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Hurthle Cell Lesion: Controversies, Challenges, and Debates

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Abstract

Hurthle cell lesion is one of the most questionable clinico-pathological entities in most of its aspects. Literature has used the terms oncocytic, oxyphilic, Hurthle, and Ashkanazy interchangeably; what does each term denote? Who first described these cells? What is the cell of origin? How much Hurthle cells should be present to define the lesion as Hurthle cell one? Is it possible to differentiate hyperplastic from neoplastic and benign from malignant Hurthle cell lesion on a non-histopathologic ground? Does it belong to follicular or to papillary neoplasms or should it be classified separately? Can we anticipate its clinical behavior or predict its outcome? How can we manage? We will try to answer these questions in light of the ongoing relevant arguments with the aim of resolving some uncertainties and suggesting how to solve others.

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References

  1. Wakely PE Jr (2008) Oncocytic and oncocyte-like lesions of the head and neck. Ann Diagn Pathol 12(3):222–230

    Article  PubMed  Google Scholar 

  2. Kontaxis A, Zanarotti U, Kainz J, Beham A (2004) Die diffuse Onkozytose der Glandula Parotidea. Laryngo-Rhino-Otologie 83(03):185–188

    Article  CAS  PubMed  Google Scholar 

  3. Prabakaran SS, Chen F, Aguirre A (2010) Oncocytoma of the parotid gland and its mimickers: a comprehensive review. N Am J Med Sci 3:171–180

    Article  Google Scholar 

  4. Mete O, Asa SL (2010) Oncocytes, oxyphils, Hurthle, and Askanazy cells: morphological and molecular features of oncocytic thyroid nodules. Endocr Pathol 21(1):16–24

    Article  PubMed  Google Scholar 

  5. Hurthle K (1894) BeitrÃgezurKenntniss des Secretionsvorgangs in der. SchilddrÃse. Pflugers Arch Physiol 56:10–44

    Article  Google Scholar 

  6. Ashkanazy M (1898) Pathologisch-anatomischeBeitrÃgezurKenntniss des. MorbusBasedowii, insbesondere über die dabeiauftretendeMuskelerkrankung. Dtsch Arch Klin Med 61:118–186

    Google Scholar 

  7. Johnson TL, Lloyd RV, Burney RE, Thompson NW (1987) Hurthle cell thyroid tumors. An immunohistochemical study. Cancer 59(1):107–112

    Article  CAS  PubMed  Google Scholar 

  8. Clark OH, Gerend PL (1985) Thyrotropin receptor-adenylate cyclase system in Hurthle cell neoplasms. J Clin Endocrinol Metab 61(4):773–778

    Article  CAS  PubMed  Google Scholar 

  9. Chen H, Udelsman R (2005) Chapter 14 - Hürthle cell adenoma and carcinoma. In: Kebebew OHC-YD (ed) Textbook of endocrine surgery, 2nd edn. W.B. Saunders, Philadelphia, pp 123–128

    Chapter  Google Scholar 

  10. Evans HL, Vassilopoulou-Sellin R (1998) Follicular and Hurthle cell carcinomas of the thyroid: a comparative study. Am J Surg Pathol 22(12):1512–1520

    Article  CAS  PubMed  Google Scholar 

  11. Sanders LE, Silverman M (1998) Follicular and Hürthle cell carcinoma: predicting outcome and directing therapy. Surgery 124(6):967–974

    Article  CAS  PubMed  Google Scholar 

  12. Masood S, Auguste L-J, Westerband A et al (1993) Differential oncogenic expression in thyroid follicular and Hürthle cell carcinomas. Am J Surg 166(4):366–368

    Article  CAS  PubMed  Google Scholar 

  13. Stankov K, Romeo G (2003) Oxyphilic carcinoma of the thyroid gland. Arch Oncol 11(2):81–89

    Article  Google Scholar 

  14. Rosai J, Kuhn E, Carcangiu ML (2006) Pitfalls in thyroid tumour pathology. Histopathology 49(2):107–120

    Article  CAS  PubMed  Google Scholar 

  15. Asa S (2004) My approach to oncocytic tumours of the thyroid. J Clin Pathol 57(3):225–232

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Kroeker T, Prisman E, Shah M et al (2014) Hurthle cell lesions-a retrospective review of final surgical pathology. Thyroid Disord Ther 3(155):2

    Google Scholar 

  17. Elliott DD, Pitman MB, Bloom L, Faquin WC (2006) Fine-needle aspiration biopsy of Hurthle cell lesions of the thyroid gland: a cytomorphologic study of 139 cases with statistical analysis. Cancer 108(2):102–109

