The International Medullary Thyroid Carcinoma Grading System (IMTCGS) appears to be superior to other grading systems for predicting disease-free survival (DFS) and overall risk stratification in patients with medullary thyroid carcinoma (MTC), according to a study recently published in Endocrine Pathology.

“We suggest the implementation of the IMTCGS scheme in routine clinical practice: one of the main advantages of this grading scheme is that both mitoses and tumor necrosis are relatively well-defined and objective histologic features, less prone to interobserver variability than other parameters (for example, vascular invasion or cell morphology),” the authors wrote.

The researchers studied 111 individuals with MTC from 2 different hospitals in Italy, grading each tumor with the IMTCGS and the Memorial Sloan Kettering Cancer Center and Royal North Shore Hospital (referred to as “Sydney”) grading systems. There were 32, 26, and 18 patients classified as high grades, and 69, 85, and 49 patients classified as low grades by each system, respectively. The Sydney grading system also distinguishes an intermediate grade, which included 34 cases in this cohort. 

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All 3 systems could accurately predict disease recurrence; nonetheless, only the tumors considered high grade by the IMTCGS showed a statistical association with shorter DFS. However, none of them could predict overall survival, the authors said. Moreover, a 2-tiered scale appeared to be superior to a 3-tiered scale since high-grade tumors of the Sydney grading system only exhibited statistical differences when compared to the low-grade tumors. 

When analyzing the individual variants assessed in each system, the investigators pinpointed tumor necrosis as a predictor for recurrence, while Ki67, a mitotic activity or proliferation index, correlated with DFS. Male sex, lymph node invasion, and stage 4 tumors, according to the American Joint Committee on Cancer/Union for International Cancer Control, also had a higher association with disease recurrence. Interestingly, multiple tumor foci had a similar relationship only with sporadic MTC as opposed to familial MTC cases.

“A possible explanation for the different Ki67 significance is that DFS considers the role of time to relapse. In other words, the Ki67 index might predict early relapse, rather than relapse in general,” the authors explained.

Although the inclusion of these grading systems, preferably the IMTCGS, as part of the medical care of MTC cases could represent benefits to the patient by allowing the healthcare team to acknowledge the prognosis of each case and hence make better decisions regarding treatment, follow-up, and counseling, the authors still suggest determining the somatic RET and RAS mutations status as part of the prognosis estimation.


Vissio E, Maletta F, Fissore J, et al. External validation of three available grading systems for medullary thyroid carcinoma in a single institution cohort. Endocr Pathol. Published online May 18, 2022. doi:10.1007/s12022-022-09719-z