Fine Needle Biopsy of Thyroid Nodules. Is it cancer or just a benign nodule?

Fine Needle Biopsy of Thyroid Nodules

Is it cancer or just a benign nodule?

Written by James Norman MD, FACS, FACE
This page is written assuming you have read the introductory page on thyroid nodules first. If you have not, please do so because it will make this page easier to understand.1

Solitary dominant nodule of right thyroid lobeThyroid nodules increase with age and are present in almost 10% of the adult population. Autopsy studies reveal the presence of thyroid nodules in 50% of the population, so they are fairly common. 95% of solitary thyroid nodules are benign, and therefore, only 5% of thyroid nodules are malignant.

Common types of the benign thyroid nodules are adenomas (overgrowths of normal thyroid tissue), thyroid cysts, and Hashimoto’s thyroiditis.

Uncommon types of benign thyroid nodules are due to subacute thyroiditis, painless thyroiditis, unilateral lobe agenesis, or Riedel’s struma. As noted on previous pages, those few nodules that are cancerous are usually due to the most common types of thyroid cancers that are the differentiated thyroid cancers. Papillary carcinoma accounts for 60%, follicular carcinoma accounts for 12%, and the follicular variant of papillary carcinoma accounts for 6%. These well differentiated thyroid cancers are usually curable, but they must be found first. Fine needle biopsy is a safe, effective, and easy way to determine if a nodule is cancerous.

Thyroid cancers typically present as a dominant solitary nodule that can be felt by the patient or even seen as a lump in the neck by his/her family and friends. This is illustrated in the picture above.

As pointed out on our page introducing thyroid nodules, we must differentiate benign nodules from cancerous solitary thyroid nodules. While history, examination by a physician, laboratory tests, ultrasound, and thyroid scans (shown in the image on the right) can all provide Solitary cold nodule of thyroidinformation regarding a solitary thyroid nodule, the only test that can differentiate benign from cancerous thyroid nodules is a biopsy (the term biopsy means to obtain a sample of the tissue and examine it under the microscope to see if the cells have taken on the characteristics of cancer cells).

Thyroid cancer is no different in this situation from all other tissues of the body; the only way to see if something is cancerous is to biopsy it. However, thyroid tissues are easily accessible to needles, so rather than operating to remove a chunk of tissue with a knife, we can stick a very small needle into it and remove cells for microscopic examination. This method of biopsy is called a fine needle aspiration biopsy (FNA).

What is a Cold or Hot Nodule?
Nodules detected by thyroid scans are classified as cold, hot, or warm. Thyroid cells absorb iodine so they can make thyroid hormone out of it. When radioactive iodine is given, a butterfly image will be obtained on x-ray film showing the outline of the thyroid. If a nodule is composed of cells that do not make thyroid hormone (don’t absorb iodine), then it will appear “cold” on the x-ray film. A nodule that is producing too much hormone will show up darker and is called “hot.”

85% of thyroid nodules are cold, 10% are warm, and 5% are hot. Remember that 85% of cold nodules are benign, 90% of warm nodules are benign, and 95% of hot nodules are benign.

Although thyroid scanning can give a probability that a nodule is benign or malignant, it cannot truly differentiate benign or malignant nodules and usually should not be used as the only basis for recommending treatment of the nodule, including thyroid surgery.

The evaluation of a solitary thyroid nodule should always include history and examination by a physician. Certain aspects of the history and physical exam will suggest a benign or malignant condition. Remember, a biopsy of some sort is the only way to tell for sure.

The Following Features Favor a Benign Thyroid Nodule:

  • Family history of Hashimoto’s thyroiditis
  • Family history of benign thyroid nodule or goiter
  • Symptoms of hyperthyroidism or hypothyroidism
  • Pain or tenderness associated with a nodule
  • A soft, smooth, mobile nodule
  • Multi-nodular goiter without a predominant nodule (lots of nodules, not one main nodule)
  • “Warm” nodule on thyroid scan (produces normal amount of hormone)
  • Simple cyst on an ultrasound


The Following Features Increase the Suspicion of a Malignant Nodule:

  • Age less than 20
  • Age greater than 70
  • Male gender
  • New onset of swallowing difficulties
  • New onset of hoarseness
  • History of external neck irradiation during childhood
  • Firm, irregular, and fixed nodule
  • Presence of cervical lymphadenopathy (swollen, hard lymph nodes in the neck)
  • Previous history of thyroid cancer
  • Nodule that is “cold” on scan (shown in picture above, meaning the nodule does not make hormone)
  • Solid or complex on an ultrasound

Thyroid hormone levels are usually normal in the presence of a nodule, and normal thyroid hormone levels do not differentiate benign from cancerous nodules. However, the presence of hyperthyroidism or hypothyroidism favors a benign nodule (that’s why a “warm” or a “hot” nodule favors a benign condition).

