Tumours of the nervous system

Bull. Org. mond. Sant} 1974, 50, 53-69 Bull. Wid Hlth Org.J V. Tumours of the nervous system R. FANKHAUSER,1 H. LUGINBOHL,2 & J. T. McGRATH 3 Tumours of the nervous system of animals are not as rare as has been commonly believed. In dogs, especially the brachycephalic breeds, these tumours occur as frequently as in man. The tumours are grouped according to tissue of origin as follows: nerve cells, neuroepithelium, glia, peripheral nerves and nerve sheaths, meninges and vessels, the pineal and pituitary glands, and the craniopharyngeal duct. Tumours of the glia are relatively common and are divided into the following types: astrocytoma, oligodendroglioma, glio- blastoma, spongioblastoma, medulloblastoma, and unclassified gliomas. Neoplasms of the nervous system in animals have long been considered to be extremely rare. Whereas this might be true of farm animals, it is certainly not true of dogs, especially certain brachycephalic breeds, in which tumours are as common as in man. In farm animals more accurate methods of investi- gation of large series are necessary to obtain reliable information on the occurrence of tumours of the central nervous system and of the various types. For several reasons, clinical examination is not a very reliable means of detecting these tumours, espe- cially in farm animals. The high incidence of brain tumours, particularly gliomas, in boxers and Boston terriers has often been thought to be associated with brachycephaly, but possibly this is only a coincidence, as boxers are also abnormally susceptible to tumours elsewhere. This classification is based on a study of approxi- mately 1 000 tumours of the nervous system of animals. Owing to the limitations of space it deals only with the more typical aspects and does not discuss controversial points. It does not cover tu- mours of various soft tissues and paraganglia or secondary tumours. We have been handicapped by the lack of biological information, such as detailed clinical history and prolonged follow-up, and post- surgical behaviour, which is an important factor in the classification of human tumours. Statistical data are similarly lacking. Because it has been impossible to relate the numbers of particular types of tumour 1Leiter, Institut fur Vergleichende Neurologie, Univer- sitat Bern, Berne, Switzerland. 'Direktor, Institut fur Tierpathologie der Universitat Bern, Berne, Switzerland. 'Head, Laboratory of Pathology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pa., USA. to population or even numbers of autopsies, the frequency of each type is indicated only in general terms relative to the total number of nervous system tumours studied. Our intention is to outline the most characteristic aspects of the clearly defined groups of tumours of the nervous system. It has not been possible to consider variations of the histological picture, often observed within one and the same tumour, and details about the unclassified or controversial forms- especially in the glioma group. Therefore, certain differences that exist between nervous tumours in animals and in man, and between spontaneous and experimentally produced tumours in animals, may be understated. The prevalence of mesenchymal tumours in animals (with the exception of brachy- cephalic dogs) compared with that in man, and the pronounced tendency to " mesenchymation " (pro- liferation of vessels and accompanying mesenchymal tissue) in animal gliomas must be stressed. GRADING OF TUMOURS OF THE NERVOUS SYSTEM Kernohan et al.4 proposed, within the morpho- logically defined types of tumour of the nervous system, a grading according to increasing degrees of malignancy, judged by the following features: dedif- ferentiation, pleomorphism, mitotic index, invasive- ness, regressive changes, and metastasis in the cere- brospinal fluid pathways. In man, such a grading can be correlated with biological data and is there- fore a useful guide for prognosis in routine diagnosis. Since such correlations are generally lacking for ' KERNOHAN, J. W. ET AL. A simplified classification of the gliomas. Proceedings of the Staff Meetings of the Mayo Clinic, 24 (3): 71-75 (1949). 