Management of Cytologically Indeterminate Thyroid Nodule

Thyroid nodules are a common clinical problem particularly with the recent increased use of imaging such as computed tomography, ultrasonography or magnetic resonance imaging (MRI) of the neck, or fluorodeoxyglucose (FDG) positron emission tomography. Several studies have demonstrated that thyroid nodules are found in 4–8% of the general population with the use of palpation in 19-67% of patients with the use of ultrasound, and in 50% of autopsies. The clinical importance of thyroid nodules is that ~5% are potentially malignant. In 2007, the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) was established to standardize the reporting of thyroid cytopathology and includes six distinct categories. Up to 30% of cytology results will fall into one of three indeterminate categories, using the Bethesda classification.The indeterminate category includes atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS); follicular neoplasm/suspicious for follicular neoplasm (FN/SFN), a category that also encompasses the diagnosis of Hürthle cell neoplasm/suspicious for Hürthle cell neoplasm; and suspicious for malignancy (SUSP). The rate of malignancy within each category varies with a predicted probability of cancer of 5-15% for AUS/FLUS, 15–30% for FN/SFN, and 60-75% for SUSP. Because of these variable malignancy rates, the management of patients with cytologically indeterminate thyroid nodules can be problematic. The diagnostic difficulty is due to the nonspecific follicular pattern identified by cytologic evaluation that can be found in nodules with benign hyperplastic changes, follicular adenomas, follicular thyroid carcinomas (FTC), and follicular variant of papillary carcinoma (FV-PTC). Other rare lesions, which can also present with follicular-patterned cytology, include medullary thyroid cancer, parathyroid glands, and metastatic malignancies to the thyroid. The histologic malignancies associated with preoperative indeterminate FNA biopsy results are usually conventional papillary thyroid cancer (PTC), but up to 30% are either FV-PTC or FTC. FTC requires capsular and/or vascular invasion which is not readily apparent on cytology analysis. FV-PTC is the second most common variant of PTC. FV-PTC is the most frequent histology associated with false-negative cytology and intraoperative frozen section results. To further complicate interpretation of diagnostic testing, interobserver variability for cancer type is up to 30% even among expert thyroid pathologists. A Hürthle cell neoplasm is the oncocytic variant of follicular-patterned lesions and may correspond to the histology of Hürthle cell adenoma, Hürthle cell carcinoma, or PTC with Hürthle cell/oncocytic features which also all require histology for diagnosis