Skip to main content

Advertisement

Log in

Follicular-Patterned Afflictions of the Thyroid Gland: Reappraisal of the Most Discussed Entity in Endocrine Pathology

  • Published:
Endocrine Pathology Aims and scope Submit manuscript

Abstract

The past 25 years has seen a marked increase in our understanding of thyroid neoplasia, from the interrelationship with radiation exposure, the definition of variants of papillary carcinoma, to the application of molecular biology techniques to capture a more basic definition of tumor development, diagnosis, and prognostic implications. No other group of thyroid tumors has been studied as much as those with follicular pattern. In this review, we present a reappraisal of these controversial lesions in light of the issues with the diagnostic problems and classification schemes of follicular thyroid lesions, with emphasis on the progress made in the past quarter century and a focus on the current persistent controversies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Rosai J: The continuing role of morphology in the molecular age. Mod Pathol 2001, 14(3):258–260.

    Article  PubMed  CAS  Google Scholar 

  2. Baloch ZW, Livolsi VA: Follicular-patterned lesions of the thyroid: the bane of the pathologist. Am J Clin Pathol 2002, 117(1):143–150.

    Article  PubMed  Google Scholar 

  3. Williams ED, Abrosimov A, Bogdanova TI, Rosai J, Sidorov Y, Thomas GA: Two proposals regarding the terminology of thyroid tumors. Guest Editorial. Int J Surg Pathol 2000, 8(3):181–183.

    Article  PubMed  Google Scholar 

  4. Rosai J, Carcangui ML, DeLellis RA: Tumors of The Thyroid Gland, vol. 3rd Series, Fascicle 5. Washington, DC: Armed Forces Institute of Pathology; 1992.

    Google Scholar 

  5. Elsheikh TM, Asa SL, Chan JK, DeLellis RA, Heffess CS, LiVolsi VA, Wenig BM: Interobserver and intraobserver variation among experts in the diagnosis of thyroid follicular lesions with borderline nuclear features of papillary carcinoma. Am J Clin Pathol 2008, 130(5):736–744.

    Article  PubMed  Google Scholar 

  6. Lloyd RV, Erickson LA, Casey MB, Lam KY, Lohse CM, Asa SL, Chan JK, DeLellis RA, Harach HR, Kakudo K et al: Observer variation in the diagnosis of follicular variant of papillary thyroid carcinoma. Am J Surg Pathol 2004, 28(10):1336–1340.

    Article  PubMed  Google Scholar 

  7. Chan JK: Strict criteria should be applied in the diagnosis of encapsulated follicular variant of papillary thyroid carcinoma. Am J Clin Pathol 2002, 117:16–18.

    Article  PubMed  Google Scholar 

  8. LiVolsi VA: Surgical Pathology of The Thyroid. Philadelphia, PA: WB. Saunders; 1990.

    Google Scholar 

  9. Murray D: The Thyroid Gland. Malden, MA: Blackwell Science; 1998.

    Google Scholar 

  10. Apel RL, Ezzat S, Bapat BV, Pan N, LiVolsi VA, Asa SL: Clonality of thyroid nodules in sporadic goiter. Diagnostic Molecular Pathology 1995, 4(2):113–121.

    Article  PubMed  CAS  Google Scholar 

  11. Baloch ZW, LiVolsi VA: Post fine-needle aspiration histologic alterations of thyroid revisited. Am J Clin Pathol 1999, 112(3):311–316.

    PubMed  CAS  Google Scholar 

  12. LiVolsi VA, Merino MJ: Worrisome histologic alterations following fine-needle aspiration of the thyroid (WHAFFT). Pathol Annu 1994, 29( Pt 2):99–120.

    PubMed  Google Scholar 

  13. LiVolsi VA, Asa SL: The demise of follicular carcinoma of the thyroid gland. Thyroid 1994, 4(2):233–236.

    Article  PubMed  CAS  Google Scholar 

  14. Otto KJ, Lam JS, MacMillan C, Freeman JL: Diminishing diagnosis of follicular thyroid carcinoma. Head Neck 2010, 32(12):1629–1634.

    Article  PubMed  Google Scholar 

  15. Baloch ZW, LiVolsi VA: Our approach to follicular-patterned lesions of the thyroid. J Clin Pathol 2007, 60(3):244–250.

    Article  PubMed Central  PubMed  Google Scholar 

  16. Thompson LD, Wieneke JA, Paal E, Frommelt RA, Adair CF, Heffess CS: A clinicopathologic study of minimally invasive follicular carcinoma of the thyroid gland with a review of the English literature. Cancer 2001, 91(3):505–524.