    Article  PubMed  Google Scholar 

  18. Barnabei A, Ferretti E, Baldelli R et al (2009) Hurthle cell tumours of the thyroid. Personal experience and review of the literature. Acta Otorhinolaryngol Ital 29(6):305–311

    CAS  PubMed  PubMed Central  Google Scholar 

  19. McHenry CR, Thomas SR, Slusarczyk SJ, Khiyami A (1999) Follicular or Hu ̈rthle cell neoplasm of the thyroid: can clinical factors be used to predict carcinoma and determine extent of thyroidectomy? Surgery 126(4):798–804

    Article  CAS  PubMed  Google Scholar 

  20. Pisanu A, Di Chiara B, Reccia I, Uccheddu A (2010) Oncocytic cell tumors of the thyroid: factors predicting malignancy and influencing prognosis, treatment decisions, and outcomes. World J Surg 34(4):836–843

    Article  PubMed  Google Scholar 

  21. Yang YJ, Khurana KK (2001) Diagnostic utility of intracytoplasmic lumen and transgressing vessels in evaluation of Hurthle cell lesions by fine-needle aspiration. Arch Pathol Lab Med 125(8):1031–1035

    CAS  PubMed  Google Scholar 

  22. Lee KH, Shin JH, Ko ES et al (2013) Predictive factors of malignancy in patients with cytologically suspicious for Hurthle cell neoplasm of thyroid nodules. Int J Surg 11(9):898–902

    Article  PubMed  Google Scholar 

  23. Mills SC, Haq M, Smellie WJ, Harmer C (2009) Hurthle cell carcinoma of the thyroid: retrospective review of 62 patients treated at the Royal Marsden Hospital between 1946 and 2003. Eur J Surg Oncol 35(3):230–234

    Article  CAS  PubMed  Google Scholar 

  24. Hoos A, Stojadinovic A, Singh B et al (2002) Clinical significance of molecular expression profiles of Hurthle cell tumors of the thyroid gland analyzed via tissue microarrays. Am J Pathol 160(1):175–183

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Maizlin ZV, Wiseman SM, Vora P et al (2008) Hurthle cell neoplasms of the thyroid: sonographic appearance and histologic characteristics. J Ultrasound Med 27(5):751–757, quiz 9

    PubMed  Google Scholar 

  26. Cannon J (2011) The significance of Hürthle cells in thyroid disease. Oncologist 16(10):1380–1387

    Article  PubMed  PubMed Central  Google Scholar 

  27. Melck A, Bugis S, Baliski C et al (2006) Hemithyroidectomy: the preferred initial surgical approach for management of Hurthle cell neoplasm. Am J Surg 191(5):593–597

    Article  CAS  PubMed  Google Scholar 

  28. Chao T-C, Lin J-D, Chen M-F (2005) Surgical treatment of Hurthle cell tumors of the thyroid. World J Surg 29(2):164–168

    Article  PubMed  Google Scholar 

  29. Chen H, Nicol TL, Zeiger MA et al (1998) Hurthle cell neoplasms of the thyroid: are there factors predictive of malignancy? Ann Surg 227(4):542–546

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Hudak K, Mazeh H, Sippel RS, Chen H (2012) Hürthle cell metaplasia on fine-needle aspiration biopsy is not by itself an indication for thyroid surgery. Am J Surg 203(3):287–291

    Article  PubMed  Google Scholar 

  31. Montone KT, Baloch ZW, LiVolsi VA (2008) The thyroid Hurthle (oncocytic) cell and its associated pathologic conditions: a surgical pathology and cytopathology review. Arch Pathol Lab Med 132(8):1241–1250

    PubMed  Google Scholar 

  32. Cooper DS, Doherty GM, Haugen BR et al (2009) Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 19(11):1167–1214

    Article  PubMed  Google Scholar 

  33. Pu RT, Yang J, Wasserman PG et al (2006) Does Hurthle cell lesion/neoplasm predict malignancy more than follicular lesion/neoplasm on thyroid fine-needle aspiration? Diagn Cytopathol 34(5):330–334

    Article  PubMed  Google Scholar 

  34. Alaedeen DI, Khiyami A, McHenry CR (2005) Fine-needle aspiration biopsy specimen with a predominance of Hürthle cells: a dilemma in the management of nodular thyroid disease. Surgery 138(4):650–657

    Article  PubMed  Google Scholar 

  35. Galera-Davidson H, González-Cámpora R (2008) Chapter 23 - thyroid. In: Wilbur MB (ed) Comprehensive cytopathology, 3rd edn. W.B. Saunders, Edinburgh, pp 633–670

