DICER1 Mutations in Thyroid Cytology Samples: A Multicenter Study

Summary: Introduction: Approximately 1/3 of thyroid cytology specimens fall into a Bethesda indeterminate category where molecular testing plays a key role in guiding clinical management decisions. DICER1 is an uncommon and poorly understood mutation found in thyroid nodule specimens. This study aimed to investigate Bethesda III/IV thyroid nodules with DICER1 gene mutations detected in thyroid cytology samples using ThyroSeq molecular testing, with a focus on exploring the clinical and histopathological outcomes of such nodules. Materials and Methods: In this multicenter retrospective study, between 1/2017-1/2023, patients with Bethesda III/IV thyroid nodules testing positive for DICER1 mutation on ThyroSeq v3 were included. Charts were collated for demographics, clinical presentation, surgery, histopathology, other molecular alterations and clinical outcomes. Data was analyzed using Microsoft excel. Results: 88 patients with somatic DICER1 gene mutation were included, with a mean age of 39.6 years and a female predominance (Table 1). All mutations were in the somatic hotspot region, most commonly at the 5428 site (Table 2). Majority of the excised nodules exhibited benign features (65.9%). Among the 44 patients who underwent surgery, 31% of were diagnosed with malignancy. For patients with malignant histopathology, the mean age was 37 years, females outnumbered males. The most common histopathology diagnoses were encapsulated follicular variant of papillary thyroid carcinoma and follicular carcinoma. DICER1 mutations were found to be associated with other mutations in 11 cases (Table 3). Conclusions: In conclusion, the mean age at malignant diagnoses was lower compared to that of the general population with DICER1 mutation (Table 1). The most common histopathology architecture noted in this group was follicular patterned lesions, in both benign and malignant thyroid nodules harboring DICER1 mutations. This study displays one of the largest datasets of DICER1 mutations in adult thyroid specimens, demonstrating that DICER1 mutations confer an increased risk of malignancy, necessitating close follow-up.