External Validation of Three Available Grading Systems for Medullary Thyroid Carcinoma in a Single Institution Cohort

Medullary thyroid carcinoma (MTC) is a rare thyroid carcinoma with a variable clinical behavior. Potential clinical and pathological prognostic markers have been investigated, but studies are limited and controversial. In neuroendocrine neoplasms of various other sites, necrosis and proliferation (mitotic activity and/or Ki67 index) are integrated to provide a histological grade. Recently, an International Medullary Thyroid Carcinoma Grading System (IMTCGS) has been designed to define high- or low-grade MTC by combining proliferative activity and necrosis. This proposal integrates two previously published grading schemes by American (2-tiered grading, low- and high-grade MTC) and Australian authors (3-tiered grading, low-, intermediate-, and high-grade MTC). To validate the clinical role of these systems, their prognostic impact was evaluated in an independent cohort of 111 MTCs. Necrosis, which was the only parameter integrated into the 3 grading systems, proved to be individually correlate with tumor relapse, while no association was found with the proliferation (mitotic count and Ki67 index); however, by combining the different parameters according to all three grading systems, “high-grade” MTCs turned out to be significantly associated with the disease recurrence ( p