Grading Medullary Thyroid Carcinoma by Ki67 Proliferation Index on Cell Block Material

Summary: Introduction: International grading system for medullary thyroid carcinoma (MTCs) has been recently proposed. High grade MTCs are defined as tumors with one of the following features: mitotic index ≥ 5 per 2 mm2, Ki67 proliferative index ≥ 5%, or tumor necrosis. Fine needle aspiration (FNA) is the primary tool for diagnosing MTCs. Grading these tumors on cell blocks (CBs) is not well studied. Materials and Methods: Total 11 FNA cases were retrieved. All specimens have CBs with > 500 cells and surgical resection performed within 6 months of FNA. Ki67 proliferation index was manually counted on hotspots with at least 500 tumor cells included per specimen. Results: The patient population comprised three pediatric/adolescents and eight adults with a mean age of 44 (range: 8 to 76). Eight specimens were primary and three were metastases. Five cases were classified as high grade MTCs based on Ki67 rate on surgical resections. Ki67 index ranged from 8% to 24% and mitotic figures ranged from 3 to 14 per 2 mm2. Ki67 showed heterogenous expression on all surgical resections with high-grade MTCs. For these five cases, only one specimen had Ki67 of 5% on CB. The Ki67 rate was ≤ 2% on remaining CBs. The six cases with low grade MTCs, Ki67 rate ranged from 1% to 4% on surgical resections. All CBs showed ≤ 1% in Ki67 proliferation index. Two of five patients with high grade MTCs had distant metastasis involving liver or lung. During follow up, only one patient with high grade MTC died of the disease at 35 months post-diagnosis. Conclusions: FNA cell block grading of MTCs by Ki67 proliferation index identified only 1 of 5 high-grade MTCs. This discrepancy is probably caused by Ki67 heterogeneity and the inherent sampling error.