Spread of malignant lymphoid cells into rat central nervous system with intact and disrupted blood–brain barrier

Abstract

The pathways of spread of malignant lymphoid cells into the central nervous system (CNS) were studied using a T lymphoblastic leukaemia/lymphoma model of inbred PVG rats. The effects of intraperitoneal, intracarotid, intravenous, intrathecal and intracerebral routes of transplantation were analysed, and the significance of the blood-brain barrier (BBB) in preventing neoplastic cell invasion was studied by disrupting the BBB with focal cold injury. Extraneurally transplanted cells appeared first in the dura and subarachnoid space. From the latter they spread further into the perivascular space of penetrating cortical vessels. Parenchymal tumour cell foci were only seen in terminally ill rats, usually associated with damage to the vessel wall. Intrathecal transplantation did not accelerate the progression of the disease. Intracerebrally transplanted cells readily produced parenchymal infiltrates with diffuse invasion into the white matter, perivascular spreading into the cortex, and contralateral extension along the corpus callosum. Parenchymal invasion did not occur immediately after disruption of the BBB, but in the chronic phase neoplastic cells infiltrated the injured area. In conclusion, the model closely resembles human CNS leukaemia. Malignant cells appeared to enter the CNS through the deficient BBB of the subarachnoid vessels, whereas the BBB of the intracerebral vessels and perivascular glia limitans were very resistant to leukaemic cell invasion. This underlines the difference between the subarachnoid and perivascular v. intraparenchymal compartments. Preceding BBB damage may predispose to brain metastases. The parenchymal dissemination of malignant cells was similar to that in primary CNS lymphoma and it followed the same spreading pathways as the extracellular fluid.

Summary Statement on Primary Central Nervous System Lymphomas From the Eighth International Conference on Malignant Lymphoma, Lugano, Switzerland, June 12 to 15, 2002

“…Even though animal lymphoma models with differing CNS dissemination exist, [7][8][9] no model demonstrated ocular infiltration by the lymphoma cells. This stems, in part, from the lack of adequate in vivo experimental models.…”

Secondary central nervous system lymphoma surrounding a region injured by subarachnoid hemorrhage and subsequent aneurysmal clipping

“…However, lymphoma cells hypothetically spread from retroperitoneal lymph nodes or bone marrow to the leptomeninges via the intervertebral nervous plexus (9). Aho et al (4) reported that malignant cells appeared to enter the CNS through a deficiency in the BBB around the subarachnoid vessels. Composite meningioma and lymphoma has been reported as a form of tumor-to-tumor metastasis (10).…”

“…Furthermore, computed tomography (CT) and magnetic resonance imaging (MRI) abnormalities surrounding hemorrhagic and postoperative changes make it difficult to distinguish between onset of disease and postoperative complications, including metal artifacts. However, malignant cells that enter the CNS appear first in the dura and subarachnoid space in rats with a blood brain barrier (BBB) disrupted by focal injury following exposure to a cold temperature (4). Previous history of subarachnoid hemorrhage (SAH) and aneurysm clipping may be associated with CNS infiltration in systemic lymphoma.…”