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Hürthle cell carcinoma is a rare subtype of well-differentiated thyroid cancer representing 3% to 4% of all thyroid malignancies.1 First described by Max Askanazy in 1898 and then erroneously attributed to Karl Hürthle 30 years later, Hürthle cell carcinoma continues to perplex even experienced endocrine surgeons and surgical oncologists due to the rarity of disease as well as the somewhat variable natural history.

Classically, Hürthle cell carcinoma was thought to represent a more malevolent form of well-differentiated thyroid cancer given its multifocality and high incidence of metastasis at the time of presentation. However, more precise molecular, genetic, and histopathologic characterization of Hürthle cell tumors has led us to recognize that while Hürthle cell carcinoma carries a worse prognosis as compared to papillary thyroid cancer (PTC), the prognosis of Hürthle cell carcinoma in fact mirrors that of follicular thyroid carcinoma.


Patients with Hürthle cell carcinoma are typically euthyroid women between 50 to 70 years of age. As in most cases of well-differentiated thyroid cancer, women outnumber men by approximately 3 to 1.2,3 While bilateral or multifocal disease is commonly identified at presentation, the vast majority of Hürthle cell carcinoma patients present with a single, palpable, nontender thyroid nodule. Approximately one-third of Hürthle cell carcinoma patients have nodal (10% to 25%) or distant (10% to 29%) metastatic disease at the time of diagnosis.4,5

Risk Factors

The risk factors for Hürthle cell carcinoma are consistent with those of other well-differentiated thyroid cancers and include childhood head and neck radiation and/or a family history of thyroid cancer. Interestingly, in contrast to follicular thyroid carcinoma, Hürthle cell carcinoma is more common in iodine-rich areas as opposed to regions where iodine deficiency is seen. Previous radiation exposure correlates not only with increased bilaterality and multicentricity of Hürthle cell carcinoma at presentation but also with an increased incidence of contralateral, non-Hürthle cell carcinoma. To date, no genetic syndromes have been reported to be associated with Hürthle cell cancer.

Size is an important risk factor for malignancy in Hürthle cell tumors. Tumors greater than 4 cm are reported to be malignant in 44% to 65% of cases as compared with only 10% to 13% in tumors less than 4 cm in size. Advanced age is also a risk factor, with patients over 50 years of age noted to be at higher risk for malignant disease.6,7


Hürthle cells are large, polygonal cells characterized by an intensely eosinophilic, granular cytoplasm with abundant mitochondria and a prominent nucleolus (Fig. 36-1A, B). They are derived from the follicular epithelium and are seen in both benign and malignant disease. In terms of benign disease, Hürthle cells are classically detected in Hashimoto’s thyroiditis as well as in Graves’ disease. Patients with multinodular goiter ...

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