Pediatric Radiology

, Volume 48, Issue 9, pp 1307–1323 | Cite as

Thoracoabdominal imaging of tuberous sclerosis

  • Cara E. Morin
  • Nicholas P. Morin
  • David N. Franz
  • Darcy A. Krueger
  • Andrew T. Trout
  • Alexander J. TowbinEmail author
Pediatric Body MRI


Imaging of tuberous sclerosis complex has rapidly evolved over the last decade in association with increased understanding of the disease process and new treatment modalities. Tuberous sclerosis complex is best known for the neurological symptoms and the associated neuroimaging findings, and children with tuberous sclerosis complex require active surveillance of associated abnormalities in the chest, abdomen and pelvis. Common findings that require regular imaging surveillance are angiomyolipomas in the kidneys and lymphangioleiomyomatosis in the chest. However multiple rarer associations have been attributed to tuberous sclerosis complex and should be considered by radiologists reviewing any imaging in these children. In this review the authors discuss the spectrum of imaging findings in people with tuberous sclerosis complex, focusing on MR imaging findings in the chest, abdomen and pelvis.


Angiomyolipoma Children Magnetic resonance imaging Tuberous sclerosis complex 


Compliance with ethical standards

Conflicts of interest

Drs Franz and Krueger declared potential conflicts of interest.


  1. 1.
    Northrup H, Krueger DA, International Tuberous Sclerosis Complex Consensus Group (2013) Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol 49:243–254PubMedCentralCrossRefPubMedGoogle Scholar
  2. 2.
    Caban C, Khan N, Hasbani DM, Crino PB (2017) Genetics of tuberous sclerosis complex: implications for clinical practice. Appl Clin Genet 10:1–8CrossRefPubMedGoogle Scholar
  3. 3.
    Roach ES, Gomez MR, Northrup H (1998) Tuberous sclerosis complex consensus conference: revised clinical diagnostic criteria. J Child Neurol 13:624–628CrossRefPubMedGoogle Scholar
  4. 4.
    O’Callaghan FJ, Shiell AW, Osborne JP, Martyn CN (1998) Prevalence of tuberous sclerosis estimated by capture-recapture analysis. Lancet 351:1490CrossRefPubMedGoogle Scholar
  5. 5.
    Sampson JR, Scahill SJ, Stephenson JB et al (1989) Genetic aspects of tuberous sclerosis in the west of Scotland. J Med Genet 26:28–31PubMedCentralCrossRefPubMedGoogle Scholar
  6. 6.
    Randle SC (2017) Tuberous sclerosis complex: a review. Pediatr Ann 46:e166–e171CrossRefPubMedGoogle Scholar
  7. 7.
    Manoukian SB, Kowal DJ (2015) Comprehensive imaging manifestations of tuberous sclerosis. AJR Am J Roentgenol 204:933–943CrossRefPubMedGoogle Scholar
  8. 8.
    Au KS, Williams AT, Roach ES et al (2007) Genotype/phenotype correlation in 325 individuals referred for a diagnosis of tuberous sclerosis complex in the United States. Genet Med 9:88–100CrossRefPubMedGoogle Scholar
  9. 9.
    Webb DW, Clarke A, Fryer A, Osborne JP (1996) The cutaneous features of tuberous sclerosis: a population study. Br J Dermatol 135:1–5CrossRefPubMedGoogle Scholar
  10. 10.
    Jóźwiak S, Schwartz RA, Janniger CK et al (1998) Skin lesions in children with tuberous sclerosis complex: their prevalence, natural course, and diagnostic significance. Int J Dermatol 37:911–917CrossRefPubMedGoogle Scholar
  11. 11.
    Curatolo P, Bombardieri R, Jozwiak S (2008) Tuberous sclerosis. Lancet 372:657–668CrossRefPubMedGoogle Scholar
  12. 12.
    Curatolo P, Moavero R, Roberto D, Graziola F (2015) Genotype/phenotype correlations in tuberous sclerosis complex. Semin Pediatr Neurol 22:259–273CrossRefPubMedGoogle Scholar
  13. 13.
    Franz DN, Belousova E, Sparagana S et al (2013) Efficacy and safety of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis complex (EXIST-1): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet 381:125–132CrossRefPubMedGoogle Scholar
  14. 14.
    Bissler JJ, Kingswood JC, Radzikowska E et al (2013) Everolimus for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis (EXIST-2): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet 381:817–824CrossRefPubMedGoogle Scholar
  15. 15.
