Clinical characteristics and prognosis of familial non-medullary thyroid carcinoma: a retrospective study of 98 families

The differences in clinicopathological features and prognosis between familial non-medullary thyroid carcinoma (FNMTC) and sporadic non-medullary thyroid carcinoma (SNMTC) remain a subject of debate. This study aims to compare the clinicopathological features and recurrence-free survival (RFS) between FNMTC and SNMTC, with a particular focus on the subgroup differences based on the number of affected relatives. A retrospective analysis was conducted on 672 NMTC patients who underwent thyroidectomy at West China Hospital between 2015 and 2024. The cohort included 224 FNMTC patients (from 98 families) and 448 SNMTC patients. FNMTC patients were further stratified into families with two affected members (FNMTC-2, n = 160) and families with ≥ three affected members (FNMTC-3, n = 64) subgroups. Clinicopathological characteristics and RFS were compared among the groups. Compared to the SNMTC group, the FNMTC group demonstrated a smaller tumor diameter (1.03 ± 0.60 cm vs. 1.15 ± 0.96 cm, p = 0.0255) but higher rates of multifocality (43.75% vs. 34.82%, p = 0.024), bilaterality (32.59% vs. 23.88%, p = 0.0163), and lymph node metastasis (52.68% vs. 44.42%, p = 0.0432). Subgroup analysis revealed that the FNMTC-3 group, compared to SNMTC, was associated with a younger age at diagnosis (43.76 ± 14.53 vs. 47.01 ± 11.28 years, p = 0.039), a smaller tumor diameter (0.89 ± 0.46 cm vs. 1.15 ± 0.96 cm, p = 0.0343), and increased rates of multifocality (50.00% vs. 34.82%, p = 0.0185), bilaterality (37.50% vs. 23.88%, p = 0.0195), lymph node metastasis (57.81% vs. 44.42%, p = 0.0444), and thyroid follicular nodular disease (57.81% vs. 44.20%, p = 0.0409). Furthermore, the FNMTC-3 group had a significantly smaller tumor diameter than the FNMTC-2 group (0.89 ± 0.46 cm vs. 1.08 ± 0.64 cm, p = 0.0343). However, no statistically significant differences in RFS were observed among the SNMTC and FNMTC groups during follow-up. FNMTC-3 exhibits more aggressive clinicopathological features than SNMTC, including earlier onset, higher multifocality, bilaterality, and metastatic potential. These findings support that the number of affected family members is a significant indicator of tumor aggressiveness in FNMTC. Although no difference in RFS was observed, the distinct pathological profile of FNMTC-3 warrants more vigilant surveillance.