Rare Primary Central Nervous System Tumors in Adults: An Overview

Abstract

Overall, tumors of primary central nervous system (CNS) are quite common in adults with an incidence rate close to 30 new cases/100,000 inhabitants per year. Significant clinical and biological advances have been accomplished in the most common adult primary CNS tumors (i.e., diffuse gliomas). However, most CNS tumor subtypes are rare with an incidence rate below the threshold defining rare disease of 6.0 new cases/100,000 inhabitants per year. Close to 150 entities of primary CNS tumors have now been identified by the novel integrated histomolecular classification published by the World Health Organization (WHO) and its updates by the c-IMPACT NOW consortium (the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy). While these entities can be better classified into smaller groups either by their histomolecular features and/or by their location, assessing their treatment by clinical trials and improving the survival of patients remain challenging. Despite these tumors are rare, research, and advances remain slower compared to diffuse gliomas for instance. In some cases (i.e., ependymoma, medulloblastoma) the understanding is high because single or few driver mutations have been defined. The European Union has launched European Reference Networks (ERNs) dedicated to support advances on the clinical side of rare diseases including rare cancers. The ERN for rare solid adult tumors is termed EURACAN. Within EURACAN, Domain 10 brings together the European patient advocacy groups (ePAGs) and physicians dedicated to improving outcomes in rare primary CNS tumors and also aims at supporting research, care and teaching in the field. In this review, we discuss the relevant biological and clinical characteristics, clinical management of patients, and research directions for the following types of rare primary CNS tumors: medulloblastoma, pineal region tumors, glioneuronal and rare glial tumors, ependymal tumors, grade III meningioma and mesenchymal tumors, primary central nervous system lymphoma, germ cell tumors, spinal cord tumors and rare pituitary tumors.

Glioneuronal Tumors: Insights into a Rare Tumor Entity

“…Previous limitations in diagnosis were related to limited ability to elicit radiographic differences, scant material for pathological analysis and the overall rarity of glioneuronal tumors. Ganglioglioma, paraganglioma, central neurocytoma and DNET have been reported on for some time (Figure 1) (1)(2)(3)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44). RGNT (39)(40)(41), PGNT (42,43) and GNTNI (44) were added to the WHO classification in 2007 (1).…”

“…The common feature of glioneuronal tumors is the presence of both glial and neuronal tissue as evidenced by glial fibrillary acid protein-positive cells and synaptophysin-positive neuronal cells forming solid areas (Figure 2A 3% of all primary brain tumors), neurocytoma (Figure 2D (55); 0.1-0.5% of all brain tumors), makes diagnosis difficult (1)(2)(3)(4). While each glioneuronal tumor can display certain distinct features (Figure 2), in some instances a tumor may demonstrate overlapping histologic features with mixed components (36) making diagnosis challenging.…”

“…Glioneuronal tumors are rare tumors comprised of both neural and glial components present in heterogenous proportions displaying indolent WHO grade I behavior (1)(2)(3). More recently, molecular characterization has allowed for more robust classification (4)(5)(6)(7)(8)(9).…”

“…Patients can present with increased intracranial pressure, acute neurological deficits, hydrocephalus, diffuse leptomeningeal spread and symptoms of cord impingement or compression. Overall, the data surrounding glioneuronal tumors remains scant, largely comprised of small retrospective series and reviews of literature (1)(2)(3). Management involves seizure and symptom control, including resection when possible (12,13).…”

Rare Brain Tumors with Infrequent Clinical Manifestations: Illustrative Cases

“…Brain tumors according to their location and growth rate can produce very typical clinical manifestations [1], in addition to the classic characteristics of imaging studies that provide the possibility of approaching the diagnosis of the specific type of tumor and guide to establish the treatment modality [2]. However, when the incidence of some of these tumors is very low and they present with very varied clinical manifestations, added to the radiological findings that do not provide too much information to approximate the diagnosis, these cases condition stricter study protocols where the undoubtedly diagnoses alters the treatment modality for each particular case [3]. For this reason, knowledge of the existence of some of these tumors should be the subject of study, to understand the difficulty in diagnosis and treatment, seeking to reduce errors in addressing these cases and improve the result.…”