Thyroid Hürthle Cell Carcinoma: Clinical, Pathological, and Molecular Features

Abstract

Hürthle cell carcinoma (HCC) represents 3-4% of thyroid carcinoma cases. It is considered to be more aggressive than non-oncocytic thyroid carcinomas. However, due to its rarity, the pathological characteristics and biological behavior of HCC remain to be elucidated. The Hürthle cell is characterized cytologically as a large cell with abundant eosinophilic, granular cytoplasm, and a large hyperchromatic nucleus with a prominent nucleolus. Cytoplasmic granularity is due to the presence of numerous mitochondria. These mitochondria display packed stacking cristae and are arranged in the center. HCC is more often observed in females in their 50-60s. Preoperative diagnosis is challenging, but indicators of malignancy are male, older age, tumor size > 4 cm, a solid nodule with an irregular border, or the presence of psammoma calcifications according to ultrasound. Thyroid lobectomy alone is sufficient treatment for small, unifocal, intrathyroidal carcinomas, or clinically detectable cervical nodal metastases, but total thyroidectomy is recommended for tumors larger than 4 cm. The effectiveness of radioactive iodine is still debated. Molecular changes involve cellular signaling pathways and mitochondria-related DNA. Current knowledge of Hürthle cell carcinoma, including clinical, pathological, and molecular features, with the aim of improving clinical management, is reviewed.

Keywords: Hürthle cell carcinoma; oncocytic; thyroid cancer.

Figure 1

Cytological images of the Hürthle cell carcinoma (HCC). (A) The Papanicolaou-stained smear shows a monotonous cells oncocytic cells with prominent nucleoli arranged in loosely cohesive clusters. Papanicolaou stain, original magnification ×200. (B) The cells have prominent nucleoli, bland chromatin, and granular cytoplasm. Papanicolaou stain, original magnification ×600.

Figure 2

Gross findings of the HCC. (A) The tumor is mahogany brown color. Several foci of hemorrhage are noted. (B) Widely invasive HCC. Macroscopically, capsular invasion is evident (arrows). Scale bar indicates 2 cm.

Figure 3

Histological images of HCCs. (A) HCC is diagnosed in cases where a Hürthle cell tumor shows capsular invasion, and/or (B) vascular invasion. (C) HCC is composed of polygonal large cells with abundant granular and acidophilic cytoplasm. HCC cells have large nuclei with prominent nucleoli. (D) Tumor cells are diffuse and strongly positive for anti-mitochondria antibodies. Hematoxylin and eosin stain (A–C), immunohistochemistry of anti-mitochondrial antibody (D). Original magnification, ×1.25 (A), ×40 (B), ×100 (D), and ×400 (C).

Figure 4

Electron microscopic images of HCC. (A) An HCC cell contains an irregular and notched nucleus. Cytoplasm is filled with numerous mitochondria. The bar indicates 2.0 micrometers. (B) Mitochondria display packed stacking cristae, arranged in the center. The bar indicates 200.0 nanometers.