Association Between Allele Frequency and Aggressive Behavior in Papillary Thyroid Microcarcinoma.

: Papillary thyroid microcarcinoma (MPTC), a subset of papillary thyroid carcinoma (PTC), is increasingly detected with advanced imaging. While most MPTCs are indolent, some exhibit aggressive behavior, complicating clinical management. The mutation, common in PTC, is linked to aggressive features, and its allele frequency (AF) may serve as a biomarker for tumor aggressiveness. This study explored the association between AF and aggressive histopathological features in MPTC. : Data from 1 January 2016 to 23 December 2023 were retrieved from two McGill University teaching hospitals. Inclusion criteria comprised patients aged ≥ 18 years with thyroid nodules ≤ 1 cm, documented mutation and AF results, and available surgical pathology reports. Tumor aggressiveness was defined as the presence of lymph node metastasis, aggressive histological subtype (tall cell, hobnail, columnar, solid/trabecular or diffuse sclerosing), extra thyroidal extension, or extensive lymphovascular extension. Associations were explored using -tests. : Among 1564 records, 34 met the inclusion criteria and were included in analyses. The mean AF was significantly higher in aggressive tumors (23.58) compared to non-aggressive tumors (13.73) (95% CI: -18.53 to -1.16, = 0.03). Although not statistically significant, trends were observed for higher AF in tumors with lymph node metastasis (mean AF: 25.4) compared to those without (mean AF: 16.67, = 0.08). No significant difference was noted in AF by histological subtype (mean AF for aggressive: 19.57; non-aggressive: 19.15, = 0.94). : Elevated AF is associated with aggressive behavior in MPTC, highlighting its potential as a biomarker to inform treatment strategies. Larger studies are warranted to validate these findings and enhance clinical management of MPTC patients.