Thyroid Lesion with a Novel Concurrent ETV6-NTRK3 Translocation and DICER1 Mutation

Abstract Introduction/Objective Understanding of the behavior of thyroid tumors expand as the basis of their classification gradually move from morphologic to molecular/genetic. The use of molecular methods in detecting mutations in fine needle aspiration (FNA) specimens further helped in tailoring patient management. Here, we describe a case of a thyroid lesion which was diagnosed with atypia of undetermined significance (AUS) on FNA and discovered to have an unreported concurrent mutation pattern. Methods/Case Report The patient is a 26 year-old female with long standing history of prominent anterior neck mass. New onset of neck pain prompted sonographic analysis which revealed a 1.1 cm hypoechoic left thyroid nodule with microcalcification. FNA was done, and was signed out as AUS which initiated molecular genetic testing. The lesion was found to have both ETV6/NTRK3 translocation and DICER1 p.P375R mutation. Existing literature on NTRK3 rearrangements in thyroid tumors confer a >95% risk of malignancy. It is commonly associated with BRAF-negative papillary thyroid carcinomas (PTC) with both in BRAF-like behavior in terms of nodal metastases and extrathyroidal extension. On the other hand, there are no existing literature specifying the malignancy risk of the exact DICER1 mutation identified since it has been linked to follicular neoplasms in general. Furthermore, isolated DICER1 mutations in the thyroid showed RAS-like behavior. Subsequent resection of the thyroid revealed that the tumor is morphologically a PTC, with lymphovascular invasion. Results (if a Case Study enter NA) NA Conclusion Molecular testing in thyroid lesions with morphologically indeterminable features on FNA significantly aided in prognostication of patients and prediction of malignancy risk. In this case with a previously unreported combination of mutations, existing literature helped in describing the probable behavior of the patient’s tumor. Thus, the researchers emphasize the importance of databases of identified mutations in tumors and their associated characteristics such as The Cancer Genomic Atlas (TCGA) and The Catalogue of Somatic Mutations in Cancer (COSMIC).