MON-556 Sex-Bias in Clinicopathological Presentation of Patients with Differentiated Thyroid Cancer

Background: Sex dimorphism strongly impacts tumor biology with most cancers having a male predominance. Uniquely, thyroid cancer is the only non-reproductive cancer that has a striking female predominance with 3-4 fold higher incidence among females, although males generally have more aggressive disease. Objective: To evaluate the sex-specific differences in clinicopathological characteristics of patients with differentiated thyroid cancer Method: We performed a retrospective study of 140 patients (≥ 18 years) with differentiated thyroid cancer (DTC) who had thyroidectomy at two tertiary care centers between 2010-2018. Females requiring hormone replacement therapy and patients undergoing gender transformation were excluded. Associations between sex and age controlling for race were explored using recursive partitioning, to find optimal thresholds for age at which tumor size is different. Linear regression was used to estimate the effect size difference between older and younger women. Results: Seventy males and 70 age-matched females were included in the study. Overall, average age was 59 years and majority of patients were of white (white 52%, black 24% and other race 29%). There was no association between race and gender. There were no significant differences in frequency of major histological types (follicular vs papillary) of thyroid cancer between male and female patients. Follicular thyroid cancers were diagnosed in 5/70 (7%) female and in 4/70 (6%) male patients. Papillary thyroid cancers (PTC) were found in 61/70 (87%) female and 64/70 (91%) male patients (p=0.623). However, analysis of histopathological subtypes of PTC revealed a sex-related difference. Classical variant of PTC was more frequently diagnosed in males (44/64 or 69%) compared to females (32//61 or 52%). In contrast, follicular variant PTC was more prevalent in females (29/61 or 48%) compared to males (20/64 or 31%). These differences were statistically significant (p=0.04). In addition, analysis of pathological features showed that average tumor size was significantly larger among males compared to females (2.7 vs 1.5 cm, p<0.001). Women age 60 and older tended to have larger tumors in comparison to younger women. Conclusion: Female and male patients with differentiated DTC have different pathological characteristics. Males present more frequently with classical PTC and have larger tumors compared to females. Moreover, an age cut-off of ≥60 years among females divided tumors into different size categories, suggesting a role for sex hormones in tumor development and progression. Potential molecular mechanisms underlying these observations are being explored.