THE PATHOLOGY of INTRACRANIAL TUMOURS by DOROTHY S

log Postgrad Med J: first published as 10.1136/pgmj.26.293.109 on 1 March 1950. Downloaded from Protected by copyright.

FIG. 5. Acoustic Schw annoma. THE PATHOLOGY OF INTRACRANIAL TUMOURS By DOROTHY S. RUSSELL, M.D.(Lond.), Sc.D.(Camb.), F.R.C.P.(Lond.) Professor of Morbid Anatomy, London University. From the Bernhard Baron Institute of Pathology, the London Hospital http://pmj.bmj.com/

The following account of the pathology of that involve the ethmoid cells and orbital region intracranial tumours, first published in 1939, has are of importance (Cushing, 1927) since they may been revised. As before, limitations of space pre- project into the anterior fossa causing cerebral clude- more than scanty reference to the rarer compression. tumours, but references are provided for readers 2. Chondrotrata and chondrosarcomata may arise who desire greater detail. from the bones preformed in cartilage at the base on September 30, 2021 by guest. of the skull and project into the middle or posterior A. PRIMARY TUMOURS fossae, or both. In two examples of myxochondro- sarcoma, examined at the London Hospital, a 1. Skull smooth lobulated mass of brittle, translucent grey Primary tumours of the vault or base of the tissue projected from the dura into the middle and skull are rare. Cushing (1932) records 14 examples posterior fossae of one side, invading or dis- only in his series of 2,023 verified cases of intracranial tumours.* * This series includes 4.2 per cent. of secondary i. Osteomata are composed either of dense tumours, obviously too low a figure because such cases ivory or spongy bone. The ivory variety pre- tend to be excluded from any neurosurgical clinic. In addition 2.2 per cent. of cases are listed as ' inflam- dominates in the skull where it usually protrudes matory tumours,' i.e. granulomata. In the following as an exostosis from the inner or outer table or pages Cushing's figures have been adjusted so that the projects into one or more of the air sinuses. Those percentages refer to primary intracranial tumours only. I0 POSTGRADUATE MEDICAL JOURNAI, March I950 Postgrad Med J: first published as 10.1136/pgmj.26.293.109 on 1 March 1950. Downloaded from

:S i Protected by copyright.

FIG i.-Chordoma. H. & E. X 265. FIG. 2.-Meningioma.

placing the pituitary body and indenting the tumours and are most frequent in the middle and adjacent temporal lobe and brain stem. In both later decades The regions in which most are death was due to subdural haemorrhage. In one found are (a) parasagittal, (b) over the cerebral subject Ollier's disease was also present. Micro- convexities, especially the frontal region, (c) scopically the tumours are composed of typical olfactory groove, (d) sphenoidal ridge, (e) tubercu- and atypical cartilage, the stroma being largely lum sellae, (f) near the lateral sinuses. The fre- myxomatous and focally calcified. Chondromata quent situation of these tumours in the neighbour- may also arise from the vault, especially the hood of the arachnoid villi, and their histology, parietal bone (see Chorobski, et al., I99 for strongly support the theory 'that they are of

review). arachnoid origin. The finding of tumours at http://pmj.bmj.com/ 3F.Chordoma, derived from notochordal rem- more remote points, for example over the lateral nants in the basisphenoid or basioccipital bone, aspect of the cerebrum, does not nullify this may resemble (2)macroscopically. Microscopic- theory since Schmidt (1902) demonstrated isolated ally such tumours are composed of alveolar masses nests of arachnoid cells within the dura remote of large ' physaliphorous' cells of characteristic from the sinuses. These nests increase in fre- foamy appearance due to the presence of mucin quency with age. Study of the spinal meningio- (Fig. i), which is also present to a variable extent mata and of certain intraventricular tumours in the stroma. Glycogen has also been demon- arising from the stroma of the choroid plexuses on September 30, 2021 by guest. strated in the cells (see also Burrow and Stewart, shows that the pial and arachnoid membranes may 1923-24). also, though more rarely, be the site of origin of Cholesteatoma, solitary plasmacytoma and these tumours- cavernous angioma are all very rare tumours of the The meningioma typically is a firm, ovoid or diploe. bun-shaped mass with an encapsulated, irregularly lobulatednor smooth surface traversed by many 2. Meninges small veins and capillaries (Fig. 2). Tumours I. Meningioma (syn.: dural endothelioma, arach- arising from the falx or tentorium may be of noidfibroblastoma, meningealfibroblastoma). These dumb-bell shape owing to their growih from *are benign, circumscribed tumours usually arising either side of the dura. Less, frequently the from and firmly attached to the dura, and em- tumour forms a thin layer on the inner surface of bedded in but seldom invading the brain. They the dura (pmeningioma-en-plaque') or, more constitute 14 per cent. of all primary intracranial rarely is villous The surfaces are usually March 1950 RUSSELL: The Pathology of Intracranial Tumours III Postgrad Med J: first published as 10.1136/pgmj.26.293.109 on 1 March 1950. Downloaded from

1t1 Protected by copyright.