3167 -53 R. FANKHAUSER ET AL. animals, attempts to grade animal brain tumours are little more than interesting exercises without a biological basis. TECHNICAL REMARKS In order to obtain reliable results in examining tumours of the nervous system, the whole central nervous system and related structures must be removed and fixed in an appropriate manner. It is preferable to fix the intact brain, spinal cord, and other tissues in large jars with sufficient quantities of neutral buffered formol-saline (1: 9) on a bed of cotton wool. Generally the material should not be cut before it has been properly fixed, which needs two or more days depending on the size of the organ. With large brains (e.g., ox, horse), one or two frontal (coronal) sections may be useful in allowing quicker penetration of the fixative. When properly fixed, the brain can be cut into regular frontal slices 5-10 mm thick, depending on its size. With this technique, distortion can be avoided and, although the colours may change, haemorrhage, liquefaction, mucinous degeneration, and oedema can easily be recognized. For small brains (e.g., dog, cat), embedding of whole coronal blocks containing the tumour is recom- mended. With large brains, or if the technical facili- ties are limited, blocks of sufficient size should be taken from several (5-10) sites together with an appropriate part of neighbouring brain substance to facilitate topographical orientation. Even in this case, it is strongly recommended that all blocks should be cut in the frontal plane. HISTOLOGY Under the conditions outlined above, most tu- mours can be diagnosed satisfactorily by means of sections stained with haematoxylin-eosin. However, sometimes a reticulum stain may be required for the critical differentiation of neuroectodermal and meso- dermal tumours. We routinely use the following set of stains: haematoxylin-eosin, Goldner's trichrome, Wilder's or Gomori's reticulum stain, luxol-fast blue- cresyl violet, and luxol-fast blue-Holmes silver ni- trate, and for special purposes yet other methods may be used. Maurer's impregnation method for astrocytes on frozen sections works very satisfac- torily. In general, an excellent haematoxylin-eosin stain is probably more useful than a series of special stains not performed efficiently. HISTOLOGICAL CLASSIFICATION AND NOMENCLATURE OF TUMOURS OF THE NERVOUS SYSTEM I. TUMOURS OF NERVE CELLS A. GANGLIOCYTOMA II. TUMOURS OF NEUROEPITHELIUM A. EPENDYMOMA B. PLEXUS PAPILLOMA III. TUMOURS OF GLIA A. ASTROCYTOMA B. OLIGODENDROGLIOMA C. GLIOBLASTOMA D. SPONGIOBLASTOMA E. MEDULLOBLASTOMA F. GLIOMAS, UNCLASSIFIED IV. TUMOURS OF PERIPHERAL NERVES AND NERVE SHEATHS A. NEURINOMA (SCHWANNOMA) B. NEUROFIBROMA C. NEUROFIBROSARCOMA V. TUMOURS OF THE MENINGES, VESSELS, AND OTHER MESODERMAL STRUCTURES A. MENINGIOMA B. ANGIOBLASTOMA C. SARCOMA D. RETICULOSIS VI. TUMOURS OF THE PINEAL AND PITUITARY GLANDS AND OF THE CRANIOPHARYNGEAL DUCT A. PINEALOMA B. PITUITARY ADENOMA C. CRANIOPHARYNGIOMA 54 NERVOUS SYSTEM DESCRIPTION OF TUMOURS I. TUMOURS OF NERVE CELLS A. Gangliocytoma (Fig. 1) These tumours contain more or less differentiated ganglioid cells. In the cases studied the tumour was located in the cerebellum. Gangliocytomas have been seen in dogs, but are very rare. II. TUMOURS OF NEUROEPITHELIUM A. Ependymoma (Fig. 2-4) These tumours are highly cellular and very vas- cular. The cells are usually uniform, with scant or invisible cytoplasm. Their nuclei are round to oval or slightly elongated, and are rich in chromatin. The nuclei may be arranged in groups somewhat resem- bling rosettes and there may be nucleus-free areas around vessel walls. Typical ependymal cells and classical rosette formation are seen only occasionally. The number of mitoses is variable. Haemorrhages of varying extent are often present, as well as mucinous and cystic degeneration and capillary proliferation, but to a somewhat lesser extent than in oligodendrogliomas. Ependymomas are topographically related to epen- dymal surfaces, mainly in the lateral ventricles and more rarely in the third or fourth ventricle. They are rather large, ill-defined, infiltrating tumours and cause extensive tissue damage. There may be inva- sion of ventricular system and meninges owing to metastasis in cerebrospinal fluid pathways. These tumours are soft, bulging, and