BackgroundThe first and most important step in characterizing familial nonmedullary thyroid carcinoma (NMTC) is to distinguish the true familial patients, which is the prerequisite for all accurate analyses. This study aimed to investigate whether patients from families with ≥3 first-degree relatives affected with NMTC have different characteristics than patients from families with only two affected members, and to compare these patients with those with sporadic disease.

Methods:We analyzed the clinicopathological features and prognosis of 209 familial and 1120 sporadic cases of NMTC. Familial patients were further divided into two subgroups: families with two affected members and families with ≥3 affected members.

Results:The familial group had a significantly higher risk of bilateral growth, multifocality, extrathyroidal extension, and lateral lymph node metastasis than the sporadic group (P < 0.05). These main features were also different between the group with ≥3 affected members and the sporadic group. The only difference between the two affected members' group and the sporadic group was incidence of multifocality (P < 0.05). The probability of disease recurrence in patients from families with ≥3 affected members was significantly higher than that in sporadic cases (14.46% vs. 5.27%; P = 0.001), while the probability in patients from families with two affected members was similar to that in sporadic patients (6.35% vs. 5.27%; P = 0.610). The Kaplan-Meier survival analysis showed a statistically significant difference in disease-free survival between the two subgroups (85.54% vs. 93.65%; P = 0.045).

Conclusions:Patients from families with ≥3 members affected by NMTC have more aggressive features and a worse prognosis than those from families with only two affected members. Patients from families with ≥3 affected first-degree relatives may be considered to have true familial NMTC.