Cerebral metastases pathology after radiosurgery: a multicenter study

BACKGROUND: To the authors' knowledge, comprehensive human pathologic investigations that explore fundamental radiosurgical effects on metastatic brain tumors are sparse in the literature. The objective of this study was to analyze histopathologic findings in a set of clinically recurrent cerebral metastases after patients underwent stereotactic radiosurgery (SRS). METHODS: In a series of 7500 patients who underwent radiosurgery, 2020 patients (27%) harbored cerebral metastases. Eighteen of 2020 patients (0.9%) underwent subsequent craniotomy for tumor removal anywhere from 1 month to 59 months after they received high-dose irradiation. Histologic and immunohistochemical investigations were performed on the surgically resected tissue specimens. These specimens were within the radiosurgical treatment volume of the metastatic tumor. RESULTS: Light microscopy revealed 3 basic categories of histologic responses: acute-type, subacute-type, and chronic-type tissue reactions. A moderate-to-intense inflammatory cell reaction was seen in the tissue responses of well controlled neoplasms (i.e., in patients who had neoplasms that required craniotomy for recurrent disease > 5 months after SRS), whereas the inflammatory reaction was missing or sparse in poorly controlled neoplasms (patients who required craniotomy for recurrent disease < 5 months after SRS). This reaction was seen within the irradiated tumor volume and not in the peritumoral area nor in areas remote from the radiosurgical treatment volume. Immunohistochemical characterization demonstrated the presence of prominent CD68-positive macrophage and CD3-positive T-lymphocyte populations. A progressively severe vasculopathy also was observed with increasing time after radiosurgery. CONCLUSIONS: Although causality has not been established, a brisk inflammatory response and more severe vasculopathy were observed in lesions in which recurrences were more delayed.