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Pediatric Surgical Pathology of the Thyroid and Parathyroid

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Abstract

Diseases of the thyroid occur frequently in children and range from developmental abnormalities through to inflammatory diseases, benign neoplasms and highly aggressive carcinomas. Papillary thyroid carcinoma is the most common malignancy arising within the thyroid in the pediatric population, and this entity is discussed at length. New concepts, including noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), are discussed, and for all entities, differential diagnostic considerations, genetic features and ancillary tests are described together with the gross and microscopic pathological findings. Parathyroid pathology is uncommon in childhood, although parathyroid adenomas and diseases associated with familial syndromes are seen in association with specific gene mutations. This chapter aims to give a broad overview of pediatric thyroid and parathyroid pathology.

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Abbreviations

DSPTC:

diffuse sclerosing papillary thyroid carcinoma

EFVPTC:

encapsulated follicular variant of papillary thyroid carcinoma

FA:

follicular adenoma

FC:

follicular carcinoma

GD:

Graves’ disease

HT:

Hashimoto’s thyroiditis

MTC:

medullary thyroid carcinoma

PA:

parathyroid adenoma

PTC:

papillary thyroid carcinoma

TG:

thyroglobulin

TPO:

thyroid peroxidase

TSH:

thyroid-stimulating hormone

References

  1. Carcangui ML. Thyroid. In: Sternberg SS, editor. Histology for pathologists. Second ed. Philadelphia, PA: Lippincott, Willliams & Wilkins; 1997. p. 1075–92.

    Google Scholar 

  2. Pankow BG, Michalak J, McGee MK. Adult human thyroid weight. Health Phys. 1985 Dec;49(6):1097–103.

    Article  CAS  PubMed  Google Scholar 

  3. Mullur R, Liu YY, Brent GA. Thyroid hormone regulation of metabolism. Physiol Rev 2014 Apr;94(2):355–382. Pubmed Central PMCID: 4044302.

    Google Scholar 

  4. Khan A, Nose V. Pathology of thyroid gland. In: Lloyd RV, editor. Endocrine Pathology: Differential Diagnosis and Molecular Advances. Second ed. New York, NY: Springer; 2010. p. 181–235.

    Chapter  Google Scholar 

  5. DeLellis RA, Nikiforov YE. Thyroid and parathyroid glands. In: Gnepp DR, editor. Diagnostic Surgical Pathology of the Head and Neck. Second ed. Philadelphia, PA: Saunders Elsevier; 2009. p. 563–646.

    Chapter  Google Scholar 

  6. Fagman H, Nilsson M. Morphogenetics of early thyroid development. J Mol Endocrinol. 2011 Feb;46(1):R33–42.

    Article  CAS  PubMed  Google Scholar 

  7. Szinnai G. Genetics of normal and abnormal thyroid development in humans. Best Pract Res Clin Endocrinol Metab. 2014 Mar;28(2):133–50.

    Article  CAS  PubMed  Google Scholar 

  8. De Felice M, Di Lauro R. Thyroid development and its disorders: genetics and molecular mechanisms. Endocr Rev. 2004 Oct;25(5):722–46.

    Article  PubMed  CAS  Google Scholar 

  9. Villacorte M, Delmarcelle AS, Lernoux M, Bouquet M, Lemoine P, Bolsee J, et al. Thyroid follicle development requires Smad1/5- and endothelial cell-dependent basement membrane assembly. Development 2016 Jun 01;143(11):1958–1970. Pubmed Central PMCID: 4920163.

    Google Scholar 

  10. Sturniolo G, Violi MA, Galletti B, Baldari S, Campenni A, Vermiglio F, et al. Differentiated thyroid carcinoma in lingual thyroid. Endocrine. 2016 Jan;51(1):189–98.

    Article  CAS  PubMed  Google Scholar 

  11. Conran RM, Chung E, Dehner LP, Shimada H. The pineal, pituitary, parathyroid, thyroid and adrenal glands. In: Stocker JT, Dehner LP, Husain AN, editors. Stocker & Dehner’s pediatric pathology. Third ed. Philadelphia, PA: Lippincott, Williams & Wilkins; 2011. p. 911–74.

    Google Scholar 

  12. Stocker JT, Mani H, Husain AN. Respiratory tract. In: Stocker JT, Dehner LP, Husain AN, editors. Stocker and Dehner’s pediatric pathology. Third ed. Philadelphia, PA: Lippincott, Williams & Wilkins; 2011. p. 441–515.

