Skip to main content
SpringerLink
Log in

Studies on experimental malignant nerve sheath tumors maintained in tissue and organ culture systems

III. Melanin pigment and melanogenesis in experimental neurogenic tumors: a reappraisal of the histogenesis of pigmented nerve sheath tumors

  • Original Investigations
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Summary

Four melanin pigment-containing intracranial tumors were found in three Long-Evans rats in the course of experimental oncogenesis by transplacental ethylnitrosourea (ENU). One of them was a leptomeningeal melanoma. Aside from the presence of scattered melanin-pigmented cells, the other three had the typical histological features of ENU-induced malignant nerve sheath tumors. Two of the three tumors were studied by electron microscopy and in tissue and organ culture systems. One of them demonstrated progressive melanogenesis in vitro; the other failed to produce more melanin and showed increasing differentiation, with a Schwannoma-like pattern by light microscopy. Melanosomes and premelanosomes were identified in both tumors by electron microscopy; the other fine structural features were those of malignant Schwannomas.

These observations are relevant to the controversy on the histogenesis of pigmented nerve sheath tumors occasionally encountered in man and on the relationship of these tumors to pigmented nevi. The findings in the present study support the view of Masson that neoplastic nerve sheath cells are capable of melanogenesis.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Bednář, B.: Storiform neurofibromas of the skin, pigmented and nonpigmented. Cancer10, 368–376 (1957)

    Google Scholar 

  2. Bednář, B.: Storiform neurofibroma in the core of naevocellular naevi. J. Path.101, 199–201 (1970)

    Google Scholar 

  3. Benevolenskava, S. V., Staroverova, N. S.: On malignization of rat fibroblasts in tissue culture. Acta Un. int. Cancr.19, 624–628 (1963)

    Google Scholar 

  4. Bergdahl, L., Boquist, L., Liliequist, B., Thulin, C.-A., Tovi, D.: Primary melanoma of the central nervous system. A report of 10 cases. Acta neurochir. (Wien)26, 139–149 (1972)

    Google Scholar 

  5. Bird, C. C., Willis, R. A.: The histogenesis of pigmented neurofibromas. J. Path.97, 631–637 (1969)

    Google Scholar 

  6. Conley, F. K., Rubinstein, L. J., Spence, A. M.: Studies on experimental malignant nerve sheath tumors maintained in tissue and organ culture systems. II. Electron microscopy observations. Acta neuropath. (Berl.) (in press)

  7. Costa, J., Rosai, J., Philpott, G. W.: Pigmentation of “amelanotic” melanoma in culture. A finding of diagnostic relevance. Arch. Path.95, 371–373 (1973)

    Google Scholar 

  8. Cravioto, H., Weiss, J. F., Weiss, E. de C., Goebel, H. H., Ransohoff, J.: Biologica characteristics of peripheral nerve tumors induced with ethylnitrosourea. Acta neuropath. (Berl.)23, 265–280 (1973)

    Google Scholar 

  9. Dastur, D. K., Sinh, G., Pandya, S. K.: Melanotic tumor of the acoustic nerve. Case report. J. Neurosurg.27, 166–170 (1967)

    Google Scholar 

  10. Druckrey, H., Ivankovic, S., Preussmann, R., Zülch, K. J., Mennel, H. D.: Selective induction of malignant tumors of the nervous system by resorptive carcinogens. In: The experimental biology of brain tumors (eds. W. M. Kirsch, E. Grossi-Paoletti and P. Paoletti), pp. 85–147. Springfield, Ill.: Ch. C Thomas 1972

    Google Scholar 

  11. Egeberg, J., Jensen, O. A.: Malignant melanomas of the human choroid and ciliary body. A comparison of light microscopical and ultrastructural morphology. Acta path. microbiol. scand., Sect. A,80, 519–538 (1972)

    Google Scholar 

  12. Fortner, J. G., Allen, A. C.: Comparative oncology of melanomas in hamsters and man. In: Pigment cell biology (ed. M. Gordon), pp. 85–98. New York: Academic Press 1959

    Google Scholar 

  13. Gey, G. O.: Cytological and cultural observations on transplantable rat sarcomata produced by the inoculation of altered normal cells maintained in continuous culture. Cancer Res.1, 737 (1941)

    Google Scholar 

  14. Gey, G. O., Gey, M. K., Firor, W. M., Self, W. O.: Cultural and cytologic studies on autologous normal and malignant cells of specific in vitro origin. Conversion of normal into malignant cells. Acta Un. int. Cancr.6, 706–712 (1949)

    Google Scholar 

  15. Gibson, J. B., Burrows, D., Weir, W. P.: Primary melanoma of the meninges. J. Path. Bact.74, 419–438 (1957)

    Google Scholar 

  16. Graham, D. I., Paterson, A., McQueen, A., McQueen, A. Milne, J. A., Urich, H.: Melanotic tumours (blue naevi) of spinal nerve roots. J. Path.118, 83–89 (1976)

