This comprehensive guide explains how doctors distinguish between harmless and potentially cancerous thyroid nodules. Thyroid nodules are extremely common, found in up to 67% of adults, but only 7-15% are malignant. The process relies on a combination of a physical exam, a blood test for Thyroid-Stimulating Hormone (TSH), a thyroid ultrasound, and sometimes a fine-needle aspiration (FNA) biopsy. New guidelines help doctors categorize nodules by their ultrasound appearance to determine the risk of cancer and decide on the best course of action, which for most patients is simple monitoring rather than immediate surgery.

A Patient's Guide to Understanding Thyroid Nodules: Benign vs. Malignant

Table of Contents

• Background: What Are Thyroid Nodules?
• Evaluation: The First Steps in Your Doctor's Office
• Laboratory Tests: The Crucial Blood Work
• Imaging: Ultrasound and Other Scans
• The Fine-Needle Aspiration (FNA) Biopsy
• Management: What Your Results Mean
• Special Considerations for Children and Pregnancy
• Conclusion and Key Takeaways
• Source Information

Background: What Are Thyroid Nodules?

Thyroid nodules are small, discrete lumps that form within your thyroid gland, which is located at the base of your neck. These nodules are very common. A doctor can feel them during an examination in about 4–7% of people. However, when sensitive imaging tests like ultrasound are used, they can be found in a staggering 67% of adults.

The vast majority of these nodules are benign (non-cancerous). Despite this, the potential risk that a nodule could be malignant (cancerous) is a serious concern, ranging from 7% to 15% in adults. Because these nodules are so common, doctors have developed clear, evidence-based guidelines to evaluate them properly, avoiding both missed diagnoses and unnecessary procedures.

There are many different types of thyroid nodules. They can be non-neoplastic, which means they are not true tumors, or neoplastic, which means they are growths that can be either benign or malignant.

• Non-neoplastic nodules: These include hyperplastic nodules (overgrowth of normal tissue), colloid nodules, inflammatory nodules, and cysts (which are nearly always benign).
• Neoplastic (tumor) nodules:
  • Benign: Follicular adenoma.
  • Malignant: Papillary carcinoma, Follicular carcinoma, Medullary carcinoma, Anaplastic carcinoma, Lymphoma, or Metastasis from another cancer.

Evaluation: The First Steps in Your Doctor's Office

Many thyroid nodules are discovered by accident when a scan is done for an unrelated reason. Others are found because you or your doctor notice a lump in your neck. Larger nodules can sometimes cause symptoms like shortness of breath (dyspnoea), a feeling of a lump in the throat (globus), or difficulty swallowing (dysphagia).

Your doctor will take a thorough history and perform a physical exam. They will ask about important risk factors, such as a history of radiation to your head or neck as a child, which significantly increases the chance a nodule is cancerous. They will also ask about your family history, as certain rare genetic syndromes can predispose people to thyroid cancer.

During the exam, the doctor will feel your thyroid gland and the lymph nodes in your neck. They are assessing the nodule's size, how firm it feels, and if it moves when you swallow. A firm, fixed nodule or swollen lymph nodes on the same side are later signs that could suggest cancer and warrant prompt further investigation.

Laboratory Tests: The Crucial Blood Work

The first and most important blood test is for Thyroid-Stimulating Hormone (TSH). This test should be done for every patient with a suspected or incidentally found thyroid nodule. Most patients will have normal TSH levels, meaning their thyroid is functioning normally (euthyroid).

If your TSH level is suppressed (low), it indicates you might have a hyperfunctioning nodule (an "overactive" nodule). The key point for patients is that these hyperfunctioning nodules have an "exceedingly small risk" of being cancerous. If your TSH is low, your doctor will refer you to an endocrinologist for further management.

It's important to know what tests are not routinely helpful. A serum thyroglobulin level is not sensitive or specific for detecting cancer and should not be ordered for initial evaluation. A serum calcitonin level is expensive and is only requested if there is a specific suspicion for a rare type of cancer called medullary thyroid carcinoma.

Imaging: Ultrasound and Other Scans

Ultrasonography is the most important imaging test for thyroid nodules. High-resolution machines are incredibly sensitive, able to detect nodules as small as 1–3 mm. All patients with a suspected nodule should be referred for a thyroid and neck ultrasound. This test provides detailed information on the nodule's size and, more importantly, its sonographic features, which are used to estimate the risk of cancer.

Based on the 2015 American Thyroid Association (ATA) guidelines, nodules are now categorized into five groups. This risk stratification system helps doctors decide if a biopsy is needed. The ultrasound features with the highest specificity for cancer are microcalcifications (tiny white specks), irregular margins (jagged edges), and a "taller than wide" shape.

Thyroid Nodule Classification and Malignancy Risk:

• Benign Pattern: Purely cystic nodules. Malignancy risk: <1%. Action: No biopsy needed.
• Very Low Suspicion: Spongiform or partially cystic nodules. Malignancy risk: <3%. Action: Monitor or consider biopsy if ≥2 cm.
• Low Suspicion: Solid, isoechoic or hyperechoic nodules, or partially cystic nodules with eccentric solid areas. Malignancy risk: 5–10%. Action: Biopsy recommended if ≥1.5 cm.
• Intermediate Suspicion: Solid, hypoechoic nodules with smooth margins. Malignancy risk: 10–20%. Action: Biopsy recommended if ≥1 cm.
• High Suspicion: Solid hypoechoic nodule with irregular margins, microcalcifications, taller-than-wide shape, or other worrying features. Malignancy risk: 70–90%. Action: Biopsy recommended if ≥1 cm.

