Poorly Differentiated and Undifferentiated Thyroid Carcinomas

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


The definition of poorly differentiated thyroid carcinoma has been the source of great controversy in the pathology literature.1 Many definitions and schemes have been proposed, but little consensus exists about what defines a poorly differentiated thyroid carcinoma (PDTCA). Because of this, the clinical behavior is not well defined and the clinicopathologic features affecting prognosis remain largely unknown.


Thyroid Carcinoma Papillary Carcinoma Differentiate Thyroid Carcinoma Anaplastic Thyroid Carcinoma Hurthle Cell Carcinoma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Volante M, Collini P, Nikiforov Y, et al. Poorly differentiated thyroid carcinoma: the Turin proposal for the use of uniform diagnostic criteria and an algorithmic diagnostic approach. Am J Surg Pathol. 2007;31(8):1256–1264.CrossRefPubMedGoogle Scholar
  2. 2.
    Cady B. Hayes Martin Lecture. Our AMES is true: how an old concept still hits the mark: or, risk group assignment points the arrow to rational therapy selection in differentiated thyroid cancer. Am J Surg. 1997;174(5):462–468.CrossRefPubMedGoogle Scholar
  3. 3.
    Akslen LA, LiVolsi VA. Poorly differentiated thyroid carcinoma - it is important. Am J Surg Pathol. 2000;24(2):310–313.CrossRefPubMedGoogle Scholar
  4. 4.
    Patel KN, Shaha AR. Locally advanced thyroid cancer. Curr Opin Otolaryngol Head Neck Surg. 2005;13(2):112–116.CrossRefPubMedGoogle Scholar
  5. 5.
    Haq M, Harmer C. Differentiated thyroid carcinoma with distant metastases at presentation: prognostic factors and outcome. Clin Endocrinol. 2005;63(1):87–93.CrossRefGoogle Scholar
  6. 6.
    Volante M, Landolfi S, Chiusa P, et al. Poorly differentiated carcinomas of the thyroid with trabecular, insular, and solid patterns: a clinicopathologic study of 183 patients. Cancer. 2004;100(5):950–957.CrossRefPubMedGoogle Scholar
  7. 7.
    Nishiyama RH. Another dissertation on poorly differentiated carcinomas: is it really necessary? Adv Anat Pathol. 1999;6(5):281–286.CrossRefPubMedGoogle Scholar
  8. 8.
    Albores-Saavedra J, Carrick K. Where to set the threshold between well differentiated and poorly differentiated follicular carcinomas of the thyroid. Endocr Pathol. 2004;15(4):297–305.CrossRefPubMedGoogle Scholar
  9. 9.
    Kebebew E, Greenspan FS, Clark OH, et al. Anaplastic thyroid carcinoma. Treatment outcome and prognostic factors. Cancer. 2005;103(7):1330–1335.CrossRefPubMedGoogle Scholar
  10. 10.
    Sanders Jr EM, Jr LiVolsi V, Brierly J, et al. An evidence-based review of poorly differentiated thyroid cancer. World J Surg. 2007;31(5):934–945.CrossRefPubMedGoogle Scholar
  11. 11.
    Pilotti S, Collini P, Mariani L, et al. Poorly differentiated forms of papillary thyroid carcinoma: distinctive entities or morphological patterns? Semin Diagn Pathol. 1995;12(3):249–255.PubMedGoogle Scholar
  12. 12.
    Sywak M, Pasieka JL, Ogilvie T. A review of thyroid cancer with intermediate differentiation. J Surg Oncol. 2004;86(1):44–54.CrossRefPubMedGoogle Scholar
  13. 13.
    Sakamoto A, Kasai N, Sugano H. Poorly differentiated carcinoma of the thyroid. A clinicopathologic entity for a high-risk group of papillary and follicular carcinomas. Cancer. 1983;52(10):1849–1855.CrossRefPubMedGoogle Scholar
  14. 14.
    Yamashita H, Noguchi Y, Noguchi S, et al. Significance of an insular component in follicular thyroid carcinoma with distant metastasis at initial presentation. Endocr Pathol. 2005;16(1):41–48.CrossRefPubMedGoogle Scholar
  15. 15.
    Volante M, Cavallo GP, Papotti M. Prognostic factors of clinical interest in poorly differentiated carcinomas of the thyroid. Endocr Pathol. 2004;15(4):313–317.CrossRefPubMedGoogle Scholar
  16. 16.