    Krueger DA, Wilfong AA, Holland-Bouley K et al (2013) Everolimus treatment of refractory epilepsy in tuberous sclerosis complex. Ann Neurol 74:679–687CrossRefPubMedGoogle Scholar
  16. 16.
    Capal JK, Franz DN (2016) Profile of everolimus in the treatment of tuberous sclerosis complex: an evidence-based review of its place in therapy. Neuropsychiatr Dis Treat 12:2165–2172PubMedCentralCrossRefPubMedGoogle Scholar
  17. 17.
    French JA, Lawson JA, Yapici Z et al (2016) Adjunctive everolimus therapy for treatment-resistant focal-onset seizures associated with tuberous sclerosis (EXIST-3): a phase 3, randomised, double-blind, placebo-controlled study. Lancet 388:2153–2163CrossRefPubMedGoogle Scholar
  18. 18.
    Siroky BJ, Towbin AJ, Trout AT et al (2017) Improvement in renal cystic disease of tuberous sclerosis complex after treatment with mammalian target of rapamycin inhibitor. J Pediatr 187:318–322.e2CrossRefPubMedGoogle Scholar
  19. 19.
    Koenig MK, Hebert AA, Roberson J et al (2012) Topical rapamycin therapy to alleviate the cutaneous manifestations of tuberous sclerosis complex: a double-blind, randomized, controlled trial to evaluate the safety and efficacy of topically applied rapamycin. Drugs R D 12:121–126PubMedCentralCrossRefPubMedGoogle Scholar
  20. 20.
    Krueger DA, Northrup H, International Tuberous Sclerosis Complex Consensus Group (2013) Tuberous sclerosis complex surveillance and management: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol 49:255–265PubMedCentralCrossRefPubMedGoogle Scholar
  21. 21.
    Halpenny D, Snow A, McNeill G, Torreggiani WC (2010) The radiological diagnosis and treatment of renal angiomyolipoma — current status. Clin Radiol 65:99–108CrossRefPubMedGoogle Scholar
  22. 22.
    Lopes Vendrami C, Parada Villavicencio C, DeJulio TJ et al (2017) Differentiation of solid renal tumors with multiparametric MR imaging. Radiographics 37:2026–2042CrossRefPubMedGoogle Scholar
  23. 23.
    Lienert AR, Nicol D (2012) Renal angiomyolipoma. BJU Int 110 Suppl 4:25–27CrossRefPubMedGoogle Scholar
  24. 24.
    Thway K, Fisher C (2015) PEComa: morphology and genetics of a complex tumor family. Ann Diagn Pathol 19:359–368CrossRefPubMedGoogle Scholar
  25. 25.
    Katabathina VS, Vikram R, Nagar AM et al (2010) Mesenchymal neoplasms of the kidney in adults: imaging spectrum with radiologic-pathologic correlation. Radiographics 30:1525–1540CrossRefPubMedGoogle Scholar
  26. 26.
    Jinzaki M, Silverman SG, Akita H et al (2014) Renal angiomyolipoma: a radiological classification and update on recent developments in diagnosis and management. Abdom Imaging 39:588–604PubMedCentralCrossRefPubMedGoogle Scholar
  27. 27.
    Fricke BL, Donnelly LF, Casper KA, Bissler JJ (2004) Frequency and imaging appearance of hepatic angiomyolipomas in pediatric and adult patients with tuberous sclerosis. AJR Am J Roentgenol 182:1027–1030CrossRefPubMedGoogle Scholar
  28. 28.
    Lu J, Xiong X-Z, Cheng N-S (2014) Education and imaging. Hepatobiliary and pancreatic: hepatic and renal angiomyolipomas associated with tuberous sclerosis complex. J Gastroenterol Hepatol 29:421CrossRefPubMedGoogle Scholar
  29. 29.
    Asayama Y, Fukuya T, Honda H et al (1998) Chronic expanding hematoma of the spleen caused by angiomyolipoma in a patient with tuberous sclerosis. Abdom Imaging 23:527–530CrossRefPubMedGoogle Scholar
  30. 30.
    Hulbert JC, Graf R (1983) Involvement of the spleen by renal angiomyolipoma: metastasis or multicentricity? J Urol 130:328–329CrossRefPubMedGoogle Scholar
  31. 31.
    Morita K, Shida Y, Shinozaki K et al (2012) Angiomyolipomas of the mediastinum and the lung. J Thorac Imaging 27:W21–W23CrossRefPubMedGoogle Scholar
  32. 32.
