What is the role of fine-needle aspiration biopsy (FNAB) in the evaluation of a solitary thyroid nodule?

Updated: Aug 19, 2020
  • Author: Daniel J Kelley, MD; Chief Editor: Arlen D Meyers, MD, MBA  more...
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Fine-needle aspiration biopsy (FNAB) has become the diagnostic tool of choice for the initial evaluation of solitary thyroid nodule because of its accuracy, safety, and cost effectiveness. Fewer patients have undergone thyroidectomy for benign disease as a result of FNAB, with resultant decreased health care costs. [17, 18] Although needle biopsy can be performed easily, consistently obtaining adequate tissue and processing the specimens to achieve accurate cytopathological interpretation requires expertise and experience. A satisfactory specimen should contain at least 5 or 6 groups of 10-15 well-preserved cells. Aspirated specimen is placed on glass slides and air-dried or fixed for staining. The adequacy of the specimen should be determined before the patient leaves.

FNAB specimens are classified as malignant, benign, indeterminate (suspicious for follicular or Hürthle cell neoplasm), or insufficient for diagnosis. In a comprehensive review of 28 series in which FNAB was performed on 10,872 patients with thyroid nodules, cytology was found to be benign in 53-90%, indeterminate or suspicious in 5-23%, malignant in 1-10%, and nondiagnostic in 2-21% of patients. Overall sensitivity, specificity, and accuracy of the FNAB technique have been reported to be 83%, 92%, and 95%, respectively. The effectiveness of FNAB of solitary thyroid nodules may be improved with the use of ultrasound guidance rather than simple palpation.

Accuracy of FNAB is closely related to the histologic type of thyroid carcinoma that is being evaluated. Papillary thyroid carcinoma is readily identified using FNAB because of its unique cytologic features. Diagnosis is correct for papillary thyroid carcinoma in approximately 90-100% of FNAB specimens when correlated with the histology of the final surgical specimen. Undifferentiated (anaplastic) carcinoma, medullary thyroid carcinoma, and primary thyroid lymphoma also have characteristic cytologic features, which aid correct diagnosis in approximately 90% of FNAB specimens.

A study by Kaliszewski et al indicated that FNAB rarely produces false-negative results in patients with solitary malignant thyroid tumors, while in contrast, the results in patients with multiple malignant thyroid tumors are often false negative. Compared with the thyroid cancer prediction rate for FNAB in patients with multiple malignant nodules, the prediction rate for those with cancer in single nodules was three times higher. [19]

A study by Arul and Masilamani indicated that in cases of solitary thyroid nodules, fine-needle aspiration cytology reports using the Bethesda System for Reporting Thyroid Cytopathology correlate well with histopathologic diagnosis of these nodules, having a sensitivity, a specificity, an accuracy, a positive predictive value, and a negative predictive value of 94.4%, 97.6%, 95.8%, 98.1%, and 93.2%, respectively. [20]

However, a study by Bakkar et al suggested that solitary thyroid nodules of 3 cm in size or greater that have been diagnosed on fine-needle aspiration cytology as Bethesda classification II (ie, benign) have a significant malignancy risk. In the study, which involved 202 patients with solitary thyroid nodules sized 3 cm or more, the cancer risk was 22.8%. The investigators reported an 11.4% risk of cancer for which there was a recommendation of surgery and a 9.4% risk of cancer for which total thyroidectomy was needed. It was also found that the malignancy risk was greater in predominantly cystic nodules than in predominantly solid ones. [21]

The main limitation of FNAB is the differentiation of benign from malignant follicular neoplasms. FNAB specimens of follicular neoplasms and Hürthle cells are commonly interpreted as indeterminate or suspicious. This has resulted in low FNAB accuracy rates of approximately 40% for follicular carcinomas. Diagnosis of follicular carcinoma also requires the identification of capsular and/or vascular invasion, which is not a possibility with FNAB techniques. Therefore, several techniques in addition to FNAB have been developed to increase the accuracy of FNAB for follicular carcinomas, including immunocytochemistry techniques, large needle biopsy, and intraoperative frozen section analysis.

Thyroid peroxidase (TPO) immunocytochemistry with a monoclonal antibody termed MoAb 47 has been reported to significantly increase the accuracy of FNAB in patients with follicular lesions. Large-needle biopsy can also increase the diagnostic accuracy of FNAB, but it also increases the risk of hematoma, tracheal injury, laryngeal nerve injury or injury to other neck structures, and cutaneous implantation of malignant cells. Intraoperative frozen section analysis of thyroid nodules requires excisional biopsy in the form of thyroidectomy and may provide no additional information. Some authors report a high degree of accuracy with intraoperative frozen section; however, its contribution to the management of solitary thyroid nodules remains controversial.

The application of molecular genetics to fine-needle aspiration biopsy holds great promise as an additional technique to help differentiate benign from malignant nodules and avoid surgery for benign thyroid disease. Several molecular markers, including BRAF, RAS, PAX8-PPARγ, microRNAs, and loss of heterozygosity, have been studied as potential molecular tools for predicting malignancy in cytology specimens and may potentially help guide decisions regarding surgical management of nodular thyroid disease. The addition of cytologic molecular markers to nomograms of other clinically relevant information may also help the thyroid surgeon's ability to select those patients with solitary thyroid nodules at highest risk for malignancy.

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