    Google Scholar 

  13. Knobel M. Etiopathology, clinical features, and treatment of diffuse and multinodular nontoxic goiters. J Endocrinol Investig. 2016 Apr;39(4):357–73.

    Article  CAS  Google Scholar 

  14. Gaitan E, Nelson NC, Poole GV. Endemic goiter and endemic thyroid disorders. World J Surg. 1991 Mar–Apr;15(2):205–15.

    Article  CAS  PubMed  Google Scholar 

  15. Kohrle J. Selenium and the thyroid. Curr Opin Endocrinol Diabetes Obes. 2015 Oct;22(5):392–401.

    Article  PubMed  CAS  Google Scholar 

  16. Adair C. Non-neoplastic lesions of the thyroid gland. In: LDR T, editor. Endocrine pathology. Foundations in diagnostic pathology. Philadelphia, PA: Churchill Livingstone; 2006. p. 1–50.

    Google Scholar 

  17. Mete O, Asa SL. Pitfalls in the diagnosis of follicular epithelial proliferations of the thyroid. Adv Anat Pathol. 2012 Nov;19(6):363–73.

    Article  PubMed  Google Scholar 

  18. Lacka K, Maciejewski A. Rare thyroid non-neoplastic diseases. Thyroid Res 2015;8:5. Pubmed Central PMCID: 4407423.

    Google Scholar 

  19. Szinnai G. Clinical genetics of congenital hypothyroidism. Endocr Dev. 2014;26:60–78.

    Article  PubMed  Google Scholar 

  20. Targovnik HM, Esperante SA, Rivolta CM. Genetics and phenomics of hypothyroidism and goiter due to thyroglobulin mutations. Mol Cell Endocrinol. 2010 Jun 30;322(1–2):44–55.

    Article  CAS  PubMed  Google Scholar 

  21. Spitzweg C, Morris JC. Genetics and phenomics of hypothyroidism and goiter due to NIS mutations. Mol Cell Endocrinol 2010 Jun 30;322(1–2):56–63. Pubmed Central PMCID: 2876245.

    Google Scholar 

  22. Avbelj M, Tahirovic H, Debeljak M, Kusekova M, Toromanovic A, Krzisnik C, et al. High prevalence of thyroid peroxidase gene mutations in patients with thyroid dyshormonogenesis. Eur J Endocrinol. 2007 May;156(5):511–9.

    Article  CAS  PubMed  Google Scholar 

  23. Kopp P. Mutations in the Pendred Syndrome (PDS/SLC26A) gene: an increasingly complex phenotypic spectrum from goiter to thyroid hypoplasia. J Clin Endocrinol Metab. 2014 Jan;99(1):67–9.

    Article  CAS  PubMed  Google Scholar 

  24. Moreno JC, Bikker H, Kempers MJ, van Trotsenburg AS, Baas F, de Vijlder JJ, et al. Inactivating mutations in the gene for thyroid oxidase 2 (THOX2) and congenital hypothyroidism. N Engl J Med. 2002 Jul 11;347(2):95–102.

    Article  CAS  PubMed  Google Scholar 

  25. Moreno JC, Visser TJ. New phenotypes in thyroid dyshormonogenesis: hypothyroidism due to DUOX2 mutations. Endocr Dev. 2007;10:99–117.

    Article  CAS  PubMed  Google Scholar 

  26. Alexander EK, Marqusee E, Lawrence J, Jarolim P, Fischer GA, Larsen PR. Timing and magnitude of increases in levothyroxine requirements during pregnancy in women with hypothyroidism. N Engl J Med. 2004 Jul 15;351(3):241–9.

    Article  CAS  PubMed  Google Scholar 

  27. Ghossein RA, Rosai J, Heffess C. Dyshormonogenetic Goiter: A Clinicopathologic Study of 56 Cases. Endocr Pathol. 1997 Winter;8(4):283–92.

    Article  PubMed  Google Scholar 

  28. Ajjan RA, Weetman AP. The pathogenesis of Hashimoto’s Thyroiditis: further developments in our understanding. Horm Metab Res. 2015 Sep;47(10):702–10.

    Article  CAS  PubMed  Google Scholar 

  29. Dong YH, Fu DG. Autoimmune thyroid disease: mechanism, genetics and current knowledge. Eur Rev Med Pharmacol Sci. 2014;18(23):3611–8.

