Click here for Frequently Asked Questions on Thyroid Biopsies.
A fine needle aspiration (FNA) biopsy or thyroid biopsy, is usually carried out to determine the nature of the cells in a thyroid nodule. The biopsy is done with a small needle, and local anesthesia is not generally required. Your physician should be advised if you have any medical conditions that increase your risk of bleeding, or if you are taking drugs that may increase your chances of bleeding during the biopsy, such as aspirin, other non-steroidal agents, anti-platelet agents, or blood thinners such as coumadin or warfarin. There is a great deal of background information supporting the decision to carry out a FNA. Furthermore, there are consensus guidelines for the decision to carry out a biopsy, the actual procedure itself, the interpretation of the results, and other biopsy-related issues. To review the opinions of experts in the field in the area of thyroid biopsies, see the NCI State of the Art FNA Conference website. Individuals with a strong interest and science/medical background may also wish to peruse the final April 2008 FNA Consensus Conference Summary (109 pages in total).
Most studies have shown that the greater number of separate needle aspirations done at the time of the biopsy, the greater yield and ultimate accuracy of the biopsy procedure. Hence it is common practice for several attempts to be made in the course of the biopsy procedure, or for the needle to be inserted into a few different locations within the thyroid nodule.
Firm pressure applied locally to the biopsy site for about 5 minutes is usually sufficient to stop any bleeding that may develop following the biopsy. Some minor degree of discomfort in the neck, perhaps soreness or occasionally ear pain, may be noticeable for 1-3 days after the biopsy, but the majority of patients do not experience these complaints after thyroid biopsy.
Patients should be aware that thyroid biopsies may frequently not be diagnostic, and there are limitations to the success and utility of the biopsy procedure. These limitations include the local anatomy of the patients neck, the skill of the person carrying out the biopsy, and the experience of the cytopathologist examining the biopsy material. Furthermore, it is often not possible for even a superb experienced pathologist to make a determination of benign versus malignant thyroid cells, even if an excellent biopsy is obtained, depending on the nature of the underlying thyroid pathology.
Most patients are surprised to learn that a biopsy may not always give 100% accurate or informative results, as outlined in Malignancy risk for fine-needle aspiration of thyroid lesions according to the bethesda system for reporting thyroid cytopathology Am J Clin Pathol. 2010 Sep;134(3):450-6. Although good centers will end up with informative and accurate results about 80-90% of the time a biopsy is done, certain types of nodules showing lots of follicular cells or Hurthle cells result in an inability to make an accurate preoperative diagnosis. See The accuracy of fine-needle aspiration biopsy and frozen section in patients with thyroid cancer. Thyroid. 2002 Jul;12(7):619-26. and False-negative fine-needle aspiration cytology results delay treatment and adversely affect outcome in patients with thyroid carcinoma. Thyroid. 2004 Mar;14(3):207-15. Given the limitations of the test, it is not uncommon for a patient to have more than one biopsy in the first year of assessment, depending on the size of the nodule, the clinical appearance of the nodule, and the judgment of the physician as outlined in Repeat thyroid nodule fine-needle aspiration in patients with initial benign cytologic results. Am J Clin Pathol. 2006 May;125(5):698-702
It is important to remember that all diagnostic procedures, including thyroid fine needle aspiration biopsies, have their limitations. For a representative overview of the sensitivity and specificity and predictive value of biopsy results from several centers, see Clin Endocrinol (Oxf) 1999 Oct;51(4):509-515 Sensitivity and specificity of the fine needle aspiration biopsy of the thyroid: clinical point of view and Usefulness of fine-needle aspiration in the diagnosis of thyroid carcinoma: a retrospective study in 37,895 patients. Cancer. 2000 Dec 25;90(6):357-63. and Use and accuracy of fine-needle aspiration cytology in histologically proven thyroid carcinoma: an audit using a national pathology database. Cancer. 2000 Dec 25;90(6):330-4. In some centers, the reported results using ultrasound guided (FNAB) biopsies are very accurate when correlated with the final surgical diagnosis, as shown in Fine needle aspiration cytology of thyroid nodules: how accurate is it and what are the causes of discrepant cases? Cytopathology. 2001 Dec;12(6):399-405. In contrast, even academic teaching centers report less than optimal accuracy of thyroid biopsies when correlated with the final diagnosis after surgical removal of the thyroid gland Errors in thyroid gland fine-needle aspiration. Am J Clin Pathol. 2006 Jun;125(6):873-82
