Abstract
Differentiated thyroid cancer in childhood is rare. Apart from family history, radiation exposure is a major risk factor. Although its clinical course is quite aggressive with higher rates of lymph node and pulmonary metastases as compared to adults, the final outcome tends to be favorable with mortality rates less than 2%. we herein review the clinical picture, genetic background response to treatment and recurrence rates of differentiated thyroid cancer in children and young adolescents are thoroughly reviewed and the main differences with adult differentiated thyroid cancer are highlighted.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Hogan AR, Zhuge Y, Perez EA, Koniaris LG, Lew JI, Sola JE, 2009 Pediatric thyroid carcinoma: incidence and outcomes in 1753 patients. J Surg Res 156: 167–172.
Vergamini LB, Frazier AL, Abrantes FL, Ribeiro KB, Rodriguez-Galindo C, 2014 Increase in the incidence of differentiated thyroid carcinoma in children, adolescents, and young adults: a population-based study. J Pediatr 164: 1481–1485.
Wu XC, Chen VW, Steele B, et al, 2003 Cancer incidence in adolescents and young adults in the United States, 1992–1997. J Adolesc Health 32: 405–415.
Ward E, DeSantis C, Robbins A, Kohler B, Jemal A, 2014 Childhood and adolescent cancer statistics, 2014. CA Cancer J Clin 64: 83–103.
Demidchik YE, Saenko VA, Yamashita S, 2007 Childhood thyroid cancer in Belarus, Russia, and Ukraine after Chernobyl and at present. Arq Bras Endocrinol Metabol 51: 748–762.
Harness JK, Thompson NW, McLeod MK, Pasieka JL, Fukuuchi A, 1992 Differentiated thyroid carcinoma in children and adolescents. World J Surg 16: 547–553.
Monaco SE, Pantanowitz L, Khalbuss WE, et al, 2012 Cytomorphological and molecular genetic findings in pediatric thyroid fine-needle aspiration. Cancer Cytopathol 120: 342–350.
Halac I, Zimmerman D, 2005 Thyroid nodules and cancers in children. Endocrinol Metab Clin North Am 34: 725–744.
Chan CM, Young J, Prager J, Travers S, 2017 Pediatric thyroid cancer. Adv Pediatr 64: 171–190.
Zhou H, Baloch ZW, Nayar R, et al, 2017 Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP): Implications for the risk of malignancy (ROM) in the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). Cancer.
Khan A, Smellie J, Nutting C, Harrington K, Newbold K, 2010 Familial nonmedullary thyroid cancer: a review of the genetics. Thyroid 20: 795–801.
Tucker MA, Jones PH, Boice JD, Jr., et al, 1991 Therapeutic radiation at a young age is linked to secondary thyroid cancer. The Late Effects Study Group. Cancer Res 51: 2885–2888.
Sinnott B, Ron E, Schneider AB, 2010 Exposing the thyroid to radiation: a review of its current extent, risks, and implications. Endocr Rev 31: 756–773.
Cardis E, Hatch M, 2011 The Chernobyl accident—an epidemiological perspective. Clin Oncol (R Coll Radiol) 23: 251–260.
Schonfeld SJ, Lee C, Berrington de Gonzalez A, 2011 Medical exposure to radiation and thyroid cancer. Clin Oncol (R Coll Radiol) 23: 244–250.
Stsjazhko VA, Tsyb AF, Tronko ND, Souchkevitch G, Baverstock KF, 1995 Childhood thyroid cancer since accident at Chernobyl. BMJ 310: 801.
Williams D, 2008 Twenty years’ experience with post-Chernobyl thyroid cancer. Best Pract Res Clin Endocrinol Metab 22: 1061–1073.
Tuttle RM, Vaisman F, Tronko MD, 2011 Clinical presentation and clinical outcomes in Chernobyl-related paediatric thyroid cancers: what do we know now? What can we expect in the future? Clin Oncol (R Coll Radiol) 23: 268–275.
Iwaku K, Noh JY, Sasaki E, et al, 2014 Changes in pediatric thyroid sonograms in or nearby the Kanto region before and after the accident at the Fukushima Daiichi nuclear power plant. Endocr J 61: 875–881.
Bongarzone I, Fugazzola L, Vigneri P, et al, 1996 Age-related activation of the tyrosine kinase receptor protooncogenes RET and NTRK1 in papillary thyroid carcinoma. J Clin Endocrinol Metab 81: 2006–2009.
