Advertisement

Benign Nodular Thyroid Disease

  • Jennifer L. Hunt
Chapter
Part of the Molecular Pathology Library book series (MPLB, volume 3)

Abstract

Benign nodular disease of the thyroid gland is exceedingly common in most of the world. In fact, some estimates have suggested that up to 70% of the population in the United States will have thyroid nodules detectable by ultrasound. The diagnostic categories for benign nodular thyroids include both multinodular disease and dominant single nodules, which can be of neoplastic or nonneoplastic origin. The benign nodular thyroid diseases are discussed in this chapter, along with the relevant molecular pathogenesis.

Keywords

Thyroid Gland Thyroid Nodule Congenital Hypothyroidism Follicular Carcinoma Multinodular Goiter 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Apel RL, Ezzat S, Bapat BV, Pan N, LiVolsi VA, Asa SL. Clonality of thyroid nodules in sporadic goiter. Diagn Mol Pathol. 1995;4:113–121.CrossRefPubMedGoogle Scholar
  2. 2.
    Baloch ZW, LiVolsi VA. Cytologic and architectural mimics of papillary thyroid carcinoma. Diagnostic challenges in fine-needle aspiration and surgical pathology specimens. Am J Clin Pathol. 2006;125 Suppl:S135-S144.PubMedGoogle Scholar
  3. 3.
    Bignell GR, Canzian F, Shayeghi M, et al. Familial nontoxic multinodular thyroid goiter locus maps to chromosome 14q but does not account for familial nonmedullary thyroid cancer. Am J Hum Genet. 1997;61:1123–1130.CrossRefPubMedGoogle Scholar
  4. 4.
    Brix TH, Hegedus L. Genetic and environmental factors in the aetiology of simple goitre. Ann Med. 2000;32:153–156.CrossRefPubMedGoogle Scholar
  5. 5.
    Castro P, Eknaes M, Teixeira MR, et al. Adenomas and follicular carcinomas of the thyroid display two major patterns of chromosomal changes. J Pathol. 2005;206:305–311.CrossRefPubMedGoogle Scholar
  6. 6.
    Denning KM, Smyth PC, Cahill SF, et al. A molecular expression signature distinguishing follicular lesions in thyroid carcinoma using preamplification RT-PCR in archival samples. Mod Pathol. 2007;20:1095–1102.CrossRefPubMedGoogle Scholar
  7. 7.
    Derrien C, Sonnet E, Gicquel I, et al. Non-hyperfunctioning nodules from multinodular goiters: a minor role in pathogenesis for somatic activating mutations in the TSH-receptor and Gsalpha subunit genes. J Endocrinol Invest. 2001;24:321–325.PubMedGoogle Scholar
  8. 8.
    Derwahl M. Molecular aspects of the pathogenesis of nodular goiters, thyroid nodules and adenomas. Exp Clin Endocrinol Diabetes. 1996;104(Suppl 4):32–35.CrossRefPubMedGoogle Scholar
  9. 9.
    Djemli A, Van Vliet G, Delvin EE. Congenital hypothyroidism: from paracelsus to molecular diagnosis. Clin Biochem. 2006;39:511–518.CrossRefPubMedGoogle Scholar
  10. 10.
    Drut R. Aspiration cytology of papillary hyperplastic thyroid nodule. Arch Pathol Lab Med. 2002;126:1156. author reply 1156–1157.PubMedGoogle Scholar
  11. 11.
    Ezzat S, Zheng L, Kolenda J, Safarian A, Freeman JL, Asa SL. Prevalence of activating ras mutations in morphologically characterized thyroid nodules. Thyroid. 1996;6:409–416.CrossRefPubMedGoogle Scholar
  12. 12.
    Gabriel EM, Bergert ER, Grant CS, van Heerden JA, Thompson GB, Morris JC. Germline polymorphism of codon 727 of human thyroid-stimulating hormone receptor is associated with toxic multinodular goiter. J Clin Endocrinol Metab. 1999;84:3328–3335.CrossRefPubMedGoogle Scholar
  13. 13.
    Gozu H, Avsar M, Bircan R, et al. Mutations in the thyrotropin receptor signal transduction pathway in the hyperfunctioning thyroid nodules from multinodular goiters: a study in the Turkish population. Endocr J. 2005;52:577–585.CrossRefPubMedGoogle Scholar
