Diagnostic Utility of Ki‐67 Index on Cell Block Material for Grading Medullary Thyroid Carcinoma

ABSTRACT Introduction An international grading system for medullary thyroid carcinoma (IMTCGS) was established in 2022. High‐grade MTC is defined by the presence of one or more of the following features: mitotic index ≥ 5 per 2 mm 2 , Ki‐67 proliferative index ≥ 5%, or tumor necrosis. Fine‐needle aspiration (FNA) is the primary diagnostic tool for MTC; however, tumor grading in cell blocks remains underexplored. Materials and Methods A total of 60 FNA cases diagnosed as MTC or metastatic MTC between 2000 and 2025 were identified. Of these, 15 met the inclusion criteria: cell blocks with > 500 tumor cells and corresponding surgical specimens available. The Ki‐67 proliferation index was assessed in hotspot regions using an online platform. Results The study included 11 adults and 4 pediatric/adolescents with a median age of 50 years (range: 8–76). Based on the IMTCGS grading criteria, six cases were classified as high‐grade and nine as low‐grade. In low‐grade tumors, the Ki‐67 proliferation index on surgical resections ranged from < 1% to 4%, and all corresponding cell blocks showed Ki‐67 rates of ≤ 1%. High‐grade tumors exhibited Ki‐67 indices ranging from 7% to 24%, with mitotic figures ranging from 1 to 14 per 2 mm 2 . Among these, two cell blocks showed Ki‐67 rates of 5%, while the remaining four had rates between < 1% and 2%. Four of six patients with high‐grade MTC developed distant metastases to the liver, lung, or bone, and one died of disease 35 months after diagnosis. None of the low‐grade tumors developed distant metastasis. Conclusions Grading MTC using the Ki‐67 proliferation index on cell blocks is challenging because of low cellularity and intratumoral heterogeneity in Ki‐67 expression. In our study, this approach tended to undergrade high‐grade MTC.