FIG. 3.- Meningioma invading bone. H. & E. x 80. FIG. 4.Meningioma. H. & i:. x I9. 'pinkish-red or grey and when cut are tough and The microscopical appearances of these tumours fibrous, *with* a * grained. appearance. 1% either of vary considerably. Bailey and Bucy ^('93') whorled character or of streaks radiating fan-wise recognized nine types. Analysis of IO4 surgical from the dural attachment. The haemangio- specimens at the London Hospital has led to their matous variety appears highly vascular ; the subdivision into the following groups, arranged in xanthomatous is distinguished by opaque ochreous order of frequency :-(i) endotheliomatous, 56.6 areas, especially beneath the capsule. The skull per cent., (ii) fibroblastic, 29.2 per cent., (iii) at the site of dural attachment often shows a angioblastic, 7.5 per cent., (iv) xanthomatous, diffuse thickening or ' hyperostosis.' Both tables 3.8 per cent., (v) myxomatous, 2.8 per cent. Full http://pmj.bmj.com/ may bulge, or the inner table only may show a histological details are published elsewhere (Bland conical projection. Cushing (1922a) estimates and Russell, I938), but the following summaries that hyperostoses occur in about 25 per cent. of provide the main points. all meningiomas. It has usually been assumed (i) Endotheliomatous. Alveolar masses or sheets that this change is accompanied by an invasion of of large polygonal cells often with indefinite the medullary spaces by tumour. Where the bony borders. Whorls and psammoma bodies often thickening is great, as in meningioma-en-plaque, present, sometimes abundant. Fibroglia fibrils on September 30, 2021 by guest. SUChl invasion iS microscopically COIlSpiCUOUS absent. Reticulin fibres confined to vessels and (Fig. 3) and may even extend into the temporal trabeculae. Many, transitions between (i) and muscle. But where t'he thickening is slight and (ii) (Fig. 4). confined to the inner table the medullary spaces (ii) Fibroblastic. Interlacing bundles of long often show merely enlargement and fibrosis. spindle cells containing fibroglia fibrils. Coarse Thickening and invasion of the bone by tumour reticulin and collagen fibres often present. Whorls is frequent in the basal meningiomata. It has and psammoma bodies scarcer than in (i). been noted in five of eight examples occurring (iii) Angioblastic. Rich network of capillary in the anterior fossa at the London Hospital, an spaces lined with plump endothelial cells. Similar observation which suggests that direct trauma cells filling tissue between capillaries. Abundant plays little part itn the production of this bony reticulin but no fibroglia fibrils present. Inter- change, although it seems likely that trauma is an stitial cells may be xanthomatous. aetiologic'al factor in the production of men- (iv) Xanthomatous. Like (i) but cells in many ingiomas as a class (Cushing, 1922b). areas filled with anisotropic lipoid. I 12 POSTGRADUATE MEDICAL JOURNAI, March i95o Postgrad Med J: first published as 10.1136/pgmj.26.293.109 on 1 March 1950. Downloaded from (v) MWyxomatous. Spindle and stellate cells un- is a rare congenital condition associated with evenly distributed in a stroma giving reactions for pigmented naevi in the skin, and is one of the mucin, and rich in reticulin fibrils. Fibroglial many causes of congenital hydrocephalus. The fibrils absent. areas affected show a diffuse discoloration varying Examples of (i) or (ii) may, exceptionally, be of from cafe-au-lait to brownish-black. Micro- a melanotic character. Others in these two groups scopically the leptomeninges are infiltrated with occasionally form lamellar bone ; such are more pigmented naevoid cells which infiltrate the likely to occur in the spinal canal than within the adjacent nervous tissue along the sheaths of the cranium. perforating vessels (see review of published cases Apart from the tendency towards excessive by Schnitker and Ayer, I938). haemorrhage during operative removal in group 4. Lipoma. These rare tumours, arising in de- (iii) this histological subdivision does not appear velopmental rests, may be found in the mid-line to be of much clinical significance. A detailed over the corpus callosum, tuber cinereum or mid- account of the meningiomas has been published brain. Although sometimes deeply embedded in by Cushing and Eisenhardt (1938). the brain their pial connection is always retained. 2. Sarcoma. Circumscribed and diffuse prim- They rarely cause symptoms (Ewing, I922). A ary sarcomata of the meninges have been de- review of the literature with an account of a case scribed; they are exceedingly rare. It must be showing extensive lipomatosis of the meninges remembered that the term ' sarcomatosis ' was often has been published by Baker and Adams (1938). used in the older literature for a condition in which . 5. Cholesteatoma (syn.: pearly tumour of the leptomeninges were infiltrated with ' small Cruveilhier). These epidermoid tumours are also round cells' now known to be of neurogenic derived from developmental rests, and may arise origin (see medulloblastoma). in the leptomeninges at the base of the brain, the 3. Melanoma. The pial cells over the base of posterior fossa and in the ventricles. They areProtected by copyright. the brain, particularly the medulla oblongata, rare, constituting, with dermoid cysts to which often contain melanin. Benign and malignant they are closely akin, only I5 in Cushing's series melanomata may arise from these cells but are of cases. Externally they are circumscribed and extremely rare. Before claiming that such smooth. Their glistening, pearly appearance is tumours are primary it is necessary to make an due to the accumulation within the tumour of exhaustive autopsy, including an examination of concentric layers of horny and waxy material the eyes. Diffuse melanosis (Virchow), of the pia which have been exfoliated from the epidermal http://pmj.bmj.com/

'I W

- ~ V - on September 30, 2021 by guest.

