Primary central nervous system lymphomas with massive intratumoral hemorrhage: Clinical, radiological, pathological, and molecular features of six cases

Primary central nervous system lymphomas (PCNSLs) rarely exhibit intratumoral hemorrhage. The differential diagnosis of hemorrhagic neoplasms of the central nervous system (CNS) currently includes metastatic carcinomas, melanomas, choriocarcinomas, oligodendrogliomas, and glioblastomas. Here we present the clinical, radiological, pathological, and molecular genetic features of six cases of PCNSL associated with intratumoral hemorrhage. The median age of patients was 75 years, with male predominance. While conventional PCNSLs were associated with low cerebral blood volume (CBV), perfusion magnetic resonance imaging (MRI) revealed elevated CBV in three cases, consistent with vascular proliferation. All six cases were diagnosed pathologically as having diffuse large B-cell lymphoma (DLBCL) with a non-germinal center B-cell-like (non-GCB) phenotype; marked histiocytic infiltrates and abundant non-neoplastic T-cells were observed in most cases. Expression of vascular endothelial growth factor and CD105 in the lymphoma cells and the small vessels, respectively, suggested angiogenesis within the neoplasms. Neoplastic cells were immunohistochemically negative for programmed cell death ligand 1 (PD-L1), while immune cells in the microenvironment were positive for PD-L1. Mutations in the MYD88 gene (MYD88) (L265P) and the CD79B gene (CD79B) were detected in five and one case, respectively. As therapeutic modalities used for PCNSLs differ from those that target conventional hemorrhagic neoplasms, full tissue diagnoses of all hemorrhagic CNS tumors are clearly warranted.