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Salivary Gland, Thyroid, and Parathyroid Neoplasms: Molecular Features

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Precision Molecular Pathology of Neoplastic Pediatric Diseases

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Abstract

Tumors involving the salivary, thyroid, and parathyroid glands in the pediatric age group range from benign tumors, to indeterminant malignant potential tumors to frankly malignant tumors. In addition, certain tumors may be associated with hereditary syndromes. During the past several decades, cytogenetics and molecular genetics have provided certain tumor-defining features. With the advent of rapid sequencing techniques, further definition of these tumors and identification of molecular targets for diagnosis, prognosis, and treatment have been identified. This chapter reviews the molecular features of salivary, thyroid, and parathyroid gland tumors.

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References

  1. Lennon P, Silvera VM, Perez-Atayde A, Cunningham MJ, Rahbar R. Disorders and tumors of the salivary glands in children. Otolaryngol Clin N Am. 2015;48:153–73.

    Article  Google Scholar 

  2. Sultan I, Rodriguez-Galindo C, Al-Sharabati GM, Casanova M, Ferrari A. Salivary gland carcinomas in children and adolescents: a population-based study, with comparison to adult cases. Head Neck. 2011;33:1476–81.

    Article  PubMed  Google Scholar 

  3. Xu B, Aneja A, Ghossein R, Katabi N. Salivary gland epithelial neoplasms in pediatric population: a single institute experience with a focus on the histologic spectrum and clinical outcomes. Human Pathol. 2017;67:37–44. https://doi.org/10.10016/j.humanpath.2017.07.007.

    Article  Google Scholar 

  4. Guzzo M, Ferrari A, Marcon I, Collini P, Gandola L, et al. Salivary gland neoplasms in children: the experience of the Instituto Nazionale Tumori of Milan. Pediatr Blood Cancer. 2006;47:806–10.

    Article  PubMed  Google Scholar 

  5. Allan BJ, Tashiro J, Diaz S, Edens J, Younis R, Thaller SR. Malignant tumor of the parotid gland in children: incidence and outcomes. J Craniofac Surg. 2013;24:1660–4.

    Article  PubMed  Google Scholar 

  6. Rebours C, Couloigner V, Galmiche L, Casiraghi O, Badoual C, et al. Pediatric salivary gland carcinomas: diagnostic and therapeutic management. Laryngoscope. 2017;127:140–7.

    Article  PubMed  Google Scholar 

  7. Chiaravalli S, Guzzon M, Bisogno G, DePasquale D, Migliorati R, et al. Salivary gland carcinomas in children and adolescents: the Italian TREP project experience. Pediatr Blood Cancer. 2014;61:1961–8.

    Article  PubMed  Google Scholar 

  8. Goyal G, Mehdi SA, Ganti AK. Salivary gland cancers: biology and systemic therapy. Oncology. 2015;29:773–80.

    PubMed  Google Scholar 

  9. Simpson RHW, Skalova A, DiPalma S, Leivo I. Recent advances in the diagnostic pathology of salivary carcinomas. Virchows Arch. 2014;465:371–84.

    Article  CAS  PubMed  Google Scholar 

  10. Gupta R, Balasubramanian D, Clark JR. Salivary gland lesions: recent advances and evolving concepts. Oral Surg Oral Med Oral Pathol Oral Radiol. 2015;119:661–74.

    Article  PubMed  Google Scholar 

  11. Ochal-Choinska A, Osuch-Wojcikiewicz E. Particular aspects in the cytogenetics and molecular biology of salivary gland tumors–current review of reports. Contemp Oncol. 2016;4:281–6.

    Google Scholar 

  12. Yin LX, Ha PK. Genetic alterations in salivary gland cancers. Cancer. 2016;122:1822–31.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Stenman G. Fusion oncogenes in salivary gland tumors: molecular and clinical consequences. Head Neck Pathol. 2013;7:S12–9.

