Follicular and Hürthle Cell Carcinoma

  • Naris NilubolEmail author
  • Xavier Keutgen
  • Electron Kebebew


Follicular neoplasms are uncommon thyroid tumors with several histologic subtypes, such as follicular adenoma, Hürthle cell adenoma, and minimally invasive and widely invasive follicular and Hürthle thyroid carcinoma. The diagnosis of a malignant follicular thyroid tumor is based on the presence of capsular and/or vascular invasion on histologic examination. In this chapter, we review the clinical, radiographic, and pathological characteristics of follicular and Hürthle cell carcinoma. The role of molecular diagnostic assays to distinguish benign tumors from malignant counterparts is still limited. The difference in tumor behavior between follicular and Hürthle cell carcinoma is discussed. Although controversies related to the optimal management of these tumors remain due to their rarity, this chapter includes the management of minimally invasive follicular thyroid carcinoma based on clinicopathological risk factors. We summarize the treatments of widely invasive follicular and Hürthle cell carcinoma, including the role of lymphadenectomy in treating these tumors. Postoperative management methods, such as the use of radioactive iodine ablation, thyroid-stimulating hormone (TSH) suppression therapy in follicular and Hürthle cell carcinoma, as well as surveillance for recurrent disease, are included. Lastly, we provide the summary of the outcome that shows shorter survival in patients with Hürthle cell carcinoma, as compared with those with follicular and papillary thyroid carcinoma.


Follicular thyroid carcinoma Hürthle cell carcinoma Minimally invasive follicular thyroid carcinoma Widely invasive follicular thyroid carcinoma Follicular neoplasm Hürthle cell neoplasm 


  1. 1.
    DeLellis RA, Lloyd RV, Heitz PU. World Health Organization classification of tumours. In: Pathology and genetics of tumours of endocrine organs. Lyon: IARC Press; 2004.Google Scholar
  2. 2.
    Franssila KO, Ackerman LV, Brown CL, Hedinger CE. Follicular carcinoma. Semin Diagn Pathol. 1985;2(2):101–22.PubMedGoogle Scholar
  3. 3.
    Kushchayeva Y, Duh QY, Kebebew E, D’Avanzo A, Clark OH. Comparison of clinical characteristics at diagnosis and during follow-up in 118 patients with Hurthle cell or follicular thyroid cancer. Am J Surg. 2008;195(4):457–62.CrossRefPubMedGoogle Scholar
  4. 4.
    Correa P, Chen VW. Endocrine gland cancer. Cancer. 1995;75(1 Suppl):338–52.PubMedGoogle Scholar
  5. 5.
    Baloch ZW, LiVolsi VA. Our approach to follicular-patterned lesions of the thyroid. J Clin Pathol. 2007;60(3):244–50.CrossRefPubMedGoogle Scholar
  6. 6.
    Kim HJ, Sung JY, Oh YL, Kim JH, Son YI, Min YK, et al. Association of vascular invasion with increased mortality in patients with minimally invasive follicular thyroid carcinoma but not widely invasive follicular thyroid carcinoma. Head Neck. 2014;36(12):1695–700.CrossRefPubMedGoogle Scholar
  7. 7.
    Shaha AR, Shah JP, Loree TR. Patterns of nodal and distant metastasis based on histologic varieties in differentiated carcinoma of the thyroid. Am J Surg. 1996;172(6):692–4.CrossRefPubMedGoogle Scholar
  8. 8.
    Lo CY, Chan WF, Lam KY, Wan KY. Follicular thyroid carcinoma: the role of histology and staging systems in predicting survival. Ann Surg. 2005;242(5):708–15.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Phitayakorn R, McHenry CR. Follicular and Hurthle cell carcinoma of the thyroid gland. Surg Oncol Clin N Am. 2006;15(3):603–23, ix–x.CrossRefPubMedGoogle Scholar
  10. 10.
    Ewing J. Neoplastic disease: a treatise on tumors. 3rd ed. Philadelphia: W. B. Saunders Company; 1928.Google Scholar
  11. 11.
