Folia Dsychiatrica e t Neurologica Japonica, Vol. 11, No. 3, 1957

NERVE FlBERS REMAINING IN GLIOMAS OF THE CEREBRUM AND T H E PONS

bsr Sadao Shirota

1st Surgical Division, Kyoto IJniversity School of Medicine, Kyoto (Director : Prof. Dr. Ch;safo Araki)

It is our occasional clinical experience to find an unexpectedly wide spreading glioma a t surgical operation or autopsy in spite of slight preoperative neurological manifestations. Several authors, such as Bailey and Cicshing, Bergstrand, Alpers and Yaskin, etc. have reported the preservation of preexisting nerve fibers in gliomas of the cerebrum and the pons. It may be assumed that clinical symptoms vary depend- ing on the amount of the residual nerve fibers. In the present work, I have investigated the relationship between the histological changes of nerve fibers in tumor tissue and the clinical manifestations, chiefly motor and sensory paralysis, in autopsy cases of various kinds of g 1 iomas .

I. Material

Twenty autopsy cases in this Clinic in these three years were subjected to examination.

Cerebrum : Glioblastoma multiforme Astrocytoma Ependyrnoma Spongioblstoma polare

Pons : (;lioblastoma multiforme Astrocytoma hledullohlastoma, partially constated as Glioblastoma multiforme

Total : _ _ - ~ - .--

9 cases 4 cases 1 case 1 case 1 case 3 cases

~ -. 1 case

20 cases

11. Staining techniques

1 I

2 I ll‘cigrrt-Pal‘s method.

Biclscl~o~usk~~-C~ross’ impregnation method modified by Masaja Araki, Professor of Pathology. Kyoto Prefectural Medical School.

111. Results and clinical correlation

Generally, nerve fibers in the slirroundings of a glioma were scarcely destroyed. but toward the interior of the tumor they diminished suddenly or gradually in number ; some of them showed the evidences of degenera-

~~ - ~~~

Received for publication February 11. 14;;

Nerve Fibers Remaining in Gliomas 275

tion. The degree of diminution was different case by case. In the normal areas nerve fibers looked like a meshwork of wires, but some of them ran straight in bundles. Approaching toward the center of glioma from the peripheral portion, nerve fibers diminished in number, parallel fibers became scattered and wave and the degenerative features of nerve fibers, such as swelling, spindle-shaped or beaded swelling, fragmentation, etc., could be seen here and there. In the necrotic areas no normal nerve fibers could be seen any longer. Usually, fragments of nerve fibers were scattered in those areas, but sometimes

Fig. 1. Nerve fiber meshwork in normal brain tissue. Baelschowsky-Gross stain modified by Araki. x603

Fig. 2. I degree diminution of nerve fibers. x63:!

276 S. Shirota:

Fig. 3. I1 degree diminution of ne rve fibers. x6iJ(l

Fig 4 . 111 degree diminution of nerve fibers Y 60 1

it was difficult to find even a trace of them. In accordance with the number of existing nerve fibers still maintaining normal appearances in tumor tissue, the degrees of their diminution were classified into four, i.e. I, 11, 111, and IV (Fig. 1, 2, 3, 4. 5). In the zones of I11 and IV degree, not only quantitative but also qualitative (degenerative) changes of nerve fibers were observed. The persistent nerve fibers in each glioma were investigated and a comparative study between histological

Nerve Fibers Remaining in Gliomas 277

Fig. 5. IV degree diminution of nerve fibers. x6OC

findings and clinical features was made. In deciding the degree of diminution of nerve fibers in tumor tissue, the finding in pathological areas was compared with that in corresponding intact areas on the opposite side of the same case.

A. Insltrnws oaf ce l zb id gliomcr

1) Glioblastoma multiforme Case 1 , M. O., a man aged 53. He complained of mental disturbance

from 5 months before his admission. Disturbance of skilled movements developed one month ago and paresis of the left upper and lower limbs ten days before. On admission right facial paresis with distur- bance of sensation in the left half of his face was noticed.

Gross examination of the brain: A rather well defined tumor as large as the fist of a child in the right frontoparietal lobe, largely occupying the subcortex, but partially infiltrating the cortex. Many small hemorrhagic and necrotic foci were observed.

Histological features: Tumor tissue was rich in cells of different shapes and types. Giant multinucleated cells and small blood vessels were scattered and endothelial hyperplasia and wreath rosettes were also seen.

