RET/PTC rearrangement is prevalent in follicular Hurthle cell carcinomas

Aims: The molecular alterations underlying follicular Hurthle cell carcinomas (FHCCs) are largely unknown. In an attempt to clarify this issue, we analysed a series of Hurthle cell tumours for the presence of RET/PTC and PAX8/PPARG rearrangements and BRAF, HRAS and NRAS mutations. Methods and results: We investigated a series of 20 follicular Hurthle cell tumours [17 FHCCs and three follicular Hurthle cell adenomas (FHCAs)]. RET/PTC rearrangements were found in 33% of FHCAs and in 38% of FHCCs. All RET/PTC-positive FHCCs had a solid pattern of growth. PAX8/PPARG rearrangement was present in 27% of the FHCCs which displayed, in most cases, a follicular architecture. NRAS mutation was detected in one FHCC. An FHCC with a solid/microfollicular growth pattern scored positive for both RET/PTC and PAX8/PPARG rearrangement. Conclusions: Our study has shown a significant association between RET/PTC rearrangements and FHCCs with a solid growth pattern, thus raising the possibility of using tyrosine kinase inhibitors for the treatment of patients with FHCCs, which are often refractory to radioiodine treatment.