    Bissler JJ, Kingswood JC (2004) Renal angiomyolipomata. Kidney Int 66:924–934CrossRefPubMedGoogle Scholar
  33. 33.
    Yamakado K, Tanaka N, Nakagawa T et al (2002) Renal angiomyolipoma: relationships between tumor size, aneurysm formation, and rupture. Radiology 225:78–82CrossRefPubMedGoogle Scholar
  34. 34.
    O’Callaghan FJ, Noakes MJ, Martyn CN, Osborne JP (2004) An epidemiological study of renal pathology in tuberous sclerosis complex. BJU Int 94:853–857CrossRefPubMedGoogle Scholar
  35. 35.
    Ouzaid I, Autorino R, Fatica R et al (2014) Active surveillance for renal angiomyolipoma: outcomes and factors predictive of delayed intervention. BJU Int 114:412–417PubMedGoogle Scholar
  36. 36.
    Dickinson M, Ruckle H, Beaghler M, Hadley HR (1998) Renal angiomyolipoma: optimal treatment based on size and symptoms. Clin Nephrol 49:281–286PubMedGoogle Scholar
  37. 37.
    Amin S, Lux A, Calder N et al (2017) Causes of mortality in individuals with tuberous sclerosis complex. Dev Med Child Neurol 59:612–617CrossRefPubMedGoogle Scholar
  38. 38.
    Ramamurthy NK, Moosavi B, McInnes MDF et al (2015) Multiparametric MRI of solid renal masses: pearls and pitfalls. Clin Radiol 70:304–316CrossRefPubMedGoogle Scholar
  39. 39.
    Chung MS, Choi HJ, Kim M-H, Cho K-S (2014) Comparison of T2-weighted MRI with and without fat suppression for differentiating renal angiomyolipomas without visible fat from other renal tumors. AJR Am J Roentgenol 202:765–771CrossRefPubMedGoogle Scholar
  40. 40.
    Bissler JJ, McCormack FX, Young LR et al (2008) Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis. N Engl J Med 358:140–151PubMedCentralCrossRefPubMedGoogle Scholar
  41. 41.
    Casper KA, Donnelly LF, Chen B, Bissler JJ (2002) Tuberous sclerosis complex: renal imaging findings. Radiology 225:451–456CrossRefPubMedGoogle Scholar
  42. 42.
    Ewalt DH, Sheffield E, Sparagana SP et al (1998) Renal lesion growth in children with tuberous sclerosis complex. J Urol 160:141–145CrossRefPubMedGoogle Scholar
  43. 43.
    Dillman JR, Trout AT, Smith EA, Towbin AJ (2017) Hereditary renal cystic disorders: imaging of the kidneys and beyond. Radiographics 37:924–946CrossRefPubMedGoogle Scholar
  44. 44.
    Brook-Carter PT, Peral B, Ward CJ et al (1994) Deletion of the TSC2 and PKD1 genes associated with severe infantile polycystic kidney disease — a contiguous gene syndrome. Nat Genet 8:328–332CrossRefPubMedGoogle Scholar
  45. 45.
    Back SJ, Andronikou S, Kilborn T et al (2015) Imaging features of tuberous sclerosis complex with autosomal-dominant polycystic kidney disease: a contiguous gene syndrome. Pediatr Radiol 45:386–395CrossRefPubMedGoogle Scholar
  46. 46.
    Black ME, Hedgire SS, Camposano S et al (2012) Hepatic manifestations of tuberous sclerosis complex: a genotypic and phenotypic analysis. Clin Genet 82:552–557CrossRefPubMedGoogle Scholar
  47. 47.
    Tello R, Blickman JG, Buonomo C, Herrin J (1998) Meta analysis of the relationship between tuberous sclerosis complex and renal cell carcinoma. Eur J Radiol 27:131–138CrossRefPubMedGoogle Scholar
  48. 48.
    National Cancer Institute (2014) Cancer stat facts: kidney and renal pelvis cancer. Accessed 12 Nov 2017
  49. 49.
    Rakowski SK, Winterkorn EB, Paul E et al (2006) Renal manifestations of tuberous sclerosis complex: incidence, prognosis, and predictive factors. Kidney Int 70:1777–1782CrossRefPubMedGoogle Scholar
  50. 50.
    Lendvay TS, Broecker B, Smith EA (2002) Renal cell carcinoma in a 2-year-old child with tuberous sclerosis. J Urol 168:1131–1132CrossRefPubMedGoogle Scholar
  51. 51.