Thyroglobulin levels are useful tumor markers once the diagnosis of malignancy has been made, but they are non-specific in regard to differentiating a benign from a cancerous thyroid nodule.

Ultrasound accurately determines thyroid gland volume, number, and size of nodules, separates thyroid from nonthyroidal masses, helps guide fine needle biopsy when necessary, and can identify solid nodules as small as 3mm and cystic nodules as small as 2mm.

Although several ultrasound features favor the presence of a benign nodule, and other ultrasound features favor the presence of a cancerous nodule, ultrasound alone cannot differentiate benign from malignant nodules. This is covered more completely on our nodule/ultrasound page. And since 15% of cystic thyroid nodules are malignant, ultrasound determination that a nodule is cystic does not rule out thyroid cancer.

Thyroid fine needle aspiration (FNA) biopsy is the only non-surgical method that can differentiate malignant and benign nodules in most, but not all, cases. The needle is placed into the nodule several times and cells are aspirated into a syringe. The cells are placed on a microscope slide, stained, and examined by a pathologist. The nodule is then classified as non-diagnostic, benign, suspicious, or malignant.

  • Non-diagnostic indicates that there are an insufficient number of thyroid cells in the aspirate and no diagnosis is possible. A non-diagnostic aspirate should be repeated, as a diagnostic aspirate will be obtained approximately 50% of the time when the aspirate is repeated. Overall, 5 to 10% of biopsies are non-diagnostic, and the patient should then undergo either an ultrasound or a thyroid scan for further evaluation.
  • Benign thyroid aspirations are the most common (as we would suspect since most nodules are benign) and consist of benign follicular epithelium with a variable amount of thyroid hormone protein (colloid).
  • Malignant thyroid aspirations can diagnose the following thyroid cancer types: papillary, follicular variant of papillary, medullary, anaplastic, thyroid lymphoma, and metastases to the thyroid. Follicular carcinoma and Hurthle cell carcinoma cannot be diagnosed by FNA biopsy. This is an important point. Since benign follicular adenomas cannot be differentiated from follicular cancer (~12% of all thyroid cancers) these patients often end up needing a formal surgical biopsy, which usually entails removal of the thyroid lobe that harbors the nodule.
  • Suspicious cytologies make up approximately 10% of FNAs. The thyroid cells on these aspirates are neither clearly benign nor malignant. 25% of suspicious lesions are found to be malignant when these patients undergo thyroid surgery. These are usually follicular or Hurthle cell cancers. Therefore, surgery is recommended for the treatment of thyroid nodules from which a suspicious aspiration has been obtained.

FNA is the first, and in the vast majority of cases, the only test required for the evaluation of a solitary thyroid nodule. (A TSH value should also be obtained to evaluate thyroid function.) Thyroid ultrasound and thyroid scans are usually not required for evaluation of a solitary thyroid nodule. FNA has reduced the cost for evaluation and treatment of thyroid nodules and has improved yield of cancer found at thyroid surgery. Although a solitary thyroid nodule can enlarge or shrink over time, the natural history of solitary nodules reveals that most nodules change little with time.

Can I Make the Nodule Go Away by Taking Thyroid Hormone?
Several studies reveal that suppression with thyroid hormone does not decrease the size of thyroid nodules. Therefore, unless a nodule is growing or becoming symptomatic, it is not necessary to suppress the nodule. In addition, suppression of a thyroid nodule would require long-term thyroid-stimulating hormone (TSH) suppression, potentially increasing the risk of osteoporosis in these patients.

While there has been a traditional distinction between thyroid glands with a solitary nodule and multi-nodular goiters, it has been shown that approximately 50% of patients with a solitary nodule on exam will have additional nodules on thyroid ultrasound. Therefore, the differentiation between solitary nodules and multinodular goiters is becoming less clear-cut.

It has also been believed for many years that the presence of a multinodular goiter reduces the likelihood that a thyroid cancer is present, yet recent studies indicate that there might be an equal likelihood for developing thyroid cancer in a multinodular goiter just as in a solitary thyroid nodule. If a multinodular goiter has a predominant nodule, the predominant nodule should be biopsied.

In conclusion, FNA of the thyroid is a safe, inexpensive, and effective way to distinguish a benign from a malignant nodule and usually should be the first diagnostic test performed.

Much of this information was obtained from an article published in The Endocrinologist (November 1996), which was written by Mark Stesin, MD. His expertise is acknowledged.

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