What is the management of Hürthle cell neoplasm of the thyroid?

Management of Hürthle Cell Neoplasm of the Thyroid

Primary Surgical Management

Total thyroidectomy is the standard treatment for Hürthle cell carcinoma, not lobectomy, due to its more aggressive behavior compared to other differentiated thyroid cancers. 1

Initial Diagnostic Workup

Before surgery, perform the following evaluations 2:

• Chest x-ray to assess for distant metastases
• Lateral neck ultrasound to evaluate lymph node involvement
• CT/MRI for fixed, bulky, or substernal lesions (avoid iodinated contrast unless essential)
• Vocal cord mobility assessment to evaluate recurrent laryngeal nerve function

Surgical Approach Based on Pathology

For Hürthle cell neoplasm or lesion of undetermined significance 2:

• Total thyroidectomy is indicated if invasive cancer is confirmed or based on patient preference
• Preserve cervical sensory nerves when possible 2

Lymph node management 2, 1:

• If lymph nodes are positive: Perform central neck dissection (level VI) AND lateral neck dissection (levels II-IV, consider level V), sparing the spinal accessory nerve, internal jugular vein, and sternocleidomastoid muscle
• If nodes are negative: Consider prophylactic central neck dissection (category 2B recommendation, balancing potential recurrence reduction against hypoparathyroidism risk) 2, 1

For minimally invasive Hürthle cell carcinoma (well-defined tumor with microscopic capsular and/or few foci of vascular invasion) 2:

• Lobectomy/isthmusectomy may be sufficient
• Observation is acceptable for small, unifocal, intrathyroidal carcinomas without nodal metastases

Important Surgical Considerations

The aggressive surgical approach with total thyroidectomy results in significantly better outcomes compared to limited surgery, with recurrence rates of 21% versus 59% and fewer operations per patient (1.7 versus 2.9) 3. This is particularly important because Hürthle cell carcinoma has a 10-year survival rate of only 76%, which is lower than papillary (93%) and follicular (85%) carcinomas 1.

Postsurgical Management

Radioactive Iodine (RAI) Therapy

RAI ablation should be considered for residual thyroid tissue, though effectiveness in Hürthle cell carcinoma is debated 1, 4:

2-12 weeks post-thyroidectomy with adequate TSH stimulation (thyroid withdrawal or rhTSH) 2:

• If thyroglobulin <1 ng/mL with negative antithyroglobulin antibodies and negative radioiodine imaging: No RAI treatment needed
• If suspected or proven thyroid bed uptake: Adjuvant RAI ablation (30-100 mCi) to destroy residual thyroid function with post-treatment imaging 2
• If suspected or proven radioiodine-responsive residual tumor: RAI treatment (100-200 mCi) with post-treatment imaging, or consider dosimetry for distant metastases 2

Critical caveat: Radioiodine therapy is less likely to be beneficial in Hürthle cell tumors compared to follicular carcinoma, as these tumors often do not concentrate iodine effectively 4.

TSH Suppression Therapy

All patients should receive TSH suppression therapy with levothyroxine 1. For benign lesions, maintain TSH in the normal range 2. For malignant disease, suppress TSH according to risk stratification 2.

Management of Advanced or Recurrent Disease

For clinically progressive or symptomatic disease not amenable to surgery 2, 1:

1. First priority: Enroll in clinical trials investigating novel targeted therapies
2. If trials unavailable: Consider small molecule kinase inhibitors such as lenvatinib, sorafenib, or sunitinib (though not FDA-approved specifically for thyroid cancer) 2, 1
3. For bone metastases: Consider bisphosphonate therapy and embolization of metastases 2
4. For solitary brain lesions: Neurosurgical resection or stereotactic radiosurgery preferred 2
5. External beam radiation therapy: Consider for non-radioiodine responsive disease with gross residual disease in the neck 2

Important note: Cytotoxic chemotherapy has minimal efficacy in Hürthle cell carcinoma 2.

Risk Stratification and Prognosis

High-risk features requiring aggressive management 5:

• Gross extrathyroidal extension (66% recurrence rate)
• Extensive vascular invasion (>4 foci, 30-55% recurrence risk) 1
• Tumor size >4 cm 6
• Distant metastases at presentation

The AMES criteria (age, distant metastasis, capsular extent, tumor size) are useful for predicting recurrence and death, with high-risk patients experiencing 48% recurrence or death rates 5.

Critical Pitfalls to Avoid

Do not treat Hürthle cell carcinoma with lobectomy alone for tumors >2 cm or those with malignant features, as this leads to inadequate management of this potentially aggressive cancer 1, 3.

Do not rely on molecular diagnostics for Hürthle cell neoplasms, as they have historically high false-positive rates (86% unnecessary surgeries), though newer tests show improved performance 1.

Do not assume radioiodine will be effective as it would be for papillary or follicular carcinoma—Hürthle cell tumors are often radioiodine-resistant 4.

Definitive diagnosis requires surgical excision with histological evidence of capsular and/or vascular invasion; FNA alone cannot reliably distinguish benign from malignant Hürthle cell neoplasms 1.