria of tuberous sclerosis complex in pediatric patients[J].J Child Neurol,2000,15(10):652-9.
[16]Roach ES,Gomez MR,Northrup H.Tuberous sclerosis complex consensus conference:revised clinical diagnostic criteria[J].J Child Neurol,1998,13(12):624-8.
[17]Fitzpatrick TB.History and significance of white macules,earliest visible sign of tuberous sclerosis[J].Ann N Y Acad Sci,1991,615:26-35.
[18]Tilgen W.Ultrastructure of white leaf-shaped macules in tuberous sclerosis(author’s transl)[J].Arch Dermatol Forsch,1973,248(1):13-27.
[19]Jó?wiak S,Schwartz RA,Janniger CK,Micha?owicz R,Chmielik J.Skin lesions in children with tuberous sclerosis complex:their prevalence,natural course,and diagnostic significance[J].Int J Dermatol,1998,37(12):911-7.
[20]Webb DW,Clarke A,Fryer A,Osborne JP.The cutaneous features of tuberous sclerosis:a population study[J].Br J Dermatol,1996,135(1):1-5.
[21]Lagos JC,Gomez MR.Tuberous sclerosis:reappraisal of a clinical entity[J].Mayo Clin Proc,1967,42(1):26-49.
[22]Kim H,Kerr A,Morehouse H.The association between tuberous sclerosis and insulinoma[J].AJNR Am J Neuroradiol,1995,16(7):1543-4.
[23]Ilgren EB,Westmoreland D.Tuberous sclerosis:unusual associations in four cases[J].J Clin Pathol,1984,37(3):272-8.
[24]WERMER P.Genetic aspects of adenomatosis of endocrine glands[J].Am JMed,1954,16(3):363-71.
[25]Kobayasi T,Wolf-Jürgensen P,Danielsen L.Ultrastructure of shagreen patch[J].Acta Derm Venereol,1973,53(4):275-8.
[26]NICKEL WR,REED WB.Tuberous sclerosis.Special reference to the microscopic alterations in the cutaneous hamartomas[J].Arch Dermatol,1962,85:209-26.
[27]Ward PE,McCarthy DJ.Periungual fibroma[J].Cutis,1990,46(2):118-24.
[28]Sampson JR,Attwood D,al Mughery AS,Reid JS.Pitted enamel hypoplasia in tuberous sclerosis[J].Clin Genet,1992,42(1):50-2.
[29]Curatolo P,Maria BL.Tuberous sclerosis[J].Handb Clin Neurol,2013,111:323-31.
[30]Northrup H,Krueger DA,International Tuberous Sclerosis Complex Consensus Group.Tuberous sclerosis complex diagnostic criteria update:recommendations of the 2012 Iinternational Tuberous Sclerosis Complex Consensus Conference[J].Pediatr Neurol,2013,49(4):243-54.
[31]Flanagan N,O’Connor WJ,McCartan B,et al.Developmental enamel defects in tuberous sclerosis:a clinical genetic marker[J].J Med Genet,1997,34(8):637-9.
[32]Lygidakis NA,Lindenbaum RH.Oral fibromatosis in tuberous sclerosis[J].Oral Surg Oral Med Oral Pathol,1989,68(6):725-8.
[33]Jaiarj N.Drug-induced gingival overgrowth[J].J Mass Dent Soc,2003,52(3):16-20.
[34]Gutierrez GC,Smalley SL,Tanguay PE.Autism in tuberous sclerosis complex[J].J Autism Dev Disord,1998,28(2):97-103.
[35]Holley DG,Martin GR,Brenner JI,et al.Diagnosis and management of fet al cardiac tumors:a multicenter experience and review of published reports[J].J Am Coll Cardiol,1995,26(2):516-20.
[36]Jó?wiak S,Kotulska K,Kasprzyk-Obara J,et al.Clinical and genotype studies of cardiac tumors in 154 patients with tuberous sclerosis complex[J].Pediatrics,2006,118(4):e1146-51.
[37]Nir A,Tajik AJ,Freeman WK,et al.Tuberous sclerosis and cardiac rhabdomyoma[J].Am J Cardiol,1995,76(5):419-21.
