Studies in comparative neuropathology. I. Gliomas of the domestic fowl: their pathology with special reference to histogenesis and pathogenesis; and their relationship to other diseases

1. Fowl glioma has erroneously been classified as astrocytoma. 2. Two chief variants occur, more rarely astroblastoma and much more commonly a glioma closely related structurally to glioblastoma (spongioblastoma) multiforme of man, but in general more slowly growing. This commoner type must either be identified for purposes of classification with low-grade glioblastoma multiforme or assessed as intermediate between astroblastoma and glioblastoma. 3. "Microcystic degeneration" leading to cystic cavitation of avian gliomas is associated with the secretory ability of neoplastic glia cells. This secretion is often of demonstrably mucinous nature. The question is raised whether this phenomenon may perhaps be merely an exaggeration of the normal physiology of glia. 4. The growth of avian gliomas occurs overwhelmingly by conversion of neighbouring (adult) astrocytes to tumour cells. 5. The histopathology of a non-purulent disseminated perivascular encephalitis of fowls has been closely studied and is identical with that of the brain tissue at the spreading margin of glioma. 6. Very commonly these focal inflammatory lesions exist side by side with glioma in the same brain. 7. All possible gradations occur between these inflammatory foci and glioma. The earliest gliomas of fowls have been shown to be nothing but encephalitic foci in which glia proliferation becomes exaggerated and predominant over haematogenous cellular infiltrative changes. 8. The reacting marginal brain tissue around fowl glioma is identical in all details of its histopathology with this chronic perivascular encephalitis. Thus not only does glioma arise from encephalitis, but its continued growth and spread are similarly due to conversion of chronically inflamed brain tissue at its periphery into tumour tissue. 9. The very common occurrence of multiplicity of avian gliomas is explained as due to the progression of multiple scattered pre-existent encephalitic foci to tumours. 10. The characteristic lobulation of avian glioma is explained as due to an initial concentration of encephalitic foci which fuse as they become converted into gliomas. 11. Multiplicity of avian glioma should not be thought of as a secondary multiplicity Although gliomas may break into the ventricles, there is no evidence whatever of a spread by transplantation of tumour cells transported by the C.S.F., or by any other means. On the other hand, each of the multiple tumours is primary and bas arisen from a pre-existent focus of encephalitis. 12. The protrusion of gliomas into the ventricles is due to prior location in or near the ventricular walls of encephalitic foci which later become converted to gliomas. 13. The ependymal cells lining such stimulated ventricles readily de-differentiate into ependymal spongioblasts, but such cells have not been observed to participate in neoplasia in birds. 14. All gradations exist between the non-purulent encephalitic foci mentioned and purulent encephalitis including cerebral abscess. 15. All gradations occur between non-purulent encephalitic (and especially meningo-encephalitic) foci and lymphocytoma of the C.N.S.- or in cases where it is the plasma cell transformation of lymphocytes which becomes predominant- between encephalitis and plasmacytoma. 16. The occurrence of haemangioblastoma of the brain of the fowl is reported. The idea is entertained that these tumours also are related to glioma in the sense that they too may arise as encephalitic foci. 17. The proliferation of haematogenous infiltrating cells in gliomas as well as in disseminated meningo-encephalitis may reach neoplastic grade Thus from foci of leptomeningitis, lymphocytoma may arise and invade the brain. Neoplastic proliferation of lymphocytes in glioma lead to a variant designated glioma lymphomatosum. Neoplastic proliferation of the emigrated haematogenous monocytes gives rise to other mixed tumours designated glioma monoblastomatosum. 18. In four cases of avian glioma [three of the present author's and one of Fox (1912)] there have been concomitant liver tumours of a peculiar type. These - as might have been anticipated - are not metastatic gliomas in the liver(!) In my own cases they were cholangiocellular adenocarcinoma, cholangiocellular carcinoma, or mixed hepatocellular and cholangiocellular adenoma or adenocarcinoma; in all cases admixed with myelocytomatous neoplasia. It is suspected that these unusual findings are to be explained by the assumption that an unknown factor causing glioma (or encephalitis) may in some cases operate simultaneously on the liver, and that much more constantly in the liver than has above been mentioned in the C.N.S., this factor tends to evoke simultaneous neoplastic proliferation of emigrated haematogenous cells. 19. The relationship of a spectacular case of diffuse gliosis of the brain to glioma has been discussed. 20. Avian glioma (as well as the related lesions of non-purulent and purulent encephalitis, lymphocytomatous tumours and solid haemangioblastomas of the C.N.S., and the peculiar concomitant liver neoplasms) is characterised by the presence of an iron-containing pigment responsible for a peculiar orange to yellow coloration of all these lesions. The author believes this pigment to be of great significance, indeed that it is derived from a parasitic agent present in these lesions. 21. The theory of origin of gliomas from embryonal cells which recapitulate their ontogenetic ancestry by differentiation towards adult types is false in the case of gliomas of birds. These gliomas on the contrary arise from previously adult cells which de-differentiate into more primitive cells - a " recapitulation in reverse order" of their embryonic ancestry. 22. A suggested pathogenesis of avian glioma and related lesions has been developed in considerable detail. 23. The histopathological, histogenetic, and pathogenetic observations suggested strongly that avian glioma is a response to some noxa which continues to spread in the brain in advance of the tumour. This led to a search for the presence of a visible agent associated with glioma and related lesions of the fowl and also later in. human gliomas. Preliminary accounts of the results of this search have been published and fuller reports are in preparation.