Imaging of Children with Cancer Predisposition Syndromes

  • Sudha A. AnupindiEmail author
  • Ethan A. Smith
  • Nancy A. Chauvin
Part of the Pediatric Oncology book series (PEDIATRICO)


Five to ten percent of all pediatric tumors are associated with a genetic predisposition. In this chapter, we will discuss the main imaging examinations used in the evaluation of specific cancer predisposition syndromes (CPS) including Wilms’ tumor predisposition syndromes, Li-Fraumeni syndrome, and neurofibromatosis type 1, as well as more rare syndromes that have specific features, including DICER1 mutations, familial paraganglioma syndromes, and multiple endocrine neoplasia syndromes. Currently, ultrasound (US) and whole-body MRI (WBMRI) are the main modalities utilized for tumor surveillance in these children with cancer predisposition syndromes. Contrast-enhanced ultrasound and WBMRI with positron emission tomography (PET) are emerging as adjunct imaging tools in oncological imaging. In our discussion, we will also highlight the advantages and limitations of US and WBMRI and emphasize the importance of expert imaging interpretation and appropriate communication to clinicians and families.


Cancer predisposition syndromes Screening Test Imaging Children WBMRI Ultrasound 


  1. 1.
    Garber JE, Offit K. Hereditary cancer predisposition syndromes. J Clin Oncol. 2005;23(2):276–92.PubMedGoogle Scholar
  2. 2.
    Maxim LD, Niebo R, Utell MJ. Screening tests: a review with examples. Inhal Toxicol. 2014;26(13):811–28.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Smith RA, Andrews KS, Brooks D, Fedewa SA, Manassaram-Baptiste D, Saslow D, et al. Cancer screening in the United States, 2017: a review of current American Cancer Society guidelines and current issues in cancer screening. CA Cancer J Clin. 2017;67(2):100–21.PubMedGoogle Scholar
  4. 4.
    Kratz CP, Achatz MI, Brugieres L, Frebourg T, Garber JE, Greer MC, et al. Cancer screening recommendations for individuals with Li-Fraumeni syndrome. Clin Cancer Res. 2017;23(11):e38–45.PubMedGoogle Scholar
  5. 5.
    Reiman TA, Siegel MJ, Shackelford GD. Wilms tumor in children: abdominal CT and US evaluation. Radiology. 1986;160(2):501–5.Google Scholar
  6. 6.
    Vutskits L, Davidson A. Update on developmental anesthesia neurotoxicity. Curr Opin Anaesthesiol. 2017;30(3):337–42.PubMedGoogle Scholar
  7. 7.
    Sood S, Hryhorczuk AL, Rissmiller J, Lee EY. Spectrum of syndromic disorders associated with pediatric tumors: evolving role of practical imaging assessment. Radiol Clin North Am. 2017;55(4):869–93.PubMedGoogle Scholar
  8. 8.
    Yikilmaz A, George M, Lee EY. Pediatric hepatobiliary neoplasms: an overview and update. Radiol Clin North Am. 2017;55(4):741–66.PubMedGoogle Scholar
  9. 9.
    Rafailidis V, Deganello A, Watson T, Sidhu PS, Sellars ME. Enhancing the role of paediatric ultrasound with microbubbles: a review of intravenous applications. Br J Radiol. 2017;90(1069):20160556.PubMedGoogle Scholar
  10. 10.
    Sidhu PS, Cantisani V, Deganello A, Dietrich CF, Duran C, Franke D, et al. Role of contrast-enhanced ultrasound (CEUS) in paediatric practice: an EFSUMB position statement. Ultraschall Med. 2017;38(1):33–43.PubMedGoogle Scholar
  11. 11.
    Greer MC, Voss SD, States LJ. Pediatric cancer predisposition imaging: focus on whole-body MRI. Clin Cancer Res. 2017;23(11):e6–e13.PubMedGoogle Scholar
  12. 12.
    Anupindi SA, Bedoya MA, Lindell RB, Rambhatla SJ, Zelley K, Nichols KE, et al. Diagnostic performance of whole-body MRI as a tool for cancer screening in children with genetic cancer-predisposing conditions. AJR Am J Roentgenol. 2015;205(2):400–8.PubMedGoogle Scholar
  13. 13.
    Villani A, Malkin D. Biochemical and imaging surveillance in Li-Fraumeni syndrome - authors’ reply. Lancet Oncol. 2016;17(11):e473.PubMedGoogle Scholar
  14. 14.