[38]Fesslova V,Villa L,Rizzuti T,Mastrangelo M,Mosca F.Natural history and long-term outcome of cardiac rhabdomyomas detected prenatally[J].Prenat Diagn,2004,24(4):241-8.
[39]Bader RS,Chitayat D,Kelly E,et al.Fet al rhabdomyoma:prenatal diagnosis,clinical outcome,and incidence of associated tuberous sclerosis complex[J].JPediatr,2003,143(5):620-4.
[40]Pipitone S,MongiovìM,Grillo R,et al.Cardiac rhabdomyoma in intrauterine life:clinical features and natural history.A case series and review of published reports[J].Ital Heart J,2002,3(1):48-52.
[41]Smythe JF,Dyck JD,Smallhorn JF,et al.Natural history of cardiac rhabdomyoma in infancy and childhood[J].Am J Cardiol,1990,66(17):1247-9.
[42]Bosi G,Lintermans JP,Pellegrino PA,et al.The natural history of cardiac rhabdomyoma with and without tuberous sclerosis[J].Acta Paediatr,1996,85(8):928-31.
[43]Jó?wiak S,Kotulska K.Are all prenatally diagnosed multiple cardiac rhabdomyomas a sign of tuberous sclerosis[J].Prenat Diagn,2006,26(9):867-9.
[44]Khanna PC,Godinho S,Pungavkar SA,Patkar DP.Ultrafast MRI in the prenatal diagnosis of Bourneville’s tuberous sclerosis[J].Neurol India,2005,53(3):349-50.
[45]Chen CP,Liu YP,Huang JK,et al.Contribution of ultrafast magnetic resonance imaging in prenatal diagnosis of sonographically undetected cerebral tuberous sclerosis associated with cardiac rhabdomyomas[J].Prenat Diagn,2005,25(6):523-4.
[46]Henske EP,McCormack FX.Lymphangioleiomyomatosis-a wolf in sheep’s clothing[J].J Clin Invest,2012,122(11):3807-16.
[47]Adriaensen ME,Schaefer-Prokop CM,Duyndam DA,Zonnenberg BA,Prokop M.Radiological evidence of lymphangioleiomyomatosis in female and male patients with tuberous sclerosis complex[J].Clin Radiol,2011,66(7):625-8.
[48]Aubry MC,Myers JL,Ryu JH,et al.Pulmonary lymphangioleiomyomatosis in a man[J].Am J Respir Crit Care Med,2000,162(2 Pt 1):749-52.
[49]Franz DN,Brody A,Meyer C,et al.Mutational and radiographic analysis of pulmonary disease consistent with lymphangioleiomyomatosis and micronodular pneumocyte hyperplasia in women with tuberous sclerosis[J].Am J Respir Crit Care Med,2001,164(4):661-8.
[50]Strizheva GD,Carsillo T,Kruger WD,et al.Sullivan EJ,Ryu JH,Henske EP.The spectrum of mutations in TSC1 and TSC2 in women with tuberous sclerosis and lymphangiomyomatosis[J].Am J Respir Crit Care Med,2001,163(1):253-8.
[51]Logginidou H,Ao X,Russo I,Henske EP.Frequent estrogen and progesterone receptor immunoreactivity in renal angiomyolipomas from women with pulmonary lymphangioleiomyomatosis[J].Chest,2000,117(1):25-30.
[52]Knudson AG.Hereditary cancer:two hits revisited[J].J Cancer Res Clin Oncol,1996,122(3):135-40.
[53]Hayashi T,Kumasaka T,Mitani K,Yao T,Suda K,Seyama K.Loss of heterozygosity on tuberous sclerosis complex genes in multifocal micronodular pneumocyte hyperplasia[J].Mod Pathol,2010,23(9):1251-60.
[54]Song MG,Park KB,Lee ES.Resurfacing of facial angiofibromas in tuberous sclerosis patients using CO2 laser with flashscanner[J].Dermatol Surg,1999,25(12):970-3.