    CAS  PubMed  Google Scholar 

  30. Mori K, Yoshida K. Viral infection in induction of Hashimoto’s thyroiditis: a key player or just a bystander? Curr Opin Endocrinol Diabetes Obes. 2010 Oct;17(5):418–24.

    Article  PubMed  Google Scholar 

  31. Smith TJ, Hegedus L. Graves’ Disease. N Engl J Med. 2016 Oct 20;375(16):1552–65.

    Article  PubMed  Google Scholar 

  32. Tomer Y. Mechanisms of autoimmune thyroid diseases: from genetics to epigenetics. Annu Rev Pathol 2014;9:147–156. Pubmed Central PMCID: 4128637.

    Google Scholar 

  33. Pujol-Borrell R, Gimenez-Barcons M, Marin-Sanchez A, Colobran R. Genetics of Graves’ Disease: Special Focus on the Role of TSHR Gene. Horm Metab Res. 2015 Sep;47(10):753–66.

    Article  CAS  PubMed  Google Scholar 

  34. Casey MB, Lohse CM, Lloyd RV. Distinction between papillary thyroid hyperplasia and papillary thyroid carcinoma by immunohistochemical staining for cytokeratin 19, galectin-3, and HBME-1. Endocr Pathol. 2003 Spring;14(1):55–60.

    Article  PubMed  Google Scholar 

  35. Erickson LA, Yousef OM, Jin L, Lohse CM, Pankratz VS, Lloyd RV. p27kip1 expression distinguishes papillary hyperplasia in Graves’ disease from papillary thyroid carcinoma. Mod Pathol. 2000 Sep;13(9):1014–9.

    Article  CAS  PubMed  Google Scholar 

  36. Liu YY, Morreau H, Kievit J, Romijn JA, Carrasco N, Smit JW. Combined immunostaining with galectin-3, fibronectin-1, CITED-1, Hector Battifora mesothelial-1, cytokeratin-19, peroxisome proliferator-activated receptor-{gamma}, and sodium/iodide symporter antibodies for the differential diagnosis of non-medullary thyroid carcinoma. Eur J Endocrinol. 2008 Mar;158(3):375–84.

    Article  CAS  PubMed  Google Scholar 

  37. Frank TS, LiVolsi VA, Connor AM. Cytomegalovirus infection of the thyroid in immunocompromised adults. Yale J Biol Med 1987 Jan–Feb;60(1):1–8. Pubmed Central PMCID: 2590227.

    Google Scholar 

  38. Paes JE, Burman KD, Cohen J, Franklyn J, McHenry CR, Shoham S, et al. Acute bacterial suppurative thyroiditis: a clinical review and expert opinion. Thyroid: Official Journal of the American Thyroid Association. 2010 Mar;20(3):247–55.

    Article  Google Scholar 

  39. McAninch EA, Xu C, Lagari VS, Kim BW. Coccidiomycosis thyroiditis in an immunocompromised host post-transplant: case report and literature review. J Clin Endocrinol Metab. 2014 May;99(5):1537–42.

    Article  CAS  PubMed  Google Scholar 

  40. Leckie RG, Buckner AB, Bornemann M. Seat belt-related thyroiditis documented with thyroid Tc-99m pertechnetate scans. Clin Nucl Med. 1992 Nov;17(11):859–60.

    Article  CAS  PubMed  Google Scholar 

  41. Engkakul P, Mahachoklertwattana P, Poomthavorn P. Eponym: de Quervain thyroiditis. Eur J Pediatr. 2011 Apr;170(4):427–31.

    Article  PubMed  Google Scholar 

  42. Nikiforov YE. Molecular diagnostics of thyroid tumors. Arch Pathol Lab Med. 2011 May;135(5):569–77.

    Article  CAS  PubMed  Google Scholar 

  43. Nikiforov YE. Recent developments in the molecular biology of the thyroid. In: Lloyd RV, editor. Endocrine Pathology: Differential Diagnosis and Molecular Advances. 2nd ed. New York, NY: Springer; 2010. p. 237–60.

    Chapter  Google Scholar 

  44. Motoi N, Sakamoto A, Yamochi T, Horiuchi H, Motoi T, Machinami R. Role of ras mutation in the progression of thyroid carcinoma of follicular epithelial origin. Pathol Res Pract. 2000;196(1):1–7.

    Article  CAS  PubMed  Google Scholar 

  45. Suarez HG, du Villard JA, Severino M, Caillou B, Schlumberger M, Tubiana M, et al. Presence of mutations in all three ras genes in human thyroid tumors. Oncogene. 1990 Apr;5(4):565–70.

