Molecular Detection of PPARγ Rearrangements and Thyroid Carcinoma in Preoperative Fine-Needle Aspiration Biopsies

The pathologic diagnosis of thyroid follicular tumors is difficult, particularly in preoperative fine-needle aspiration biopsies. To investigate whether the molecular diagnosis of PPARγ rearrangements can detect thyroid carcinomas in fine-needle aspiration biopsies, we performed interphase fluorescence in situ hybridization on 24 thyroid fine-needle aspiration and 17 follow-up thyroidectomy specimens. Two of the 24 fine-needle aspiration biopsies contained PPARγ rearrangements, and both were diagnosed suggestive of a thyroid follicular neoplasm by cytology. The two corresponding thyroidectomies each contained PPARγ rearrangements in all tumor cells and, both were diagnosed follicular-patterned thyroid carcinomas—one a follicular carcinoma and the other a follicular variant of papillary carcinoma, the latter by majority of expert endocrine pathologists. Our experiments demonstrate that PPARγ rearrangements can detect a subset of follicular-patterned thyroid carcinomas in preoperative thyroid fine-needle aspiration biopsies. The ultimate utility of mutations such as PPARγ rearrangements in diagnosis of thyroid carcinoma must be proven by direct correlation of mutation status with thyroid tumor biology and not just with thyroid tumor morphology, a subjective and imprecise marker of clinical behavior. The application of specific mutations to preoperative diagnosis of thyroid carcinoma is predicted to improve the accuracy and reduce the costs of treating patients with thyroid tumors.