Does confirmed thyroid malignancy warrant investigation for metastasis?

Investigation for Metastasis in Confirmed Thyroid Malignancy

Yes, confirmed thyroid malignancy warrants investigation for metastasis, with the extent and modality of investigation determined by the specific histological subtype, risk stratification, and clinical presentation.

Differentiated Thyroid Cancer (Papillary and Follicular)

Initial Staging Workup

All patients with confirmed differentiated thyroid cancer (DTC) require neck ultrasound as the primary imaging modality to evaluate the thyroid bed and cervical lymph nodes. 1 This is the first-line investigation regardless of risk category.

For intermediate- and high-risk patients, additional staging is warranted:

• Neck CT with contrast should be performed to detect metastases in the central compartment, mediastinum, and retrotracheal areas that may be missed on ultrasound 1
• Chest CT is indicated in high-risk patients with elevated thyroglobulin (>10 ng/mL) or rising thyroglobulin antibodies, as it effectively detects small pulmonary metastases 1
• PET/CT is reserved for high-risk patients with elevated thyroglobulin (>10 ng/mL) and negative whole-body scan and ultrasound, particularly in those with aggressive histological subtypes (poorly differentiated, tall cell, Hürthle cell) 1

Risk-Stratified Approach

The extent of metastatic workup depends on the American Thyroid Association risk stratification 1:

Low-risk patients (intrathyroidal disease, no vascular invasion, non-aggressive histology):

• Neck ultrasound is typically sufficient
• Estimated recurrence risk: 1-3% 1

Intermediate-risk patients (microscopic extrathyroidal extension, vascular invasion, clinical N1 with ≤5 nodes <3 cm):

• Neck ultrasound plus consideration for neck CT
• Estimated recurrence risk: 6-20% 1

High-risk patients (gross extrathyroidal extension, nodal metastases >3 cm, extranodal extension, distant metastases, incomplete resection):

• Comprehensive staging with neck ultrasound, neck CT, chest CT, and consideration for PET/CT
• Estimated recurrence risk: >20% 1

Medullary Thyroid Cancer

All patients with suspected or confirmed MTC require comprehensive preoperative staging. 1

Mandatory Preoperative Workup

• Neck ultrasound in all patients 1
• Serum calcitonin and CEA levels as tumor markers 1
• Biochemical screening for pheochromocytoma (plasma or 24-hour urine metanephrines/normetanephrines) and hyperparathyroidism (calcium) to exclude MEN syndrome 1

Extended Imaging Based on Calcitonin Levels

The extent of imaging is guided by serum calcitonin concentration 1:

• Calcitonin <150 pg/mL: Neck ultrasound alone is usually adequate, as disease is typically limited to locoregional sites 1
• Calcitonin >400 pg/mL or documented lymph node metastases: Perform chest CT, neck CT, and three-phase contrast-enhanced liver CT or MRI to detect distant metastases 1

Common distant metastatic sites in MTC include lungs, bones, and liver. 2

Anaplastic Thyroid Cancer

Anaplastic thyroid cancer (ATC) requires immediate and comprehensive staging, as nearly 50% of patients present with distant metastases at diagnosis. 2

Mandatory Staging Workup

• Neck ultrasound to rapidly assess tumor extension and invasion 1
• Neck CT with contrast to determine extent of thyroid tumor and identify invasion of great vessels and upper aerodigestive tract 1
• PET/CT is recommended to accurately stage disease and detect distant metastases 1, 2
• Complete blood count, comprehensive chemistry panel, and TSH level 1

The most common sites of distant metastases in ATC are lungs, bones, liver, and brain. 2 All ATCs are considered stage IV disease at diagnosis 1.

Critical Pitfalls to Avoid

• Do not assume low-risk histology excludes metastatic disease: Even papillary microcarcinomas can present with nodal metastases, occurring in 2.9% of cases as the first manifestation 3
• Do not delay imaging in patients with aggressive histological variants: BRAF V600E-mutated tumors, tall cell variant, and Hürthle cell carcinomas have higher metastatic potential 1
• Do not overlook the possibility of distant metastases in follicular carcinoma: Unlike papillary carcinoma, follicular cancer more commonly spreads hematogenously to lungs and bones rather than lymph nodes 4
• Do not use iodinated contrast as a contraindication: Recent evidence shows contrast does not significantly interfere with subsequent radioiodine therapy 1

Post-Treatment Surveillance

After initial treatment, the response to therapy determines ongoing surveillance intensity 1:

• Excellent response (negative imaging, undetectable thyroglobulin): Minimal surveillance required
• Biochemical incomplete response (elevated thyroglobulin, negative imaging): Serial monitoring with consideration for additional imaging
• Structural incomplete response (imaging evidence of disease): Comprehensive restaging with multiple modalities 1