creation date: 2025-12-08 14:25
tags: Pathologies
Thyroid Cancer
Background
Definitions
Thyroid cancer is a malignancy of the thyroid parenchymal cells. The parenchyma consist of two major cell types which give rise to various variants of thyroid cancer.
Thyroid follicular cells give rise to differentiated thyroid cancer (DTC) which comprises of:
- Papillary thyroid cancer (PTC)
- Follicular thyroid cancer (FTC)
- Oncocytic carcinoma
DTC accounts for 90-95% of thyroid malignancies. This page will focus on DTC.
Parafollicular or C-cells give rise to medullary thyroid carcinoma (MTC) which accounts for 1-2% and discussed separately.
Risk Factors, Etiology, and Pathogenesis
Family occurrence of thyroid cancer is approximately 5% for PTC and FTC. Mutations and translocation of the genes encoding for mitogen-activated protein kinase (MAPK) has been implicated in the genetic basis of most thyroid cancers.
Common mutations are for the respective cancers are:
PTC
- BRAF point mutation to BRAF V600E (29-69%)
- RET (7%)
- RAS proto-oncogene (10-20%)
FTC
- RAS proto-oncogene (40-50%)
- Translocation of PX8-peroxisome proliferator-activated receptor gamma (30-35%)
The risk factors associated with thyroid cancers include:
- Female sex
- Family history of thyroid cancer
- Radiaction exposure of the thyroid gland during childhood
Clinical Presentation
Signs & Symptoms
DTC can be asymptomatic. The most common presenting symptoms are:
- Neck swelling
- Incidentally detected thyroid nodules
Sudden increase in nodule size may manifest as pressure symptoms:
- Hoarseness of voice
- Dysphagia
- Dyspnea
- Horner’s syndrome (partial ptosis, miosis, facial anhidrosis) due to disruption of sympathetic nerve supply
Systemic symptoms may present:
- Weight loss
- Fatigue
History & Physical Exam
History should elicit possible risk factors for thyroid cancer.
Physical exam of the neck/thyroid may appreciate signs of suspicious nodules:
- Firmness
- Immobility
- Presence of neck lymph nodes
Diagnosis
Criteria
Papillary thyroid cancer
Diagnosis is made using fine needle aspiration biopsy (FNAB). It should be noted that accuracy is dependent on the clinician aspirating and interpreting (approximately 20% of FNAB are insufficient samples).
Follicular thyroid cancer
Diagnosis cannot be made by FNAB due to the inability to detect vascular invasions. As such FNAB can only indicate suspicion but definitive diagnosis cannot be made until a pathology is completed following surgical resection.
Work-up
Initial evaluation of patients with a thyroid nodule is a thyroid function panel.
If patients are in hyperthyroid state, a radionuclide uptake scan is used. Fine-needle aspiration biopsy is avoided if the nodule(s) are hyperfunctioning as they are associated with low risk of malignancy.
If patients are euthyroid or hypothyroid, a diagnostic thyroid ultrasound is indicated. High-risk features as described by the TIRADS criteria include:
- Significant increase in size from prior imaging
- Hypoechogenicity
- Irregular/lobulated margins
- Size taller than wide
- Microcalcifications
- Solid internal structure
- Extra-thyroidal extension
- Central vascularity
Risk stratification by TIRADS directs fine-needle aspiration biopsy (FNAB) for diagnosis.
CT and MRI are not routinely used for evaluation but may be indicated for assessment of advance disease spread.
Differential
- Benign thyroid nodule
- Toxic nodular goiter
- Primary thyroid lymphoma
- Cervical lymphadenopathy
Red Flags / Complications
Prognosis is generally good with 95% 5 year survival rate. However, poor prognostic factors include:
- Large tumour size
- Presence of extra-thyroidal extensions or metastases
- Older age
- Unfavourable tumour types
Complication of untreated thyroid cancer generally involve invasion:
- Local invasion of the airway, esophagus, neurovascular structures
- Distant metastasis to the lungs, bones, soft tissue structures
Treatment (thyroid lobectomy and total thyroidectomy) carry risk of damage to neurovascular structures, specifically the recurrent laryngeal nerve. Additionally, damage to the parathyroid gland can result in hypocalcemia.
Management
Surgical
Surgical resection is the main treatment modality for both PTC and FTC. Appropriate procedure is determined by pre-operative neck ultrasound. Options for surgical resection include:
- Hemithyroidectomy
- Total thyroidectomy
- Including or without lymph node dissection
Typically, thyroid lobectomy is preferred for unilateral DTC <1 cm without extra-thyroidal involvement unless there are clear indication for total thyroidectomy (eg. head and neck irradiation or strong family history of thyroid cancer).
For tumours between 1-4 cm, with no extrathyroidal or lymphatic invasion, choice of lobectomy or total thyroidectomy depends on patient preference and risk factors.
For tumours >4 cm or tumours with extrathyroidal or lymphatic invasion, a total thyroidectomy is preferred due to risk of multifocal carcinoma.
Post-surgical
Following surgery, risk stratification is completed based on clinicopathologic findings.
In high or some intermediate risk patients, radioiodine ablation therapy is indicated for subclinical micrometastases and apparently metastases.