Summary
Neurological complications are a major cause of morbidity and mortality in patients with disseminated malignant melanoma. We have studied and correlated clinical and cerebrospinal fluid (CSF) findings in 20 patients with central nervous system metastases from malignant melanoma including 8 patients with metastatic meningeal melanomatosis (MMM) and 12 patients with solid cerebral metastases (SCM). The putative CSF tumor markers, fibronectin and β2-microglobulin, were elevated significantly in MMM but not in SCM patients. A prominent increase in the IgM index, which reflects intrathecal B-cell stimulation, and a rise of IgG index, interleukin-6, and tumor necrosis factor-α in MMM patients provide preliminary evidence for a local intrathecal immune response triggered by melanoma cell invasion of the subarachnoid space.
Similar content being viewed by others
References
Wasserstrom WR, Glass JP, Posner JB: Diagnosis and treatment of leptomeningeal metastases from solid tumors: experience with 90 patients. Cancer 49: 759–772, 1982
Mendez IM, Del Maestro RF: Cerebral metastases from malignant melanoma. Can J Neurol Sci 15: 119–123, 1988
Byrne TN, Cascino TL, Posner JB: Brain metastasis from melanoma. J Neuro-Oncol 1: 313–317, 1983
Brega K, Robinson WA, Winston K, Wittenberg W: Surgical treatment of brain metastases in malignant melanoma. Cancer 66: 2105–2110, 1990
Weller M, Stevens A, Sommer N, Schabet M, Wiethölter H: Tumor cell dissemination triggers an intrathecal immune response in neoplastic meningitis. Cancer 69: 1475–1480, 1992
Weller M, Stevens A, Sommer N, Wiethölter H: Tumor necrosis factor-α in malignant melanomatous meningitis. J Neurol Neurosurg Psychiatry 55: 74, 1992
Bjerrum OW, Birgens HS: Measurement of beta-2-microglobulin in serum and plasma by an enzyme-linked immunosorbent assay (ELISA). Clin Chim Acta 155: 69–76, 1986
Weller M, Sommer N, Stevens A, Wiethölter H: Increased intrathecal fibronectin synthesis in bacterial and carcinomatous meningitis. Acta Neurol Scand 82: 138–142, 1990
Weller M, Stevens A, Sommer N, Melms A, Dichgans J, Wiethölter H: A comparative analysis of cytokine patterns in immunological, infectious, and oncological neurological disorders. J Neurol Sci 104: 215–221, 1991
Weller M, Stevens A, Sommer N, Wiethölter H, Dichgans J: CSF interleukins, immunoglobulins, and fibronectin in neuroborreliosis. Arch Neurol 48: 837–841, 1991
Reiber H, Felgenhauer K: Protein transfer at the blood cerebrospinal fluid barrier and the quantitation of the humoral immune response within the central nervous system. Clin Chim Acta 163: 319–328, 1987
Patel JK, Didolkar MS, Pickren JW, Moore RH: Metastatic pattern of malignant melanoma. A study of 216 autopsy cases. Am J Surg 135: 807–810, 1978
Merimsky O, Inbar M, Reider-Groswasser I, Chaitchik S: Brain metastases of malignant melanoma in interferon complete responders: clinical and radiological observations. J Neuro-Oncol 12: 137–140, 1992
Fitzpatrick TB, Sober AJ, Mihm MC: Malignant melanoma of the skin. In: Braun Wald E, Isselbacher KJ, Petersdorf RG, Wilson JD, Martin JB, Fauci AS (eds) Principles of Internal Medicine. McGraw Hill, New York, 1987, pp 1595–1597
Koh HK: Cutaneous melanoma. N Engl J Med 325: 171–182, 1991
Vassalli P: The pathophysiology of tumor necrosis factors. Annu Rev Immunol 10: 411–452, 1992
Sawada M, Kondo N, Suzumura A, Marunouchi T: Production of tumor necrosis factor-alpha by microglia and astrocytes in culture. Brain Research 491: 394–397, 1989
Chung IY, Benveniste EN: Tumor necrosis factor-α production by astrocytes. Induction by lipopolysaccharide, IFNγ, and IL-1β. J Immunol 144: 2999–3007, 1990
Lugassy C, Escande JP: Immunolocation of TNF-Alpha/cachectin in human melanoma cells: studies on co-cultivated malignant melanoma. J Invest Dermatol 96: 238–242, 1991
Zouboulis CC, Schröder K, Garbe C, Krasagakis K, Krüger S, Orfanos CE: Cytostatic and cytotoxic effects of recombinant tumor necrosis factor-α on sensitive human melanoma cellsin vitro may result in selection of cells with enhanced markers of malignancy. J Invest Dermatol 95: 223S-230S, 1990
Engelberts I, Stephens S, Francot GJM, Van der Linden CJ, Buurman WA: Evidence for different effects of soluble TNF-receptors on various TNF measurements in human biological fluids. Lancet 338: 515–516, 1991
Aderka D, Engelmann H, Maor Y, Brakebusch C, Wallach D: Stabilization of the bioactivity of tumor necrosis factor by its soluble receptors. J Exp Med 175: 323–329, 1992
Møller B, Mogensen SC, Wendelboe C, Bendtzen K, Petersen CM: Bioactive and inactive forms of tumor necrosis factor-α in spinal fluid from patients with meningitis. J Infect Dis 163: 886–889, 1991
Weller M, Stevens A, Sommer N, Schabet M, Wiethölter H: Humoral CSF parameters in the differential diagnosis of hematologic CNS neoplasia. Acta Neurol Scand 86: 129–133, 1992
Schipper HI, Bardosi A, Jacobi C, Felgenhauer K: Meningeal carcinomatosis: origin of local IgG production in the CSF. Neurology 38: 413–416, 1988
Sharief MK, Keir G, Thompson EJ: Glutaraldehyde-enhanced immunofixation: a sensitive new method for detecting oligoclonal IgM. J Neuroimmunol 23: 149–156, 1989
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Weller, M., Stevens, A., Sommer, N. et al. Intrathecal IgM response in disseminated cerebrospinal metastasis from malignant melanoma. J Neuro-Oncol 16, 55–59 (1993). https://doi.org/10.1007/BF01324835
Issue Date:
DOI: https://doi.org/10.1007/BF01324835