Surg Neural 1989;32:131-6

Multiple Meningiomas Review of the Literature M. S. M. Eljamel,

F.R.C.S.,

The Mersey Regional Department

131

and Their Relation to Neurofibromatosis

and Report

of Seven Cases

and P. M. Foy, F.R.C.S. of Neurosciences,

Walton Hospital, Liverpool, England

Eljamel MSM, Foy PM. Multiple meningiomas and their relation to neurofibromatosis. Review of the literature and report of seven cases. Surg Neural 1989;32:131-6. A review

of 158 cases of multiple meningiomas reported in the literature and 7 additional cases are presented. The average incidence of multiple meningiomas is 2.5% of all meningiomas. In the absence of cutaneous manifestations of von Reckhnghausen’s disease, it is extremely difficult between cases associated with central neuto distinguish rofibromatosis and those representing true multiple meningiomas. There are no specific pathognomonic features that distinguish true multiple meningiomas as a separate disease entity.

KEY WORDS: Intracranial tumors; Intraspinal ple meningiomas; Neurofibromatosis

tumors;

Multi-

--.-_._.

Introduction Cushing and Eisenhardt [9] defined true multiple meningiomas as “more than one and less than a diffusion in the absence of stigmata of von Recklinghausen’s disease.” On the other hand, the occurrence of meningiomas in association with other intracranial and/or intraspinal tumors of neuroectodermal origin, that is, acoustic neuroma, pilocytic astrocytoma, optic nerve glioma, or neurofibroma, in the presence of a family history of neurofibromatosis 2, are sufficient criteria to make the diagnosis of central neurofibromatosis (neurofibromatosis 2) {27,37]. However, these definitions are arbitrary and based on simple clinical observations. The clinical and laboratory features of solitary or multiple, separate or diffuse meningiomas are indistinguishable and probably represent the same disease process 16,34,481. The first case of multiple meningiomas was reported

Addrm reprint requests to: M. S. M. Eljamel, F.R.C.S., Walton Hospital, Rice Lane, Liverpool L9 lAE, United Kingdom. Received January 5, 1989; accepted February 22, 1989.

0 1989 by Else&r Science Publishing Co., Inc.

by Anfimow and Blumenau 131 a century ago. To date, more than 158 cases have been reported, describing the different aspects of the disease and trying to distinguish these cases of true multiple meningiomas from those associated with neurofibromatosis 2 [ 1- 13,15-l&2026,29-37,39,43-49,51). In the first review of the literature, Hosio [22] reviewed 22 cases, 5 of which were cases of neurofibromatosis forme fruste. Three cases were associated with bilateral, and two with unilateral acoustic tumors. Among 288 patients operated on for meningiomas in the Mersey Regional Department of Neurosciences, seven cases (2.4%) had multiple meningiomas with no external manifestations or a familv history of neurofibromatosis. There was no famil istory of meningiomas in any of these patients.

Case Reports Case 1 A 38-year-old man presented with a left foot drop and paresthesia. Two separate parasagittal meningiomas were shown on computed tomography (CT). The right parasagittal meningioma was excised and, apart from postoperative seizures, he made a good recovery. Two years later, the seizures became more frequent and CT showed a new lesion in the left parietal region that was excised. The patient returned to work. Histologically, both tumors were transitional meningiomas.

Case 2 A 28-year-old woman presented in 197 3 with left-sided hemiparesis and diplopia. She had bilateral papilloedema and a left sixth nerve palsy. An isotope brain scan suggested a right parietal meningioma, and, at operation three other right convexity and left parasagittal meningiomas were discovered and removed. Postoperatively, she received radiotherapy and chemotherapy. In March 1985, she presented with a spastic paraparesis and sensory level at T12. Computed tomography 0090.3019/891$3.50

132

Surg Neurol 1989;32:131-6

Eljamel and Foy

showed small bilateral parasagittal and right convexity meningiomas. Myelography revealed an intradural extramedullary lesion at T3. A thoracic laminectomy was performed, and a meningioma was removed. Following this, the parasagittal meningioma was excised. She made a good recovery but follow-up CT scan in 1986 showed left frontal and two right parasagittal lesions. The parasagittal meningiomas were removed at operation. A year later, 1987, a repeat CT showed that she has developed right falcine and three left convexity tumors. In May 1988, she deteriorated, was unable to walk, and had intermittent paresthesia on the right side. Further CT showed that the left frontal lesion was bigger; this tumor was removed, and once more she made a good postoperative recovery. The histology of all tumors removed showed syncytial meningiomas.

