Randomized Prospective Evaluation of Frozen-Section Analysis for Follicular Neoplasms of the Thyroid

The term “follicular neoplasm” is broadly applied to a heterogeneous group of thyroid tumors characterized by a proliferation of thyroid epithelial cells growing in a follicular pattern. Because this group encompasses both benign and malignant tumors, treatment decisions and prognosis ultimately rely on more specific classification. Regrettably, further classification is often not possible by fine-needle aspiration (FNA). In the case of follicular and Hurthle cell carcinomas, FNA is ineffectual in recognizing tumor invasion, an obligatory diagnostic feature. 1,2 In the case of the follicular variant of papillary carcinoma, FNA tends to underappreciate specific nuclear alterations because of their focal and random distribution. 3,4 The probability of malignancy in a thyroid lesion demonstrated by FNA to be a follicular neoplasm is approximately 20%. 2,5 Accordingly, excision is recommended for patients harboring this heterogeneous group of nodules. Confusion surrounding optimal patient management is compounded in the operating room. Many surgeons perform an ipsilateral thyroid lobectomy and isthmusectomy and then rely on intraoperative frozen-section analysis to establish a more precise diagnosis. If the lesion is found to be malignant, a one-stage total thyroidectomy is advocated. If the lesion is benign, most surgeons and endocrinologists believe that an ipsilateral thyroid lobectomy is adequate treatment. 6,7 Unfortunately, intraoperative frozen-section evaluation can rarely distinguish benign from malignant neoplasms. 1,2,5,8–11 The focal nature of tumor invasion may elude detection because of the limited sampling inherent to frozen-section evaluation. Moreover, the artifact and cellular distortion induced by tissue freezing may mask the subtle morphologic atypia that characterizes the follicular variant of papillary carcinoma. As a result, some have called into question the standard practice of frozen-section evaluation as a reliable means to guide the surgical management of thyroid nodules. 1,2,8,11,12 In a large retrospective study, we previously showed that intraoperative frozen section failed to render useful information in 87% of patients with follicular neoplasms of the thyroid. 2 Further, frozen section appropriately modified the surgical procedure in only 4 of 120 (3.3%) patients. Likewise, Hamburger and Hamburger 11 showed that only 3 of 359 (0.8%) frozen-section analyses contributed decisively to surgical treatment; Shaha et al 13 reported similar limitations of frozen-section analysis for follicular neoplasms. Based on these results, we questioned the routine use of intraoperative frozen section as a useful and cost-effective diagnostic tool for classifying follicular neoplasms of the thyroid. 2 Although most investigators agree with this recommendation, some believe that this technique is a useful routine intraoperative diagnostic adjunct. 9,14 In addition, clinical factors such as age, sex, and tumor size may not be helpful in differentiating benign from malignant follicular neoplasms. 10 Despite growing concern regarding its efficacy, frozen-section analysis remains entrenched as a standard practice in the surgical management of thyroid nodules. Many surgeons are reluctant to abandon this ritualistic, albeit dubious, exercise in the absence of randomized prospective studies that either confirm or contest retrospective observations. With this in mind, we designed a randomized prospective trial evaluating the clinical utility of intraoperative frozen-section analyses for follicular neoplasms of the thyroid.