Disclaimer: The information contained within the Grand Rounds Archive is intended for use by doctors and other health care professionals. These documents were prepared by resident physicians for presentation and discussion at a conference held at Baylor College of Medicine in Houston, Texas. No guarantees are made with respect to accuracy or timeliness of this material. This material should not be used as a basis for treatment decisions, and is not a substitute for professional consultation and/or peer-reviewed medical literature. Hürthle Cell Neoplasms of the Thyroid Although Hürthle cells were initially described by Askanasy in 1898, they mistakenly bear the name of the German physiologist who had, in fact, described the interfollicular C-cell. The Hürthle cell is a large, polygonal, eosinophilic cell with distinct cell borders, and one or more nucleoli which is found in association with a variety of benign and malignant thyroid disease. Hürthle cell changes are found in a variety of inflammatory conditions including subacute and Hashimoto's thyroiditis, Graves' disease, and multinodular goiter. Ewing coined the term Hürthle cell tumor in his 1928 text entitled Neoplastic Disease. By definition, these neoplasms have cell populations which are composed of greater than 50% Hürthle cells and are encapsulated. The terminology of HCN remains somewhat confusing. Although more appropriate terms include Askanasy cell tumor, oxyphil tumors, or oncocytoma, the term Hürthle cell tumor is too well established to be changed. More recently, the term Hürthle cell neoplasm (HCN) has come into use. The HCN are then designated either Hürthle cell adenoma or Hürthle cell carcinoma based on histologic findings. It is difficult to predict the clinical behavior of these neoplasms. Currently there are no specific immunohistochemical markers or features on electron microscopy that allow us to differentiate between benign and malignant lesions. The histologic criteria for malignancy include capsular or vascular invasion, or the presence of local or distant metastases. Size is no longer felt to be useful as a differentiating criterion. Grossly, both HCA and HCC are frequently tan, but may be red to brown. HCC are more frequently firm and lobulated, while HCA are more frequently soft and smooth. Both HCA and HCC may be multiple, especially the HCC which may be multiple in up to 40% of cases. Recently, attempts to differentiate the benign from the malignant lesion have turned to nuclear DNA and ploidy status. From these studies, it can be concluded that DNA content and ploidy analysis are not useful parameters to distinguish benign from malignant HCN since both aneuploid and euploid or diploid DNA content are found in both HCA and HCC. Clinically, the presence of aneuploid or diploid DNA in the adenoma makes no difference, as these behave in a benign fashion. However, the presence of an aneuploid DNA content in a HCC has consistently been shown to be associated with a higher risk of recurrence, distant metastasis, and in death. Clinical characteristics of HCN include a clear-cut female predominance ranging from 2:1 to 10:1 in the literature. The peak incidence is between the 5th and 6th decades for HCA and between the 7th or 8th decade for HCC. Seven to 39% of patients with HCN have a previous history of head and neck irradiation. The most common symptom for both HCA and HCC is a solitary thyroid mass. This varies from 60% to 100% in the literature. This is most frequently nonfunctional on thyroid scan due to the fact that HCN do not take up iodine. Thyroid functional tests most frequently are normal; however, hyperthyroidism may be present due to associated inflammatory thyroid disease. HCN comprise 0.4% to 10% of thyroid neoplasms. The proportion of HCC is between 20-30%. Because adjuvant forms of therapy, including radioactive iodine, external beam radiation, and chemotherapy are ineffective, the mainstay of therapy is surgical. Although there is not a consensus in the literature, general treatment guidelines can be drawn. When a fine needle aspirate is performed on a cold nodule and is suspicious for a HCN, a total lobectomy with isthmusectomy is performed for definitive diagnosis. If on frozen section, the Hürthle cells appear to be related to an inflammatory process, then the procedure is terminated. If the Hürthle cells appear to be encapsulated, then several additional sections are taken to ensure that there is no capsular or vascular invasion. If this is the case, then the procedure is terminated pending final diagnosis. If carcinoma is apparent on frozen section, then a total thyroidectomy is performed. If cartilaginous structures are involved, then the specimen is resected en-block. Most authors agree that a selective neck dissection should be performed only when palpable disease is present. Completion thyroidectomy is indicated if a HCN is suspicious for HCC on final section. Adverse prognostic indicators for HCC include advanced age, presence of metastasis, inadequate initial surgical resection, and the presence of aneuploid DNA content as determined by flow cytometry. Case Presentation A 40 year-old male was found, on routine physical examination, to have a right thyroid mass. Past medical history was significant for left thyroid lobectomy and isthmusectomy 18 years prior for an unknown neoplasm. He had no history of radiation exposure or family history of thyroid disease. He denied odynophagia, hoarseness, weight loss, or lethargy. He had been treated with synthroid since his original thyroid procedure. On physical examination he had a two centimeter firm, non-tender mass in the right anterior neck. The remainder of the head and neck exam was unremarkable. A radioactive thyroid scan demonstrated a cold nodule in the right lobe of the thyroid. Thyroid functional tests were normal with the exception of a TSH of 0.2 mIU (normal 0.5 to 5.5). A fine needle aspirate was suggestive of a Hürthle cell neoplasm. He was taken to the operating room where he underwent an uncomplicated right thyroid lobectomy. A frozen section diagnosis of "oncocytic neoplasm without vascular or capsular invasion" was rendered. Permanent section evaluation resulted in a diagnosis of Hürthle cell adenoma. The remainder of his hospital course was uncomplicated and he was discharged three days later. He is currently doing well in his third postoperative week. Bibliography Abdel Nabi H, Hinkle GH, Falko JM, Kelly D, Olsen JO, Martin EW,Jr. Iodine131 labeled antiCEA antibodies uptake by Hürthle cell carcinoma. 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