Furthermore, analysis of ultrasound guided biopsies at a Harvard teaching hospital demonstrated that only 63% of biopsies done under ultrasound yielded sufficient cells for accurate initial assessment. See Assessment of Nondiagnostic Ultrasound-Guided Fine Needle Aspirations of Thyroid Nodules. J Clin Endocrinol Metab. 2002 Nov 1;87(11):4924-4927. Nevertheless, there is evidence that biopsies done under ultrasound guidance yield more accurate results than biopsies done by a physician without the use of ultrasound Comparison of palpation-guided fine-needle aspiration biopsy to ultrasound-guided fine-needle aspiration biopsy in the evaluation of thyroid nodules. Thyroid. 2006 Jun;16(6):555-61
There are ongoing research studies examining whether newer molecular techniques can improve the diagnostic accuracy of the thyroid biopsy. Some studies have shown that a combination of gene expression profiles can improve the ability of scientists to distinguish benign versus malignant follicular tumors, but these studies are still experimental and not widely available. See A preoperative diagnostic test that distinguishes benign from malignant thyroid carcinoma based on gene expression. J Clin Invest. 2004 Apr;113(8):1234-42. Independent evaluation of one commercially available molecular test, the Gene Expression Classifier "Afirma GEC' assay, involved requesting the molecular analysis in subjects with biopsy results, analyzed at an academic medical center, described as follicular neoplasm or atypia or Follicular Lesion of Undetermined Significance (AUS/FLUS). Subsequently, of 60 such biopsy samples available for Afirma analysis, 17 (28%) were "benign", while 43 (72%) were "suspicious". After surgical removal of the lesions, the rate of confirmed malignancy in GEC-suspicious nodules was only 16%. Hence, rigorous independent evaluation of any new test is required to establish the sensitivity, specificity, and predictive value. An Independent Study of a Gene Expression Classifier (Afirma™) in the Evaluation of Cytologically Indeterminate Thyroid Nodules J Clin Endocrinol Metab. 2014 Apr 29:jc20133584
Nodules that are partly cystic may yield only cyst fluid and degenerating cells, with little in the way of informative thyroid cells for a pathologist to review. Alternatively, despite several reasonable attempts, only blood cells and inflammatory cells may be obtained, precluding a definitive cytology interpretation. Thyroid adenomas that are benign and follicular thyroid cancers may look the same following a thyroid biopsy to even the most experienced cytopathologist, and sometimes the only way to make a definitive diagnosis in these cases is to remove the nodule surgically.
Depending on the size of the nodule, the anatomical location, the local anatomy, and skill of the individual physician, a nodule may be biopsied in the office, or under ultrasound guidance. Ultrasound-guided biopsies may be particularly valuable for small nodules that are difficult to access, or for nodules that are partly cystic, where biopsy of the solid component is desired.
Why do most physicians recommend that small nodules less than 1 or 1.4 cm not always be biopsied?
This is a controversial area where judgment may vary from case to case. Since nodules are usually slow growing, careful ongoing surveillance is helpful in instances where a nodules, even if not biopsied, may exhibit a growth pattern. Nevertheless, many small 'sub-centimeter' nodules exhibit the same rates of thyroid cancer as somewhat larger nodules The value of fine-needle aspiration biopsy in subcentimeter thyroid nodules. Thyroid. 2008 Jun;18(6):603-8. Nevertheless, many experts concur that careful observation of nodules up to 14 mm in size is a reasonable approach to management of thyroid nodules Decision analysis of discordant thyroid nodule biopsy guideline criteria J Clin Endocrinol Metab. 2008 Aug;93(8):3037-44.
