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Cellular and Molecular Pathology of Head and Neck Tumors

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Head and Neck Cancer

Abstract

Head and neck pathology encompasses a multitude of organs of diverse histogenesis. Malignances arising from head and neck sites accordingly are diverse in origins, morphogenesis, and biological behavior. Excluding connective tissue and vascular entities, the main entities that are presented in this chapter include squamous mucosal sites, salivary, thyroid and sinonasal, and skull base tumors. The histopathological classification remains the main reference to the diagnosis and to a large extent, malignancy grading. Advances in immunohistochemical techniques and the development of reagents to cellular intermediate filaments and lineage markers have led to better diagnosis and categorization of undifferentiated entities with overlapping morphologic features. More recently, major strides have been achieved in the molecular genetic characterization and understanding of head and neck tumorigenesis. Although clinically applicable and validated molecular biomarkers have yet to be realized, it is important to address the recent discoveries and their potential integration with the phenotypic and pathologic features. This chapter concisely presents the relevant pathomorphologic and molecular features of the tumors of the major head and neck sites for clinical management.

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References

  1. El-Naggar AK. Pathobiology of head and neck squamous tumorigenesis. Curr Cancer Drug Targets. 2007;7:606–12.

    PubMed  CAS  Google Scholar 

  2. Mao L, El-Naggar AK. Molecular changes in the multistage pathogenesis of head and neck cancer. In: Srivastava S et al., editors. Molecular pathology of early cancer. Amsterdam: IOS; 1999.

    Google Scholar 

  3. Mandal M, Myers JN, Lippman SM, et al. Epithelial to mesenchymal transition in head and neck squamous carcinoma: association of Src activation with E-cadherin down-regulation, vimentin expression, and aggressive tumor features. Cancer. 2008;112:2088–100.

    PubMed  CAS  Google Scholar 

  4. Shear M, Pindborg JJ. Verrucous hyperplasia of the oral mucosa. Cancer. 1980;46:1855–62.

    PubMed  CAS  Google Scholar 

  5. Choi HR, Roberts DB, Johnigan RH, et al. Molecular and clinicopathologic comparisons of head and neck squamous carcinoma variants: common and distinctive features of biological significance. Am J Surg Pathol. 2004;28:1299–310.

    PubMed  Google Scholar 

  6. Begum S, Westra WH. Basaloid squamous cell carcinoma of the head and neck is a mixed variant that can be further resolved by HPV status. Am J Surg Pathol. 2008;32:1044–50.

    PubMed  Google Scholar 

  7. Choi HR, Sturgis EM, Rosenthal DI, et al. Sarcomatoid carcinoma of the head and neck: molecular evidence for evolution and progression from conventional squamous cell carcinomas. Am J Surg Pathol. 2003;27:1216–20.

    PubMed  Google Scholar 

  8. Dahlstrand H, Nasman A, Romanitan M, et al. Human papillomavirus accounts both for increased incidence and better prognosis in tonsillar cancer. Anticancer Res. 2008;28:1133–8.

    PubMed  Google Scholar 

  9. Dahlstrom KR, Adler-Storthz K, Etzel CJ, et al. Human papillomavirus type 16 infection and squamous cell carcinoma of the head and neck in never-smokers: a matched pair analysis. Clin Cancer Res. 2003;9:2620–6.

    PubMed  Google Scholar 

  10. Kumar B, Cordell KG, Lee JS, et al. Response to therapy and outcomes in oropharyngeal cancer are associated with biomarkers including human papillomavirus, epidermal growth factor receptor, gender, and smoking. Int J Radiat Oncol Biol Phys. 2007;69:S109–11.

    PubMed  CAS  Google Scholar 

  11. Nichols AC, Faquin WC, Westra WH, et al. HPV-16 infection predicts treatment outcome in oropharyngeal squamous cell carcinoma. Otolaryngol Head Neck Surg. 2009;140:228–34.

    PubMed  Google Scholar 

  12. Sand L, Jalouli J, Larsson PA, et al. Human papilloma viruses in oral lesions. Anticancer Res. 2000;20:1183–8.

    PubMed  CAS  Google Scholar 

  13. Westra WH, Taube JM, Poeta ML, et al. Inverse relationship between human papillomavirus-16 infection and disruptive p53 gene mutations in squamous cell carcinoma of the head and neck. Clin Cancer Res. 2008;14:366–9.

    PubMed  CAS  Google Scholar 

  14. Barnes L, Eveson JW, Reichart P, et al. World Health Organization classification of tumours. Pathology & genetics. Head and neck tumours. Lyon: IARC; 2005.

    Google Scholar 

  15. Janot F, Klijanienko J, Russo A, et al. Prognostic value of clinicopathological parameters in head and neck squamous cell carcinoma: a prospective analysis. Br J Cancer. 1996;73:531–8.

    PubMed  CAS  Google Scholar 

  16. Braakhuis BJ, Tabor MP, Kummer JA, et al. A genetic explanation of Slaughter’s concept of field cancerization: evidence and clinical implications. Cancer Res. 2003;63:1727–30.

    PubMed  CAS  Google Scholar 

  17. Forastiere A, Koch W, Trotti A, et al. Head and neck cancer. N Engl J Med. 2001;345:1890–900.

    PubMed  CAS  Google Scholar 

  18. Jang SJ, Chiba I, Hirai A, et al. Multiple oral squamous epithelial lesions: are they genetically related? Oncogene. 2001;20:2235–42.

    PubMed  CAS  Google Scholar 

  19. El-Naggar AK, Hurr K, Huff V, et al. Microsatellite instability in preinvasive and invasive head and neck squamous carcinoma. Am J Pathol. 1996;148:2067–72.

    PubMed  CAS  Google Scholar 

  20. El-Naggar AK, Hurr K, Huff V, et al. Allelic loss and replication errors at microsatellite loci on chromosome 11p in head and neck squamous carcinoma: association with aggressive biological features. Clin Cancer Res. 1996;2:903–7.

    PubMed  CAS  Google Scholar 

  21. El-Naggar AK, Hurr K, Luna MA, et al. Intratumoral genetic heterogeneity in primary head and neck squamous carcinoma using microsatellite markers. Diagn Mol Pathol. 1997;6:305–8.

    PubMed  CAS  Google Scholar 

  22. El-Naggar AK, Lai S, Clayman GL, et al. p73 gene alterations and expression in primary oral and laryngeal squamous carcinomas. Carcinogenesis. 2001;22:729–35.

    PubMed  CAS  Google Scholar 

  23. Coombes MM, Briggs KL, Bone JR, et al. Resetting the histone code at CDKN2A in HNSCC by inhibition of DNA methylation. Oncogene. 2003;22:8902–11.

    PubMed  CAS  Google Scholar 

  24. Papadimitrakopoulou VA, Izzo J, Mao L, et al. Cyclin D1 and p16 alterations in advanced premalignant lesions of the upper aerodigestive tract: role in response to chemoprevention and cancer development. Clin Cancer Res. 2001;7:3127–34.

    PubMed  CAS  Google Scholar 

  25. Wang D, Grecula JC, Gahbauer RA, et al. p16 gene alterations in locally advanced squamous cell carcinoma of the head and neck. Oncol Rep. 2006;15:661–5.

    PubMed  CAS  Google Scholar 

  26. Nakahara Y, Shintani S, Mihara M, et al. Alterations of Rb, p16(INK4A) and cyclin D1 in the tumorigenesis of oral squamous cell carcinomas. Cancer Lett. 2000;160:3–8.

