Hurthle Cell Thyroid Neoplasms

Abstract

Hurthle cell adenomas and carcinomas are thyroid neoplasms that are composed predominantly (>75 %) or exclusively of Hurthle cells and lack cytologic features of papillary thyroid carcinoma (PTC). Hurthle cell neoplasms are classified by the World Health Organization as oncocytic variants of follicular neoplasms. Hurthle cell neoplasms present as a thyroid mass, affect women more often than men, and usually occur in adults. The mean patient age for a Hurthle cell adenoma is 45 years, which is 5–10 years younger than that for Hurthle cell carcinomas. Hurthle cell adenomas are benign and lack the capsular and/or vascular invasion seen in Hurthle cell carcinomas. Hurthle cell adenomas usually are smaller than carcinomas but may overlap in size. Hurthle cell adenomas have a lower Ki67 proliferative labeling index and less often have diffuse nuclear cyclin D1 staining compared with Hurthle cell carcinomas. However, in evaluating an individual lesion, no immunohistochemical or genetic marker can separate Hurthle cell adenoma from carcinoma definitively. Hurthle cell tumors show a low prevalence of RAS mutation or PAX8–peroxisome proliferator-activated receptor-γ translocation. Many chromosomal abnormalities have been identified, and chromosomal gains are more common than losses in both benign and malignant Hurthle cell neoplasms. Hurthle cell carcinomas tend to have more chromosome losses than adenomas, and among carcinomas, losses, particularly of chromosome 22, are more frequent in tumors associated with death from disease. GRIM-19 (gene associated with retinoic-interferon–induced mortality 19) point mutations, thought to be involved in tumorigenesis via mitochondrial metabolism and cell death, have been identified in Hurthle cell tumors and are more specific than other markers for Hurthle cell neoplasms. Unlike hyperplastic or adenomatous nodules, Hurthle cell neoplasms generally are solitary encapsulated lesions. Hurthle cell neoplasms with papillary growth are differentiated from oxyphilic PTC by the lack of characteristic nuclear features of PTC. Hurthle cell adenomas are benign, treated by lobectomy, and have an excellent prognosis. Hurthle cell carcinomas invade soft tissue and show nodal involvement more often than conventional follicular carcinomas. Hurthle cell carcinoma accounts for 2–3 % of thyroid carcinomas and 20 % of follicular carcinomas. Hurthle cell carcinomas are thought to be somewhat more aggressive than follicular carcinomas and have a 5-year survival rate of 50–60 %. Features associated with aggressive behavior include large tumor size and vascular invasion. Tumors with only capsular invasion and no vascular invasion usually behave less aggressively than those with vascular invasion.