Grading medullary thyroid carcinoma on fine-needle aspiration cytology specimens with the International Medullary Thyroid Carcinoma Grading System: A cytologic–histologic correlation

Background

Medullary thyroid carcinoma (MTC) is a rare cancer of parafollicular C-cell origin. The International MTC Grading System (IMTCGS) incorporates mitotic activity, the presence of necrosis, and the Ki67 proliferation rate (PR) to classify MTCs as low or high grade. The ability to predict IMTCGS grade in cytology was assessed.

Methods

MTCs with cytology and subsequent surgical follow-up were reviewed. Cytology slides were reviewed for mitotic figures, apoptoses, and necrosis, and a Ki67 PR was calculated when possible. Findings were correlated with final IMTCGS grade.

Results

Twenty-five MTC fine-needle aspirations (FNAs) were identified, with nine identified as high grade (36%). By using a PR cutoff of 5%, Ki67 on FNA material (Ki67FNA) showed 92% concordance (n = 22 of 24) with surgical Ki67 and a correlation coefficient (R²) of 0.72. Sensitivity and specificity of Ki67FNA for predicting high-grade MTC were 38% and 100%, respectively. Multiple mitotic figures were present in a single slide of 43% (n = 3 of 7) of evaluable high-grade MTCs, whereas only one of 16 low-grade MTCs showed a single mitotic figure. Definitive apoptoses were present in five of seven high-grade MTC FNAs but were absent in 16 low-grade MTCs. The sensitivity and specificity of apoptoses/necrosis on cytology for high-grade MTCs were 71% and 88%, respectively.

Conclusions

Ki67FNA ≥5% shows low sensitivity but high specificity for predicting high-grade MTC. The presence of multiple mitotic figures in a single slide or definitive apoptotic bodies are both highly suggestive of high-grade MTC, and should warrant a close examination for necrosis and a careful Ki67 PR count.