Role of frozen section in the surgical management of indeterminate thyroid nodules

Indeterminate thyroid nodules (ITNs) correspond to the categories III (atypia of undetermined significance or follicular lesion of undetermined significance) and IV (follicular neoplasm or suspicious for a follicular neoplasm) of the Bethesda system for reporting thyroid cytopathology. Their malignancy risk is 5-15% and 15-30% respectively, imposing surgical treatment for definitive diagnosis. Thus, they represent a diagnostic and therapeutic challenge given the risk of over or under treatment. Several teams continue to perform systematic intraoperative frozen sections (FS) in order to guide the initial extent of surgery and to avoid a two-stage thyroidectomy. FS have a very high specificity and positive predictive value for the diagnosis of malignancy allowing a one-stage total thyroidectomy if the result is positive. However, this attitude is highly controversial; and this review of the literature demonstrates that FS is of little contribution in this setting, due to low sensitivity and high false-negative rates. In fact, for these lesions, a careful and comprehensive evaluation of the tumor capsule is mandatory in order to visualize a capsular or a vascular invasion permitting to make the diagnosis of malignancy. However, this assessment is only possible on permanent section. Moreover, FS can jeopardize the detection of signs of capsular invasion on final pathologic examination. The recent development of molecular testing results in a better preoperative diagnosis, thus reducing even more the need for intraoperative FS. Contrasting with their limited role in Bethesda III and IV categories, FS are useful in guiding the preoperative management of Bethesda V category nodules, given their high negative and positive predictive values. Intraoperative FS of ITNs are of little use and are not recommended systematically. Their use should be restricted to elderly, high anesthetic risk, or poorly compliant patients for whom an eventual subsequent complementary surgery may be problematic.