  14. 14.
    Gruters A, Krude H, Biebermann H. Molecular genetic defects in congenital hypothyroidism. Eur J Endocrinol. 2004;151(Suppl 3):U39-U44.CrossRefPubMedGoogle Scholar
  15. 15.
    Holzapfel HP, Fuhrer D, Wonerow P, Weinland G, Scherbaum WA, Paschke R. Identification of constitutively activating somatic thyrotropin receptor mutations in a subset of toxic multinodular goiters. J Clin Endocrinol Metab. 1997;82:4229–4233.CrossRefPubMedGoogle Scholar
  16. 16.
    Hunt JL, Livolsi VA, Baloch ZW, et al. A novel microdissection and genotyping of follicular-derived thyroid tumors to predict aggressiveness. Hum Pathol. 2003;34:375–380.CrossRefPubMedGoogle Scholar
  17. 17.
    Hunt JL, Yim JH, Carty SE. Fractional allelic loss of tumor suppressor genes identifies malignancy and predicts clinical outcome in follicular thyroid tumors. Thyroid. 2006;16:643–649.CrossRefPubMedGoogle Scholar
  18. 18.
    Iliszko M, Kuzniacka A, Lachinski A, Babinska M, Kobierska-Gulida G, Limon J. Karyotypic characterization of 64 nonmalignant thyroid goiters. Cancer Genet Cytogenet. 2005;161:178–180.CrossRefPubMedGoogle Scholar
  19. 19.
    Karga H, Lee JK, Vickery AL Jr, Thor A, Gaz RD, Jameson JL. Ras oncogene mutations in benign and malignant thyroid neoplasms. J Clin Endocrinol Metab. 1991;73:832–836.CrossRefPubMedGoogle Scholar
  20. 20.
    Khurana KK, Baloch ZW, LiVolsi VA. Aspiration cytology of pediatric solitary papillary hyperplastic thyroid nodule. Arch Pathol Lab Med. 2001;125:1575–1578.PubMedGoogle Scholar
  21. 21.
    Kratzsch J, Pulzer F. Thyroid gland development and defects. Best Pract Res Clin Endocrinol Metab. 2008;22:57–75.CrossRefPubMedGoogle Scholar
  22. 22.
    Krohn K, Paschke R. Somatic mutations in thyroid nodular disease. Mol Genet Metab. 2002;75:202–208.CrossRefPubMedGoogle Scholar
  23. 23.
    Lemoine NR, Mayall ES, Wyllie FS, et al. High frequency of ras oncogene activation in all stages of human thyroid tumorigenesis. Oncogene. 1989;4:159–164.PubMedGoogle Scholar
  24. 24.
    Lofrano-Porto A, Barra GB, Nascimento PP, et al. Pendred syndrome in a large consanguineous Brazilian family caused by a homozygous mutation in the SLC26A4 gene. Arq Bras Endocrinol Metabol. 2008;52:1296–1303.PubMedGoogle Scholar
  25. 25.
    Mai KT, Landry DC, Thomas J, et al. Follicular adenoma with papillary architecture: a lesion mimicking papillary thyroid carcinoma. Histopathology. 2001;39:25–32.CrossRefPubMedGoogle Scholar
  26. 26.
    Mazzaferri EL. Solitary thyroid nodule. 1. Clinical characteristics. Postgrad Med. 1981;70:98–103.PubMedGoogle Scholar
  27. 27.
    Namba H, Gutman RA, Matsuo K, Alvarez A, Fagin JA. H-ras protooncogene mutations in human thyroid neoplasms. J Clin Endocrinol Metab. 1990;71:223–229.CrossRefPubMedGoogle Scholar
  28. 28.
    Namba H, Matsuo K, Fagin JA. Clonal composition of benign and malignant human thyroid tumors. J Clin Invest. 1990;86:120–125.CrossRefPubMedGoogle Scholar
  29. 29.
    Namba H, Rubin SA, Fagin JA. Point mutations of ras oncogenes are an early event in thyroid tumorigenesis. Mol Endocrinol. 1990;4:1474–1479.CrossRefPubMedGoogle Scholar
  30. 30.
    Neumann S, Willgerodt H, Ackermann F, et al. Linkage of familial euthyroid goiter to the multinodular goiter-1 locus and exclusion of the candidate genes thyroglobulin, thyroperoxidase, and Na+/I- symporter. J Clin Endocrinol Metab. 1999;84:3750–3756.CrossRefPubMedGoogle Scholar
  31. 31.
