Novel cutaneous effects of combination chemotherapy with BRAF and MEK inhibitors: a report of two cases

The discovery that some melanoma tumours harbour mutations in the BRAF gene (e.g. V600E) and the subsequent development of specific BRAF inhibitors have greatly improved the treatment of metastatic melanoma. Resistance of tumour cells to BRAF inhibitors is reduced by the addition of an MEK inhibitor; both BRAF and MEK inhibitors have been reported to produce a variety of dermatological toxic effects. Benign naevi often harbour BRAF mutations but few reports exist that document the response of naevus cells to BRAF inhibition. We report sarcoidal-type granulomatous inflammation in two patients with metastatic melanoma undergoing treatment with combination BRAF and MEK inhibitor therapy. This inflammation manifested in one patient as a nonspecific papular eruption; in the other, in association with clinical regression of multiple benign-appearing naevi during the course of therapy. The significance of sarcoidal-type inflammation occurring during treatment of metastatic melanoma with a combination of BRAF and MEK inhibitors is unclear. Its association with the clinical regression of benign-appearing naevi suggests a possible exaggerated inflammatory response to degenerating naevus cells in these lesions.