    Villani A, Shore A, Wasserman JD, Stephens D, Kim RH, Druker H, et al. Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: 11 year follow-up of a prospective observational study. Lancet Oncol. 2016;17(9):1295–305.PubMedGoogle Scholar
  15. 15.
    Landier W, Ahern J, Barakat LP, Bhatia S, Bingen KM, Bondurant PG, et al. Patient/family education for newly diagnosed pediatric oncology patients. J Pediatr Oncol Nurs. 2016;33(6):422–31.PubMedPubMedCentralGoogle Scholar
  16. 16.
    Sahni VA, Silveira PC, Sainani NI, Khorasani R. Impact of a structured report template on the quality of MRI reports for rectal cancer staging. AJR Am J Roentgenol. 2015;205(3):584–8.Google Scholar
  17. 17.
    Valdez JM, Nichols KE, Kesserwan C. Li-Fraumeni syndrome: a paradigm for the understanding of hereditary cancer predisposition. Br J Haematol. 2017;176(4):539–52.PubMedGoogle Scholar
  18. 18.
    Correa H. Li-Fraumeni syndrome. J Pediatr Genet. 2016;5(2):84–8.PubMedPubMedCentralGoogle Scholar
  19. 19.
    Reinhardt HC, Schumacher B. The p53 network: cellular and systemic DNA damage responses in aging and cancer. Trends Genet. 2012;28(3):128–36.PubMedPubMedCentralGoogle Scholar
  20. 20.
    Mai PL, Best AF, Peters JA, DeCastro RM, Khincha PP, Loud JT, et al. Risks of first and subsequent cancers among TP53 mutation carriers in the National Cancer Institute Li-Fraumeni syndrome cohort. Cancer. 2016;122(23):3673–81.PubMedPubMedCentralGoogle Scholar
  21. 21.
    Bougeard G, Renaux-Petel M, Flaman JM, Charbonnier C, Fermey P, Belotti M, et al. Revisiting Li-Fraumeni syndrome from TP53 mutation carriers. J Clin Oncol. 2015;33(21):2345–52.PubMedGoogle Scholar
  22. 22.
    Hisada M, Garber JE, Fung CY, Fraumeni JF Jr, Li FP. Multiple primary cancers in families with Li-Fraumeni syndrome. J Natl Cancer Inst. 1998;90(8):606–11.PubMedGoogle Scholar
  23. 23.
    Villani A, Tabori U, Schiffman J, Shlien A, Beyene J, Druker H, et al. Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: a prospective observational study. Lancet Oncol. 2011;12(6):559–67.PubMedGoogle Scholar
  24. 24.
    Kalish JM, Deardorff MA. Tumor screening in Beckwith-Wiedemann syndrome-to screen or not to screen? Am J Med Genet A. 2016;170(9):2261–4.PubMedPubMedCentralGoogle Scholar
  25. 25.
    Eggermann T, Algar E, Lapunzina P, Mackay D, Maher ER, Mannens M, et al. Clinical utility gene card for: Beckwith-Wiedemann syndrome. Eur J Hum Genet. 2014;22(3)Google Scholar
  26. 26.
    Ibrahim A, Kirby G, Hardy C, Dias RP, Tee L, Lim D, et al. Methylation analysis and diagnostics of Beckwith-Wiedemann syndrome in 1,000 subjects. Clin Epigenetics. 2014;6(1):11.PubMedPubMedCentralGoogle Scholar
  27. 27.
    Mussa A, Molinatto C, Baldassarre G, Riberi E, Russo S, Larizza L, et al. Cancer risk in Beckwith-Wiedemann syndrome: a systematic review and meta-analysis outlining a novel (Epi)genotype specific histotype targeted screening protocol. J Pediatr. 2016;176:142–9 e1.PubMedGoogle Scholar
  28. 28.
    Maas SM, Vansenne F, Kadouch DJ, Ibrahim A, Bliek J, Hopman S, et al. Phenotype, cancer risk, and surveillance in Beckwith-Wiedemann syndrome depending on molecular genetic subgroups. Am J Med Genet A. 2016;170(9):2248–60.PubMedGoogle Scholar
  29. 29.
    Davidoff AM. Wilms’ tumor. Curr Opin Pediatr. 2009;21(3):357–64.PubMedPubMedCentralGoogle Scholar
  30. 30.
    Zarate YA, Mena R, Martin LJ, Steele P, Tinkle BT, Hopkin RJ. Experience with hemihyperplasia and Beckwith-Wiedemann syndrome surveillance protocol. Am J Med Genet A. 2009;149A(8):1691–7.PubMedGoogle Scholar
  31. 31.
