Clinical Manifestations 

• The typical patient with ATC has a long-standing neck mass:
  • Which starts to rapidly enlarge and may be painful.
• Associated symptoms such as dysphonia, dysphagia, and dyspnea are common:
  • Due to local invasion of the recurrent laryngeal nerve, esophagus, and trachea.
• The tumor is often large and may be fixed to surrounding structures:
  • May ulcerate through the skin with areas of necrosis.
• Lymph nodes usually are palpable at presentation.
• Evidence of metastatic spread also may be present:
  • Sites of metastases include:
    • Lung (25%)
    • Mediastinum (25%)
    • Liver (10%)
    • Bone (6%)
    • Kidney/adrenals (5%)
    • Heart (5%)
    • Brain (3%).

Diagnostic Workup

• The most important consideration in the evaluation of patients with suspected ATC is to complete the assessment quickly with a focus on establishing disease burden and the status of the airway, as tumors often grow rapidly.
• Diagnosis is confirmed by fine-needle aspiration (FNA) biopsy:
  • Revealing characteristic giant and multinucleated cells.
• Differential diagnoses on FNA can include:
  • Poorly differentiated cancer
  • Lymphoma
  • Medullary carcinoma
  • Direct extension from a laryngeal carcinoma
  • Primary thyroid squamous cell carcinoma
  • Other metastatic carcinomas
  • Melanoma.
• Immunohistochemistry is often needed to distinguish between these diagnostic possibilities:
  • ATCs often lack markers of thyroid and epithelial differentiation:
    • Such as thyroid transcription factor-1 (TTF-1) and thyroglobulin (Tg)
  •  ATC is positive for p53 (50% to 80% of the cases).
• Core or incisional biopsy is occasionally needed to confirm the diagnosis, especially when there is predominantly necrotic material on the FNA.
• Hyperthyroidism, hypocalcemia, and leucocytosis have been reported in ATC patients:
  • Therefore, laboratory evaluation should include a CBC, electrolytes, creatinine, liver profile, coagulation factors, and thyroid function tests.
  • Measurement of albumin and prealbumin levels provides an assessment of nutrition levels.
• Anatomic imaging with contrast-enhanced neck CT or MRI helps to evaluate the extent of locoregional disease.
  • Neck ultrasonography is also used for this purpose. 
• In patients with symptoms suggestive of advanced locoregional spread,:
  • Esophagoscopy and/or bronchoscopy can assess for esophageal or airway involvement.
• Vocal cord paralysis is common in these patients and hence laryngoscopy in indicated:
  • It also allows for assessment of direct laryngeal or subglottic involvement.
• PET-CT is useful to assess the extent of distant disease and may be more accurate than conventional neck, chest, abdomen, and pelvis CT.
• Preoperative radiologic imaging and diagnostic biopsies of suspected tumors at distant sites should be conducted expeditiously, so as to not delay therapeutic interventions.

Staging

• Due to its inherent aggressive nature:
  • ATC is automatically classified as stage IV (A, B, or C) at presentation.
• According to AJCC 7th edition staging criteria:
  • T4a referred to ATC limited to the thyroid
  • T4b referred to tumors with gross extrathyroidal extension.
• The AJCC 8th edition has changed the T classification so that rather than automatically being T4 disease, anaplastic cancers will now follow the same T definitions as differentiated thyroid cancer:
  • Intrathyroidal disease (T1 to T3a) is stage IVA
  • Gross extrathyroidal extension or cervical lymph node metastases is stage IVB,
  • Distant metastases are stage IVC.
• Approximately:
  • 10% of patients with ATC present with only an intrathyroidal tumor
  • 40% have extrathyroidal invasion and/or lymph node disease.
  • 50% of patients present with diffusely metastatic disease.