Simultaneous occurrence of PAX8-PPARg and RET-PTC3 rearrangements in a follicular variant of papillary thyroid carcinoma

• Published in: The American journal of surgical pathology Vol. 36; no. 9; p. 1415
• Main Authors: Caria, Paola, Dettori, Tinuccia, Frau, Daniela Virginia, Di Oto, Enrico, Morandi, Luca, Parmeggiani, Alfredo, Tallini, Giovanni, Vanni, Roberta
• Format: Journal Article
• Language: English
• Published: United States 01.09.2012
• Subjects: Carcinoma, Papillary, Follicular - genetics; Carcinoma, Papillary, Follicular - pathology; Cells, Cultured; DNA, Neoplasm - analysis; Female; Gene Rearrangement; Humans; In Situ Hybridization, Fluorescence; Middle Aged; Nuclear Receptor Coactivators - genetics; Oncogene Proteins, Fusion - genetics; Thyroid Neoplasms - genetics; Thyroid Neoplasms - pathology; Thyroidectomy
• ISSN: 1532-0979
• DOI: 10.1097/PAS.0b013e318264bdd6

Specific genotype-phenotype correlations have been identified in conventional-type papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC). In contrast, the genetic alterations underlying the pathogenesis of the follicular variant of PTC (FV-PTC), which shares some clinicopathologic and molecular features with both PTC and FTC, remain to be clarified. This entity shows a PAX8-PPARg fusion gene (associated with FTC), more frequently than BRAF or RET-PTC alterations (associated with PTC). Herein, we report, for the first time, an FV-PTC with the simultaneous occurrence of both RET-PTC and PAX8-PPARg alterations. Neoplastic cells were of the wild type for BRAF and H,K,N-RAS, had an apparently normal karyotype by conventional cytogenetics, and had a balanced genome by array comparative genomic hybridization analysis. In fact, submicroscopic chromosome rearrangements producing RET-PTC3 and PAX8-PPARg chimeric genes were found by interphase fluorescence in situ hybridization. We demonstrated that these 2 genetic alterations coexisted in the same tumor and were confined to 2 different clones. Our findings indicate that molecular heterogeneity, although an uncommon phenomenon, may occur in thyroid carcinoma and demonstrate the coexistence in a case of FV-PTC not only of the histologic but also of the molecular features of both PTC (RET-PTC) and FTC (PAX8-PPARg).