Molecular pathogenesis of primary central nervous system lymphoma

Abstract

<jats:p>✓ Primary central nervous system lymphoma (PCNSL) is an aggressive form of non-Hodgkin lymphoma (NHL) typically associated with a worse prognosis than other localized extranodal lymphomas with similar histological characteristics. The defining feature of PCNSL is its confinement to the central nervous system (CNS), with proclivity for growth within the leptomeningeal as well as intraocular compartments. Primary CNS lymphoma rarely disseminates outside the CNS and accounts for less than 5% of all primary brain neoplasms. At least 95% of PCNSLs are of large B-cell histology, the most common subtype of NHL. Consistent with the trend seen in systemic NHLs, the incidence of PCNSL has markedly increased over the past three decades, both in immunocompromised and immunocompetent patients. Because PCNSL is relatively rare, the identification of molecular prognostic biomarkers and the definition of a standard therapeutic strategy have been challenging. The authors discuss the current knowledge of the molecular pathogenesis of CNS lymphomas and review the recent advances in gene expression profile analysis and identification of novel prognostic biomarkers.</jats:p>

Primary Central Nervous System Lymphoma: A Clinicopathological and Cytomorpholgical Study from A Tertiary Care Centre in Chennai, India

“…More than 90% of PCNSL tumors are high-grade, CD20-positive, diffuse large B-cell NHLs; despite the fact that B-cells are absent from the normal brain. CNS lymphomas exhibit a distinct gene expression profile compared with nodal lymphomas of the same histological type (Kadoch et al, 2006). In the early 1970s, PCNSL was a rare tumour (Henry et al, 1974).…”

Classification and pathogenesis of brain tumors

“…PCNSLs occurring in immunocompromised individuals are usually related to latent Epstein-Barr virus (EBV) infection (Forsyth & DeAngelis 1996). Elevated expression as well as mutations of the proto-oncogenes, MYC and PIM, ectopic expression of the B lymphocyte growth factor, interleukin-4 (IL4), and deletions and promoter methylation affecting the p14ARF/p53/ MDM2 pathway are the commonest among a very large number of molecular-genetic alterations seen in PCNSLs (Montesinos-Rongen et al 2004; Rubenstein et al 2006;Kadoch et al 2006). Unusual forms of lymphoma involving the CNS include anaplastic large cell lymphoma, lymphomatosis cerebri and intravascular lymphoma (Gonzales 2003;Rollins et al 2005;Ponzoni & Ferreri 2006).…”

“…Approximately 90% are CD20 + diffuse large B cell lymphomas. Burkitt's and Burkitt-like lymphomas, lymphoblastic B cell lymphoma and T cell lymphomas make up the remaining 10% (Kadoch et al 2006). PCNSLs occurring in immunocompromised individuals are usually related to latent Epstein-Barr virus (EBV) infection (Forsyth & DeAngelis 1996).…”

Novel approaches to treating leptomeningeal metastases

“…Chemokines represent an important class of molecules that regulate the trafficking, proliferation, and adhesion of leukocytes [30]. Cell adhesion is a crucial step in tumor cell migration and is regulated by a cytoskeletal matrix of focal adhesion molecules.…”

“…Evidence suggests that other correlative biomarkers also may help identify patients at risk of LM. Among these are molecules involved in chemotactic signaling, cell motility/adhesion, and stromal-cell interactions [29][30][31].…”