    CAS  PubMed  Google Scholar 

  46. Dwight T, Thoppe SR, Foukakis T, Lui WO, Wallin G, Hoog A, et al. Involvement of the PAX8/peroxisome proliferator-activated receptor gamma rearrangement in follicular thyroid tumors. J Clin Endocrinol Metab. 2003 Sep;88(9):4440–5.

    Article  CAS  PubMed  Google Scholar 

  47. Parma J, Duprez L, Van Sande J, Hermans J, Rocmans P, Van Vliet G, et al. Diversity and prevalence of somatic mutations in the thyrotropin receptor and Gs alpha genes as a cause of toxic thyroid adenomas. J Clin Endocrinol Metab. 1997 Aug;82(8):2695–701.

    CAS  PubMed  Google Scholar 

  48. Rosai J, de Lellis RA, Carcangui ML, Frable WJ, Tallini G. Tumors of the thyroid and parathyroid glands. AFIP atlas of tumor pathology, vol. 21. Fourth ed. Silver Spring, MD: American Registry of Pathology Press; 2014.

    Book  Google Scholar 

  49. Thompson LDR. Benign neoplasms of the thyroid gland. In: LDR T, editor. Endocrine pathology. Foundations in diagnostic pathology. Philadelphia, PA: Churchill Livingstone; 2006. p. 51–75.

    Google Scholar 

  50. Thompson LD, Rosai J, Heffess CS. Primary thyroid teratomas: a clinicopathologic study of 30 cases. Cancer. 2000 Mar 01;88(5):1149–58.

    Article  CAS  PubMed  Google Scholar 

  51. Lloyd RV, Buehler D, Khanafshar E. Papillary thyroid carcinoma variants. Head Neck Pathol 2011 Mar;5(1):51–56. Pubmed Central PMCID: 3037461.

    Google Scholar 

  52. Nikiforova MN, Nikiforov YE. Molecular genetics of thyroid cancer: implications for diagnosis, treatment and prognosis. Expert Rev Mol Diagn. 2008 Jan;8(1):83–95.

    Article  CAS  PubMed  Google Scholar 

  53. Rowe LR, Bentz BG, Bentz JS. Detection of BRAF V600E activating mutation in papillary thyroid carcinoma using PCR with allele-specific fluorescent probe melting curve analysis. J Clin Pathol 2007 Nov;60(11):1211–1215. Pubmed Central PMCID: 2095462.

    Google Scholar 

  54. Nikiforova MN, Kimura ET, Gandhi M, Biddinger PW, Knauf JA, Basolo F, et al. BRAF mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas. J Clin Endocrinol Metab. 2003 Nov;88(11):5399–404.

    Article  CAS  PubMed  Google Scholar 

  55. Kimura ET, Nikiforova MN, Zhu Z, Knauf JA, Nikiforov YE, Fagin JA. High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma. Cancer Res. 2003 Apr 01;63(7):1454–7.

    CAS  PubMed  Google Scholar 

  56. Namba H, Rubin SA, Fagin JA. Point mutations of ras oncogenes are an early event in thyroid tumorigenesis. Mol Endocrinol. 1990 Oct;4(10):1474–9.

    Article  CAS  PubMed  Google Scholar 

  57. 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 Oct;73(4):832–6.

    Article  CAS  PubMed  Google Scholar 

  58. Liu T, Wang N, Cao J, Sofiadis A, Dinets A, Zedenius J, et al. The age- and shorter telomere-dependent TERT promoter mutation in follicular thyroid cell-derived carcinomas. Oncogene. 2014 Oct 16;33(42):4978–84.

    Article  CAS  PubMed  Google Scholar 

  59. Vinagre J, Almeida A, Populo H, Batista R, Lyra J, Pinto V, et al. Frequency of TERT promoter mutations in human cancers. Nat Commun. 2013;4:2185.

    Article  PubMed  CAS  Google Scholar 

  60. Melo M, da Rocha AG, Vinagre J, Batista R, Peixoto J, Tavares C, et al. TERT promoter mutations are a major indicator of poor outcome in differentiated thyroid carcinomas. J Clin Endocrinol Metab 2014 May;99(5):E754–E765. Pubmed Central PMCID: 4191548.

    Google Scholar 

  61. Cohen Y, Xing M, Mambo E, Guo Z, Wu G, Trink B, et al. BRAF mutation in papillary thyroid carcinoma. J Natl Cancer Inst. 2003 Apr 16;95(8):625–7.

