PATHOGENESIS OF PRIMARY CENTRAL-NERVOUS-SYSTEM LYMPHOMA - INVASION OFMALIGNANT LYMPHOID-CELLS INTO AND WITHIN THE BRAIN PARENCHYME

The pattern of invasion of lymphoid cells to the central nervous syste m (CNS) was analyzed for malignant lymphocytes in 19 primary CNS lymph omas (PCNSL) and six intracerebral metastatic lymphomas, and for react ive lymphocytes in four encephalitides and three astrocytomas. The ide ntical spreading pattern in both primary and metastatic lymphomas sugg ests that even in the so-called primary CNSL the malignant transformat ion has occurred outside the CNS. The compact perivascular cuffs of bo th malignant and reactive lymphocytes were never seen around the small est capillaries, and they were most common around vessels larger than 15 mum in diameter. Perivascular lymphocytes resided within the reticu lin network, which was immunopositive for collagen type III and IV, la minin and fibronectin. These findings imply that lymphocytes extravasa te at the level of arterioles and venules and spread along the enlarge d perivascular space. When the outer boundary of the perivascular netw ork was broken, malignant lymphocytes spread diffusely into the CNS pa renchyme; a pattern which is different from that of other CNS metastas es. The widespread immunopositivity for the homing cell adhesion molec ule CD44 in the CNS vessels and parenchyme, especially in the white ma tter which is the predilection site of PCNSL, suggest that this adhesi on molecule and its ligands participate in spreading of malignant lymp hocytes within the CNS parenchyme.