Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor that originates from the calcitonin secreting C cells of the thyroid and represents about 1–3 % of thyroid malignancies [1], [2]. Up to a quarter of these tumors are hereditary and associated with activating germline RET (REarranged during Transfection) mutations in MEN2 syndrome [2], [3]. Multiple prognostic factors for MTC's have been investigated and described in the literature [4], [5], [6].

Although the description of MTC was made over 60 years ago by Hazard et al. [7], it is only recently that an attempt to create and validate an international MTC grading scheme has been made, following the paradigm of neuroendocrine tumors in other organs. Grading schemes in other systems have been based on mitotic count, Ki-67 proliferative index, and extent of necrosis present [3]. In 2020 Alzumaili et al. put together a cohort of 144 MTC cases in order to develop a grading scheme based on mitotic count and tumor necrosis [8]. They proposed a two-tiered system in which high-grade tumors had a mitotic index ≥5 per 10 high powered field (HPF) and/or tumor necrosis [8].

In the same year the group Fuchs et al. also proposed a grading system similarly based on proliferative activity and tumor necrosis. Fuchs et al. used a sample of 76 MTC's in order to validate a three-tiered grading system (low-grade, intermediate grade and high grade) based on the mitotic indices, Ki-67 proliferative index and tumor necrosis [9].

More recently in 2021 an international collaboration sought to unify and validate these prior schemes to create an internationally accepted grading system for MTC. After reviewing 327 cases from the United States, Europe, and Australia, Xu et al. developed a two-tiered consensus grading system in which high grade MTC is defined as cases with either a mitotic index ≥5 per 2mm2 or a Ki-67 proliferative index ≥5 % or tumor necrosis [10].

In this study we seek to apply the recently proposed two-tier grading system [8] to our institutional cohort of MTC cases along with the evaluation of other histologic variables. We have evaluated different histologic features in order to compare them among different grades, as well as their association with lymph node metastasis.