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

Abstract

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.

Transcriptomic Hallmarks of Tumor Plasticity and Stromal Interactions in Brain Metastasis

“…The most common primary tumor types to spread to the CNS include melanoma, breast, and lung cancer (Kamar and Posner, 2010). Metastasis often forms within the brain parenchyma but may also develop in the dura and/or leptomeninges, either independently or in conjunction with intraparenchymal tumors (Takei et al, 2016). Finally, brain metastasis may present as a single tumor, oligometastases (2–4 tumor foci), or multiple metastases (>4 tumor foci) (Iuchi et al, 2015; Takei et al, 2016) with varying patterns of invasive outgrowth (Berghoff et al., 2013b; Kamp et al, 2018).…”

Epigenetic Profiling for the Molecular Classification of Metastatic Brain Tumors

“…In this study, we constructed and validated novel DNAm classifiers for the accurate diagnosis of brain metastases. Routinely, the first step in the diagnosis of metastatic brain tumors is to exclude a possible primary central nervous system neoplasm 9,31,32 . Here, we found substantial differences in the DNAm landscapes of primary and metastatic brain tumors.…”

Immunophenotyping of HER4/YAP axis in breast cancer brain metastasis

“…Relapse of breast cancer (BC) in the brain leads to significant morbidity and a poor life expectancy, generally less than two years from diagnosis 1. The exact incidence of brain metastases (BrM) is difficult to determine because it is not routinely documented in patients with disseminated disease, nor screened for in asymptomatic patients, but the most recent epidemiological data indicate high incidence of up to 40% of intracranial metastases in cancer patients 1-4. Moreover, with prolonged overall survival of cancer patients due to good systemic control 5, the incidence of BrM is increasing 6. Treatment modalities can include stereotactic radiosurgery, surgical resection, focused external beam radiosurgery, whole-brain radiotherapy and conventional chemotherapy 7.…”

“…95% positivity, 357 out of 373 cases, in all subtypes of breast cancers). Interestingly, pHER4 was positive and membranous in only 16 cases out of 270, with few cases displaying moderate positivity(10) and few showing strong staining(6) (fig 2A). As observed previously infigure 1B, activation of HER4 was significantly associated with its dimerizing partners in brain metastasis.…”