Skip to main content
Log in

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

  • Regular Papers
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Summary

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 encepphalitides 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 μm 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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Aruffo A, Stamenkovic I, Melnick M, Underhill CB, Seed B (1990) CD44 is the principal cell surface receptor for hyaluronate. Cell 61:1303–1313

    Google Scholar 

  2. Asher R, Perides G, Vanderhaeghen J-J, Bignami A (1991) Extracellular matrix of central nervous system white matter: demonstration of an hyaluronate-protein complex. J Neurosci Res 28:410–421

    Google Scholar 

  3. Azzarelli B, Mirkin LD, Goheen M, Muller J, Crockett C (1984) The leptomeningeal vein, a site of re-entry of leukemic cells into the systemic circulation. Cancer 54:1333–1343

    Google Scholar 

  4. Bonnin JM, Garcia JH (1987) Primary malignant non-Hodgkin's lymphoma of the central nervous system. Pathol Annu 22:353–375

    Google Scholar 

  5. Brosnan CF, Kress Y, Gaskin F, Levine S (1982) Further studies on the inflammatory response induced by zinc wire implants in the central nervous system of rats. J Neuropathol Exp Neurol 41:221–232

    Google Scholar 

  6. Burger PC, Scheithauer BW, Vogel FS (1991) Surgical pathology of the nervous system and its coverings, 3rd edn. Churchill Livingstone, New York, pp 359–365

    Google Scholar 

  7. Cserr HF, Harling-Berg CJ, Knopf PM (1992) Drainage of brain extracellular fluid into blood and deep cervical lymph and its immunological significance. Brain Pathol 2:269–276

    Google Scholar 

  8. Faustmann PM, Dermietzel R (1985) Extravasation of polymorphonuclear leukocytes from the cerebral microvasculature. Inflammatory response induced by alpha-bungarotoxin. Cell Tissue Res 242:399–407

    Google Scholar 

  9. Frederickson RG, Low FN (1969) Blood vessels and tissue space associated with the brain of the rat. Am J Anat 125:123–146

    Google Scholar 

  10. Hauser SL, Bhan AK, Gilles FH, Hoban CJ, Reinherz EL, Schlossmann SF, Weiner HL (1983) Immunohistochemical staining of human brain with monoclonal antibodies that identify lymphocytes, monocytes, and the Ia antigen. J Neuroimmunol 5:197–205

    Google Scholar 

  11. Helle TL, Britt RH, Colby TV (1984) Primary lymphoma of the central nervous system. Clinicopathological study of experience at Stanford. J Neurosurg 60:94–103

    Google Scholar 

  12. Hickey WF, Hsu BL, Kimura H (1991) T-lymphocyte entry into the central nervous system. Neurosci Res 28:254–260

    Google Scholar 

  13. Hochberg FH, Miller DC (1988) Primary central nervous system lymphoma. J Neurosurg 68:835–853

    Google Scholar 

  14. Horst E, Meijer CJLM, Radaszkiewicz T, Ossekoppele GJ, Van Kricken JHJM, Pals ST (1990) Adhesion molecules in the prognosis of diffuse large cell lymphoma: expression of a lymphocyte homing receptor (CD44), LFA-1 (CD11a/18), and ICAM-1 (CD45). Leukemia 4:595–599

    Google Scholar 

  15. Hutchings M, Weller RO (1986) Anatomical relationships of the pia mater to cerebral blood vessels in man. J Neurosurg 65:316–325

    Google Scholar 

  16. Jalkanen S, Bargatze RF, de los Toyos J, Butcher EC (1987) Lymphocyte recognition of high endothelium: antibodies to distinct epitopes of an 85-95-kD glycoprotein antigen differentially inhibit lymphocyte binding to lymph node, mucosal, or synovial endothelial cells. J Cell Biol 105:983–990

    Google Scholar 

  17. Jalkanen S, Aho R, Kallajoki M, Ekfors T, Nortamo P, Gahmberg C, Duijvestijn A, Kalimo H (1989) Lymphocyte homing receptors and adhesion molecules in intravascular malignant lymphomatosis. Int J Cancer 44:777–782

    Google Scholar 

  18. Kuppner MC, Hamou M-F, De Tribolet N (1990) Activation and adhesion molecule expression on lymphoid infiltrates in human glioblastomas. J Neuroimmunol 29:229–238

    Google Scholar 

  19. Kuttner BJ, Woodruff JJ (197) Selective adherence of lymphocytes to myelinated areas of rat brain. J Immunol 122:1666–1671