    Goffredo P, Roman SA, Sosa JA. Hurthle cell carcinoma: a population-level analysis of 3311 patients. Cancer. 2013;119(3):504–11.CrossRefPubMedGoogle Scholar
  12. 12.
    Lopez-Penabad L, Chiu AC, Hoff AO, Schultz P, Gaztambide S, Ordonez NG, et al. Prognostic factors in patients with Hurthle cell neoplasms of the thyroid. Cancer. 2003;97(5):1186–94.CrossRefPubMedGoogle Scholar
  13. 13.
    Arganini M, Behar R, Wu TC, Straus 2nd F, McCormick M, DeGroot LJ, et al. Hurthle cell tumors: a twenty-five-year experience. Surgery. 1986;100(6):1108–15.PubMedGoogle Scholar
  14. 14.
    Gundry SR, Burney RE, Thompson NW, Lloyd R. Total thyroidectomy for Hurthle cell neoplasm of the thyroid. Arch Surg. 1983;118(5):529–32.CrossRefPubMedGoogle Scholar
  15. 15.
    Panda SK, Patro B, Samantaroy MR, Mishra J, Mohapatra KC, Meher RK. Unusual presentation of follicular carcinoma thyroid with special emphasis on their management. Int J Surg Case Rep. 2014;5(7):408–11.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Dionigi G, Kraimps JL, Schmid KW, Hermann M, Sheu-Grabellus SY, De Wailly P, et al. Minimally invasive follicular thyroid cancer (MIFTC) – a consensus report of the European Society of Endocrine Surgeons (ESES). Langenbecks Arch Surg. 2014;399(2):165–84.CrossRefPubMedGoogle Scholar
  17. 17.
    Rosai J, Carcargiu ML, DeLellis RA. Tumors of the thyroid gland, 3rd series. In: Rosai J, Sobin L, editors. Atlas of tumor pathology. Washington, DC: Armed Forces Institute of Pathology; 1992.Google Scholar
  18. 18.
    Sillery JC, Reading CC, Charboneau JW, Henrichsen TL, Hay ID, Mandrekar JN. Thyroid follicular carcinoma: sonographic features of 50 cases. AJR Am J Roentgenol. 2010;194(1):44–54.CrossRefPubMedGoogle Scholar
  19. 19.
    Seo HS, Lee DH, Park SH, Min HS, Na DG. Thyroid follicular neoplasms: can sonography distinguish between adenomas and carcinomas? J Clin Ultrasound JCU. 2009;37(9):493–500.CrossRefPubMedGoogle Scholar
  20. 20.
    Iared W, Shigueoka DC, Cristofoli JC, Andriolo R, Atallah AN, Ajzen SA, et al. Use of color Doppler ultrasonography for the prediction of malignancy in follicular thyroid neoplasms: systematic review and meta-analysis. J Ultrasound Med Off J Am Inst Ultrasound Med. 2010;29(3):419–25.Google Scholar
  21. 21.
    Lee SK, Rho BH, Woo SK. Hurthle cell neoplasm: correlation of gray-scale and power Doppler sonographic findings with gross pathology. J Clin Ultrasound JCU. 2010;38(4):169–76.PubMedGoogle Scholar
  22. 22.
    Maizlin ZV, Wiseman SM, Vora P, Kirby JM, Mason AC, Filipenko D, et al. Hurthle cell neoplasms of the thyroid: sonographic appearance and histologic characteristics. J Ultrasound Med Off J Am Inst Ultrasound Med. 2008;27(5):751–7; quiz 9.Google Scholar
  23. 23.
    LiVolsi VA. Surgical pathology of the thyroid. Philadelphia: Saunders; 1990.Google Scholar
  24. 24.
    McLeod MK, Thompson NW. Hurthle cell neoplasms of the thyroid. Otolaryngol Clin North Am. 1990;23(3):441–52.PubMedGoogle Scholar
  25. 25.