Ricarte-Filho JC, Li S, Garcia-Rendueles ME, et al, 2013 Identification of kinase fusion oncogenes in post-Chernobyl radiation-induced thyroid cancers. J Clin Invest 123: 4935–4944.
Fusco A, Santoro M, 2007 20 years of RET/PTC in thyroid cancer: clinico-pathological correlations. Arq Bras Endocrinol Metabol 51: 731–735.
Cordioli MI, Moraes L, Cury AN, Cerutti JM, 2015 Are we really at the dawn of understanding sporadic pediatric thyroid carcinoma? Endocr Relat Cancer 22: R311–324.
Rabes HM, Demidchik EP, Sidorow JD, et al, 2000 Pattern of radiation-induced RET and NTRK1 rearrangements in 191 post-chernobyl papillary thyroid carcinomas: biological, phenotypic, and clinical implications. Clin Cancer Res 6: 1093–1103.
Elisei R, Romei C, Soldatenko PP, et al, 2000 New breakpoints in both the H4 and RET genes create a variant of PTC-1 in a post-Chernobyl papillary thyroid carcinoma. Clin Endocrinol (Oxf) 53: 131–136.
Damiola F, Byrnes G, Moissonnier M, et al, 2014 Contribution of ATM and FOXE1 (TTF2) to risk of papillary thyroid carcinoma in Belarusian children exposed to radiation. Int J Cancer 134: 1659–1668.
Fenton CL, Lukes Y, Nicholson D, Dinauer CA, Francis GL, Tuttle RM, 2000 The ret/PTC mutations are common in sporadic papillary thyroid carcinoma of children and young adults. J Clin Endocrinol Metab 85: 1170–1175.
Patel A, Jhiang S, Dogra S, et al, 2002 Differentiated thyroid carcinoma that express sodium-iodide symporter have a lower risk of recurrence for children and adolescents. Pediatr Res 52: 737–744.
Faggiano A, Coulot J, Bellon N, et al, 2004 Age-dependent variation of follicular size and expression of iodine transporters in human thyroid tissue. J Nucl Med 45: 232–237.
Espadinha C, Santos JR, Sobrinho LG, Bugalho MJ, 2009 Expression of iodine metabolism genes in human thyroid tissues: evidence for age and BRAFV600E mutation dependency. Clin Endocrinol (Oxf) 70: 629–635.
Welch Dinauer CA, Tuttle RM, Robie DK, et al, 1998 Clinical features associated with metastasis and recurrence of differentiated thyroid cancer in children, adolescents and young adults. Clin Endocrinol (Oxf) 49: 619–628.
Grigsby PW, Gal-or A, Michalski JM, Doherty GM, 2002 Childhood and adolescent thyroid carcinoma. Cancer 95: 724–729.
Josefson J, Zimmerman D, 2008 Thyroid nodules and cancers in children. Pediatr Endocrinol Rev 6: 14–23.
Gupta A, Ly S, Castroneves LA, et al, 2013 A standardized assessment of thyroid nodules in children confirms higher cancer prevalence than in adults. J Clin Endocrinol Metab 98: 3238–3245.
Niedziela M, 2006 Pathogenesis, diagnosis and management of thyroid nodules in children. Endocr Relat Cancer 13: 427–453.
Gharib H, Papini E, Valcavi R, et al, 2006 American Association of Clinical Endocrinologists and Associazione Medici Endocrinologi medical guidelines for clinical practice for the diagnosis and management of thyroid nodules. Endocr Pract 12: 63–102.
Niedziela M, Breborowicz D, Trejster E, Korman E, 2002 Hot nodules in children and adolescents in western Poland from 1996 to 2000: clinical analysis of 31 patients. J Pediatr Endocrinol Metab 15: 823–830.
Dremier S, Coppee F, Delange F, Vassart G, Dumont JE, Van Sande J, 1996 Clinical review 84: Thyroid autonomy: mechanism and clinical effects. J Clin Endocrinol Metab 81: 4187–4193.
Papendieck P, Gruneiro-Papendieck L, Venara M, et al, 2015 Differentiated thyroid cancer in children: prevalence and predictors in a large cohort with thyroid nodules followed prospectively. J Pediatr 167: 199–201.
Francis GL, Waguespack SG, Bauer AJ, et al, 2015 Management guidelines for children with thyroid nodules and differentiated thyroid cancer. Thyroid 25: 716–759.
Partyka KL, Huang EC, Cramer HM, Chen S, Wu HH, 2016 Histologic and clinical follow-up of thyroid fine-needle aspirates in pediatric patients. Cancer Cytopathol 124: 467–471.