My doctor says that my biopsy result is inconclusive and is recommending surgery even though no cancer cells were detected. Is this possible?
There are many factors that influence the diagnostic utility of a biopsy result, including the quality of the biopsy, and the nature of the underlying cells obtained. A common and frustrating problem results when one obtains primarily follicular cells in the biopsy. As follicular cells may be obtained from either a benign follicular adenoma, nodular hyperplasia, or a follicular carcinoma, it is not possible, in many instances, for the cytopathologist to call a biopsy result benign or suspicious for malignancy when follicular cells make up the dominant form of cell type obtained in the biopsy. Some studies suggest that the risk of thyroid cancer is about 25% when the biopsy report suggests a "follicular lesion" One in Four Patients with Follicular Thyroid Cytology (THY3) Has a Thyroid Carcinoma Thyroid. 2008 Nov 3. [Epub ahead of print]. Indeed, even when the whole thyroid has been removed, it can be difficult to differentiate benign from malignant thyroid tissue. See Follicular-patterned lesions of the thyroid: the bane of the pathologist. Am J Clin Pathol. 2002 Jan;117(1):143-50. Review. Not surprisingly, the larger the nodule, the greater the risk of thyroid cancer, with nodules of 3-4 cm in size or greater exhibiting a 20-25% risk of harboring thyroid cancer. The incidence of cancer and rate of false-negative cytology in thyroid nodules greater than or equal to 4 cm in size Surgery. 2007 Dec;142(6):837-44.
There is currently much interest in using genetic and biochemical analyses to improve the diagnostic accuracy in these type of circumstances.
My first biopsy was inconclusive-when should another biopsy be scheduled?
There is no universal agreement about the timing of a second biopsy. Although some guidelines advocate surveillance and repeat biopsy in 3 months, the available data suggests that the timing of the second biopsy is not critical, and should be based on size of the lesion and clinical judgement. Diagnostic yield of nondiagnostic thyroid nodules is not altered by timing of repeat biopsy. Thyroid. 2012 Jun;22(6):590-4
My biopsy result shows "follicular cells" and the possibility of a follicular neoplasm. What does this mean?
Follicular cells are normal thyroid cells, that form follicles. However, patients with either benign growth of the thyroid (hyperplasia or adenoma) or cancer of the thyroid (follicular carcinoma) can also show abundant follicular cells on biopsy. In some studies, the risk of thyroid cancer in a patient showing abundant follicular cells is about 20%. For example, see Risk factors for malignancy of thyroid nodules initially identified as follicular neoplasia by fine-needle aspiration: results of a prospective study of one hundred twenty patients Thyroid 2000 Aug;10(8):709-12. In other retrospective reviews, the cytology diagnosis of "follicular neoplasm" was associated with a 30% risk of thyroid cancer at the time of surgery for definitive diagnosis. See Diagnosis of "follicular neoplasm": A gray zone in thyroid fine-needle aspiration cytology. Diagn Cytopathol. 2002 Jan;26(1):41-4.
What are the risks and complications associated with a fine needle aspiration biopsy?
Pain, local bruising and neck discomfort are the major lingering effects associated with FNAB. Although the discomfort is usually mild and temporary, rarely, patients may have neck tenderness and discomfort that can persist for a few weeks. A comprehensive overview of common and rare side effects associated with FNAB is provided in Clinical complications following thyroid fine needle biopsy: a systematic review. Clin Endocrinol (Oxf). 2009 Jan 19. [Epub ahead of print]
My biopsy result does not show any evidence for cancer cells, but my physician still suggests I consider surgery. What are the chances that I might have cancer?