    Google Scholar 

  20. Lachance DH, O'Neill BP, Macdonald DR, Jaeckle KA, Witzig TE, Li C-Y, Posner JB (1991) Primary leptomeningeal lymphoma: report of 9 cases, diagnosis with immunocytochemical analysis, and review of the literature. Neurology 41:95–100

    Google Scholar 

  21. Möller P, Eichelmann A, Mechtersheimer G, Koretz K (1991) Expression of β1-integrins, H-CAM (CD44) and LECAM-1 in primary gastro-intestinal B-cell lymphomas as compared to the adhesion receptor profile of the gut-associated lymphoid system, tonsil and peripheral lymph node. Int J Cancer 49:846–855

    Google Scholar 

  22. Niemelä O, Risteli L, Parkkinen J, Risteli J (1985) Purification and characterization of the N-terminal propeptide of human type III procollagen. Biochem J 232:146–150

    Google Scholar 

  23. Picker LJ, Nakache M, Butcher EC (1989) Monoclonal antibodies to human lymphocyte homing receptors define a novel class of adhesion molecules on diverse cell types. J Cell Biol 109:927–937

    Google Scholar 

  24. Price RA, Johnson WW (1973) The central nervous system in childhood leukemia. I. The arachnoid. Cancer 31:520–533

    Google Scholar 

  25. Pryce G, Male DK, Sarkar C (1991) Control of lymphocyte migration into brain: Selective interactions of lymphocyte subpopulations with brain endothelium. Immunology 72:393–398

    Google Scholar 

  26. Raine CS, Cannella B, Duijvestijn AM, Cross AH (1990) Homing to central nervous system vasculature by antigen-specific lymphocytes. II. Lymhocyte/endothelial cell adhesion during the initial stages of autoimmune demyelination. Lab Invest 63:476–489

    Google Scholar 

  27. Rennels ML, Gregory TF, Blaumanis OR, Fujimoto K, Grady PA (1985) Evidence for “paravascular” fluid circulation in the mammalian central nervous system, provided by the rapid distribution of tracer protein throughout the brain from the subarachnoid space. Brain Res 326:47–63

    Google Scholar 

  28. Rincon J, Prieto J, Patarroyo M (1992) Expression of integrins and other adhesion molecules in Epstein-Barr virus-transformed B lymphoblastoid cells and Burkitt's lymphoma cells. Int J Cancer 51:452–458

    Google Scholar 

  29. Risteli J, Bechinger H, Engel J, Furthmayer H, Timpl R (1980) 7-S collagen: characterization of an unusual basement membrane structure. Eur J Biochem 108:239–250

    Google Scholar 

  30. Risteli L, Timpl R (1981) Isolation and characterization of pepsin fragment of laminin from human placental and renal basement membrane. Biochem J 193:749–755

    Google Scholar 

  31. Ritzen ME (1990) Testicular relapse of acute lymphoblastic leukemia (ALL). J Reprod Immunol 18:117–121

    Google Scholar 

  32. Rössler K, Neuchrist C, Kitz K, Scheiner O, Kraft D, Lassmann H (1992) Expression of leucocyte adhesion molecules at the human blood-brain barrier (BBB). J Neurosci Res 31:365–374

    Google Scholar 

  33. Sloan DJ, Wood MJ, Charlton HM (1992) Leucocyte recuitment and inflammation in the CNS. Trends Neurosc: 15:276–278

    Google Scholar 

  34. Wagner H-J, Pilgrim Ch, Brandl J (1974) Penetration and removal of horseradish peroxidase injected into the cerebrospinal fluid: role of cerebral perivascular spaces, endothelium and microglia. Acta Neuropathol (Berl) 27:299–315

    Google Scholar 

  35. Weller RO, Kida S, Zhang E-T (1992) Pathways of fluid drainage from the brain — Morphological aspects and immunological significance in rat and man. Brain Pathol 2:277–284

    Google Scholar 

  36. Westergaard E (1977) The blood-brain barrier to horseradish peroxidase under normal and experimental conditions. Acta Neuropathol (Berl) 39:181–187

    Google Scholar 

  37. Xerri L, Gambarelli D, Horschowski N, Andrax L, Hassoun J (1990) What's new in primary central nervous system lymphomas? Pathol Res Pract 186:809–816

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Supported by a grant from the Finnish Cancer Foundation

Rights and permissions

Reprints and permissions

About this article

Cite this article

Aho, R., Ekfors, T., Haltia, M. et al. Pathogenesis of primary central nervous system lymphoma: invasion of malignant lymphoid cells into and within the brain parenchyme. Acta Neuropathol 86, 71–76 (1993). https://doi.org/10.1007/BF00454901

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00454901

Key words

Navigation