Radionuclide imaging (a thyroid scan) is not a routine test. It is only used for patients who have a low TSH level. In Australia, the most common type uses technetium-99m pertechnetate (99m Tc), which is accessible and effective at identifying "hot" (overactive) nodules.

The Fine-Needle Aspiration (FNA) Biopsy

An FNA biopsy is a procedure where a very thin needle is used to extract cells from the thyroid nodule. It is a valuable tool that has greatly reduced the number of unnecessary thyroid surgeries. When performed by an experienced doctor, its diagnostic accuracy is approximately 95%.

The decision to perform a biopsy depends entirely on the nodule's ultrasound appearance and its size, as outlined in the classification above. For example, a 1.2 cm nodule with "high suspicion" features would require a biopsy, while a 1.8 cm "very low suspicion" nodule might just be monitored.

All biopsy results are reported using the Bethesda System, which places the findings into one of six categories, each with an associated risk of cancer.

1. Non-diagnostic/Unsatisfactory (5-10% of samples): The sample didn't have enough cells. Cancer risk: 5-10%. Action: The biopsy usually needs to be repeated.
2. Benign (55-75% of samples): The cells look normal. Cancer risk: 0-3%. Action: Monitoring with ultrasound, no surgery needed.
3. Atypia of Undetermined Significance (AUS)/Follicular Lesion of Undetermined Significance (FLUS) (2-18% of samples): The cells aren't clearly normal or cancerous. Cancer risk: 10-30%. Action: Referral to an endocrinologist; often a repeat biopsy or molecular testing is needed.
4. Follicular Neoplasm/Suspicious for Follicular Neoplasm (FN/SFN) (2-25% of samples): The cells look like a follicular tumor, which can only be diagnosed as benign or cancerous after it is surgically removed. Cancer risk: 25-40%. Action: Referral to a surgeon for discussion of removing part of the thyroid.
5. Suspicious for Malignancy (1-6% of samples): The cells are highly suspicious for cancer. Cancer risk: 50-75%. Action: Referral to a high-volume thyroid surgeon.
6. Malignant (2-5% of samples): The cells are definitely cancerous. Cancer risk: 97-99%. Action: Immediate referral to a high-volume thyroid surgeon.

Management: What Your Results Mean

The primary goal is to correctly identify the small number of nodules that are cancerous so they can be treated, while avoiding unnecessary procedures for the many benign nodules. The majority of patients will have a benign FNA result. These patients do not need surgery but will require follow-up ultrasound scans to ensure the nodule isn't growing. The timing of these follow-up scans depends on the original ultrasound risk category:

• High suspicion nodules: Repeat ultrasound in 6-12 months.
• Intermediate or Low suspicion nodules: Repeat ultrasound in 12-24 months.
• Very low suspicion nodules (<1 cm): These grow very little over five years and do not require routine follow-up.

Any result other than "Benign" should be referred to a specialist—either an endocrinologist or a thyroid surgeon. This is especially important for indeterminate results (Bethesda categories III and IV), which can be complex to manage. Malignant or suspicious results should be sent directly to a high-volume thyroid surgeon, as surgeon experience is directly linked to better patient outcomes.

Many nodules are found incidentally on scans like CT or MRI done for other reasons (these are called incidentalomas). These nodules carry the same risk of cancer as ones found during an exam and should be evaluated with an ultrasound. Small incidentalomas that don't meet the size criteria for a biopsy can simply be monitored. Special attention is given to nodules found on FDG-PET scans, as about 35% of these turn out to be cancerous, so a biopsy is recommended for any that are larger than 1 cm.

Special Considerations for Children and Pregnancy

Paediatric Thyroid Nodules: While less common in children (palpable in 1.8–5.1%), thyroid nodules in this age group have a much higher risk of being cancerous. The overall malignancy rate in children is about 26%, compared to 5–10% in adults. The evaluation is similar, but because children are smaller, the decision to biopsy is based more on the ultrasound features than a strict size cutoff. Due to the higher cancer risk, indeterminate biopsies in children are more likely to lead directly to surgery.

Pregnancy: Nodules discovered during pregnancy should be evaluated with a TSH test. If TSH is normal or high, an FNA biopsy can and should be performed. The good news is that thyroid cancer does not appear to behave more aggressively during pregnancy, and patients have an excellent prognosis. A discussion with a surgeon will help decide whether to operate during pregnancy or wait until after delivery.

Conclusion and Key Takeaways

Thyroid nodules are extremely common, and most are harmless. A systematic, evidence-based approach using TSH testing, ultrasound, and FNA biopsy allows doctors to accurately identify the few nodules that need treatment. The key points for patients to remember are:

• You are not alone; nodules are found in most adults.
• The vast majority of nodules are benign and only require monitoring.
• The ultrasound appearance is critical for determining the next steps.
• A biopsy is a highly accurate test that prevents unnecessary surgery.
• If your results are unclear or suggest cancer, you will be referred to a specialist with expertise in managing these conditions.

Source Information

Original Article Title: Differentiating between benign and malignant thyroid nodules: An evidence-based approach in general practice
Authors: Stuart Bailey, Benjamin Wallwork
Publication: Reprinted from AJGP Vol. 47, NO. 11, November 2018 © The Royal Australian College of General Practitioners 2018
Note: This patient-friendly article is based on peer-reviewed research and aims to translate the original medical content for educational purposes. It is not a substitute for professional medical advice.