Skip to main content
SpringerLink
Log in

Diagnosis and Management of Hereditary Thyroid Cancer

  • Chapter
  • First Online:
Rare Hereditary Cancers

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 205))

Abstract

Thyroid cancers are largely divided into medullary (MTC) and non-medullary (NMTC) cancers , depending on the cell type of origin. Familial non-medullary thyroid cancer (FNMTC) comprises about 5–15 % of NMTC and is a heterogeneous group of diseases, including both non-syndromic and syndromic forms. Non-syndromic FNMTC tends to manifest papillary thyroid carcinoma , usually multifocal and bilateral . Several high-penetrance genes for FNMTC have been identified, but they are often confined to a few or single families, and other susceptibility loci appear to play a small part, conferring only small increments in risk. Familial susceptibility is likely to be due to a combination of genetic and environmental influences. The current focus of research in FNMTC is to characterise the susceptibility genes and their role in carcinogenesis. FNMTC can also occur as a part of multitumour genetic syndromes such as familial adenomatous polyposis , Cowden’s disease , Werner’s syndrome and Carney complex . These tend to present at an early age and are multicentric and bilateral with distinct pathology. The clinical evaluation of these patients is similar to that for most patients with a thyroid nodule. Medullary thyroid cancer (MTC) arises from the parafollicular cells of the thyroid which release calcitonin. The familial form of MTC accounts for 20–25 % of cases and presents as a part of the multiple endocrine neoplasia type 2 (MEN 2) syndromes or as a pure familial MTC (FMTC). They are caused by germline point mutations in the RET oncogene on chromosome 10q11.2. There is a clear genotype–phenotype correlation, and the aggressiveness of FMTC depends on the specific genetic mutation, which should determine the timing of surgery.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Bennett KL, Mester J, Eng C (2010) Germline epigenetic regulation of KILLIN in Cowden and Cowden-like syndrome. JAMA 304(24):2724–2731

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bignell GR, Canzian F, Shayeghi M, Stark M, Shugart YY, Biggs P et al (1997) Familial nontoxic multinodular thyroid goiter locus maps to chromosome 14q but does not account for familial nonmedullary thyroid cancer. Am J Hum Genet 61(5):1123–1130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bonora E, Tallini G, Romeo G (2010) Genetic predisposition to familial nonmedullary thyroid cancer: an update of molecular findings and state-of-the-art studies. J Oncol 2010:1–7

    Article  Google Scholar 

  • Canzian F, Amati P, Harach HR, Kraimps JL, Lesueur F, Barbier J et al (1998) A gene predisposing to familial thyroid tumors with cell oxyphilia maps to chromosome 19p13.2. Am J Hum Genet 63(6):1743–1748

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cavaco BM, Batista LG, Sobrinho VL (2008) Mapping a new familial thyroid epithelial neoplasia susceptibility locus to chromosome 8p23. 1-p22 by high density single-nucleotide polymorphism genome-wide linkage analysis. J Clin Endocrinol Metab 93(11):4426–4430

    Google Scholar 

  • Chen AY, Jemal A, Ward EM (2009) Increasing incidence of differentiated thyroid cancer in the United States, 1988–2005. Cancer 115(16):3801–3807

    Article  PubMed  Google Scholar 

  • Daumerie C, Maiter D1, Gruson D (2013) Serum calcitonin estimation in medullary thyroid cancer: basal or stimulated levels? Thyroid Res 6(Suppl 1):S4

    Google Scholar 

  • Davies L, Welch HG (2006) Increasing incidence of thyroid cancer in the United States, 1973–2002. JAMA 295(18):2164–2167

    Article  CAS  PubMed  Google Scholar 

  • Elisei R, Alevizaki M, Conte-Devolx B, Frank-Raue K, Leite V, Williams GR (2012) European thyroid association guidelines for genetic testing and its clinical consequences in medullary thyroid cancer. Eur Thyroid J 1(4):216–231