    Carcangiu ML, Zampi G, Rosai J. Poorly differentiated (“insular”) thyroid carcinoma. A reinterpretation of Langhans’ “wuchernde Struma”. Am J Surg Pathol. 1984;8(9):655–668.CrossRefPubMedGoogle Scholar
  17. 17.
    Chao TC, Lin JD, Chen MF. Insular carcinoma: infrequent subtype of thyroid cancer with aggressive clinical course. World J Surg. 2004;28(4):393–396.CrossRefPubMedGoogle Scholar
  18. 18.
    Pilotti S, Collini P, Mariani L, et al. Insular carcinoma: a distinct de novo entity among follicular carcinomas of the thyroid gland. Am J Surg Pathol. 1997;21(12):1466–1473.CrossRefPubMedGoogle Scholar
  19. 19.
    Falvo L, Catania A, Diandrea V, et al. Prognostic factors of insular versus papillary/follicular thyroid carcinoma. Am Surg. 2004;70(5):461–466.PubMedGoogle Scholar
  20. 20.
    Collini P, Sampietro G, Rosai J, et al. Minimally invasive (encapsulated) follicular carcinoma of the thyroid gland is the low-risk counterpart of widely invasive follicular carcinoma but not of insular carcinoma. Virchows Arch. 2003;442(1):71–76.PubMedGoogle Scholar
  21. 21.
    Sobrinho-Simoes M, Sambade C, Fonseca E, et al. Poorly differentiated carcinomas of the thyroid gland: a review of the clinicopathologic features of a series of 28 cases of a heterogeneous, clinically aggressive group of thyroid tumors. Int J Surg Pathol. 2002;10(2):123–131.CrossRefPubMedGoogle Scholar
  22. 22.
    Sasaki A, Daa T, Kashima K, et al. Insular component as a risk factor of thyroid carcinoma. Pathol Int. 1996;46(12):939–946.CrossRefPubMedGoogle Scholar
  23. 23.
    Hiltzik DD, Carlson DL, Tuttle RM, et al. Poorly differentiated thyroid carcinomas defined on the basis of mitosis and necrosis: a clinicopathologic study of 58 patients. Cancer. 2006;106(6):1286–1295.CrossRefPubMedGoogle Scholar
  24. 24.
    Lam KY, Lo CY, Chan KW, et al. Insular and anaplastic carcinoma of the thyroid: a 45-year comparative study at a single institution and a review of the significance of p53 and p21. Ann Surg. 2000;231(3):329–338.CrossRefPubMedGoogle Scholar
  25. 25.
    Takeuchi Y, Das T, Kashima K, et al. Mutations of p53 in thyroid carcinoma with an insular component. Thyroid. 1999;9(4):377–381.CrossRefPubMedGoogle Scholar
  26. 26.
    Rubin BP, Heinrich MC, Corless CL. Gastrointestinal stromal tumour. Lancet. 2007;369(9574):1731–1741.CrossRefPubMedGoogle Scholar
  27. 27.
    Fletcher JA, Rubin BP. KIT mutations in GIST. Curr Opin Genet Dev. 2007;17(1):3–7.CrossRefPubMedGoogle Scholar
  28. 28.
    Broecker-Preuss M, Sheiu SY, Worm K, et al. Expression and mutation analysis of the tyrosine kinase c-kit in poorly differentiated and anaplastic thyroid carcinoma. Horm Metab Res. 2008;40(10):685–691.CrossRefPubMedGoogle Scholar
  29. 29.
    Pulcrano M, Boukheris H, Talbot M, et al. Poorly differentiated follicular thyroid carcinoma: prognostic factors and relevance of histological classification. Thyroid. 2007;17(7):639–646.CrossRefPubMedGoogle Scholar
  30. 30.
    Montero-Conde C, Martin-Campos JM, Lerma E, et al. Molecular profiling related to poor prognosis in thyroid carcinoma. Combining gene expression data and biological information. Oncogene. 2008;27(11):1554–1561.CrossRefPubMedGoogle Scholar
  31. 31.
    Rodrigues RF, Roque L, King T, et al. Poorly differentiated and anaplastic thyroid carcinomas: chromosomal and oligo-array profile of five new cell lines. Br J Cancer. 2007;96(8):1237–1245.CrossRefPubMedGoogle Scholar
  32. 32.
    Wiseman SM, Masoudi H, Niblock P, et al. Anaplastic thyroid carcinoma: expression profile of targets for therapy offers new insights for disease treatment. Ann Surg Oncol. 2007;14(2):719–729.CrossRefPubMedGoogle Scholar
  33. 33.
