mixed mesenchymal differentiation in meningiomas

M I X E D MESENCHYMAL D I F F E R E N T I A T I O N I N MENINGIOMAS

J. BALL, T. A. COOK, P. G. LYNCH AND W. R. TIMPERLEY* Departments of Pathology, University of Manchester, Monash University, Victoria, Australia,

and Preston Royal Infirmary; Department of Neuropathology, Royal Infirmary, Shefield

PLATES LXXVI-LXXVIII

T UMOURS containing a variety of mesenchymal components such as cartilage, osteoid, and bone are rare in the intracranial meninges. Most examples have been pure chondromas or chondrosarcomas (Wolf and Echlin, 1936; Cushing and Eisenhardt, 1938; Ramamurthi, Iyer and Vedachalam, 1961 ; Kernohan and Uihlein, 1962; Rasking and Grant, 1966; Tom, 1971). A rare chondroblastic variant was described by Siris and Angrist (1942). More recently Lynch and Uriburu (1973) described an intracranial tumour in a 13-yr-old boy with a variety of mesenchymal components, including cartilage, osteoid and osseous tissue. The present paper describes five similar intracranial meningeal tumours showing mixed mesenchymal differentiation.

CASE REPORTS

Case 1 A 16-yr-old girl admitted to the Department of Neurosurgery, Sheffield Royal Infirmary

in 1971, complaining of spots in front of her eyes on and off for about 2 yr. The spots were of different colours and appeared for spells of 5 to 10 min. and the episodes had increased in frequency. During one episode she fell down and her right arm was pulled backwards irresistably. On examination, the visual acuity was J.l in both eyes but she was unable to read entire words in many places. There was bilateral papilloedema; the right corneal reflex was depressed; there was a right facial weakness; abnormal arm drift on the right on sustained arm raising; and the right plantar reflex was extensor.

An echogram showed a 2-mm shift from left to right and an electroencephalogram demonstrated an abnormal focus in the left occipital region. A small arterio-venous mal- formation was seen in the left occipital lobe on angiography.

At operation a yellowish area of discoloration was noticed in the cortex of the left occipital lobe. Three vessels of venous type ran from the abnormality, across the surface of the cortex to the posterior sagittal sinus. One of these vessels was carrying arterial blood; the other two were carrying venous blood. A firm nodule of tumour was identified in the postero- lateral aspect of the hemisphere, near the occipital lobe. The nodule and the surrounding tissue, including the occipital pole, were removed. The patient made a good post-operative recovery. She was discharged on anticonvulsants, having experienced visual hallucinations in which she felt that she was moving bodily in space towards various objects. There is no evidence of recurrence 3 yr afterwards.

On the day of admission she lost consciousness at a friend’s home.

Received 20 June 1974; accepted 2 Aug. 1974.

Department of Neuropathology, The Royal Infirmary, Sheffield S6 3DA. * Requests for Reprints to be sent to: Dr W. R. Timperley, Consultant Neuropathologist,

I . PATH.-VOL. 116 (1975)

254 J. BALL, T. A. COOK, P. G. LYNCH AND W. R. TIMPERLEY

Operation specimen The specimen was composed of a piece of cerebral cortex, measuring 5.0 x 2.5 X 1.5 cm

and containing a firm, almost spherical nodule 1.3 cm maximum diameter. Over the surface of the cortex there were several large blood vessels which appeared to be venous in type. On section, the tumour mass had well-defined edges and there were two small satellite tumour nodules adjacent to the main mass.

Histology. The tumour was composed of compact sheets and small groups of cuboidal, stellate or spindle-shaped cells with round or slightly lobulated nuclei with an open Chromatin network. Many of the cells had a vacuolated cytoplasm which in a small percentage of cells gave a positive reaction for glycogen; in most of the cells this reaction was negative. Fat stains were negative. A very occasional mitotic figure could be found. In places the cells were producing pseudo-alveolar structures (fig. 1). An occasional multinucleate tumour giant cell could be found (fig. 2). Here and there the tumour cells were producing variable amounts of hyaline eosinophilic birefringent matrix, parts of which were calcified (fig. 3). Trabeculae of bone were also present. Some of the tumour vessels were of an angiomatous type.