    Article  PubMed  CAS  Google Scholar 

  17. Lang W, Georgii A, Stauch G, Kienzle E: The differentiation of atypical adenomas and encapsulated follicular carcinomas in the thyroid gland. Virchows Arch [A] 1980, 385:125–141.

    Article  CAS  Google Scholar 

  18. Kahn NF, Perzin KH: Follicular carcinoma of the thyroid: an evaluation of the histologic criteria used for diagnosis. Pathology Annual 1983, 18(Pt 1):221–253.

    PubMed  Google Scholar 

  19. D’Avanzo A, Treseler P, Ituarte PH, Wong M, Streja L, Greenspan FS, Siperstein AE, Duh QY, Clark OH: Follicular thyroid carcinoma: histology and prognosis. Cancer 2004, 100(6):1123–1129.

    Article  PubMed  Google Scholar 

  20. Evans HL (1984) Follicular neoplasms of the thyroid. A study of 44 cases followed for a minimum of 10 years with emphasis on differential diagnosis. Cancer 54:535–540.

    Article  PubMed  CAS  Google Scholar 

  21. Mazzaferri EL: Papillary and follicular thyroid cancer: selective therapy. Compr Ther 1981, 7(5):6–14.

    PubMed  CAS  Google Scholar 

  22. Mazzaferri EL: An overview of the management of papillary and follicular thyroid carcinoma. Thyroid 1999, 9(5):421–427.

    Article  PubMed  CAS  Google Scholar 

  23. Franssila KO, Ackerman LV, Brown CL, Hedinger CE: Follicular carcinoma. Seminars in Diagnostic Pathology 1985, 2(2):101–122.

    PubMed  CAS  Google Scholar 

  24. Collini P, Sampietro G, Rosai J, Pilotti S: 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.

    PubMed  Google Scholar 

  25. Segal K, Arad A, Lubin E, Shpitzer T, Hadar T, Feinmesser R: Follicular carcinoma of the thyroid. Head & Neck 1994, 16(6):533–538.

    Article  CAS  Google Scholar 

  26. 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.

    Article  PubMed  Google Scholar 

  27. DeLellis RA, Lloyd RD, Heitz PU, Eng C (eds.): WHO: Pathology and Genetics. Tumours of Endocrine Organs. Lyon, France: IARC Press; 2004.

    Google Scholar 

  28. Sobrinho-Simoes M, Eloy C, Magalhaes J, Lobo C, Amaro T: Follicular thyroid carcinoma. Mod Pathol 2011, 24 Suppl 2:S10–18.

    Article  PubMed  CAS  Google Scholar 

  29. Evans HL: Encapsulated columnar-cell carcinoma of the thyroid. A report of four cases suggesting a favorable outcome. Am J Surg Pathol 1996, 20:1205–1211.

    Article  PubMed  CAS  Google Scholar 

  30. Zidan J, Kassem S, Kuten A: Follicular carcinoma of the thyroid gland: prognostic factors, treatment, and survival. Am J Clin Oncol 2000, 23(1):1–5.

    Article  PubMed  CAS  Google Scholar 

  31. Shaha AR, Loree TR, Shah JP: Prognostic factors and risk group analysis in follicular carcinoma of the thyroid. Surgery 1995, 118(6):1131–1136; discussion 1136–1138.

    Article  PubMed  CAS  Google Scholar 

  32. Crile G, Jr., Pontius KI, Hawk WA: Factors influencing the survival of patients with follicular carcinoma of the thyroid gland. Surgery, Gynecology & Obstetrics 1985, 160(5):409–413.

    Google Scholar 

  33. Schmidt RJ, Wang CA: Encapsulated follicular carcinoma of the thyroid: diagnosis, treatment, and results. Surgery 1986, 100(6):1068–1077.

    PubMed  CAS  Google Scholar 

  34. Jorda M, Gonzalez-Campora R, Mora J, Herrero-Zapatero A, Otal C, Galera H: Prognostic factors in follicular carcinoma of the thyroid. Arch Pathol Lab Med 1993, 117(6):631–635.

    PubMed  CAS  Google Scholar 

  35. Simpson H, Orr DJ, John PJ, Wilson K, Braidwood AS: Follicular carcinoma of thyroid presenting as back pain leading to a delay in diagnosis. British Journal of Clinical Practice 1994, 48(6):334–336.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  37. Nikiforov YE: Molecular analysis of thyroid tumors. Mod Pathol 2011, 24 Suppl 2:S34–43.

