High incidence of naevi-associated BRAF wild-type melanoma and dysplastic naevi under treatment with the class I BRAF inhibitor vemurafenib.

There is growing evidence that not only malign keratinocytic but also melanocytic tumours can arise during treatment with vemurafenib. During an on-going early access trial, 13 patients harbouring a BRAF-V600E mutation received vemurafenib (Zelboraf®) 960 mg twice daily to test the safety, tolerability, efficacy and response rate for advanced melanoma. Clinically or dermatoscopically suspicious cutaneous tumours under treatment with vemurafenib were excised. The BRAF-V600E status of confirmed new primary melanoma and dysplastic naevi was tested using a genetic mutation assay and immunohistochemistry. Four of the 13 patients (31%) developed 4 new naevi-associated malignant melanomas and 5 dysplastic naevi between 6 weeks and 6 months after the start of treatment. With the exception of one in situ melanoma, all tumours were BRAF wild-type. Immunohistochemistry revealed increased expression of ERK, pERK and active Rac1-GTP in the naevi-associated melanoma and dysplastic naevi. Careful and continuous skin examination, including dermoscopy, appears to be required during treatment with vemurafenib.