6913 Clinical Prognosis in Patients with Thyroid Nodules Expressing PPAR-Gamma Gene Fusion on Thyroid FNA Cytology
Authors: Hammoudeh Rawan , Morariu Elena , Wald Abigail , Doerfler William R , Linwah Yip , Nikiforova Marina , Nikiforov Yuri E 
Published: October 2024

Disclosure: R. Hammoudeh: None. E. Morariu: None. A. Wald: Other; Self; Technical consultant to Sonic Healthcare USA.. W.R. Doerfler: None. Y. Linwah: None. M. Nikiforova: Owner/Co-Owner; Self; Owner of intellectual property related to ThyroSeq, receive royalties through the University of Pittsburgh; consultants for Sonic Healthcare USA. Y.E. Nikiforov: Owner/Co-Owner; Self; Owner of intellectual property related to ThyroSeq, receive royalties through the University of Pittsburgh; consultants for Sonic Healthcare USA.

Background: PPARG rearrangements, typically PAX8-PPARG, are common genetic alterations in follicular thyroid carcinoma and follicular variant of papillary thyroid carcinoma (FVPTC). Most tumors appear to be indolent, however distant metastasis has been reported. The aim of this study was to determine the prevalence and type of malignancy in a series of thyroid nodules positive for PAX8 rearrangement in thyroid fine-needle aspiration (FNA) samples. We also aimed to evaluate the impact on patient management, prognosis and outcomes. Methods: Thyroid nodules positive for PAX8 fusion on ThyroSeq v2 and v3 genomic classifier testing of FNA samples from May 2008 to February 2022 were identified. Clinical data was obtained by retrospective chart review. Results: Overall, 44 nodules positive for PAX8/PPARG fusion were identified. None of these nodules expressed additional genetic mutations on molecular testing. Surgical pathology was available for 40 patients, which identified 35 (87.5%) malignant, 3 NIFTP (7.5%), and 2 benign (5%) lesions. In the malignant group, FNA cytology revealed 1 (2.8%) benign, 13 (37.1%) AUS/FLUS, 12 (34.2%) suspicious for SFN/FN, 5 (14.3%) suspicious for PTC and 4 were not classified. In the non-malignant group, FNA cytology revealed 2 (40%) benign, 2 (40%) AUS/FLUS, 1 (20%) SFN/FN. With regards to surgical intervention, 30 (75%) patients had total thyroidectomy and 10 (25%) underwent lobectomy, of which 8 were followed by completion thyroidectomy. Among the malignant and non-malignant groups, there was no difference in sex (82.8% vs 100% female, p=1), age (43.6 vs 50.2 years, p=0.2), or tumor size on surgical pathology (3.26 vs 4 cm, p=0.23). In the malignant group, histology showed 30 (85.7%) FVPTC, 2 (5.7%) conventional PTC, 2 (5.7%) follicular carcinoma and 1 (2.9%) solid variant PTC. Of the FVPTC group, 9 had oncocytic cell features, 3 focal solid patterns, and 1 showed focal solid growth and progression to poorly differentiated thyroid carcinoma. Only 1 showed lymphatic invasion, 10 showed angioinvasion. Following the ATA thyroid cancer risk stratification, 23 (65.7%%) had low risk, 9 (25.7%) intermediate risk and 3 (8.6%) high risk. 18 patients in the malignant group underwent RAI ablation. Average follow up for the malignant nodules was 49.7 months (0-170). 1 had suspected recurrence on thyroid ultrasound after a year. No evidence of distant metastasis was documented. Conclusions: The majority of thyroid nodules with PAX8/PPARG rearrangement found on FNA were cancers, predominantly follicular variant PTC, and some were benign or NIFTP. The majority were low risk, but intermediate and high-risk cancers with more aggressive histology, angioinvasion, and poorly differentiated cancer were also identified. While only one recurrence was identified on short follow-up, longer follow-up duration is required for better understanding the behavior of these tumors.

Presentation: 6/3/2024