    Article  CAS  PubMed  Google Scholar 

  62. Xing M. BRAF mutation in thyroid cancer. Endocr Relat Cancer. 2005 Jun;12(2):245–62.

    Article  CAS  PubMed  Google Scholar 

  63. Ciampi R, Nikiforov YE. Alterations of the BRAF gene in thyroid tumors. Endocr Pathol. 2005 Fall;16(3):163–72.

    Article  CAS  PubMed  Google Scholar 

  64. Adeniran AJ, Zhu Z, Gandhi M, Steward DL, Fidler JP, Giordano TJ, et al. Correlation between genetic alterations and microscopic features, clinical manifestations, and prognostic characteristics of thyroid papillary carcinomas. Am J Surg Pathol. 2006 Feb;30(2):216–22.

    Article  PubMed  Google Scholar 

  65. Namba H, Nakashima M, Hayashi T, Hayashida N, Maeda S, Rogounovitch TI, et al. Clinical implication of hot spot BRAF mutation, V599E, in papillary thyroid cancers. J Clin Endocrinol Metab. 2003 Sep;88(9):4393–7.

    Article  CAS  PubMed  Google Scholar 

  66. Begum S, Rosenbaum E, Henrique R, Cohen Y, Sidransky D, Westra WH. BRAF mutations in anaplastic thyroid carcinoma: implications for tumor origin, diagnosis and treatment. Mod Pathol. 2004 Nov;17(11):1359–63.

    Article  CAS  PubMed  Google Scholar 

  67. Xing M. BRAF mutation in papillary thyroid cancer: pathogenic role, molecular bases, and clinical implications. Endocr Rev. 2007 Dec;28(7):742–62.

    Article  CAS  PubMed  Google Scholar 

  68. Nasirden A, Saito T, Fukumura Y, Hara K, Akaike K, Kurisaki-Arakawa A, et al. In Japanese patients with papillary thyroid carcinoma, TERT promoter mutation is associated with poor prognosis, in contrast to BRAF V600E mutation. Virchows Archiv. 2016 Dec;469(6):687–96.

    Article  CAS  PubMed  Google Scholar 

  69. Liu C, Chen T, Liu Z. Associations between BRAF(V600E) and prognostic factors and poor outcomes in papillary thyroid carcinoma: a meta-analysis. World J Surg Oncol 2016 Sep 06;14(1):241. Pubmed Central PMCID: 5012084.

    Google Scholar 

  70. Abd Elmageed ZY, Sholl AB, Tsumagari K, Al-Qurayshi Z, Basolo F, Moroz K, et al. Immunohistochemistry as an accurate tool for evaluating BRAF-V600E mutation in 130 samples of papillary thyroid cancer. Surgery. 2017 Apr;161(4):1122–8.

    Article  PubMed  Google Scholar 

  71. Pyo JS, Sohn JH, Kang G. BRAF Immunohistochemistry Using Clone VE1 is Strongly Concordant with BRAF(V600E) Mutation Test in Papillary Thyroid Carcinoma. Endocr Pathol. 2015 Sep;26(3):211–7.

    Article  CAS  PubMed  Google Scholar 

  72. Thompson LDR. Malignant neoplasms of the thyroid gland. In: LDR T, editor. Endocrine pathology. Foundations in diagnostic pathology. Philadelphia, PA: Churchill Livingstone; 2006. p. 77–144.

    Google Scholar 

  73. Osamura RY, Hunt JL. Current practices in performing frozen sections for thyroid and parathyroid pathology. Virchows Archiv. 2008 Nov;453(5):433–40.

    Article  PubMed  Google Scholar 

  74. Vuong HG, Kondo T, Pham TQ, Oishi N, Mochizuki K, Nakazawa T, et al. Prognostic significance of diffuse sclerosing variant papillary thyroid carcinoma: a systematic review and meta-analysis. Eur J Endocrinol. 2017 Apr;176(4):431–9.

    Article  Google Scholar 

  75. Pillai S, Gopalan V, Smith RA, Lam AK. Diffuse sclerosing variant of papillary thyroid carcinoma—an update of its clinicopathological features and molecular biology. Crit Rev Oncol Hematol. 2015 Apr;94(1):64–73.

    Article  PubMed  Google Scholar 

  76. Koo JS, Hong S, Park CS. Diffuse sclerosing variant is a major subtype of papillary thyroid carcinoma in the young. Thyroid. 2009 Nov;19(11):1225–31.

