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World Journal of Surgery

, Volume 32, Issue 7, pp 1237–1246 | Cite as

Do Benign Thyroid Nodules Have Malignant Potential? An Evidence-Based Review

  • Nimmi Arora
  • Theresa Scognamiglio
  • Baixin Zhu
  • Thomas J. Fahey III
Article

Abstract

Background

Benign thyroid tumors account for most nodular thyroid disease. Determination of whether a thyroid nodule is benign or malignant is a major clinical dilemma and underlies the decision to proceed to surgery in many patients. Although the accuracy of thyroid nodule fine-needle aspiration (FNA) has reduced the need for surgery over the years, questions regarding how to follow FNA-designated benign nodules remain unresolved. This is true at least in part because of uncertainty over whether some benign nodules harbor malignant potential.

Methods

An evidence-based review of recent clinical, pathologic, and molecular data is presented. A summary of data and observations from our own experience is also provided.

Results

Review of our recent 10-year experience indicates that 2% of thyroid malignancies arise within a preexisting benign thyroid nodule. In addition, both cytologic and molecular tumor markers, including Gal-3, CITED1, HBME-1, Ras, RET/PTC, and PAX8/PPARγ, have been identified in some histopathologically classified benign nodules. Gene expression profiling suggests that follicular adenomas and Hürthle cell adenomas have similarities to both benign and malignant tumors, suggesting that some of these tumors are premalignant. In addition, 10% of surgically excised follicular tumors are encapsulated follicular lesions with nuclear atypia, which have been termed “well-differentiated tumors of uncertain malignant potential.” The data available suggest that these tumors could be precursors to carcinoma.

Conclusion

Some benign thyroid nodules have malignant potential. Further molecular testing of these tumors can shed light on the pathogenesis of early malignant transformation.

Keywords

Goiter Papillary Thyroid Carcinoma Thyroid Nodule Papillary Carcinoma BRAF Mutation 
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.

Notes

Acknowledgments

This study was supported by The Dancer’s Care Foundation.