[55]Fischer K,Blain B,Zhang F,Richards L,Lineaweaver WC.Treatment of facial angiofibromas of tuberous sclerosis by shave excision and dermabrasion in a dark-skinned patient[J].Ann Plast Surg,2001,46(3):332-5.
[56]Ewalt DH,Sheffield E,Sparagana SP,Delgado MR,Roach ES.Renal lesion growth in children with tuberous sclerosis complex[J].J Urol,1998,160(1):141-5.
[57]Henske EP,Wessner LL,Golden J,et al.Loss of tuberin in both subependymal giant cell astrocytomas and angiomyolipomas supports a two-hit model for the pathogenesis of tuberous sclerosis tumors[J].Am JPathol,1997,151(6):1639-47.
[58]Robb VA,Karbowniczek M,Klein-Szanto AJ,Henske EP.Activation of the mTOR signaling pathway in renal clear cell carcinoma[J].J Urol,2007,177(1):346-52.
[59]Karbowniczek M,Yu J,Henske EP.Renal angiomyolipomas from patients with sporadic lymphangiomyomatosis contain both neoplastic and nonneoplastic vascular structures[J].Am J Pathol,2003,162(2):491-500.
[60]Manoukian SB,Kowal DJ.Comprehensive imaging manifestations of tuberous sclerosis[J].AJR Am J Roentgenol,2015,204(5):933-43.
[61]Evans JC,Curtis J.The radiological appearances of tuberous sclerosis[J].Br JRadiol,2000,73(865):91-8.
[62]Martignoni G,Bonetti F,Pea M,Tardanico R,Brunelli M,Eble JN.Renal disease in adults with TSC2/PKD1 contiguous gene syndrome[J].Am J Surg Pathol,2002,26(2):198-205.
[63]Sampson JR,Maheshwar MM,Aspinwall R,et al.Renal cystic disease in tuberous sclerosis:role of the polycystic kidney disease 1 gene[J].Am J Hum Genet,1997,61(4):843-51.
[64]Brook-Carter PT,Peral B,Ward CJ,et al.Deletion of the TSC2 and PKD1genes associated with severe infantile polycystic kidney disease--a contiguous gene syndrome[J].Nat Genet,1994,8(4):328-32.
[65]Guo J,Tretiakova MS,Troxell ML,et al.Tuberous sclerosis-associated renal cell carcinoma:a clinicopathologic study of 57 separate carcinomas in 18patients[J].Am J Surg Pathol,2014,38(11):1457-67.
[66]De Waele L,Lagae L,Mekahli D.Tuberous sclerosis complex:the past and the future[J].Pediatr Nephrol,2015,30(10):1771-80.
[67]Muglia VF,Prando A.Renal cell carcinoma:histological classification and correlation with imaging findings[J].Radiol Bras,2015,48(3):166-74.
[68]Crino PB,Nathanson KL,Henske EP.The tuberous sclerosis complex[J].NEngl J Med,2006,355(13):1345-56.
[69]Robertson DM.Ophthalmic manifestations of tuberous sclerosis[J].Ann NY Acad Sci,1991,615:17-25.
[70]Rowley SA,O’Callaghan FJ,Osborne JP.Ophthalmic manifestations of tuberous sclerosis:a population based study[J].Br J Ophthalmol,2001,85(4):420-3.
[71]Braun RA,Milito CF,Goldman SM,et al.Ivory vertebra:imaging findings in different diagnoses[J].Radiol Bras,2016,49(2):117-21.
[72]Andrade Neto F,Teixeira MJ,et al.Knee bone tumors:findings on conventional radiology[J].Radiol Bras,2016,49(3):182-9.
[73]Lima Júnior FV,Savarese LG,Monsignore LM,et al.Computed tomography findings of paracoccidiodomycosis in musculoskelet al system[J].Radiol Bras,2015,48(1):1-6.
[74]Petrilli M,Senerchia AA,Petrilli AS,et al.Computed tomography-guided percutaneous trephine removal of the nidus in osteoid osteoma patients:experience of a single center in Brazil[J].Radiol Bras,2015,48(4):211-5.