Pathogenesis of primary central nervous system lymphoma: invasion of malignant lymphoid cells into and within the brain parenchyme

Abstract

The pattern of invasion of lymphoid cells to the central nervous system (CNS) was analyzed for malignant lymphocytes in 19 primary CNS lymphomas (PCNSL) and six intracerebral metastatic lymphomas, and for reactive lymphocytes in four encephalitides and three astrocytomas. The identical spreading pattern in both primary and metastatic lymphomas suggests that even in the so-called primary CNSL the malignant transformation has occurred outside the CNS. The compact perivascular cuffs of both malignant and reactive lymphocytes were never seen around the smallest capillaries, and they were most common around vessels larger than 15 microns in diameter. Perivascular lymphocytes resided within the reticulin network, which was immunopositive for collagen type III and IV, laminin and fibronectin. These findings imply that lymphocytes extravasate at the level of arterioles and venules and spread along the enlarged perivascular space. When the outer boundary of the perivascular network was broken, malignant lymphocytes spread diffusely into the CNS parenchyme; a pattern which is different from that of other CNS metastases. The widespread immunopositivity for the homing cell adhesion molecule CD44 in the CNS vessels and parenchyme, especially in the white matter which is the predilection site of PCNSL, suggest that this adhesion molecule and its ligands participate in spreading of malignant lymphocytes within the CNS parenchyme.