Nerve fibers: With the increasing infiltration of tumor cells the number of remaining nerve fibers diminished and waving nerve fibers increased in proceeding toward the interior of the tumor. The transi- tion from I to I1 degree zone in the marginal area of the tumor was sharp. Nerve fibers disappeared at the center of the tumor where necrotic and hemorrhagic foci were found and fragments of them were scattered here and there (Fig. 5 ) . The greater par t of this tumor showed IV degree and partially I11 degree. In the motor cortex entirely involved by the tumor changes of I1 or I11 degree were found, whereas

278 S. Shirota:

motor paralysis was comparatively slight. It may be assumed that many nerve fibers remaining in the motor cortex were still functioning.

Since three and a half years beforc his admission, he had fits of unconsciousness of about ten minutes’ duration once a week. After three months he had general epileptic seizures twice a t intervals of two hours. Since then he was given sedativa and the seizure disappeared. But he lost consciousness a t irregular intervals. Twenty days before admission, disturbances in memory and speech were noticed. Two weeks later paresis of right upper limb developed. On admission choked disc of 3D. in the right and 2D. in the left eye were constated. The visual power was 0.1 (-3.5 D-2.0, in the right and 4m.lfinger count I - -4.OD -1.0) in the left. No changes were observed in visual fields.

Gross examination of the bra in : A diffusely infiltrating tumor, as large as an apple, was situated subcortically in the left parietal region. partially extending to the temporal lobe and projecting into left lateral ventricle. The tumor had small cystic portions containing colloid sub- stance by missing necrotic nor hemorrhagic areas.

Histological fcatures : Small blood vessels and necrotic foci were seen. Around the necrotic foci, tumor cells with nuclei containing heavy chromatin network were found. They varied in size and shape.

Nerve fibers: Diminished more gradually toward the center than in case 1. Several nerve fibers were seen passing among gemistocytes and spongioblasts in bundles [Fig. 6 : , showing a clear contrast with the brownish stained glia syncytium. As compared with the finding in case 1, degenerative changes in nerve fibers were less conspicuous. Waving nerve fibers were fewer in number and swelling or metachro- masia could be found only sparsely. It was considered that changes of I1 or 111 degree were predominant. Comparing sections stained by Bielsrhoiosky’s method with those by Weigert-Pal’s from the same block,

Case 2, H . O., a man aged 32.

Fig. ti. Nerve fiber bundles in case 2 of glioblastoma multiforme. x606

Nerve Fibers Remainiug in Gliomas 279

Fig. 7. The same section with Fig. 6 stained by Weigert-Pal method. x600

there were preserved a good number of myelin sheaths a s shown in Fig. 7. Evidences of degeneration such a s globular swelling, thinning with beaded swelling, globule formation, atrophy etc. were found in about one third of the nerve fibers stained by Weigert. We can hardly know in what percentage the nerve fibers in Bielschowsky’s preparation are myelinated, but it is certain that normal myelinated fibers have been still preserved in a fairly good number in this tumor. Motor aphasia and changes in visual field, which might be expected in tumors of this localization, were absent in this case and paresis was unex- pectedly slight. The presence of these surviving nerve fibers in the tumor might have something to do with the lack of symptoms. Histo- logically, case 2 may be considered less malignant than case 1, angio- necrotic foci being fewer. The benign nature of the tumor can be accepted from their clinical course, too, as three years and seven months elapsed before admission from the onset of symptoms in case 2 and only seven months in case 1.

Case 3, Y. K., a man aged 47. He had Jacksonian seizures for the first time seven years before his admission. The frequency of the seizures gradually increased from once a month or two in the early stage to once a week or several times a day of late. The attack began as clonic convulsions of right upper extremities and was followed by generalized tonic convulsions. Since about a year diplopia, headache, vomiting, facial twitching etc. developed. On admission the left facial paresis of the central type, disorientation, hyperactive patellar and achilles jerks, Babinski, Oppenheim and Gordon signs on the left side were observed.

There was found a huge, diffusely infiltrative, frontoparietal tumor larger than a man’s fist chiefly occupy- ing subcortex and partially extending into the left lateral ventricle. Several sharply defined hemorrhagic foci of 1.0 - 2.0 cm. in diameter were seen. The greater part of the genu of the internal capsule,

Gross examination of the brain:

"80 S . Shirota:

putamen and globus pallidus on the left side was involved by the tumor (Fig. 8 ) .

Fig. 8. Case 3 of glioblastoma multiforme. Genu of left internal capsule, globus pallidus and putaman are invaded.