    Article  PubMed  PubMed Central  Google Scholar 

  • Frich L, Glattre E, Akslen LA (2001) Familial occurrence of nonmedullary thyroid cancer: a population based study of 5673 first-degree relatives of thyroid cancer patients from Norway. Cancer Epidemiol Biomarkers Prev 10(2):113–117

    CAS  PubMed  Google Scholar 

  • Ganeshan D, Paulson E, Duran C, Cabanillas ME, Busaidy NL, Charnsangavej C (2013) Current update on medullary thyroid carcinoma. AJR 201(6):W867–W876

    Article  PubMed  Google Scholar 

  • Giordano TJ, Kuick R, Thomas DG, Misek DE, Vinco M, Sanders D et al (2005) Molecular classification of papillary thyroid carcinoma: distinct BRAF, RAS, RET/PTC mutation-specific gene expression profiles discovered by DNA microarray analysis. Oncogene 24(44):6646–6656

    Article  CAS  PubMed  Google Scholar 

  • Grieco A, Miranda C, Pierotti MA (2009) Rearrangements of NTRK 1 gene in papillary thyroid carcinoma. Mol Cell Endocrinol 321(1):44–49

    Article  Google Scholar 

  • Grogan RH, Mitmaker EJ, Clark OH (2010) The evolution of biomarkers in thyroid cancer—from mass screening to a personalized biosignature. Cancers V 2(2):885–912

    Article  CAS  Google Scholar 

  • Gu Y, Liu X, Yu Y, Shi J, Ai L, Sun H, Kanu JS, Wang C, Liu Y (2014) Association of ATM gene polymorphism with PTC Metastasis in female patients. Int J Endocr 2014:1–8

    Google Scholar 

  • Harach HR (2001) Familial nonmedullary thyroid neoplasia. Endocr Pathol 12(2):97–112

    Article  Google Scholar 

  • Hemminki K, Dong C (2000) Familial relationships in thyroid cancer by histo-pathological type. Int J Cancer 85(2):201–205

    Article  CAS  PubMed  Google Scholar 

  • Hodgson SV, Foulkes WD, Eng C, Maher ER (2014) A practical guide to human genetics, 4th edn. London, pp 31–46

    Google Scholar 

  • Ishikawa Y, Sugano H, Matsumoto T, Furuichi Y, Miller RW, Goto M (1999) Unusual features of thyroid carcinomas in Japanese patients with Werner syndrome and possible genotype-phenotype relations to cell type and race. Cancer 85(6):1345–1352

    Article  CAS  PubMed  Google Scholar 

  • Jossart GH, Epstein HD, Shaver JK, Weier HU, Greulich KM, Tezelman S et al (1996) Immunocytochemical detection of p53 in human thyroid carcinomas is associated with mutation and immortalization of cell lines. J Clin Endocrinol Metab 81(10):3498–3504

    CAS  PubMed  Google Scholar 

  • Krampitz GW, Norton JA (2014) Gene mutations (genotype and phenotype) of multiple endocrine neoplasia Type 2 and familial medullary thyroid carcinoma. Cancer 120(13):1920–1931

    Article  CAS  PubMed  Google Scholar 

  • Krol TG, Sarraf P, Pecciarini L, Chen CJ, Mueller E, Spiegelman BM et al (2000) PAX8-PPARgamma fusion oncogene in human thyroid carcinoma. Science 289(5483):1357–1360

    Article  Google Scholar 

  • Kula D, Kalemba M, Jurecka-Lubieniecka B, Puch Z, Kowalska M, Tyszkiewicz T, Kowal M, Handkiewicz-Junak D (2010) Genetic predisposition to papillary thyroid cancer. Endokrynol Pol 61(5):486–489

    CAS  PubMed  Google Scholar 

  • Malchoff CD, Sarfarazi M, Tendler B, Forouhar F, Whalen G, Joshi V et al (2000) Papillary thyroid carcinoma associated with papillary renal neoplasia: genetic linkage analysis of a distinct heritable tumor syndrome. J Clin Endocrinol Metab 85(5):1758–1764

