A. R. Marcadis1, B. A. Shah2, D. A. Kerr2, O. Picado1, S. Liu1, J. I. Lew1 1University Of Miami,Division Of Endocrine Surgery, DeWitt Daughtry Family Department Of Surgery,Miami, FL, USA 2University Of Miami,Department Of Pathology,Miami, FL, USA
Introduction: Thyroid nodules with Atypia of Undetermined Significance/Follicular Lesion of Undermined Significance (AUS/FLUS, Bethesda III) on fine needle aspiration (FNA) pose a management dilemma for clinicians, and molecular assays have been developed in order to better predict thyroid malignancy or benignity. The Gene Expression Classifier (GEC) is one commonly used molecular test, with suspicious results corresponding to a 40% malignancy risk. Recently, encapsulated, non-invasive follicular variants of papillary thyroid carcinoma were reclassified as benign Non-Invasive Follicular Thyroid neoplasms with Papillary-like nuclear features (NIFTP). With this reclassification, such neoplasms previously considered malignant are now benign, which may alter the positive predictive value (PPV) of suspicious GEC results for malignancy. This study examines the impact of NIFTP reclassification on the PPV of GEC for thyroid malignancy.
Methods: A retrospective, single-institution review of 75 surgical patients with AUS/FLUS thyroid cytology and suspicious GEC was conducted. For all patients, preoperative neck ultrasound and FNA reports were reviewed, and the lobe (right/left/isthmus), location (upper/middle/lower), and size of the suspicious thyroid nodule were correlated with final pathology. All encapsulated, non-invasive follicular variants of papillary carcinoma were re-evaluated by an endocrine pathologist and re-classified as NIFTP when appropriate. The PPV of GEC for malignancy in AUS/FLUS thyroid nodules was calculated both before and after NIFTP reclassification.
Results: Of the 75 patients with AUS/FLUS thyroid nodules and suspicious GEC results, 61 (81%) were female, and 14 (19%) were male. 58 (77%) underwent total thyroidectomy, while 17 (23%) underwent thyroid lobectomy. On final pathology of the GEC suspicious nodule, 7 patients (9.3%) had encapsulated non-invasive follicular variants of papillary thyroid carcinoma which on pathology re-review were classified as NIFTP. The other 68 patients had final pathology which did not change after NIFTP reclassification; 25 of whom (33%) had malignancy (21 papillary thyroid cancer, 3 follicular thyroid cancer, 1 papillary microcarcinoma), and 43 (57%) of whom had benign pathology. Before NIFTP reclassification, the PPV for malignancy in AUS/FLUS nodules with suspicious GEC was 42% (32/75 malignant), whereas after NIFTP reclassification, the PPV was 33% (25/75 malignant). This decrease in PPV for malignancy after NIFTP reclassification was not statistically significant (p >0.05).
Conclusion: NIFTP reclassification as a benign thyroid neoplasm lowers, but does not cause a statistically significant change in the PPV of suspicious GEC results for malignancy in AUS/FLUS thyroid nodules. Surgeons and other clinicians should take this into consideration when evaluating AUS/FLUS thyroid nodules with suspicious GEC results.