    Alexander EK, Kennedy GC, Baloch ZW, Cibas ES, Chudova D, Diggans J, et al. Preoperative diagnosis of Benign thyroid nodules with indeterminate cytology. N Engl J Med. 2012;367:705–15.CrossRefPubMedGoogle Scholar
  26. 26.
    Mathur A, Olson MT, Zeiger MA. Follicular lesions of the thyroid. Surg Clin North Am. 2014;94(3):499–513.CrossRefPubMedGoogle Scholar
  27. 27.
    Li H, Robinson KA, Anton B, Saldanha IJ, Ladenson PW. Cost-effectiveness of a novel molecular test for cytologically indeterminate thyroid nodules. J Clin Endocrinol Metab. 2011;96(11):E1719–26.CrossRefPubMedGoogle Scholar
  28. 28.
    Nikiforov YE, Steward DL, Robinson-Smith TM, Haugen BR, Klopper JP, Zhu Z, et al. Molecular testing for mutations in improving the fine-needle aspiration diagnosis of thyroid nodules. J Clin Endocrinol Metab. 2009;94(6):2092–8.CrossRefPubMedGoogle Scholar
  29. 29.
    Yip L, Kebebew E, Milas M, Carty SE, Fahey 3rd TJ, Parangi S, et al. Summary statement: utility of molecular marker testing in thyroid cancer. Surgery. 2010;148(6):1313–5.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Ohori NP, Nikiforova MN, Schoedel KE, LeBeau SO, Hodak SP, Seethala RR, et al. Contribution of molecular testing to thyroid fine-needle aspiration cytology of “follicular lesion of undetermined significance/atypia of undetermined significance”. Cancer Cytopathol. 2010;118(1):17–23.CrossRefPubMedGoogle Scholar
  31. 31.
    Nikiforov YE, Carty SE, Chiosea SI, Coyne C, Duvvuri U, Ferris RL, et al. Highly accurate diagnosis of cancer in thyroid nodules with follicular neoplasm/suspicious for a follicular neoplasm cytology by ThyroSeq v2 next-generation sequencing assay. Cancer. 2014;120(23):3627–34.CrossRefPubMedGoogle Scholar
  32. 32.
    Alevizaki M, Papageorgiou G, Rentziou G, Saltiki K, Marafelia P, Loukari E, et al. Increasing prevalence of papillary thyroid carcinoma in recent years in Greece: the majority are incidental. Thyroid. 2009;19(7):749–54.CrossRefPubMedGoogle Scholar
  33. 33.
    Baloch ZW, Fleisher S, LiVolsi VA, Gupta PK. Diagnosis of “follicular neoplasm”: a gray zone in thyroid fine-needle aspiration cytology. Diagn Cytopathol. 2002;26(1):41–4.CrossRefPubMedGoogle Scholar
  34. 34.
    Sobrinho-Simoes M, Eloy C, Magalhaes J, Lobo C, Amaro T. Follicular thyroid carcinoma. Mod Pathol. 2011;24 Suppl 2:S10–8.CrossRefPubMedGoogle Scholar
  35. 35.
    LiVolsi VA, Baloch ZW. Follicular-patterned tumors of the thyroid: the battle of benign vs. malignant vs. so-called uncertain. Endocr Pathol. 2011;22(4):184–9.CrossRefPubMedGoogle Scholar
  36. 36.
    Rosai J. Handling of thyroid follicular patterned lesions. Endocr Pathol. 2005;16(4):279–83.CrossRefPubMedGoogle Scholar
  37. 37.
    Ghossein R. Update to the College of American Pathologists reporting on thyroid carcinomas. Head Neck Pathol. 2009;3(1):86–93.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Saade N, Sadler C, Goldfarb M. Impact of regional lymph node dissection on disease specific survival in adrenal cortical carcinoma. Horm Metab Res. 2015;47:820–5.CrossRefPubMedGoogle Scholar
  39. 39.