    Article  PubMed  Google Scholar 

  77. Balachandar S, La Quaglia M, Tuttle RM, Heller G, Ghossein RA, Sklar CA. Pediatric differentiated thyroid carcinoma of follicular cell origin: prognostic significance of histologic subtypes. Thyroid 2016 Feb;26(2):219–226. Pubmed Central PMCID: 4855728.

    Google Scholar 

  78. Nikiforov YE, Seethala RR, Tallini G, Baloch ZW, Basolo F, Thompson LD, et al. Nomenclature revision for encapsulated follicular variant of papillary thyroid carcinoma: a paradigm shift to reduce overtreatment of indolent tumors. JAMA Oncology. 2016 Aug 01;2(8):1023–9.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Thompson LD. Ninety-four cases of encapsulated follicular variant of papillary thyroid carcinoma: a name change to noninvasive follicular thyroid neoplasm with papillary-like nuclear features would help prevent overtreatment. Mod Pathol. 2016 Jul;29(7):698–707.

    Article  CAS  PubMed  Google Scholar 

  80. Patel KN. Noninvasive encapsulated follicular variant of papillary thyroid “cancer” (or not): time for a name change. JAMA Oncology. 2016 Aug 01;2(8):1005–6.

    Article  PubMed  Google Scholar 

  81. Jeon MJ, Song DE, Jung CK, Kim WG, Kwon H, Lee YM, et al. Impact of reclassification on thyroid nodules with architectural atypia: from non-invasive encapsulated follicular variant papillary thyroid carcinomas to non-invasive follicular thyroid neoplasm with papillary-like nuclear features. PLoS One 2016;11(12):e0167756. Pubmed Central PMCID: 5147963.

    Google Scholar 

  82. Scharpf J, Kamani D, Sadow PM, Randolph GW. The follicular variant of papillary thyroid cancer and noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Curr Opin Oncol. 2017 Jan;29(1):20–4.

    Article  PubMed  Google Scholar 

  83. Scognamiglio T, Hyjek E, Kao J, Chen YT. Diagnostic usefulness of HBME1, galectin-3, CK19, and CITED1 and evaluation of their expression in encapsulated lesions with questionable features of papillary thyroid carcinoma. Am J Clin Pathol. 2006 Nov;126(5):700–8.

    Article  CAS  PubMed  Google Scholar 

  84. Garcia-Rostan G, Costa AM, Pereira-Castro I, Salvatore G, Hernandez R, Hermsem MJ, et al. Mutation of the PIK3CA gene in anaplastic thyroid cancer. Cancer Res. 2005 Nov 15;65(22):10199–207.

    Article  CAS  PubMed  Google Scholar 

  85. Moghaddam PA, Virk R, Sakhdari A, Prasad ML, Cosar EF, Khan A. Five top stories in thyroid pathology. Arch Pathol Lab Med. 2016 Feb;140(2):158–70.

    Article  PubMed  Google Scholar 

  86. Nose V. Familial thyroid cancer: a review. Mod Pathol. 2011 Apr;24(Suppl 2):S19–33.

    Article  CAS  PubMed  Google Scholar 

  87. Machens A, Niccoli-Sire P, Hoegel J, Frank-Raue K, van Vroonhoven TJ, Roeher HD, et al. Early malignant progression of hereditary medullary thyroid cancer. N Engl J Med. 2003 Oct 16;349(16):1517–25.

    Article  CAS  PubMed  Google Scholar 

  88. Frank-Raue K, Rybicki LA, Erlic Z, Schweizer H, Winter A, Milos I, et al. Risk profiles and penetrance estimations in multiple endocrine neoplasia type 2A caused by germline RET mutations located in exon 10. Hum Mutat. 2011 Jan;32(1):51–8.

    Article  CAS  PubMed  Google Scholar 

  89. Hoppener JW, Lips CJ. RET receptor tyrosine kinase gene mutations: molecular biological, physiological and clinical aspects. Eur J Clin Investig. 1996 Aug;26(8):613–24.

    Article  CAS  Google Scholar 

  90. Chiefari E, Russo D, Giuffrida D, Zampa GA, Meringolo D, Arturi F, et al. Analysis of RET proto-oncogene abnormalities in patients with MEN 2A, MEN 2B, familial or sporadic medullary thyroid carcinoma. J Endocrinol Investig. 1998 Jun;21(6):358–64.

