What Is a Thyroid Biopsy? Which Nodules Should Be Biopsied?

The thyroid is a butterfly-shaped gland in the lower half of the neck, between the windpipe and the skin. Thyroid hormones, which play a key role in the proper functioning of all body tissues and organs, are produced, stored and secreted in the thyroid gland. Other functions of thyroid hormones include ensuring efficient use of the body's energy stores, controlling body temperature and coordinating proper muscle function.

The functions of the thyroid gland are summarized below:

Thyroid dysfunction is more common at an early age and is particularly common in women. It means hypothyroidism (an underactive thyroid gland) and hyperthyroidism (an overactive thyroid gland). Most thyroid patients are euthyroid (their thyroid gland functions normally).

What are the first tests to request for thyroid diseases?

• As a screening test for thyroid diseases, TSH is usually sufficient. It is an extremely sensitive test. It has a 99% negative predictive value for ruling out primary hypothyroidism and hyperthyroidism (that is, the ability to exclude disease in people with a negative test result). It is valuable for follow-up.
• In addition, T3 and T4 may be requested if there is clinical suspicion of thyroid disease.
• It is appropriate to request anti-TPO and anti-TG when autoimmune thyroid diseases are suspected.

The table below can give an idea of how thyroid dysfunction should be interpreted according to hormone measurements:

What Is a Thyroid Nodule?

Thyroid nodules are round or oval formations that develop within the thyroid gland and have a different density from the surrounding tissue.

Thyroid nodules are relatively common in the community. They occur more frequently in women than men. Some people may develop one nodule, while others may develop more than one. Like goiter (diffuse enlargement of the thyroid gland), the formation of thyroid nodules may result from dietary iodine deficiency as the underlying cause.

What Are the Symptoms of Thyroid Nodules?

• Thyroid nodules are usually discovered incidentally during a doctor's manual examination, a neck ultrasound or a computed tomography examination performed as part of a health assessment for other reasons.
• They generally go unnoticed unless they grow in size or cause any symptoms.
• When they grow in size, patients or their relatives may notice them as swelling in the neck.
• Rapidly growing thyroid nodules can cause complaints such as difficulty swallowing or pain after swallowing, difficulty breathing and hoarseness.

Self-Examination of the Neck for Thyroid Nodules

The American Association of Clinical Endocrinologists (American Association of Clinical Endocrinologists - AACE) recommends that everyone perform a "neck check" to help detect possible thyroid enlargement. However, this may be inadequate because of the possibility of human error and differences in individual neck structure (for example, a muscular neck may conceal an enlarged thyroid). A personal neck check in no way replaces a doctor's specific diagnosis through manual examination and/or ultrasound.

The Most Common Method for Diagnosing Thyroid Nodules: USG

The size, structure and characteristics of thyroid nodules are determined by ultrasonography (USG). Ultrasound examination of nodules is completely painless and harmless. Other methods used to examine nodules are fine-needle biopsy and, less commonly, scintigraphy.

Fine-Needle Aspiration Biopsy (İİAB)

A fine-needle biopsy of a thyroid nodule is a reliable examination without serious pain or side effects. A thyroid biopsy shows with near certainty whether a nodule is benign or malignant (cancer). If the nodule is cancerous, the biopsy does not cause it to spread or similar problems. Even if surgery is being considered, a biopsy is also important so that the surgeon knows what they are operating on and can choose the correct surgical approach.

What Is Thyroid Cancer? How Is It Diagnosed?

With its incidence having increased over the last 20 years, thyroid cancer is more common in developed countries.

2020 Turkey Cancer Statistics reports that 13,682 cases of thyroid cancer were diagnosed in Turkey in 2020, making it the 4th most common type of cancer. In the same year, 795 deaths due to thyroid cancer were recorded.

Thyroid cancer is generally treatable; it can be definitively cured with surgery and radioactive treatment methods when needed. Thyroid cancers are classified according to the patient's age and the cancer's type, size and pathological type, which determines its tendency to spread. There are four main types of thyroid cancer:

1. Papillary thyroid cancer: This is the most common type. It accounts for 80-90% of cases. It is a slow-growing tumor that tends to spread to lymph nodes in the neck rather than cause distant metastasis as a pattern of spread.
2. Follicular thyroid cancer: This accounts for 5-10% of all thyroid cancers. It grows slowly and can metastasize to lymph nodes and, through the bloodstream, to more distant tissues, including the bones and lungs.
3. Medullary thyroid cancer: This accounts for approximately 2% of cases. It grows slowly. 25% of cases occur through hereditary transmission as the cause. Complete family genetic screening is extremely important for a patient with medullary thyroid cancer. It usually presents with abnormally high calcitonin levels.
4. Anaplastic thyroid cancer: This is the rarest type of thyroid cancer. It accounts for < 2% of cases. It is a rapidly growing and quickly spreading tumor that is difficult to treat.