    Tallini G, Garcia-Rostan G, Herreo A, et al. Downregulation of p27KIP1 and Ki67/Mib1 labeling index support the classification of thyroid carcinoma into prognostically relevant categories. Am J Surg Pathol. 1999;23(6):678–685.CrossRefPubMedGoogle Scholar
  34. 34.
    Garcia-Rostan G, Camp RL, Herrero A, et al. Beta-catenin dysregulation in thyroid neoplasms: down-regulation, aberrant nuclear expression, and CTNNB1 exon 3 mutations are markers for aggressive tumor phenotypes and poor prognosis. Am J Pathol. 2001;158(3):987–996.PubMedGoogle Scholar
  35. 35.
    Garcia-Rostan G, Tallini G, Herrero A, et al. Frequent mutation and nuclear localization of beta-catenin in anaplastic thyroid carcinoma. Cancer Res. 1999;59(8):1811–1815.PubMedGoogle Scholar
  36. 36.
    Smith LW. Certain so-called sarcomas of the thyroid. Arch Pathol. 1930;10:524–530.Google Scholar
  37. 37.
    Hutter RV, Tollefson HR, DeCosse J, et al. Spindle and giant cell metaplasia in papillary carcinoma of the thyroid. Am J Surg. 1965;110(4):660–668.CrossRefPubMedGoogle Scholar
  38. 38.
    Maddox WA, Knott HW, Dowling EA. Carcinoma of the thyroid: review of fifteen years’ experience. 1. Origin of spindle and giant cell carcinoma. 2. Occurrence of thyroid cancer in ectopic thyroid tissue. Am Surg. 1971;37(11):653–660.PubMedGoogle Scholar
  39. 39.
    Bronner MP, LiVolsi VA. Spindle cell squamous carcinoma of the thyroid: an unusual anaplastic tumor associated with tall cell papillary cancer. Mod Pathol. 1991;4(5):637–643.PubMedGoogle Scholar
  40. 40.
    Wolf BC, Sheahan K, DeCosste D, et al. Immunohistochemical analysis of small cell tumors of the thyroid gland: an Eastern Cooperative Oncology Group study. Hum Pathol. 1992;23(11):1252–1261.CrossRefPubMedGoogle Scholar
  41. 41.
    Mendelsohn G, Baylin SB, Bigner SH, et al. Anaplastic variants of medullary thyroid carcinoma: a light-microscopic and immunohistochemical study. Am J Surg Pathol. 1980;4(4):333–341.CrossRefPubMedGoogle Scholar
  42. 42.
    O’Neill JP, O’Neill B, Conaron C, et al. Anaplastic (undifferen­tiated) thyroid cancer: improved insight and therapeutic strategy into a highly aggressive disease. J Laryngol Otol. 2005;119(8):585–591.PubMedGoogle Scholar
  43. 43.
    Jiang JY, Tseng FY. Prognostic factors of anaplastic thyroid carcinoma. J Endocrinol Invest. 2006;29(1):11–17.PubMedGoogle Scholar
  44. 44.
    Aratake Y, Nomura H, Katami T, et al. Coexistent anaplastic and differentiated thyroid carcinoma. Am J Clin Pathol. 2006;125(3):399–406.Google Scholar
  45. 45.
    Hunt JL. Unusual thyroid tumors: a review of pathologic and molecular diagnosis. Expert Rev Mol Diagn. 2005;5(5):725–734.CrossRefPubMedGoogle Scholar
  46. 46.
    Besic N, Hocevar M, Zogjnar J, et al. Prognostic factors in anaplastic carcinoma of the thyroid - a multivariate survival analysis of 188 patients. Langenbecks Arch Surg. 2005;390(3):203–208.CrossRefPubMedGoogle Scholar
  47. 47.
    Goutsouliak V, Hay JH. Anaplastic thyroid cancer in British Columbia 1985-1999: a population-based study. Clin Oncol (R Coll Radiol). 2005;17(2):75–78.Google Scholar
  48. 48.
    Yau T, Lo CY, Epstein RJ, et al. Treatment outcomes in anaplastic thyroid carcinoma: survival improvement in young patients with localized disease treated by combination of surgery and radiotherapy. Ann Surg Oncol. 2008;15(9):2500–2505.CrossRefPubMedGoogle Scholar
  49. 49.