    Article  PubMed  Google Scholar 

  14. Fonseca FP, Filho MS, Altemani A, Speight PM, Vargas PA. Molecular signature of salivary gland tumors: potential use as diagnostic and prognostic marker. J Oral Pathol Med. 2016;45:101–10.

    Article  CAS  PubMed  Google Scholar 

  15. Techavichit P, Hicks MJ, Lopez-Terrada DH, Quintanilla NM, Guillerman RP, et al. Mucoepidermoid carcinoma in children: a single institutional experience. Pediatr Blood Cancer. 2016;63:27–31.

    Article  CAS  PubMed  Google Scholar 

  16. Coca-Pelaz A, Rodrigo JP, Triantafyliou A, Hunt JL, Rinaldo A, et al. Salivary mucoepidermoid carcinoma revisited. Eur Arch Otorhinolaryngol. 2015;272:799–819.

    Article  PubMed  Google Scholar 

  17. Saade RE, Bell D, Garcia J, Roberts D, Weber R. Role of CRTC1/MAML2 translocation in the prognosis and clinical outcomes of mucoepidermoid carcinoma. JAMA Otolaryngol Head Neck Surg. 2016;142:234–40.

    Article  PubMed  Google Scholar 

  18. Noda H, Okumura Y, Nakayama T, Miyabe S, Fujiyoshi Y, et al. Clinicopathological significance of MAML2 gene split in mucoepidermoid carcinoma. Cancer Sci. 2013;104:85–92.

    Article  CAS  PubMed  Google Scholar 

  19. Jee KJ, Persson M, Heikinheimo K, Passador-Santos F, Aro K, et al. Genomic profiles and CRTC1-MAML2 fusion distinguish different types of mucoepidermoid carcinoma. Mod Pathol. 2013;26:213–22.

    Article  CAS  PubMed  Google Scholar 

  20. Chen J, Li JL, Chen Z, Griffin JD, Wu L. Gene expression profiling analysis of CRTCL1-MAML2 fusion oncogene-induced transcriptional program in human mucoepidermoid carcinoma cells. BMC Cancer. 2015;803(1–13):15.

    Google Scholar 

  21. Nakano T, Yamamoto H, Hashimoto K, Tamiya S, Shiratsuchi H, et al. HER2 and EGFR gene copy number alterations in high-grade salivary gland mucoepidermoid carcinoma irrespective of MAML2 fusion status. Histopathology. 2013;63:378–92.

    Article  PubMed  Google Scholar 

  22. Chen Z, Chen J, Gu Y, Hu C, LI JL, et al. Aberrantly activated AREG-EGFR signaling is required for the growth and survival of CRTC1-MAML2 fusion-positive mucoepidermoid carcinoma cells. Oncogene. 2014;33:3869–77.

    Article  CAS  PubMed  Google Scholar 

  23. Cai BL, Li Y, Shen LL, Zhao JL, Wu JZ, et al. Nuclear multidrug resistance-related protein 1 is highly associated with better prognosis of human mucoepidermoid carcinoma through suppression of cell proliferation, migration and invasion. PLoS One. 2016;11(2):e0148223.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Dillon PM, Chakraborty S, Moskaluk CA, Thomas CY. Adenoid cystic carcinoma: a review of recent advances, molecular targets and clinical trials. Head Neck. 2016;38:620–7.

    Article  PubMed  Google Scholar 

  25. Chae YK, Chung SY, Davis AA, Carneiro BA, Chandra S, et al. Adenoid cystic carcinomas: current therapy and potential therapeutic advances based on genomic profiling. Oncotarget. 2015;6:37117–34.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Shen Z, Li T, Chen DA, Jia S, Yang X, et al. The CCL5/CCR5 axis contributes to the perineural invasion of human salivary adenoid cystic carcinoma. Oncol Rep. 2014;31:800–6.