    Olson SE, Starling J, Chen H. Symptomatic benign multinodular goiter: unilateral or bilateral thyroidectomy? Surgery. 2007;142:458-461. discussion 461–462.CrossRefPubMedGoogle Scholar
  32. 32.
    Palos-Paz F, Perez-Guerra O, Cameselle-Teijeiro J, et al. Prevalence of mutations in TSHR, GNAS, PRKAR1A and RAS genes in a large series of toxic thyroid adenomas from Galicia, an iodine-deficient area in NW Spain. Eur J Endocrinol. 2008;159:623–631.CrossRefPubMedGoogle Scholar
  33. 33.
    Park SM, Chatterjee VK. Genetics of congenital hypothyroidism. J Med Genet. 2005;42:379–389.CrossRefPubMedGoogle Scholar
  34. 34.
    Paschke R. Constitutively activating TSH receptor mutations as the cause of toxic thyroid adenoma, multinodular toxic goiter and autosomal dominant non autoimmune hyperthyroidism. Exp Clin Endocrinol Diabetes. 1996;104:129–132.CrossRefPubMedGoogle Scholar
  35. 35.
    Polak M. Hyperfunctioning thyroid adenoma and activating mutations in the TSH receptor gene. Arch Med Res. 1999;30:510–513.CrossRefPubMedGoogle Scholar
  36. 36.
    Rodrigues-Serpa A, Catarino A, Soares J. Loss of heterozygosity in follicular and papillary thyroid carcinomas. Cancer Genet Cytogenet. 2003;141:26–31.CrossRefPubMedGoogle Scholar
  37. 37.
    Roque L, Rodrigues R, Pinto A, Moura-Nunes V, Soares J. Chromosome imbalances in thyroid follicular neoplasms: a comparison between follicular adenomas and carcinomas. Genes Chromosomes Cancer. 2003;36:292–302.CrossRefPubMedGoogle Scholar
  38. 38.
    Sarquis MS, Weber F, Shen L, et al. High frequency of loss of heterozygosity in imprinted, compared with nonimprinted, genomic regions in follicular thyroid carcinomas and atypical adenomas. J Clin Endocrinol Metab. 2006;91:262–269.CrossRefPubMedGoogle Scholar
  39. 39.
    Satta MA, Nanni S, Della Casa S, Pontecorvi A. Molecular biology of thyroid neoplasms. Rays. 2000;25:151–161.PubMedGoogle Scholar
  40. 40.
    Sykiotis GP, Sgourou A, Papachatzopoulou A, et al. A somatic mutation in the thyrotropin receptor gene in a patient with an autonomous nodule within a multinodular goiter. Hormones (Athens). 2002;1:42–46.Google Scholar
  41. 41.
    Tezelman S, Borucu I, Senyurek Giles Y, Tunca F, Terzioglu T. The change in surgical practice from subtotal to near-total or total thyroidectomy in the treatment of patients with benign multinodular goiter. World J Surg. 2009;33(3):400–405.CrossRefPubMedGoogle Scholar
  42. 42.
    Tonacchera M, Chiovato L, Pinchera A, et al. Hyperfunctioning thyroid nodules in toxic multinodular goiter share activating thyrotropin receptor mutations with solitary toxic adenoma. J Clin Endocrinol Metab. 1998;83:492–498.CrossRefPubMedGoogle Scholar
  43. 43.
    Vaiman M, Nagibin A, Hagag P, Buyankin A, Olevson J, Shlamkovich N. Subtotal and near total versus total thyroidectomy for the management of multinodular goiter. World J Surg. 2008;32:1546–1551.CrossRefPubMedGoogle Scholar
  44. 44.
    Weber F, Shen L, Aldred MA, et al. Genetic classification of benign and malignant thyroid follicular neoplasia based on a three-gene combination. J Clin Endocrinol Metab. 2005;90:2512–2521.CrossRefPubMedGoogle Scholar
  45. 45.
    Zhao J, Leonard C, Gemsenjager E, Heitz PU, Moch H, Odermatt B. Differentiation of human follicular thyroid adenomas from carcinomas by gene expression profiling. Oncol Rep. 2008;19:329–337.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Jennifer L. Hunt
    • 1
  1. 1.Department of PathologyHarvard Medical School, Massachusetts General HospitalBostonUSA

Personalised recommendations