Neuropathology of brain metastases

Metastatic tumors are the most common neoplasms encountered in the central nervous system (CNS), and continue to be major cause for mortality and morbidity. Macroscopic features and corresponding radiological findings can be diagnostic in majority of the cases, however, microscopic evaluation would be necessary when the differential diagnosis includes a primary CNS tumor, unknown primary tumor site, and when the resection of the tumor is either considered therapeutic or palliative. The first step in the diagnosis of a metastatic brain lesion is to exclude a primary CNS tumor, followed by verification or identification of the primary tumor and the site. Although general approach to a metastatic lesion from an unknown primary tumor is the same everywhere else, there are slight variations for the metastatic lesions in the CNS versus other regions. When morphological features are not enough to establish a definitive diagnosis, additional studies including immunohistochemical stains are applied. With the expending immunohistochemical armamentarium for pathologists, more accurate assessments are possible even in cases of unknown primary tumor. This review summarizes the diagnostic approach to CNS metastases, immunohistochemical assessment of neoplasm of unknown primary, and primary CNS lesions entering in the differential diagnosis of metastases.