Role of Age at Diagnosis in Defining Potential Familial Nonmedullary Thyroid Cancer in Kindreds With Two Affected Members

Context The definition of familial nonmedullary thyroid cancer (FNMTC) in 2 or more first-degree relatives is controversial due to the high probability of observing a sporadic association when only 2 members of first-degree relatives are affected. Objective To evaluate the role of age at diagnosis in differentiating the true cases of FNMTC. Design, Setting, Participants, and Main Outcome From a group of 721 papillary thyroid cancer (PTC) patients, 95 familial PTC (FPTC) patients with 2 first-degree relatives have been identified. They were split in 2 groups: Group 1 consisted of both the proband and the affected relative, with age at diagnosis <= 45 years; Group 2 consisted of proband and/or the affected family member, with age at diagnosis > 45 years. The clinical-pathological features and outcome of both FPTC groups were compared with 626 sporadic PTC patients (SPTC). Results Familial PTC patients with age at diagnosis <= 45 years, compared with the matched group of sporadic PTCs, had a more frequent multifocal, bilateral, and extrathyroidal extension of tumor and showed worse outcome. No differences were found between FPTC and SPTC patients with age > 45 years. At multivariate analysis, distant metastases, American Thyroid Association (ATA) risk, and FPTC <= 45 years were independent predictors of outcome. Conclusions Based on the observation that PTC is more aggressive when the diagnosis is made in 2 family members, both with age < 45years, we suggest that the definition of FPTC in kindreds with 2 affected members should also take into account the age at diagnosis as a key element of familial cancer.

Automated summary

Based on the study findings, age at diagnosis plays a significant role in determining the aggressiveness and prognosis of familial thyroid cancer when two family members are affected. Therefore, when defining familial cancer, the age at diagnosis of family members should be taken into consideration.