Thyroid Carcinoma

Types:

• Papillary Thyroid Carcinoma

• Medullary Thyroid Carcinoma

• Follicular Thyroid Carcinoma

• Hurthle Cell Carcinoma

• Anaplastic Thyroid Carcinoma

Suspicious features of thyroid nodules on US:

• Irregular margins

• Microcalcifications

• Taller than wide shape

• Rim calcifications with small extrusive soft tissue component

• Extrathyroidal extension

• Central vascularity

Treatment:

• Treatment typically entails surgery (lobectomy vs. thyroidectomy)

• Indications for thyroidectomy:

  • History of prior radiation exposure (Category 2B)

  • Extrathyroidal extension

  • Poorly differentiated and differentiated high-grade carcinoma

  • Lateral cervical LN metastases or gross central neck LN metastases

  • Tumor >4 cm

  • Bilateral nodularity

  • Known distant metastases

• Post thyroidectomy

  • Post-operative thyroglobulin should be negative. If positive, concerning for residual disease. 

  • Obtain Radioactive Iodine (RAI) uptake scan if has any high risk features:

    • Largest primary tumor >2 cm in size

    • Detectable anti-Tg antibodies

    • High-risk subtypes (poorly differentiated, tall cell, columnar cell, hobnail variants, diffuse sclerosing, and insular)

    • Lymphatic invasion

    • Cervical LN metastases

    • Macroscopic multifocality (one focus > 1 cm)

    • Postoperative unstimulated thyroglobulin 1 - 10 ng/mL

    • Microscopic positive margins

  • Can defer RAI if all criteria met:

    • Papillary thyroid cancer

    • Small primary tumor (≤ 2 cm)

    • Intrathyroidal

    • Unifocal or multifocal (all foci ≤ 1 cm)

    • No detectable Tg antibodies

    • Postoperative unstimulated thyroglobulin <1 ng/mL or stimulated Tg <2ng/mL

    • Negative postoperative ultrasound, if done

  • RAI is not indicated in the treatment of Medullary thyroid cancers.

  • Levothyroxine

    • To maintain low TSH levels in the treatment of patients with papillary, follicular, or Hurthle cell carcinoma

Papillary Thyroid Cancer

• Highly curable

• Localized disease is treated with surgery as above

  • In patients who undergo thyroid lobectomy + isthmusectomy and are found to have any of the following features, should undergo a complete thyroidectomy:

    • Tumor >4 cm

    • Gross positive resection margins

    • Confirmed nodal metastasis

    • Vascular invasion

    • Confirmed contralateral disease

    • Gross extra-thyroidal extension

• Metastatic Disease

  • Responds well to RAI if it takes up radioiodine on scans- can be curative

  • Can use lenvatinib or sorafenib if no other actionable mutations

  • If NTRK gene fusion:

    • Larotrectinib

    • Entrectinib

  • If BRAF mutation:

    • Dabrafenib

    • Trametinib

  • If RET fusion positive:

    • Pralsetinib

    • Selpercatinib

  • Can consider cabozantinib if progressed following prior VEGFR-targeted therapy

    
    

Medullary Thyroid Cancer

• Arise from parafollicular C cells of the thyroid

• Workup:

  • Screening for germline RET proto-oncogene mutations

  • CEA level

  • Calcitonin level

  • Screen for pheochromocytoma

  • Contrast-enhanced CT of Neck/Chest and Liver MRI (or 3-phase CT of liver) or Ga-68 DOTATATE PET-CT scan if there is a high concern of distant metastases. 

    • Systemic imaging is considered for patients who have a high burden of disease, calcitonin level >500 pg/mL, or elevated CEA levels.  

• Treatment:

  • ≥ 1 cm in diameter OR bilateral thyroid disease: Total thyroidectomy with bilateral central neck dissection.

  • <1 cm in diameter AND unilateral thyroid disease: Total thyroidectomy with consideration of a bilateral central neck dissection.

  • Post-operative levothyroxine to normalize the TSH.

  • RAI is not indicated

  • Calcitonin can be used to monitor for disease recurrence

    • If slightly rising: continue to monitor CEA and calcitonin levels

      • In patients with stable or slowly progressive indolent disease, can be closely monitored and not be started immediately on kinase inhibitor

    • If calcitonin level rises to ≥ 150 pg/mL: CT with contrast of the neck, liver, and chest and possibly a bone scan

• Metastatic Disease:

  • Treatment includes kinase inhibitors use:

    • Vandetanib

    • Cabozantinib

    • Selpercatinib (if RET mutated)

Anaplastic Thyroid Cancer

• Very aggressive- worst prognosis of all types of thyroid cancer

  • All patients classified as having Stage IV disease

• Originate from the follicular cells of the thyroid

• Often invade the surrounding tissues including the trachea, esophagus and larynx

• They do not have any uptake of iodine nor do they synthesize thyroglobulin. 

  • RAI therapy is ineffective as treatment

• Should be genomically profiled to see if the tumor harbors a BRAF V600E mutation, RET fusion, or NTRK gene fusion is present

• Treatment: 

  • Locoregional disease:

    • Consider total thyroidectomy with therapeutic LN dissection. 

    • Can consider adjuvant EBRT/IMRT with radiosensitizing chemotherapy.

  • Locally advanced/unresectable:

    • EBRT/IMRT + chemotherapy (weekly Carboplatin/Taxol). 

    • Reconsider surgery after neoadjuvant therapy depending on the response.

    • Can consider targeted neoadjuvant therapy for patients with borderline resectable disease.

  • Metastatic: 

    • Consider surgery or RT for local palliative control

      Same:

    • If NTRK gene fusion:

      • Larotrectinib

      • Entrectinib

    • If BRAF mutation:

      • Dabrafenib

      • Trametinib

    • If RET fusion positive:

      • Pralsetinib

      • Selpercatinib