    Article  CAS  Google Scholar 

  91. Elisei R, Cosci B, Romei C, Bottici V, Renzini G, Molinaro E, et al. Prognostic significance of somatic RET oncogene mutations in sporadic medullary thyroid cancer: a 10-year follow-up study. J Clin Endocrinol Metab. 2008 Mar;93(3):682–7.

    Article  CAS  PubMed  Google Scholar 

  92. Eng C, Clayton D, Schuffenecker I, Lenoir G, Cote G, Gagel RF, et al. The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2. International RET mutation consortium analysis. JAMA. 1996 Nov 20;276(19):1575–9.

    Article  CAS  PubMed  Google Scholar 

  93. Albores-Saavedra J. C-cell hyperplasia. Am J Surg Pathol. 1989 Nov;13(11):987–9.

    Article  CAS  PubMed  Google Scholar 

  94. Katoh R, Miyagi E, Nakamura N, Li X, Suzuki K, Kakudo K, et al. Expression of thyroid transcription factor-1 (TTF-1) in human C cells and medullary thyroid carcinomas. Hum Pathol. 2000 Mar;31(3):386–93.

    Article  CAS  PubMed  Google Scholar 

  95. Bejarano PA, Nikiforov YE, Swenson ES, Biddinger PW. Thyroid transcription factor-1, thyroglobulin, cytokeratin 7, and cytokeratin 20 in thyroid neoplasms. Appl Immunohistochem Mol Morphol. 2000 Sep;8(3):189–94.

    Article  CAS  PubMed  Google Scholar 

  96. Lam KY, Lui MC, Lo CY. Cytokeratin expression profiles in thyroid carcinomas. Eur J Surg Oncol. 2001 Nov;27(7):631–5.

    Article  CAS  PubMed  Google Scholar 

  97. Satoh F, Umemura S, Yasuda M, Osamura RY. Neuroendocrine marker expression in thyroid epithelial tumors. Endocr Pathol. 2001 Fall;12(3):291–9.

    Article  CAS  PubMed  Google Scholar 

  98. Faggiano A, Talbot M, Lacroix L, Bidart JM, Baudin E, Schlumberger M, et al. Differential expression of galectin-3 in medullary thyroid carcinoma and C-cell hyperplasia. Clin Endocrinol. 2002 Dec;57(6):813–9.

    Article  CAS  Google Scholar 

  99. Aozasa K. Hashimoto’s thyroiditis as a risk factor of thyroid lymphoma. Acta Pathol Jpn. 1990 Jul;40(7):459–68.

    CAS  PubMed  Google Scholar 

  100. Harach HR. The Parathyroid. In: Lloyd RV, editor. Endocrine pathology: differential diagnosis and molecular advances. Second ed. New York, NY: Springer; 2010. p. 131–56.

    Chapter  Google Scholar 

  101. Johnson SJ, Sheffield EA, McNicol AM. Best practice no 183. Examination of parathyroid gland specimens. J Clin Pathol 2005 Apr;58(4):338–342. Pubmed Central PMCID: 1770637.

    Google Scholar 

  102. Roth SI, Abu-Jawdeh G. Parathyroid glands. In: Sternberg SS, editor. Histology for pathologists. Second ed. Philadelphia, PA: Lippincott, Williams & Wilkins; 1997. p. 1093–105.

    Google Scholar 

  103. Zajac JD, Danks JA. The development of the parathyroid gland: from fish to human. Curr Opin Nephrol Hypertens. 2008 Jul;17(4):353–6.

    Article  CAS  PubMed  Google Scholar 

  104. Grigorieva IV, Mirczuk S, Gaynor KU, Nesbit MA, Grigorieva EF, Wei Q, et al. Gata3-deficient mice develop parathyroid abnormalities due to dysregulation of the parathyroid-specific transcription factor Gcm2. J Clin Invest 2010 Jun;120(6):2144–2155. Pubmed Central PMCID: 2877956.

    Google Scholar 

  105. Chojnowski JL, Masuda K, Trau HA, Thomas K, Capecchi M, Manley NR. Multiple roles for HOXA3 in regulating thymus and parathyroid differentiation and morphogenesis in mouse. Development 2014 Oct;141(19):3697–3708. Pubmed Central PMCID: 4197593.

    Google Scholar 

  106. Uludag M, Isgor A, Yetkin G, Atay M, Kebudi A, Akgun I. Supernumerary ectopic parathyroid glands. Persistent hyperparathyroidism due to mediastinal parathyroid adenoma localized by preoperative single photon emission computed tomography and intraoperative gamma probe application. Hormones. 2009 Apr–Jun;8(2):144–9.

