Skip to main content
SpringerLink
Log in

Localization of factor VIII/von willebrand factor and glial fibrillary acidic protein in the hemangioblastoma: Implications for stromal cell histogenesis

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

Summary

The histogenesis of hemangioblastoma stromal cells is unresolved. Ultrastructural observations suggest that the stromal cells, endothelial cells, and pericytes that compose this neoplasm are all derived from angiogenic mesenchyme. The expression of factor VIII/von Willebrand factor (FVIII/vWF), a specific marker for endothelial cells, and of glial fibrillary acidic protein (GFAP), a specific marker for glial cells, was examined in 16 hemangioblastomas using the peroxidase-antiperoxidase immunohistochemical method. Endothelial cell staining for FVIII/vWF was intense in 14 tumors, weak in one, and absent in another. There was no stromal cell staining in any of the neoplasms. Process-bearing, GFAP-positive cells were observed near the tumor margin in 13 cases, and deeper in the neoplasm in 8. In two of these tumors there were also occasional GFAP-positive cells that lacked processes and had a vacuolated cytoplasm. Virtually all of the GFAP-positive cells were interpreted as trapped astrocytes rather than stromal cells. The lack of expression of FVIII/vWF by the stromal cells indicates that they are antigenically distinct from endothelial cells. Several alternatives for stromal cell histogenesis remain open. The stromal cells may be derived from endothelial cells that have undergone antigenic loss, or from angiogenic mesenchymal cells that do not express FVIII/vWF. Alternatively, the stromal cells may originate from nonangiogenic mesenchymal cells derived from the mesoderm or neuroectoderm.

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

  • Alitalo K, Keski-Oja J, Vaheri A (1981) Extracellular matrix proteins characterize human tumor cell lines. Int J Cancer 27:755–761

    Google Scholar 

  • Bailey OT, Ford R (1942) Sclerosing hemangiomas of the central nervous system: Progressive tissue changes in hemangioblastomas of the brain and in so-called angioblastic meningiomas. Am J Pathol 18:1–27

    Google Scholar 

  • Burger PC, Vogel FS (1976) Surgical pathology of the nervous system and its coverings. Wiley, New York

    Google Scholar 

  • Cancilla PA, Zimmerman HM (1965) The fine structure of a cerebellar hemangioblastoma. J Neuropathol Exp Neurol 24:621–628

    Google Scholar 

  • Castaigne P, David M, Pertuiset B, Escourolle R, Poirier J (1968) L'ultrastructure des hemangioblastomes du systeme nerveux central. Rev Neurol (Paris) 118:5–26

    Google Scholar 

  • Cervos-Navarro J (1971) Elektronenmikroskopie der Hamangioblastome des ZNS und der angioblastischen Meningiome. Acta Neuropathol (Berl) 19:184–207

    Google Scholar 

  • Chaudhry AP, Montes M, Cohn GA (1978) Ultrastructure of cerebellar hemangioblastoma. Cancer 42:1834–1850

    Google Scholar 

  • Cramer F, Kimsey W (1952) The cerebellar hemangioblastomas: Review of fifty-three cases, with special reference to cerebellar cysts and the association of polycythemia. Arch Neurol Psychiatry 67:237–252

    Google Scholar 

  • Cushing H, Bailey P (1928) Tumors arising from the blood vessels of the brain: Angiomatous malformations and hemangioblastomas. Thomas, Springfield, IL

    Google Scholar 

  • Davidsohn I (1972) Early immunologic diagnosis and prognosis of carcinoma. Am J Clin Pathol 57:715–730

    Google Scholar 

  • Deck JHN, Eng LF, Bigbee J, Woodcock SM (1978) The role of glial fibrillary acidic protein in the diagnosis of central nervous system tumors. Acta Neuropathol (Berl) 42:183–190

    Google Scholar 

  • Deck JHN, Rubinstein LJ (1981) Glial fibrillary acidic protein in stromal cells of some capillary hemangioblastomas: Significance and possible implications of an immunoperoxidase study. Acta Neuropathol (Berl) 54:173–181

    Google Scholar 

  • Friedland J, Setton C, Silverstein E (1978) Induction of angiotensin converting enzyme in human monocytes in culture. Biochem Biophys Res Commun 83:843–849

    Google Scholar 

  • Hovi T, Mosher D, Vaheri A (1977) Cultured human monocytes synthesize and secrete α2-macroglobulin. J Exp Med 145:1580–1589

    Google Scholar 

  • Hoyer LW (1981) The factor VIII complex: Structure and function. Blood 58:1–13

    Google Scholar 

  • Hoyer LW, de los Santos RP, Hoyer JR (1973) Antihemophilic factor antigen: Localization in endothelial cells by immunofluorescent microscopy. J Clin Invest 52:2737–2744

    Google Scholar 

  • Hurth M (1975) Les hemangioblastomes intrarachidiens. Neurochirurgie [Suppl 1] 21:1–136

    Google Scholar 

  • Isaacson P, Jones DB, Judd MA (1979) α1-antitrypsin in human macrophages. Lancet 2:964–965

    Google Scholar 

  • Ishwar S, Taniguchi RM, Vogel FS (1971) Multiple supratentorial hemangioblastomas: Case study and ultrastructural characteristics. J Neurosurg 35:396–405

    Google Scholar 

  • Jaffe EA (1977) Endothelial cells and the biology of factor VIII. N Engl J Med 296:377–383

    Google Scholar 

  • Jaffe EA, Hoyer LW, Nachman RL (1973) Synthesis of antihemophilic factor antigen by cultured human endothelial cells. J Clin Invest 52:2757–2764

    Google Scholar 

  • Jaffe EA, Hoyer LW, Nachman RL (1973) Synthesis of von Willebrand factor by cultured human endothelial cells. Proc Natl Acad Sci USA 71:1906–1909