    Dumoucel S, Gauthier-Villars M, Stoppa-Lyonnet D, Parisot P, Brisse H, Philippe-Chomette P, et al. Malformations, genetic abnormalities, and Wilms tumor. Pediatr Blood Cancer. 2014;61(1):140–4.PubMedGoogle Scholar
  32. 32.
    Chittiboina P, Lonser RR. Von Hippel-Lindau disease. Handb Clin Neurol. 2015;132:139–56.PubMedPubMedCentralGoogle Scholar
  33. 33.
    Poulsen ML, Budtz-Jorgensen E, Bisgaard ML. Surveillance in von Hippel-Lindau disease (vHL). Clin Genet. 2010;77(1):49–59.PubMedGoogle Scholar
  34. 34.
    Rednam SP, Erez A, Druker H, Janeway KA, Kamihara J, Kohlmann WK, et al. Von Hippel-Lindau and hereditary pheochromocytoma/paraganglioma syndromes: clinical features, genetics, and surveillance recommendations in childhood. Clin Cancer Res. 2017;23(12):e68–75.PubMedGoogle Scholar
  35. 35.
    Priesemann M, Davies KM, Perry LA, Drake WM, Chew SL, Monson JP, et al. Benefits of screening in von Hippel-Lindau disease--comparison of morbidity associated with initial tumours in affected parents and children. Horm Res. 2006;66(1):1–5.PubMedGoogle Scholar
  36. 36.
    Prasad R, Johnston LB, Savage MO, Martin L, Perry LA, Storr HL. Pediatric endocrine screening for von Hippel-Lindau disease: benefits and the challenge of compliance. J Endocrinol Invest. 2011;34(4):296–9.PubMedGoogle Scholar
  37. 37.
    Santos P, Pimenta T, Taveira-Gomes A. Hereditary pheochromocytoma. Int J Surg Pathol. 2014;22(5):393–400.PubMedGoogle Scholar
  38. 38.
    Fishbein L, Nathanson KL. Pheochromocytoma and paraganglioma: understanding the complexities of the genetic background. Cancer Genet. 2012;205(1-2):1–11.PubMedPubMedCentralGoogle Scholar
  39. 39.
    Evans DGR, Salvador H, Chang VY, Erez A, Voss SD, Schneider KW, et al. Cancer and central nervous system tumor surveillance in pediatric neurofibromatosis 1. Clin Cancer Res. 2017;23(12):e46–53.PubMedGoogle Scholar
  40. 40.
    Ferner RE, Huson SM, Thomas N, Moss C, Willshaw H, Evans DG, et al. Guidelines for the diagnosis and management of individuals with neurofibromatosis 1. J Med Genet. 2007;44(2):81–8.PubMedGoogle Scholar
  41. 41.
    Evans DGR, Salvador H, Chang VY, Erez A, Voss SD, Druker H, et al. Cancer and central nervous system tumor surveillance in pediatric neurofibromatosis 2 and related disorders. Clin Cancer Res. 2017;23(12):e54–61.PubMedGoogle Scholar
  42. 42.
    Evans DG, Huson SM, Donnai D, Neary W, Blair V, Newton V, et al. A clinical study of type 2 neurofibromatosis. Q J Med. 1992;84(304):603–18.PubMedGoogle Scholar
  43. 43.
    Schultze-Florey RE, Graf N, Vorwerk P, Koscielniak E, Schneider DT, Kratz CP. DICER1 syndrome: a new cancer syndrome. Klin Padiatr. 2013;225(3):177–8.PubMedGoogle Scholar
  44. 44.
    Slade I, Bacchelli C, Davies H, Murray A, Abbaszadeh F, Hanks S, et al. DICER1 syndrome: clarifying the diagnosis, clinical features and management implications of a pleiotropic tumour predisposition syndrome. J Med Genet. 2011;48(4):273–8.PubMedGoogle Scholar
  45. 45.
    Rothschild PR, Levy D, Savignoni A, Lumbroso-Le Rouic L, Aerts I, Gauthier-Villars M, et al. Familial retinoblastoma: fundus screening schedule impact and guideline proposal. A retrospective study. Eye (Lond). 2011;25(12):1555–61.Google Scholar
  46. 46.
    Kamihara J, Bourdeaut F, Foulkes WD, Molenaar JJ, Mosse YP, Nakagawara A, et al. Retinoblastoma and neuroblastoma predisposition and surveillance. Clin Cancer Res. 2017;23(13):e98–e106.PubMedGoogle Scholar
  47. 47.
