Advertisement

Pediatric Radiology

, Volume 48, Issue 9, pp 1364–1375 | Cite as

Imaging of cancer predisposition syndromes

  • Mary-Louise C. Greer
Pediatric Body MRI
  • 128 Downloads

Abstract

Pediatric cancer predisposition syndromes comprise a group of diseases characterized by specific tumors or a concomitance of tumors in infants, children and adolescents, suggesting a genetic cancer susceptibility condition. Most but not all have germline pathogenic variants on genetic testing. For some children with cancer predisposition syndromes, this diagnosis is based on their own or a family history of related neoplasms, or associated clinical manifestations. These tumors have variable incidence and age of onset. Imaging encompasses investigation in symptomatic children for diagnosis, staging and monitoring for treatment response and metastatic disease, as well as surveillance for primary tumors in asymptomatic children. In this review the author focuses on the role of surveillance imaging in childhood cancer predisposition syndromes, whole-body magnetic resonance imaging (whole-body MRI) in particular. Diagnosis and staging of specific tumors are addressed elsewhere in this series. The benefits of surveillance imaging include early detection and improved outcomes and are still being established for a number of cancer predisposition syndromes. The benefits must be weighed against risks including potential technique-related issues relating to sedation or contrast agents, false-positive imaging findings, and cost — both financial and psychosocial. The author discusses general principles for whole-body MRI interpretation along with findings in specific syndromes where whole-body MRI screening is recommended, such as Li–Fraumeni syndrome.

Keywords

Cancer predisposition syndrome Children Genetics Li–Fraumeni syndrome Oncology Surveillance Whole-body magnetic resonance imaging 