    PubMed  CAS  Google Scholar 

  27. Thurfjell N, Coates PJ, Uusitalo T, et al. Complex p63 mRNA isoform expression patterns in squamous cell carcinoma of the head and neck. Int J Oncol. 2004;25:27–35.

    PubMed  CAS  Google Scholar 

  28. Weber A, Bellmann U, Bootz F, et al. Expression of p53 and its homologues in primary and recurrent squamous cell carcinomas of the head and neck. Int J Cancer. 2002;99:22–8.

    PubMed  CAS  Google Scholar 

  29. Maruya S, Issa JP, Weber RS, et al. Differential methylation status of tumor-associated genes in head and neck squamous carcinoma: incidence and potential implications. Clin Cancer Res. 2004;10:3825–30.

    PubMed  CAS  Google Scholar 

  30. Viswanathan M, Tsuchida N, Shanmugam G. Promoter hypermethylation profile of tumor-associated genes p16, p15, hMLH1, MGMT and E-cadherin in oral squamous cell carcinoma. Int J Cancer. 2003;105:41–6.

    PubMed  CAS  Google Scholar 

  31. Chen YJ, Lin SC, Kao T, et al. Genome-wide profiling of oral squamous cell carcinoma. J Pathol. 2004;204:326–32.

    PubMed  CAS  Google Scholar 

  32. Chung CH, Parker JS, Karaca G, et al. Molecular classification of head and neck squamous cell carcinomas using patterns of gene expression. Cancer Cell. 2004;5:489–500.

    PubMed  CAS  Google Scholar 

  33. Giri U, Ashorn CL, Ramdas L, et al. Molecular signatures associated with clinical outcome in patients with high-risk head-and-neck squamous cell carcinoma treated by surgery and radiation. Int J Radiat Oncol Biol Phys. 2006;64:670–7.

    PubMed  CAS  Google Scholar 

  34. Roepman P, Wessels LF, Kettelarij N, et al. An expression profile for diagnosis of lymph node metastases from primary head and neck squamous cell carcinomas. Nat Genet. 2005;37:182–6.

    PubMed  CAS  Google Scholar 

  35. Li J, Huang H, Sun L, et al. MiR-21 indicates poor prognosis in tongue squamous cell carcinomas as an apoptosis inhibitor. Clin Cancer Res. 2009;15:3998–4008.

    PubMed  CAS  Google Scholar 

  36. Ramdas L, Giri U, Ashorn CL, et al. miRNA expression profiles in head and neck squamous cell carcinoma and adjacent normal tissue. Head Neck. 2009;31:642–54.

    PubMed  Google Scholar 

  37. Wong TS, Liu XB, Wong BY, et al. Mature miR-184 as potential oncogenic microRNA of squamous cell carcinoma of tongue. Clin Cancer Res. 2008;14:2588–92.

    PubMed  CAS  Google Scholar 

  38. Hazan RB, Norton L. The epidermal growth factor receptor modulates the interaction of E-cadherin with the actin cytoskeleton. J Biol Chem. 1998;273:9078–84.

    PubMed  CAS  Google Scholar 

  39. Rubin Grandis J, Melhem MF, Gooding WE, et al. Levels of TGF-alpha and EGFR protein in head and neck squamous cell carcinoma and patient survival. J Natl Cancer Inst. 1998;90:824–32.

    PubMed  CAS  Google Scholar 

  40. Temam S, Kawaguchi H, El-Naggar AK, et al. Epidermal growth factor receptor copy number alterations correlate with poor clinical outcome in patients with head and neck squamous cancer. J Clin Oncol. 2007;25:2164–70.

    PubMed  CAS  Google Scholar 

  41. Ang KK, Berkey BA, Tu X, et al. Impact of epidermal growth factor receptor expression on survival and pattern of relapse in patients with advanced head and neck carcinoma. Cancer Res. 2002;62:7350–6.

    PubMed  CAS  Google Scholar 

  42. Gallo O, Franchi A, Magnelli L, et al. Cyclooxygenase-2 pathway correlates with VEGF expression in head and neck cancer. Implications for tumor angiogenesis and metastasis. Neoplasia. 2001;3:53–61.

    PubMed  CAS  Google Scholar 

  43. Janot F, El-Naggar AK, Morrison RS, et al. Expression of basic fibroblast growth factor in squamous cell carcinoma of the head and neck is associated with degree of histologic differentiation. Int J Cancer. 1995;64:117–23.

    PubMed  CAS  Google Scholar 

  44. Joo YH, Jung CK, Kim MS, et al. Relationship between vascular endothelial growth factor and Notch1 expression and lymphatic metastasis in tongue cancer. Otolaryngol Head Neck Surg. 2009;140:512–8.

    PubMed  Google Scholar 

  45. Lopez-Graniel CM, Tamez de Leon D, Meneses-Garcia A, et al. Tumor angiogenesis as a prognostic factor in oral cavity carcinomas. J Exp Clin Cancer Res. 2001;20:463–8.

    PubMed  CAS  Google Scholar 

  46. Montag M, Dyckhoff G, Lohr J, et al. Angiogenic growth factors in tissue homogenates of HNSCC: expression pattern, prognostic relevance, and interrelationships. Cancer Sci. 2009;100:1210–8.

    PubMed  CAS  Google Scholar 

  47. Rafii S, Avecilla ST, Jin DK. Tumor vasculature address book: identification of stage-specific tumor vessel zip codes by phage display. Cancer Cell. 2003;4:331–3.

    PubMed  CAS  Google Scholar 

  48. Schultz-Hector S, Haghayegh S. Beta-fibroblast growth factor expression in human and murine squamous cell carcinomas and its relationship to regional endothelial cell proliferation. Cancer Res. 1993;53:1444–9.

    PubMed  CAS  Google Scholar 

  49. Williams JK, Carlson GW, Cohen C, et al. Tumor angiogenesis as a prognostic factor in oral cavity tumors. Am J Surg. 1994;168:373–80.

    PubMed  CAS  Google Scholar 

  50. Qiu W, Schonleben F, Li X, et al. PIK3CA mutations in head and neck squamous cell carcinoma. Clin Cancer Res. 2006;12:1441–6.

    PubMed  CAS  Google Scholar 

  51. Chan G, Boyle JO, Yang EK, et al. Cyclooxygenase-2 expression is up-regulated in squamous cell carcinoma of the head and neck. Cancer Res. 1999;59:991–4.

    PubMed  CAS  Google Scholar 

  52. Avizienyte E, Wyke AW, Jones RJ, et al. Src-induced de-regulation of E-cadherin in colon cancer cells requires integrin signalling. Nat Cell Biol. 2002;4:632–8.

    PubMed  CAS  Google Scholar 

  53. Batlle E, Sancho E, Franci C, et al. The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat Cell Biol. 2000;2:84–9.

    PubMed  CAS  Google Scholar 

  54. Christiansen JJ, Rajasekaran AK. Reassessing epithelial to mesenchymal transition as a prerequisite for carcinoma invasion and metastasis. Cancer Res. 2006;66:8319–26.

    PubMed  CAS  Google Scholar 

  55. Maeda M, Shintani Y, Wheelock MJ, et al. Src activation is not necessary for transforming growth factor (TGF)-beta-mediated epithelial to mesenchymal transitions (EMT) in mammary epithelial cells. PP1 directly inhibits TGF-beta receptors I and II. J Biol Chem. 2006;281:59–68.