Case 3 A 61-year-old woman was admitted with an 8-month history of grand ma1 seizures. Computed tomography showed a right frontoparietal meningioma, which was removed. The histology showed a syncytial meningioma. She made a good postoperative recovery. She represented 6 years later with intractable seizures. Computed tomography showed two new lesions in the right falcine and right frontal regions.

CT showed that she had developed sion in the falx.

A 20-year-old man presented with spastic paraparesis. He had bilateral facial palsies and bilateral deafness owing to previous surgery for bilateral acoustic tumors. Computed tomography showed no fresh intracranial lesion, but a myelogram demonstrated multiple intradural extramedullary tumors and, at thoracic laminectomy, five atypical meningiomas were removed. In 1988, he developed seizures; CT showed a left frontal tumor, which was removed surgically and was described histologically as an atypical meningioma.

Discussion One hundred fifty-eight cases reported in the literature and our series of seven new cases were critically reviewed. The incidence ranged from l%-8.9% (Table 1) with an average incidence rate of 2.5%. Lusins and

1. Quoted Incidence of Multiple Meningiomas Author/year

Case4

Case 5 A 57-year-old woman presented with raised intracranial pressure and left-sided weakness. Computed tomography showed a left convexity and right frontal parasagittal tumors. The histology of the excised tumors showed a syncytial meningioma.

Case 6 A 33-year-old woman was admitted with bance. She had right facial weakness and neural deafness following previous surgery acoustic tumors. Computed tomography frontal and tentorial opening meningiomas. tal tumor was excised; it was angioblastic.

visual disturleft sensorifor bilateral showed a biThe bifronA follow-up

small le-

Case 7

Table

A 46-year-old woman was admitted in 1974 with epilepsy, right hemiparesis, and lack of concentration. An isotope brain scan suggested bilateral parietal parasagittal meningiomas. Two separate tumors were removed at operation, and the histology showed a syncytial meningioma.

a further

Frazier

et al

Incidence

%

1175

1.3

(1933) Cushing et al

31295

(1938) Horrax

4160

6.7

(19391 Mufson and Davidoff

2158

3.4

51187

2.7

(1944) Vestergaard ( 1944) Levin et al

-

(1964) Waga et al (1972) Stowsand (1975) Abtahi (1975) Ekong et al (1978) Lusins and Nakagawa (1981) Sheehy and Crockard (1983) Neuss et al (1988) Eljamel et al The average

incidence

l-2

41261

1.5

121351

3.4

l/80

1.2

15/168

8.9

101566

1.8

8/500

1.7

71288

2.4

rate is 2.5% of all meningiomas

Sug Neurol 1989;32:131-6

Review of Multiple Meningiomas

133

Figure 1. The age distribution of muitiple meningiomas. The female: male ratio is 2S : 1.