Fig Remaining nerve fibers in case '3 of j:lioblastma multiforme .t900

Histologically, this w a s the least malignant glioblastoma of these three cases.

Nerve fibers: They went diminishing in number more gradually toward the interior than in case 2 and even parallel nerve bundles were observed in the tumor (Fig. 91. In the central part of the tumor hemorrhagic foci were found. The changes were judged largely a s I1

Nerve Fibers Remaining in Gliomas 28 1

Fig. 10. The same section with Fig. 9 stained by Weigert-Pal method. x6UO

degree and partially as 111. When stained with Pal-Weigert's method normal myelin sheaths were seen in a larger number than in case 2, as shown in Fig. 10. Histological evidences of malignancy decreased in the order of case 1, 2 and 3, and the survival periods of the patients from the onset of symptoms increased in the reverse order. Further- more, the number of preserved nerve fibers in the tumor increased in the same order. In spite of the wide tumor invasion of the internal capsule on the left side, no paralysis was observed in case 3. It is assumed that the comparatively slight clinical symptoms a re related to the survival of many nerve fibers in the tumor. The other six cases of glioblastoma multiforme in this series may be summarized in Table 1.

2) Astrocytoma Case 1, H. Y., a man aged 21. Headache in the frontal region since

about 2 years before his admission. Vomiting from 9 months before. Generalized convulsions, sometimes focal in the left upper and lower extremities since 6 months ago. Some speech disturbance and visual disturbance ensued later accompanied with difficulty in walking and urinary incontinence.

Gross examination of the brain: A sharply defined elastic hard tumor, as large as a hen's egg, occupying the subcortex of right tem- poroparietal lobe and partially infiltrating into the cortex of lingual gyrus and extending into the posterior horn of right ventricle was discovered.

Histological features : Fibrillary astrocytoma. Nerve fibers : By our stain (M. Araki's modification of Bielschowsky's

stain) processes of pathological astrocytes were sometimes stained light brown o r grey, but nerve fibers could be easily distinguished from the former. The fibers with clear outline and stained deep in color were considered to be nerve fibers even if they were crooked o r

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Nerve Fibers Remaining in Gliomas 283

Fig. 11. Remaining nerve fibers in case 1 of Astrocytoma. x600

irregular in thickness, while glia processes were comparatively short, crooked irregularly, constant in thickness and light in color. In this case nerve fibers diminished in number rather rapidly toward the interior, 111, partially I1 degree changes being predominant. Glia pro. cesses which were rather thick and less argyrophylic than nerve fibers were stained together. Degenerative features were rare.

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Fig. 12. Remaining nerve fibers in case 2 of Astrocytoma. x690

284 S. Shirota :

month ago, the right upper and lower extremities became completely paralysed. On admission spinal fluid pressure showed 550 mm. of water. Right Babinski sign was positive. There was detected a left frontoparietel tumor a s large as hen's egg. partially extending into left lateral ventricle. In spite of the presence of such a tumor, there were no signs of paresis and motor aphasia until five months before his admission.

Histological diagnosis was a fibrillary astrocytoma. Nerve fibers: They diminished gradually toward the center and

changes of 111 and I1 degree were mainly seen (Fig. 12) . Case 3, K . K., a man aged 34. About two years before his admission,

he fell from a height of two meters to the ground and was hit severely on his parietal region and lied unconscious for a short time. Since about three months ago, severe headache, especially in the parietal region, and tinnitus occurred. He had sometimes become suddenly unconscious during his work. From about two months ago, paresis of the right upper and lower limbs was noticed.

Gross examination of the brain: 'There was found a dark brown soft tumor as large as an apple, occupying posterior half of left lateral ventricle and extending into the contralateral ventricle and infiltrating the genu of the left internal capsule.

Histological features : Mixed protoplasmic and fibrillary astro- cytoma.

Nerve fibers: Changes were of I1 and 111 degree, and nerve fibers diminished very gradually toward the interior of the tumor.

Case 4, R. K., a girl aged 5. This case deals with a fibrillary astrocytoma arising supposedly from the right temporal lobe and growing chiefly extracerebrally. The size of the tumor was as large as a man's fist (Fig. 13, 1-11. Nerve fibers were hardly found in the

Fig. 13. Case 4 of Astrocytoma

Nerve Fibers Remaining in Gliomas 285

Fig. 14. Frontal section of the tumor shown in Fig. 13.

tumor tissue. Since the tumor seemed to have grown outward and ex- pansively, it is supposed that the absence of nerve fibers in the tumor means not the disappearance of preexisting ones, but the original lacking of nerve fibers.