    Article  CAS  PubMed  Google Scholar 

  27. Stevens TM, Parekh V. Mammary analogue secretory carcinoma. Arch Pathol Lab Med. 2016;140:997–1001.

    Article  CAS  PubMed  Google Scholar 

  28. Damjanov I, Skenderi F, Vranic S. Mammary analogue secretory carcinoma (MASC) of the salivary gland: a new tumor entity. Bosn J Basic Med Sci. 2016;16:237–8.

    PubMed  PubMed Central  Google Scholar 

  29. Bishop JA. Unmasking MASC: bringing to light the unique morphologic, immunohistochemical, and genetic features of the newly recognized mammary analogue secretory carcinoma of salivary glands. Head Neck Pathol. 2013;7:35–9.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Sethi R, Kozin E, Remenschneider A, Meier J, VanderLaan P, et al. Mammary analogue secretory carcinoma: update on a new diagnosis of salivary gland malignancy. Laryngoscope. 2014;124:188–95.

    Article  PubMed  Google Scholar 

  31. Skalova A. Mammary analogue secretory carcinoma of salivary gland origin: an update and expanded morphologic and immunohistochemical spectrum of recently described entity. Head Neck Pathol. 2013;7:S30–7.

    Article  PubMed  Google Scholar 

  32. Choudhary K, Panda S, Beena VT, Rajeev R, Sivakumar R, Krishanan S. Sialoblastoma: a literature review from 1996–2011. Nat J Maxillofac Surg. 2013;4:13–8.

    Article  Google Scholar 

  33. Irace AL, Adil EA, Archer NM, Silvera VM, Perez-Atayde A, Rahbar R. Pediatric sialoblastoma: evaluation and management. Int J Pediatr Otorhinolaryngol. 2016;87:44–9.

    Article  PubMed  Google Scholar 

  34. Batsakis JG. Myoepithelioma. Ann Otol Rhinol Laryngol. 1985;94:52304.

    Article  Google Scholar 

  35. Said MS. Myoepithelioma pathology. http://emedicine.medscape.com/article/1692199-overvieww#a10. Accessed 1 Aug 2017.

  36. Shah AA, LeGallo RD, van Zante A, Frierson HF Jr, Mills SE, et al. EWSR1 genetic rearrangements in salivary gland tumors: a specific and very common feature of hyalinizing clear cell carcinoma. Am J Surg Pathol. 2013;37:571–9.

    Article  PubMed  Google Scholar 

  37. Francis GL, Waguespack SG, Bauer AJ, Angelos P, Benvenga S, et al. Management guidelines for children with thyroid nodules and differentiated thyroid cancer. Thyroid. 2015;25:716–59.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Fagin JA, Wells SA Jr. Biologic and clinical perspectives on thyroid cancer. N Engl J Med. 2016;375:1054–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Brehar AC, Terzea DC, Ioachim DL, Procopiuc C, Brehar FM, et al. Cribriform-morula variant of papillary thyroid carcinoma at pediatric age–case report and review of the literature. Romanian J Morphol Embryol. 2016;57:531–7.

    Google Scholar 

  40. Pires BP, Alve PAG, Bordallo MA, Bulzico DA, Lopes FPPL, et al. Prognostic factors of early and long-term remission in pediatric differentiated thyroid carcinoma: the role of sex, age, clinical presentation, and the newly proposed American thyroid association risk stratification system. Thyroid. 2016;26:1480–7.

    Article  CAS  PubMed  Google Scholar 

  41. Kim J, Sun Z, Adam MA, Adibe OO, Rice HE, et al. Predictors of nodal metastasis in pediatric differentiated thyroid cancer. J Pediatr Surg. 2017;52:120–3.

    Article  PubMed  Google Scholar 

  42. Cordioli MICV, Moraes L, Cury AN, Cerutti JM. Are we really at the dawn of understanding sporadic thyroid carcinoma? Endocr Relat Cancer. 2015;22:R311–24.

    Article  CAS  PubMed  Google Scholar 

  43. Dermody S, Wall A, Harley EH Jr. Pediatric thyroid cancer: an update from the SEER database 2007–2012. Int J Pediatr Otorhinolaryngol. 2016;89:121–6.