    Article  PubMed  CAS  Google Scholar 

  38. Hirokawa M, Carney JA, Goellner JR, DeLellis RA, Heffess CS, Katoh R, Tsujimoto M, Kakudo K: Observer variation of encapsulated follicular lesions of the thyroid gland. Am J Surg Pathol 2002, 26(11):1508–1514.

    Article  PubMed  Google Scholar 

  39. Chen KTC, Rosai J: Follicular variant of thyroid papillary carcinoma: a clinicopathologic study of six cases. Am J Surg Pathol 1977, 1:123–130.

    Article  Google Scholar 

  40. Ghossein RA, Rosai J, Heffess C: Dyshormonogenetic Goiter: A Clinicopathologic Study of 56 Cases. Endocr Pathol 1997, 8(4):283–292.

    Article  PubMed  Google Scholar 

  41. Baloch ZW, Shafique K, Flannagan M, Livolsi VA: Encapsulated classic and follicular variants of papillary thyroid carcinoma: comparative clinicopathologic study. Endocr Pract 2010, 16(6):952–959.

    Article  PubMed  Google Scholar 

  42. Baloch ZW, LiVolsi VA: Encapsulated follicular variant of papillary thyroid carcinoma with bone metastases. Mod Pathol 2000, 13(8):861–865.

    Article  PubMed  CAS  Google Scholar 

  43. Liu J, Singh B, Tallini G, Carlson DL, Katabi N, Shaha A, Tuttle RM, Ghossein RA: Follicular variant of papillary thyroid carcinoma: a clinicopathologic study of a problematic entity. Cancer 2006, 107(6):1255–1264.

    Article  PubMed  Google Scholar 

  44. Renshaw AA, Gould EW: Why there is tendency to “overdiagnose” the follicular variant of papillary thyroid carcinoma. Am J Clin Pathol 2002, 117:19–21.

    Article  PubMed  Google Scholar 

  45. Connor MP, Wells D, Schmalbach CE: Variables predictive of bilateral occult papillary microcarcinoma following total thyroidectomy. Otolaryngol Head Neck Surg 2011, 144(2):210–215.

    Article  PubMed  Google Scholar 

  46. Eusebi V, Tallini G, Rosai J: Nuclear alterations and RET/PTC activation. Am J Surg Pathol 2004, 28(7):974–975.

    Article  PubMed  Google Scholar 

  47. Liu Z, Zhou G, Nakamura M, Koike E, Li Y, Ozaki T, Mori I, Taniguchi E, Kakudo K: Encapsulated follicular thyroid tumor with equivocal nuclear changes, so-called well-differentiated tumor of uncertain malignant potential: a morphological, immunohistochemical, and molecular appraisal. Cancer Sci 2011, 102(1):288–294.

    Article  PubMed  CAS  Google Scholar 

  48. Cheung CC, Ezzat S, Freeman JL, Rosen IB, Asa SL: Immunohistochemical diagnosis of papillary thyroid carcinoma. Mod Pathol 2001, 14(4):338–342.

    Article  PubMed  CAS  Google Scholar 

  49. Baloch Z, LiVolsi VA, Henricks WH, Sebak BA: Encapsulated follicular variant of papillary thyroid carcinoma. Am J Clin Pathol 2002, 118(4):603–605; discussion 605–606.

    PubMed  Google Scholar 

  50. Nikiforov YE: Molecular diagnostics of thyroid tumors. Arch Pathol Lab Med 2011, 135(5):569–577.

    PubMed  CAS  Google Scholar 

  51. Giordano TJ, Kuick R, Thomas DG, Misek DE, Vinco M, Sanders D, Zhu Z, Ciampi R, Roh M, Shedden K et al: Molecular classification of papillary thyroid carcinoma: distinct BRAF, RAS, and RET/PTC mutation-specific gene expression profiles discovered by DNA microarray analysis. Oncogene 2005, 24(44):6646–6656.

    Article  PubMed  CAS  Google Scholar 

  52. Xing M: BRAF mutation in thyroid cancer. Endocr Relat Cancer 2005, 12(2):245–262.

    Article  PubMed  CAS  Google Scholar 

  53. Trovisco V, Vieira de Castro I, Soares P, Maximo V, Silva P, Magalhaes J, Abrosimov A, Guiu XM, Sobrinho-Simoes M: BRAF mutations are associated with some histological types of papillary thyroid carcinoma. J Pathol 2004, 202(2):247–251.