    Washecka R, Hanna M (1991) Malignant renal tumors in tuberous sclerosis. Urology 37:340–343CrossRefPubMedGoogle Scholar
  52. 52.
    Crino PB, Nathanson KL, Henske EP (2006) The tuberous sclerosis complex. N Engl J Med 355:1345–1356CrossRefPubMedGoogle Scholar
  53. 53.
    Guo J, Tretiakova MS, Troxell ML et al (2014) Tuberous sclerosis-associated renal cell carcinoma: a clinicopathologic study of 57 separate carcinomas in 18 patients. Am J Surg Pathol 38:1457–1467CrossRefPubMedGoogle Scholar
  54. 54.
    Yang P, Cornejo KM, Sadow PM et al (2014) Renal cell carcinoma in tuberous sclerosis complex. Am J Surg Pathol 38:895–909PubMedCentralCrossRefPubMedGoogle Scholar
  55. 55.
    Bjornsson J, Short MP, Kwiatkowski DJ, Henske EP (1996) Tuberous sclerosis-associated renal cell carcinoma. Clinical, pathological, and genetic features. Am J Pathol 149:1201–1208PubMedCentralPubMedGoogle Scholar
  56. 56.
    Li H, Liang L, Li A et al (2017) Monoexponential, biexponential, and stretched exponential diffusion-weighted imaging models: quantitative biomarkers for differentiating renal clear cell carcinoma and minimal fat angiomyolipoma. J Magn Reson Imaging 46:240–247CrossRefPubMedGoogle Scholar
  57. 57.
    Ding Y, Zeng M, Rao S et al (2016) Comparison of biexponential and monoexponential model of diffusion-weighted imaging for distinguishing between common renal cell carcinoma and fat poor angiomyolipoma. Korean J Radiol 17:853–863PubMedCentralCrossRefPubMedGoogle Scholar
  58. 58.
    Darden JW, Teeslink R, Parrish A (1975) Hamartoma of the spleen: a manifestation of tuberous sclerosis. Am Surg 41:564–566PubMedGoogle Scholar
  59. 59.
    Ramani M, Reinhold C, Semelka RC et al (1997) Splenic hemangiomas and hamartomas: MR imaging characteristics of 28 lesions. Radiology 202:166–172CrossRefPubMedGoogle Scholar
  60. 60.
    Torres GM, Terry NL, Mergo PJ, Ros PR (1995) MR imaging of the spleen. Magn Reson Imaging Clin N Am 3:39–50PubMedGoogle Scholar
  61. 61.
    Paterson A, Frush DP, Donnelly LF et al (1999) A pattern-oriented approach to splenic imaging in infants and children. Radiographics 19:1465–1485CrossRefPubMedGoogle Scholar
  62. 62.
    Wang J-H, Ma X-L, Ren F-Y et al (2013) Multi-modality imaging findings of splenic hamartoma: a report of nine cases and review of the literature. Abdom Imaging 38:154–162CrossRefPubMedGoogle Scholar
  63. 63.
    Arva NC, Pappas JG, Bhatla T et al (2012) Well-differentiated pancreatic neuroendocrine carcinoma in tuberous sclerosis — case report and review of the literature. Am J Surg Pathol 36:149–153CrossRefPubMedGoogle Scholar
  64. 64.
    Díaz Díaz D, Ibarrola C, Goméz Sanz R et al (2012) Neuroendocrine tumor of the pancreas in a patient with tuberous sclerosis: a case report and review of the literature. Int J Surg Pathol 20:390–395CrossRefPubMedGoogle Scholar
  65. 65.
    Larson AM, Hedgire SS, Deshpande V et al (2012) Pancreatic neuroendocrine tumors in patients with tuberous sclerosis complex. Clin Genet 82:558–563CrossRefPubMedGoogle Scholar
  66. 66.
    Koc G, Sugimoto S, Kuperman R et al (2017) Pancreatic tumors in children and young adults with tuberous sclerosis complex. Pediatr Radiol 47:39–45CrossRefPubMedGoogle Scholar
  67. 67.
    Buehler D, Weisman P (2017) Soft tissue tumors of uncertain histogenesis: a review for dermatopathologists. Clin Lab Med 37:647–671CrossRefPubMedGoogle Scholar
  68. 68.
    Fletcher CDM, Krishnan Unni K, Mertens F (2002) Pathology and genetics of tumours of soft tissue and bone. IARC, LyonGoogle Scholar
  69. 69.
    Martignoni G, Pea M, Reghellin D et al (2008) PEComas: the past, the present and the future. Virchows Arch 452:119–132CrossRefPubMedGoogle Scholar
  70. 70.