    Google Scholar 

  • Jakobiec FA, Font RL, Johnson FB (1976) Angiomatosis retinae: An ultrastructural study and lipid analysis. Cancer 38:2042–2056

    Google Scholar 

  • Jellinger K, Denk II (1974) Blood group isoantigens in angioblastic meningiomas and hemangioblastomas of the central nervous system. Virchows Arch A [Pathol Anat] 364:137–144

    Google Scholar 

  • Kawamura J, Garcia JH, Kamijyo Y (1973) Cerebellar hemangioblastoma: Histogenesis of stroma cells. Cancer 31:1528–1540

    Google Scholar 

  • Kepes JJ, Rengachary SS, Lee SH (1979) Astrocytes in hemangioblastomas of the central nervous system and their relationship to stromal cells. Acta Neuropathol (Berl) 47:99–104

    Google Scholar 

  • Lindau A (1926) Studien über Kleinhirncysten: Bau, Pathogenese und Beziehungen zur Angiomatosis Retinae. Acta Pathol Microbiol Scand [Suppl] 1:1–128

    Google Scholar 

  • Lindau A (1931) Discussion on vascular tumours of the brain and spinal cord. Proc R Soc Med 24:363–370

    Google Scholar 

  • Madri JA, Dreyer B, Pitlick FA, Furthmayr H (1980) The collagenous components of the subendothelium: Correlation of structure and function. Lab Invest 43:303–315

    Google Scholar 

  • McComb RD, Jones TR, Pizzo SV, Bigner DD (1982) Specificity and sensitivity of immunohistochemical detection of factor VIII/von Willebrand factor antigen in formalin-fixed paraffin-embedded tissue. J Histochem Cytochem (in press)

  • McGovern VJ, Wyke BD (1948) Hemangioxanthoma of the brain: A study of eight cases of so-called “pseudoxanthomatous” hemagioblastoma. Med J Aust 1:297–302

    Google Scholar 

  • Morahan PS (1980) Macrophage nomenclature: Where are we going? J Reticuloendothel Soc 27:223–245

    Google Scholar 

  • Mukai K, Rosai J, Burgdorf WHC (1980) Localization of factor VIII-related antigen in vascular endothelial cells using an immunoperoxidase method. Am J Surg Pathol 4:273–276

    Google Scholar 

  • Nachman R, Levine R, Jaffe EA (1977) Synthesis of factor VIII antigen by cultured guinea pig megakaryocytes. J Clin Invest 60:914–921

    Google Scholar 

  • Noden DM (1978) The control of avian cephalic neural crest cytodifferentiation. I. Skeletal and connective tissues. Dev Biol 67:296–312

    Google Scholar 

  • Olivecrona H (1952) The cerebellar angioreticulomas. J Neurosurg 9:317–330

    Google Scholar 

  • Pinkas GS, Said JW (1977) Profile of intracytoplasmic lysozyme in normal tissues, myeloproliferative disorders, hairy cell leukemia, and other pathologic processes: An immunoperoxidase study of paraffin sections and smears. Am J Pathol 89:351–366

    Google Scholar 

  • Roussy G, Oberling C (1930) Les tumeurs angiomateuses des centres nerveux. Presse Med 38:179–185

    Google Scholar 

  • Russell DS, Rubinstein LJ (1977) Pathology of tumours of the nervous system. 4th edn. Williams and Wilkins, Baltimore

    Google Scholar 

  • Sensenig EC (1951) The early development of the meninges of the spinal cord in human embryos. Contrib Embryol 134:145–158

    Google Scholar 

  • Silver ML, Hennigar G (1952) Cerebellar hemangioma (hemangioblastoma): A clinicopathological review of 40 cases. J Neurosurg 9:484–494

    Google Scholar 

  • Spence AM, Rubinstein LJ (1975) Cerebellar capillary hemangioblastoma: Its histogenesis studied by organ culture and electron microscopy. Cancer 35:326–341

    Google Scholar 

  • Timpl R, Wick G, Gay S (1977) Antibodies to distinct types of collagens and procollagens and their application in immunohistology. J Immunol Methods 18:165–182

    Google Scholar 

  • Weston JA (1970) The migration and differentiation of neural crest cells. Adv Morphogen 8:41–114

    Google Scholar 

  • Wisoff HS, Suzuki Y, Llena JF, Fine DIM (1978) Extramedullary hemangioblastoma of the spinal cord: Case report. J Neurosurg 48:461–464

    Google Scholar 

  • Wyburn-Mason R (1943) The vascular abnormalities and tumours of the spinal cord and its membranes. Kimpton, London

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Dept. of Pathology, Duke University Medical Center, 27710, Durham, NC, USA

    R. D. McComb, T. R. Jones, S. V. Pizzo & D. D. Bigner

  2. Dept. of Biochemistry, Duke University Medical Center, 27710, Durham, NC, USA

    S. V. Pizzo

Authors
  1. R. D. McComb
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. R. Jones
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. V. Pizzo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D. D. Bigner
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Supported by Grants CA-11898 and CA-22790 from the National Cancer Institute, HL-24066 from the National Heart, Lung, and Blood Institute, and IM-150 from the American Cancer Society. R.D.M. was supported by Training Grant 5T32 GM-0740304 from The National Institute of General Medical Services

Rights and permissions

Reprints and permissions

About this article

Cite this article

McComb, R.D., Jones, T.R., Pizzo, S.V. et al. Localization of factor VIII/von willebrand factor and glial fibrillary acidic protein in the hemangioblastoma: Implications for stromal cell histogenesis. Acta Neuropathol 56, 207–213 (1982). https://doi.org/10.1007/BF00690637

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00690637

Key words

Search

Navigation