Notes

Compliance with ethical standards

Conflicts of interest

None

References

  1. 1.
    American Society of Clinical Oncology (2003) American Society of Clinical Oncology policy statement update: genetic testing for cancer susceptibility. J Clin Oncol 21:2397–2406CrossRefGoogle Scholar
  2. 2.
    Monsalve J, Kapur J, Malkin D et al (2011) Imaging of cancer predisposition syndromes in children. Radiographics 31:263–280CrossRefPubMedGoogle Scholar
  3. 3.
    van Engelen K, Villani A, Wasserman JD et al (2017) DICER1 syndrome: approach to testing and management at a large pediatric tertiary care center. Pediatr Blood Cancer 65(1)Google Scholar
  4. 4.
    Druker H, Zelley K, McGee RB et al (2017) Genetic counselor recommendations for cancer predisposition evaluation and surveillance in the pediatric oncology patient. Clin Cancer Res 23:e91–e97CrossRefPubMedGoogle Scholar
  5. 5.
    Jongmans MC, Loeffen JL, Waanders E et al (2016) Recognition of genetic predisposition in pediatric cancer patients: an easy-to-use selection tool. Eur J Med Genet 59:116–125CrossRefPubMedGoogle Scholar
  6. 6.
    Greer MC, Voss SD, States LJ (2017) Pediatric cancer predisposition imaging: focus on whole-body MRI. Clin Cancer Res 23:e6–e13CrossRefPubMedGoogle Scholar
  7. 7.
    Villani A, Tabori U, Schiffman J et al (2011) Biochemical and imaging surveillance in germline TP53 mutation carriers with li-Fraumeni syndrome: a prospective observational study. Lancet Oncol 12:559–567CrossRefPubMedGoogle Scholar
  8. 8.
    Villani A, Shore A, Wasserman JD et al (2016) Biochemical and imaging surveillance in germline TP53 mutation carriers with li-Fraumeni syndrome: 11 year follow-up of a prospective observational study. Lancet Oncol 17:1295–1305CrossRefPubMedGoogle Scholar
  9. 9.
    McNeil DE, Brown M, Ching A et al (2001) Screening for Wilms tumor and hepatoblastoma in children with Beckwith-Wiedemann syndromes: a cost-effective model. Med Pediatr Oncol 37:349–356CrossRefPubMedGoogle Scholar
  10. 10.
    Friedman DN, Lis E, Sklar CA et al (2014) Whole-body magnetic resonance imaging (WB-MRI) as surveillance for subsequent malignancies in survivors of hereditary retinoblastoma: a pilot study. Pediatr Blood Cancer 61:1440–1444CrossRefPubMedGoogle Scholar
  11. 11.
    Zhang J, Walsh MF, Wu G et al (2015) Germline mutations in predisposition genes in pediatric cancer. N Engl J Med 373:2336–2346CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Brodeur GM, Nichols KE, Plon SE et al (2017) Pediatric cancer predisposition and surveillance: an overview, and a tribute to Alfred G. Knudson Jr. Clin Cancer Res 23:e1–e5CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Foulkes WD, Kamihara J, Evans DGR et al (2017) Cancer surveillance in Gorlin syndrome and rhabdoid tumor predisposition syndrome. Clin Cancer Res 23:e62–e67CrossRefPubMedGoogle Scholar
  14. 14.
    Bueno MT, Martinez-Rios C, la Puente Gregorio A et al (2017) Pediatric imaging in DICER1 syndrome. Pediatr Radiol 47:1292–1301CrossRefPubMedGoogle Scholar
  15. 15.
    Brenner DJ, Shuryak I, Einstein AJ (2011) Impact of reduced patient life expectancy on potential cancer risks from radiologic imaging. Radiology 261:193–198CrossRefPubMedGoogle Scholar
  16. 16.
    Mathews JD, Forsythe AV, Brady Z et al (2013) Cancer risk in 680,000 people exposed to computed tomography scans in childhood or adolescence: data linkage study of 11 million Australians. BMJ 346:f2360CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Kratz CP, Achatz MI, Brugieres L et al (2017) Cancer screening recommendations for individuals with li-Fraumeni syndrome. Clin Cancer Res 23:e38–e45CrossRefPubMedGoogle Scholar
  18. 18.
    Anupindi SA, Bedoya MA, Lindell RB et al (2015) Diagnostic performance of whole-body MRI as a tool for cancer screening in children with genetic cancer-predisposing conditions. AJR Am J Roentgenol 205:400–408CrossRefPubMedGoogle Scholar
  19. 19.
    Teixeira SR, Elias Junior J, Nogueira-Barbosa MH et al (2015) Whole-body magnetic resonance imaging in children: state of the art. Radiol Bras 48:111–120CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Guimaraes MD, Noschang J, Teixeira SR et al (2017) Whole-body MRI in pediatric patients with cancer. Cancer Imaging 17:6CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Lecouvet FE (2016) Whole-body MR imaging: musculoskeletal applications. Radiology 279:345–365CrossRefPubMedGoogle Scholar
  22. 22.
    Anupindi SA, Chauvin NA, Nichols KE (2016) Reply to 'Whole-body MRI screening in children with li-Fraumeni and other cancer-predisposition syndromes. AJR Am J Roentgenol 206:W53CrossRefPubMedGoogle Scholar
  23. 23.
    Tijerin Bueno M, Malkin D, Villani A, Moineddin R (2015) Whole body MRI in children with cancer predisposition syndromes. Pediatr Radiol 45:71Google Scholar
  24. 24.
    Davidson AJ, Disma N, de Graaff JC et al (2016) Neurodevelopmental outcome at 2 years of age after general anaesthesia and awake-regional anaesthesia in infancy (GAS): an international multicentre, randomised controlled trial. Lancet 387:239–250CrossRefPubMedGoogle Scholar
  25. 25.
    Sadowski EA, Bennett LK, Chan MR et al (2007) Nephrogenic systemic fibrosis: risk factors and incidence estimation. Radiology 243:148–157CrossRefPubMedGoogle Scholar
  26. 26.
    Evans DGR, Salvador H, Chang VY et al (2017) Cancer and central nervous system tumor surveillance in pediatric neurofibromatosis 1. Clin Cancer Res 23:e46–e53CrossRefPubMedGoogle Scholar
  27. 27.
