Response and rare disease progression on targeted therapy. (A) Photographs showing response of skin lesions in case 30 with RDD/ECD to conventional therapies and targeted treatment with cobimetinib. (B) Axial PET-computed tomography (CT) images of case 17 with ECD showing increased fluorodeoxyglucose (FDG) uptake of a left acetabular lesion (indicated by a white arrow) during intermittent dosing of dabrafenib/trametinib. After returning to continuous therapy, PET-CT showed decreased FDG uptake in the acetabular lesion, consistent with a recaptured PR. (C) Axial T1-weighted gadolinium-enhanced MRI images of case 36 with CNS-RDD showing an initial PR of contrast-enhanced brain lesions to treatment with cobimetinib, and subsequent progression of brain stem lesions after dose reduction to 20 mg/d. After return to full dose (60 mg/d), lesions decreased again, indicating a recaptured response. (D) Axial CT and PET images of case 16 with ECD showing progression of an FDG-avid lung nodule during treatment with dabrafenib, and partial resolution of this nodule after switch to treatment with trametinib. 2-CDA, cladribine; DEX, dexamethasone; BRAFi, BRAF inhibitor; MEKi, MEK inhibitor.