Figure 2.

Radiation necrosis and chronic inflammation in a patient with brain metastases of a B-Raf proto-oncogene (BRAF)-mutated malignant melanoma who had been treated with whole-brain radiation therapy combined with concurrent dabrafenib plus trametinib. Twenty-four months later, the contrast-enhanced magnetic resonance imaging (MRI) indicates a recurrence of the brain metastases (left panel), whereas the O-(2-[¹⁸F]fluoroethyl)-L-tyrosine ([¹⁸F]FET) positron-emission tomography (PET) shows only insignificant metabolic activity and is consistent with the findings of treatment-related MRI changes. Neuropathological findings (right panel) after stereotactic biopsy show signs of radiation necrosis as well as considerable T-cell infiltration. (A) Hyaline, eosinophilic necrosis with evidence of a necrotic vessel wall (arrowhead). (B) Vital brain parenchyma besides necrosis with activated microglia cells (arrowhead), and blood vessels with lymphocyte infiltrates (arrows) without evidence of tumor cells (inserted box). (C) Adjacent to inflamed blood vessels (arrows), a resorption of necroses by macrophages (block arrows) as well as activated microglia cells (arrowheads) and astrocytes in the brain parenchyma (inserted box). (D) The main population of intra- and perivascular T-cell infiltrates are CD3⁺ (arrow), but also CD4⁺ (inserted box left) and CD8⁺ (inserted box right) T-cells contribute to the infiltrates (modified from Galldiks et al. [10], with permission from Oxford University Press).