    Bonetti F, Pea M, Martignoni G, Zamboni G (1992) PEC and sugar. Am J Surg Pathol 16:307–308CrossRefPubMedGoogle Scholar
  71. 71.
    Agaram NP, Sung Y-S, Zhang L et al (2015) Dichotomy of genetic abnormalities in PEComas with therapeutic implications. Am J Surg Pathol 39:813–825PubMedCentralCrossRefPubMedGoogle Scholar
  72. 72.
    Hartley CP, Kwiatkowski DJ, Hamieh L et al (2016) Pancreatic PEComa is a novel member of the family of tuberous sclerosis complex-associated tumors: case report and review of the literature. Virchows Arch 469:707–710CrossRefPubMedGoogle Scholar
  73. 73.
    Okamoto S, Komura M, Terao Y et al (2017) Pneumothorax caused by cystic and nodular lung metastases from a malignant uterine perivascular epithelioid cell tumor (PEComa). Respir Med Case Rep 22:77–82PubMedCentralPubMedGoogle Scholar
  74. 74.
    Starbuck KD, Drake RD, Budd GT, Rose PG (2016) Treatment of advanced malignant uterine perivascular epithelioid cell tumor with mTOR inhibitors: single-institution experience and review of the literature. Anticancer Res 36:6161–6164CrossRefPubMedGoogle Scholar
  75. 75.
    Tan Y, Zhang H, Xiao E-H (2013) Perivascular epithelioid cell tumour: dynamic CT, MRI and clinicopathological characteristics — analysis of 32 cases and review of the literature. Clin Radiol 68:555–561CrossRefPubMedGoogle Scholar
  76. 76.
    Calcagni G, Gesualdo F, Tamisier D et al (2008) Arterial aneurysms and tuberous sclerosis: a classic but little known association. Pediatr Radiol 38:795–797CrossRefPubMedGoogle Scholar
  77. 77.
    Jost CJ, Gloviczki P, Edwards WD et al (2001) Aortic aneurysms in children and young adults with tuberous sclerosis: report of two cases and review of the literature. J Vasc Surg 33:639–642CrossRefPubMedGoogle Scholar
  78. 78.
    Arora A, Bansal K, Sureka B (2015) Vascular, gastrointestinal, and urogenital associations of tuberous sclerosis: classic but less known. AJR Am J Roentgenol 205:W566CrossRefPubMedGoogle Scholar
  79. 79.
    Rolfes DB, Towbin R, Bove KE (1985) Vascular dysplasia in a child with tuberous sclerosis. Pediatr Pathol 3:359–373CrossRefPubMedGoogle Scholar
  80. 80.
    Dunet V, Qanadli SD, Lazor R (2013) Beigelman-Aubry C (2013) multiple pulmonary artery aneurysms in tuberous sclerosis complex. BMJ Case Rep.
  81. 81.
    Wong H, Hadi M, Khoury T et al (2006) Management of severe hypertension in a child with tuberous sclerosis-related major vascular abnormalities. J Hypertens 24:597–599CrossRefPubMedGoogle Scholar
  82. 82.
    Kimura Y, Sugimura H, Toda M et al (2005) A case of a 2-year-old boy with tuberous sclerosis complicated with descending aortic aneurysm. Pediatr Int 47:224–226CrossRefPubMedGoogle Scholar
  83. 83.
    Patiño Bahena E, Calderón-Colmenero J, Buendía A, Juanico A (2005) Giant aortic aneurysm and rhabdomyomas in infant with tuberous sclerosis (case report). Arch Cardiol Mex 75:448–450PubMedGoogle Scholar
  84. 84.
    Moon S-B, Shin W-Y, Park Y-J, Kim S-J (2009) An abdominal aortic aneurysm in an 8-month-old girl with tuberous sclerosis. Eur J Vasc Endovasc Surg 37:569–571CrossRefPubMedGoogle Scholar
  85. 85.
    Carette M-F, Antoine M, Bazelly B et al (2006) Primary pulmonary artery aneurysm in tuberous sclerosis: CT, angiography and pathological study. Eur Radiol 16:2369–2370CrossRefPubMedGoogle Scholar
  86. 86.
    Burrows NJ, Johnson SR (2004) Pulmonary artery aneurysm and tuberous sclerosis. Thorax 59:86PubMedCentralCrossRefPubMedGoogle Scholar
  87. 87.