References

  1. 1.
    Mazzaferri EL (1981) Solitary thyroid nodule. 2. Selective approach to management. Postgrad Med 70:107–109, 112, 116PubMedGoogle Scholar
  2. 2.
    Mortensen JD, Woolner LB, Bennett WA (1955) Gross and microscopic findings in clinically normal thyroid glands. J Clin Endocrinol Metab 15:1270–1280PubMedGoogle Scholar
  3. 3.
    Lang W, Borrusch H, Bauer L (1988) Occult carcinomas of the thyroid: evaluation of 1,020 sequential autopsies. Am J Clin Pathol 90:72–76PubMedGoogle Scholar
  4. 4.
    Rosai J, Carcangiu ML, DeLellis RA (1992) Atlas of Tumor Pathology. 3rd edition. Vol 5. Armed Forces Institute of Pathology, Washington, DCGoogle Scholar
  5. 5.
    Sackett DL (1989) Rules of evidence and clinical recommendations on the use of antithrombotic agents. Chest 95:2S–4SPubMedCrossRefGoogle Scholar
  6. 6.
    Barden CB, Shister KW, Zhu B, et al (2003) Classification of follicular thyroid tumors by molecular signature: results of gene profiling. Clin Cancer Res 9:1792–1800PubMedGoogle Scholar
  7. 7.
    Finley DJ, Arora N, Zhu B, et al (2004) Molecular profiling distinguishes papillary carcinoma from benign thyroid nodules. J Clin Endocrinol Metab 89:3214–3223PubMedCrossRefGoogle Scholar
  8. 8.
    Nikiforova MN, Kimura ET, Gandhi M, et al (2003) BRAF mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas. J Clin Endocrinol Metab 88:5399–5404PubMedCrossRefGoogle Scholar
  9. 9.
    Alexander EK, Hurwitz S, Heering JP, et al (2003) Natural history of benign solid and cystic thyroid nodules. Ann Intern Med 138:315–318PubMedGoogle Scholar
  10. 10.
    Kuma K, Matsuzuka F, Yokozawa T, et al (1994) Fate of untreated benign thyroid nodules: results of long-term follow-up. World J Surg 18:495–498PubMedCrossRefGoogle Scholar
  11. 11.
    Evans HL, Vassilopoulou-Sellin R (1998) Follicular and Hurthle cell carcinomas of the thyroid: a comparative study. Am J Surg Pathol 22:1512–1520PubMedCrossRefGoogle Scholar
  12. 12.
    Park SH, Suh EH, Chi JG (1988) A histopathologic study on 1,095 surgically resected thyroid specimens. Jpn J Clin Oncol 18:297–302PubMedGoogle Scholar
  13. 13.
    Pennelli N, Pennelli G, Merante Boschin I, et al (2005) Thyroid intrafollicular neoplasia (TIN) as a precursor of papillary microcarcinoma. Ann Ital Chir 76:219–224PubMedGoogle Scholar
  14. 14.
    Hazard JB, Kenyon R (1954) Atypical adenoma of the thyroid. AMA Arch Pathol 58:554–563PubMedGoogle Scholar
  15. 15.
    Vickery AL Jr (1983) Thyroid papillary carcinoma: pathological and philosophical controversies. Am J Surg Pathol 7:797–807PubMedCrossRefGoogle Scholar
  16. 16.
    Chan JK (2002) Strict criteria should be applied in the diagnosis of encapsulated follicular variant of papillary thyroid carcinoma. Am J Clin Pathol 117:16–18PubMedCrossRefGoogle Scholar
  17. 17.
    Franc B, de la Salmoniere P, Lange F, et al (2003) Interobserver and intraobserver reproducibility in the histopathology of follicular thyroid carcinoma. Hum Pathol 34:1092–1100PubMedCrossRefGoogle Scholar
  18. 18.
    Lloyd RV, Erickson LA, Casey MB, et al (2004) Observer variation in the diagnosis of follicular variant of papillary thyroid carcinoma. Am J Surg Pathol 28:1336–1340PubMedCrossRefGoogle Scholar
  19. 19.
    Saxen E, Franssila K, Bjarnason O, et al (1978) Observer variation in histologic classification of thyroid cancer. Acta Pathol Microbiol Scand [A] 86A:483–486Google Scholar
  20. 20.
    Hirokawa M, Carney JA, Goellner JR, et al (2002) Observer variation of encapsulated follicular lesions of the thyroid gland. Am J Surg Pathol 26:1508–1514PubMedCrossRefGoogle Scholar
  21. 21.
    Williams ED (2000) Guest editorial: two proposals regarding the terminology of thyroid tumors. Int J Surg Pathol 8:181–183PubMedCrossRefGoogle Scholar
  22. 22.