    Chapter  Google Scholar 

  36. Clark D, Faquin W (2010) Hurthle cell lesions. Thyroid cytopathology. Springer, US, pp 93–107

    Google Scholar 

  37. Kasper K, Stewart J III, Das K (2012) Fine needle aspiration cytology of thyroid nodules with Hürthle cells: cytomorphologic predictors for neoplasms, improving diagnostic accuracy and overcoming pitfalls. J Am Soc Cytopathol 1(1):S62–S63

    Article  Google Scholar 

  38. Baloch ZW, LiVolsi VA, Asa SL et al (2008) Diagnostic terminology and morphologic criteria for cytologic diagnosis of thyroid lesions: a synopsis of the National Cancer Institute Thyroid Fine-Needle Aspiration State of the Science Conference. Diagn Cytopathol 36(6):425–437

    Article  PubMed  Google Scholar 

  39. Chiappetta G, Toti P, Cetta F et al (2002) The RET/PTC oncogene is frequently activated in oncocytic thyroid tumors (Hurthle cell adenomas and carcinomas), but not in oncocytic hyperplastic lesions. J Clin Endocrinol Metab 87(1):364–369

    Article  CAS  PubMed  Google Scholar 

  40. Zhang YW, Greenblatt DY, Repplinger D et al (2008) QS264. Factors that predict malignancy in Hürthle cell neoplasms of the thyroid. J Surg Res 144(2):371–372

    Article  Google Scholar 

  41. Stojadinovic A, Ghossein RA, Hoos A et al (2001) Hurthle cell carcinoma: a critical histopathologic appraisal. J Clin Oncol 19(10):2616–2625

    CAS  PubMed  Google Scholar 

  42. Pisanu A, Sias L, Uccheddu A (2004) Factors predicting malignancy of Hürthle cell tumors of the thyroid: influence on surgical treatment. World J Surg 28(8):761–765

    Article  PubMed  Google Scholar 

  43. Lopez-Penabad L, Chiu AC, Hoff AO et al (2003) Prognostic factors in patients with Hurthle cell neoplasms of the thyroid. Cancer 97(5):1186–1194

    Article  PubMed  Google Scholar 

  44. Zhang Y, Greenblatt D, Repplinger D et al (2008) Older age and larger tumor size predict malignancy in Hürthle cell neoplasms of the thyroid. Ann Surg Oncol 15(10):2842–2846

    Article  PubMed  Google Scholar 

  45. Suh I, Vriens MR, Guerrero MA et al (2010) Serum thyroglobulin is a poor diagnostic biomarker of malignancy in follicular and Ḧurthle-cell neoplasms of the thyroid. Am J Surg 200(1):41–46

    Article  CAS  PubMed  Google Scholar 

  46. Parikh PP, Allan BJ, Lew JI (2013) Surgeon-performed ultrasound predictors of malignancy in patients with Hürthle cell neoplasms of the thyroid. J Surg Res 184(1):247–252

    Article  PubMed  Google Scholar 

  47. Sugino K, Ito K, Mimura T et al (2001) Hürthle cell tumor of the thyroid: analysis of 188 cases. World J Surg 25(9):1160–1163

    Article  CAS  PubMed  Google Scholar 

  48. Sippel RS, Elaraj DM, Khanafshar E et al (2008) Tumor size predicts malignant potential in Hurthle cell neoplasms of the thyroid. World J Surg 32(5):702–707

    Article  PubMed  Google Scholar 

  49. Paunovic I, Krgovic K, Tatic S et al (2006) Surgery for thyroid Hürthle cell tumours—a single institution experience. Eur J Surg Oncol 32(4):458–461

    Article  CAS  PubMed  Google Scholar 

  50. Petric R, Besic H, Besic N (2014) Preoperative serum thyroglobulin concentration as a predictive factor of malignancy in small follicular and Hürthle cell neoplasms of the thyroid gland. World J Surg Oncol 12(1):1–7

    Article  Google Scholar 

  51. Arduc A, Dogan BA, Tuna MM, et al (2015) Higher body mass index and larger waist circumference may be predictors of thyroid carcinoma in patients with Hurthle-cell lesion/neoplasm fine-needle aspiration diagnosis. Clin Endocrinol (Oxf) 83(3):405–411

  52. Erickson LA, Jin L, Goellner JR et al (2000) Pathologic features, proliferative activity, and cyclin D1 expression in Hurthle cell neoplasms of the thyroid. Mod Pathol 13(2):186–192

