Follicular thyroid cancer pathophysiology

Follicular thyroid cancer arises from follicular cells of thyroid, which are secretory cells that are normally involved in production and secretion of thyroid hormones, thyroxine (T4) and triiodothyronine (T3). Genes involved in the pathogenesis of follicular thyroid cancer include RAS, PAX8/PPARγ, and PTEN.

• Follicular thyroid cancer is the second most common type of cancer. It constitutes about 15% of thyroid cancers.

• Follicular thyroid cancer 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.
• Follicular carcinoma tends to metastasize to the lungs and bone via the bloodstream.
• Follicular thyroid cancer metastasizes to lymph nodes late in the course of the disease, with only 5 – 10% of patients having nodal metastases at the time of diagnosis.
• Hematogenous spread is however much more common with 20% of the patients having distant hematogenous metastases at at the time of diagnosis.^[1]
• A Hürthle cell (also known as Askanazy cell) is an oncocytic cell in the thyroid that is often associated with Hashimoto’s thyroiditis as well as follicular thyroid cancer.^[2]

• The Ras oncogene is positive in a significant proportion of individuals.^[3]
• The Ras oncogene acts through the RAF-MEK-MAPK kinase pathway.
• Other genes involved in the pathogenesis of follicular thyroid cancer are:^[4]

• RET/PTC (translocation) associated with MAPK and PI3K–AKT signaling pathways.

• HRAS, KRAS, NRAS (mutation) associated with mitogen-activated protein kinase and PI3K–AKT signaling pathways.

• PAX8/PPARγ (translocation) associated with PAX8-associated nuclear transcription signaling pathways. PAX8 is responsible for the follicular cell differentiation.

• PTEN (mutation) associated with PI3K–AKT signaling pathways.

• PTEN (deletion) associated with PI3K–AKT signaling pathways.

• IDH1 (mutation) assciated with IDH1-associated metabolic pathways signaling pathways.

• Phosphatase and tensin homologue suppressor gene and the phosphatidylinositol 3-kinase pathway are also involved in the pathogenesis of follicular thyroid tumor.
• P53 (protein), c-myc, c-fos, and the thyrotropin (TSH) receptor are some other factors involved in the pathogenesis of follicular thyroid cancer.
• MicroRNAs namely miR-192, miR-197, miR-328, and miR-346 have increased expression in follicular cell carcinoma.

• Cowden disease
• Carney complex, type I

• Encapsulated tumors

• On microscopic examination, trabecular, solid, follicular tumor cells that invade tumor capsule or surrounding vascular structures, are found.

• 
  Metastatic follicular thyroid carcinoma^[5]
• 
  Metastatic follicular thyroid carcinoma^[6]

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