Case 2 A 16-yr-old girl was first seen in 1964 at North Staffordshire Royal Infirmary with signs

of a space occupying lesion in the left parietal area. At operation a tumour was found attached to the dura, but most of the tumour was extradural with extensive bone involvement. Most of the tumour was removed. The patient remained well until Feb. 1972 when she developed left-sided headaches and right-sided Jacksonian epilepsy. She was found to have right-sided pyramidal signs on examination. A focus in the left frontal region was demonstrated by electroencephalography and on angiography the left anterior cerebral artery was shifted to the right side; a left-sided vascular parasagittal parietal mass was seen and a gammascan showed a hot-spot in this area. At operation a tumour, measuring 6 5 cm in diameter was seen to be arising from the dura mater; it was compressing the underlying brain. The patient made a good recovery after its removal and was well 1 yr later with no fits and no neurological deficit.

Operation specimen Histology. The tumour was composed of stellate or spindle-shaped cells with round,

slightly elongated or lobulated nuclei with an open chromatin network. Many of the cells had a vacuolated cytoplasm which gave a negative reaction for fat on frozen sections. In parts the tumour was moderately pleomorphic although mitotic figures were few. The cells were producing chondroid nodules (fig. 4) and an intercellular matrix of osteoid type which in parts was calcified (fig. 5). In some areas the cells were situated around blood vessels in a pericytomatous fashion (fig. 6) and there were a few angiomatous formations (fig. 7).

Case 3 A 65-yr-old man was first seen in 1971 with a 9-mth history of a swelling slowly increasing

in size in the left temporal region. A plain X-ray of the skull showed a 7-cm left parieto- temporal skull deficit; a gammascan showed the presence of a " hot " mass in this area and a left carotid angiogram showed a tumour expanding in the extradural situation. At operation a mass of firm tumour was removed and the tumour was noted to be arising from within the dura mater. The patient was given radiotherapy post-operatively (5200 R over 26 days to a depth of 3 cm). The patient was seen 18 mth later with no evidence of recurrence.

Operation specimen Histology. The tumour was composed of spindle-shaped and stellate cells forming

streams and whorls. The tumour was more pleomorphic than in cases 1 and 2 and mitotic figures, some of which were abnormal, were easily found; many of the nuclei contained large nucleoli which in some cases were multiple. Multinucleate giant cells were present. Some of the cells were more spheroidal in type and had a vacuolated cytoplasm (fig. 8); these

BALL, COOK, LYNCH AND TIMPERLEY MENINGIOMAS

PLATE LXXVI

FIG. 1 .-Case 1 . Tumour cells producing pseudo-alveolar FIG. 2.-Case 1. Multinucleate tumour giant-cells sur- structures. Haematoxyiln and eosin (HE). x 750. rounded by cuboidal cells with vacuolated cytoplasm.

HE x750.

FIG. 3.-Case 1. Tumour cells producing hyaline eosino- FIG. 4.-Case 2. Tumour cells producing chondroid philic matrix, in parts calcified. HE. x 750. nodule. HE. x240.


PLATE LXXVIT

FIG. 5.-Case 2. Tumour cells producing matrix of FIG. 6.-Case 2. Tumour cells situated around vessels in osteoid type, in parts calcified. HE. x 750. a pericytomatous fashion. HE. x 750.

FIG. 7.-Case2. Angiomatous blood vessels. HE. x 96. FIG. 8.-Case 3 . Tumour cells resembling chordoma. H.E. X750.


PLATE LXXVIII

FIG. 9.-Case 4. Stellate and spindle-shaped cells with FIG. 10.-Case 4. Multinucleate tumour giant cells. HE. marked pleomorphism. HE. x 750. x 750.

FIG. 11 .-Case 4. Osteosarcomatous-like trabeculae with FIG. 12.-Case 5. Vacuolated cuboidal cells in small foci of calcification. HE. x 750. groups. HE. 750.