    Hyman MH, Whittemore VH (2000) National Institutes of Health consensus conference: tuberous sclerosis complex. Arch Neurol 57:662–665CrossRefPubMedGoogle Scholar
  88. 88.
    Salerno AE, Marsenic O, Meyers KEC et al (2010) Vascular involvement in tuberous sclerosis. Pediatr Nephrol 25:1555–1561CrossRefPubMedGoogle Scholar
  89. 89.
    Flynn PM, Robinson MB, Stapleton FB et al (1984) Coarctation of the aorta and renal artery stenosis in tuberous sclerosis. Pediatr Radiol 14:337–339CrossRefPubMedGoogle Scholar
  90. 90.
    Maruyama H, Ohbayashi C, Hino O et al (2001) Pathogenesis of multifocal micronodular pneumocyte hyperplasia and lymphangioleiomyomatosis in tuberous sclerosis and association with tuberous sclerosis genes TSC1 and TSC2. Pathol Int 51:585–594CrossRefPubMedGoogle Scholar
  91. 91.
    Castro M, Shepherd CW, Gomez MR et al (1995) Pulmonary tuberous sclerosis. Chest 107:189–195CrossRefPubMedGoogle Scholar
  92. 92.
    Taveira-DaSilva AM, Pacheco-Rodriguez G, Moss J (2010) The natural history of lymphangioleiomyomatosis: markers of severity, rate of progression and prognosis. Lymphat Res Biol 8:9–19PubMedCentralCrossRefPubMedGoogle Scholar
  93. 93.
    Johnson SR, Cordier JF, Lazor R et al (2010) European Respiratory Society guidelines for the diagnosis and management of lymphangioleiomyomatosis. Eur Respir J 35:14–26CrossRefPubMedGoogle Scholar
  94. 94.
    Darling TN, Pacheco-Rodriguez G, Gorio A et al (2010) Lymphangioleiomyomatosis and TSC2−/− cells. Lymphat Res Biol 8:59–69PubMedCentralCrossRefPubMedGoogle Scholar
  95. 95.
    Glasgow CG, Taveira-DaSilva A, Pacheco-Rodriguez G et al (2009) Involvement of lymphatics in lymphangioleiomyomatosis. Lymphat Res Biol 7:221–228PubMedCentralCrossRefPubMedGoogle Scholar
  96. 96.
    Di Marco F, Terraneo S, Imeri G et al (2016) Women with TSC: relationship between clinical, lung function and radiological features in a genotyped population investigated for lymphangioleiomyomatosis. PLoS One 11:e0155331PubMedCentralCrossRefPubMedGoogle Scholar
  97. 97.
    Franz DN, Brody A, Meyer C et al (2001) Mutational and radiographic analysis of pulmonary disease consistent with lymphangioleiomyomatosis and micronodular pneumocyte hyperplasia in women with tuberous sclerosis. Am J Respir Crit Care Med 164:661–668CrossRefPubMedGoogle Scholar
  98. 98.
    Costello LC, Hartman TE, Ryu JH (2000) High frequency of pulmonary lymphangioleiomyomatosis in women with tuberous sclerosis complex. Mayo Clin Proc 75:591–594CrossRefPubMedGoogle Scholar
  99. 99.
    Moss J, Avila NA, Barnes PM et al (2001) Prevalence and clinical characteristics of lymphangioleiomyomatosis (LAM) in patients with tuberous sclerosis complex. Am J Respir Crit Care Med 164:669–671CrossRefPubMedGoogle Scholar
  100. 100.
    Taylor JR, Ryu J, Colby TV, Raffin TA (1990) Lymphangioleiomyomatosis. Clinical course in 32 patients. N Engl J Med 323:1254–1260CrossRefPubMedGoogle Scholar
  101. 101.
    Hammes SR, Krymskaya VP (2013) Targeted approaches toward understanding and treating pulmonary lymphangioleiomyomatosis (LAM). Horm Cancer 4:70–77CrossRefPubMedGoogle Scholar
  102. 102.
    Umeoka S, Koyama T, Miki Y et al (2008) Pictorial review of tuberous sclerosis in various organs. Radiographics 28:e32CrossRefPubMedGoogle Scholar
  103. 103.
    Tobino K, Johkoh T, Fujimoto K et al (2015) Computed tomographic features of lymphangioleiomyomatosis: evaluation in 138 patients. Eur J Radiol 84:534–541CrossRefPubMedGoogle Scholar
  104. 104.
    von Ranke FM, Zanetti G, e Silva JLP et al (2015) Tuberous sclerosis complex: state-of-the-art review with a focus on pulmonary involvement. Lung 193:619–627Google Scholar
  105. 105.
