Thyroid nodules are a common clinical problem, and differentiating benign nodules from malignant ones is important to guide management. While some guidelines recommend biopsy of all nodules, others recommend selective biopsy based on clinical and ultrasound features. Here we review the evidence around biopsy of all vs selective biopsy of thyroid nodules.
What is the prevalence of thyroid nodules?
Thyroid nodules are very common, with a prevalence of around 50% when high-resolution ultrasound is used. The prevalence increases with age, and is higher in women than men. Autopsy studies have shown that 50% of people have thyroid nodules by age 50, and this increases to 60% by age 60.
What proportion of thyroid nodules are malignant?
The vast majority of thyroid nodules are benign. Only around 5-15% of all thyroid nodules are malignant. However, thyroid cancer incidence has been increasing over the past few decades, likely due to increased detection on imaging.
What are the different types of thyroid malignancies?
There are several different histological types of thyroid cancer:
- Papillary thyroid cancer – Most common type (80% of cases)
- Follicular thyroid cancer
- Medullary thyroid cancer
- Poorly differentiated thyroid cancer
- Anaplastic thyroid cancer – Least common but most aggressive type
Papillary and follicular cancers are referred to as differentiated thyroid cancers and generally have a good prognosis. Medullary, poorly differentiated and anaplastic cancers are more aggressive.
What are the risks of thyroid biopsy?
Thyroid biopsy is generally a very safe procedure, with a low overall risk of complications. However, there are some risks to consider:
- Bleeding – 1-2% risk
- Infection –
- Damage to adjacent structures like the trachea or laryngeal nerve – rare
- Discomfort during the procedure
Serious risks like bleeding or damage to adjacent structures are quite uncommon when biopsy is performed by an experienced physician.
What is the accuracy of thyroid biopsy?
Fine needle aspiration (FNA) biopsy is the recommended technique for evaluating thyroid nodules. This has a high degree of diagnostic accuracy:
- Sensitivity for malignancy: 83-98%
- Specificity for malignancy: 72-100%
- False negative rate: 1-5%
- False positive rate: 1-7%
- Nondiagnostic biopsy: 5-20%
So FNA biopsy has a good sensitivity and specificity for diagnosing thyroid malignancy. However, nondiagnostic biopsies are not uncommon.
What are the major guidelines on thyroid biopsy?
There are guidelines from multiple professional societies on evaluating and managing thyroid nodules. Here is a summary of recommendations on biopsy:
| Guidelines | Recommendations on biopsy |
|---|---|
| American Thyroid Association | FNA for nodules ≥1 cm unless low suspicion on ultrasound |
| American Association of Clinical Endocrinologists | Consider biopsy of nodules ≥1 cm |
| British Thyroid Association | FNA for nodules ≥1 cm unless very low risk on ultrasound |
| American College of Radiology | FNA for nodules ≥1.5 cm and other suspicious features |
Most guidelines agree that FNA biopsy is recommended for nodules ≥1 cm, unless the nodule has very low risk features on ultrasound.
What are pros and cons of biopsying all nodules?
Here are some potential pros and cons of biopsying all thyroid nodules compared to selective biopsy based on risk stratification:
Potential pros:
- Maximize detection of thyroid cancers
- Provide definitive diagnosis and avoid need for continued surveillance
- Guide extent of thyroidectomy if cancer detected
Potential cons:
- Increased costs and utilization of scarce health resources
- Potential complications and pain from large number of biopsies
- Detection of small cancers that may never cause harm (overdiagnosis)
- Unnecessary thyroidectomies for biologically irrelevant cancers
What features predict higher risk nodules?
Several clinical and ultrasound features predict a higher risk that a thyroid nodule is malignant:
- Firm or hard on palpation
- Rapid growth
- Fixed rather than mobile
- Ultrasound features:
- Hypoechogenicity
- Irregular margins
- Taller than wide shape
- Microcalcifications
- Internal vascularity
Nodules with these features have a higher pretest probability of malignancy. Selective biopsy of high risk nodules improves diagnostic yield.
Is there a role for molecular testing?
For nodules with nondiagnostic cytology, molecular testing may be helpful to determine need for repeat biopsy vs continued surveillance. Tests like Afirma and Thyroseq analyze gene expression in FNA samples to determine risk of malignancy. However, molecular testing increases costs and has reduced sensitivity compared to cytology.
What is the role of clinical context?
Clinical context is important in determining biopsy needs. In patients at higher risk such as:
- History of thyroid cancer
- Family history of thyroid cancer
- History of external beam radiation exposure
- Patients with syndromes like Cowden’s
There may be a lower threshold to biopsy nodules. In patients with limited life expectancy where results would not change management, biopsy may not be needed.
Conclusion
In summary, while some guidelines recommend biopsy of all thyroid nodules ≥1 cm, selective biopsy based on risk stratification is also reasonable. Biopsying all nodules increases detection of thyroid cancer, but also increases costs, risks and overdiagnosis. Selective biopsy based on clinical features and ultrasound characteristics can help optimize diagnostic yield while minimizing harms. Clinical context is important in determining biopsy needs. Further research is needed to clarify the ideal biopsy approach for optimal health outcomes.