    PubMed  CAS  Google Scholar 

  56. Papadimitrakopoulou VA, Hong WK. Biology of oral premalignant lesions: concepts and implications for chemoprevention. Eur J Cancer Prev. 1996;5 Suppl 2:87–93.

    PubMed  Google Scholar 

  57. Day TA, Deveikis J, Gillespie MB, et al. Salivary gland neoplasms. Curr Treat Options Oncol. 2004;5:11–26.

    PubMed  Google Scholar 

  58. Pinkston JA, Cole P. Incidence rates of salivary gland tumors: results from a population-based study. Otolaryngol Head Neck Surg. 1999;120:834–40.

    PubMed  CAS  Google Scholar 

  59. Speight PM, Barrett AW. Salivary gland tumours. Oral Dis. 2002;8:229–40.

    PubMed  CAS  Google Scholar 

  60. Pinto AE, Fonseca I, Martins C, et al. Objective biologic parameters and their clinical relevance in assessing salivary gland neoplasms. Adv Anat Pathol. 2000;7:294–306.

    PubMed  CAS  Google Scholar 

  61. Luna MA, Batsakis JG, El-Naggar AK. Salivary gland tumors in children. Ann Otol Rhinol Laryngol. 1991;100:869–71.

    PubMed  CAS  Google Scholar 

  62. Shapiro NL, Bhattacharyya N. Clinical characteristics and survival for major salivary gland malignancies in children. Otolaryngol Head Neck Surg. 2006;134:631–4.

    PubMed  Google Scholar 

  63. Wu L, Aster JC, Blacklow SC, et al. MAML1, a human homologue of Drosophila mastermind, is a transcriptional co-activator for NOTCH receptors. Nat Genet. 2000;26:484–9.

    PubMed  CAS  Google Scholar 

  64. Bradley PJ. Recurrent salivary gland pleomporphic adenoma: etiology, management and results. Curr Opin Otolaryngol Head Neck Surg. 2001;9:100–8.

    Google Scholar 

  65. Califano J, Eisele DW. Benign salivary gland neoplasms. Otolaryngol Clin North Am. 1999;32:861–73.

    PubMed  CAS  Google Scholar 

  66. Stennert E, Guntinas-Lichius O, Klussmann JP, et al. Histopathology of pleomorphic adenoma in the parotid gland: a prospective unselected series of 100 cases. Laryngoscope. 2001;111:2195–200.

    PubMed  CAS  Google Scholar 

  67. Gillenwater A, Hurr K, Wolf P, et al. Microsatellite alterations at chromosome 8q loci in pleomorphic adenoma. Otolaryngol Head Neck Surg. 1997;117:448–52.

    PubMed  CAS  Google Scholar 

  68. Declercq J, Van Dyck F, Braem CV, et al. Salivary gland tumors in transgenic mice with targeted PLAG1 proto-oncogene overexpression. Cancer Res. 2005;65:4544–53.

    PubMed  CAS  Google Scholar 

  69. El-Naggar A, Batsakis JG, Kessler S. Benign metastatic mixed tumours or unrecognized salivary carcinomas? J Laryngol Otol. 1988;102:810–2.

    PubMed  CAS  Google Scholar 

  70. Schoenmakers EF, Kools PF, Mols R, et al. Physical mapping of chromosome 12q breakpoints in lipoma, pleomorphic salivary gland adenoma, uterine leiomyoma, and myxoid liposarcoma. Genomics. 1994;20:210–22.

    PubMed  CAS  Google Scholar 

  71. Mark G, Dahlenfors R, Ekedahl C, et al. The mixed salivary gland tumor – a normally benign human neoplasm frequently showing specific chromosome abnormalities. Cancer Genet Cytogenet. 1980;2:231–41.

    Google Scholar 

  72. Leivo I, Jee KJ, Heikinheimo K, et al. Characterization of gene expression in major types of salivary gland carcinomas with epithelial differentiation. Cancer Genet Cytogenet. 2005;156:104–13.

    PubMed  CAS  Google Scholar 

  73. Martins C, Fonseca I, Roque L, et al. PLAG1 gene alterations in salivary gland pleomorphic adenoma and carcinoma ex-pleomorphic adenoma: a combined study using chromosome banding, in situ hybridization and immunocytochemistry. Mod Pathol. 2005;18:1048–55.

    PubMed  CAS  Google Scholar 

  74. Foschini MP, Malvi D, Betts CM. Oncocytic carcinoma arising in Warthin tumour. Virchows Arch. 2005;446:88–90.

    PubMed  Google Scholar 

  75. Enlund F, Behboudi A, Andren Y, et al. Altered Notch signaling resulting from expression of a WAMTP1-MAML2 gene fusion in mucoepidermoid carcinomas and benign Warthin’s tumors. Exp Cell Res. 2004;292:21–8.

    PubMed  CAS  Google Scholar 

  76. Martins C, Fonseca I, Roque L, et al. Cytogenetic characterisation of Warthin’s tumour. Oral Oncol. 1997;33:344–7.

    PubMed  CAS  Google Scholar 

  77. Nordkvist A, Mark J, Dahlenfors R, et al. Cytogenetic observations in 13 cystadenolymphomas (Warthin’s tumors). Cancer Genet Cytogenet. 1994;76:129–35.

    PubMed  CAS  Google Scholar 

  78. Batsakis JG, Luna MA, El-Naggar AK. Basaloid monomorphic adenomas. Ann Otol Rhinol Laryngol. 1991;100:687–90.

    PubMed  CAS  Google Scholar 

  79. Choi HR, Batsakis JG, Callender DL, et al. Molecular analysis of chromosome 16q regions in dermal analogue tumors of salivary glands: a genetic link to dermal cylindroma? Am J Surg Pathol. 2002;26:778–83.

    PubMed  Google Scholar 

  80. el-Naggar AK, Lovell M, Callender DL, et al. Cytogenetic analysis of a primary salivary gland myoepithelioma. Cancer Genet Cytogenet. 1999;113:49–53.

    PubMed  CAS  Google Scholar 

  81. Hungermann D, Roeser K, Buerger H, et al. Relative paucity of gross genetic alterations in myoepitheliomas and myoepithelial carcinomas of salivary glands. J Pathol. 2002;198:487–94.

    PubMed  CAS  Google Scholar 

  82. Magrini E, Pragliola A, Farnedi A, et al. Cytogenetic analysis of myoepithelial cell carcinoma of salivary gland. Virchows Arch. 2004;444:82–6.

    PubMed  Google Scholar 

  83. Bullerdiek J, Haubrich J, Meyer K, et al. Translocation t(11;19)(q21;p13.1) as the sole chromosome abnormality in a cystadenolymphoma (Warthin’s tumor) of the parotid gland. Cancer Genet Cytogenet. 1988;35:129–32.

    PubMed  CAS  Google Scholar 

  84. Dahlenfors R, Wedell B, Rundrantz H, et al. Translocation(11;19)(q14-21;p12) in a parotid mucoepidermoid carcinoma of a child. Cancer Genet Cytogenet. 1995;79:188.

    PubMed  CAS  Google Scholar 

  85. El-Naggar AK, Lovell M, Killary AM, et al. A mucoepidermoid carcinoma of minor salivary gland with t(11;19)(q21;p13.1) as the only karyotypic abnormality. Cancer Genet Cytogenet. 1996;87:29–33.