    Article  CAS  PubMed  Google Scholar 

  53. Cheung CC, Ezzat S, Ramyar L et al (2000) Molecular basis of Hurthle cell papillary thyroid carcinoma. J Clin Endocrinol Metab 85(2):878–882

    CAS  PubMed  Google Scholar 

  54. Histopathology A (2004) Histopathology of thyroid tumors. An overview. Hormones 3(2):100–110

    Article  Google Scholar 

  55. Berho M, Suster S (1997) The oncocytic variant of papillary carcinoma of the thyroid: a clinicopathologic study of 15 cases. Hum Pathol 28(1):47–53

    Article  CAS  PubMed  Google Scholar 

  56. Sabino de Matos P (2008) Thyroid epithelial tumours. Diagn Histopathol 14(5):236–246

    Article  Google Scholar 

  57. Lloyd RV, Buehler D, Khanafshar E (2011) Papillary thyroid carcinoma variants. Head Neck Pathol 5(1):51–56

    Article  PubMed  PubMed Central  Google Scholar 

  58. Belchetz G, Cheung CC, Freeman J et al (2002) Hürthle cell tumors: using molecular techniques to define a novel classification system. Arch Otolaryngol Head Neck Surg 128(3):237–240

    Article  PubMed  Google Scholar 

  59. Musholt PB, Imkamp F, von Wasielewski R et al (2003) RET rearrangements in archival oxyphilic thyroid tumors: new insights in tumorigenesis and classification of Hürthle cell carcinomas? Surgery 134(6):881–889

    Article  PubMed  Google Scholar 

  60. Nikiforov YE, Biddinger PW, Thompson LDR (2012) Diagnostic pathology and molecular genetics of the thyroid: a comprehensive guide for practicing thyroid pathology. USA, Wolters Kluwer Health

    Google Scholar 

  61. Haigh PI, Urbach DR (2005) The treatment and prognosis of Hürthle cell follicular thyroid carcinoma compared with its non-Hürthle cell counterpart. Surgery 138(6):1152–1158

    Article  PubMed  Google Scholar 

  62. Khafif A, Khafif RA, Attie JN (1999) Hürthle cell carcinoma: a malignancy of low-grade potential. Head Neck 21(6):506–511

    Article  CAS  PubMed  Google Scholar 

  63. Kushchayeva Y, Duh Q-Y, Kebebew E et al (2008) Comparison of clinical characteristics at diagnosis and during follow-up in 118 patients with Hurthle cell or follicular thyroid cancer. Am J Surg 195(4):457–462

    Article  PubMed  Google Scholar 

  64. Dettori T, Frau DV, Lai ML et al (2003) Aneuploidy in oncocytic lesions of the thyroid gland: diffuse accumulation of mitochondria within the cell is associated with trisomy 7 and progressive numerical chromosomal alterations. Genes Chromosom Cancer 38(1):22–31

    Article  CAS  PubMed  Google Scholar 

  65. Wada N, Duh QY, Miura D et al (2002) Chromosomal aberrations by comparative genomic hybridization in hurthle cell thyroid carcinomas are associated with tumor recurrence. J Clin Endocrinol Metab 87(10):4595–4601

    Article  CAS  PubMed  Google Scholar 

  66. Máximo V, Soares P, Lima J et al (2002) Mitochondrial DNA somatic mutations (point mutations and large deletions) and mitochondrial DNA variants in human thyroid pathology: a study with emphasis on Hürthle cell tumors. Am J Pathol 160(5):1857–1865

    Article  PubMed  PubMed Central  Google Scholar 

  67. Carcangiu ML, Bianchi S, Savino D et al (1991) Follicular Hurthle cell tumors of the thyroid gland. Cancer 68(9):1944–1953

    Article  CAS  PubMed  Google Scholar 

  68. Finley DJ, Zhu B, Fahey Iii TJ (2004) Molecular analysis of Hurthle cell neoplasms by gene profiling. Surgery 136(6):1160–1168

    Article  PubMed  Google Scholar 

  69. Chindris A-M, Casler JD, Bernet VJ, et al (2014) Clinical and molecular features of Hürthle cell carcinoma of the thyroid. J Clin Endocrinol Metab 0(0):jc.2014-1634

  70. Papotti M, Torchio B, Grassi L et al (1996) Poorly differentiated oxyphilic (Hurthle cell) carcinomas of the thyroid. Am J Surg Pathol 20(6):686–694

    Article  CAS  PubMed  Google Scholar 

  71. Dedivitis RA, Di Giovanni JH, Silva GF et al (2004) Oncocytic variant of medullary thyroid carcinoma: case report. Arq Bras Endocrinol Metabol 48(2):315–317