    Lai ML, Faa G, Senes C, et al. Rhabdoid tumor of the thyroid gland: a variant of anaplastic carcinoma. Arch Pathol Lab Med. 2005;129(3):e55-e57.PubMedGoogle Scholar
  50. 50.
    Carda C, Ferrer J, Vilanova M, et al. Anaplastic carcinoma of the thyroid with rhabdomyosarcomatous differentiation: a report of two cases. Virchows Arch. 2005;446(1):46–51.CrossRefPubMedGoogle Scholar
  51. 51.
    Sato K, Waseda R, Tatsuzawa Y, et al. Papillary thyroid carcinoma with anaplastic transformation showing a rhabdoid phenotype solely in the cervical lymph node metastasis. Pathol Res Pract. 2006;202(1):55–59.CrossRefPubMedGoogle Scholar
  52. 52.
    Carcangiu ML, Steeper T, Zampi G, et al. Anaplastic thyroid carcinoma. A study of 70 cases. Am J Clin Pathol. 1985;83(2):135–158.PubMedGoogle Scholar
  53. 53.
    Shikama Y, Mizukami H, Yagihashi N, et al. Spindle cell metaplasia arising in thyroid adenoma: characterization of its pathology and differential diagnosis. J Endocrinol Invest. 2006;29(2):168–171.PubMedGoogle Scholar
  54. 54.
    Aker FV, Bas Y, Ozkara S, et al. Spindle cell metaplasia in follicular adenoma of the thyroid gland: case report and review of the literature. Endocr J. 2004;51(5):457–461.CrossRefPubMedGoogle Scholar
  55. 55.
    Vergilio J, Baloch ZW, LiVolsi VA. Spindle cell metaplasia of the thyroid arising in association with papillary carcinoma and follicular adenoma. Am J Clin Pathol. 2002;117(2):199–204.CrossRefPubMedGoogle Scholar
  56. 56.
    Baloch ZW, Wu H, LiVolsi VA. Post-fine-needle aspiration spindle cell nodules of the thyroid (PSCNT). Am J Clin Pathol. 1999;111(1):70–74.PubMedGoogle Scholar
  57. 57.
    Chan JK, Carcangiu ML, Rosai J. Papillary carcinoma of thyroid with exuberant nodular fasciitis-like stroma: report of three cases. Am J Clin Pathol. 1991;95(3):309–314.PubMedGoogle Scholar
  58. 58.
    Naganuma H, Iwama N, Nakamura Y, et al. Papillary carcinoma of the thyroid gland forming a myofibroblastic nodular tumor: report of two cases and review of the literature. Pathol Int. 2002;52(1):54–58.CrossRefPubMedGoogle Scholar
  59. 59.
    Wan SK, Chan JK, Tang SK. Paucicellular variant of anaplastic thyroid carcinoma. A mimic of Reidel’s thyroiditis. Am J Clin Pathol. 1996;105(4):388–393.PubMedGoogle Scholar
  60. 60.
    Roka S, Kojnek G, Schuller J, et al. Carcinoma showing thymic-like elements - a rare malignancy of the thyroid gland. Br J Surg. 2004;91(2):142–145.CrossRefPubMedGoogle Scholar
  61. 61.
    Dorfman DM, Shahsafaei A, Miyauchi A. Intrathyroidal epithelial thymoma (ITET)/carcinoma showing thymus-like differentiation (CASTLE) exhibits CD5 immunoreactivity: new evidence for thymic differentiation. Histopathology. 1998;32(2):104–109.CrossRefPubMedGoogle Scholar
  62. 62.
    Berezowski K, Grimes M, Gal AA, et al. CD5 immunorea-ctivity of epithelial cells in thymic carcinoma and CASTLE using paraffin-embedded tissue. Am J Clin Pathol. 1996;106(4):483–486.PubMedGoogle Scholar
  63. 63.
    Chan JK, Rosai J. Tumors of the neck showing thymic or related branchial pouch differentiation: a unifying concept. Hum Pathol. 1991;22(4):349–367.CrossRefPubMedGoogle Scholar
  64. 64.
    Erickson ML, Tapia E, Moreno ER, et al. Early metastasizing spindle epithelial tumor with thymus-like differentiation (SETTLE) of the thyroid. Pediatr Dev Pathol. 2005;8(5):599–606.CrossRefPubMedGoogle Scholar
  65. 65.
    Booya F, Sebo TJ, Kasperbauer JL, et al. Primary squamous cell carcinoma of the thyroid: report of ten cases. Thyroid. 2006;16(1):89–93.CrossRefPubMedGoogle Scholar
  66. 66.