S. A., a boy aged 2. From about two months bebore his admission, Paresis of the right upper

3) Ependymoma

he complained of headache and vomiting

Fig. 15. A boy aged 2 , Ependymoma.

286 S. Shirota:

and bilateral lower extremities, choked disk, bilateral Oppenheim sign and ankle clonus, central paresis of the right facial nerve, and Macewen sign were observed. The spinal fluid pressure showed 450 mm. of water. He died af ter two months.

As is seen in Fig. 15, a huge, well defined, elastic, soft tumor larger than a fist of a man, occupying the greater part of the left frontoparietal lobe was present. Softening areas of yellowish color were found here and there. The lateral part of the left frontal lobe was totally invaded by the tumor, but in the mesial portion the cortex could be distinguished, though it was as thin a s paper.

Nerve fibers: In the thinned cortex, nerve fibers were waving intensively but the diminution of them was not marked. Toward the interior of the tumor, they diminished rapidly in number, being hardly found inside of the tumor more than two millimeters from the edge of invasion. It is therefore supposed that this huge tumor developed not infiltratively but expansively pushing aside the surrounding nerve tissues in the same way as the preceding case (as t rocytoma~, so that no nerve fibers were found in the interior of the tumor.

Not only in these two cases, but in all cases of gliomas that a r e well defined, there may not be nerve fibers. It is surprising that in spite of the pressure of this huge tumor, only slight paresis of the right upper and lower extremities were observed from about two months before his admission. It is supposed that thc oppression by the tumor developed so slowly that the function of the thinned cortex was well compensated by other parts of the brain.

Gross examination of the brain:

11 Spongiohlastoma polare A . A’., a man aged 16. From three months beforc his admission,

he complained of headache and vomiting, and often dropped a bowl from his hand. At the same time he had a tendency to stagger to

Fig. 16 Remaining nerve fibers in spongioblastoma polare. u600

Nerve Fibers Remaining in Glioinas 287

the left. convulsions of four extremities.

widely invading the right wall of the third ventricle.

Two weeks ago, he suddenly became unconscious, suffering

Gross examination of the brain: A tumor a s large as a hen’s egg,

Nerve fibers give change of I1 to I11 degree (Fig. 16). In cerebral gliomas occurring in such regions from which no focal

motor or sensory symptoms originate, i.e. silent areas, correlations between the amount of remaining nerve fibers in the tumor and clinical manifestations can not be known.

B. Instcrncrs 0.f the pons glioirztt

Case I , M. T., a girl aged 12. From about two months before her admission, she gradually complained of the motor disturbances of the left hand and fingers beside a sudden paresis of the left lower ex- tremity. Speech disturbance, diplopia, difficulty in swallowing were also noticed ; food dropped from the right corner of her mouth. There was left hemiparesis on the day of her admission, which was followed by the left hemiplegia four days later, before she died on the next day of respiratory paralysis. When she was admitted, the abducent and facial nerve were paralysed and the glossopharyngeal and hypoglos- sal nerve were paretic on the right side. Bilateral Babinski, Oppenheiwz and the left Gordon sign were positive, while bilateral knee and ankle jerks were hyperactive. There was no papilledema and spinal fluid pressure showed 100 mm. of water. Survival from the onset of symptoms

Fig. 17. Case 1 of pons glioma.

288 S. Shirota:

Fig. 18. Frontal section of the tumor shown in Fig. 17

was about two months. Gross examination of the brain: Pons was enlarged as a whole,

especially on the right side. The tumor extended rostrally to the level of the root of trigeniinal nerve and caudally to the caudal one third of the olive on the right and to the rostral part of it on the left. Cerebral peduncles were not enlarged. Transverse sections revealed a huge softening area extending from the level of facial colliculus to Lhe rostral end of the olive and approaching dorsally to the tegmentum in the rostral part and ventrally to the basis in the caudal portion. The softening area was filled with blood in its ventral one-third portion and in the rest with agar-like substance (Fig. 17, 181.