FIG. 6.-Schwannoma of posterior spinal root in von FIG. 7.Same as Fig 6 LaidIavv x 420 Recklinghausen's disease. H. & E. x 141. March I95C RUSSELL: The Pathology of Intracranial Tumours IIX Postgrad Med J: first published as 10.1136/pgmj.26.293.109 on 1 March 1950. Downloaded from

OWE'

FIG. 8.-Capillary haemangioblastoma. P.T.A.H. FIG. 9.-Neurofibroma of spinal nerve root showing X 237. elongated Schwann cells. H. & E. lining. This lining, which microscopically may cranial tumours (Cushing). It forms a solid, either be of a simple squamous or prickle-celled rarely cystic, encapsulated, lobulated mass occupy- character, rests upon a collagenous basement ing the course of the eighth nerve in the cerebello- membrane derived from the pia, which forms its pontine angle and deeply indenting the adjacentProtected by copyright. outer boundary. These tumours should be dis- cerebellum and brain stem. It frequently extends, tinguished both from the cholesteatomata of the by the internal auditory meatus, into the petrous middle ear, which are of a chronic inflammatory bone. Opaque yellow xanthomatous areas may be nature, and from the cholesteatomata of the visible to the naked eye, especially beneath the choroid plexus, which are degenerative products. capsule. It is benign and never invades adjacent 6. Gliomatosis. Rare examples occur, usually structures. Microscopically it is composed of in young children, in which the leptomeninges are interlacing bundles of long spindle cells which diffusely infiltrated with glial tumour cells of a sometimes show regimentation of their nuclei or polymorphic character and in which no primary ' palisading' (Fig. 6). Whorls are often present tumour can be demonstrated within the brain or but are less definite than in the meningiomata. retinae. The most plausible explanation of such Psammoma bodies do not occur. Fibroglial fibrils cases is that the tumour has arisen superficially, are often demonstrable within the cytoplasm of either in the marginal glia or within an island of the cells, but are seldom as conspicuous as in the http://pmj.bmj.com/ neuroglial tissue present as a developmental fibroblastic type of meningioma. Reticulin fibrils, abnormality within the leptomeninges. Such on the other hand, are present between all the islands are sometimes met, especially about the cells in well preserved areas with a regularity and brain stem, in the microscopic examination of un- richness that is highly distinctive (Fig. 7). selected necropsy material. The importance of The schwannoma may also occur, though rarely, making a full examination of the central nervous on other cranial nerve roots, notably the trigeminal. system must, however, be remembered since an The Gasserian ganglion is also involved in such intramedullary glioma of the spinal cord may instances with the formation of a dumb-bell on September 30, 2021 by guest. spread secondarily through the leptomeninges, shaped tumour, the greater part of which is be- even reaching the brain (Mallory,d9;iv Eden, neath the tentorium (Krayenbiihl, 1936). I938). Neurofibroma is the characteristic tumour of Secondary gliomatosis of the leptomeninges may von Recklinghausen's disease, in the ' central ' occur in . wide variety of gliomata of the brain, form of which tumours are to be found on both but especially iti medulloblastoma (Cairns and acoustic nerves together with a variety of other Russell, 193)I roots, both cranial and spinal. Sensory roots are usually so affected. Other tumours, such as 3. Nerve Roots meningiomata and gliomata, may also occur in the Schwanliyma(syn.w: neurilemmoma, perineurial central nervous system, notably glioma of the fibroblastoma, neurinoma). This most commonly optic chiasm and ependymoma in the spinal cord. occurs as th esolitary acoustic nerve tumour (Fig. 5) Neurofibroma is distinguished from schwannoma which constitutes 9.3 per cent. of primary intra- by its plexiform character, the elongated sheath of x14 POSTGRADUATE MEDICAL JOURNAL March I9,- o Postgrad Med J: first published as 10.1136/pgmj.26.293.109 on 1 March 1950. Downloaded from Schwann cells being separated by stout, wavy, superficial layers of the cerebral cortex. The collagen fibres instead of reticulin (Fig. 9); there affected gyri are atrophied, the sulci widened, and is no palisading; the tumour also is widely the double contours appear through impinging of penetrated bv nerve fibres that are frequently the X-rays upon the vertical calcium-containing medullated. This last feature is generally held to walls of the sulci. Sturge described a case as afford a clear-cut distinction between the neuro- early as I879 in which congenital glaucoma and a fibroma and the schwannoma. I have, however, port-wine stain were associated with fits referable found that in the solitary schwannoma of the to the hemisphere of the same side. The acoustic nerve delicate non-medullated fibres may radiological contribution completes the clinical often be demonstrated at points remote from the syndrome to which the name Sturge-Weber's nerve on which the tumour arises. In central Disease is widely given or, in France, ' syndrome neurofibromatosis an intimate mixture of the two neuro-cutane.' The condition is mostly seen in types of nerve-root tumour is often demonstrated. children and is rarely familial. Cobb (1915) The fact that the disease is hereditary suggests observed that a similar venous anomaly of the that a developmental disturbance of the ectoderm spinal cord might be associated with a cutaneous and mesoderm is responsible. Other manifesta- vascular naevus in the same segment. tions are pigmented moles, cafe-au-lait spots, Histologically the arteries and veins composing peripheral neurofibromata and diffuse thickenings the lesion are for the most part structurally of the nerves. It is remarkable that in examples recognizable as such, but they often undergo where peripheral tumours are numerous the hyaline and calcareous degeneration. In addition central nervous system appears free, and vice the muscular portions of their walls are often de- versa. formed by irregular hyperplastic foci or minute leiomyomata. Where the vessels penetrate the

