MON-562 Retrospective Analysis of Medullary Thyroid Carcinoma: Comparison between Individuals with and without RET Germline Mutation

Abstract

Introduction: Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor accounting for 3-5% of all thyroid cancers. MTC may be sporadic or familial, making RET analysis an indispensable diagnostic tool. This study compares demographic and pathological characteristics of MTC in patients followed at our institution, according to the presence of germline RET mutation. Methods: Data files of 93 patients to whom genetic screening was requested were analysed. Among these, 78 patients were diagnosed with MTC between 1984-2018; 2 were lost for follow-up. Results: Germline mutation in RET gene was reported in 27,63% of patients, while 72,37% presented a sporadic form. Among familial cases, 20 correspond to MEN type 2A and 1 MEN type 2B. In this series, 69.7% of our patients were women and the median age of diagnosis was 49 years old (IQR 33.50-60.00). The median value of preoperative calcitonin (CT) was 1121 ng/mL (IQR 445-4387) and demonstrated correlation with the primary tumor size (r=0.655; p < 0.001). Seventy-five patients were submitted to thyroid surgery, 66,67% at our institution while the remaining were referred to us after surgery. The sensitivity of fine needle aspiration citology was 61,29% with results corresponding to MTC or suspected MTC. Results of preoperative CT revealed a sensitivity of 97,9%. Although not statistically significant, the prevalence in women was higher in sporadic group (72,7%) vs familial (61,9%). Patients with MEN2 were younger than those with sporadic MTC (median 32 vs. 56 years, respectively; p < 0.001). Pre and postoperative CT levels were not statistically different between both groups. Comparing tumors’ histological features, only multifocality and bilaterality had statistically significant differences. Multifocality was more common in the presence of RET mutation (94,4% vs 30.4%; OR=38.857; p<0.001) and these patients also had more chance to have bilateral disease (73,7% vs 5.8%; OR= 45.733; p<0.001). There were no significant differences regarding tumor size, encapsulation, linfovascular, perineural or capsula invasion, extrathyroidal extension or margins invasion among both groups. Using TNM classification system (AJCC 8th ed), 35.9% of patients were in stage 1, 15,6% in 2, 1,6% in 3 and 46,9% in stage 4. There were no statistically differences between familial and sporadic group. Most cases of MEN2 were in stage 1 (40%) and 4 (46,7%), probably due to the presentation form (familiar screening vs. index case). There were no significant differences between groups on the disease progression and current state. Conclusion: In our series, patients with MEN2 were younger and their tumors were more often multifocal and bilateral. However, presence of RET mutation does not influence current disease status, probably due to early detection. This study highlights the importance of genetic screening allowing earlier diagnosis and appropriate treatment.