grey-white to red on the cut surface. Ependymomas have been found in horses, cattle, dogs, and cats, but are rare. B. Plexus papilloma (Fig. 5) These tumours have an arborizing, vasculoconnec- tive tissue stroma covered by cuboidal or cylindrical epithelium, forming a more or less pronounced papilliform structure resembling the choroid plexus. Plexus papillomas may occur in the third, fourth, or lateral ventricles. Macroscopically they appear as well-circumscribed, expansive growths with a gra- nular-to-papillomatous appearance and are grey- white to red. Only occasionally do they show inva- sive, destructive growth or metastasis via the cerebro- spinal fluid pathways. They occur in dogs, without any predilection for brachycephalic breeds, and also in horses and cattle. They are moderately common. III. TUMOURS OF GLIA A. Astrocytoma (Fig. 6-9) These tumours are composed of rather loosely arranged, large or small cells, often with distinct ramifying processes. The nuclei are of varying size and form, but are often more rich in chromatin than are normal astrocytic nuclei. They appear to be intimately associated with the fibrillary network. Suckerfeet may be seen. Occasionally one sees large cells, rich in protoplasm, with nuclei of varying size, which may be regarded as a type of swollen astro- cyte. Fibrillary or protoplasmatic types of cells may dominate locally or generally or may be mixed together. The arrangement of the tumour cells is often not very dense and parts of the infiltrated parenchyma (e.g., neurons) may persist. The bound- aries are not sharp. The cells tend to be arranged around and along vessels. Many microhaemorrhages from thin-walled vessels and capillaries may occur, sometimes coalescing to form larger haemorrhagic areas. There may be mucinous degeneration, cyst- formation, and a mesenchymal vascular reaction similar to that seen in oligodendrogliomas. Astrocytomas are most commonly located in the piriform area in the dog, but also occur on the con- vexity of the cerebral hemispheres, the thalamus and hypothalamus, the midbrain, and rarely the cere- bellum and spinal cord. They appear as rather solid, grey-white tumours only poorly demarcated from the surrounding or infiltrated parenchyma, and some- times as a diffuse swelling of the affected area, with blurring of its structures. These tumours do not penetrate the ventricular system and do not metas- tasize. They occur in cattle, dogs, and cats, and are moderately common. B. Oligodendroglioma (Fig. 10, 11) These tumours are highly cellular, the cells being densely packed. The nuclei are rich in chromatin and round in shape, with clear perinuclear haloes producing a honeycomb appearance. The cells are often arranged in rows (especially in infiltrating areas at the periphery) or in semicircles. Occasionally the nuclei are oval or elongated. The tumours grow by infiltration and sometime infiltrate the meninges locally. Only exceptionally do they spread through cerebrospinal fluid pathways. There is pronounced proliferation of vessels, especially capillaries, with 55 R. FANKHAUSER ET AL. the formation of loops and glomerular-like struc- tures. There are many thin-walled sinusoidal vessels, giving rise to haemorrhages. Extensive mucinous degeneration and cyst formation occur, but necrosis is rare. Calcification is seen only occasionally. Many of these tumours may contain areas of diverse mor- phology, sometimes having local features suggestive of astrocytoma or ependymoma. Such neoplasms may be diagnosed as oligodendrogliomas, based on their most typical areas, or as glioblastomas or non- classifiable gliomas, according to the diverging histo- logical appearance of their individual parts. Oligodendrogliomas are nearly always located in the cerebral hemispheres and seem to originate from the white matter. They often break through the ventricular or meningeal surface. The tumours are usually of considerable size and are red, pink-red, or grey in colour. There are often extensive gelati- nous areas and haemorrhage. The tumours may be soft and the cut surface may collapse, but some parts may be more solid. They are sometimes dis- crete, but the borders with normal tissue may be indistinct. These tumours are common in dogs and a few cases