A normal human thyroid gland contains 20 to 30 million spherical follicles lined with follicular epithelial cells filled with colloid and stores a 3 months' supply of thyroid hormone.1 Among the several differentiated thyroid cancers that originate from thyroid follicular cells, 10% to 15% are follicular thyroid carcinomas (FTCs) and 3% to 5% are oncocytic (Hürthle) cell carcinomas (HCCs).2 Recent studies suggest that FTC may represent only 5% of differentiated thyroid cancer in geographical regions with well-supplemented iodine diets. In iodine-deficient regions, however, FTC may account for up to 25% to 40% of thyroid carcinomas.3 In contrast, HCC may be more common in areas with iodine-rich diets.4 The mean age at presentation is higher for HCC (55 years) than for FTC (48 years). In most reports, both disorders are approximately twofold more common in women than men.5
Hürthle cells are also called oncocytic or oxyphilic cells. According to the most recent World Health Organization (WHO) classification, the current correct term for HCC is actually oncocytic carcinoma.6 Hürthle cells were first described by Hürthle in 1894. Although it is now thought that the cells he described were actually parafollicular C cells, what we today call Hürthle cells are derived from follicular cells and may develop in response to defects in mitochondrial DNA.7 Histologically, they are large and characterized by abundant eosinophilic (pink) cytoplasm with a large nucleus. Hürthle cells are seen in patients with benign reactive thyroid diseases such as autoimmune thyroiditis, multinodular goiter, and Graves' disease and in patients treated with systemic chemotherapy.8
HCC is often classified as a variant of FTC, but a number of differences are seen (Table 5-1). Compared with FTC, HCC is associated with a higher risk of local recurrence (24% vs. 3%),5 and unlike other differentiated thyroid carcinomas, HCC is not as iodine avid.9 Distant metastatic disease develops in up to 20% of FTC patients (most commonly to the bone and lung) and in 30% of HCC patients (to the lung and lymph nodes). Survival is equivalent when stratified by stage and at 5 years, but at 10 years, patients with HCC have a poorer survival (76% vs. 85%).2,10
Table 5-1. Characteristic Features of Follicular and Oncocytic (Hürthle Cell) Carcinomas |Favorite Table|Download (.pdf)
Table 5-1. Characteristic Features of Follicular and Oncocytic (Hürthle Cell) Carcinomas
|Histologic Subtype||Follicular||Oncocytic (Hürthle Cell)||References|
|Age at presentation (mean)||40–50 years||50–60 years||5, 52, 54, 48, 49|
|Risk factors||Iodine deficiency||Radiation exposure||3, 4, 14, 15, 18, 19|
|Ras mutation or PAX8-PPARγ rearrangement||≤85%||10%||38, 39, 42, 43, 46|
|Multifocal||<2%||10% to 30%||4, 49, 52|
|Lymph node metastasis||<10%||20% to 25%||49, 52, 68, 72|
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