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Follicular thyroid cancer accounts for 15% of thyroid cancer and occurs more commonly in women over 50 years of age. Thyroglobulin (Tg) can be used as a tumor marker for well-differentiated follicular thyroid cancer. Thyroid follicular cells are the thyroid cells responsible for the production and secretion of thyroid hormones. Approximately one-half of follicular thyroid carcinomas have mutations in the Ras subfamily of oncogenes, most notably HRAS, NRAS, and KRAS. Mutations in MINPP1 have likewise been observed, as well as germline PTEN gene mutations responsible for Cowden syndrome of which follicular thyroid cancer is a feature. Also, a chromosomal translocation specific for follicular thyroid carcinomas is one between paired box gene 8 (PAX-8), a gene important in thyroid development, and the gene encoding peroxisome proliferator-activated receptor γ 1 (PPARγ1), a nuclear hormone receptor contributing to terminal differentiation of cells. The PAX8-PPARγ1 fusion is present in approximately one-third of follicular thyroid carcinomas, specifically those cancers with a t(2;3)(q13;p25) translocation, permitting juxtaposition of portions of both genes. This subtype may potentially be treated with pioglitazone, a thiazolidinedione-class drug that potentiates PPARγ to boost insulin sensitivity. Tumors tend to carry either a RAS mutation or a PAX8-PPARγ1 fusion, and only rarely are both genetic abnormalities present in the same case. Thus, follicular thyroid carcinomas seem to arise by two distinct and virtually nonoverlapping molecular pathways. Hurthle cell thyroid cancer is often considered a variant of follicular cell carcinoma. Hurthle cell forms are more likely than follicular carcinomas to be bilateral and multifocal and to metastasize to lymph nodes. Like follicular carcinoma, unilateral hemithyroidectomy is performed for non-invasive disease, and total thyroidectomy for invasive disease. It is difficult to correctly diagnose follicular neoplasms (FNs) on fine-needle aspiration cytology (FNAC) because it shares many cytological features with other mimicking lesions.
Johan Auwerx, Kristina Schoonjans, Dongryeol Ryu
Tobias Kober, Tom Hilbert, Yong Zhang, Meng Yang, Jie Liu