    PubMed  CAS  Google Scholar 

  86. Nordkvist A, Gustafsson H, Juberg-Ode M, et al. Recurrent rearrangements of 11q14-22 in mucoepidermoid carcinoma. Cancer Genet Cytogenet. 1994;74:77–83.

    PubMed  CAS  Google Scholar 

  87. Komiya T, Park Y, Modi S, et al. Sustained expression of Mect1-Maml2 is essential for tumor cell growth in salivary gland cancers carrying the t(11;19) translocation. Oncogene. 2006;25:6128–32.

    PubMed  CAS  Google Scholar 

  88. Kyakumoto S, Kito N, Sato N. Expression of cAMP response element binding protein (CREB)-binding protein (CBP) and the implication in retinoic acid-inducible transcription activation in human salivary gland adenocarcinoma cell line HSG. Endocr Res. 2003;29:277–89.

    PubMed  CAS  Google Scholar 

  89. Bell DA, Thompson CL, Taylor J, et al. Genetic monitoring of human polymorphic cancer susceptibility genes by polymerase chain reaction: application to glutathione transferase mu. Environ Health Perspect. 1992;98:113–7.

    PubMed  CAS  Google Scholar 

  90. Tirado Y, Williams MD, Hanna EY, et al. CRTC1/MAML2 fusion transcript in high grade mucoepidermoid carcinomas of salivary and thyroid glands and Warthin’s tumors: implications for histogenesis and biologic behavior. Genes Chromosomes Cancer. 2007;46:708–15.

    PubMed  CAS  Google Scholar 

  91. Tonon G, Gehlhaus KS, Yonescu R, et al. Multiple reciprocal translocations in salivary gland mucoepidermoid carcinomas. Cancer Genet Cytogenet. 2004;152:15–22.

    PubMed  CAS  Google Scholar 

  92. Tonon G, Modi S, Wu L, et al. t(11;19)(q21;p13) translocation in mucoepidermoid carcinoma creates a novel fusion product that disrupts a Notch signaling pathway. Nat Genet. 2003;33:208–13.

    PubMed  CAS  Google Scholar 

  93. Lewis JE, Olsen KD, Sebo TJ. Carcinoma ex pleomorphic adenoma: pathologic analysis of 73 cases. Hum Pathol. 2001;32:596–604.

    PubMed  CAS  Google Scholar 

  94. Olsen KD, Lewis JE. Carcinoma ex pleomorphic adenoma: a clinicopathologic review. Head Neck. 2001;23:705–12.

    PubMed  CAS  Google Scholar 

  95. El-Naggar AK, Callender D, Coombes MM, et al. Molecular genetic alterations in carcinoma ex-pleomorphic adenoma: a putative progression model? Genes Chromosomes Cancer. 2000;27:162–8.

    PubMed  CAS  Google Scholar 

  96. el-Naggar AK, Hurr K, Kagan J, et al. Genotypic alterations in benign and malignant salivary gland tumors: histogenetic and clinical implications. Am J Surg Pathol. 1997;21:691–7.

    PubMed  CAS  Google Scholar 

  97. el-Naggar AK, Lovell M, Callender DL, et al. Concurrent cytogenetic, interphase fluorescence in situ hybridization and DNA flow cytometric analyses of a carcinoma ex-pleomorphic adenoma of parotid gland. Cancer Genet Cytogenet. 1998;107:132–6.

    PubMed  CAS  Google Scholar 

  98. Hellquist HB, Karlsson MG, Nilsson C. Salivary duct carcinoma – a highly aggressive salivary gland tumour with overexpression of c-erbB-2. J Pathol. 1994;172:35–44.

    PubMed  CAS  Google Scholar 

  99. Johns 3rd MM, Westra WH, Califano JA, et al. Allelotype of salivary gland tumors. Cancer Res. 1996;56:1151–4.

    PubMed  CAS  Google Scholar 

  100. Williams MD, Chakravarti N, Kies MS, et al. Implications of methylation patterns of cancer genes in salivary gland tumors. Clin Cancer Res. 2006;12:7353–8.

    PubMed  CAS  Google Scholar 

  101. Williams MD, Roberts D, Blumenschein Jr GR, et al. Differential expression of hormonal and growth factor receptors in salivary duct carcinomas: biologic significance and potential role in therapeutic stratification of patients. Am J Surg Pathol. 2007;31:1645–52.

    PubMed  Google Scholar 

  102. Batsakis JG, Luna MA, El-Naggar AK. Histopathologic grading of salivary gland neoplasms: III. Adenoid cystic carcinomas. Ann Otol Rhinol Laryngol. 1990;99:1007–9.

    PubMed  CAS  Google Scholar 

  103. Kasamatsu A, Endo Y, Uzawa K, et al. Identification of candidate genes associated with salivary adenoid cystic carcinomas using combined comparative genomic hybridization and oligonucleotide microarray analyses. Int J Biochem Cell Biol. 2005;37:1869–80.

    PubMed  CAS  Google Scholar 

  104. Fordice J, Kershaw C, El-Naggar A, et al. Adenoid cystic carcinoma of the head and neck: predictors of morbidity and mortality. Arch Otolaryngol Head Neck Surg. 1999;125:149–52.

    PubMed  CAS  Google Scholar 

  105. Freier K, Flechtenmacher C, Walch A, et al. Copy number gains on 22q13 in adenoid cystic carcinoma of the salivary gland revealed by comparative genomic hybridization and tissue microarray analysis. Cancer Genet Cytogenet. 2005;159:89–95.

    PubMed  CAS  Google Scholar 

  106. Holst VA, Marshall CE, Moskaluk CA, et al. KIT protein expression and analysis of c-kit gene mutation in adenoid cystic carcinoma. Mod Pathol. 1999;12:956–60.

    PubMed  CAS  Google Scholar 

  107. Rutherford S, Yu Y, Rumpel CA, et al. Chromosome 6 deletion and candidate tumor suppressor genes in adenoid cystic carcinoma. Cancer Lett. 2006;236:309–17.

    PubMed  CAS  Google Scholar 

  108. Sandros J, Mark J, Happonen RP, et al. Specificity of 6q- markers and other recurrent deviations in human malignant salivary gland tumors. Anticancer Res. 1988;8:637–43.

    PubMed  CAS  Google Scholar 

  109. Stallmach I, Zenklusen P, Komminoth P, et al. Loss of heterozygosity at chromosome 6q23-25 correlates with clinical and histologic parameters in salivary gland adenoid cystic carcinoma. Virchows Arch. 2002;440:77–84.

    PubMed  CAS  Google Scholar 

  110. Jeng YM, Lin CY, Hsu HC. Expression of the c-kit protein is associated with certain subtypes of salivary gland carcinoma. Cancer Lett. 2000;154:107–11.

    PubMed  CAS  Google Scholar 

  111. Patel KJ, Pambuccian SE, Ondrey FG, et al. Genes associated with early development, apoptosis and cell cycle regulation define a gene expression profile of adenoid cystic carcinoma. Oral Oncol. 2006;42:994–1004.

    PubMed  CAS  Google Scholar 

  112. Queimado L, Reis A, Fonseca I, et al. A refined localization of two deleted regions in chromosome 6q associated with salivary gland carcinomas. Oncogene. 1998;16:83–8.

    PubMed  CAS  Google Scholar 

  113. Batsakis JG, Luna MA, El-Naggar AK. Histopathologic grading of salivary gland neoplasms: II. Acinic cell carcinomas. Ann Otol Rhinol Laryngol. 1990;99:929–33.