    Mai KT, Landry DC, Thomas J, et al (2001) Follicular adenoma with papillary architecture: a lesion mimicking papillary thyroid carcinoma. Histopathology 39:25–32PubMedCrossRefGoogle Scholar
  23. 23.
    Liu J, Singh B, Tallini G, et al (2006) Follicular variant of papillary thyroid carcinoma: a clinicopathologic study of a problematic entity. Cancer 107:1255–1264PubMedCrossRefGoogle Scholar
  24. 24.
    Bartolazzi A, Gasbarri A, Papotti M, et al (2001) Application of an immunodiagnostic method for improving preoperative diagnosis of nodular thyroid lesions. Lancet 357:1644–1650PubMedCrossRefGoogle Scholar
  25. 25.
    Prasad ML, Pellegata NS, Huang Y, et al (2005) Galectin-3, fibronectin-1, CITED-1, HBME1 and cytokeratin-19 immunohistochemistry is useful for the differential diagnosis of thyroid tumors. Mod Pathol 18:48–57PubMedCrossRefGoogle Scholar
  26. 26.
    Scognamiglio T, Hyjek E, Kao J, et al (2006) 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 126:700–708PubMedCrossRefGoogle Scholar
  27. 27.
    Park YJ, Kwak SH, Kim DC, et al (2007) Diagnostic value of galectin-3, HBME-1, cytokeratin 19, high molecular weight cytokeratin, cyclin D1 and p27(kip1) in the differential diagnosis of thyroid nodules. J Korean Med Sci 22:621–628PubMedGoogle Scholar
  28. 28.
    Beesley MF, McLaren KM (2002) Cytokeratin 19 and galectin-3 immunohistochemistry in the differential diagnosis of solitary thyroid nodules. Histopathology 41:236–243PubMedCrossRefGoogle Scholar
  29. 29.
    de Matos PS, Ferreira AP, de Oliveira Facuri F, et al (2005) Usefulness of HBME-1, cytokeratin 19 and galectin-3 immunostaining in the diagnosis of thyroid malignancy. Histopathology 47:391–401PubMedCrossRefGoogle Scholar
  30. 30.
    Cheung CC, Ezzat S, Freeman JL, et al (2001) Immunohistochemical diagnosis of papillary thyroid carcinoma. Mod Pathol 14:338–342PubMedCrossRefGoogle Scholar
  31. 31.
    Erkilic S, Aydin A, Kocer NE (2002) Diagnostic utility of cytokeratin 19 expression in multinodular goiter with papillary areas and papillary carcinoma of thyroid. Endocr Pathol 13:207–211PubMedCrossRefGoogle Scholar
  32. 32.
    Lam KY, Lui MC, Lo CY (2001) Cytokeratin expression profiles in thyroid carcinomas. Eur J Surg Oncol 27:631–635PubMedCrossRefGoogle Scholar
  33. 33.
    Nasr MR, Mukhopadhyay S, Zhang S, et al (2006) Immunohistochemical markers in diagnosis of papillary thyroid carcinoma: utility of HBME1 combined with CK19 immunostaining. Mod Pathol 19:1631–1637PubMedCrossRefGoogle Scholar
  34. 34.
    Sahoo S, Hoda SA, Rosai J, et al (2001) Cytokeratin 19 immunoreactivity in the diagnosis of papillary thyroid carcinoma: a note of caution. Am J Clin Pathol 116:696–702PubMedCrossRefGoogle Scholar
  35. 35.
    Aron M, Kapila K, Verma K (2006) Utility of galectin 3 expression in thyroid aspirates as a diagnostic marker in differentiating benign from malignant thyroid neoplasms. Indian J Pathol Microbiol 49:376–380PubMedGoogle Scholar
  36. 36.
    Mehrotra P, Okpokam A, Bouhaidar R, et al (2004) Galectin-3 does not reliably distinguish benign from malignant thyroid neoplasms. Histopathology 45:493–500PubMedCrossRefGoogle Scholar
  37. 37.
    Papotti M, Rodriguez J, De Pompa R, et al (2005) Galectin-3 and HBME-1 expression in well-differentiated thyroid tumors with follicular architecture of uncertain malignant potential. Mod Pathol 18:541–546PubMedCrossRefGoogle Scholar
  38. 38.
    Fukushima T, Suzuki S, Mashiko M, et al (2003) BRAF mutations in papillary carcinomas of the thyroid. Oncogene 22:6455–6457PubMedCrossRefGoogle Scholar
  39. 39.
    Kimura ET, Nikiforova MN, Zhu Z, et al (2003) 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 63:1454–1457PubMedGoogle Scholar
  40. 40.
    Xu X, Quiros RM, Gattuso P, et al (2003) High prevalence of BRAF gene mutation in papillary thyroid carcinomas and thyroid tumor cell lines. Cancer Res 63:4561–4567PubMedGoogle Scholar