The answer to this question depends on the size of the thyroid nodule, the ultrasound findings, the rate of growth, family history, presence or absence of associated risk factors, clinical findings and history, and the actual findings on biopsy. In summary, it is not possible to give a uniform answer to this question that applies to all patients. Nevertheless, patients need to be aware that biopsies are not always 100% reliable as sole predictors of the presence or absence of cancer. For example, in one study from the Sloan Kettering Cancer Centre, fine needle aspiration biopsy correctly identified only 50% of the cancers that were confirmed later at surgery Role of fine-needle aspiration biopsy and frozen section analysis in the surgical management of thyroid tumors. Ann Surg Oncol. 2001 Mar;8(2):92-100. Similarly, patients with previous exposure to radiation may have a higher rate of "false negative" biopsy results, as suggested in Accuracy of fine-needle aspiration cytology in patients with radiation-induced thyroid neoplasms. Br J Surg. 2003 Jun;90(6):755-8.
Hence the biopsy should be viewed as one of many helpful tools in the diagnosis, but not as the only gold standard.
My biopsy result was benign. Does this mean that I don't have thyroid cancer?
In most centers with considerable experience, the sensitivity and specificity of the thyroid biopsy approaches 90%. Hence, one or more thyroid biopsies that are benign should provide considerable reassurance that a thyroid malignancy is unlikely. Indeed, one long term study of this issue demonstrated that the risk of thyroid cancer in a patient with one or more normal or "benign" biopsies is very low, as shown in Long-term follow-up of patients with initially benign thyroid fine-needle aspirations. Thyroid. 2001 Aug;11(8):775-8. and similar results here A large thyroid fine needle aspiration biopsy cohort with long-term population-based follow-up Thyroid. 2020 Dec 28. doi: 10.1089/thy.2020.0689
Nevertheless, the size of the nodule, associated risk factors, rate of growth, development of new local symptoms and patient management preferences should all be considered when planning a strategy for ongoing follow-up of patients with thyroid nodules. It must be emphasized that it is not unheard of to have cancer diagnosed in a nodule several years after one or more benign biopsies, hence a plan for follow-up is an important part of the management of thyroid nodules. Most thyroid nodules and the majority of thyroid cancers grow slowly and some physicians may recommend follow up after a year or so following the first benign biopsy, depending on the history, previous rate of growth, characteristics of the nodule, and other mitigating factors Determination of the Optimal Time Interval for Repeat Evaluation following a Benign Thyroid Nodule Aspiration J Clin Endocrinol Metab. 2013 Nov 25
Are there no genetic tests that can be done on my FNA biopsy specimen to make it more informative and reliable?
It seems likely that analysis for genetic mutations may be incorporated into clinical practice and this should enhance our diagnostic accuracy in the future. For example, in a research study, detection of a specific genetic rearrangement in biopsy cells refined or enhanced the diagnosis of papillary thyroid cancer in some subjects where FNA alone was less than completely informative. See Analysis of ret/PTC Gene Rearrangements Refines the Fine Needle Aspiration Diagnosis of Thyroid Cancer. J Clin Endocrinol Metab. 2001 May;86(5):2187-90 and Detection of BRAF Mutation on Fine Needle Aspiration Biopsy Specimens: A New Diagnostic Tool for Papillary Thyroid Cancer. J Clin Endocrinol Metab. 2004 Jun;89(6):2867-72. Nevertheless, genetic rearrangements of the RET gene have also been detected in the setting of benign thyroid nodules, often in the presence of thyroid inflammation characteristic of Hashimoto's thyroiditis as described in RET/PTC rearrangement in non-neoplastic thyrocytes: follicular cells of Hashimoto's thyroiditis share low level recombination events with a subset of papillary carcinoma. J Clin Endocrinol Metab. 2006 Apr 4; [Epub ahead of print] . More recently, commercial gene expression tests, such as the Gene Expression Classifier have been approved as a decision aid in assessing the likelihood that an indeterminate biopsy will actually be benign vs. malignant. Although some studies have shown considerable promise for this test, independent analyses have not always validated its utility, as outlined Effect of Gene Expression Classifier Molecular Testing on the Surgical Decision-Making Process for Patients With Thyroid Nodules JAMA Otolaryngol Head Neck Surg. 2015 Dec 1;141(12):1082-8
The performance of these genetic test systems for indeterminate biopsies may vary somewhat from study to study and from center to center. Ideally, one should have a very good discussion about the accuracy of the test being used, and the experience of the local health care providers The real-world performance of ThyroSeqV.2 to diagnose thyroid "neoplasm requiring surgery" Am J Cancer Res. 2020 Nov 1;10(11):3838-3851
Can a PET scan be used to differentiate benign from malignant nodules and guide the decision about surgery when the biopsy results show follicular cells are are not conclusive?
