J. Neurol. Neurosurg. Psychiat., 1970, 33, 824-827

Malignant change in an intraspinal nerve sheathtumour

D. J. B. ASHLEY AND P. J. E. WILSON

From the Departments ofPathology and Neurosurgery, Morriston Hospital, Swansea

SUMMARY A spinal neurofibroma with malignant change leading to 'sarcomatous meningitis' isdescribed in a woman of 73. Three similar cases have been found in the literature. This is an exceed-ingly rare complication of nerve sheath tumours in the spinal canal.

Primary intraspinal tumours are less common thanprimary intracranial neoplasms and are more oftenderived from extra-medullary tissues. Kernohan andSayre (1952) described a collection of 979 intraspinallesions, more than half of which were nerve sheathtumours (293 cases) and meningiomas (254 cases).Russell and Rubinstein (1963) likewise found nervesheath tumours to be as frequent as meningiomas inthe spinal canal. Hosoi (1931) found that 13% ofpatients with neurofibromatosis eventually developedneurofibrosarcomata and Stout (1949) found thatover half of the neurofibrosarcomata reported hadarisen in nodules of neurofibromatosis. Malignantchange in solitary or ostensibly solitary nerve sheathtumours is rare. Having been able to find only threesuch cases in the literature, we feel justified in report-ing a further case because of the rarity of thecondition and because of its misleading clinicalpresentation.

CASE HISTORY

A widow aged 73 years was referred to one of us(P.J.E.W.) on 19 December 1968 because of severe weak-ness and numbness of both legs, of one day's duration.She had been an alert and energetic woman until

November 1968, when she began to suffer from bouts ofsevere frontal headache accompanied by nausea andvomiting. Her relatives then noticed that she was mentallyconfused, rambling, and at times drowsy. On admissionto hospital on 6 December 1969, she was found to be awell-nourished, alert woman, but disorientated and unableto give a clear account of herself. Her initial alertness gaveplace to fluctuating drowsiness. Neurological examinationshowed no papilloedema, no defects of cranial nervefunctions, no weakness, tremor, dystonia, or incoordin-ation of the limbs, no abnormality of limb reflexes, and noovert sensory disturbance, but the left plantar responsewas extensor. General physical examination was not

contributory; there was no evidence of generalizedneurofibromatosis. The peripheral blood was normal, theESR 18 mm in one hour, and serological tests werenegative. Skull radiographs showed no abnormality. Thechest radiograph showed slight unfolding of the aorta anda small indefinite opacity in the lower zone of the rightlung-field. Lumbar puncture revealed yellow CSF at lowpressure, containing protein 3300 mg/100 ml., no redcells, and 1 white cell per c.mm. No manometric blockwas found on jugular compression.The patient was seen by Dr. B. M. Phillips, consultant

neurologist, who suspected the presence of a chronicsubdural haematoma. However, an ultrasonic echogramshowed no shift of the midline echo, and an EEG showedno lateralized abnormality, although it was grosslyabnormal by virtue of persistent high-amplitude deltaactivity at 1 to 2 Hz over both fronto-temporal regions.Left carotid angiography showed irregularity and tortu-osity of the carotid syphon and its major branches,particularly the pericallosal artery. Right carotid angi-ography failed.On 18 December 1968 the patient was noticed for the

first time to have difficulty in walking. By the followingday, she exhibited a flaccid paraparesis, more dense in theright leg than the left, with bilateral extensor plantarresponses, a sensory level to pinprick at T6 dermatomeand acute urinary retention. Myelography revealed acomplete spinal block opposite T5 vertebral body, with a'smear' effect for some four segments caudal to this,suggestive of arachnoidal adhesions (Fig. 1).

Immediate spinal exploration was performed by one ofus (P.J.E.W.), the laminae of T2 to T6 vertebrae inclusivebeing removed. No extradural abnormality was found,but opening the dura at the level of T4 to 5 revealed alarge sausage-shaped, firm, pink, smooth tumour,displacing the spinal cord forwards and to the left. Thepia-arachnoid was thickened and infiltrated in a nodularfashion by pink and yellow tissue almost to the lim-iits ofthe operative exposure, with here and there small loculi ofclear yellow fluid. The tumour was easily mobilized andremoved in toto, together with posterior rootlets of the

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Malignant change in an intraspinal nerve sheath tumour

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FIG. 1. Myelogram showing a complete spinal block at thelevel of the 5th thoracic vertebra.

right T5 spinal root from which it clearly arose. As muchas possible of the infiltrated arachnoid was also removed,which amply decompressed the cord but did not restorecerebrospinal fluid flow.

