[Squamous cell carcinoma in a patient receiving sorafenib]

Sorafenib is a multikinase inhibitor approved for the treatment of renal cell carcinoma and hepatocellular carcinoma. Associated short-term cutaneous adverse events are well known. Regarding long-term adverse events, keratoacanthoma has been reported more recently and, more rarely, invasive squamous cell carcinoma.

A 56-year-old man was treated with sorafenib in December 2008 for renal cell carcinoma with cutaneous metastases. The patient had a skin phototype IV and no history of intense sun exposure. Within five months of starting sorafenib, he developed deeply invasive well-differentiated retroauricular squamous cell carcinoma.

Sorafenib modifies the immunostimulatory capacity of dendritic cells by reducing cytokine secretion and CD1a expression. Blockade of autocrine vascular endothelial growth factor (VEGF) signalling in keratinocytes can also select tumoural clones with increased oncogenic Ras mutation, increased activation of phospholipase D and modulation of the Ras/Raf/MAP kinase signalling pathway involved in cutaneous squamous cell carcinogenesis.

Cases of keratoacanthomas and deeply invasive squamous cell carcinomas reported in patients on sorafenib emphasise the need for multidisciplinary follow-up of this population and the important role of dermatologists in managing the short and long-term adverse effects of multitarget tyrosine inhibitors.