A Case of Multiple Pyogenic Granuloma during BRAF/MEK Inhibitor Therapy

Abstract

A 65-year-oldwoman was treatedwith a combination of encorafenib＋binimetinib (BRAF/MEK inhibitor) andcetuximab for stage IV BRAF mutation-positive rectal cancer 1 month prior to her rst visit. She was referred to our department because multiple small nodules developed on her limbs andtrunk 2 weeks later. At the rst visit, 1-5 mm bright redsmall nodules with a shiny surface resembling cherry hemangioma were observedon her limbs andtrunk. Histopathological examination demonstrated lobular proliferation of dilated capillaries in the supercial dermis. A diagnosis of pyogenic granuloma (PG) was made. After discontinuation of BRAF/MEK inhibitor, the number and size of the small nodules decreased, without development of new lesions, which led to the conclusion that the PG was causedby the BRAF inhibitor. PG can be causedby inammatory reactions, such as infection or trauma, andit can also be triggeredby drugs such as BRAF inhibitor and ramucirumab, a vascular endothelial growth factor receptor-2 monoclonal antibody. In the present case, ramucirumab was administered prior to BRAF/MEK inhibitors ; thus, BRAF inhibitor as well as ramucirumab may have been involvedin the development of PG. In recent years, genetic mutations in the MAPK pathway, including BRAF, have been reported in PG, suggesting that PG is a vascular tumor causedby activation of the MAPK pathway. In the present case, we examined, but could not detect genetic mutations. Further studies are needed to clarify the mechanism of druginduced PG. Skin Research, 23 : 177-182, 2024