  41. 41.
    Kebebew E, Weng J, Bauer J, et al (2007) The prevalence and prognostic value of BRAF mutation in thyroid cancer. Ann Surg 246:466–470PubMedCrossRefGoogle Scholar
  42. 42.
    Lee JH, Lee ES, Kim YS (2007) Clinicopathologic significance of BRAF V600E mutation in papillary carcinomas of the thyroid: a meta-analysis. Cancer 110:38–46PubMedCrossRefGoogle Scholar
  43. 43.
    Ishizaka Y, Kobayashi S, Ushijima T, et al (1991) Detection of retTPC/PTC transcripts in thyroid adenomas and adenomatous goiter by an RT-PCR method. Oncogene 6:1667–1672PubMedGoogle Scholar
  44. 44.
    Chua EL, Wu WM, Tran KT, et al (2000) Prevalence and distribution of ret/ptc 1, 2, and 3 in papillary thyroid carcinoma in New Caledonia and Australia. J Clin Endocrinol Metab 85:2733–2739PubMedCrossRefGoogle Scholar
  45. 45.
    Learoyd DL, Messina M, Zedenius J, et al (1998) RET/PTC and RET tyrosine kinase expression in adult papillary thyroid carcinomas. J Clin Endocrinol Metab 83:3631–3635PubMedCrossRefGoogle Scholar
  46. 46.
    Santoro M, Papotti M, Chiappetta G, et al (2002) RET activation and clinicopathologic features in poorly differentiated thyroid tumors. J Clin Endocrinol Metab 87:370–379PubMedCrossRefGoogle Scholar
  47. 47.
    Tallini G, Santoro M, Helie M, et al (1998) RET/PTC oncogene activation defines a subset of papillary thyroid carcinomas lacking evidence of progression to poorly differentiated or undifferentiated tumor phenotypes. Clin Cancer Res 4:287–294PubMedGoogle Scholar
  48. 48.
    Capella G, Matias-Guiu X, Ampudia X, et al (1996) Ras oncogene mutations in thyroid tumors: polymerase chain reaction-restriction-fragment-length polymorphism analysis from paraffin-embedded tissues. Diagn Mol Pathol 5:45–52PubMedCrossRefGoogle Scholar
  49. 49.
    Garcia-Rostan G, Zhao H, Camp RL, et al (2003) Ras mutations are associated with aggressive tumor phenotypes and poor prognosis in thyroid cancer. J Clin Oncol 21:3226–3235PubMedCrossRefGoogle Scholar
  50. 50.
    Karga H, Lee JK, Vickery AL Jr, et al (1991) Ras oncogene mutations in benign and malignant thyroid neoplasms. J Clin Endocrinol Metab 73:832–836PubMedCrossRefGoogle Scholar
  51. 51.
    Lemoine NR, Mayall ES, Wyllie FS, et al (1989) High frequency of ras oncogene activation in all stages of human thyroid tumorigenesis. Oncogene 4:159–164PubMedGoogle Scholar
  52. 52.
    Liu RT, Hou CY, You HL, et al (2004) Selective occurrence of ras mutations in benign and malignant thyroid follicular neoplasms in Taiwan. Thyroid 14:616–621PubMedCrossRefGoogle Scholar
  53. 53.
    Namba H, Rubin SA, Fagin JA (1990) Point mutations of ras oncogenes are an early event in thyroid tumorigenesis. Mol Endocrinol 4:1474–1479PubMedGoogle Scholar
  54. 54.
    Vasko V, Ferrand M, Di Cristofaro J, et al (2003) Specific pattern of RAS oncogene mutations in follicular thyroid tumors. J Clin Endocrinol Metab 88:2745–2752PubMedCrossRefGoogle Scholar
  55. 55.
    Kroll TG, Sarraf P, Pecciarini L, et al (2000) PAX8-PPARgamma1 fusion oncogene in human thyroid carcinoma [corrected]. Science 289:1357–1360PubMedCrossRefGoogle Scholar
  56. 56.
    Dwight T, Thoppe SR, Foukakis T, et al (2003) Involvement of the PAX8/peroxisome proliferator-activated receptor gamma rearrangement in follicular thyroid tumors. J Clin Endocrinol Metab 88:4440–4445PubMedCrossRefGoogle Scholar
  57. 57.
    Lacroix L, Lazar V, Michiels S, et al (2005) Follicular thyroid tumors with the PAX8-PPARgamma1 rearrangement display characteristic genetic alterations. Am J Pathol 167:223–231PubMedGoogle Scholar
  58. 58.
    Marques AR, Espadinha C, Catarino AL, et al (2002) Expression of PAX8-PPAR gamma 1 rearrangements in both follicular thyroid carcinomas and adenomas. J Clin Endocrinol Metab 87:3947–3952PubMedCrossRefGoogle Scholar
  59. 59.