Histological features: The tumor w a s composed mainly of small cclls with scanty cytoplasm and round or oval nucleus containing dense chromatin network. These cells were particularly dense around the softening area. Mitotic figures were found here and there, but not so numerous. Abundant thin-walled blood vessels without endothelial hyperplasia were found here and there, but not so numerous. Around the blood vessels, pseudorosettes were seen. This tumor was diagnosed as medulloblastoma partially mixed with glioblastoma multiforme. Serial sections revealed that the greater parts of the corticospinal and corticopontine t racts and nuclei pontis on the right side were involved in the softening area and medial lemniscus. thalamoolivary tract , upper

Nerve Fibers Remaining in Glioinas 339

and lower olivary nuclei were situated in the surroundings of the softening focus but the medial par ts of the corticospinal and cortico- pontine tracts on the left side were involved by the tumor.

Nerve fibers: It was the striking feature here that tumor cells tended to infiltrate along nerve fiber bundles. As is shown in Fig. 19, nerve fibers could be found in I1 or I11 degree even in the vicinity of softening focus. Tumor cells, infiltrating a t first outside the nerve bundles, finally penetrated into the bundles which then became loose. In the areas where the infiltration of tumor cells was slight, nerve fibers remained in I1 degree and in more slightly invaded areas, the number of nerve fibers was nearly normal. At the level of the middle portion of the olive, the infiltration of tumor cells occurred only in the corticospinal tract and in a part of the inferior olivary nucleus on the right side and in the corticospinal tract thus infiltrated, nerve fibers were preserved in I1 or 111 degree. It was surprising that she could move her left extremities, though with difficulty, until two or three days before her death. It may be said that the diminution of nerve fibers in I1 or 111 degree cause paresis but not paralysis. It might be due to bleeding in the tumor that paralysis suddenly deve- loped two days before death.

Fig. 19. Remaining nerve fibers i n case 1 of pons glioma in the vicinity of softening focus. x600

Case 2, I. S., a boy aged 11. Abducens paresis on the right side accompanying diplopia since 13 months before his admission. Right facial paresis three months later. Intention tremor of right fingers, motor disturbance of the right lower extremity, difficulty in walking nine months later. On admission, 1) visual disturbance, especially on the right side, 2) paralysis of the right abducent, trigeminal, facial, acoustic and glossopharyngeal nerves, 3) static ataxia, increase of bilateral pateilar and achilles tendon reflexes were noticed. Abnormal

S. Shirotx:

F.g 2 ~ ' Remaining nerve fibers in case 2 of pons glioma j. 000

Fig. 21 Remaining nerve fibers in case 3 of pons glioma. \ 6 U

reflexes were not observed. T h e greater pa r t of the right side of the pons was invaded, while the left side was oppressed markedly but not involved by the tumor. In spite of the pressure of such a huge tumor, there was no more than paresis in the left lower extremity.

Histologically, the tumor was a fibrillary astrocytoma partially mixed with a spongioblastoma polare.

Nerve f ibers : Change stood mostly in I1 degree, partially in iii degree I Fig. 201.

Survival period from the onset of symptoms was 14 months.

Nerve Fibers Remaining in Gliomas 291

Case 3, E. K., a girl aged 5. Her complaint consisted of nausea, severe headache (in the left frontal region) from 6 months before her admission. She had difficulty in holding a bowl and also in walking since two months ago. Gradual development of motor disturbances in four extremities finally caused inability to walk these 10 days. Death af ter two weeks of admission. Tumor invaded bilateral corticospinal tracts widely from the level of trigeminal nerve to that of facial col- liculus.

Histlogically. the tumor presented an astrocytoma and nerve fiber changes were found in I1 or 111 degree (Fig. 21).

Case 4 , M. Y., a boy aged 9. Astrocytoma. Standing in 11 degree of change (Fig. 22).

Fig. 22. Remaining nerve fibers in case 4 of pons glioma. x600

Case 5, K . H., a girl aged 8. Glioblastoma multiforme. Standing in I11 degree of change.

In cases 4 and 5, the specimens large enough to cover the whole extent of the pons were not available so that the boundaries of the tumor were not certain. It is therefore impossible to correlate the extent of the tumor with clinical manifestations. So I only showed the degree of preservation of nerve fibers in several parts of the tumor tissue. Generally speaking, the number of remaining nerve fibers in a unit area of microscopic field was larger in pons gliomas than in cerebral gliomas. But i t was also apparent that more nerve fibers were preserved in astrocytomas than in medulloblastomas or glioblas- tomas.

IV Comment

In studying the correlation between clinical features, especially

292 S. Shirota:

motor and sensory paralysis, and surviving nerve fibers in the tumor, following factors must be czrefully considered.