    Evans DGR, Salvador H, Chang VY et al (2017) Cancer and central nervous system tumor surveillance in pediatric neurofibromatosis 2 and related disorders. Clin Cancer Res 23:e54–e61CrossRefPubMedGoogle Scholar
  28. 28.
    Kamihara J, Bourdeaut F, Foulkes WD et al (2017) Retinoblastoma and neuroblastoma predisposition and surveillance. Clin Cancer Res 23:e98–e106CrossRefPubMedGoogle Scholar
  29. 29.
    Rednam SP, Erez A, Druker H et al (2017) Von Hippel-Lindau and hereditary pheochromocytoma/paraganglioma syndromes: clinical features, genetics, and surveillance recommendations in childhood. Clin Cancer Res 23:e68–e75CrossRefPubMedGoogle Scholar
  30. 30.
    Tabori U, Hansford JR, Achatz MI et al (2017) Clinical management and tumor surveillance recommendations of inherited mismatch repair deficiency in childhood. Clin Cancer Res 23:e32–e37CrossRefPubMedGoogle Scholar
  31. 31.
    Schultz KAP, Rednam SP, Kamihara J et al (2017) PTEN, DICER1, FH, and their associated tumor susceptibility syndromes: clinical features, genetics, and surveillance recommendations in childhood. Clin Cancer Res 23:e76–e82CrossRefPubMedGoogle Scholar
  32. 32.
    Walsh MF, Chang VY, Kohlmann WK et al (2017) Recommendations for childhood cancer screening and surveillance in DNA repair disorders. Clin Cancer Res 23:e23–e31CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Mehollin-Ray AR, Kozinetz CA, Schlesinger AE et al (2008) Radiographic abnormalities in Rothmund-Thomson syndrome and genotype-phenotype correlation with RECQL4 mutation status. AJR Am J Roentgenol 191:W62–W66CrossRefPubMedGoogle Scholar
  34. 34.
    Ballinger ML, Ferris NJ, Moodie K et al (2017) Surveillance in germline TP53 mutation carriers utilizing whole-body magnetic resonance imaging. JAMA Oncol 3:1735–1736CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Ballinger ML, Best A, Mai PL et al (2017) Baseline surveillance in Li-Fraumeni syndrome using whole-body magnetic resonance imaging: a meta-analysis. JAMA Oncol 3:1634–1639CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Garritano S, Gemignani F, Palmero EI et al (2010) Detailed haplotype analysis at the TP53 locus in p.R337H mutation carriers in the population of southern Brazil: evidence for a founder effect. Hum Mutat 31:143–150CrossRefPubMedGoogle Scholar
  37. 37.
    Ricketts CJ, Forman JR, Rattenberry E et al (2010) Tumor risks and genotype-phenotype-proteotype analysis in 358 patients with germline mutations in SDHB and SDHD. Hum Mutat 31:41–51CrossRefPubMedGoogle Scholar
  38. 38.
    Assadipour Y, Sadowski SM, Alimchandani M et al (2017) SDHB mutation status and tumor size but not tumor grade are important predictors of clinical outcome in pheochromocytoma and abdominal paraganglioma. Surgery 161:230–239CrossRefPubMedGoogle Scholar
  39. 39.
    Jasperson KW, Kohlmann W, Gammon A et al (2014) Role of rapid sequence whole-body MRI screening in SDH-associated hereditary paraganglioma families. Familial Cancer 13:257–265CrossRefPubMedGoogle Scholar
  40. 40.
    Ricketts CJ, Shuch B, Vocke CD et al (2012) Succinate dehydrogenase kidney cancer: an aggressive example of the Warburg effect in cancer. J Urol 188:2063–2071CrossRefPubMedGoogle Scholar
  41. 41.
    Evans DG, Howard E, Giblin C et al (2010) Birth incidence and prevalence of tumor-prone syndromes: estimates from a UK family genetic register service. Am J Med Genet A 152A:327–332CrossRefPubMedGoogle Scholar
  42. 42.
    Van Royen K, Brems H, Legius E et al (2016) Prevalence of neurofibromatosis type 1 in congenital pseudarthrosis of the tibia. Eur J Pediatr 175:1193–1198CrossRefPubMedGoogle Scholar
  43. 43.
    DeBella K, Szudek J, Friedman JM (2000) Use of the national institutes of health criteria for diagnosis of neurofibromatosis 1 in children. Pediatrics 105:608–614CrossRefPubMedGoogle Scholar
  44. 44.
    Ahlawat S, Fayad LM, Khan MS et al (2016) Current whole-body MRI applications in the neurofibromatoses: NF1, NF2, and schwannomatosis. Neurology 87:S31–S39CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Boyd KP, Korf BR, Theos A (2009) Neurofibromatosis type 1. J Am Acad Dermatol 61:1–14CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Asthagiri AR, Parry DM, Butman JA et al (2009) Neurofibromatosis type 2. Lancet 373:1974–1986CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Evans DG (2011) Neurofibromatosis 2. In: Adam MP, Ardinger HH, Pagon RA et al (eds) GeneReviews®. University of Washington, SeattleGoogle Scholar
  48. 48.
    Yamanaka R, Hayano A, Takashima Y (2017) Trilateral retinoblastoma: a systematic review of 211 cases. Neurosurg Rev.  https://doi.org/10.1007/s10143-017-0890-4
  49. 49.
    de Jong MC, Kors WA, de Graaf P et al (2014) Trilateral retinoblastoma: a systematic review and meta-analysis. Lancet Oncol 15:1157–1167CrossRefPubMedGoogle Scholar
  50. 50.
    Dimaras H, Heon E, Doyle J et al (2011) Multifaceted chemotherapy for trilateral retinoblastoma. Arch Ophthalmol 129:362–365CrossRefPubMedGoogle Scholar
  51. 51.
    Wimmer K, Kratz CP, Vasen HF et al (2014) Diagnostic criteria for constitutional mismatch repair deficiency syndrome: suggestions of the European consortium 'care for CMMRD' (C4CMMRD). J Med Genet 51:355–365CrossRefPubMedGoogle Scholar

Copyright information

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

Authors and Affiliations

  1. 1.Department of Diagnostic Imaging, The Hospital for Sick Children, Department of Medical ImagingUniversity of TorontoTorontoCanada

Personalised recommendations