UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Overview of follicular thyroid cancer

Authors
Stephanie L Lee, MD, PhD
Sonia Ananthakrishnan, MD
Section Editor
Douglas S Ross, MD
Deputy Editor
Jean E Mulder, MD

INTRODUCTION

Follicular thyroid cancer, a well-differentiated tumor of thyroid epithelium, is the second most common type of thyroid cancer after papillary thyroid cancer. In iodine-sufficient areas, up to 10 percent of all thyroid cancers are follicular cancers. An overview of follicular thyroid cancer will be provided here. Papillary thyroid cancer and the management of differentiated thyroid cancer are discussed separately. (See "Overview of papillary thyroid cancer" and "Differentiated thyroid cancer: Overview of management".)

PATHOLOGIC FEATURES

Microscopically, the diagnosis of follicular cancer requires distinguishing adenoma from cancer, through identification of tumor extension through the tumor capsule and/or vascular invasion. The histology ranges from normal well-differentiated epithelium with follicular development and colloid (findings associated with a good prognosis) to poorly-differentiated with solid growth, absence of follicles, marked nuclear atypia, and extensive vascular and/or capsular invasion (characteristics that are associated with a worse prognosis) (picture 1) [1]. (See 'Prognostic features' below.)

Typically, the microfollicular architecture is uniform with an invariant collection of cuboidal cells lining the follicles. In addition, features consistent with papillary cancer, such as psammoma bodies and nuclear changes (ground-glass appearance, longitudinal grooves, nuclear overlapping, and inclusions), should be absent.

There are two patterns of growth that relate to capsular invasion; minimally invasive follicular cancer (MIFC) is limited to microscopic penetration of the tumor capsule without vascular invasion, while widely invasive follicular cancer (WIFC) extends beyond the tumor capsule into blood vessels and adjacent thyroid parenchyma (picture 2 and picture 3) [1,2]. Newer terminology also includes angioinvasive follicular cancer, but current prognosis scoring does not yet include this type of pathology. Angioinvasive cancer may be associated with distant metastases [3].

Less common pathologic features are associated with the variants of follicular thyroid cancer. Though considered by some to be a distinct type of tumor, Hürthle cell cancer is classified by the World Health Organization as a variant of follicular thyroid cancer. It includes the presence of a cell population of "oncocytes," mostly eosinophilic oxyphilic cells with abundant cytoplasm, closely packed mitochondria, and round oval nuclei with prominent nucleoli (picture 4) [4]. Insular thyroid cancer (ITC), another rare subtype sometimes classified under follicular thyroid cancer, shows poor differentiation, an aggressive clinical course, and an unfavorable prognosis.

                       