    Lang W, Choritz H, Hundeshagen H. Risk factors in follicular thyroid carcinomas. A retrospective follow-up study covering a 14-year period with emphasis on morphological findings. Am J Surg Pathol. 1986;10(4):246–55.CrossRefPubMedGoogle Scholar
  40. 40.
    van Heerden JA, Hay ID, Goellner JR, Salomao D, Ebersold JR, Bergstralh EJ, et al. Follicular thyroid carcinoma with capsular invasion alone: a nonthreatening malignancy. Surgery. 1992;112(6):1130–6; discussion 6–8.PubMedGoogle Scholar
  41. 41.
    Ito Y, Hirokawa M, Masuoka H, Yabuta T, Kihara M, Higashiyama T, et al. Prognostic factors of minimally invasive follicular thyroid carcinoma: extensive vascular invasion significantly affects patient prognosis. Endocr J. 2013;60(5):637–42.CrossRefPubMedGoogle Scholar
  42. 42.
    Lang BH, Lo CY, Chan WF, Lam KY, Wan KY. Staging systems for follicular thyroid carcinoma: application to 171 consecutive patients treated in a tertiary referral centre. Endocr Relat Cancer. 2007;14(1):29–42.CrossRefPubMedGoogle Scholar
  43. 43.
    Goldstein NS, Czako P, Neill JS. Metastatic minimally invasive (encapsulated) follicular and Hurthle cell thyroid carcinoma: a study of 34 patients. Mod Pathol. 2000;13(2):123–30.CrossRefPubMedGoogle Scholar
  44. 44.
    Ghossein RA, Hiltzik DH, Carlson DL, Patel S, Shaha A, Shah JP, et al. Prognostic factors of recurrence in encapsulated Hurthle cell carcinoma of the thyroid gland: a clinicopathologic study of 50 cases. Cancer. 2006;106(8):1669–76.CrossRefPubMedGoogle Scholar
  45. 45.
    Cibas ES, Ali SZ, Conference NCITFSotS. The bethesda system for reporting thyroid cytopathology. Am J Clin Pathol. 2009;132(5):658–65.CrossRefPubMedGoogle Scholar
  46. 46.
    Chen H, Nicol TL, Udelsman R. Follicular lesions of the thyroid. Does frozen section evaluation alter operative management? Ann Surg. 1995;222(1):101–6.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    LiVolsi VA, Baloch ZW. Use and abuse of frozen section in the diagnosis of follicular thyroid lesions. Endocr Pathol. 2005;16(4):285–93.CrossRefPubMedGoogle Scholar
  48. 48.
    Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid. 2016;26(1):1–133.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Huang CC, Hsueh C, Liu FH, Chao TC, Lin JD. Diagnostic and therapeutic strategies for minimally and widely invasive follicular thyroid carcinomas. Surg Oncol. 2011;20(1):1–6.CrossRefPubMedGoogle Scholar
  50. 50.
    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(1):35–9.CrossRefPubMedGoogle Scholar
  51. 51.
    Gemsenjager E, Heitz PU, Martina B. Selective treatment of differentiated thyroid carcinoma. World J Surg. 1997;21(5):546–51; discussion 51–2.CrossRefPubMedGoogle Scholar
  52. 52.
    Sugino K, Kameyama K, Ito K, Nagahama M, Kitagawa W, Shibuya H, et al. Outcomes and prognostic factors of 251 patients with minimally invasive follicular thyroid carcinoma. Thyroid. 2012;22(8):798–804.CrossRefPubMedGoogle Scholar
  53. 53.
    Chen H, Nicol TL, Zeiger MA, Dooley WC, Ladenson PW, Cooper DS, et al. Hurthle cell neoplasms of the thyroid: are there factors predictive of malignancy? Ann Surg. 1998;227(4):542–6.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Zhang YW, Greenblatt DY, Repplinger D, Bargren A, Adler JT, Sippel RS, et al. Older age and larger tumor size predict malignancy in hurthle cell neoplasms of the thyroid. Ann Surg Oncol. 2008;15(10):2842–6.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Thompson NW, Dunn EL, Batsakis JG, Nishiyama RH. Hurthle cell lesions of the thyroid gland. Surg Gynecol Obstet. 1974;139(4):555–60.PubMedGoogle Scholar
  56. 56.