    Nikiforova MN, Biddinger PW, Caudill CM, et al (2002) PAX8-PPARgamma rearrangement in thyroid tumors: RT-PCR and immunohistochemical analyses. Am J Surg Pathol 26:1016–1023PubMedCrossRefGoogle Scholar
  60. 60.
    Castro P, Rebocho AP, Soares RJ, et al (2006) PAX8-PPARgamma rearrangement is frequently detected in the follicular variant of papillary thyroid carcinoma. J Clin Endocrinol Metab 91:213–220PubMedCrossRefGoogle Scholar
  61. 61.
    Elisei R, Romei C, Vorontsova T, et al (2001) RET/PTC rearrangements in thyroid nodules: studies in irradiated and not irradiated, malignant and benign thyroid lesions in children and adults. J Clin Endocrinol Metab 86:3211–3216PubMedCrossRefGoogle Scholar
  62. 62.
    Cerilli LA, Mills SE, Rumpel CA, et al (2002) Interpretation of RET immunostaining in follicular lesions of the thyroid. Am J Clin Pathol 118:186–193PubMedCrossRefGoogle Scholar
  63. 63.
    Fusco A, Chiappetta G, Hui P, et al (2002) 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 160:2157–2167PubMedGoogle Scholar
  64. 64.
    Oyama T, Suzuki T, Hara F, et al (1995) N-ras mutation of thyroid tumor with special reference to the follicular type. Pathol Int 45:45–50PubMedGoogle Scholar
  65. 65.
    Esapa CT, Johnson SJ, Kendall-Taylor P, et al (1999) Prevalence of Ras mutations in thyroid neoplasia. Clin Endocrinol (Oxf) 50:529–535CrossRefGoogle Scholar
  66. 66.
    Nikiforova MN, Lynch RA, Biddinger PW, et al (2003) RAS point mutations and PAX8-PPAR gamma rearrangement in thyroid tumors: evidence for distinct molecular pathways in thyroid follicular carcinoma. J Clin Endocrinol Metab 88:2318–2326PubMedCrossRefGoogle Scholar
  67. 67.
    Cheung L, Messina M, Gill A, et al (2003) Detection of the PAX8-PPAR gamma fusion oncogene in both follicular thyroid carcinomas and adenomas. J Clin Endocrinol Metab 88:354–357PubMedCrossRefGoogle Scholar
  68. 68.
    Huang Y, Prasad M, Lemon WJ, et al (2001) Gene expression in papillary thyroid carcinoma reveals highly consistent profiles. Proc Natl Acad Sci U S A 98:15044–15049PubMedCrossRefGoogle Scholar
  69. 69.
    Lubitz CC, Gallagher LA, Finley DJ, et al (2005) Molecular analysis of minimally invasive follicular carcinomas by gene profiling. Surgery 138:1042–1048PubMedCrossRefGoogle Scholar
  70. 70.
    Lubitz CC, Ugras SK, Kazam JJ, et al (2006) Microarray analysis of thyroid nodule fine-needle aspirates accurately classifies benign and malignant lesions. J Mol Diagn 8:490–498PubMedCrossRefGoogle Scholar
  71. 71.
    Studer H, Derwahl M (1995) Mechanisms of nonneoplastic endocrine hyperplasia-a changing concept: a review focused on the thyroid gland. Endocr Rev 16:411–426PubMedCrossRefGoogle Scholar
  72. 72.
    Cerci C, Cerci SS, Eroglu E, et al (2007) Thyroid cancer in toxic and non-toxic multinodular goiter. J Postgrad Med 53:157–160PubMedGoogle Scholar
  73. 73.
    Santoro M, Carlomagno F, Hay ID, et al (1992) Ret oncogene activation in human thyroid neoplasms is restricted to the papillary cancer subtype. J Clin Invest 89:1517–1522PubMedCrossRefGoogle Scholar
  74. 74.
    Finley DJ, Zhu B, Barden CB, et al (2004) Discrimination of benign and malignant thyroid nodules by molecular profiling. Ann Surg 240:425–436PubMedCrossRefGoogle Scholar
  75. 75.
    Finley DJ, Lubitz CC, Wei C, et al (2005) Advancing the molecular diagnosis of thyroid nodules: defining benign lesions by molecular profiling. Thyroid 15:562–568PubMedCrossRefGoogle Scholar
  76. 76.
    McHenry CR, Sandoval BA (1998) Management of follicular and Hurthle cell neoplasms of the thyroid gland. Surg Oncol Clin N Am 7:893–910PubMedGoogle Scholar
  77. 77.
    Pisani T, Pantellini F, Centanni M, et al (2003) Immunocytochemical expression of Ki67 and laminin in Hurthle cell adenomas and carcinomas. Anticancer Res 23:3323–3326PubMedGoogle Scholar
  78. 78.