    Google Scholar 

  17. Grossi-Paoletti, E., Paoletti, P., Schiffer, D., Fabiani, A.: Experimental brain tumors induced in rats by nitrosourea derivatives. Part 2. Morphological aspects of nitrosoethylurea tumors obtained by transplacental induction. J. neurol. Sci.11, 573–581 (1970)

    Google Scholar 

  18. Harkin, J. C., Reed, R. J.: Tumors of the peripheral nervous system. Atlas of tumor pathology, second series, fasc. 3. Washington, D.C.: Armed Forces Institute of Pathology 1969

    Google Scholar 

  19. Hodson, J. J.: An intra-osseous tumour combination of biological importance-invasion of a melanotic schwannoma by an adamantinoma. J. Path. Bact.82, 257–266 (1961)

    Google Scholar 

  20. Hodson, J. J.: A morphological study of dermal melanocytes and cytocrine activity in relation to certain Schwann cells and epithelial cells. J. Path. Bact.82, 267–272 (1961)

    Google Scholar 

  21. Hu, F.: Proliferation and melanin production in melanoma cell cultures. In: Pigmentation: Its genesis and biologic control (ed. V. Riley), pp. 479–496. New York: Appleton-Century-crofts 1972

    Google Scholar 

  22. Husband, E. M., Conway, A. D., Curran, R. C.: Ultrastructural differences between pigmented naevi and malignant melanomas. J. Path. Bact.101, Proc. Path. Soc. Great Britain and Ireland, XVII-XVIII (1970)

    Google Scholar 

  23. Ishikawa, T., Nishi, T., Shimada, H., Yamaguchi, K.: Two cases of mélanose neurocutanée with development of malignant melanoma: a microspectrophotometric and electron microscopic study. Gann66, 277–289 (1975)

    Google Scholar 

  24. Koestner, A., Swenberg, J. A., Wechsler, W.: Transplacental production with ethylnitrosourea of neoplasms of the nervous system in Sprague-Dawley rats. Amer. J. Path.63, 37–56 (1971)

    Google Scholar 

  25. Koestner, A., Swenberg, J. A., Wechsler, W.: Experimental tumors of the nervous system induced by resorptive N-nitrosourea compounds. Progr. exp. Tumor Res.17, 9–30 (1972)

    Google Scholar 

  26. Lapis, K., Radnót, M.: Surface properties of human melanoma cells. Amer. J. Ophthal.71, 740–750 (1971)

    Google Scholar 

  27. Leopold, J. G., Richards, D. B.: Cellular blue naevi. J. Path. Bact.94, 247–255 (1967)

    Google Scholar 

  28. Limas, C., Tio, F. O.: Meningeal melanocytoma (“melanotic meningioma”). Its melanocytic origin as revealed by electron microscopy. Cancer30, 1286–1294 (1972)

    Google Scholar 

  29. Lund, H. Z., Stobbe, G. D.: The natural history of the pigmented nevus; factors of age and anatomic location. Amer. J. Path.25, 1117–1155 (1949)

    Google Scholar 

  30. Mandybur, T. I.: Melanotic nerve sheath tumors. J. Neurosurg.41, 187–192 (1974)

    Google Scholar 

  31. Masson, P.: Les naevi pigmentaires, tumeurs nerveuses Ann. Anat. path.3, 417–453, 657–696 (1926)

    Google Scholar 

  32. Masson, P.: Neuro-nevi “bleu”. Arch. De Vecchi Anat. pat.14, 1–28 (1950)

    Google Scholar 

  33. Masson, P.: My conception of cellular nevi. Cancer4, 9–38 (1951)

    Google Scholar 

  34. Masson, P.: Melanogenic system: nevi and melanomas. Path. Ann.2, 351–397 (1967)

    Google Scholar 

  35. Mawdesley-Thomas, L. E., Newman, A. J.: Some observations on spontaneously occurring tumours of the central nervous system of Sprague-Dawley derived rats. J. Path.112, 107–116 (1974)

    Google Scholar 

  36. Mennel, H. D., Zülch, K. J.: Formale Pathogenese experimenteller Hirntumoren. Acta neuropath. (Berl.)21, 140–153 (1972)

    Google Scholar 

  37. Mennel, H. D., Zülch, K. J.: Zur Morphologie transplacentar erzeugter neurogener Tumoren beim Goldhamster. Acta neuropath. (Berl.)21, 194–203 (1972)

    Google Scholar 

  38. Merkow, L. P., Burt, R. C., Hayeslip, D. W., Newton, F. J., Slifkin, M., Pardo, M.: A cellular and malignant blue nevus: a light and electron microscopic study. Cancer24, 888–896 (1969)

    Google Scholar 

  39. Mishima, Y.: Melanotic tumors. In: Ultrastructure of normal and abnormal skin (ed. A. S. Zelickson), pp. 388–424. Philadelphia: Lea and Febiger 1967

    Google Scholar 

  40. Nakai, T., Rappaport, H.: A study of the histogenesis of experimental melanotic tumors resembling cellular blue nevi: the evidence in support of their neurogenic origin. Amer. J. Path.43, 175–199 (1963)

