Clinical Presentation and Diagnosis of Hürthle Cell Thyroid Cancer

Abstract

Hürthle cell carcinoma is a rare thyroid malignancy of follicular cell origin with variable classification, behavior, and prognosis, although it is similar to follicular thyroid carcinoma when adjusted for disease stage. Risk factors include a personal history of radiation exposure, a family history of thyroid cancer, iodine excess, and female sex. Although Hürthle cells are often found in a variety of benign thyroid conditions, Hürthle cell carcinoma is defined by a 75% or greater proportion of Hürthle cells with evidence of capsular and/or vascular invasion on surgical pathology. Hürthle cell carcinoma has a unique molecular and genetic profile compared to papillary and follicular thyroid cancer; mutations in mitochondrial DNA and upregulation of PIK3CA-Akt-mTOR and Wnt/β-catenin pathways are commonly seen, while mutations usually seen in papillary and follicular thyroid carcinomas are rarely identified. Most patients present with a solitary painless thyroid nodule, although Hürthle cell carcinoma is more likely to be multifocal and have regional and distant metastases at diagnosis. The workup of thyroid nodules includes history-taking, physical examination, measurement of serum TSH, and diagnostic thyroid ultrasonography with fine needle aspiration biopsy of suspicious nodules. Although fine needle aspiration can raise suspicion for Hürthle cell carcinoma, surgical pathology is required to establish the diagnosis. Molecular diagnostic testing with gene expression classifiers and oncogene mutational analysis are not yet able to distinguish benign from malignant Hürthle cell lesions. Hemithyroidectomy is the surgical procedure of choice unless the lesion is large, or contralateral disease is suspected, in which case preoperative ultrasound, CT, and MRI and a total thyroidectomy should be considered.