    Article  PubMed  CAS  Google Scholar 

  54. Baloch ZW, LiVolsi VA, Asa SL, Rosai J, Merino MJ, Randolph G, Vielh P, DeMay RM, Sidawy MK, Frable WJ: 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 2008, 36(6):425–437.

    Article  PubMed  Google Scholar 

  55. Cibas ES, Ali SZ: The bethesda system for reporting thyroid cytopathology. Thyroid 2009, 19(11):1159–1165.

    Article  PubMed  Google Scholar 

  56. Baloch ZW, LiVolsi VA: Cytologic and architectural mimics of papillary thyroid carcinoma. Diagnostic challenges in fine-needle aspiration and surgical pathology specimens. Am J Clin Pathol 2006, 125 Suppl:S135–144.

    PubMed  Google Scholar 

  57. Faquin WC, Baloch ZW: Fine-needle aspiration of follicular patterned lesions of the thyroid: Diagnosis, management, and follow-up according to National Cancer Institute (NCI) recommendations. Diagn Cytopathol 2010, 38(10):731–739.

    PubMed  Google Scholar 

  58. 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):41–44.

    Article  PubMed  Google Scholar 

  59. Renshaw AA: Follicular lesions of the thyroid. American journal of clinical pathology 2001, 115(5):782–785.

    PubMed  CAS  Google Scholar 

  60. Schlinkert RT, van Heerden JA, Goellner JR, Gharib H, Smith SL, Rosales RF, Weaver AL: factots that predict malignant thyroid lesions when fine-needle aspiration is “suspicious for follicular neoplam”. Mayo Clin Proc 1997, 72:913–916.

    Article  PubMed  CAS  Google Scholar 

  61. Wang CC, Friedman L, Kennedy GC, Wang H, Kebebew E, Steward DL, Zeiger MA, Westra WH, Wang Y, Khanafshar E et al: A large multicenter correlation study of thyroid nodule cytopathology and histopathology. Thyroid 2011, 21(3):243–251.

    Article  PubMed Central  PubMed  Google Scholar 

  62. Wu S, Demay RM, Papas P, Yan B, Reeves W: Follicular lesions of the thyroid: A retrospective study of 1,348 fine needle aspiration biopsies. Diagnostic cytopathology 2010.

  63. Wu HH, Jones JN, Grzybicki DM, Elsheikh TM: Sensitive cytologic criteria for the identification of follicular variant of papillary thyroid carcinoma in fine-needle aspiration biopsy. Diagnostic cytopathology 2003, 29(5):262–266.

    Article  PubMed  Google Scholar 

  64. Nikiforov YE, Steward DL, Robinson-Smith TM, Haugen BR, Klopper JP, Zhu Z, Fagin JA, Falciglia M, Weber K, Nikiforova MN: Molecular Testing for Mutations in Improving the Fine Needle Aspiration Diagnosis of Thyroid Nodules. J Clin Endocrinol Metab 2009.

  65. Chudova D, Wilde JI, Wang ET, Wang H, Rabbee N, Egidio CM, Reynolds J, Tom E, Pagan M, Rigl CT et al: Molecular classification of thyroid nodules using high-dimensionality genomic data. J Clin Endocrinol Metab 2010, 95(12):5296–5304.

    Article  PubMed  CAS  Google Scholar 

  66. Alexander EK, Kennedy GC, Baloch ZW, Cibas ES, Chudova D, Diggans J, Friedman L, Kloos RT, LiVolsi VA, Mandel SJ et al: Preoperative diagnosis of benign thyroid nodules with indeterminate cytology. N Engl J Med 2012, 367(8):705–715.

    Article  PubMed  CAS  Google Scholar 

  67. Arora N, Turbendian HK, Kato MA, Moo TA, Zarnegar R, Fahey TJ, 3rd: Papillary thyroid carcinoma and microcarcinoma: is there a need to distinguish the two? Thyroid 2009, 19(5):473–477.

    Article  PubMed  Google Scholar 

  68. Nikiforova MN, Wald AI, Roy S, Durso MB, Nikiforov YE: Targeted Next-Generation Sequencing Panel (ThyroSeq) for Detection of Mutations in Thyroid Cancer. J Clin Endocrinol Metab 2013, 98(11):E1852–1860.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Zubair W. Baloch.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Baloch, Z.W., LiVolsi, V.A. Follicular-Patterned Afflictions of the Thyroid Gland: Reappraisal of the Most Discussed Entity in Endocrine Pathology. Endocr Pathol 25, 12–20 (2014). https://doi.org/10.1007/s12022-013-9293-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12022-013-9293-4

Keywords

Navigation