have been reported in other species. C. Glioblastoma (Fig. 12-14) Histologically these tumours vary; in some, the cells are uniform. Nuclei are of varying size and giant cells with one or more nuclei may occur. There is infiltrating and destructive growth. Usually glio- blastomas are very vascular, with many abnormal thin-walled vessels and haemorrhages. There may be bands or irregular foci of necrosis, the latter often demarcated by pseudo-palisades of tumour cells. Capillary proliferation is similar to that in oligodendrogliomas. Glioblastomas may be located in the convexity of the cerebral hemispheres, in the piriform area, or in the thalamus and hypothalamus. Sometimes they are closely associated with inner surfaces (epen- dyma). Usually they are large and more or less cir- cumscribed, and present a rather striking picture owing to haemorrhage, necrosis, fatty degeneration, and mesenchymal reaction. Glioblastomas have been found fairly often in cattle, dogs, and pigs. D. Spongioblastoma (Fig. 15) The histology of these tumours is poorly defined. They infiltrate preexisting tissue. Their nuclei are elongated and sometimes arranged in rows. There are no sharp boundaries with surrounding tissues. There may be a dense network of vessels. Spongio- blastomas may be located near ependymal surfaces or the midline, in the brain stem, or in the cere- bellum. Occasionally, they are found in the optic nerve and tract. These very rare tumours have been reported in dogs, and there are unsubstantiated teports of their occurrence in goats and calves. E. Medulloblastoma (Fig. 16, 17) These tumours are uniform and highly cellular. The nuclei are densely packed, oval to carrot-shaped, and rich in chromatin. The cytoplasm is scanty and pale. There are many mitoses. Some tendency to form pseudo-rosettes may be seen. Pyknosis and karyorrhexis are common and widely distributed. Haemorrhages, liquefaction, and inflammatory re- action are absent or slight. These tumours are located almost exclusively in the cerebellum. They appear as soft, bulging, grey-red, and rather circumscribed tumours. Medulloblastomas compress or invade the fourth ventricle and infiltrate neighbouring struc- tures and meninges. They metastasize in the cerebro- spinal fluid pathways. These fairly common tumours have been seen in calves and dogs (mainly young animals), and in cats and pigs. F. Gliomas, unclassified Of the tumours in our series, 15-20% could not be classified in the system adopted. The percentage was higher in farm animals. Many of these tumours show different types of differentiation and suggest a topo- graphical relationship to the neighbourhood of the ventricular system. In so far as their neuroectodermal nature seems to be established (especially by the use of reticulin-staining methods), they may tentatively be called " undifferentiated gliomas or glioblasto- mas ". There are, however, remarkable differences between these tumours and glioblastoma multiforme, which is so frequent in man. IV. TUMOURS OF PERIPHERAL NERVES AND NERVE SHEATHS A. Neurinoma (schwannoma) (Fig. 18) These tumours consist of bands of densely packed cells with oval or elongated nuclei that have a medium or large chromatin content. The cells form an interlacing network that sometimes has charac- teristic features giving the appearance of a palm tree or herring shoal. These tumours show hardly any collagen or reticulin formation, in contrast to other tumours of peripheral nerves in animals (see Neurofibroma). Macroscopically, neurinomas appear 56 Fig. 1. Gangliocytoma, cerebellum, ganglioid cells interspersed with glial elements and vessels (dog). Fig. 3. Ependymoma, arrangement of the tumour cells more irregular than in Fig. 2 (dog). Fig. 2. Ependymoma, densely packed nuclei in bands around vessels, nucleus-free zones along vessels (dog). Fig. 4. Ependymoma (cow). Fig. 5. Plexus papilloma, ventricular wall at bottom Fig. 6. Astrocytoma; silver stain (boxer). (terrier). Fig. 7. Astrocytoma, parenchyma invaded by tumour cells of fibrillary type, and microhaemorrhages; silver stain (bulldog). Fig. 8. Astrocytoma, higher magnification of Fig. 7 (bulldog). Fig. 9. Astrocytoma, cerebellum, large cells of proto- plasmatic type, considerable polymorphism (pointer). Fig. 11. Oligodendroglioma, glomerulum-like struc- tures; silver stain (boxer). Fig. 1 0. Oligodendroglioma (boxer). Fig. 12. Glioblastoma (pig). Fig. 13. Glioblastoma, same case as Fig. 12 (pig). Fig. 15. Spongioblastoma (boxer). Fig. 14. Glioblastoma, considerable pleomorphism (pomeranian). Fig. 16. Medulloblastoma, several rosette-like struc- tures; luxol-fast blue-cresyl violet (cat). ,% 'Du.