    Article  PubMed  Google Scholar 

  44. Vertamini LB, Frazier AL, Abrantes FL, Ribeiro KB, Rodriguez-Galindo C. Increase in the incidence of differentiated thyroid carcinoma in children, adolescents and young adults: a population-based study. J Pediatr. 2014;164:1481–5.

    Article  Google Scholar 

  45. Ballester LY, Sarabia SF, Sayeed H, Patel N, Baalwa J, et al. Integrating molecular testing in the diagnosis and management of children with thyroid lesions. Pediatr Develop Pathol. 2016;19:94–100.

    Article  Google Scholar 

  46. Picarsic JL, Buryk MA, Ozolek J, Ranganathan S, Monaco SE, et al. Molecular characterization of sporadic thyroid carcinoma with the DNA/RNA ThryroSeq v2 next-generation sequencing assay. Pediatr Develop Pathol. 2016;19:115–22.

    Article  Google Scholar 

  47. Alzahrani AS, Murugan AK, Qasem E, Alswailem M, Al-Hindi H, Shi Y. Single point mutations in pediatric differentiated thyroid cancer. Thyroid. 2017;27:189–96.

    Article  CAS  PubMed  Google Scholar 

  48. Prescott JD, Zeiger MA. The RET oncogene in papillary thyroid carcinoma. Cancer. 2015;121:2137–46.

    Article  CAS  PubMed  Google Scholar 

  49. Romei C, Ciampi R, Elisei R. A comprehensive overview of the role to the RET proto-oncogene in thyroid carcinoma. Nat Rev Endocrinol. 2014;12:192–202.

    Article  CAS  Google Scholar 

  50. Bhatia P, Elmageed ZYA, Friedlander P, Aslam R, Kandil E. The utility of molecular markers in pre-operative assessement of thyroid nodules. Future Oncol. 2015;11:2343–50.

    Article  CAS  PubMed  Google Scholar 

  51. Soares P, Celestinon R, Melo M, Fonseca E, Sobrinho-Simoes M. Prognostic biomarkers in thyroid cancer. Virchows Arch. 2014;464:333–46.

    Article  CAS  PubMed  Google Scholar 

  52. Nikiforov YE. Thyroid cancer in 2015. Molecular landscape of thyroid cancer continues to be deciphered. Nat Rev Endocrinol. 2016;12:67–8.

    Article  CAS  PubMed  Google Scholar 

  53. Xing M, Haugen BR, Schlumberger M. Progress in molecular-based management of differentiated thyroid cancer. Lancet. 2013;381:1058–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Tavares C, Melo M, Cameselle-Teijeiro JM, Soares P, Sobrinho-Simoes M. Genetic predictors of thyroid cancer outcome. Eur J Endocrinol. 2016;174:R117–26.

    Article  CAS  PubMed  Google Scholar 

  55. Costa V, Esposito R, Pallante P, Ciccodicola A, Fusco A. The “next-generation” knowledge of papillary thyroid carcinoma. Cell Cycle. 2015;14(13):2018–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Giordano TJ. Follicular cell thyroid neoplasia: insights from genomics and the cancer genome atlas research network. Curr Opin Oncol. 2016;28:1–4.

    Article  CAS  PubMed  Google Scholar 

  57. Tennakoon TMPB, Ranasinghe ADCU, Dassanayake RS. Values of molecular markers in the differentiated diagnosis of thyroid abnormalities. J Cancer Res Clin Oncol. 2017;143:913–31.

    Article  CAS  PubMed  Google Scholar 

  58. Petrulea MS, Plantinga TS, Smit JW, Georgescu CE, Netea-Maier RT. PI3K/AKT/mTOR: a promising therapeutic targe for non-medullary thyroid carcinoma. Cancer Treat Rev. 2015;41:707–13.

    Article  CAS  PubMed  Google Scholar 

  59. Zhang Y, Yu J, Grachtchouk V, Quin T, Lumeng CN, et al. Genomic binding of PAX8-PPARG fusion protein regulates cancer-related pathways and alters immune landscape of thyroid cancer. Oncotarget. 2017;8:5761–73.