MENINGIOMAS 255

cells were producing abundant mucoid matrix superficially resembling that seen in chordomas. There were also chondromatous nodules and osteoid trabeculae, some of which were calcified. Blood vessels were abundant, of variable size and shape and of the angiomatous type.

Case 4 A 58-yr-old man was first seen in 1971 complaining of infrequent epileptic attacks over a

period of 12 yr. He had noticed slight weakness of the left leg for 3 yr and 3 mth prior to admission he had collapsed following weakness of the left leg. On examination he had a slight weakness of the lower part of the left side of the face and the left plantar response was extensor. On investigation a right carotid angiogram demonstrated a large blushing tumour near the junction of the right petrous bone and the tentorium. At operation a mass of tumour was seen to be arising from the tentorium and was extending up into the right lateral ventricle. A mass of tumour weighing 50 g was removed. Much of the tumour was multi- cystic and the cysts contained a yellowishcoloured fluid.

Post-operatively the patient was given radiotherapy. He had to be re-admitted to Preston Royal Infirmary in Feb. 1972 after complaining of drowsiness and difficulty in speaking. A myodil ventriculogram showed hydrocephalus but no block was demonstrated. A Pudenz ventriculo-atrial shunt was inserted but this made little improvement in the patient’s condition. A second craniotomy had to be performed and a diffuse recurrence was noted. The patient gradually deteriorated and died 1 mth later.

Necropsy findings Nodules of hard grey tumour were noted in the lateral region of the right occipital lobe

extending backwards towards the occipital pole. A coronal section of the brain demonstrated widespread deposits of tumour in the white matter immediately surrounding the anterior horns of both lateral ventricles and in the tegmentum of the midbrain and pons.

Histology. The tumour was composed of stellate of spindle-shaped cells with marked pleomorphism (fig. 9). Numerous mitotic figures were present and many of these were abnormal. The nuclei were round, slightly lobulated or elongated with prominent nucleoli. The chromatin patterns were open with marked clumping around the periphery. Multi- nucleate giant cells were present (fig. 10). In parts the tumour cells were densely packed with no intercellular matrix but in other areas they had a loose texture and were producing eosinophilic strands and nodules. A few small areas of chondromatous matrix were present and the post-mortem specimen showed widespread osteosarcomatous-like trabeculae with foci of calcification (fig. 11). The tumour was actively invading the brain around the edges.

Case 5

A 52-yr-old woman presented in Nov. 1971 complaining of blurred vision in the left eye for about 1 yr and pain over the left orbit for 3 mth. She was noted to have a left-sided proptosis. Skull X-rays showed an osteolytic defect of the left lesser and greater sphenoidal wings and the left anterior clinoid process. The lesion was also involving the optic canal.

At operation a mass of grey tumour, attached to the dura mater, was seen spreading in an extradural situation. The tumour was extending over the sella turcica and was involving the optic foramen. There was no subdural or intracerebral tumour. Most of the tumour was removed. The patient made a good post-operative recovery but experienced some facial pain. The pain gradually became worse and she experienced intermittent vomiting. A skull X-ray in Dec. 1972 showed gross destruction of the walls of the pituitary fossa with enlargement of the cavity. There was clear evidence of a soft tissue mass projecting downwards and for- wards behind the eye and in the post-nasal space. She deteriorated and died in Apr. 1973. No necropsy was performed.

Operation specimen Histology. The tumour was composed of fusiform cells producing variable amounts of

collagen. Some cells were cuboidal with vacuolated cytoplasm; these cells tended to occur


in small groups (fig. 12). In most areas there was marked pleomorphism and many abnormal mitotic figures were seen. There was no evidence of cartilage, osteoid or bone formation.

Multinucleate giant cells were also present.

DISCUSSION There is still a difference of opinion regarding the embryological origin of

the pia-arachnoid. It is commonly regarded as arising from the neural crest and is regarded as ectodermal or mesectodermal in origin. Zulch (1956, 1957) lists meningiomas as mesodermal in origin and Willis (1948) feels that both the embryological and pathological evidence show the mesenchymal properties of meningeal tissues and tumours. Tumours of the meninges certainly show wide variations in cytology and pattern and may contain fibrous tissue, bone, vascular or adipose tissue. The majority, however, show only a few lines of mesenchymal differentiation and they usually show evidence of differentiation to arachnoidal endothelium.