- - , -I j. . . Xf i Fig. 17. Medulloblastoma, cerebellum, tumour cells Fig. 18. Neurinoma (schwannoma) (dog). around or along vessels (calf). Fig. 19. Neurofibroma, nerve bundles rich in connective tissue; reticulum stain (ox). Fig. 20. Neurofibromatosis, brachial plexus, loose and densely arranged fibres; Goldner's trichrome (cow). Fig. 21. Neurofibrosarcoma, tumour infiltrating spinal ganglion (labrador). Fig. 23. Meningioma, cellular areas separated by vessels (dachshund). Fig. 22. Meningioma, endotheliomatous cells separ- ated by connective tissue; silver stain (cat). Fig. 24. Meningioma, fibroblastic area with cholesterol clefts (cat). Fig. 25. Angioblastoma (cat). * PA %. -_r. Fig. 27. Sarcoma of the brain (dog). Fig. 26. Angioblastoma (haemangioendothelioma), edge of tumour (pig). Fig. 28. Sarcoma of the brain, pleomorphism, and multi- nucleated cells (terrier). Fig. 29. Sarcoma of the brain, cells in network of reticular fibres; reticulum stain (dog). Fig. 31. Reticulosis, histiocyte-type cells around vessels, with " inflammatory" cells, necrosis of parenchyma Jairedale). Fig. 30. Reticulosis, tumour in parenchyma, in lepto- meninges, and around vessels; luxol-fast blue-cresyl violet (airedale). Fig. 32. Reticulosis, histiocytes and lymphoid cells in enlarged adventitial space (labrador). Fig. 33. Reticulosis, histiocytic and lymphoid cells along reticular fibres (cow). Fig. 35. Pinealoma, isomorphic (cow). Fig. 34. Reticulosis (microgliomatosis), cerebellum and leptomeninges (right) diffusely invaded by tumour (bull mastiff). Fig. 36. Pituitary adenoma, chromophobe type (dachs- hund). Fig. 37. Pituitary adenoma, eosinophilic type (cow). Fig. 38. Pituitary adenoma, fetal type, mitoses (collie). NERVOUS SYSTEM as ovoid or lobular, grey-white, rather solid masses. They are usually closely associated with the intra- cranial part of cranial nerves and often compress neighbouring parts of brain stem. Neurinomas are rare, but have been found in cattle and in dogs. B. Neurofibroma (Fig. 19, 20) These tumours are rich in connective tissue com- ponents and seem to originate from the endoneural and perineural connective tissue cells. There may be areas with a mainly neurinoma-like or a mainly fibroma-like appearance. The neurinoma-like areas consist of neurilemmoma-type cells with structures of repeating periodicity-bands, herring-bone, pali- sades, and whorls (Antoni type A). The cells are elongated and fusiform, and the nuclei are oval or elongated and fairly uniform, with finely distiibuted chromatin granules and 1-2 nucleoli. Regressive changes are rarely seen. Sometimes reticular struc- tures may be seen (Antoni type B). The fibroma-like areas show a dense, interwoven network of collagen fibres, with elongated, fusiform cells and nuclei of the fibroblast and fibrocyte type. There is no distinct pattern of cell arrangement except for concentric layers around nerve fibres or fibre bundles. In bovine neurofibromatosis, there may be large amounts of a gelatinous material between the fibrous layers of the proliferating endoneurium and perineurium, and the persisting nerve fibres (Fig. 20). Neurofibromas do not metastasize. Cases of a more dedifferentiated and histologically malignant aspect have been de- scribed as neurofibrosarcomas. Neurofibromas occur at the roots of cranial (tri- geminal or acoustic) and spinal nerves, spinal roote and ganglia, peripheral nerves, and sympathetic nerves. They appear as firm, grey-white, nodular, encapsulated growths, which eventually compress the brain or cord if located intracranially or intra- vertebrally. Peripheral location is rather rare and there it may be difficult to differentiate neurofibromas from simple fibromas. The morphological continuity with nerves must be established. Neurofibromas rep- resent the usual type of tumour of peripheral nerves in animals (cf. Neurinoma). They are fairly common, and have been seen mainly in cattle and dogs. C. Neurofibrosarcoma (Fig. 21) Continuity with a nerve has to be postulated for the differentiation of neurofibrosarcoma from fibro- sarcoma. Histologically, neurofibrosarcomas have the same characteristics as neurofibromas, but they show a higher degree of cellularity, pleomorphism, and anaplasia, a higher mitotic index, and a less regular arrangement of the cells. These tumours have been reported mainly in dogs, and rarely in other species (horse and cat). V. TUMOURS OF THE MENINGES, VESSELS, AND OTHER MESODERMAL STRUCTURES A. Meningioma (Fig. 22-24) The cellular structure is often not uniform, but a mixture of endotheliomatous and fibromatous areas, one or other type sometimes predominating. Pure angioblastic forms have not been observed in animals. The endotheliomatous type shows nests, whorls, and bands of meningothelial cells with large cytoplasmic bodies and elongated, oval, or twisted nuclei with peripheral arrangement of the chromatin. Typical whorls (onion-shaped figures) are formed by varying numbers of cells, from a few to several hundred. The cell bodies often appear without sharp boundaries, as a syncytial network. In the centre of whorls the cells may disintegrate. Here and in the more fibrous parts, calcifications occur. Hyaliniza- tion of connective tissue and deposition of fat, lipo- pigments, or cholesterol may be found, sometimes with reactive inflammatory infiltrations. There are usually no vessels in the centre of the whorls. The fibroblastic part is composed of strands, streams, and networks of fibre-forming, elongated cells. There may be regressive changes, haemorrhage, cavernous vas- cular formations, and infiltrative growth. Mitoses are sometimes (but not regularly) present. Meningiomas may be found in parasagittal areas, on the convexity of the cerebral hemispheres, in the cerebellar-tentorial area, on the spinal cord, and in the tela chorioidea of the third ventricle (cat). Soli- tary tumours have been found in dogs and other species and multiple tumours have been found in cats and occasionally cattle. The tumours grow under the dura mater and generally expand towards the brain, causing pressure atrophy and occasionally infiltrating. Rarely, there may be atrophy of over- lying structures. The tumours are generally solid- to-very-firm, unilobulated or multilobulated masses, grey-white, yellow, or red in colour. The surface is usually smooth, often encapsulated, and sometimes rough. On section, the appearance is usually grey- white and fibrous, sometimes with softer red, brown, or grey areas of haemorrhage and necrosis. There may be a sprinkling of cholesterol crystals or yellow foci of fatty degeneration and deposits of lipid pig- ment (cat). The tumours are adherent to the pia or 67 R. FANKHAUSER ET AL. the inner surface of the dura mater. Meningiomas are common in horses, cattle, sheep, dogs, and cats. B. Angioblastoma (Fig. 25, 26) These tumours consist of a network of interlacing strands of fusiform cells, with varying degrees of maturation towards becoming endothelial elements, surrounding blood-filled spaces. Some cells may form capillary rings. Angioblastomas are haemorrhagic tumours of varying size. They have been described as located in the cerebral hemispheres, the choroid plexus, and the medulla or spinal cord. Rare cases have been reported in horses, pigs, and dogs. C. Sarcoma (Fig. 27-29) The cells are densely packed. Small or large, round, oval, polygonal, or fusiform in shape, they have a close topographical relationship to a more or less dense reticulin network. Varying degrees of poly- morphism, with multinucleated and giant cells, may be observed in some cases. Mitoses are usually numerous. The tumours tend to infiltrate. Haemor- rhages may occur, but necrosis and mucinous degen- eration are absent. Macroscopically, sarcomas may be categorized according to location and extent: sarcoma of men- inges (circumscribed), sarcomatosis of meninges (dif- fuse), or sarcoma of the brain and cord. They are usually firm and grey or white. Often there are exten- sive haemorrhages. There are no predilection sites. These tumours are fairly common and have been reported in horses, cattle, dogs, and