Haugen BR, Alexander EK, Bible KC, et al, 2016 2015 American Thyroid Association Management Guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: The American Thyroid Association Guidelines Task Force on thyroid nodules and differentiated thyroid cancer. Thyroid 26: 1–133.
Dzodic R, Buta M, Markovic I, et al, 2014 Surgical management of well-differentiated thyroid carcinoma in children and adolescents: 33 years of experience of a single institution in Serbia. Endocr J 61: 1079–1086.
Hay ID, Gonzalez-Losada T, Reinalda MS, Honetschlager JA, Richards ML, Thompson GB, 2010 Long-term outcome in 215 children and adolescents with papillary thyroid cancer treated during 1940 through 2008. World J Surg 34: 1192–1202.
Zaydfudim V, Feurer ID, Griffin MR, Phay JE, 2008 The impact of lymph node involvement on survival in patients with papillary and follicular thyroid carcinoma. Surgery 144: 1070–1078.
Ahn BH, Kim JR, Jeong HC, Lee JS, Chang ES, Kim YH, 2015 Predictive factors of central lymph node metastasis in papillary thyroid carcinoma. Ann Surg Treat Res 88: 63–68.
Pawelczak M, David R, Franklin B, Kessler M, Lam L, Shah B, 2010 Outcomes of children and adolescents with well-differentiated thyroid carcinoma and pulmonary metastases following (1)(3)(1)I treatment: a systematic review. Thyroid 20: 1095–1101.
Quaglia L, Cornaggia C, 2000 Experimental evidence of excited multicharged atomic fragments coming from laser-induced coulomb explosion of molecules. Phys Rev Lett 84: 4565–4568.
Handkiewicz-Junak D, Wloch J, Roskosz J, et al, 2007 Total thyroidectomy and adjuvant radioiodine treatment independently decrease locoregional recurrence risk in childhood and adolescent differentiated thyroid cancer. J Nucl Med 48: 879–888.
Newman KD, Black T, Heller G, et al, 1998 Differentiated thyroid cancer: determinants of disease progression in patients <21 years of age at diagnosis: a report from the Surgical Discipline Committee of the Children’s Cancer Group. Ann Surg 227: 533–541.
Schlumberger M, De Vathaire F, Travagli JP, et al, 1987 Differentiated thyroid carcinoma in childhood: long term follow-up of 72 patients. J Clin Endocrinol Metab 65: 1088–1094.
Hay ID, 1987 Brain metastases from papillary thyroid carcinoma. Arch Intern Med 147: 607–611.
Mao XC, Yu WQ, Shang JB, Wang KJ, 2017 Clinical characteristics and treatment of thyroid cancer in children and adolescents: a retrospective analysis of 83 patients. J Zhejiang Univ Sci B 18: 430–436.
Vassilopoulou-Sellin R, Klein MJ, Smith TH, et al, 1993 Pulmonary metastases in children and young adults with differentiated thyroid cancer. Cancer 71: 1348–1352.
O’Gorman CS, Hamilton J, Rachmiel M, Gupta A, Ngan BY, Daneman D, 2010 Thyroid cancer in childhood: a retrospective review of childhood course. Thyroid 20: 375–380.
Wada N, Sugino K, Mimura T, et al, 2009 Treatment strategy of papillary thyroid carcinoma in children and adolescents: clinical significance of the initial nodal manifestation. Ann Surg Oncol 16: 3442–3449.
Giuffrida D, Scollo C, Pellegriti G, et al, 2002 Differentiated thyroid cancer in children and adolescents. J Endocrinol Invest 25: 18–24.
Lamartina L, Durante C, Filetti S, Cooper DS, 2015 Low-risk differentiated thyroid cancer and radioiodine remnant ablation: a systematic review of the literature. J Clin Endocrinol Metab 100: 1748–1761.
Verburg FA, Biko J, Diessl S, et al, 2011 I-131 activities as high as safely administrable (AHASA) for the treatment of children and adolescents with advanced differentiated thyroid cancer. J Clin Endocrinol Metab 96: E1268–1271.
Kuijt WJ, Huang SA, 2005 Children with differentiated thyroid cancer achieve adequate hyperthyrotropinemia within 14 days of levothyroxine withdrawal. J Clin Endocrinol Metab 90: 6123–6125.
Beckers C, 1997 Regulations and policies on radioiodine 131I therapy in Europe. Thyroid 7: 221–224.