    Parkin DM, Stiller CA, Draper GJ, Bieber CA. The international incidence of childhood cancer. Int J Cancer. 1988;42(4):511–20.PubMedGoogle Scholar
  48. 48.
    Staffieri SE, McGillivray G, Elder JE, Bristowe A, Cole S, McKenzie JD, et al. Managing fetuses at high risk of retinoblastoma: lesion detection on screening MRI. Prenat Diagn. 2015;35(2):174–8.PubMedGoogle Scholar
  49. 49.
    Monsalve J, Kapur J, Malkin D, Babyn PS. Imaging of cancer predisposition syndromes in children. Radiographics. 2011;31(1):263–80.PubMedGoogle Scholar
  50. 50.
    Grajo JR, Paspulati RM, Sahani DV, Kambadakone A. Multiple endocrine neoplasia syndromes: a comprehensive imaging review. Radiol Clin North Am. 2016;54(3):441–51.PubMedGoogle Scholar
  51. 51.
    Shinagare AB, Giardino AA, Jagannathan JP, Van den Abbeele AD, Ramaiya NH. Hereditary cancer syndromes: a radiologist’s perspective. AJR Am J Roentgenol. 2011;197(6):W1001–7.PubMedGoogle Scholar
  52. 52.
    Wasserman JD, Tomlinson GE, Druker H, Kamihara J, Kohlmann WK, Kratz CP, et al. Multiple endocrine neoplasia and hyperparathyroid-jaw tumor syndromes: clinical features, genetics, and surveillance recommendations in childhood. Clin Cancer Res. 2017;23(13):e123–e32.PubMedPubMedCentralGoogle Scholar
  53. 53.
    Farrell WE, Azevedo MF, Batista DL, Smith A, Bourdeau I, Horvath A, et al. Unique gene expression profile associated with an early-onset multiple endocrine neoplasia (MEN1)-associated pituitary adenoma. J Clin Endocrinol Metab. 2011;96(11):E1905–14.PubMedPubMedCentralGoogle Scholar
  54. 54.
    Morris LF, Waguespack SG, Edeiken-Monroe BS, Lee JE, Rich TA, Ying AK, et al. Ultrasonography should not guide the timing of thyroidectomy in pediatric patients diagnosed with multiple endocrine neoplasia syndrome 2A through genetic screening. Ann Surg Oncol. 2013;20(1):53–9.PubMedGoogle Scholar
  55. 55.
    Wells SA Jr, Asa SL, Dralle H, Elisei R, Evans DB, Gagel RF, et al. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid. 2015;25(6):567–610.PubMedPubMedCentralGoogle Scholar
  56. 56.
    American Thyroid Association Guidelines Task F, Kloos RT, Eng C, Evans DB, Francis GL, Gagel RF, et al. Medullary thyroid cancer: management guidelines of the American Thyroid Association. Thyroid. 2009;19(6):565–612.Google Scholar
  57. 57.
    Elisei R, Romei C, Renzini G, Bottici V, Cosci B, Molinaro E, et al. The timing of total thyroidectomy in RET gene mutation carriers could be personalized and safely planned on the basis of serum calcitonin: 18 years experience at one single center. J Clin Endocrinol Metab. 2012;97(2):426–35.PubMedGoogle Scholar
  58. 58.
    Rohmer V, Vidal-Trecan G, Bourdelot A, Niccoli P, Murat A, Wemeau JL, et al. Prognostic factors of disease-free survival after thyroidectomy in 170 young patients with a RET germline mutation: a multicenter study of the Groupe Francais d’Etude des Tumeurs Endocrines. J Clin Endocrinol Metab. 2011;96(3):E509–18.PubMedGoogle Scholar
  59. 59.
    Rowland KJ, Chernock RD, Moley JF. Pheochromocytoma in an 8-year-old patient with multiple endocrine neoplasia type 2A: implications for screening. J Surg Oncol. 2013;108(4):203–6.PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Sudha A. Anupindi
    • 1
    Email author
  • Ethan A. Smith
    • 2
  • Nancy A. Chauvin
    • 3
  1. 1.Department of RadiologyChildren’s Hospital of PhiladelphiaPhiladelphiaUSA
  2. 2.Department of RadiologyCincinnati Children’s Hospital Medical CenterCincinnatiUSA
  3. 3.Department of RadiologyHershey Children’s HospitalHersheyUSA

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