    Crausman RS, Lynch DA, Mortenson RL et al (1996) Quantitative CT predicts the severity of physiologic dysfunction in patients with lymphangioleiomyomatosis. Chest 109:131–137CrossRefPubMedGoogle Scholar
  106. 106.
    King MA (1996) MR diagnosis of lymphangioleiomyomatosis: visibility of pulmonary cysts on spin-echo images. Magn Reson Imaging 14:361–363CrossRefPubMedGoogle Scholar
  107. 107.
    Popper HH, Juettner-Smolle FM, Pongratz MG (1991) Micronodular hyperplasia of type II pneumocytes — a new lung lesion associated with tuberous sclerosis. Histopathology 18:347–354CrossRefPubMedGoogle Scholar
  108. 108.
    Guinee D, Singh R, Azumi N et al (1995) Multifocal micronodular pneumocyte hyperplasia: a distinctive pulmonary manifestation of tuberous sclerosis. Mod Pathol 8:902–906PubMedGoogle Scholar
  109. 109.
    Avila NA, Dwyer AJ, Rabel A, Moss J (2007) Sporadic lymphangioleiomyomatosis and tuberous sclerosis complex with lymphangioleiomyomatosis: comparison of CT features. Radiology 242:277–285CrossRefPubMedGoogle Scholar
  110. 110.
    Taniguchi H, Abo H, Uchiyama A, Noto H (2016) Multifocal micronodular pneumocyte hyperplasia with tuberous sclerosis. Intern Med 55:3407–3408PubMedCentralCrossRefPubMedGoogle Scholar
  111. 111.
    Ristagno RL, Biddinger PW, Pina EM, Meyer CA (2005) Multifocal micronodular pneumocyte hyperplasia in tuberous sclerosis. AJR Am J Roentgenol 184:S37–S39CrossRefPubMedGoogle Scholar
  112. 112.
    Kobashi Y, Sugiu T, Mouri K et al (2008) Multifocal micronodular pneumocyte hyperplasia associated with tuberous sclerosis: differentiation from multiple atypical adenomatous hyperplasia. Jpn J Clin Oncol 38:451–454CrossRefPubMedGoogle Scholar
  113. 113.
    Datta AN, Hahn CD, Sahin M (2008) Clinical presentation and diagnosis of tuberous sclerosis complex in infancy. J Child Neurol 23:268–273CrossRefPubMedGoogle Scholar
  114. 114.
    Beghetti M, Gow RM, Haney I et al (1997) Pediatric primary benign cardiac tumors: a 15-year review. Am Heart J 134:1107–1114CrossRefPubMedGoogle Scholar
  115. 115.
    Grebenc ML, Rosado de Christenson ML, Burke AP et al (2000) Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation. Radiographics 20:1073–1103CrossRefPubMedGoogle Scholar
  116. 116.
    Jóźwiak S, Kotulska K, Kasprzyk-Obara J et al (2006) Clinical and genotype studies of cardiac tumors in 154 patients with tuberous sclerosis complex. Pediatrics 118:e1146–e1151CrossRefPubMedGoogle Scholar
  117. 117.
    Harding CO, Pagon RA (1990) Incidence of tuberous sclerosis in patients with cardiac rhabdomyoma. Am J Med Genet 37:443–446CrossRefPubMedGoogle Scholar
  118. 118.
    Jóźwiak S, Kawalec W, Dłuzewska J et al (1994) Cardiac tumours in tuberous sclerosis: their incidence and course. Eur J Pediatr 153:155–157CrossRefPubMedGoogle Scholar
  119. 119.
    Beroukhim RS, Prakash A, Valsangiacomo Buechel ER et al (2011) Characterization of cardiac tumors in children by cardiovascular magnetic resonance imaging. J Am Coll Cardiol 58:1044–1054CrossRefPubMedGoogle Scholar
  120. 120.
    Shaaya EA, Hirshberg JS, Rabe OT et al (2013) Cardiac fat-containing lesions are common in tuberous sclerosis complex. Am J Med Genet A 161A:1662–1665CrossRefPubMedGoogle Scholar
  121. 121.
    Adriaensen MEAPM, Schaefer-Prokop CM, Duyndam DAC et al (2009) Fatty foci in the myocardium in patients with tuberous sclerosis complex: common finding at CT. Radiology 253:359–363CrossRefPubMedGoogle Scholar
  122. 122.