4. Blood Vessels brain they are separated by nervous tissue which Protected by copyright. The blood-vessel tumours as a group compose has undergone gliosis. Macrophages containing 2 per cent. of intracranial tumours (Cushing). iron pigment are often abundant in this tissue. They may be subdivided as follows:- (b) Capillary telangiectasis. This rare lesion is i. Congenital maldevelopments. This class com- usually a chance finding at necropsy and seldom prises certain vascular lesions which, although causes symptoms. The commonest site is in the tumour-Jike, are more correctly termed hamarto- pons and mid-brain and in this situation rupture mata, as defined by Albrecht (I904), from has been known to cause death. Telangiectases aJapTta, error. The vascular hamartomata to be may be multiple and may also be associated with considered are:- multiple cutaneous foci (Osler's disease), a com- (a) Cirsoid or serpentine angioma. bination that tends to be familial (Kufs, I928). (b) Capillary telangiectasis. Histologically the area contains a large number of (c) Cavernous haemangioma. greatly distended capillaries of normal structure

(a) The cirsoid or serpentine angioma is com- separated everywhere by unaltered nervous tissue. http://pmj.bmj.com/ posed of abnormally large and tortuous vessels (c) Cavernous haemangioma (syn.: cavernoma). forming a tangled mass in the leptomeninges and This is closely allied to and has often been con- penetrating the underlying brain for a variable fused with (b). It is rarely met in the brain, the distance. The contributing vessels can be usual sites being the basal ganglia or subcortical recognized and named anatomically. The angioma white matter. In the former position they may may be composed of veins alone or of veins and give rise to internal hydrocephalus, in the latter, arteries. The latter is also known as arterio- from their predilection for the Rolandic area, to venous aneurysm, an unfortunate term, and Jacksonian epilepsy. Microscopically this lesion on September 30, 2021 by guest. characteristically pulsates causing a bruit which is essentially similar to the cavernous haemangioma can be heard over the skull. Any part of the brain of the liver, the walls of the blood spaces being of may be involved but the commonest site is in the capillary structure and contiguous except at the area supplied by the middle cerebral artery. periphery where tongues of glia intervene. An Venous malformations are sometimes associated important distinguishing feature from (a) is the with a homolateral port-wine stain or naevus in absence of any large vessels of supiply, the adjacent the skin supplied by the trigeminal nerve, and leptomeninges appearing normal except for the with congenital glaucoma, or buphthalmus. The presence in some instances of slight rusty pig- characteristic radiographic appearance, of ' tram- mentation. line' character, to which Parkes Weber (1922-23) 2. Capillary haemangioblastoma (syn.: Lindau's first drew attention, is now known to be due not tumour, angior6ticulome). This is a true tumour to calcification of the vessels, but to the profuse capable of growth, invasion and of recurrence deposition of calcium as calcospherites in the after incomplete removal. It occurs almost ex- March 1950 RUSSELL: The Pathology of Intracranial Tumours II5 Postgrad Med J: first published as 10.1136/pgmj.26.293.109 on 1 March 1950. Downloaded from clusively in the cerebellum or medulla oblongata. Some examples are solid and cystic, others entirely solid. On opening a cystic tumour the walls appear everywhere to be composed of smooth neuroglial tissue except at one point where a ' mural nodule ' of yellowish-red tissue is situated. - 1 This nodule may be relatively minute but is nevertheless responsible for the cyst which will not be refilled if the nodule is removed. These -~ tumours are finely spongy, occasionally showing cavernous spaces. Their cut surfaces are frequently ochreous from the presence of large quantities of intracellular lipoid. Microscopically (Fig. 8) the tumour is composed of capillaries of varying calibre lined with rather plump endothelial cells and separated by closely packed polygonal cells many of which are filled with Sudanophil, anisotropic lipoid. With suitable silver stains a rich net-work of reticulin is demonstrated constituting the capillary basement membranes and branching between the interstitial cells. The question of the origin and nature of these interstitial cells has been rather neglected. It is clear that they are neither of Protected by copyright. neuroglial nor of microglial origin. They are identical in appearance with the cells in many meningiomata, especially the angioblastic and FIG. 25.-Neuroblastloma of cerebrum showing rosettes. xanthomatous types, and there can be little doubt Bielschowsky. X 200. that they are of pial origin. This view is supported by the fact that many of these cerebellar tumours drome is, ho'wever, confined to a minority of are obviously contiguous with, and in some in- cases exhibiting the cerebellar tumour ; it was stances involve the pia. Tumours that appear to demonstrated in two only of nine cases that came be deeply embedded in the parenchyma may to necropsy at the London Hospital within recent nevertheless show continuity with the pia in the years. Further details of the blo-od-vessel tumours depths of a sulcus. Moreover in some examples of of the brain are given in the excellent mono- capillary haemangioblastoma there are cellular, graphs by Cushing and Bailey (1928) and by relatively avascular areas indistinguishable in ap- Bergstrand, Olivecrona and T6nnis (1936). http://pmj.bmj.com/ pearance from the endotheliomatous meningioma. Again, in two cerebellar examples examined at 5. Brain Proper necropsy, pial tumours of identical appearance The overwhelming majority of tumours in this were also found in the spinal cord. The close class are gliomata, tumours of the neuroglia or resemblance between the capillary haemangio- supporting tissue of the -brain, while those com- blastoma and the angioblastic meningioma cannot posed of neurones or of neuroblasts are rare. be dismissed as superficial and the claim of Globus Together comprise per cent. of they 45.5 primary on September 30, 2021 by guest. (Iy937) that' the Lindau tumour is little more than intracranial tumours (Cushing). a hemangioendotheliomatous variety of men- i. (a) Neuroblastoma. Apart from the medullo- ingioma ' seems justifiable. blastomas which, as will be seen below, can Nevertheless, even if this is conceded, the differentiate towards this type, the neuroblastomas Lindau tumour has certain important and distinc- are extremely rare. Recently, however, we have tive associations, to which the name of Lindau's seen two cerebral examples in young children. syndrome has been given. In examples of this Both were massive tumours of soft mucinous con- syndrome, which is often familial, the cerebellar sistency and relatively well defined. Micro- tumour is associated with one or more of the scopically they were richly cellular growths com- following conditions :-angiomatosis retinae (von posed of polygonal cells, with nuclei of neurone Hippel's disease), congenital cysts of the pancreas type, arranged in rosettes in some areas (Fig. 25) and kidneys, and benign tumours of the kidneys and containing many mitoses. Reticulin and and suprarenal glands (collectively termed' hyper- collagen fibres were conspicuous in many places. nephroma' by Lindau). Evidence of the syn- (b) Ganglioneuroma. Tumours containing differ- POSTGRADUATE MEDICAL JOURNAL M27rch I950 Postgrad Med J: first published as 10.1136/pgmj.26.293.109 on 1 March 1950. Downloaded from entiated, sometimes multinucleate, neurones con- ;I uLet-ea- -ET 2 rl T met in the taining Nissl substance have rarely been .... frontal and temporal lobes, tuberal region, pineal body and cerebellum. They are usually well defined and are of slow growth. The neurones are separated by somewhat sparse bipolar cells, apparently of glial origin. Calcospherites are usually abundant. While Cushing (1932) quotes only three cases, two of which were pineal, Globus (I938) has identified ' I2 cases of ganglioglioma and io instances of spongioneuroblastoma' in a group of I78 ' supratentorial gliogenous neo- plasms' in the Mount Sinai Hospital. From his observations it appears almost certain that many tumours containing neoplastic neurones and neuroblasts have been overlooked. Within recent years I have examined several biopsy specimens FIG. io.-Diagram: Rosettes. from the cerebral cortex and subcortical tissues in which the tumour was compcsed of numerous well (b) Neuroepithelioma. This term should be re- differentiated neurones of variable size and shape, tained for the retinal tumour originally described containing Nisst substance, accompanied by by Flexner (I89I) and for cerebral tumours of abundant plump fibrillary astrocytes and some- similar structure. The retinal tumour, of which times astroblasts. In two examples the overlying a good example has been seen at the London pia mater contained leashes of nerve fibres derived Hospital and described (Cairns and Russell, i93) Protected by copyright. from the tumour. Such growths appear to merit is a highly malignant tumour, arising in the rod the name Ganglioglioma, and it may be assumed and cone layer where it forms rosettes composed of that both they and ganglioneuroma are hamarto- a group of cells arranged round a central lumen. mata of benign character. So far none of my cases The cell margin bordering the lumen is defined by has come to necropsy. a fenestrated membrane, stainable with phospho- 2. The gliomas. The nomenclature introduced tungstic acid haematoxylin, through which small by Bailey and Cushing for these tumours (I926) blunt cytopla,mic processes protrude in an will be followed since this has found the widest attempt to form rods and cones. Contrary to what acceptance in English-speaking countries. As is has frequently been stated, blepharoplasts and well known this classification rests upon the cilia are not seen in this situation. A certain correlation of type cells in different varieties of confusion in the use of the term ' rosette ' is glioma with morphological stages in the normal explained in Fig. io. Neuroepithelioma of the development of the neuroglia. Without dis- retina is highly malignant, spreading diffusely http://pmj.bmj.com/ cussing here either the theoretical basis of such a through the leptomeninges of the brain and spinal classification or the possible criticisms that may cord. In this and in the morphology of the cells, be levelled against it, it may be stated that it is apart from rosettes, it resembles medulloblastoma. serviceable in practice and, subject to certain A strictly comparable tumour of the cerebrum modifications, appears likely to stand the test of ha.s less certainly been established, but is recog- time. Lack of space forbids any description of the nized by Penfield. A possible example is Case morphology of embryonic and adult forms of neu- i of Davie's publication on medulloepithelioma roglia. A good account is given by Penfield (I932). (1932). Many of the other reported cases, in- on September 30, 2021 by guest. (a) Medulloepithelioma. This is a somewhat cluding those of Bailey and Cushing (I926) should hypothetical tumour theoretically derived from, more properly be regarded as well-differentiated and resembling in its structure, the primitive ependymomas in as much as the tumour cells form medullary epithelium. A few examples have been the rosettes of Bailey and bear blepharoplasts and described in the pars ciliaris retinae and in relation occasionally cilia along their central borders. to the third ventricle. The short account by The curious misapprehension has gained cur- Bailey and Cushing (I926) of their two examples rency that the ependyma is ciliated and provided illustrates the difficulty of diagnosing with with blepharoplasts during a short period of intra- certainty so poorly differentiated a tumour. This uterine life only. Actually this is true of the and Bailey's later admission (1932) that the epithelium of the choroid plexuses alone. It is, medulloepitheliomas are often classified with the however, generally agreed that the primitive neuroepitheliomas casts doubt upon the existence medullary epithelium is non-ciliated. As shown by of this as a true type of glioma. His (I889) cilia begin to appear in the embryo at Mlarch i RUSSELL: The Pathology of Intracranial Tumours I 17 Postgrad Med J: first published as 10.1136/pgmj.26.293.109 on 1 March 1950. Downloaded from

