Advances in primary large B-cell lymphoma of immune-privileged sites

Primary large B-cell lymphoma of immune-privileged sites (IP-LBCL) encompasses a spectrum of relatively rare aggressive B-cell lymphomas, such as primary central nervous system lymphoma (PCNSL), primary testicular large B-cell lymphoma (PTL), and primary vitreoretinal large B-cell lymphoma (PVRL). Macroscopically, the development of IPI-LBCL may be associated with the dysfunction of meningeal lymphatic vessels (mLVs) and the perivascular channel system formed by astrocytes. Microscopically, mutation in MYD88 and CD79B genes plays a pivotal role in the pathogenesis of IP-LBCL. Pathological examination remains the cornerstone for establishing a diagnosis of IP-LBCL. Moreover, traditional imaging is now supplemented by a suite of advanced diagnostic methods, including cytological, genetic, immunological, multiple omics, and molecular biological, which collectively enhance the diagnostic accuracy of IP-LBCL. Despite these advancements, the high recurrence rates and attendant high mortality rates pose significant challenges to achieving long-term survival in IP-LBCL patients. However, the emergence of novel therapeutic agents, such as Bruton's tyrosine kinase inhibitors (BTKi), immune checkpoint inhibitors, immunomodulators, and anti-CD19 chimeric antigen receptor T (CAR-T) cell therapy, has offered promising new avenues for the treatment of IP-LBCL, demonstrating remarkable anti-tumor efficacy in recent years. This review delves into the epidemiology, pathogenesis mechanisms, diagnosis approaches, therapeutic strategies, and prognosis factors associated with IP-LBCL. It meticulously examines the parallels and divergences between the National Comprehensive Cancer Network (NCCN) and European Society for Medical Oncology (ESMO) guidelines, enhancing the professional comprehension of the complexities inherent to IP-LBCL.