    Winterkorn EB, Dodd JD, Inglessis I et al (2007) Tuberous sclerosis complex and myocardial fat-containing lesions: a report of four cases. Clin Genet 71:371–373CrossRefPubMedGoogle Scholar
  123. 123.
    Adriaensen MEAPM, van Oosterhout MFM, Feringa HHH et al (2011) Mature fat cells in the myocardium of patients with tuberous sclerosis complex. J Clin Pathol 64:244–245CrossRefPubMedGoogle Scholar
  124. 124.
    Connell FC, Gordon K, Brice G et al (2013) The classification and diagnostic algorithm for primary lymphatic dysplasia: an update from 2010 to include molecular findings. Clin Genet 84:303–314CrossRefPubMedGoogle Scholar
  125. 125.
    Geffrey AL, Shinnick JE, Staley BA et al (2014) Lymphedema in tuberous sclerosis complex. Am J Med Genet A 164A:1438–1442CrossRefPubMedGoogle Scholar
  126. 126.
    Hoshika Y, Hamamoto T, Sato K et al (2013) Prevalence and clinical features of lymphedema in patients with lymphangioleiomyomatosis. Respir Med 107:1253–1259CrossRefPubMedGoogle Scholar
  127. 127.
    Hirsch RJ, Silverberg NB, Laude T, Weinberg JM (1999) Tuberous sclerosis associated with congenital lymphedema. Pediatr Dermatol 16:407–408PubMedGoogle Scholar
  128. 128.
    Voudris KA, Skardoutsou A, Vagiakou EA (2003) Tuberous sclerosis and congenital lymphedema. Pediatr Dermatol 20:371–373CrossRefPubMedGoogle Scholar
  129. 129.
    Lucas M, Andrade Y (2011) Congenital lymphedema with tuberous sclerosis and clinical Hirschsprung disease. Pediatr Dermatol 28:194–195CrossRefPubMedGoogle Scholar
  130. 130.
    Sukulal K, Namboodiri N (2012) Congenital lymphedema: another unique and gender specific stigmata of tuberous sclerosis? Indian Pediatr 49:845CrossRefPubMedGoogle Scholar
  131. 131.
    Cottafava F, Cosso D, Brida di Priò S et al (1986) A case of Bourneville’s tuberous sclerosis with elephantiasis (caused by lymphedema) of the left leg. Minerva Pediatr 38:49–52PubMedGoogle Scholar
  132. 132.
    Prato G, Mancardi MM, Baglietto MG et al (2014) Congenital segmental lymphedema in tuberous sclerosis complex with associated subependymal giant cell astrocytomas treated with Mammalian target of rapamycin inhibitors. J Child Neurol 29:NP54–NP57CrossRefPubMedGoogle Scholar
  133. 133.
    Pollack SF, Geffrey AL, Thiele EA, Shah U (2015) Primary intestinal lymphangiectasia treated with rapamycin in a child with tuberous sclerosis complex (TSC). Am J Med Genet A 167A:2209–2212CrossRefPubMedGoogle Scholar
  134. 134.
    Adams DM, Trenor CC 3rd, Hammill AM et al (2016) Efficacy and safety of sirolimus in the treatment of complicated vascular anomalies. Pediatrics 137:e20153257PubMedCentralCrossRefPubMedGoogle Scholar
  135. 135.
    Holt JF, Dickerson WW (1952) The osseous lesions of tuberous sclerosis. Radiology 58:1–7CrossRefPubMedGoogle Scholar
  136. 136.
    Boronat S, Barber I, Pargaonkar V et al (2016) Sclerotic bone lesions at abdominal magnetic resonance imaging in children with tuberous sclerosis complex. Pediatr Radiol 46:689–694CrossRefPubMedGoogle Scholar
  137. 137.
    Jonard P, Lonneux M, Boland B et al (2001) Tc-99m HDP bone scan showing bone changes in a case of tuberous sclerosis or Bourneville’s disease. Clin Nucl Med 26:50–52CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Cara E. Morin
    • 1
  • Nicholas P. Morin
    • 2
  • David N. Franz
    • 3
  • Darcy A. Krueger
    • 3
  • Andrew T. Trout
    • 1
  • Alexander J. Towbin
    • 1
    Email author
  1. 1.Department of RadiologyCincinnati Children’s Hospital Medical CenterCincinnatiUSA
  2. 2.Division of Emergency MedicineCincinnati Children’s Hospital Medical CenterCincinnatiUSA
  3. 3.Division of NeurologyCincinnati Children’s Hospital Medical CenterCincinnatiUSA

Personalised recommendations