- 4E A1:1 ~4 k, -9. Z,

4 #

IL' G. i i.-Ependymoma: A rosette with fibrils in peri- FIG. I 2.-Ependymoma: Fibrillated area. Blepharo- pheral processes of cells. P.T.A.H. x 735. plasts indicated by arrows. P.T.A.H. x 375. Protected by copyright. about the end of the fifth week. My own observa- conception both of the neuroepithelioma and of tions on fresh human material confirm this. In a the ependymoma. The former, as described by seven to eight weeks embryo cilia were restricted Bailey and Cushing, is composed of cells arranged to the low columnar epithelium of the roof-plate in rosettes, bearing blepharoplasts and sometimes and choroid plexuses of the hind brain. At io to cilia along the free borders of their central ends 12 weeks cilia were present on the choroid plexuses while the other end extends as a process into the but not the walls of the lateral ventricles ; they surrounding tissue. Such tumours are macro- were also present in the Sylvian aqueduct and scopically well defined, occupy the neighbourhood parts of the third ventricle. At i8 weeks fewer of the ventricles and are clinically benign. In no cilia were present on the choroid plexuses ; they feature do they suggest a primitive type of tumour. -extended over the medial walls of the lateral (c) Ependymoma. The ependymal tumours are ventricles but were absent where proliferation of relatively benign and of slow growth. They arise the primitive epithelium was still in progress. both in children and in adults in relationship to http://pmj.bmj.com/ Well-formed cilia were present throughout the some part of the ventricular system. They are rest of the ventricular system and in the central also found in the spinal cord and filum terminale. canal of the spinal cord. In a foetus Of 22 weeks In some examples the tumour may project into the cilia had almost disappeared from the choroid the ventricular cavity, and is then often soft and plexuses but were more wide-spread in the lateral papillary; in others it forms a circumscribed mass ventricles. They were conspicuous in the third in the adjacent nerve tissue. There is considerable and fourth ventricles and in the central canal of the variation in the microscopic appearances, and sub- spinal cord. In a premature infant the' appearances divisions have been formed accordingly (Kernohan on September 30, 2021 by guest. were similar except that the choroid plexuses were and Kernohan, I937). Here it may be said now free from cilia. The lateral ventricles were briefly that the cells in well-differentiated types well ciliated except over the basal ganglia. In tend to form rosettes, the free margin of the cell fresh adult material cilia and blepharoplasts can being occupied by a row of blepharoplasts and, always be demonstrated along the free borders of sometimes, cilia. The other end of the cell is ependymal cells. They are not, as is often claimed, prolonged into a process in which neuroglial fibrils restricted to a few sites such as the floor of the can usually be demonstrated (Fig. i i). These fourth ventricle and the central canal of the spinal processes tend to radiate towards vessels. In cord. some examples this tendency leads to the pre- From the above it appears incontestable that, dominance of perivascular pseudo-rosettes. Such far from being primitive, the ciliated ependymal tumours may only be distinguished from astro- cell is the mature, fully differentiated form. It is blastomata by careful examination and, in par- necessary to insist upon this because it affects our ticular, by the demonstration of blepharoplasts. POSTGRADUATE MEDICAL JOURNAL March 1950 Postgrad Med J: first published as 10.1136/pgmj.26.293.109 on 1 March 1950. Downloaded from A search should be made for these in the best an example of medulloblastoma is described by preserved and most cellular parts of the tumour. Nelson (1936). Microscopically it is composed of When ependymal cells become displaced from small, closely packed cells with relatively large their normal position lining a cavity, as in oblitera- nuclei, containing a dense net of chromatin and tion of the central canal of the spinal cord, they inconspicuous nucleoli. Multinucleate giant cells lose their cilia and the blepharoplasts are shifted are occasionally seen and mitoses are usually into a more central position in the cell. They are abundant. The cytoplasm is scanty and is some- then demonstrated by phosphotungstic acid times drawn out into a short, carrot-shaped pro- haematoxylin as a group of minute spherical or cess. In some examples such cells are clustered rod-shaped bodies occupying a faintly stained area into spheres, their processes being directed to- in the cytoplasm near the nucleus. Small isolated wards the centre (the rosettes of Wright, Fig. groups of such cells are frequently found in normal I3). Such tumours resemble the well-known brains near any fold in the ependyma, for example neuroblastoma of the suprarenal medulla and, the horns of the lateral ventricles and the foramina with silver techniques, the presence of character- of Luschka. istic neuroblasts can be demonstrated. In other As originally described by Mallory (1902), examples of medulloblastoma, the cells may be whose classical description of these tumours ap- slender uni- or bi-polar spongioblast-like cells, pears to have been somewhat neglected, the the processes of which contain delicate neuroglial ependymomas often contain relatively acellular fibrils. Evidence of differentiation along two areas in which neuroglial fibrils are abundant. divergent lines is therefore to be found within the Such areas may even simulate an astrocytoma group. A great many display no differentiation at all (Fig. I2). The histogenesis of the medulloblastoma and (d) Medulloblastoma (syn.: neuroblastoma its relationship to the gliomas as a whole is un- (Wright), neurospongiome (Roussy and Oberling)). settled. Its virtual confinement to the cerebellumProtected by copyright. This highly malignant tumour of children and, and its obviously embryonic character render more rarely, of young adults, appears to be con- attractive the suggestion of Stevenson and Echlin fined to the cerebellum. It arises as an ill- (I934) that it arises in the foetal granular layer of defined, soft, grey, crumbly mass in the vermis or Obersteiner. This subpial layer (Fig. 14), dis- lateral lobes and tends to spread rapidly through appears during the first year of extra-uterine the subarachnoid space, especially of the spinal life. It is composed of indifferent cells which cord. Retrograde metastasis in the ventricles may migrate inwards to form the neurones of the also take place, a favourite site being the floor of granular layer proper. It is less certain whether the third ventricle. An apparently authentic in- they differentiate also into neuroglial cells. stance of metastasis outside the nervous system in Should this hypothesis be correct it would explain http://pmj.bmj.com/ on September 30, 2021 by guest.

H.&fE. xin7

I FIG. 14.-Cerebellum of new-born infant showing FIG. 3.-Medulloblastoma showing rosettes of Wright. Obersteiner's laver. H. & E. x io6. Mach 1950 RUSSELL: The Pathology of Intracranial Tumours Postgrad Med J: first published as 10.1136/pgmj.26.293.109 on 1 March 1950. Downloaded from

K (g) Astrocytoma. This is one of the commonest t types of glioma, and perhaps the most benign. In children it occurs chiefly in the cerebellum and is then often well defined and sometimes cystic. The cerebral examples, on the other hand, are more commonly found in adults and are often diffuse. The pons is a fairly common site of diffuse astrocytoma, giving rise to what is sometimes called ' diffuse hypertrophy.' Other sites are the mid-brain and optic chiasm. The astrocytoma varies in its macroscopic appearances. Characteristically it is uniformly smooth and milky-white, the more fibrous examples being exceedingly tough and rubbery. In the cerebellum they are often rather soft or even gelatinous in places; their texture is sometimes spongy from the development of minute cysti- spaces through degeneration. Calcified particles are moderately frequent. Although benign they FIG. I5.-Astroblastoma. H. & E. x 58. often infiltrate the overlying leptomeninges, especially in the cerebellar examples. Areas of many of the observed characteristics of the haemorrhage and necrosis are rarely present. tumour. The microscopic appearances also vary and they (e) Spongioblastoma polare. A group of tumours have been divrided by Elvidge, Penfield and Cone Protected by copyright. has been described under this name (Russell and (I937) into three groups :-(i) piloid, (2) gemi- Cairns, I947) that we believe to be appropriate. stocytic, and (3) diffuse. Tumours of the piloid We are convinced, both on morphological grounds group, mainly cerebellar examples, are composed and on the evidence of tissue-culture (Russell and of bundles of long slender hair-like cells con- Bland, 1934) that the gliomas usually described as taining neuroglial fibrils (Fig. i6). Tumours of spongioblastoma polare (following Bailey and the other two groups are confined to the cere- Cushing, 1926, and Bailey and Eisenhardt, 1932) brum. The gemistocytic astrocytoma (Fig. 17) is are the piloid (or pilocytic) variety of astrocytoma. macroscopically well defined and is composed of According to our interpretation the polar plump cells with bulky cytoplasm and stout spongioblastoma is a potentially malignant glioma neuroglial fibrils which tend to be confined to the arising in young subjects in the neighbourhood of periphery of the cell. This type has been named the ventricular system. It is composed of packets of thin, tadpole-shaped, delicately fibrillated cells, http://pmj.bmj.com/ the groups being separated by a connective-tissue vascular stroma. Palisading of the nuclei is a conspicuous feature (Fig. 26). The tumour is -. -i!Sl much rarer than the piloid astrocytoma. (f) Astroblastoma. According to Bailey (Bailey and Bucy, 1930) this is a somewhat rare glioma,

chiefly found in the subcortical areas of the on September 30, 2021 by guest. cerebrum in young adults. The average survival period is about 28 months after diagnosis. Macro- scopically the tumour is poorly defined and has a greyish cut surface with occasional cysts or areas of necrosis in the central parts. Characteristic examples show a regular arrangement of bulky astroblastic cells in dense rows along the trabeculae and blood vessels of the stroma (Fig. 15). These cells have a few short processes from the head end where the nucleus is situated and a longer angiotropic process ending in a slight expansion or foot. Neuroglial fibrils are rarely found. Many cells are multinucleate but mitotic figures are IFIG. I6. Astrocytoma: Piloid tvpe with calcospherites. rare. H. &E. x425. 120 POST"GRADUATE MEDIC(Al, JOURNAL March 1950 Postgrad Med J: first published as 10.1136/pgmj.26.293.109 on 1 March 1950. Downloaded from