    Article  PubMed  Google Scholar 

  72. Sobrinho-Simões M, Magalhães J, Fonseca E, Amendoeira I (2005) Diagnostic pitfalls of thyroid pathology. Curr Diagn Pathol 11(1):52–59

    Article  Google Scholar 

  73. Ain K (2000) Unusual types of thyroid cancer. Rev Endocr Metab Disord 1(3):225–231

    Article  CAS  PubMed  Google Scholar 

  74. Bhattacharyya N (2003) Survival and prognosis in Hürthle cell carcinoma of the thyroid gland. Arch Otolaryngol Head Neck Surg 129(2):207–210

    Article  PubMed  Google Scholar 

  75. Ozlem Kucuk N, Kulak H, Tokmak E et al (2006) Hurthle cell carcinoma: a clinicopathological study of thirteen cases. Nucl Med Commun 27(4):377–379

    Article  CAS  PubMed  Google Scholar 

  76. Yutan E, Clark O (2001) Hürthle cell carcinoma. Curr Treat Options in Oncol 2(4):331–335

    Article  CAS  Google Scholar 

  77. Shaha AR, Shah JP, Loree TR (1996) Patterns of nodal and distant metastasis based on histologic varieties in differentiated carcinoma of the thyroid. Am J Surg 172(6):692–694

    Article  CAS  PubMed  Google Scholar 

  78. Ruegemer JJ, Hay ID, Bergstralh EJ et al (1988) Distant metastases in differentiated thyroid carcinoma: a multivariate analysis of prognostic variables. J Clin Endocrinol Metab 67(3):501–508

    Article  CAS  PubMed  Google Scholar 

  79. Schneider DF, Chen H (2013) New developments in the diagnosis and treatment of thyroid cancer. CA Cancer J Clin 63(6):373–394

    Article  PubMed Central  Google Scholar 

  80. Shaha AR, Loree TR, Shah JP (1995) Prognostic factors and risk group analysis in follicular carcinoma of the thyroid. Surgery 118(6):1131–1138

    Article  CAS  PubMed  Google Scholar 

  81. Herrera M, Hay I, Wu PC et al (1992) Hürthle cell (oxyphilic) papillary thyroid carcinoma: a variant with more aggressive biologic behavior. World J Surg 16(4):669–674

    Article  CAS  PubMed  Google Scholar 

  82. McDonald MP, Sanders LE, Silverman ML et al (1996) Hürthle cell carcinoma of the thyroid gland: prognostic factors and results of surgical treatment. Surgery 120(6):1000–1005

    Article  CAS  PubMed  Google Scholar 

  83. Stojadinovic A, Hoos A, Ghossein R et al (2002) Hürthle cell carcinoma: a 60-year experience. Ann Surg Oncol 9(2):197–203

    PubMed  Google Scholar 

  84. Goldstein NS, Czako P, Neill JS (2000) Metastatic minimally invasive (encapsulated) follicular and Hurthle cell thyroid carcinoma: a study of 34 patients. Mod Pathol 13(2):123–130

    Article  CAS  PubMed  Google Scholar 

  85. Azadian A, Rosen IB, Walfish PG, Asa SL (1995) Management considerations in Hürthle cell carcinoma. Surgery 118(4):711–715

    Article  CAS  PubMed  Google Scholar 

  86. Kauffmann PR, Dejax C, de Latour M, Dauplat J (2004) The meaning and predictivity of Hürthle cells in fine needle aspiration cytology for thyroid nodular disease. Eur J Surg Oncol 30(7):786–789

    Article  CAS  PubMed  Google Scholar 

  87. Gallagher L, Hughes M, McMillian L (2013) National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology. Thyroid Carcinoma Version 2. 2013. Available from: http://www.nccn.org/professionals/physician_gls/pdf/thyroid.pdf

  88. Alexander EK, Kennedy GC, Baloch ZW et al (2012) Preoperative diagnosis of benign thyroid nodules with indeterminate cytology. N Engl J Med 367(8):705–715

    Article  CAS  PubMed  Google Scholar 

  89. Tuzun D, Ersoy R, Kilicyazgan A, et al (2014) Elastosonography scoring and strain index of thyroid nodules with Hurthle cells. Minerva Endocrinol [Epub ahead of print]

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Shawky, M., Sakr, M. Hurthle Cell Lesion: Controversies, Challenges, and Debates. Indian J Surg 78, 41–48 (2016). https://doi.org/10.1007/s12262-015-1381-x

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