    PubMed  CAS  Google Scholar 

  114. Lewis JE, Olsen KD, Weiland LH. Acinic cell carcinoma. Clinicopathologic review. Cancer. 1991;67:172–9.

    PubMed  CAS  Google Scholar 

  115. el-Naggar AK, Abdul-Karim FW, Hurr K, et al. Genetic alterations in acinic cell carcinoma of the parotid gland determined by microsatellite analysis. Cancer Genet Cytogenet. 1998;102:19–24.

    PubMed  CAS  Google Scholar 

  116. Edwards PC, Bhuiya T, Kelsch RD. Assessment of p63 expression in the salivary gland neoplasms adenoid cystic carcinoma, polymorphous low-grade adenocarcinoma, and basal cell and canalicular adenomas. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004;97:613–9.

    PubMed  Google Scholar 

  117. Jin C, Jin Y, Hoglund M, et al. Cytogenetic and molecular genetic demonstration of polyclonality in an acinic cell carcinoma. Br J Cancer. 1998;78:292–5.

    PubMed  CAS  Google Scholar 

  118. Kishi M, Nakamura M, Nishimine M, et al. Genetic and epigenetic alteration profiles for multiple genes in salivary gland carcinomas. Oral Oncol. 2005;41:161–9.

    PubMed  CAS  Google Scholar 

  119. Maruya S, Kim HW, Weber RS, et al. Gene expression screening of salivary gland neoplasms: molecular markers of potential histogenetic and clinical significance. J Mol Diagn. 2004;6:180–90.

    PubMed  CAS  Google Scholar 

  120. DeLellis R, Lloyd R, Heitz P, et al. Pathology and genetics of tumors of endocrine origin. Lyon: IARC; 2004.

    Google Scholar 

  121. Giuffrida D, Gharib H. Anaplastic thyroid carcinoma: current diagnosis and treatment. Ann Oncol. 2000;11:1083–9.

    PubMed  CAS  Google Scholar 

  122. Pulcrano M, Boukheris H, Talbot M, et al. Poorly differentiated follicular thyroid carcinoma: prognostic factors and relevance of histological classification. Thyroid. 2007;17:639–46.

    PubMed  Google Scholar 

  123. Kebebew E, Ituarte PH, Siperstein AE, et al. Medullary thyroid carcinoma: clinical characteristics, treatment, prognostic factors, and a comparison of staging systems. Cancer. 2000;88:1139–48.

    PubMed  CAS  Google Scholar 

  124. Kondo T, Ezzat S, Asa SL. Pathogenetic mechanisms in thyroid follicular-cell neoplasia. Nat Rev Cancer. 2006;6:292–306.

    PubMed  CAS  Google Scholar 

  125. LiVolsi VA, Baloch ZW. Follicular neoplasms of the thyroid: view, biases, and experiences. Adv Anat Pathol. 2004;11:279–87.

    PubMed  Google Scholar 

  126. Lloyd RV, Erickson LA, Casey MB, et al. Observer variation in the diagnosis of follicular variant of papillary thyroid carcinoma. Am J Surg Pathol. 2004;28:1336–40.

    PubMed  Google Scholar 

  127. Abboud B, Sleilaty G, Helou E, et al. Existence and anatomic distribution of double parathyroid adenoma. Laryngoscope. 2005;115:1128–31.

    PubMed  Google Scholar 

  128. Assaad A, Voeghtly L, Hunt JL. Thyroidectomies from patients with history of therapeutic radiation during childhood and adolescence have a unique mutational profile. Mod Pathol. 2008;21:1176–82.

    PubMed  CAS  Google Scholar 

  129. Lima J, Trovisco V, Soares P, et al. BRAF mutations are not a major event in post-Chernobyl childhood thyroid carcinomas. J Clin Endocrinol Metab. 2004;89:4267–71.

    PubMed  CAS  Google Scholar 

  130. Nikiforov YE. Radiation-induced thyroid cancer: what we have learned from chernobyl. Endocr Pathol. 2006;17:307–17.

    PubMed  CAS  Google Scholar 

  131. Bartolazzi A, D’Alessandria C, Parisella MG, et al. Thyroid cancer imaging in vivo by targeting the anti-apoptotic molecule galectin-3. PLoS One. 2008;3:e3768.

    PubMed  Google Scholar 

  132. Hofman V, Lassalle S, Bonnetaud C, et al. Thyroid tumours of uncertain malignant potential: frequency and diagnostic reproducibility. Virchows Arch. 2009;455:21–33.

    PubMed  CAS  Google Scholar 

  133. Mehrotra P, Okpokam A, Bouhaidar R, et al. Galectin-3 does not reliably distinguish benign from malignant thyroid neoplasms. Histopathology. 2004;45:493–500.

    PubMed  CAS  Google Scholar 

  134. Baloch ZW, LiVolsi VA. Our approach to follicular-patterned lesions of the thyroid. J Clin Pathol. 2007;60:244–50.

    PubMed  Google Scholar 

  135. Bartolazzi A, Gasbarri A, Papotti M, et al. Application of an immunodiagnostic method for improving preoperative diagnosis of nodular thyroid lesions. Lancet. 2001;357:1644–50.

    PubMed  CAS  Google Scholar 

  136. Vasko VV, Gaudart J, Allasia C, et al. Thyroid follicular adenomas may display features of follicular carcinoma and follicular variant of papillary carcinoma. Eur J Endocrinol. 2004;151:779–86.

    PubMed  CAS  Google Scholar 

  137. Rosai J, Kuhn E, Carcangiu ML. Pitfalls in thyroid tumour pathology. Histopathology. 2006;49:107–20.

    PubMed  CAS  Google Scholar 

  138. Sobrinho-Simoes M, Magalhaes J, Fonseca E, et al. Diagnostic pitfalls of thyroid pathology. Curr Diagn Pathol. 2005;11:52–9.

    Google Scholar 

  139. Suster S. Thyroid tumours with a follicular growth pattern: problems in differential diagnosis. Arch Pathol Lab Med. 2006;130:984–8.

    PubMed  Google Scholar 

  140. Evans HL. Follicular neoplasms of the thyroid. A study of 44 cases followed for a minimum of 10 years, with emphasis on differential diagnosis. Cancer. 1984;54:535–40.

    PubMed  CAS  Google Scholar 

  141. Hirokawa M, Carney JA, Goellner JR, et al. Observer variation of encapsulated follicular lesions of the thyroid gland. Am J Surg Pathol. 2002;26:1508–14.

    PubMed  Google Scholar 

  142. Bongarzone I, Vigneri P, Mariani L, et al. RET/NTRK1 rearrangements in thyroid gland tumors of the papillary carcinoma family: correlation with clinicopathological features. Clin Cancer Res. 1998;4:223–8.

    PubMed  CAS  Google Scholar 

  143. Castellone MD, Santoro M. Dysregulated RET signaling in thyroid cancer. Endocrinol Metab Clin North Am. 2008;37:363–74. viii.

    PubMed  CAS  Google Scholar 

  144. Fonseca E, Soares P, Cardoso-Oliveira M, et al. Diagnostic criteria in well-differentiated thyroid carcinomas. Endocr Pathol. 2006;17:109–17.

    PubMed  CAS  Google Scholar 

  145. Fagin JA, Matsuo K, Karmakar A, et al. High prevalence of mutations of the p53 gene in poorly differentiated human thyroid carcinomas. J Clin Invest. 1993;91:179–84.