FIG. 17.-Astrocytoma: Gemtistocvtic type. H. & E. FIG. I8.-Astrocytoma: Diffuse type. P.T.A.H. x 510.Protected by copyright. X 250. astrocytome giganto-cellulaire' by Roussy and cells being undifferentiated polygonal and pyri- Oberling. Astrocytoma diffusum infiltrates and form cells. Uni- and bi-polar 'spongioblasts' causes great induration of large areas in the may form pseudo-rosettes round vessels and cerebral hemispheres; it is composed of relatively palisades along the borders of necrotic foci (Fig small -cells which produce an abundant intercellular I9). In many examples every transition between tangle of neuroglial fibrils (Fig. i8). Included these and fully differentiated astrocytes may be normal elements of the brain undergo little identified. Uni- and multi-nucleated giant cells destruction. are often present and may form a conspicuous (h) Spongioblastoa multiforme (syn.: glio- feature (Fig. 20). Mitoses are usually numerous. blastoma multiforme). This is -perhaps the com- Degeneration, necrosis and haemorrhage are monest type of glioma and one of the most rapidly characteristic secondary changes; thev are often http://pmj.bmj.com/ fatal. It usually occurs in the deep parts of the associated with endothelial proliferation in the cerebral hemispheres in adults as an ill-defined smaller blood vessels which become greatly con- somewhat vascular mass the cut surfaces of which voluted, forming structures sometimes resembling present a variegated appearance. Extensive areas the renal glomeruli. of necrosis, mostly in the central parts, are inter- The position of this tumour in the glioma series mingled with haemorrhages and small cysts, has always been a difficult question. The poly- while the growing margins are composed of morphism of its cells hardly entitles it to be re- greyish-white granular tumour tissue. In many garded as an embryonic type, and the explanation on September 30, 2021 by guest. examples tougher greyish-white areas suggestive of the presence in so many of the tumours of adult of astrocytoma can be identified at one extremity forms of neuroglia as a result of differentiation is of the tumour. The corpus callosum is a favourite contrary to general experience in tumour site, extension sometimes taking place throughout pathology. The polymorphism in spongio- the greater part of this structure. Again the blastoma multiforme is far more readily explained tumour may extend from the corpus callosum into as the result of anaplasia and there is, in fact, either corona radiata. Superficial tumours are apt to abundant evidence that many of these tumours are infiltrate the adjacent leptomeninges, and to become derived from astrocytomas. Space forbids the adherent to the dura although they seldom invade it. examination of this evidence here, but it may be Microscopically there is great variation in the summarized under the following heads: appearances both in different examples and in i. Presence of considerable areas resembling different parts of the same tumour. Variability in typical astrocytoma in many examples of spongio- cell form is a characteristic feature, many of the blastoma multiforme. March 1iQ50 RUSSELL The Pathology of Inttracranial Ttniours 121 Postgrad Med J: first published as 10.1136/pgmj.26.293.109 on 1 March 1950. Downloaded from

']Ak.rr

FIG. I 9.-Spongioblastoma multiforme, showing FIG. 20.-Spongioblastoma multiforme, showing giant palisading about area of necrosis. H. & E. xc IO6. cells. H. & E. X 258. Protected by copyright. 2. Presence of anaplastic foci, resembling however, the cells remain unimpregnated by any spongioblastoma multiforme, in otherwise typical of the metallic methods although oligodendroglial astrocytomas with long .clinical histories in (a) cells in the adjacent brain tissue may be well cerebrum, (b) cerebellum, (c) pons. demonstrated in the same preparation. The 3- Consecutive examinations at biopsy and reason for this is unknown. With the gold- necropsy, separated by considerable intervals of chloride sublimate method a variable number of time, demonstrating marked dedifferentiation in astroblasts and astrocytes are almost always found. tumours primarily astrocytomatous. Similar ana- Moreover some tumours of this class contain large plastic changes have also been observed in two areaswhich histologicallyare indistinguishablefrom examples of oligodendrogliomas. Cox (I933) re- astrocytoma. The relationships between oligoden- ported anaplasia in an example of ependymoma. droglioma and astrocytoma require further investi-- (i) Oligodendroglioma. This is a rarer glioma gation. Although usually considered a relatively http://pmj.bmj.com/ occurrnng in children and young adults. It is benign form ofglioma it has been established (Beck usually found in the cerebral hemispheres and has and Russell, 1942; Blumenfeld and Gardner, I945) frequently been diagnosed radiographically by the that some examples spread throughout the cerebro- characteristic calcified deposits that appear most spinal pathway in a highly malignant manner. frequently in its periphery. Occasionally such dissemination provokes a chronic- Macroscopically it is usually a well defined, inflammatory reaction in the meninges with great firm solid tumour with-a fibrosis consequent internal hydrocephalus. greyish-white slightly land on September 30, 2021 by guest. granular cut surface. Cysts may be present and 3. Tumours of the choroidplexus. (a) Papilloma. collections of sand-like, calcified particles are This is a rare tumour (o.6 per cent. of primary frequent, especially near the periphery. intracranial tumours, Cushing, I932) occurring The microscopic appearances are characteristic, most frequently in the fourth ventricle in children. the tissue being composed of closely packed round Van Wagenen (1930) in an analysis of 45 examples- or polygonal cells with central round nuclei and found that 50 per cent. had arisen in the fourth very vacuolated cytoplasm (Fig. 2I). Groups of ventricle, I7.3 per cent. in the third and 34.7 per these cells are bounded by a well-defin'ed vascular cent. in the lateral ventricles. Almost all of the and connective-tissue stroma. Mitotic figures and lateral ventricle examples have been left-sided. giant cells are sometimes present; in some Although histologically benign these tumours are examples mitoses are numerous. With appro- apt to be disseminated throughout the meninges. priate silver methods a variable number of the through the carriage of groups of cells bv the tumour cells can be identified as oligodendroglial cerebro-spinal fluid. cells (Bailey and Bucy, 1929). In some examples, Macroscopically the tumour is a moderately- 122 POSTGRADUATE MEDICAI, JOURNAL March 1950 Postgrad Med J: first published as 10.1136/pgmj.26.293.109 on 1 March 1950. Downloaded from

Fic. 2I.-Oligodendroglioma. H. & E. x 258. FIG. 22. Papilloma of choroid plexus. Protected by copyright. firm cauliflower-like growth attached to the brain of the reticulo-endothelial system and of choroid plexus and distending the ventricle (Fig. mesodermal origin, have not in general been 22). regarded as a potential source of tumours. They Microscopically it is composed of papillae can, however, proliferate to form an ill-defined coated with a cubical or columnar epithelium re- granulomatous type of tumour which may either sembling the choroidal epithelium and usually be confined to the brain alone, or form part of a devoid of cilia and blepharoplasts (Fig. 23). The more generalized reticulosis (Russell, Marshall stroma is of connective tissue. In this it is dis- and Smith, I948). tinguished from papillary ependymomas in which the stroma always contains neuroglia. Recently 6. Cerebral Appendages I have seen two examples in which the cells, in i. Pineal gland. Tumours of this gland are in certain areas, contained cilia and blepharoplasts; general very rare (0.7 per cent. of primary intra- http://pmj.bmj.com/ evidently a perpetuation of the embryonic stage cranial tumours, Cushing, I932). They occur at which these are present. more frequently in the male than in the female. (b) Colloid cyst. This rare tumour, which is (a) Pinealoma. The tumour that generally goes globular and from I to 2 cm. in diameter, is by this name forms a circumscribed, sometimes situated in the anterior end of the velum inter- invasive mass replacing the pineal and compressing positum where it blocks the foramina of Monro, the quadrigeminal plate. In the male it is some- causing intermittent acute attacks of internal times associated with pubertas praecox (Horrax hydrocephalus. Because of its limitation to this and Bailey, 1925). Histologically the structure is on September 30, 2021 by guest. part of the ventricular system it has been suggested quite characteristic; large spheroidal cells, with a that this cyst is derived from the paraphysis, an vesicular nucleus containing one to four con- outgrowth or pocket df the third ventricle in the spicuous nucleoli, form solid masses separated by dorsal part of the lamina terminalis (McLean, trabeculae of connective tissue and blood vessels I936). The paraphysis is vestigial in man but about which are clustered numerous small lympho- persists in certain fishes. cytes (Fig. 24). It is indistinguishable in appear- Histologically these tumours are lined with a ance from the seminoma of the testis and dys- ciliated epithelium, identical with the ependyma, germinoma of the ovary. On this account, and which rests upon a collagenous basement mem- because other tissue elements may sometimes be brane continuous with the stroma of the choroid identified in the pineal tumour on careful search, plexuses. The interior of the cyst is filled with the tumour should be regirded as an atypical thick glairy fluid or solid gelatinous material. teratoma (Russell, I944). This interpretation 4. Microglia. These cells, representative in the would render explicable the so-called ' ectopic -March I950 RUSSELL; The Pathology of Intracranial Tumours I23 Postgrad Med J: first published as 10.1136/pgmj.26.293.109 on 1 March 1950. Downloaded from