Unfortunately, the majority of both benign and malignant nodules will
light up after PET scanning, so this procedure is not helpful in the
diagnosis of thyroid cancer. See 18F-Fluorodeoxyglucose
Positron Emission Tomography does not Predict Malignancy in Thyroid
Nodules Cytologically Diagnosed as Follicular Neoplasm. J
Clin Endocrinol Metab. 2007 Feb 6; [Epub ahead of print]
Should I have my biopsy done with ultrasound guidance, or without ultrasound in my physicians office?
The answer to this question depends on the size of your nodule, whether it is cystic or solid, the preference of your physician, and the skill of your physician(s) with biopsies and ultrasound assessments. In some centers, it is routine for all biopsies to be done under ultrasound guidance. In other centers, this may be requested periodically. For example, patients with very small nodules, that may be difficult to access because of their location or local anatomy, may benefit from a more accurate result if the biopsy is done under ultrasound. Similarly, patients with cystic nodules may find that the ultrasound-guided placement of the needle in the solid cellular portion of the nodule is more accurate if done under ultrasound. See Efficacy of ultrasound-guided fine-needle aspiration biopsy in the diagnosis of complex thyroid nodules. J Clin Endocrinol Metab. 2001 Sep;86(9):4089-91.
I am worried that the actual biopsy test itself may spread the cancer within my neck. Can this ever happen?
Like most rare events, this possibility has been observed, but there are only a handful of reports, and the estimated incidence of this event happening is probably about 1:100,00. Hence, although a theoretical concern, it is not likely to happen for the vast majority of patients with thyroid cancer who have a fine needle aspiration biopsy. See Implantation metastasis of head and neck cancer after fine needle aspiration biopsy. Auris Nasus Larynx. 2001 Nov;28(4):377-80 or Needle track seeding of papillary thyroid carcinoma from fine needle aspiration biopsy. A case report. Acta Cytol. 2002 May-Jun;46(3):591-5 for rare exceptions.
Are there complications associated with the biopsy procedure?
Some degree of discomfort is not uncommon, and
some patients will develop a small bruise or hematoma, that may be tender
for a few days. Rarely patients will have neck tenderness or discomfort
for a few weeks after the biopsy. In many centers, local or topical
anesthesia may be given to lessen the degree of pain associated with the
needle puncture. Additional rare complications include infections, and
very uncommonly transient impairment of the quality of the voice due to
reversible damage to the recurrent laryngeal nerve. See Transient
vocal cord paralysis after fine-needle aspiration biopsy of thyroid tumor.
2006 Jul; 16(7) :697-9.
I have more than one nodule-should they all be biopsied?
In general, physicians will elect to focus on the largest dominant nodule first; in some studies the risk of thyroid cancer is inversely correlated with the number of nodules as outlined in Prevalence and Distribution of Carcinoma in Patients with Solitary and Multiple Thyroid Nodules on Sonography. J Clin Endocrinol Metab. 2006 Jul 11; [Epub ahead of print].
My first biopsy was non-diagnostic and few cells were obtained-do I need another biopsy?
The answer to this question depends on the size of
the nodule, whether it is solid or cystic, clinical circumstances, and the
individual patient. In some studies, a repeat biopsy has revealed the
presence of thyroid cancer in 8.5% of subjects with a second biopsy. See Value
of repeating a nondiagnostic thyroid fine-needle aspiration biopsy Endocr
Pract. 2007 Nov-Dec;13(7):735-42