Clinical and Histopathological Risk Factors for Radioactive Iodine Refractory Follicular and Oncocytic Thyroid Carcinoma

Merel T Stegenga; Evert F S van Velsen; Lindsey Oudijk; Frederik A Verburg; Tessa M van Ginhoven; Robin P Peeters; Marco Medici; W Edward Visser; Folkert J van Kemenade

doi:10.1210/clinem/dgae084

Clinical and Histopathological Risk Factors for Radioactive Iodine Refractory Follicular and Oncocytic Thyroid Carcinoma

J Clin Endocrinol Metab. 2024 Feb 13:dgae084. doi: 10.1210/clinem/dgae084. Online ahead of print.

Authors

Merel T Stegenga¹, Evert F S van Velsen^{1

2}, Lindsey Oudijk³, Frederik A Verburg⁴, Tessa M van Ginhoven⁵, Robin P Peeters¹, Marco Medici¹, W Edward Visser¹, Folkert J van Kemenade³

Affiliations

¹ Erasmus MC Academic Center for Thyroid Diseases, Department of Internal Medicine, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands.
² Erasmus MC Bone Center, Department of Internal Medicine, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands.
³ Erasmus MC Academic Center for Thyroid Diseases, Department of Pathology, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands.
⁴ Erasmus MC Academic Center for Thyroid Diseases, Department of Radiology and Nuclear Medicine, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands.
⁵ Erasmus MC Academic Center for Thyroid Disease, Department of Surgery, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands.

PMID: 38349206
DOI: 10.1210/clinem/dgae084

Abstract

Introduction: Risk factors for radioactive iodine (RAI)-refractory disease in follicular (FTC) and oncocytic thyroid carcinoma (OTC) are unknown. Therefore, the aim of this study is to identify clinical and histopathological risk factors for RAI-refractory disease in FTC and OTC patients, facilitated by an extensive histopathological revision.

Methods: All adult FTC and OTC patients treated at Erasmus MC (the Netherlands) between 2000 and 2016 were retrospectively included. 2015 ATA Guidelines were used to define RAI-refractory disease. An extensive histopathological revision was performed applying the 2022 WHO Classification using Palga: Dutch Pathology Databank. Logistic regression was used to identify risk factors for RAI-refractory disease, stratified for histological subtype.

Results: Ninety FTC and 52 OTC patients were included, of which 14 FTC (15.6%) and 22 OTC (42.3%) developed RAI-refractory disease over a follow-up time of 8.5 years. RAI-refractory disease occurred in OTC after fewer cycles than in FTC (2.0 [IQR: 1.0-2.0] vs 2.5 [IQR: 2.0-3.75]), and it substantially decreased the 10-year disease specific survival, especially in OTC (46.4%; FTC 85.7%). In FTC, risk factors were higher age at diagnosis, pT3/pT4-stage, N1-stage, widely invasive tumors and extra-thyroidal extension. N1-stage and M1-stage were the strongest risk factors in OTC, rather than histopathological characteristics of the primary tumor.

Conclusion: To our knowledge, this is the first study that correlates clinical and histopathological risk factors with RAI-refractory disease in FTC and OTC, facilitated by a histopathological revision. In FTC, risk factors for RAI-refractory disease were foremost histopathological characteristics of the primary tumor, whereas in OTC presentation with lymph node and distant metastasis was associated with RAI-refractory disease. Our data can help clinical decision making, particularly in patients at risk for RAI-refractory disease.

Keywords: Thyroid neoplasms; follicular thyroid cancer; oncocytic thyroid carcinoma; radioactive iodine refractory disease.