    Rodriguez I, Ayala E, Caballero C, et al. Solitary fibrous tumor of the thyroid gland: report of seven cases. Am J Surg Pathol. 2001;25(11):1424–1428.CrossRefPubMedGoogle Scholar
  67. 67.
    Papi G, Corrado S, LiVolsi VA. Primary spindle cell lesions of the thyroid gland: an overview. Am J Clin Pathol. 2006;125(suppl):S95-S123.PubMedGoogle Scholar
  68. 68.
    Miettinen M, Franssila KO. Variable expression of keratins and nearly uniform lack of thyroid transcription factor 1 in thyroid anaplastic carcinoma. Hum Pathol. 2000;31(9):1139–1145.CrossRefPubMedGoogle Scholar
  69. 69.
    Nonaka D, Dhiriboga L, Soslow R, et al. Diagnostic utility of thyroid transcription factors Pax8 and TTF-2 (FoxE1) in thyroid epithelial neoplasms. Mod Pathol. 2008;21(2):192–200.PubMedGoogle Scholar
  70. 70.
    Elliott DD, Sherman SL, Bussaldy NL, et al. Growth factor receptors expression in anaplastic thyroid carcinoma: potential markers for therapeutic stratification. Hum Pathol. 2008;39(1):15–20.CrossRefPubMedGoogle Scholar
  71. 71.
    Nikiforov YE. Genetic alterations involved in the transition from well-differentiated to poorly differentiated and anaplastic thyroid carcinomas. Endocr Pathol. 2004;15(4):319–327.CrossRefPubMedGoogle Scholar
  72. 72.
    Begum S, Rosenbaum E, Henrique R, et al. BRAF mutations in anaplastic thyroid carcinoma: implications for tumor origin, diagnosis and treatment. Mod Pathol. 2004;17(11):1359–1363.CrossRefPubMedGoogle Scholar
  73. 73.
    Hunt JL, Tometsko M, LiVolsi V, et al. Molecular evidence of anaplastic transformation in coexisting well-differentiated and anaplastic carcinomas of the thyroid. Am J Surg Pathol. 2003;27(12):1559–1564.CrossRefPubMedGoogle Scholar
  74. 74.
    Sala E, Mologni L, Truffa S, et al. BRAF silencing by short hairpin RNA or chemical blockade by PLX4032 leads to different responses in melanoma and thyroid carcinoma cells. Mol Cancer Res. 2008;6(5):751–759.CrossRefPubMedGoogle Scholar
  75. 75.
    Leboeuf R, Baumgartner JE, Benezra M, et al. BRAFV600E mutation is associated with preferential sensitivity to mitogen-activated protein kinase kinase inhibition in thyroid cancer cell lines. J Clin Endocrinol Metab. 2008;93(6):2194–2201.CrossRefPubMedGoogle Scholar
  76. 76.
    Hoffmann S, Burchert A, Weinderlich A, et al. Differential effects of cetuximab and AEE 788 on epidermal growth factor receptor (EGF-R) and vascular endothelial growth factor receptor (VEGF-R) in thyroid cancer cell lines. Endocrine. 2007;31(2):105–113.CrossRefPubMedGoogle Scholar
  77. 77.
    Pennell NA, Daniels GH, Haddad Ri, et al. A phase II study of gefitinib in patients with advanced thyroid cancer. Thyroid. 2008;18(3):317–323.CrossRefPubMedGoogle Scholar
  78. 78.
    Stenner F, Liewen H, Zweller M, et al. Targeted therapeutic approach for an anaplastic thyroid cancer in vitro and in vivo. Cancer Sci. 2008;99(9):1847–1852.PubMedGoogle Scholar
  79. 79.
    Salvatore G, DeFalco V, Salerno P, et al. BRAF is a therapeutic target in aggressive thyroid carcinoma. Clin Cancer Res. 2006;12(5):1623–1629.CrossRefPubMedGoogle Scholar
  80. 80.
    Quiros RM, Ding H, Gattuso P, et al. Evidence that one subset of anaplastic thyroid carcinomas are derived from papillary carcinomas due to BRAF and p53 mutations. Cancer. 2005;103(11):2261–2268.CrossRefPubMedGoogle Scholar
  81. 81.
    Nikiforova MN, Kimura EJ, Gandhi M, 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;88(11):5399–5404.CrossRefPubMedGoogle Scholar
  82. 82.
