Brain metastasis: clinical characteristics, pathological findings and molecular subtyping for therapeutic implications

Metastases are the most common brain tumors especially in adults. Although they are generally considered a single disease entity which is universally fatal in patients with advanced cancer, brain metastases are remarkably heterogeneous both clinically and pathologically. As members of the multidisciplinary clinical team for the diagnosis and management of metastatic brain tumors, pathologists must be familiar not only with clinicopathologic features of brain metastases but also with any characteristic and clinically significant molecular findings. We discuss here the epidemiology, general gross and microscopic features of brain metastases with emphasis on how to differentiate them from primary brain tumors using immunohistochemistry (e.g., for identification of the primary site and differential diagnosis), and unique pathologic patterns of brain metastases (namely, dural metastasis, leptomeningeal carcinomatosis, miliary metastasis, "intravascular carcinomatosis", and tumor-to-tumor metastasis) with their clinical and radiological characteristics. We specifically address metastatic breast and non-small cell lung cancers which are the two most commonly encountered in daily practice, with emphasis on the molecular alterations related to therapy and their clinicopathologic significance.