Epstein–Barr virus (EBV; human herpesvirus 4; HHV‐4) and Kaposi sarcoma‐associated herpesvirus (KSHV; human herpesvirus 8; HHV‐8) are human gammaherpesviruses that have oncogenic properties. EBV is a lymphocryptovirus, whereas HHV‐8/KSHV is a rhadinovirus. As lymphotropic viruses, EBV and KSHV are associated with several lymphoproliferative diseases or plasmacytic/plasmablastic neoplasms. Interestingly, these viruses can also infect epithelial cells causing carcinomas and, in the case of KSHV, endothelial cells, causing sarcoma. EBV is associated with Burkitt lymphoma, classic Hodgkin lymphoma, nasopharyngeal carcinoma, plasmablastic lymphoma, lymphomatoid granulomatosis, leiomyosarcoma, and subsets of diffuse large B‐cell lymphoma, post‐transplant lymphoproliferative disorder, and gastric carcinoma. KSHV is implicated in Kaposi sarcoma, primary effusion lymphoma, multicentric Castleman disease, and KSHV‐positive diffuse large B‐cell lymphoma. Pathogenesis by these two herpesviruses is intrinsically linked to viral proteins expressed during the lytic and latent lifecycles. This comprehensive review intends to provide an overview of the EBV and KSHV viral cycles, viral proteins that contribute to oncogenesis, and the current understanding of the pathogenesis and clinicopathology of their related neoplastic entities.

Primary central nervous system lymphoma (PCNSL) is a rare form of extranodal non-Hodgkin lymphoma that primarily arises in the brain, spinal cord, leptomeninges, and vitreoretinal compartment of the eye. The term is sometimes used interchangeably with primary central nervous system diffuse large B-cell lymphoma (PCNS DLBCL) because DLBCL comprises a great majority (90–95%) of PCNSL. Although rare, other types of lymphomas can be seen in the central nervous system (CNS), and familiarity with these entities will help their recognition and further workup in order to establish the diagnosis. The latter is especially important in the case of PCNSL where procurement of diagnostic specimen is often challenging and yields scant tissue. In this review, we will discuss the most common types of primary lymphomas that can be seen in the CNS with emphasis on the diagnostic histomorphologic, immunophenotypic, and molecular genetic features. The differential diagnostic approach to these cases and potential pitfalls will also be discussed.

Key Points. 1. We identified a new pediatric type of PCNS-LBCL that has distinct molecular features compared to PCNS-LBCL occurring in adults.2. Pediatric PCNS-