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2016. | This topic last updated: Fri Jan 17 00:00:00 GMT 2014.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
References
Top
  1. 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; 442:71.
  2. D'Avanzo A, Treseler P, Ituarte PH, et al. Follicular thyroid carcinoma: histology and prognosis. Cancer 2004; 100:1123.
  3. Baloch ZW, LiVolsi VA. Prognostic factors in well-differentiated follicular-derived carcinoma and medullary thyroid carcinoma. Thyroid 2001; 11:637.
  4. Cibas ES, Ali SZ. The Bethesda System for Reporting Thyroid Cytopathology. Thyroid 2009; 19:1159.
  5. Medema RH, Bos JL. The role of p21ras in receptor tyrosine kinase signaling. Crit Rev Oncog 1993; 4:615.
  6. Lemoine NR, Mayall ES, Wyllie FS, et al. Activated ras oncogenes in human thyroid cancers. Cancer Res 1988; 48:4459.
  7. Zhu Z, Gandhi M, Nikiforova MN, et al. Molecular profile and clinical-pathologic features of the follicular variant of papillary thyroid carcinoma. An unusually high prevalence of ras mutations. Am J Clin Pathol 2003; 120:71.
  8. Garcia-Rostan G, Zhao H, Camp RL, et al. ras mutations are associated with aggressive tumor phenotypes and poor prognosis in thyroid cancer. J Clin Oncol 2003; 21:3226.
  9. Fagin JA. Molecular genetics of tumors of thyroid follicular cells. In: Werner and Ingbar's The Thyroid: A Fundamental and Clinical Text, 9th, Braverman LE, Utiger RD (Eds), Lippincott Williams & Wilkins, Philadelphia, PA 2005. p.909.
  10. Marques AR, Espadinha C, Catarino AL, et al. Expression of PAX8-PPAR gamma 1 rearrangements in both follicular thyroid carcinomas and adenomas. J Clin Endocrinol Metab 2002; 87:3947.
  11. Martelli ML, Iuliano R, Le Pera I, et al. Inhibitory effects of peroxisome poliferator-activated receptor gamma on thyroid carcinoma cell growth. J Clin Endocrinol Metab 2002; 87:4728.
  12. Pettersson B, Adami HO, Wilander E, Coleman MP. Trends in thyroid cancer incidence in Sweden, 1958-1981, by histopathologic type. Int J Cancer 1991; 48:28.
  13. Harach HR, Escalante DA, Onativia A, et al. Thyroid carcinoma and thyroiditis in an endemic goitre region before and after iodine prophylaxis. Acta Endocrinol (Copenh) 1985; 108:55.
  14. PENDERGRAST WJ, MILMORE BK, MARCUS SC. Thyroid cancer and thyrotoxicosis in the United States: their relation to endemic goiter. J Chronic Dis 1961; 13:22.
  15. Nikiforov YE. Genetic alterations involved in the transition from well-differentiated to poorly differentiated and anaplastic thyroid carcinomas. Endocr Pathol 2004; 15:319.
  16. Führer D, Tannapfel A, Sabri O, et al. Two somatic TSH receptor mutations in a patient with toxic metastasising follicular thyroid carcinoma and non-functional lung metastases. Endocr Relat Cancer 2003; 10:591.
  17. Cerilli LA, Mills SE, Rumpel CA, et al. Interpretation of RET immunostaining in follicular lesions of the thyroid. Am J Clin Pathol 2002; 118:186.
  18. Xing M. BRAF mutation in thyroid cancer. Endocr Relat Cancer 2005; 12:245.
  19. Ries LAG, Eisner MP, Kosary CL, Hankey BF, et al. SEER Cancer Statistics Review, 1975-2001. National Cancer Institute. Bethesda, MD, 2004. http://seer.cancer.gov/csr/1975_2001/ (Accessed on October 22, 2005).
  20. Rosai J, Carcangiu ML, De Lellis RA. Tumors of the thyroid gland. In: Atlas of tumor pathology, Armed Forces Institute of Pathology, Washington, DC 1992. Vol Fascicle 5.
  21. Machens A, Holzhausen HJ, Dralle H. The prognostic value of primary tumor size in papillary and follicular thyroid carcinoma. Cancer 2005; 103:2269.
  22. Grebe SK, Hay ID. Follicular thyroid cancer. Endocrinol Metab Clin North Am 1995; 24:761.
  23. Bowden WD, Jones RE. Thyrotoxicosis associated with distant metastatic follicular carcinoma of the thyroid. South Med J 1986; 79:483.
  24. Kasagi K, Takeuchi R, Miyamoto S, et al. Metastatic thyroid cancer presenting as thyrotoxicosis: report of three cases. Clin Endocrinol (Oxf) 1994; 40:429.
  25. Miyauchi A, Takamura Y, Ito Y, et al. 3,5,3'-Triiodothyronine thyrotoxicosis due to increased conversion of administered levothyroxine in patients with massive metastatic follicular thyroid carcinoma. J Clin Endocrinol Metab 2008; 93:2239.
  26. Jeh SK, Jung SL, Kim BS, Lee YS. Evaluating the degree of conformity of papillary carcinoma and follicular carcinoma to the reported ultrasonographic findings of malignant thyroid tumor. Korean J Radiol 2007; 8:192.
  27. Mazzaferri EL, Jhiang SM. Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med 1994; 97:418.
  28. Mazzaferri EL. Thyroid carcinoma: Papillary and follicular. In: Endocrine Tumors, Mazzaferri EL, Samaan NA (Eds), Blackwell Scientific, Cambridge, MA 1993. p.278.
  29. Lin JD, Hsueh C, Chao TC. Early recurrence of papillary and follicular thyroid carcinoma predicts a worse outcome. Thyroid 2009; 19:1053.
  30. Kushchayeva Y, Duh QY, Kebebew E, et al. Comparison of clinical characteristics at diagnosis and during follow-up in 118 patients with Hurthle cell or follicular thyroid cancer. Am J Surg 2008; 195:457.
  31. Lai HW, Lee CH, Chen JY, et al. Insular thyroid carcinoma: collective analysis of clinicohistologic prognostic factors and treatment effect with radioiodine or radiation therapy. J Am Coll Surg 2006; 203:715.
  32. American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer, Cooper DS, Doherty GM, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2009; 19:1167.
  33. Demeure MJ, Clark OH. Surgery in the treatment of thyroid cancer. Endocrinol Metab Clin North Am 1990; 19:663.
  34. Randolph GW, Daniels GH. Radioactive iodine lobe ablation as an alternative to completion thyroidectomy for follicular carcinoma of the thyroid. Thyroid 2002; 12:989.
  35. Kouvaraki MA, Shapiro SE, Fornage BD, et al. Role of preoperative ultrasonography in the surgical management of patients with thyroid cancer. Surgery 2003; 134:946.
  36. Leboulleux S, Girard E, Rose M, et al. Ultrasound criteria of malignancy for cervical lymph nodes in patients followed up for differentiated thyroid cancer. J Clin Endocrinol Metab 2007; 92:3590.
  37. Soh EY, Clark OH. Surgical considerations and approach to thyroid cancer. Endocrinol Metab Clin North Am 1996; 25:115.
  38. Ross DS. Long-term management of differentiated thyroid cancer. Endocrinol Metab Clin North Am 1990; 19:719.
  39. McGriff NJ, Csako G, Gourgiotis L, et al. Effects of thyroid hormone suppression therapy on adverse clinical outcomes in thyroid cancer. Ann Med 2002; 34:554.
  40. Pujol P, Daures JP, Nsakala N, et al. Degree of thyrotropin suppression as a prognostic determinant in differentiated thyroid cancer. J Clin Endocrinol Metab 1996; 81:4318.
  41. Ford D, Giridharan S, McConkey C, et al. External beam radiotherapy in the management of differentiated thyroid cancer. Clin Oncol (R Coll Radiol) 2003; 15:337.
  42. Dulgeroff AJ, Hershman JM. Medical therapy for differentiated thyroid carcinoma. Endocr Rev 1994; 15:500.