Marti JL, Jain KS, Morris LG, 2015 Increased risk of second primary malignancy in pediatric and young adult patients treated with radioactive iodine for differentiated thyroid cancer. Thyroid 25: 681–687.
Gilabert M, Prebet T, 2012 Acute leukemia arising after radioiodine treatment for thyroid cancer. Haematologica 97: e28–29; author reply e30.
Rachmiel M, Charron M, Gupta A, et al, 2006 Evidence-based review of treatment and follow up of pediatric patients with differentiated thyroid carcinoma. J Pediatr Endocrinol Metab 19: 1377–1393.
Vini L, Hyer S, Al-Saadi A, Pratt B, Harmer C, 2002 Prognosis for fertility and ovarian function after treatment with radioiodine for thyroid cancer. Postgrad Med J 78: 92–93.
Burmeister LA, Goumaz MO, Mariash CN, Oppenheimer JH, 1992 Levothyroxine dose requirements for thyrotropin suppression in the treatment of differentiated thyroid cancer. J Clin Endocrinol Metab 75: 344–350.
Cooper DS, Specker B, Ho M, et al, 1998 Thyrotropin suppression and disease progression in patients with differentiated thyroid cancer: results from the National Thyroid Cancer Treatment Cooperative Registry. Thyroid 8: 737–744.
Gorlin JB, Sallan SE, 1990 Thyroid cancer in childhood. Endocrinol Metab Clin North Am 19: 649–662.
Popovtzer A, Shpitzer T, Bahar G, Feinmesser R, Segal K, 2006 Thyroid cancer in children: management and outcome experience of a referral center. Otolaryngol Head Neck Surg 135: 581–584.
Lazar L, Lebenthal Y, Segal K, et al, 2016 Pediatric thyroid cancer: postoperative classifications and response to initial therapy as prognostic factors. J Clin Endocrinol Metab 101: 1970–1979.
Zimmerman D, Hay ID, Gough IR, et al, 1988 Papillary thyroid carcinoma in children and adults: long-term follow-up of 1039 patients conservatively treated at one institution during three decades. Surgery 104: 1157–1166.
Balachandar S, La Quaglia M, Tuttle RM, Heller G, Ghossein RA, Sklar CA, 2016 Pediatric differentiated thyroid carcinoma of follicular cell origin: prognostic significance of histologic subtypes. Thyroid 26: 219–226.
Reiners C, Biko J, Haenscheid H, et al, 2013 Twenty-five years after chernobyl: outcome of radioiodine treatment in children and adolescents with very high-risk radiation-induced differentiated thyroid carcinoma. J Clin Endocrinol Metab 98: 3039–3048.
Spencer C, 2013 Commentary on: Implications of thyroglobulin antibody positivity in patients with differentiated thyroid cancer: a clinical position statement. Thyroid 23: 1190–1192.
Verburg FA, Luster M, Cupini C, et al, 2013 Implications of thyroglobulin antibody positivity in patients with differentiated thyroid cancer: a clinical position statement. Thyroid 23: 1211–1225.
Spencer CA, 2011 Clinical review: Clinical utility of thyroglobulin antibody (TgAb) measurements for patients with differentiated thyroid cancers (DTC). J Clin Endocrinol Metab 96: 3615–3627.
Mazzaferri EL, Robbins RJ, Spencer CA, et al, 2003 A consensus report of the role of serum thyroglobulin as a monitoring method for low-risk patients with papillary thyroid carcinoma. J Clin Endocrinol Metab 88: 1433–1441.
Biko J, Reiners C, Kreissl MC, Verburg FA, Demidchik Y, Drozd V, 2011 Favourable course of disease after incomplete remission on (131)I therapy in children with pulmonary metastases of papillary thyroid carcinoma: 10 years follow-up. Eur J Nucl Med Mol Imaging 38: 651–655.
Schoelwer MJ, Zimmerman D, Shore RM, Josefson JL, 2015 The Use of 123I in Diagnostic Radioactive Iodine Scans in Children with Differentiated Thyroid Carcinoma. Thyroid 25: 935–941.
Clayman GL, Agarwal G, Edeiken BS, Waguespack SG, Roberts DB, Sherman SI, 2011 Long-term outcome of comprehensive central compartment dissection in patients with recurrent/persistent papillary thyroid carcinoma. Thyroid 21: 1309–1316.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Karapanou, O., Tzanela, M., Vlassopoulou, B. et al. Differentiated thyroid cancer in childhood: a literature update. Hormones 16, 381–387 (2017). https://doi.org/10.14310/horm.2002.1758
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.14310/horm.2002.1758