4, a

FIG. 23.-Papilloma of choroid plexus. H. & E. x 75. FIG. 24.-Pinealoma. H. & E. x 355. Protected by copyright. pinealomas' which are usually mid-line tumours wall of the sella. Nevertheless they are clinically in the cerebrum or brain-stem. Typical teratomas benign and very rarely give rise to metastases. also occur in the pineal, but are rarer. Their die- The tumour itself is usually composed of acini of -tribution and behaviour in the brain as a whole closely packed polygonal cells separated by a has recently been reviewed by Ingraham and scanty stroma of collagen and blood vessels. In Bailey (1946). other examples the structure is papillarv, the cells (b) True pinealomas, composed of undoubted being columnar or even club-shaped and arranged pineal parenchyma cells, are also rare. in rows along the vessels. In some tumours all 2. Pituitary gland. Primary tumours of the the cells have an agranular cytoplasm. In others posterior lobe are virtually unknown. some of the cells contain granules that are grey (a) Adenomata of the anterior lobe are common when stained with acid fuchsin-anilin blue:; in (19.5 per cent. of primary intracranial tumours in such tumours there are usually other cells with Cushing's series) and are of three types according terra-cotta or orange-red granules, i.e. transitional to the character of their cells :-(i) chromophobe, acidophil cells. Transitional basophil cells have http://pmj.bmj.com/ tii) chromophil, subdivided into (a) acidophil, and not been met in chromophobe adenomata. (3) basophil. (ii) Chromophil adenomata. These are rarer (i) Chromophobe adenoma. Small adenomata than the chromophobe kind, but are similar in causing no enlargement of the gland and un- that small symptomless tumours of both acidophil accompanied by clinical disturbances are ex- and basophil varieties may occasionally be found ceedingly common in the adult. Larger in adults. adenomata, up to I.5 cm. in diameter, may also be (a) Acidophil adenoma. This seldom grows to on September 30, 2021 by guest. symptomless. Symptoms are in fact dependent the size attained by the chromophobe adenoma. upon compression by larger tumours of the It is associated with gigantism in the growing residual anterior lobe, and pressure upon the subject and with acromegaly in the adult. Macro- optic tracts and base of the brain. Such a tumour scopically these tumours resemble the chromo- usually expands the sella turcica and rises, as a phobe variety but differ microscopically in being round or dome-shaped mass, behind the optic composed of transitional and mature acidophil chiasm to occupy the anterior wall of the third cells, or of mature acidophil cells only. ventricle. They are usually rather soft, granular (P) Basophil adenoma. Large tumours causing and friable. Haemorrhages are apt to occur into symptoms of intracranial pressure have rarely them. been recorded. An example, unique in that it Although apparently circumscribed, the micro- gave rise to metastases, has been reported by scope often shows invasion by groups of tumour Cohen and Dible (1936). Both in this and in a cells of the adjacent dura, brain and even the bony large number of recorded cases in which the 124 POSTGRADUATE MEDICAL JOURNAL March 1950Postgrad Med J: first published as 10.1136/pgmj.26.293.109 on 1 March 1950. Downloaded from

Fi:;. z6.-Polar spongioblastoma, showing palisading of fibrillated bipolar cells. P.T.A.H. x 220. Protected by copyright. adenoma was minute the patients displayed a The more solid portions of the tumour are tough, syndrome now named after Cushing. This con- with a smooth outer surface, while deposits of dition, which is commoner in females than in calcium or even bone may be encountered on males, is characterized by the development of section. Histologically they are lined with a obesity, cutaneous striae, plethora, hypertrichosis, squamous epithelium resting upon a layer of vascular hypertension and, less constantly, of dense collagen. In the more solid portions the glycosuria and osteoporosis. Similar clinical de- epithelium forms broad anastomosing trabeculae velopments may accompany a neoplasm of the of cells, often with prickle borders. The collagen suprarenal cortex, or of the thymus. In these, as occupying the interstices between the trabeculae in the examples where a basophil adenoma is frequently degenerates with the formation of cysts. present, the cytoplasm of the basophil cells of the In many of these tumours the cells adjacent to the anterior lobe shows a peculiar hyaline change supporting collagen are of the columnar basal type, http://pmj.bmj.com/ (Crooke, 1935), which appears to be patho- giving an appearance which has led to the mis- gnomonic of the syndrome. The significance of application of the term ' adamantinoma' to such this change and the mutual relationships of the tumours. These columnar cells are not amelo- endocrine glands in connection with Cushing's blasts although they may superficially resemble syndrome are not yet understood. them (Sprawson, I937). (b) Hypophyseal epidetmoid tumours (syn.: In rare instances these cysts are lined with a craniopharyngioma, suprasellar cyst, cyst of Rathke's columnar ciliated epithelium. Such examples are pouch). These tumours, which are usually cystic usually small, intrasellar tumours or are partlv on September 30, 2021 by guest. but may be solid, are held to arise from remnants intrasellar. of the craniopharyngeal duct. They constitute about 4.8 per cent. of primary intracranial tumours B. SECONDARY TUMOURS (Cushing). Though usually suprasellar they may Lack of space forbids any but the most cursory also be intrasellar or even infrasellar. Charac- description of these tumours. teristic examples are found in the floor of the The intracranial cavity may be invaded bv third ventricle in young subjects. They may tumours of the orbit, nasopharynx, etc. Diffuse attain a great size, obliterating the cavity of the invasion of the dura at the base of the brain gives third ventricle and causing great deformity of the rise to a variety of oculo-motor and trigeminal sella turcica. The greater part of the mass is palsies through involvement of the cranial nerves cystic with thin translucent fibrous walls and by growth. The dura beneath the vault may be straw-coloured or brownish fluid contents in diffusely permeated with growth when the which cholesterin crystals are frequently found. adjacent bone is the seat of multiple metastases. March 1950 RUSSELL: The Pathology of Intracranial Tumours 125 Postgrad Med J: first published as 10.1136/pgmj.26.293.109 on 1 March 1950. Downloaded from Such permeation causes a thickening of the dura subcortical white matter is a common site of small (' pachymeningitis carcinomatosa') and is fre- deposits. Considering its relatively small size the quently complicated by subdural haemorrhage cerebellum must be regarded as a site of pre- (Russell and Cairns, 1934). The most frequent dilection. Although metastases may be derived sites of the primary tumour in such cases are the from almost all possible primary sources the fre- lung, prostate and stomach. Discrete metastases quency with which they are attributable to car- may also be encountered in the dura. cinoma of the lung or bronchus is particularly Similarly a diffuse carcinomatosis of the noteworthy. Post-mortem examination in such leptomeninges may occur but is very rare. Search cases may fail to reveal deposits in any other reveals a discrete metastasis which, by direct tissues and, unless an exhaustive search is made spread, has gained access to the cerebro-spinal throughout the lungs, the cerebral focus may be pathway either within the ventricular system or mistaken for the primary tumour. Such a mistake at the base of the brain. The distribution of is especially apt to occur when the primary lung cells throughout the subarachnoid spaces pro- tumour is small and has been entirely symptomless. duces an effect resembling meningitis, hence the Secondary growths of the pituitary gland, term ' meningitis carcinomatosa.' The clinical whether invasive or metastatic, are remarkable in picture has much in common with that of tubercu- their predilection for the posterior lobe and it is ous meningitis. further remarkable that, in such instances, the Metastatic foci within the brain may be single posterior lobe may be completely destroyed or multiple and all parts may be affected. The without the development of diabetes insipidus.