    PubMed  CAS  Google Scholar 

  146. Wang HM, Huang YW, Huang JS, et al. Anaplastic carcinoma of the thyroid arising more often from follicular carcinoma than papillary carcinoma. Ann Surg Oncol. 2007;14:3011–8.

    PubMed  Google Scholar 

  147. Wiseman SM, Loree TR, Hicks Jr WL, et al. Anaplastic thyroid cancer evolved from papillary carcinoma: demonstration of anaplastic transformation by means of the inter-simple sequence repeat polymerase chain reaction. Arch Otolaryngol Head Neck Surg. 2003;129:96–100.

    PubMed  Google Scholar 

  148. Collini P, Sampietro G, Pilotti S. Extensive vascular invasion is a marker of risk of relapse in encapsulated non-Hurthle cell follicular carcinoma of the thyroid gland: a clinicopathological study of 18 consecutive cases from a single institution with a 11-year median follow-up. Histopathology. 2004;44:35–9.

    PubMed  CAS  Google Scholar 

  149. Cornett WR, Sharma AK, Day TA, et al. Anaplastic thyroid carcinoma: an overview. Curr Oncol Rep. 2007;9:152–8.

    PubMed  Google Scholar 

  150. Hunt J. Understanding the genotype of follicular thyroid tumors. Endocr Pathol. 2005;16:311–21.

    PubMed  CAS  Google Scholar 

  151. DeLellis RA. Pathology and genetics of thyroid carcinoma. J Surg Oncol. 2006;94:662–9.

    PubMed  CAS  Google Scholar 

  152. Dvorakova S, Vaclavikova E, Sykorova V, et al. Somatic mutations in the RET proto-oncogene in sporadic medullary thyroid carcinomas. Mol Cell Endocrinol. 2008;284:21–7.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  154. Cheung L, Messina M, Gill A, et al. Detection of the PAX8-PPAR gamma fusion oncogene in both follicular thyroid carcinomas and adenomas. J Clin Endocrinol Metab. 2003;88:354–7.

    PubMed  CAS  Google Scholar 

  155. Di Cristofaro J, Marcy M, Vasko V, et al. Molecular genetic study comparing follicular variant versus classic papillary thyroid carcinomas: association of N-ras mutation in codon 61 with follicular variant. Hum Pathol. 2006;37:824–30.

    PubMed  Google Scholar 

  156. Garcia-Rostan G, Zhao H, Camp RL, et al. ras mutations are associated with aggressive tumor phenotypes and poor prognosis in thyroid cancer. J Clin Oncol. 2003;21:3226–35.

    PubMed  CAS  Google Scholar 

  157. Nakamura N, Erickson LA, Jin L, et al. Immunohistochemical separation of follicular variant of papillary thyroid carcinoma from follicular adenoma. Endocr Pathol. 2006;17:213–23.

    PubMed  CAS  Google Scholar 

  158. Castro P, Rebocho AP, Soares RJ, et al. PAX8-PPARgamma rearrangement is frequently detected in the follicular variant of papillary thyroid carcinoma. J Clin Endocrinol Metab. 2006;91:213–20.

    PubMed  CAS  Google Scholar 

  159. Kroll TG, Sarraf P, Pecciarini L, et al. PAX8-PPARgamma1 fusion oncogene in human thyroid carcinoma [corrected]. Science. 2000;289:1357–60.

    PubMed  CAS  Google Scholar 

  160. Lui WO, Foukakis T, Liden J, et al. Expression profiling reveals a distinct transcription signature in follicular thyroid carcinomas with a PAX8-PPAR(gamma) fusion oncogene. Oncogene. 2005;24:1467–76.

    PubMed  CAS  Google Scholar 

  161. Nakabashi CC, Guimaraes GS, Michaluart Jr P, et al. The expression of PAX8-PPARgamma rearrangements is not specific to follicular thyroid carcinoma. Clin Endocrinol (Oxf). 2004;61:280–2.

    CAS  Google Scholar 

  162. Nikiforova MN, Biddinger PW, Caudill CM, et al. PAX8-PPARgamma rearrangement in thyroid tumors: RT-PCR and immunohistochemical analyses. Am J Surg Pathol. 2002;26:1016–23.

    PubMed  Google Scholar 

  163. Kebebew E, Weng J, Bauer J, et al. The prevalence and prognostic value of BRAF mutation in thyroid cancer. Ann Surg. 2007;246:466–70. discussion 470–1.

    PubMed  Google Scholar 

  164. Lee JH, Lee ES, Kim YS. Clinicopathologic significance of BRAF V600E mutation in papillary carcinomas of the thyroid: a meta-analysis. Cancer. 2007;110:38–46.

    PubMed  Google Scholar 

  165. Mitsiades CS, Negri J, McMullan C, et al. Targeting BRAFV600E in thyroid carcinoma: therapeutic implications. Mol Cancer Ther. 2007;6:1070–8.

    PubMed  CAS  Google Scholar 

  166. Trovisco V, Vieira de Castro I, Soares P, et al. BRAF mutations are associated with some histological types of papillary thyroid carcinoma. J Pathol. 2004;202:247–51.

    PubMed  CAS  Google Scholar 

  167. Elisei R, Cosci B, Romei C, 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;93:682–7.

    PubMed  CAS  Google Scholar 

  168. Fenton CL, Lukes Y, Nicholson D, et al. The ret/PTC mutations are common in sporadic papillary thyroid carcinoma of children and young adults. J Clin Endocrinol Metab. 2000;85:1170–5.

    PubMed  CAS  Google Scholar 

  169. Fusco A, Chiappetta G, Hui P, et al. Assessment of RET/PTC oncogene activation and clonality in thyroid nodules with incomplete morphological evidence of papillary carcinoma: a search for the early precursors of papillary cancer. Am J Pathol. 2002;160:2157–67.

    PubMed  CAS  Google Scholar 

  170. Gujral TS, van Veelen W, Richardson DS, et al. A novel RET kinase-beta-catenin signaling pathway contributes to tumorigenesis in thyroid carcinoma. Cancer Res. 2008;68:1338–46.

    PubMed  CAS  Google Scholar 

  171. Soares P, Fonseca E, Wynford-Thomas D, et al. Sporadic ret-rearranged papillary carcinoma of the thyroid: a subset of slow growing, less aggressive thyroid neoplasms? J Pathol. 1998;185:71–8.

    PubMed  CAS  Google Scholar 

  172. Elisei R, Romei C, Cosci B, et al. RET genetic screening in patients with medullary thyroid cancer and their relatives: experience with 807 individuals at one center. J Clin Endocrinol Metab. 2007;92:4725–9.

    PubMed  CAS  Google Scholar 

  173. Grieco M, Santoro M, Berlingieri MT, et al. PTC is a novel rearranged form of the ret proto-oncogene and is frequently detected in vivo in human thyroid papillary carcinomas. Cell. 1990;60:557–63.

    PubMed  CAS  Google Scholar 

  174. Jhiang SM, Caruso DR, Gilmore E, et al. Detection of the PTC/retTPC oncogene in human thyroid cancers. Oncogene. 1992;7:1331–7.

    PubMed  CAS  Google Scholar 

  175. Hunt JL, Tometsko M, LiVolsi VA, et al. Molecular evidence of anaplastic transformation in coexisting well-differentiated and anaplastic carcinomas of the thyroid. Am J Surg Pathol. 2003;27:1559–64.