    Article  PubMed  Google Scholar 

  107. Noussios G, Anagnostis P, Natsis K. Ectopic parathyroid glands and their anatomical, clinical and surgical implications. Exp Clin Endocrinol Diabetes. 2012 Nov;120(10):604–10.

    Article  CAS  PubMed  Google Scholar 

  108. Yousef GM, Denic N, Wadhwa J, Chandracanth SA, Smith T, Elms F, et al. Intravagal ectopic parathyroid presenting as vocal cord paralysis: case report and review of the literature. J Otolaryngol. 2007 Dec;36(6):E93–5.

    PubMed  Google Scholar 

  109. Dahlberg PJ, Borer WZ, Newcomer KL, Yutuc WR. Autosomal or X-linked recessive syndrome of congenital lymphedema, hypoparathyroidism, nephropathy, prolapsing mitral valve, and brachytelephalangy. Am J Med Genet. 1983 Sep;16(1):99–104.

    Article  CAS  PubMed  Google Scholar 

  110. Bergada I, Schiffrin A, Abu Srair H, Kaplan P, Dornan J, Goltzman D, et al. Kenny syndrome: description of additional abnormalities and molecular studies. Hum Genet. 1988 Sep;80(1):39–42.

    Article  CAS  PubMed  Google Scholar 

  111. Pellock JM, Behrens M, Lewis L, Holub D, Carter S, Rowland LP. Kearns-Sayre syndrome and hypoparathyroidism. Ann Neurol. 1978 May;3(5):455–8.

    Article  CAS  PubMed  Google Scholar 

  112. Lee M, Pellegata NS. Multiple endocrine neoplasia type 4. Front Horm Res. 2013;41:63–78.

    Article  CAS  PubMed  Google Scholar 

  113. Thompson LDR. Non-neoplastic lesions of the parathyroid gland. In: LDR T, editor. Endocrine pathology. Foundations in diagnostic pathology. Philadelphia, PA: Churchill Livingstone; 2006. p. 145–56.

    Google Scholar 

  114. Thompson LDR. Benign neoplasms of the parathyroid gland. In: LDR T, editor. Endocrine pathology. Foundations in diagnostic pathology. Philadelphia, PA: Churchill Livingstone; 2006. p. 157–64.

    Google Scholar 

  115. Hsi ED, Zukerberg LR, Yang WI, Arnold A. Cyclin D1/PRAD1 expression in parathyroid adenomas: an immunohistochemical study. J Clin Endocrinol Metab. 1996 May;81(5):1736–9.

    CAS  PubMed  Google Scholar 

  116. Hemmer S, Wasenius VM, Haglund C, Zhu Y, Knuutila S, Franssila K, et al. Deletion of 11q23 and cyclin D1 overexpression are frequent aberrations in parathyroid adenomas. Am J Pathol 2001 Apr;158(4):1355–1362. Pubmed Central PMCID: 1891928.

    Google Scholar 

  117. Lemos MC, Thakker RV. Multiple endocrine neoplasia type 1 (MEN1): analysis of 1336 mutations reported in the first decade following identification of the gene. Hum Mutat. 2008 Jan;29(1):22–32.

    Article  CAS  PubMed  Google Scholar 

  118. Davenport C, Agha A. The role of menin in parathyroid tumorigenesis. Adv Exp Med Biol. 2009;668:79–86.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Pathology, Department of Paediatric Laboratory Medicine, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada

    Gino R. Somers

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  1. Gino R. Somers
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Correspondence to Gino R. Somers .

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Editors and Affiliations

  1. Department of Otolaryngology – Head & Neck Surgery, University of Toronto, Toronto, ON, Canada

    Paolo Campisi

  2. Department of Otolaryngology – Head & Neck Surgery, University of Toronto, Toronto, ON, Canada

    Vito Forte

  3. Division of Pathology, Paediatric Laboratory, Hospital for Sick Children Division of Pathology, Toronto, ON, Canada

    Bo-Yee Ngan

  4. Division of Pathology, Department of Laboratory Medicine (retired), Hospital for Sick Children, Toronto, ON, Canada

    Glenn Taylor

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Somers, G.R. (2021). Pediatric Surgical Pathology of the Thyroid and Parathyroid. In: Campisi, P., Forte, V., Ngan, BY., Taylor, G. (eds) Pediatric Head and Neck Textbook. Springer, Cham. https://doi.org/10.1007/978-3-030-59265-3_19

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