Follicular Lesion of Undetermined Significance in Thyroid FNA--How Is It Used? Implications of the Proposed Thyroid Fine-Needle Aspiration Category of "Follicular Lesion of Undetermined Significance":

Background: Fine-needle aspiration (FNA) is the current standard for triaging patients with thyroid nodules into operative and nonoperative therapy. In 2007, the National Cancer Institute (NCI) held a Thyroid FNA State of the Science Conference, where a 6-tiered classification system was proposed to standardize reporting of thyroid FNA results. One category, designated "follicular lesion of undetermined significance" (FLUS), was proposed to incorporate cases with insufficient benign or atypical material for a definitive diagnosis of "benign" or "follicular neoplasm." This category was stated to have a 5% to 10% risk of malignancy, to represent no more than 7% of all thyroid FNA diagnoses, and be followed by repeat FNA in 3 to 6 months. Precise cytomorphologic criteria for this diagnosis were not defined. Objective: To investigate how frequently the term FLUS is used and to evaluate the histopathologic follow-up, when available. Methods: All thyroid FNAs from 3 institutions over 5 years were reviewed for a previous diagnosis of FLUS or older equivalent diagnostic terms, which included "atypia of undetermined significance," "atypical cells cannot exclude neoplasm," "atypical cells cannot exclude follicular neoplasm," or "follicular proliferation, follicular neoplasm cannot be excluded." The frequency of use for the term FLUS or its equivalents was calculated, and correlating surgical pathology reports were obtained when available. Results: Of 6872 thyroid FNAs, 664 cases (12%) were diagnosed as FLUS or its equivalent. The percentage of cases diagnosed as FLUS varied by pathologist, ranging from 2.5% to 28.6%. Correlating surgical pathology reports were available for 127 cases (19%), of which 36 cases (28%) demonstrated malignancy. The overall rate of malignancy for FLUS cases was 5% (assuming appropriate clinical follow-up and repeat FNA). The malignant histopathologic diagnoses included 8 papillary carcinomas, 17 follicular variant of papillary carcinomas, 7 follicular carcinomas, and 1 lymphoma. Of all papillary carcinomas, 12 (48%) were incidental findings, unrelated to the index nodule. Conclusions: The diagnostic category of FLUS for thyroid FNA substantially varies among pathologists, and more rigorously defined morphologic criteria are needed. Currently, it appears to be used more often than the NCI's recommendations. The risk of malignancy in this study is in concordance with the stated frequency of malignancy at 5% to 10%, which suggests that the follow-up recommendation for re-aspiration of these nodules is appropriate. Reviewer's Comments: Similar to how the category of "atypical cells of undetermined significance" in cervical cytology has undergone significant changes over the last 10 years, it is likely that the category of FLUS in thyroid FNA will undergo similar revisions. As with any change in practice, adequate education of surgeons and endocrinologists regarding the predicted risk and appropriate follow-up of patients with a diagnosis of FLUS is important for patient care. (Reviewer-Deborah J. Chute, MD).