Intratumoral Heterogeneity in Differentiated Thyroid Tumors: An Intriguing Reappraisal in the Era of Personalized Medicine

Antonio Ieni; Roberto Vita; Cristina Pizzimenti; Salvatore Benvenga; Giovanni Tuccari

doi:10.3390/jpm11050333

Intratumoral Heterogeneity in Differentiated Thyroid Tumors: An Intriguing Reappraisal in the Era of Personalized Medicine

J Pers Med. 2021 Apr 23;11(5):333. doi: 10.3390/jpm11050333.

Authors

Antonio Ieni¹, Roberto Vita², Cristina Pizzimenti³, Salvatore Benvenga^{2

4

5}, Giovanni Tuccari¹

Affiliations

¹ Department of Human Pathology in Adult and Developmental Age "Gaetano Barresi", Section of Pathology, University of Messina, 98125 Messina, Italy.
² Department of Clinical and Experimental Medicine, University of Messina, Viale Gazzi, 98125 Messina, Italy.
³ Department of Biomedical, Dental, Morphological and Functional Imaging Sciences, University of Messina, Viale Gazzi, 98125 Messina, Italy.
⁴ Master Program on Childhood, Adolescent and Women's Endocrine Health, University of Messina, Viale Gazzi, 98125 Messina, Italy.
⁵ Interdepartmental Program of Molecular & Clinical Endocrinology and Women's Endocrine Health, University Hospital, A.O.U. Policlinico G. Martino, Viale Gazzi, 98125 Messina, Italy.

Abstract

Differentiated thyroid tumors (DTTs) are characterized by significant molecular variability in both spatial and temporal intra-tumoral heterogeneity (ITH), that could influence the therapeutic management. ITH phenomenon appears to have a relevant role in tumor growth, aggressive behavior and drug resistance. Accordingly, characteristics and consequences of ITH in DTTs should be better analyzed and understood in order to guide clinical practice, improving survival. Consequently, in the present review, we investigated morphological and molecular ITH of DTTs in benign, borderline neoplasms and in malignant entities, summarizing the most significant data. Molecular testing in DTTs documents a high risk for recurrence of cancer associated with BRAF^V600E, RET/PTC 1/3, ALK and NTRK fusions, while the intermediate risk may be related to BRAF^K601E, H/K/N RAS and PAX8/PPARγ. In addition, it may be suggested that tumor genotype is associated with peculiar phenotype.

Keywords: BRAF; RAS mutation; RET/PTC rearrangements; intratumoral heterogeneity; thyroid tumor.

Publication types

Review