Hurthle Cell Carcinoma

Hurthle cell carcinoma (oncocytic carcinoma of the thyroid) is a follicular derived thyroid cancer in which over 75% of cells are oncocytic. Capsular or vascular invasion separates it from the adenoma.

It accounts for about 3 to 5% of thyroid cancers, mostly in adults aged 50 to 60 years, and is more common in women.

Compared with follicular carcinoma it more often has nodal and distant metastases (lung, bone) and takes up radioiodine poorly. Outcomes are worse than papillary carcinoma.

Pathophysiology.

The tumour has widespread mitochondrial DNA variants and chromosomal loss, causing mitochondrial accumulation. Loss of iodide trapping explains the weak radioiodine uptake.

• A solitary thyroid nodule or enlarging goitre, usually euthyroid.
• Hoarseness, dysphagia or neck nodes in advanced disease. Bone pain or cough with distant spread.

Red flags.

• Hard fixed nodule, rapid growth, voice change or lymphadenopathy.
• Bone pain or pathological fracture.

• Thyroid ultrasound with nodule features and cervical lymph node survey.
• Fine needle aspiration shows a Hurthle cell neoplasm (indeterminate), which cannot separate adenoma from carcinoma. Diagnosis needs histology after lobectomy.
• Thyroid function; serum calcitonin if medullary carcinoma is possible.
• Staging imaging (CT neck and chest with contrast, or MRI) for large or invasive tumours. Fluorodeoxyglucose PET-CT for suspected dedifferentiated or radioiodine negative disease.
• After surgery: thyroglobulin and anti-thyroglobulin antibodies.

Differential diagnosis.

• Hurthle cell adenoma and Hashimoto thyroiditis.
• Follicular and papillary carcinoma.
• Medullary carcinoma and metastasis (kidney, lung).

• Lobectomy for a solitary tumour under 4 cm without vascular invasion or nodes. Total thyroidectomy for tumours over 4 cm, extrathyroidal extension, vascular invasion, bilateral disease, nodal or distant metastasis. Central or lateral neck dissection for involved nodes.
• Radioiodine after total thyroidectomy in intermediate or high risk disease (activity 1.1 to 3.7 GBq) after thyrotropin stimulation, with a post-therapy scan. Uptake is often poor, so benefit is uncertain.
• Levothyroxine adjusted to a thyroid stimulating hormone target: 0.5 to 2 mU/L in low risk disease, under 0.1 mU/L in high risk disease for the first years.
• External beam radiotherapy for unresectable locoregional disease. For progressive radioiodine refractory disease: lenvatinib 24 mg daily or sorafenib 400 mg twice daily, with blood pressure, proteinuria and hand foot skin reaction monitoring.
• Bone metastases: denosumab or zoledronic acid, surgery or radiotherapy for symptoms.

Special groups. Pregnancy and breastfeeding: defer radioiodine and wait at least 3 months after stopping breastfeeding. Maintain the thyroid stimulating hormone target in pregnancy.

Monitoring. Thyroglobulin, antibodies and neck ultrasound every 6 to 12 months, then yearly for at least 5 years. Cross-sectional imaging for rising thyroglobulin.

Referral and escalation. Thyroid cancer multidisciplinary team; endocrine surgeon for all cases; oncology for progressive disease.