In a smoker with a cold thyroid nodule, poorly defined ultrasound margins, unilateral cervical lymphadenopathy, dysphagia, hoarseness, fatigue, and loss of appetite, what is the most likely diagnosis and what diagnostic work‑up and treatment plan should be pursued?

Anaplastic Thyroid Cancer: Immediate Diagnostic and Treatment Algorithm

This clinical presentation—smoking history, cold nodule, poorly defined margins, unilateral cervical adenopathy, and compressive symptoms (dysphagia, hoarseness)—is highly suspicious for anaplastic thyroid cancer (ATC), the most aggressive thyroid malignancy with median survival under 6 months. 1

Diagnostic Confirmation (Urgent—Within 24-48 Hours)

Immediate laryngoscopy is mandatory to assess vocal cord mobility before any other intervention, as vocal cord paralysis occurs in 47% of cases with extrathyroidal extension and fundamentally alters surgical planning. 2 Do not delay this examination waiting for imaging results. 2

Obtain contrast-enhanced CT of neck and chest immediately (before tissue biopsy) to:

• Determine tumor extent and resectability 2
• Identify invasion of great vessels, trachea, and esophagus 1, 2
• Detect distant metastases (present in 50% at diagnosis) 1
• Guide optimal biopsy approach 2

Ultrasound-guided core needle biopsy (not FNA alone) is required for definitive diagnosis, as ATC requires histological confirmation and FNA may be inadequate for this aggressive tumor. 1, 2 Core biopsy provides superior diagnostic accuracy for determining histological grade. 3

Measure serum calcitonin to exclude medullary thyroid carcinoma, which can present similarly but has different treatment implications. 1

Characteristic Features of Anaplastic Thyroid Cancer

The diagnosis is typically straightforward based on clinical presentation 1:

• Large, hard mass invading the neck causing compressive symptoms 1
• Dysphagia, hoarseness, dyspnea, and cough from local invasion 1, 2
• Poorly defined/irregular margins on ultrasound 1, 4
• Tumor necrosis (most valuable CT parameter—present in 100% of ATC) 4
• Low attenuation on contrast CT (attenuation <100 HU or muscle-to-mass ratio <1.3) 4
• Age >70 years significantly increases ATC probability 4
• Smoking history is a recognized risk factor 1

All ATCs are classified as stage IV disease regardless of size, reflecting their universally poor prognosis. 1

Immediate Surgical Referral Criteria

Refer urgently to a high-volume thyroid surgeon (>100 thyroidectomies annually) who has experience with ATC, as complication rates are 4-fold lower (4.3% vs 17%) compared to low-volume surgeons. 2 Immediate referral is indicated for:

• Confirmed or suspected ATC 2
• Critical airway compromise 2
• Evidence of extrathyroidal extension on imaging 2
• Vocal fold paralysis on laryngoscopy 2

Treatment Approach

Surgery is indicated only for potentially resectable disease without distant metastases. 1 The goal is complete resection of all gross disease when feasible. 1

For unresectable or metastatic disease, less aggressive neck surgery may be appropriate to preserve speech, swallowing, and parathyroid function while maintaining locoregional control. 1

External beam radiotherapy is often used for local invasion, particularly when surgical resection is incomplete. 1

Chemotherapy has minimal benefit (<20% response rate) in advanced disease. 1

Tyrosine kinase inhibitors (vandetanib, sorafenib, sunitinib, motesanib) show partial responses of 2-35% with disease stabilization rates of 27-87% in clinical trials, though these data primarily apply to medullary and differentiated thyroid cancers rather than ATC. 1

Critical Early Palliative Care Discussion

Initiate palliative care discussions immediately upon diagnosis of ATC, as median survival is 3-6 months regardless of treatment. 1, 2 Address:

• Airway management planning (avoid elective tracheostomy—it is morbid, temporary, and often misaligned with patient goals) 2
• Goals of care given universally poor prognosis 2
• Symptom management for dysphagia, dyspnea, and pain 1

Common Pitfalls to Avoid

Do not rely on ultrasound alone for evaluating extrathyroidal extension—sensitivity is inadequate and CT is mandatory. 2

Do not perform FNA alone—core needle biopsy is required for histological diagnosis of ATC. 3, 2

Do not delay laryngoscopy waiting for imaging—vocal cord assessment is critical for surgical planning. 2

Do not refer to low-volume surgeons—outcomes are significantly worse. 2

Do not pursue aggressive surgical debulking in patients with distant metastases or unresectable disease, as this does not improve survival and increases morbidity. 1