cats. D. Reticulosis (Fig. 30-34) This group remains controversial and covers a wide range, from granulomatous to sarcomatous forms. The characteristic feature is a predominantly perivascular cell proliferation, which may or may not remain confined to the perivascular space. These areas can fuse into more or less extensive tumour- like masses and the enclosed islands of parenchyma usually undergo necrosis. Cell proliferation is accom- panied by the formation of a reticulin network (except in microgliomatosis). Three main forms can be distinguished: (1) the granulomatous type, in which the infiltrating cells are mainly those seen in inflammatory lesions (lymphoid and large mono- nuclear cells; plasma cells; polymorphonuclear cells, especially eosinophils; reticulohistiocytes; fibro- blasts; and sometimes giant cells); (2) the neoplastic type, in which reticulo-histiocytic cells and lym- phoid cells predominate; the more mature cell types are rare; and numerous mitoses are present; and (3) microgliomatosis, in which the more or less densely arranged cells have nuclei rich in chromatin and sometimes quite pleomorphic but mainly elon- gated, curved, or twisted, and the cytoplasm is indis- tinct or invisible. There may be infiltration of the subpial cortex, either diffusely or along penetrating vessels. Also the white matter may be involved dif- fusely without perivascular arrangement. There is no clear-cut distinction between granulomatous and neoplastic forms; many cases show features of both. In reticulosis, the brain stem and cerebral white matter are frequently involved. Often there is multi- focal distribution throughout the central nervous system, or periventricular concentration of the main lesions. In many cases no obvious change may be seen macroscopically. Enlargement of parts of the brain, with a blurred structure, may be the only visible departure from normal (as with some astro- cytomas). There may be yellow, red, and grey dis- coloration of the cerebral white matter, with irre- gular, patchy distribution. Well-circumscribed, usu- ally white or grey tumour masses are seen only exceptionally. The condition occurs fairly frequently. Of our cases, 75 % were in dogs and 25 % in horses, cattle, or cats. VI. TUMOURS OF THE PINEAL AND PITUITARY GLANDS AND OF THE CRANIOPHARYNGEAL DUCT A. Pinealoma (Fig. 35) There are two forms; in one, the cells are iso- morphic; in the other, diverse. In the former, the nuclei are densely packed and round or oval, and show finely granular chromatin and one, two, or more distinct nucleoli. Sometimes the nuclei are arranged in rows. In the anisomorphic form the cells have larger nuclei and are interspersed with " lymphoid " cells. There are also atypical forms with pleomorphic cells and epithelial (ependymal?) duct structures. Pinealomas vary in size. They are located in the pineal body and may replace it. Some- times they extend into the midbrain, the dorsal thalamus, and beneath. They have been reported in horses, cattle, and dogs, but are very rare. B. Pituitary adenoma (Fig. 36-38) The cells are of epithelial type, round to poly- gonal, and of varying size. They are arranged in groups, rows, and duct-like structures, and are 68 NERVOUS SYSTEM oriented to the vessels. In most cases the cells are of the chromophobe type. Chromophil adenomas (eosinophil, basophil) are usually small. Rarely, the cells are pleomorphic and there are histological traits of malignancy (the so-called fetal type). Adenomas originating from the pituitary are usually large in dogs, and compress and invade the third ventricle and hypothalamic area. They are grey-white in colour, with areas of haemorrhage and necrosis. They are fairly common and have been reported in horses, cattle, sheep, dogs, and cats. C. Craniopharyngioma Probably less than half a dozen craniopharyn- giomas have been identified in dogs. They were located in the hypophysial and infundibular areas, compressing or replacing the pituitary and adjacent parts of the brain to a variable extent. Although the tumours differed from one another histologically, diagnosis was based upon comparison with human craniopharyngioma (bands of epithelial cells lining cystic cavities; intraepithelial and intrastromal cyst formation). 69