    CAS  PubMed  Google Scholar 

  • Mazeh H, Sippel RS (2013) Familial nonmedullary thyroid carcinoma. Thyroid. 23(9):1049–1056

    Article  PubMed  Google Scholar 

  • McKay JD, Lesueur F, Jonard L, Pastore A, Williamson J, Hoffman L et al (2001) Localization of a susceptibility gene for familial nonmedullary thyroid carcinoma to chromosome 2q21. Am J Hum Gene 69(2):440–446

    Article  CAS  Google Scholar 

  • Mears L, Diaz-Cano SJ (2003) Difference between familial and sporadic medullary thyroid carcinomas. Am J Surg Pathol 27(2):266–267

    Article  PubMed  Google Scholar 

  • Metzgera R, Milasb M (2014) Inherited cancer syndromes and the thyroid: an update. Curr Opin Oncol 26(1):51–61

    Article  Google Scholar 

  • Molatore S, Marinoni I, Lee M, Pulz E, Ambrosio MR, Degli Uberti EC, Zatelli MC, Pellegata NS (2010) A novel germline CDKN1B mutation causing multiple endocrine tumors: clinical, genetic and functional characterization. Hum Mutat 31(11):E1825–E1835

    Google Scholar 

  • Musholt TJ, Musholt PB, Petrich T et al (2000) Familial papillary thyroid carcinoma: genetics, criteria for diagnosis, clinical features, and surgical treatment. World J Surg 24(11):1409–1417

    Article  CAS  PubMed  Google Scholar 

  • Nagy R, Ringel MD (2015) Genetic predisposition for nonmedullary thyroid cancer. Horm Cancer 6(1):13–20

    Article  CAS  PubMed  Google Scholar 

  • Navas-Carrillo D, Ríos A, Rodríguez JM, Parrilla P, Orenes-Piñero E (2014) Familial nonmedullary thyroid cancer: screening, clinical, molecular and genetic findings. Biochim Biophys Acta 1846(2):468–76

    Google Scholar 

  • Ngeow J, Mester J, Rybicki LA, Ni Y, Milas M, Eng C (2011) Incidence and clinical characteristics of thyroid cancer in prospective series of individuals with Cowden and Cowden-like syndrome characterized by germline PTEN, SDH, or KLLN alterations. J Clin Endocrinol Metab 96(12):E2063–E2071

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nosé V (2011) Familial thyroid cancer: a review. Mod Pathol 24:S19–S33

    Article  PubMed  Google Scholar 

  • Pal T, Vogl FD, Chappuis PO et al (2001) Increased risk for nonmedullary thyroid cancer in the first degree relatives of prevalent cases of nonmedullary thyroid cancer: a hospital-based study. J Clin Endocrinol Metab 86(11):5307–5312

    Article  CAS  PubMed  Google Scholar 

  • Rivkees SA, Mazzaferri EL, Verburg FA, Reiners C, Luster M, Breuer CK, Dinauer CA, Udelsman R (2011) The treatment of differentiated thyroid cancer in children: emphasis on surgical approach and radioactive iodine therapy. Endocr Rev 32(6):798–826

    Google Scholar 

  • Sakorafas GH, Friess H, Peros G (2008) The genetic basis of hereditary medullary thyroid cancer: clinical implications for the surgeon, with a particular emphasis on the role of prophylactic thyroidectomy. Endocr Relat Cancer 15(4):871–884

    Article  CAS  PubMed  Google Scholar 

  • Slade I, Bacchelli C, Davies H, Murray A, Rahman N et al (2011) DICER1 syndrome: clarifying the diagnosis, clinical features and management implications of a pleiotropic tumour predisposition syndrome. J Med Genet 48(4):273–278