Thyroid cancer usually develops as masses or nodules without causing symptoms. Thyroid cancer is diagnosed with a thyroid biopsy performed on the nodule or mass.

Who Should Have a Thyroid Biopsy, and When?

Most thyroid nodules do not show a clear tendency to grow and do not require any treatment. Regular follow-up according to their type and size is sufficient. However, some nodules should be monitored more closely. Some nodules may even need a biopsy because of their ultrasound appearance to distinguish benign from malignant (cancerous) nodules.

The American College of Radiology (ACR) Thyroid Imaging, Reporting and Data System (TI-RADS) guidelines are widely used in radiology clinics around the world.

ACR TI-RADS assigns points to thyroid nodules based on 5 features:

1. composition
2. echogenicity
3. shape
4. margin
5. echogenic focus

According to this scoring, nodules are classified as:

• benign
• not suspicious
• mildly suspicious
• moderate
• or very suspicious.

While benign or nonsuspicious nodules do not need a biopsy, other nodules may require a biopsy or repeat ultrasound depending on their size.

According to ultrasound: 5 appearance categories and 5 risk categories

Using ACR TI-RADS, thyroid nodules are scored in five categories according to their ultrasound appearance:

1. Composition (content): Between 0 points for a cystic formation and 2 points for a solid formation.
2. Echogenicity: From 0 points for an anechoic image (similar brightness to normal tissue) to 3 points for a very hypoechoic (dark) image.
3. Shape: 0 points if it is wider than it is tall, and 3 points if it is taller than it is wide.
4. Margin: From 0 points for smooth to 3 points for extrathyroidal extension (irregular).
5. Echogenic foci: From 0 points for no spots of differing brightness within the nodule to 3 points for punctate echogenic foci.

At What Size in cm Is a Thyroid Nodule Dangerous? When Should It Be Biopsied?

The decision about which nodule to biopsy is not based on size alone; it is evaluated together with the other factors above. However, size is important according to the degree of suspicion.

According to their total points, nodules are then classified into 5 categories of suspicion for cancer:

• 0 points, benign: No fine-needle aspiration biopsy (İİAB) is needed.
• 2 points, not suspicious: No İİAB is needed.
• 3 points, mildly suspicious: Perform İİAB if ≥ 2.5 cm; follow up if ≥ 1.5 cm.
• 4 to 6 points, moderately suspicious: İİAB if ≥ 1.5 cm; follow up if ≥ 1 cm.
• ≥ 7 points, highly suspicious: İİAB if ≥ 1 cm; follow up if ≥ 0.5 cm.

For nodules too small to meet the İİAB criteria and for moderately suspicious nodules, follow-up imaging is recommended in years 1, 3 and 5. However, highly suspicious nodules should have annual follow-up, and regular annual follow-up should continue for up to 5 years.

Which Nodule Should Be Scheduled for Biopsy?

Contrary to expectations, a thyroid biopsy is not performed on the largest nodule. For proper biopsy sampling, the total points should guide selection of the most suspicious-looking one or at most two nodules. Biopsying three or more nodules at the same time provides little benefit and may involve some additional risks.

Conclusion

Thyroid nodules are conditions frequently seen in the community, particularly in people under 60. First, it should be known that not every nodule will become cancerous. As also recommended in the follow-up of many nodules detected without symptoms, biopsying every nodule is not the correct approach. Nodules with a low risk of thyroid cancer should be followed without a biopsy, under active surveillance ("watchful waiting") with ultrasound. If a nodule is structurally low-risk but is 2.5 cm or larger, a biopsy would be appropriate. While biopsy is recommended for intermediate-risk nodules of 1.5 cm or larger, it is recommended for highly suspicious nodules if they are 1 cm or larger. For suspicious thyroid nodules, regular doctor visits and completion of recommended follow-up ultrasounds are important for detecting progression to cancer early.

Below is a visual educational presentation on USG findings, the gold-standard tool for diagnosing thyroid nodules.

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