    Wang HM, Huang YU, Huang JS, et al. Anaplastic carcinoma of the thyroid arising more often from follicular carcinoma than papillary carcinoma. Ann Surg Oncol. 2007;14(10):3011–3018.CrossRefPubMedGoogle Scholar
  83. 83.
    Santarpia L, El Naggar AK, Cote G, et al. PI3K/Akt and Ras/Raf-MAPK pathway mutations in anaplastic thyroid cancer. J Clin Endocrinol Metab. 2008;93(1):278–284.CrossRefPubMedGoogle Scholar
  84. 84.
    Costa AM, Herrerro A, Fresno MF, et al. BRAF mutation associated with other genetic events identifies a subset of aggressive papillary thyroid carcinoma. Clin Endocrinol (Oxf). 2008;68(4):618–634.CrossRefGoogle Scholar
  85. 85.
    Rodrigues RF, Roque L, Rosa-Santos J, et al. Chromosomal imbalances associated with anaplastic transformation of follicular thyroid carcinomas. Br J Cancer. 2004;90(2):492–496.CrossRefPubMedGoogle Scholar
  86. 86.
    Miura D, Wada N, Chin K, et al. Anaplastic thyroid cancer: cytogenetic patterns by comparative genomic hybridization. Thyroid. 2003;13(3):283–290.CrossRefPubMedGoogle Scholar
  87. 87.
    Lee JJ, Au AY, Foukakis J, et al. Array-CGH identifies cyclin D1 and UBCH10 amplicons in anaplastic thyroid carcinoma. Endocr Relat Cancer. 2008;15(3):801–815.CrossRefPubMedGoogle Scholar
  88. 88.
    Liu Z, Hou P, Ji M, et al. Highly prevalent genetic alterations in receptor tyrosine kinases and phosphatidylinositol 3-kinase/akt and mitogen-activated protein kinase pathways in anaplastic and follicular thyroid cancers. J Clin Endocrinol Metab. 2008;93(8):3106–3116.CrossRefPubMedGoogle Scholar
  89. 89.
    Kitamura Y, Ahimiu K, Ito K, et al. Allelotyping of anaplastic thyroid carcinoma: frequent allelic losses on 1q, 9p, 11, 17, 19p, and 22q. Genes Chromosomes Cancer. 2000;27(3):244–251.CrossRefPubMedGoogle Scholar
  90. 90.
    Fagin JA, Matsuo L, Karmakar A, et al. High prevalence of mutations of the p53 gene in poorly differentiated human thyroid carcinomas. J Clin Invest. 1993;91(1):179–184.CrossRefPubMedGoogle Scholar
  91. 91.
    Sera N, Ashizawa K, Ando T, et al. Anaplastic changes associated with p53 gene mutation in differentiated thyroid carcinoma after insufficient radioactive iodine (131I) therapy. Thyroid. 2000;10(11):975–979.CrossRefPubMedGoogle Scholar
  92. 92.
    Hosal SA, Apel R, Freeman JL, et al. Immunohistochemical localization of p53 in human thyroid neoplasms: correlation with biological behavior. Endocr Pathol. 1997;8(1):21–28.CrossRefPubMedGoogle Scholar
  93. 93.
    Salvatore D, Celletti A, Fabien N, et al. Low frequency of p53 mutations in human thyroid tumours; p53 and Ras mutation in two out of fifty-six thyroid tumours. Eur J Endocrinol. 1996;134(2):177–183.CrossRefPubMedGoogle Scholar
  94. 94.
    Zafon C, Obois G, Castelivi J, et al. Clinical significance of RET/PTC and p53 protein expression in sporadic papillary thyroid carcinoma. Histopathology. 2007;50(2):225–231.CrossRefPubMedGoogle Scholar
  95. 95.
    Nakamura N, Carney Ja, Jin L, et al. RASSF1A and NORE1A methylation and BRAFV600E mutations in thyroid tumors. Lab Invest. 2005;85(9):1065–1075.CrossRefPubMedGoogle Scholar
  96. 96.
    Xing M, Cohen Y, Mambo E, et al. Early occurrence of RASSF1A hypermethylation and its mutual exclusion with BRAF mutation in thyroid tumorigenesis. Cancer Res. 2004;64(5):1664–1668.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Jennifer L. Hunt
    • 1
  • Virginia A. LiVolsi
    • 2
  1. 1.Department of PathologyHarvard Medical School, Massachusetts General HospitalBostonUSA
  2. 2.Department of Pathology and Laboratory MedicineUniversity of PennsylvaniaPhiladelphiaUSA

Personalised recommendations