For the first week after operation there was both motorand sensory improvement in the lower limbs, and she wasmore continuously alert, lucid, and better orientated.Thereafter an insidious deterioration occurred, until by6 January 1969 she was more densely paraplegic andj moreseverely confused than she had been before laminectomy.Repeated myelography showed a total spinal block, belowthe limit of the laminectomy.At this point it was conjectured that there was lepto-

meningeal seeding of neoplastic cells not only in the spinalcanal but also above the foramen magnum, and that shemight have a resultant communicating hydrocephaluswhich was responsible for the cerebral component of herillness. Diversion of the CSF and radiotherapy weretherefore considered, but finally rejected in view of hergenerally poor condition and the reluctance of her familythat she should undergo further surgery. She diedsuddenly on 11 January 1969.

HISTOLOGY The surgical specimen consisted of two parts.One was an ovoid smooth firm pink tumour measuring2 x 1 x 1 cm. The remainder comprised fragments ofthickened nodular pia-arachnoid.The solid tumour presented the features of a neuro-

fibroma. It consisted for the most part of spindle-shapedcells arranged in interlacing bundles in a collagenous

matrix (Fig. 2). In some areas there were groups of poly-gonal cells with foamy cytoplasm. Mitoses were infrequentand the cellular pattem was regular. There was a thincapsule. In several areas close to the capsule the histo-logical appearance was different. Here the tumourconsisted of polygonal cells with nuclei of irregular shapesand sizes (Fig. 3). The stroma comprised some collagen

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FIG. 2. A general view of the spinal tumour showingspindle shaped cells and groups ofpolygonal xanthomatouscells. H and E x 100.

fibres and masses of intercellular connective tissue mucin.The fragment from the pia-arachnoid consisted of

meningeal tissue which was heavily infiltrated withneoplastic cells resembling those in the poorly differ-entiated part of the main tumour.The histological diagnosis made was neurofibroma of

an intraspinal nerve root with malignant change andextension to the pia-arachnoid.

POST-MORTEM FINDINGS Permission for necropsy wasconfined to examination of the central nervous system.The spinal canal was opened and the cord, with its

meningeal investment, was removed. There was adepression in the posterolateral surface of the cord at thesite of the original operation and a further small nodule5 x 3 x 2 mm in size was found two segments below thedepression. The pin and arachnoid membranes over thewhole of the spinal cord were thickened and formed awhite-pink layer about 1 mm. thick.The brain appeared, on macroscopic examination, to

be normal, apart from a faint grey cloudiness of themeninges over the cerebellum. The cerebral ventricleswere of normal size.

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D. J. B. Ashley and P. J. E. Wilson

FIG. 3. Detail of the sarcomatous part of the primarytumoulr showing cellular irregularity and a lack ofpattern.HandE, x 400.

Histological examination showed the small firm nodulein the meninges to have the same histological features asthe tumour removed at operation, except that it mergedinto the neoplastic infiltration of the meninges. Themeninges covering the whole cord showed infiltration withpolygonal neoplastic cells with irregular hyperchromatic

nuclei. This malignant tissue surrounded the nerve rootsand vessels of the meninges but did not invade thesubstance of the spinal cord.

Sections of the brain showed a similar neoplasticinvasion of the meninges of the cerebellum (Fig. 4). Theextent of this infiltration was very much less than aroundthe spinal cord and in places was only two or three cellsthick. No invasion of the cerebellum was seen. No tumourwas seen in the meninges over the cerebrum.

