Clinical pathological characteristics and prognostic analysis of 140 cases of medullary thyroid carcinoma: validation of the international medullary thyroid carcinoma grading system in a chinese cohort.

BACKGROUND: Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor with variable clinical behavior. The International Medullary Thyroid Carcinoma Grading System (IMTCGS) was developed to refine prognostic stratification, but its validation in Chinese populations remains limited. This study aimed to validate the IMTCGS and evaluate the prognostic significance of Ki-67, preoperative calcitonin levels, and molecular alterations in a Chinese MTC cohort. METHODS: We conducted a retrospective analysis of 140 MTC patients who underwent initial surgery at a single center between May 2017 and June 2025. Tumors were graded using the IMTCGS criteria. Associations among clinicopathological variables, Ki-67 index, preoperative calcitonin levels, molecular characteristics (assessed by next-generation sequencing), and progression-free survival (PFS) were analyzed using Kaplan-Meier analysis, Cox proportional hazards models, and receiver operating characteristic (ROC) curves. RESULTS: High-grade MTC (47.9%) and Ki-67 index ≥ 5% (46.4%) were significantly associated with larger tumor size, higher T/N stage, greater lymph node metastasis burden, and vascular invasion (all p < 0.05). Preoperative calcitonin levels showed strong correlations with both tumor diameter (ρ = 0.623, p < 0.001) and lymph node metastasis count (ρ = 0.530, p < 0.001). RET mutations were predominant (89.5%), with exon 16 being the most frequently involved. High-grade disease, Ki-67 ≥ 5%, tumor diameter ≥ 2 cm, ≥ 5 metastatic lymph nodes, and male sex were all associated with significantly shorter PFS (all p < 0.05). Among all predictors, lymph node metastasis count showed the highest discriminatory accuracy for PFS (AUC = 0.793). CONCLUSIONS: The IMTCGS appears to effectively stratify tumor aggressiveness in Chinese MTC patients, with Ki-67 emerging as a critical component of risk assessment. Preoperative calcitonin level serves as a robust quantitative indicator of tumor burden, while the predominance of RET mutations reinforces their central pathogenic role. These findings support the clinical utility of integrating histological grading, proliferative markers, and biomarker profiling to enhance risk stratification and guide personalized management in MTC.