(Secondary) solid tumors in thyroid cancer patients treated with the multi-kinase inhibitor sorafenib may present diagnostic challenges.

BACKGROUND: Sorafenib is an orally active multikinase tyrosine kinase inhibitor (TKI) that targets B-type Raf kinase (BRAF), vascular endothelial growth factor receptors (VEGFR) 1 and 2, and rearranged during transfection (RET), inducing anti-angiogenic and pro-apoptotic actions in a wide range of solid tumors. A side effect of sorafenib is the occurrence of cutaneous squamous tumors.

CASE PRESENTATION: Here we describe three patients with a history of sorafenib treatment for advanced radioactive iodine refractory papillary thyroid cancer (two with a BRAF c.1799 T > A and one carrying a rare c.1799-1801het_delTGA mutation) who presented with secondary non-cutaneous lesions. The first patient was diagnosed with a squamous cell carcinoma (SCC) of the tongue, the second patient with a primary adenocarcinoma of the lung, and the third with a SCC originating from the cricoid. Secondary analysis was required to show that the latter two presentations were in fact recurrent thyroid cancer.

CONCLUSION: These findings suggest that drugs such as sorafenib may induce metaplasia/clonal divergence of metastatic thyroid cancer and thus cause diagnostic misclassification. Furthermore, sorafenib is potentially involved in the tumorigenesis of secondary non-cutaneous SCC. These observations should now be confirmed in larger series of patients treated with drugs such as sorafenib.