    Article  CAS  PubMed  Google Scholar 

  • Stratakis CA, Courcoutisakis NA, Abati A, Filie A, Doppman JL, Aidan Carney JA, Shawker T (1997) Thyroid gland abnormalities in patients with the syndrome of spotty skin pigmentation, myxomas, endocrine overactivity, and schwannomas (carney complex). J Clinical Endocr Metabol 82(7):2037–2043

    Google Scholar 

  • Sturgeon C, Clark OH (2005) Familial nonmedullary thyroid cancer. Thyroid 15(6):588–593

    Article  PubMed  Google Scholar 

  • Suh I, Filetti S, Vriens MR, Guerrero MA, Tumino S, Wong M et al (2009) Distinct loci on chromosome 1q21 and 6q22 predispose to familial nonmedullary thyroid cancer: a SNP array-based linkage analysis of 38 families. Surgery 146(6):1073–1080

    Article  PubMed  Google Scholar 

  • Uchino S, Noguchi S, Kawamoto H et al (2002) Familial nonmedullary thyroid carcinoma characterized by multifocality and a high recurrence rate in a large study population. World J Surg 26(8):897–902

    Article  PubMed  Google Scholar 

  • Vasko V, Hu S, Wu G, Xing JC, Larin A, Savchenko V et al (2005) High prevalence and possible de novo formation of BRAF mutation in metastasized papillary thyroid cancer in lymph nodes. J Clin Endocrinol Metab 90(9):5265–5269

    Article  CAS  PubMed  Google Scholar 

  • von Dobschuetz E, Leijon H, Schalin-Jantti C, Schiavi F, Brauckhoff M, Peczkowska M et al (2015) A registry-based study of thyroid paraganglioma: histologic and genetic characteristics. Endocr Relat Cancer 22(2):191–204

    Article  Google Scholar 

  • Wu LS, Roman SA, Sosa JA (2011) Medullary thyroid cancer: an update of new guidelines and recent developments. Curr Opin Oncol 23(1):22–27

    Article  PubMed  Google Scholar 

  • Xing M, Westra WH, Tufano RP, Cohen Y, Rosenbaum E, Rhoden KJ et al (2005) BRAF mutation predicts a poorer clinical prognosis for papillary thyroid cancer. J Clin Endocrinol Metab 90(12):6373–6379

    Article  CAS  PubMed  Google Scholar 

  • Xu B, Yoshimoto K, Miyauchi A et al (2003) Cribriform-morular variant of papillary thyroid carcinoma: a pathological and molecular genetic study with evidence of frequent somatic mutations in exon 3 of the beta-catenin gene. J Pathol 199(1):58–67

    Article  PubMed  Google Scholar 

  • Xu L, Li G, Wei Q, El-Naggar AK, Sturgis EM (2012) Family history of cancer and risk of sporadic differentiated thyroid carcinoma. Cancer 118(5):1228–1235

    Google Scholar 

  • Yang GC, Yao JL, Feiner HD, Roses DF, Kumar A, Mulder JE (1999) Lipid rich follicular carcinoma of the thyroid in a patient with McCune—Albright syndrome. Mod Pathol 12(10):969–973

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Endocrinology and Diabetes, Thomas Addison Unit, St George’s Healthcare NHS Trust, Blackshaw Road, Tooting, London, UK

    Gul Bano

  2. St. George’s, University of London, London, UK

    Shirley Hodgson

Authors
  1. Gul Bano
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shirley Hodgson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gul Bano .

Editor information

Editors and Affiliations

  1. London Bridge Hospital, London, United Kingdom

    Gabriella Pichert

  2. University College London, Guy’s & St Thomas’ NHS Foundation Trust, London, United Kingdom

    Chris Jacobs

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Bano, G., Hodgson, S. (2016). Diagnosis and Management of Hereditary Thyroid Cancer. In: Pichert, G., Jacobs, C. (eds) Rare Hereditary Cancers. Recent Results in Cancer Research, vol 205. Springer, Cham. https://doi.org/10.1007/978-3-319-29998-3_3

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-29998-3_3

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-29996-9

  • Online ISBN: 978-3-319-29998-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation