The role of the size in thyroid cancer risk stratification

Federica Vianello,Clara Benna,Francesca Galuppini,Caterina Mian,Loris Bertazza,Sara Watutantrige-Fernando,Jacopo Manso,Simona Censi,Gianmaria Pennelli,Susi Barollo,Sofia Carducci,Maurizio Iacobone,Yi Hang Zhu,Nora Albiger

doi:10.1038/s41598-021-86611-6

Abstract

Only a minority of cases of differentiated thyroid carcinoma (DTC) have a poor clinical outcome. Clinical outcomes and molecular aspects were assessed in: 144 DTC ≤ 40 mm without distant metastases (group 1); 50 DTC > 40 mm without distant metastases (group 2); and 46 DTC with distant metastases (group 3). Group 3 had a worse outcome than the other two groups: during the follow-up, patients more frequently had persistent disease, died, or underwent further treatment. The outcomes did not differ between groups 1 and 2. Group 3 had a higher prevalence of TERT promoter mutations than group 2 (32.6% vs 14%). Group 1 had a higher frequency of BRAF mutations than groups 2 or 3 (61.1% vs 16.0% and 26.1%, respectively), while RAS mutations were more common in group 2 than in groups 1 and 3 (16.0% vs 2.1% and 6.5%, respectively). Groups 1 and 2 shared the same outcome, but were genetically distinct. Only lymph node involvement, distant metastases, older age and (among the molecular markers) TERT promoter mutations were independent predictors of a worse outcome. Metastatic DTC had the worst outcome, while the outcome was identical for large and small non-metastatic DTC, although they showed different molecular patterns. TERT promoter mutations emerged as an independent factor pointing to a poor prognosis.

Highlights

A minority of cases of differentiated thyroid carcinoma (DTC) have a poor clinical outcome
A great body of evidence has demonstrated that telomerase reverse transcriptase (TERT) promoter mutations in DTC are associated with a higher stage at diagnosis, and with distant metastases[13,14,15]
Group 3 included a higher proportion of cases of widely invasive FTC (WI-FTC), with 72.7% in group 3 and 37.5% in group 2

Summary

Introduction

A minority of cases of differentiated thyroid carcinoma (DTC) have a poor clinical outcome. The most important clinical and pathological features conferring a more aggressive phenotype are: age at diagnosis; primary tumor size; soft tissue invasion; and distant metastases (found in about 2–5% of cases)[3,4,5] These variables, and other risk factors are weighted differently in the numerous staging systems available (such as the European Organization for Research and Treatment of Cancer [EORTC]; the Age, Grade, Extent, Size [AGES]; the Age, Metastases, Extent, Sex [AMES]; the Metastases, Age, Completeness of resection, Invasion, Size [MACIS] criteria; the Memorial Sloan Kettering Cancer Center [MSKCC] or the National Thyroid Cancer Treatment Cooperative Study [NTCTCS] systems), depending on the prognostic importance attributed to them, but none of these approaches have proved clearly superior. TERT promoter mutations are an independent factor for predicting patient m ortality[16] and disease-free survival (DFS)[13,15,17]

Methods

Results

Conclusion