DISCUSSION

This patient's presentation with headache, vomiting,fluctuating mental changes, and drowsiness for abouta month led to investigation for primary intracranialdisease. The symptoms referable to a spinal lesionappeared abruptly and unexpectedly late in thedisease and progressed with unusual rapidity. Anearly clue to the possibility of a spinal lesion wasgiven by the very high level of protein in the CSF butthiswas misconstruedbecause of the absence of spinalsymptoms and because manometry failed to show aspinal block.The operative and necropsy findings showed that

the primary disease was indeed spinal and thatmalignant change had occurred in two separate nervesheath tumours in the dorsal spine.Two cases have been reported previously from

Zurich (Brussatis and Zander, 1952; Zander,Barontini, and Brussatis, 1956). Both were women in.. }iZ, S X . . .:.C: 2 .............................. < ' ::

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FIG. 4. The cerebellarcortex showing infiltrationof the meninges bysarcomatous tissue.HandE, x 100.

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Malignant change in an intraspinal nerve sheath tumour

their late 30s and both gave a long history of pain inthe back with the acute development of weakness andsensory loss in the lower limbs. In each case alaminectomy showed an encapsulated tumour in thelumbar spine, the lesion was removed and was foundhistologically to have the appearance of a benignSchwannoma. Recurrence occurred in each case,after eight and two years respectively, and re-operation showed tumours compressing the spinalcord. These tumours were histologically less welldifferentiated than the initial lesions and werediagnosed as neurofibrosarcomata. A further casefromZurich, reported at the same time, presented in asimilar manner with a mass in the lower dorsal regionwhich protruded through an intervertebral forameninto the mediastinum but this patient also showedgeneralized neurofibromatosis and therefore differssignificantly from our patient.The third case was recorded from Australia

(Fowler, 1955); the patient was a man of 60 whogave six months' history of symptoms suggestive ofspinal cord tumour and at operation a tumour wasfound filling the intrathecal space at the level of thecauda equina. Histologically this lesion was inter-preted as a malignant neurilemmoma, there wereareas which microscopically were typical of benignneurilemmoma and other areas in which there was asharp transition to a less well-differentiated malig-nant form. This man died two weeks after theoperation with some cerebral symptoms suggestive ofraised intracranial pressure and papilloedema wasnoted. No necropsy was performed.The present case differs somewhat from those

previously reported as there was only a very shorthistory of symptoms and surgical intervention wasprompt. On histological examination there was veryclear evidence that the lesion comprised malignantchange in a preceding benign tumour and this wassupported by the anatomical finding of discretetumours which had indented the spinal cord. Astriking feature was the spread of the tumour in the

spinal meninges and its extension, presumably by thecerebrospinal fluid, to the meninges at the base of thebrain. It is unfortunate that no necropsy was carriedout in Fowler's case, as the cranial neurological signssuggest that a similarphenomenon may have occurredin this patient.

In retrospect, it is difficult to see any way in whichthe outcome in our patient could have been improved.The history was extremely short and the lesion wasalready beyond the scope of curative surgery at thetime of diagnosis. This and the previously reportedcases do, however, remind us that recurrence andmalignant change, although rare, can occur in nervesheath tumours of the spinal cord, that multipleasymptomatic tumours may coexist, and that theseshould be sought and, where surgically feasible,removed to avoid this complication. Disseminationof tumour cells through the CSF and the develop-ment of 'sarcomatous meningitis' was an interestingfeature in our patient and was possibly the cause ofthe cerebral symptoms in the case reported by Fowler.

REFERENCES

Brusattis, F., and Zander, E. (1952). Ober maligne Entartungspinaler Neurinome. Schwveiz. Arch. Neurol. Psychiat., 70,176-8.

Fowler, M. (1955). A malignant neurilemmoma. Med. J.Aust., 1, 236-7.

Hosoi, K. (1931). Multiple neurofibromatosis. Arch. Surg.,22, 258-281.

Kernohan, J. W., and Sayre, G. P. (1952). Tumors of thecentral nervous system. Section 10, Fascicle 35. Atlas ofTumor Pathology. Armed Forces Institute of Pathology:Washington, D.C.

Russell, D. S., and Rubinstein, L. J. (1963). Pathology ofTumours ofthe Nervous System, 2nd edn. Arnold: London.

Stout, A. P. (1949). Tumours of the peripheral nervous system,Section 2, Fascicle 6. Atlas of Tumor Pathology. ArmedForces Institute of Pathology. Washington, D.C.

Zander, E., Barontini, F., and Brusattis, F. (1956). Sulproblema della malignita nei neurinomi. Riv. Pat. nerv.ment., 77, 323-344.

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