Bethesda category III thyroid nodules more often malignant than previously estimated

In thyroid nodules classified as Bethesda category III, the risk of malignancy is higher than originally estimated, with an approximate incidence of 26.6% to 37.8%, according to recent findings.

The study researchers found that the prevalence of malignancy after an initial Bethesda category III diagnosis is similar to the rate after successive Bethesda III diagnoses, suggesting that repeat fine-needle aspiration (FNA) may have questionable value in clinical decision-making for these nodules.

In the study, researchers evaluated the records of 541 patients at Memorial Sloan-Kettering Cancer Center (MSKCC) whose thyroid nodules were classified as Bethesda category III using the Bethesda system for reporting thyroid cytopathology. These nodules, also known as “atypia of unknown significance/follicular lesion of unknown significance” (AUS/FLUS), have previously been estimated to have a malignancy rate of 5% to 15%.

All patients were seen at MSKCC between 2008 and 2011, underwent FNA and had accessible thyroid ultrasound records. The researchers evaluated these clinical and radiologic variables in terms of their predictiveness of triage to surgery. Among the characteristics analyzed were patient age, sex, size of lesion, hypoechogenicity, hypervascularity and calcifications. Associations were also analyzed between AUS/FLUS nodules and surgical pathology diagnoses. Patients with two successive AUS/FLUS diagnoses were advised to undergo surgery for diagnostic and therapeutic reasons.                                          

Of patients whose initial FNA findings were classified as AUS/FLUS, 64.7% underwent immediate surgery, 17.7% underwent repeat FNA and 17.6% were monitored. Of those who underwent repeat FNA, the cytology findings were inconclusive in 5.2%, benign in 42.7%, AUS/FLUS in 38.5%, suspicious for follicular neoplasm in 5.2%, suspicious for malignancy in 4.2% and malignant in 4.2%.

Among the patients who underwent surgical resection of two consecutively diagnosed AUS/FLUS nodules, 26.3% of the nodules were malignant.

Among AUS/FLUS nodules, whether addressed through surgery, FNA or observation, surgical pathology confirmed malignancy in 26.6% (95% CI, 22.4-31.3). Among AUS/FLUS nodules triaged to surgery, the rate of malignancy was 37.8% (95% CI, 33.1-42.8). The researchers found incidental cancers in 22.3% of patients. Variables revealed through univariate logistic regression analysis to be linked to triage to surgery were younger patient age (P<.0001), increasing nodule size (P<.0001) and nodule hypervascularity (P=.032).

“These data imply that Bethesda category III nodules in some practice settings may have a higher risk of malignancy than traditionally believed, and that guidelines recommending repeat FNA or observation merit reconsideration,” the researchers wrote.

Disclosure: The researchers report no relevant financial disclosures.