"Follicular lesion of undetermined significance/atypia of undetermined significance" is a heterogeneous category of cases that cannot be classified into 1 of the other established categories. The use of ancillary molecular studies has not been widely explored for this diagnosis.
All thyroid cytology cases diagnosed as follicular lesion of undetermined significance/atypia of undetermined significance were retrieved from April 2007 to December 2008. During this time period, samples were collected routinely at the time of aspiration for cytologic and molecular studies. Analysis for BRAF and RAS gene mutations and RET/PTC and PAX8/PPARgamma gene rearrangements were performed and correlated with the cytologic features and surgical pathology outcome.
From a total of 513 follicular lesion of undetermined significance/atypia of undetermined significance cases identified, 455 had adequate molecular results. Of these, 117 cases had cytologic-histologic correlation. In this group, 35 (29.9%) cases had a neoplastic outcome and 20 (17.1%) cases from 19 patients were carcinoma. Positive molecular results were found in 12 cases, all of which were papillary carcinoma. There were no false-positive molecular results. In correlating the molecular results with surgical pathology outcome, we found that the cancer probability for follicular lesion of undetermined significance/atypia of undetermined significance cases with molecular alteration was 100%, while the probability for follicular lesion of undetermined significance/atypia of undetermined significance cases without molecular alteration was 7.6% (P < .001).
By cytomorphology alone, follicular lesion of undetermined significance/atypia of undetermined significance specimens represent cases that are intermediate in risk between the benign and "suspicious for follicular neoplasm" categories. Although not all papillary carcinoma cases are detected by molecular testing, a positive molecular test result is very helpful in refining follicular lesion of undetermined significance/atypia of undetermined significance cases into high-risk and low-risk categories.