    PubMed  Google Scholar 

  60. Wang Z, Chen JQ, Qin XG. Clinical impact of BRAF mutation on the diagnosis and prognosis of papillary thyroid carcinoma: a systematic review and meta-analysis. Eur J Clin Investig. 2016;46:146–57.

    Article  CAS  Google Scholar 

  61. Cabanillas ME, Patel A, Danysh BP, Dadu R, Kopetz S, Falchook G. BRAF inhibitors: experience in thyroid cancer and general review of toxicity. Horm Cancer. 2015;6:21–36.

    Article  CAS  PubMed  Google Scholar 

  62. Perri F, Pezzullo L, Chiofalo MG, Lastoria S, DiGennaro F, et al. Targeted therapy: a new hope for thyroid carcinomas. Crit Rev Oncol Hematol. 2015;94:55–63.

    Article  PubMed  Google Scholar 

  63. Liu R, Xing M. TERT promoter mutations in thyroid cancer. Endocr Relat Cancer. 2016;23:R143–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Papp S, Asa SL. When thyroid carcinoma goes bad: a morphological and molecular analysis. Head Neck Pathol. 2015;9:16–23.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Han PA, Weng CH, Khawaja HT, Nagarajan N, Schneider EB, et al. MicroRNA expression and association with clinicopathologic features of papillary thyroid cancer: a systematic review. Thyroid. 2015;25:1322–9.

    Article  CAS  Google Scholar 

  66. Chruscik A, Lam AK. Clinical pathological impacts of microRNAs in papillary thyroid carcinoma: a critical review. Exp Mol Pathol. 2015;99:393–8.

    Article  CAS  PubMed  Google Scholar 

  67. Mutalib NS, Yusof AM, Mokhtar NM, Harun R, Muhammad R, Jamal R. MicroRNAs and lymph node metastasis in papillary thyroid cancers. Asian Pac J Cancer Prev. 2016;17:25–35.

    Article  PubMed  Google Scholar 

  68. Chernock RD, Hagemann IS. Molecular pathology of hereditary and sporadic medullary thyroid carcinomas. Am J Clin Pathol. 2015;143:768–77.

    Article  CAS  PubMed  Google Scholar 

  69. Moura MM, Cavaco BM, Leite V. RAS proto-oncogene in medullary thyroid carcinoma. Endocr Relat Cancer. 2015;22:R235–52.

    Article  CAS  PubMed  Google Scholar 

  70. Duan K, Hernandez KG, Mete O. Clinicopathologic correlates of hyperparathyroidism. J Clin Pathol. 2015;68:771–87.

    Article  CAS  PubMed  Google Scholar 

  71. Sharretts JM, Simonds WF. Clinical and molecular genetics of parathyroid neoplasms. Best Pract Res Clin Endocrinol Metab. 2010;24:491–502.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Duan K, Mete O. Parathyroid carcinoma: diagnosis and clinical implications. Turk Patoloji Derg. 2015;31(Suppl):80–97.

    PubMed  Google Scholar 

  73. Costa-Guda J, Arnold A. Genetic and epigenetic changes in sporadic endocrine tumors: parathyroid tumors. Mol Cell Endocrinol. 2014;386:46–54.

    Article  CAS  PubMed  Google Scholar 

  74. Verdelli C, Forno I, Vaira V, Corbetta S. Epigenetic alterations in human parathyroid tumors. Endocrine. 2015;49:324–32.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to M. John Hicks MD, DDS, MS, PhD .

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Hicks, M.J. (2018). Salivary Gland, Thyroid, and Parathyroid Neoplasms: Molecular Features. In: Furtado, L., Husain, A. (eds) Precision Molecular Pathology of Neoplastic Pediatric Diseases . Molecular Pathology Library. Springer, Cham. https://doi.org/10.1007/978-3-319-89626-7_11

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