    McDonald MP, Sanders LE, Silverman ML, Chan HS, Buyske J. Hurthle cell carcinoma of the thyroid gland: prognostic factors and results of surgical treatment. Surgery. 1996;120(6):1000–4; discussion 4–5.CrossRefPubMedGoogle Scholar
  57. 57.
    Sanders LE, Silverman M. Follicular and Hurthle cell carcinoma: predicting outcome and directing therapy. Surgery. 1998;124(6):967–74.CrossRefPubMedGoogle Scholar
  58. 58.
    Stojadinovic A, Ghossein RA, Hoos A, Urist MJ, Spiro RH, Shah JP, et al. Hurthle cell carcinoma: a critical histopathologic appraisal. J Clin Oncol. 2001;19(10):2616–25.CrossRefPubMedGoogle Scholar
  59. 59.
    Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2009;19(11):1167–214.CrossRefPubMedGoogle Scholar
  60. 60.
    Mazzaferri EL, Jhiang SM. Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med. 1994;97(5):418–28.CrossRefPubMedGoogle Scholar
  61. 61.
    Lin JD, Hsueh C, Chao TC. Early recurrence of papillary and follicular thyroid carcinoma predicts a worse outcome. Thyroid. 2009;19(10):1053–9.CrossRefPubMedGoogle Scholar
  62. 62.
    Besic N, Hocevar M, Zgajnar J, Petric R, Pilko G. Aggressiveness of therapy and prognosis of patients with Hurthle cell papillary thyroid carcinoma. Thyroid. 2006;16(1):67–72.CrossRefPubMedGoogle Scholar
  63. 63.
    Gonzalez C, Aulinas A, Colom C, Tundidor D, Mendoza L, Corcoy R, et al. Thyroglobulin as early prognostic marker to predict remission at 18–24 months in differentiated thyroid carcinoma. Clin Endocrinol (Oxf). 2014;80(2):301–6.CrossRefGoogle Scholar
  64. 64.
    Kloos RT, Mazzaferri EL. A single recombinant human thyrotropin-stimulated serum thyroglobulin measurement predicts differentiated thyroid carcinoma metastases three to five years later. J Clin Endocrinol Metab. 2005;90(9):5047–57.CrossRefPubMedGoogle Scholar
  65. 65.
    Goffredo P, Cheung K, Roman SA, Sosa JA. Can minimally invasive follicular thyroid cancer be approached as a benign lesion?: a population-level analysis of survival among 1,200 patients. Ann Surg Oncol. 2013;20(3):767–72.CrossRefPubMedGoogle Scholar
  66. 66.
    Ito Y, Hirokawa M, Masuoka H, Yabuta T, Fukushima M, Kihara M, et al. Distant metastasis at diagnosis and large tumor size are significant prognostic factors of widely invasive follicular thyroid carcinoma. Endocr J. 2013;60(6):829–33.CrossRefPubMedGoogle Scholar
  67. 67.
    Hundahl SA, Fleming ID, Fremgen AM, Menck HR. A National Cancer Data Base report on 53,856 cases of thyroid carcinoma treated in the U.S., 1985–1995 [see comments]. Cancer. 1998;83(12):2638–48.CrossRefPubMedGoogle Scholar
  68. 68.
    Bhattacharyya N. Survival and prognosis in Hurthle cell carcinoma of the thyroid gland. Arch Otolaryngol Head Neck Surg. 2003;129(2):207–10.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  • Naris Nilubol
    • 1
    Email author
  • Xavier Keutgen
    • 2
  • Electron Kebebew
    • 3
  1. 1.Endocrine Oncology BranchNational Cancer InstituteMarylandUSA
  2. 2.Department of SurgeryRush University Medical CenterChicagoUSA
  3. 3.Endocrine Oncology BranchNational Cancer Institute, National Institute of HealthBethesdaUSA

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