The presence of meningiomatous and angioblastic features in a single tumour arising from the meninges was used as an argument for the bipotentiality of mesenchymal cells by Bailey, Cushing and Eisenhardt (1928) in their discussion on the origin of angioblastic meningiomas. When these tumours are purely angioblastic histologically, it is possible that the vascular elements have out- grown the rest.

Meningeal tumours containing cartilage are very rare. Three of the tumours described in the present paper contained cartilage and all showed differentiation to a variety of mesenchymal cell types; none showed evidence of differentiation towards arachnoidal endothelial cells. Three cases showed tumour bone formation, four contained hyaline fibrous strands or nodules which in two instances were calcified, three contained angiomatous areas, one contained pericytoma-like areas, four contained pleomorphic and sometimes multinucleate giant cells, one showed alveolar formations, three contained vacuolated cells and in one case there was a mucoid matrix containing spheroidal cells superficially resembling chordoma (see table).

It is difficult to classify these tumours but they all appear to have arisen from the meninges and have the properties attributed to mesenchymal cells, i.e., the ability to differentiate into a variety of cell types such as fibrous, mucoid, adipose, synovial, meningeal, cartilagenous, osseous, haematopoeitic, vascular, muscular and reticuloendothelial tissue (Willis). There seems to be little point in subclassifying these tumours into different types according to the lines of differentiation present and we feel that it is more appropriate to regard them as a form of meningioma showing the capacity to differentiate in a variety of ways other than to arachnoidal endothelial cells.

Lynch and Uriburu point out the similarities between the cartilage containing meningeal tumour that they described and the so-called mesenchymal chondrosarcoma described by Lichtenstein and Bernstein (1959) and Dahlin and Henderson (1962); such chondrosarcomas usually grow very rapidly, are usually multifocal in origin and have only occasionally been described in extraskeletal sites. Two of our cases with osteogenic differentiation are alive and well with

MENINGIOMAS 257

no evidence of recurrence 3 yr later; the third case recurred and the patient died. Two of the cases with cartilagenous differentiation are alive and well with no evidence of recurrence after 3 and 10 yr. The third case presented 1 yr after initial diagnosis with a recurrent nodule but has been well since then; cytologically the tumour was pleomorphic and classified as sarcomatous.

In conclusion, it is important not to misinterpret mixed mesenchymal meningiomas as metastatic deposits, which is a possible error, particularly when a rapid diagnosis by frozen sections or smears is necessary.

TABLE Mesenchymal components in five meningeal tumours

Mesenchymal component

Bone Cartilage Hyaline fibrous strands

or nodules A n g i O m a Pericy tom Vacuolated cells Pleomorphic giant cells Alveolar formations Mucoid matrix

, I I I I

- +

(calcified) + + +

+

- - -

SUMMARY

Five intracranial meningiomas showing mixed mesenchymal differentiation are described. Three contained cartilage, three contained bone, four contained hyaline fibrous strands or nodules which in two instances were calcified, three contained angiomatous areas, one contained pericytoma-like areas, four contained pleomorphic and sometimes multinucleate giant cells, and one contained a mucoid matrix including spheroidal cells superficially resembling chordoma. The importance of recognising such tumours is emphasised as they can be misdiagnosed as metastatic deposits, particularly in a frozen section.

We would like to thank Mr A. A. Jefferson, Mr R. Johnson, Mr E. J. Newton and Mr G. K. Tutton for allowing access to clinical data and Mrs L. Hill for typing the manu- script.

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Springfield, Ill. LICHTENSTEIN, L., AND BERNSITIN, D. 1959. Unusual benign and malignant chondroid

tumours of bone. Cancer, 12, 1142-2257.


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Vol. 116, No. 3, July 1975 was issued on 29.8.75.

mixed mesenchymal differentiation in meningiomas

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