    Chen H, Nicol TL, Zeiger MA, et al (1998) Hurthle cell neoplasms of the thyroid: are there factors predictive of malignancy? Ann Surg 227:542–546PubMedCrossRefGoogle Scholar
  79. 79.
    Lopez-Penabad L, Chiu AC, Hoff AO, et al (2003) Prognostic factors in patients with Hurthle cell neoplasms of the thyroid. Cancer 97:1186–1194PubMedCrossRefGoogle Scholar
  80. 80.
    Nascimento MC, Bisi H, Alves VA, et al (2001) Differential reactivity for galectin-3 in Hurthle cell adenomas and carcinomas. Endocr Pathol 12:275–279PubMedCrossRefGoogle Scholar
  81. 81.
    Cheung CC, Ezzat S, Ramyar L, et al (2000) Molecular basis of Hurthle cell papillary thyroid carcinoma. J Clin Endocrinol Metab 85:878–882PubMedCrossRefGoogle Scholar
  82. 82.
    Galusca B, Dumollard JM, Chambonniere ML, et al (2004) Peroxisome proliferator activated receptor gamma immunohistochemical expression in human papillary thyroid carcinoma tissues: possible relationship to lymph node metastasis. Anticancer Res 24:1993–1997PubMedGoogle Scholar
  83. 83.
    Musholt PB, Imkamp F, von Wasielewski R, et al (2003) RET rearrangements in archival oxyphilic thyroid tumors: new insights in tumorigenesis and classification of Hurthle cell carcinomas? Surgery 134:881–889PubMedCrossRefGoogle Scholar
  84. 84.
    Finley DJ, Zhu B, Fahey TJ 3rd (2004) Molecular analysis of Hurthle cell neoplasms by gene profiling. Surgery 136:1160–1168PubMedCrossRefGoogle Scholar
  85. 85.
    Ashcraft MW, Van Herle AJ (1981) Management of thyroid nodules. I. History and physical examination, blood tests, x-ray tests, and ultrasonography. Head Neck Surg 3:216–230PubMedCrossRefGoogle Scholar
  86. 86.
    de los Santos ET, Keyhani-Rofagha S, Cunningham JJ, et al (1990) Cystic thyroid nodules: the dilemma of malignant lesions. Arch Intern Med 150:1422–1427CrossRefGoogle Scholar
  87. 87.
    Lin JD, Hsuen C, Chen JY, et al (2007) Cystic change in thyroid cancer. ANZ J Surg 77:450–454PubMedCrossRefGoogle Scholar
  88. 88.
    Rehak NN, Oertel YC, Herp A, et al (1993) Biochemical analysis of thyroid cyst fluid obtained by fine-needle aspiration. Arch Pathol Lab Med 117:625–630 PubMedGoogle Scholar
  89. 89.
    Gasbarri A, Sciacchitano S, Marasco A, et al (2004) Detection and molecular characterisation of thyroid cancer precursor lesions in a specific subset of Hashimoto’s thyroiditis. Br J Cancer 91:1096–1104PubMedGoogle Scholar
  90. 90.
    Okayasu I, Fujiwara M, Hara Y, et al (1995) Association of chronic lymphocytic thyroiditis and thyroid papillary carcinoma: a study of surgical cases among Japanese, and white and African Americans. Cancer 76:2312–2318PubMedCrossRefGoogle Scholar
  91. 91.
    Rhoden KJ, Unger K, Salvatore G, et al (2006) RET/papillary thyroid cancer rearrangement in nonneoplastic thyrocytes: follicular cells of Hashimoto’s thyroiditis share low-level recombination events with a subset of papillary carcinoma. J Clin Endocrinol Metab 91:2414–2423PubMedCrossRefGoogle Scholar
  92. 92.
    Sargent R, LiVolsi V, Murphy J, et al (2006) BRAF mutation is unusual in chronic lymphocytic thyroiditis-associated papillary thyroid carcinomas and absent in non-neoplastic nuclear atypia of thyroiditis. Endocr Pathol 17:235–241PubMedCrossRefGoogle Scholar
  93. 93.
    Sheils OM, O’Eary J J, Uhlmann V, et al (2000) ret/PTC-1 Activation in Hashimoto thyroiditis. Int J Surg Pathol 8:185–189PubMedCrossRefGoogle Scholar

Copyright information

© Société Internationale de Chirurgie 2008

Authors and Affiliations

  • Nimmi Arora
    • 1
  • Theresa Scognamiglio
    • 2
  • Baixin Zhu
    • 1
  • Thomas J. Fahey III
    • 1
    • 3
  1. 1.Department of SurgeryNew York Presbyterian Hospital-Cornell UniversityNew YorkUSA
  2. 2.Department of PathologyNew York Presbyterian Hospital-Cornell UniversityNew YorkUSA
  3. 3.New York Presbyterian Hospital-Cornell UniversityNew YorkUSA

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