    Google Scholar 

  41. Pappenheim, E., Bhattacharji, S. K.: Primary melanoma of the central nervous system. Arch. Neurol. (Chic.)7, 101–113 (1962)

    Google Scholar 

  42. Rubinstein, L. J., Herman, M. M.: Studies on the differentiation of human and experimental gliomas in organ culture systems. Recent Res. Cancer Res.,51, 35–51. New York: Springer 1975

    Google Scholar 

  43. Rubinstein, L. J., Herman, M. M., Foley, V. L.: In vitro characteristics of human glioblastomas maintained in organ culture systems. Light microscopy observations. Amer. J. Path.71, 61–80 (1973)

    Google Scholar 

  44. Rubinstein, L. J., Conley, F. K., Herman, M. M.: Studies on experimental malignant nerve sheath tumors maintained in tissue and organ culture systems. I. Light microscopy observations. Acta neuropath. (Berl.) (in press)

  45. Russell, D. S., Rubinstein, L. J.: Pathology of tumours of the nervous system, 3rd ed., p. 40, London: Edward Arnold 1971

    Google Scholar 

  46. Sanford, K. K.: “Spontaneous” neoplastic transformation of cells in vitro: some facts and theories. Nat. Cancer Inst. Monogr.26, 387–418 (1967)

    Google Scholar 

  47. Shillitoe, A. J.: Melanotic schwannoma. J. Path. Bact.90, 667–668 (1965)

    Google Scholar 

  48. Spence, A. M., Rubinstein, L. J.: Unpublished observations

  49. Stäubli, N., Loustalot, P.: Electron microscopy of transplantable melanotic and amelanotic hamster melanomas. Cancer Res.22, 84–88 (1962)

    Google Scholar 

  50. Stegmaier, O. C.: Natural regression of the melanocytic nevus. J. invest. Derm.32, 413–421 (1959)

    Google Scholar 

  51. Stegmaier, O. C., Jr., Montgomery, H.: Histopathologic studies of pigmented nevi in children. J. invest. Derm.20, 51–64 (1953)

    Google Scholar 

  52. Theodossiou, A., Segditsas, Th.: Über ein intraabdominal gelegenes melanotisches Schwannom. Zbl. allg. Path. path. Anat.114, 168–172 (1971)

    Google Scholar 

  53. Thust, R., Warzok, R., Batka, H.: Die Morphologie experimenteller Tumoren des Nervensystems in vitro. I. Transplazentar induzierte Tumoren des Nervus trigeminus der Ratte. Arch. Geschwulstforsch.40, 300–307 (1972)

    Google Scholar 

  54. Toshima, S., Moore, G. E., Sandberg, A. A.: Ultrastructure of human melanoma in cell culture. Electron microscopic studies. Cancer21, 202–216 (1968)

    Google Scholar 

  55. Unna, P. G.: The histopathology of the diseases of the skin, translated by N. Walker, pp. 1129–1140. New York: MacMillan & Co. 1896

    Google Scholar 

  56. Wechsler, W., Kleihues, P., Matsumoto, S., Zülch, K. J., Ivankovic, S., Preussmann, R., Druckrey, H.: Pathology of experimental neurogenic tumors chemically induced during prenatal and postnatal life. In: Research in the experimental and clinical aspects of brain tumors (ed. L. C. Scheinberg). Ann. N. Y. Acad. Sci.159, 360–408 (1969)

  57. Wellings, S. R., Siegel, B. V.: Electron microscopic studies on the subcellular origin and ultrastructure of melanin granules in mammalian melanomas. Ann. N. Y. Acad. Sci.100, 548–568 (1963)

    Google Scholar 

  58. Zelickson, A. S.: The fine structure of the human melanotic and amelanotic malignant melanoma. J. invest. Derm.39, 605–613 (1962)

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology (Neuropathology), Stanford University School of Medicine, 94305, Stanford, California, USA

    Alexander M. Spence, Lucien J. Rubinstein, Frances K. Conley & Mary M. Herman

  2. Euphrat Laboratories for Neurosurgery, Stanford University School of Medicine, 94305, California, Stanford, USA

    Alexander M. Spence, Lucien J. Rubinstein, Frances K. Conley & Mary M. Herman

Authors
  1. Alexander M. Spence
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lucien J. Rubinstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Frances K. Conley
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mary M. Herman
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Supported by Research Grant CA 11689 from the National Cancer Institute, Graduate Neuropathology Training Grant 5 T01 NS 5500-09 and by Special Fellowships 1F03 NS 55632 (A.M.S.) and 1F11 NS 2629 (F.K.C.) from the National Institute of Neurological Diseases and Stroke, U.S.P.H.S.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Spence, A.M., Rubinstein, L.J., Conley, F.K. et al. Studies on experimental malignant nerve sheath tumors maintained in tissue and organ culture systems. Acta Neuropathol 35, 27–45 (1976). https://doi.org/10.1007/BF00688941

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00688941

Key words

Search

Navigation