    PubMed  Google Scholar 

  176. Nikiforov YE. Genetic alterations involved in the transition from well-differentiated to poorly differentiated and anaplastic thyroid carcinomas. Endocr Pathol. 2004;15:319–27.

    PubMed  CAS  Google Scholar 

  177. Wiseman SM, Griffith OL, Deen S, et al. Identification of molecular markers altered during transformation of differentiated into anaplastic thyroid carcinoma. Arch Surg. 2007;142:717–27. discussion 727–9.

    PubMed  CAS  Google Scholar 

  178. Barden CB, Shister KW, Zhu B, et al. Classification of follicular thyroid tumors by molecular signature: results of gene profiling. Clin Cancer Res. 2003;9:1792–800.

    PubMed  CAS  Google Scholar 

  179. Bartolazzi A, Orlandi F, Saggiorato E, et al. Galectin-3-expression analysis in the surgical selection of follicular thyroid nodules with indeterminate fine-needle aspiration cytology: a prospective multicentre study. Lancet Oncol. 2008;9:543–9.

    PubMed  CAS  Google Scholar 

  180. Chevillard S, Ugolin N, Vielh P, et al. Gene expression profiling of differentiated thyroid neoplasms: diagnostic and clinical implications. Clin Cancer Res. 2004;10:6586–97.

    PubMed  CAS  Google Scholar 

  181. Rodrigues RF, Roque L, Krug T, et al. Poorly differentiated and anaplastic thyroid carcinomas: chromosomal and oligo-array profile of five new cell lines. Br J Cancer. 2007;96:1237–45.

    PubMed  CAS  Google Scholar 

  182. Vasko V, Espinosa AV, Scouten W, et al. Gene expression and functional evidence of epithelial-to-mesenchymal transition in papillary thyroid carcinoma invasion. Proc Natl Acad Sci USA. 2007;104:2803–8.

    PubMed  CAS  Google Scholar 

  183. Zhu Z, Gandhi M, Nikiforova MN, et al. Molecular profile and clinical-pathologic features of the follicular variant of papillary thyroid carcinoma. An unusually high prevalence of ras mutations. Am J Clin Pathol. 2003;120:71–7.

    PubMed  CAS  Google Scholar 

  184. Sanjuan X, Bryant BR, Sobel ME, et al. Clonality analysis of benign parathyroid lesions by Human Androgen Receptor (HUMARA) Gene Assay. Endocr Pathol. 1998;9:293–300.

    PubMed  Google Scholar 

  185. Scarpelli D, D’Aloiso L, Arturi F, et al. Novel somatic MEN1 gene alterations in sporadic primary hyperparathyroidism and correlation with clinical characteristics. J Endocrinol Invest. 2004;27:1015–21.

    PubMed  CAS  Google Scholar 

  186. Shan L, Nakamura M, Nakamura Y, et al. Comparative analysis of clonality and pathology in primary and secondary hyperparathyroidism. Virchows Arch. 1997;430:247–51.

    PubMed  CAS  Google Scholar 

  187. Sinha S, Sinha A, McPherson GA. Synchronous sporadic carcinoma and primary hyperplasia of the parathyroid glands: a case report and review of the literature. Int J Surg Pathol. 2006;14:336–9.

    PubMed  CAS  Google Scholar 

  188. DeLellis RA, Mazzaglia P, Mangray S. Primary hyperparathyroidism: a current perspective. Arch Pathol Lab Med. 2008;132:1251–62.

    PubMed  Google Scholar 

  189. Carneiro-Pla DM, Romaguera R, Nadji M, et al. Does histopathology predict parathyroid hypersecretion and influence correctly the extent of parathyroidectomy in patients with sporadic primary hyperparathyroidism? Surgery. 2007;142:930–5. discussion 930–5.

    PubMed  Google Scholar 

  190. Lumachi F, Basso SM, Basso U. Parathyroid cancer: etiology, clinical presentation and treatment. Anticancer Res. 2006;26:4803–7.

    PubMed  CAS  Google Scholar 

  191. Cetani F, Pardi E, Viacava P, et al. A reappraisal of the Rb1 gene abnormalities in the diagnosis of parathyroid cancer. Clin Endocrinol (Oxf). 2004;60:99–106.

    CAS  Google Scholar 

  192. Cryns VL, Thor A, Xu HJ, et al. Loss of the retinoblastoma tumor-suppressor gene in parathyroid carcinoma. N Engl J Med. 1994;330:757–61.

    PubMed  CAS  Google Scholar 

  193. Dotzenrath C, Teh BT, Farnebo F, et al. Allelic loss of the retinoblastoma tumor suppressor gene: a marker for aggressive parathyroid tumors? J Clin Endocrinol Metab. 1996;81:3194–6.

    PubMed  CAS  Google Scholar 

  194. Dwight T, Nelson AE, Theodosopoulos G, et al. Independent genetic events associated with the development of multiple parathyroid tumors in patients with primary hyperparathyroidism. Am J Pathol. 2002;161:1299–306.

    PubMed  CAS  Google Scholar 

  195. Miedlich S, Krohn K, Lamesch P, et al. Frequency of somatic MEN1 gene mutations in monoclonal parathyroid tumours of patients with primary hyperparathyroidism. Eur J Endocrinol. 2000;143:47–54.

    PubMed  CAS  Google Scholar 

  196. Morrison C, Farrar W, Kneile J, et al. Molecular classification of parathyroid neoplasia by gene expression profiling. Am J Pathol. 2004;165:565–76.

    PubMed  CAS  Google Scholar 

  197. Cetani F, Ambrogini E, Viacava P, et al. Should parafibromin staining replace HRTP2 gene analysis as an additional tool for histologic diagnosis of parathyroid carcinoma? Eur J Endocrinol. 2007;156:547–54.

    PubMed  CAS  Google Scholar 

  198. Gill AJ, Clarkson A, Gimm O, et al. Loss of nuclear expression of parafibromin distinguishes parathyroid carcinomas and hyperparathyroidism-jaw tumor (HPT-JT) syndrome-related adenomas from sporadic parathyroid adenomas and hyperplasias. Am J Surg Pathol. 2006;30:1140–9.

    PubMed  Google Scholar 

  199. Juhlin CC, Villablanca A, Sandelin K, et al. Parafibromin immunoreactivity: its use as an additional diagnostic marker for parathyroid tumor classification. Endocr Relat Cancer. 2007;14:501–12.

    PubMed  CAS  Google Scholar 

  200. Cetani F, Pardi E, Ambrogini E, et al. Different somatic alterations of the HRPT2 gene in a patient with recurrent sporadic primary hyperparathyroidism carrying an HRPT2 germline mutation. Endocr Relat Cancer. 2007;14:493–9.

    PubMed  CAS  Google Scholar 

  201. Cordes B, Williams MD, Tirado Y, et al. Molecular and phenotypic analysis of poorly differentiated sinonasal neoplasms: an integrated approach for early diagnosis and classification. Hum Pathol. 2009;40:283–92.

    PubMed  CAS  Google Scholar 

  202. Wenig BM. Undifferentiated malignant neoplasms of the sinonasal tract. Arch Pathol Lab Med. 2009;133:699–712.

    PubMed  Google Scholar 

  203. Califano J, Koch W, Sidransky D, et al. Inverted sinonasal papilloma: a molecular genetic appraisal of its putative status as a Precursor to squamous cell carcinoma. Am J Pathol. 2000;156:333–7.