BIBLIOGRAPHY

ALBRECHT, E. (1904), 'Verhandi. d. deutsch. path. Gesellsch.,' EDEN, K. C. (1938), Brain, 6I, 298. Protected by copyright. Siebente Tagung, p. I53. ELVIDGE, A., PENFIELD, W., and CONE, W. (1937), 'Turnors BAILEY, P., and CUSHING, H. (1926), 'Tumors of the Glioma of the Nervous System,' Proc. Assoc. Nerv. Ment. Dis., I6, I07. Group,' Philadelphia. EWING, J. (I 922), ' Neoplastic Diseases,' 2nd edition, Philadelphia. BAILEY, P., and BUCY, P. C. (I929), J. Path. Bact., 32, 735. FLEXNER, S. (i89i), Bull. Johns Hopkins Hosp., 2, 115. BAILEY, P., and BUCY, P. C. (I930), Acta Psych. et Neurol., GLOBUS, J. H., and SILBERT, S. (093i), Arch. Neur. Psychiat., 5, 439. 25, 937. BAILEY, P., and BUCY, P. C. (I93I), Amer. J. Cancer., IS, I5. GLOBUS, J. H. (1938), Amer. J7. Cancer, 32, i63. BAILEY, P. (1932), 'Cellular Types in Primary Turnors of Brain' HIS, W. (1889), ' Arch. f. Anat. u. in 'Cytology and Cellular Pathology of the Nervous System,' Phys.,' Anat. Abt. Suppl., p. 249. edited by Wilder Penfield, 3, 905, New York. HORRAX, G., and BAILEY, P. (1925), Arch. Neur. Psychiat., BAILEY, P., and EISENHARDT, L. (1932), 7. Comp. Neurol., 13, 423. 56, 39I. INGRAHAM, F. D., and BAILEY, 0. T. (1946), J. Neurosurg., BAKER, A. B., and ADAMS, J. M. (1938), Amer. Cancer, 3, 5''. J7. 34, KERNOHAN, J. W., and KERNOHAN, E. M. F. (1937), 214. 'Tumors of the Nervous System,' Proc. Assoc. Nerv. Ment. BECK, D. J. K., and RUSSELL, D. S. (1942), Brain, 65, 352. Dis., I6, I82. BERGSTRAND, H., OLIVECRONA, H., and TONNIS, W. KRAYENBUHL, H. (1936), Brain, (1936), ' Gefassmissbildung und Gefassgeschwulste des 59, 337. Gehirns,' Leipzig. KUFS, H. (I928), Ztschr. f. d. ges. Neurol. u. Psych., 113, 65i. BLAND, J. 0. W., and RUSSELL, D. S. (1938), J. Path. Bact., MALLORY, F. B. (1902), 7. Med. Res., 8, I. 47, 291. MALLORY, F. B. (ig08), J. Exp. Med., 10, 575. http://pmj.bmj.com/ BLUMENFELD, C. M., and GARDNER, J. (1945), Arch. Neur. McLEAN, A. J. (I936), Arch. Neur. Psychiat., 36, 485. and Psychiat., Chicago, 54, 274. NELSON, A. A. (1936), Amer. J. Cancer., 28, i. BURROW, J. LE F., and STEWART, M. J. (1923-24), 7. Neurol. OLIVECRONA, H. (1934), 'Die parasagittalen Meningeome,' and Psychopath., 4, 205. Leipzig. CAIRNS, H., and RUSSELL, D. S. (I93I), Brain, 54, 377. PENFIELD, W. (1932), 'Cytology and Cellular Pathology of the CHOROBSKI, J., JARZYMSKI, J., and FERENS, E. (I939), Nervous System,' 2, 423, New York. Surg., Gyn. and Obst., 68, 677. RUSSELL, D. S., and CAIRNS, H. (i934), Brain, 57, 32. COBB, S. (I915), Ann. Surg. 62, 64I. RUSSELL, D. S., and BLAND, J. 0. W. (1934), J. Path. Bat., COHEN, H., and DIBLE, J. H. (1936), Brain, 59, 395. 39, 375. COX, L. B. (I933), Amer. J. Path., 9, 839. RUSSELL, D. S. (944), J. Path. Bact., 56, I45. CROOKE, A. C. (It35), J. Path. Bact., 41, 339. RUSSELL, D. S., and CAIRNS, H. (i947), Arch. de histol. normal on September 30, 2021 by guest. CUSHING, H. (192.2a), Arch. Neur. Psychiat., 8, I39. y patolog., 3, 423. CUSHING, H. (ig:12b), Brain, 45, 282. RUSSELL, D. S., MARSHALL, A. H. E., and SMITH, F. B. CUSHING, H. (192:7), Surg. Gyn. and Obst., 44, 721. (1948), Brain, 71, I. CUSHING, H., and EISENHARDT, L. (1938), 'Meningiomas, SCHMIDT, M. B. (1902), Virchow's Arch., 170, 429. their Classification, Regional Behaviour, Life History and SCHNITKER, M. T., and AYER, D. (1938), Jour. Nerv. Ment. Surgical End Results,' Springfield, Illinois. Dis., 87, 45. CUSHING, H., and BAILEY, P. (I928), 'Blood Vessel Tumors SPRAWSON, E. (X937), Brit. Dent. Journ., 62, 177. of the Brain,' Springfield, Illinois. STEVENSON, L., and ECHLIN, F. (i934), Arch. Neur. Psychiat., CUSHING, H. (1932), 'Intracranial Tumors, Notes upon a 3', 93. Series of 2,000 Verified Cases with Surgical-Mortality Per- STURGE, W. A. (1879), Trans. Clin. Soc., 12, I62. centages Pertaining Thereto,' Springfield, Illinois. VAN WAGENEN W. P. (1930), Arch. Surg., 20, 199. DAVIE, T. B. (1932), 7. Path. Bact., 35, 359. WEBIBER. F. P. (1922-23), Jouir. Netur. Psvchopath., 3, 134. Postgrad Med J: first published as 10.1136/pgmj.26.293.109 on 1 March 1950. Downloaded from

I3IC iz6b Protected by copyright. http://pmj.bmj.com/ on September 30, 2021 by guest.

FIG. I.-Progression of virus along decussating optic pathway in mice inoculated intraocularly with virus of vesicular stomatitis. (a) Frontal section of head of mouse showing lesion (arrow) in retina of right eye, inoculated with virus. (b) Arrow points to necrotic virus lesion in left superior colliculus of same mouse. (c) Arrow points to necrotic virus lesion in right superior colliculus of another mouse, following inoculation of virus into left eye. (These illustrations are reproduced from Sabin, A. B., and Olitsky, P. K., J. Exp. Med., 1938, 67, 201-228, with permission of the Journal of Experimental Medicine.)