Hürthle cell thyroid carcinoma

Last revised by Rohit Sharma on 20 Feb 2024

Hürthle cell carcinoma, also known as oncocytic carcinoma, is a lesser-known subtype of differentiated thyroid carcinoma that was previously regarded as a variant of follicular thyroid cancer. It shares clinical presentation and patterns with follicular cancer 1,2.

Hürthle cell carcinomas comprise approximately 5% of all differentiated thyroid carcinomas 3 and are typically diagnosed after the age of 40 years with a possible slight female predominance 3.

Recognized risk factors for thyroid cancers, broadly include the following:

  • exposure to radiation (head & neck)

  • family history of thyroid cancer

To be classified as Hürthle cell neoplasms the tumor must contain more than 75% of Hürthle cells, also called oncocytes or Askanazy cells 4.

Hürthle cell tumors originate from follicular cells within thyroid follicles and they may manifest as benign Hürthle cell adenomas or malignant Hürthle cell carcinomas, with characteristics such as capsular/vascular invasion, infiltration of the thyroid gland, locoregional lymph node involvement, or metastatic spread.

Germline polymorphisms of the ATPase 6 gene are implicated in the pathogenesis, with an increased prevalence of mitochondrial DNA common deletions in Hürthle cell tumors 2,4.

Hürthle cells are eosinophilic oxyphilic cells, characterized by round to oval nuclei with prominent nucleoli and small densely packed mitochondria producing a granular appearance to the otherwise empty cytoplasm of the cell 2.

  • lesions are typically hypoechoic

  • solid (rather than cystic)

One study reports that TI-RADS was unreliable in predicting malignancy in Hürthle cell neoplasms 4.

Surgery, including thyroid lobectomy or total thyroidectomy, is the primary treatment for Hürthle cell tumors. Adjuvant radioactive iodine is used for high-risk features such as size >2 cm, locoregional cervical lymph node involvement, positive margins or microvascular invasion 5.

It is estimated that only around 10% of patients with Hürthle cell carcinoma lesions take up radioiodine; hence responses to treatment with radioactive iodine are much lower in these patients when compared to other types of thyroid carcinomas 6.

Overall survival for Hürthle cell carcinoma is similar to that of comparably staged follicular cell carcinoma. Increasing age, male sex, and increasing tumor size substantially diminish survival in patients with Hürthle cell carcinoma 7.

Hürthle cells were first reported by the German-Swiss pathologist Max Askanazy in 1898 in patients with Graves disease but erroneously named after the German physiologist and histologist Karl Hürthle who in fact discovered and described the interfollicular C-cell 8.

Hürthle cell carcinoma was reclassified in the 2017World Health Organization classification of endocrine tumors as a distinct tumor type due to significant histopathological and molecular differences, categorizing it as a follicular thyroid cell "derived" cancer rather than a variant of follicular cancer itself 1,2.

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