11 What relation exists there between the morphological changes in each nerve fiber and its conductivity of impulses? In other words, w h a t is the function of the nerve fiber contra degenerative changes'! Fragmented nerve fibers must have, as it matter of course, no function, but some of the other degenerating nerve fibers may still maintain physiological functions. It is very difficult to know with what degree of degenerative changes nerve fibers may still be able to transmit impulses to excite the next neuron beyond synapse. Isn't it reasonable to suppose that nerve fibers with obvious degenerative changes have already no functions .!

Degenerations of nerve fibers in tumor may result chiefly from mechanical compression due to the growth of the tumor and anoxemia due to the disturbances in blood circulation. However, in case of sharply defined glioma ( there a r e two such cases in this series), the changes of nerve fibers due to mechanical pressure in the surround- ings of the tumor, even when the compression seems to be very marked. a re usually unexpectedly slight, if the growth of the tumor is slow. The same may be recognized in infiltrating tumors of slow growth. On the contrary nerve fibers in rapidly growing glioma, whether the growth may be expansive or infiltrative, a r e apt to degenerate easily, a fact which may be recognized in glioblastoma multiforme, etc.

31 When a group of nerve fibers having a certain function is damaged by tumor, what percentage of nerve fibers is necessary to remain intact in order to maintain the original functions? According to the result of experiments of K . Wataiaabe in this Laboratory con- cerning crossed anastomosis between tibia1 and fibular nerves in dogs. it may be concluded that, even when nerve fibers a re reduced to 1/b- l/d. the functions of the peripheral nerve is maintained without any noticeable disturbance. Similar relations may likely exist also in the central nervous system,

In discussing the number of remaining nerve fibers in glioma. it may not be unreasonable to say that the number of nerve fibers in a microscopic unit area wil l be reduced by the loosening of nervc bundics in inversc proportion to the increase in volume of the brain due to tumor. even when all nerve fibers are preserved. But the proper method of correction is unknown. Roughly estimating, i f a certain portion of the brain is enlarged by tumor and the length of a side of a unit square becomes twice, the number of nerve fibers in the unit square diminish to 1/4. Perhaps this may be the most extreme case. Anyhow, if the brain swells by tumor the apparent diminution of nerve tihers to about 1/1 in number can be observed, even when the absolute number is unchanged. .4ccordingly it is necessary to keep in mind that the decrease to about 1 / 1 does not necessarily cause disturbances in function.

Classification into I , 11. I11 a n d I V degree w a s used tentatively to indicate the number of nerve fibers remaining in gliomas. The decision of the degree in each case was made from the average changes in the interior of the tumor ; therefore, in the margin of invasion or in slightly infiltrated areas, more nerve fibers may be found persistent Consequently whether the nerve fibers diminish in number gradually or rapidly towards the center of the tumor is closely related to clinical

2

1

.i

Nerve Fibers Remaining in G.liomas 293

manifestations. The less malignant a glioma is clinically and histologically, the

more nerve fibers can be found remaining in the tumor. In cases with I or I1 degree of the diminution of nerve fibers the original functions of nerve bundles a re often well preserved as in cases 2 and 3 of glioblastoma multiforme. In pons glioma this tendency is more remarkable. The fact that in less malignant infiltrating gliomas clinical manifestations a re often unduly slight considering the localization of the tumor may be explained by the assumption that nerve fibers remaining in the tumor still maintain their original functions.

6)

V Summary

1) Twenty autopsy cases of cerebral and pons glioma in this Clinic in these three years were taken to investigate the relationship between remaining nerve fibers in tumor and clinical manifestations.

The degree of decrease in nerve fibers in the tumor has been classified into I, 11, I11 and IV degree in accordance with the number of preexisting nerve fibers still maintaining their normal histologic features.

3) The less malignant a glioma is clinically and histologically, the more nerve fibers a re found still preserved.

4) In case of I or I1 degree of diminution the remaining nerve fibers often maintain their original functions. This tendency is more remarkable in pons gliomas.

Unduly slight clinical manifestations considering the localization of the tumor, as is often the case in patients with benign cerebral gliomas, may be due to the preservation of nerve fibers in the tumor.

6) Some gliomas grow expansively and not infiltratively. In such gliomas no nerve fibers are found even if they a re histologically benign. This is to be considered as the result of nerve fibers being pushed aside and not being destroyed.

2)

5)

In conclusion many thanks should be expressed to Prof. Musaw Aruki. Profes- sor of Pathology at the Kyoto Prefectural Medical School for his kind help in the staining techniques.

References

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