    PubMed  CAS  Google Scholar 

  204. Choi HR, Sturgis EM, Rashid A, et al. Sinonasal adenocarcinoma: evidence for histogenetic divergence of the enteric and nonenteric phenotypes. Hum Pathol. 2003;34:1101–7.

    PubMed  Google Scholar 

  205. Luna MA. Sinonasal tubulopapillary low-grade adenocarcinoma: a specific diagnosis or just another seromucous adenocarcinoma? Adv Anat Pathol. 2005;12:109–15.

    PubMed  Google Scholar 

  206. Orvidas LJ, Lewis JE, Weaver AL, et al. Adenocarcinoma of the nose and paranasal sinuses: a retrospective study of diagnosis, histologic characteristics, and outcomes in 24 patients. Head Neck. 2005;27:370–5.

    PubMed  Google Scholar 

  207. Skalova A, Cardesa A, Leivo I, et al. Sinonasal tubulopapillary low-grade adenocarcinoma. Histopathological, immunohistochemical and ultrastructural features of poorly recognised entity. Virchows Arch. 2003;443:152–8.

    PubMed  CAS  Google Scholar 

  208. Yom SS, Rashid A, Rosenthal DI, et al. Genetic analysis of sinonasal adenocarcinoma phenotypes: distinct alterations of histogenetic significance. Mod Pathol. 2005;18:315–9.

    PubMed  CAS  Google Scholar 

  209. Stelow EB, Mills SE. Squamous cell carcinoma variants of the upper aerodigestive tract. Am J Clin Pathol. 2005;124(Suppl):S96–109.

    PubMed  Google Scholar 

  210. Carbone A, Gloghini A, Rinaldo A, et al. True identity by immunohistochemistry and molecular morphology of undifferentiated malignancies of the head and neck. Head Neck. 2009;31:949–61.

    PubMed  Google Scholar 

  211. Cerilli LA, Holst VA, Brandwein MS, et al. Sinonasal undifferentiated carcinoma: immunohistochemical profile and lack of EBV association. Am J Surg Pathol. 2001;25:156–63.

    PubMed  CAS  Google Scholar 

  212. Lee DH, Cho HH, Cho YB. Typical carcinoid tumor of the nasal cavity. Auris Nasus Larynx. 2007;34:537–9.

    PubMed  Google Scholar 

  213. Lin IH, Hwang CF, Huang HY, et al. Small cell carcinoma of the nasopharynx. Acta Otolaryngol. 2007;127:206–8.

    PubMed  Google Scholar 

  214. Milroy CM, Ferlito A. Immunohistochemical markers in the diagnosis of neuroendocrine neoplasms of the head and neck. Ann Otol Rhinol Laryngol. 1995;104:413–8.

    PubMed  CAS  Google Scholar 

  215. Bourne TD, Bellizzi AM, Stelow EB, et al. p63 Expression in olfactory neuroblastoma and other small cell tumors of the sinonasal tract. Am J Clin Pathol. 2008;130:213–8.

    PubMed  Google Scholar 

  216. Fujimura Y, Ohno T, Siddique H, et al. The EWS-ATF-1 gene involved in malignant melanoma of soft parts with t(12;22) chromosome translocation, encodes a constitutive transcriptional activator. Oncogene. 1996;12:159–67.

    PubMed  CAS  Google Scholar 

  217. Kumar S, Perlman E, Pack S, et al. Absence of EWS/FLI1 fusion in olfactory neuroblastomas indicates these tumors do not belong to the Ewing’s sarcoma family. Hum Pathol. 1999;30:1356–60.

    PubMed  CAS  Google Scholar 

  218. Babin E, Rouleau V, Vedrine PO, et al. Small cell neuroendocrine carcinoma of the nasal cavity and paranasal sinuses. J Laryngol Otol. 2006;120:289–97.

    PubMed  CAS  Google Scholar 

  219. Brissett AE, Olsen KD, Kasperbauer JL, et al. Merkel cell carcinoma of the head and neck: a retrospective case series. Head Neck. 2002;24:982–8.

    PubMed  Google Scholar 

  220. Gardner LJ, Ayala AG, Monforte HL, et al. Ewing sarcoma/peripheral primitive neuroectodermal tumor: adult abdominal tumors with an Ewing sarcoma gene rearrangement demonstrated by fluorescence in situ hybridization in paraffin sections. Appl Immunohistochem Mol Morphol. 2004;12:160–5.

    PubMed  Google Scholar 

  221. Qian X, Jin L, Shearer BM, et al. Molecular diagnosis of Ewing’s sarcoma/primitive neuroectodermal tumor in formalin-fixed paraffin-embedded tissues by RT-PCR and fluorescence in situ hybridization. Diagn Mol Pathol. 2005;14:23–8.

    PubMed  CAS  Google Scholar 

  222. Chang AE, Karnell LH, Menck HR. The National Cancer Data Base report on cutaneous and noncutaneous melanoma: a summary of 84,836 cases from the past decade. The American College of Surgeons Commission on Cancer and the American Cancer Society. Cancer. 1998;83:1664–78.

    PubMed  CAS  Google Scholar 

  223. Conley J, Pack GT. Melanoma of the mucous membranes of the head and neck. Arch Otolaryngol. 1974;99:315–9.

    PubMed  CAS  Google Scholar 

  224. Lentsch EJ, Myers JN. Melanoma of the head and neck: current concepts in diagnosis and management. Laryngoscope. 2001;111:1209–22.

    PubMed  CAS  Google Scholar 

  225. Medina JE, Ferlito A, Pellitteri PK, et al. Current management of mucosal melanoma of the head and neck. J Surg Oncol. 2003;83:116–22.

    PubMed  Google Scholar 

  226. Smith SL, Hessel AC, Luna MA, et al. Sinonasal teratocarcinosarcoma of the head and neck: a report of 10 patients treated at a single institution and comparison with reported series. Arch Otolaryngol Head Neck Surg. 2008;134:592–5.

    PubMed  Google Scholar 

  227. Campo E, Cardesa A, Alos L, et al. Non-Hodgkin’s lymphomas of nasal cavity and paranasal sinuses. An immunohistochemical study. Am J Clin Pathol. 1991;96:184–90.

    PubMed  CAS  Google Scholar 

  228. Carbone A, Gloghini A, Dotti G. EBV-associated lymphoproliferative disorders: classification and treatment. Oncologist. 2008;13:577–85.

    PubMed  Google Scholar 

  229. Chan J, Jafe E, Ralfkiaer E. Extranodal NK/T-cell lymphoma, nasal type. Lyon: IARC; 2001.

    Google Scholar 

  230. Fellbaum C, Hansmann ML, Lennert K. Malignant lymphomas of the nasal cavity and paranasal sinuses. Virchows Arch A Pathol Anat Histopathol. 1989;414:399–405.

    PubMed  CAS  Google Scholar 

  231. Vidal RW, Devaney K, Ferlito A, et al. Sinonasal malignant lymphomas: a distinct clinicopathological category. Ann Otol Rhinol Laryngol. 1999;108:411–9.

    PubMed  CAS  Google Scholar 

  232. Hill DA, O’Sullivan MJ, Zhu X, et al. Practical application of molecular genetic testing as an aid to the surgical pathologic diagnosis of sarcomas: a prospective study. Am J Surg Pathol. 2002;26:965–77.

    PubMed  Google Scholar 

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El-Naggar, A.K. (2011). Cellular and Molecular Pathology of Head and Neck Tumors. In: Bernier, J. (eds) Head and Neck Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-9464-6_3

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