Nakagawa {267 reported the unusually high incidence rate of 8.9% as evaluated by CT and predicted that the true incidence rate is likely to be higher because many cases are asymptomatic. Wood et al [50] reviewed 100 cases of intracranial meningiomas found incidentally at autopsy and found 16% of these cases to be multiple. The youngest reported case of multiple meningiomas is 4 years and 5 months old 1451, and the oldest is 88 years old [26], with a peak incidence between 20 and 60 years (Figure 1). The female : male ratio was 2.5 : 1. Multiple meningiomas commonly present with focal neurological deficit, headaches, and/or seizures (70%) (Table 2). More than 60% of them are situated in the supratentorial compartment, and half of the tumors are unilateral with equal incidence on the right and left sides. Eight percent arise on both sides of the tentorium, and, in 13% of cases, there are both intracranial and intraspinal tumors. Sixteen percent are purely intraspinal, of which 86% are situated in the cervicothoracic region. There are only four reported cases in the posterior cranial fossa (PCF) [2,32,48). In 69 of the 165 reviewed cases, details of the time interval between the diagnosis of the first and subsequent tumors are given (Figure 2). The longest time was

Table

22 years [18], but, in most of the cases, the multiple meningiomas were discovered simultaneously. The largest number of meningiomas found in one patient at autopsy was 59 1451, and the greatest numbers of tumors removed surgically were 10 at four operations [9,31], 12 at three operations [20}, and 14 at one operation (Table 3) 1341. Many of these patients tolerate multiple operations surprisingly well as illustrated by case 2 and cases reported by Cushing and Eisenhardt [9] and Zervas et al [Sll. The association of multiple meningiomas with neurofibromatosis is well recognized [9,16]; some authors suggest that multiple meningiomas represent a form of neurofibromatosis [10,25]. Although neurofibromatosis is an autosomal dominant disease, the affected patient may not show any external manifestations because of variable gene expressivity [14,38-j. There may be no family history of neurofibromatosis as it is often a genetic mutation 1381. Fifty percent of the offspring of the heterogenous patient are normal, and some of the rest will be overlooked because of variable gene penetration [14]. It is difficult to explain why multiple meningiomas, which are mesodermal tumors, occur in assocation with neurofibromatosis, an essentially ectodermal disease. Research in molecular genetics of neuroectoder-

2. Clinical Presentation of Multiple Meningiomas

Clinical features

Focal neurological signs Headaches and raised intracranial pressure Seizures Myelopathy Backache Proptosis Ataxia Behavioral change

%

34 20.8 17 13.2 7.5 3.7 1.9 1.9

Table

3. Number of Meningiomas

the Number

of Operations

Removed Surgically

versus

(43 cases) Number of operations

Number of meningiomas removed

2-4 5-8 >8

1-2

3-4

> 4

29 3 3

2 2 3

1

Eljamel and Foy

Surg Neural 1989;32:131-6

134

Patients % 501

Figure 2. The time intewal between the diagnosh of tbejrst and subsequent meningionzrts in the same patient.

0

Simultaneous

1-5

6-10

)10Years

Interval ma1 and meningeal tumors suggested a common pathogenetic mechanism related to aberrations of chromosome 22, possibly the loss of a tumor suppressor gene [27,28,42,43]. Hereditary factors have been demonstrated by the occurrence of multiple meningiomas in families [10,17,29,33,36,41], and aberrations of chromosome 22 in multiple meningiomas has been described. Arinami et al [4] described a patient with constitutional ring chromosome 22 who had multifocal meningiomas. Neuss et al [341 also described monosomy 22 in one of three analyzed cases. There is no evidence to suggest that meningiomas occurring in association with neurofibromatosis have any unique or different chromosomal findings from those that occur sporadically {5,42]. Cushing and Eisenhardt [9] stated that “a meningioma rarely if ever changes its histological type.” How-

ever, transformation of benign to malignant meningioma was demonstrated by Mufson and Davidoff 131). The most common histological types reported in multiple meningiomas were mixed and meningiothelial types (59%) (Figure 3). The multiplicity of these tumors could be explained in the following ways: 1. Multifocal origin especially in those cases occurring simultaneously; possibly owing to chromosomal aberrations leading to the loss of a tumor suppressor gene or the expression of an abnormal recessive gene responsible for a tumogenesis factor [271. 2. Dissemination in the cerebrospinal fluid pathways, particularly in those occurring after previous surgery as demonstrated by Hoffman and Earle E191, Schope 1401, and Zulch et al 152). [24], although 3. Spread along the venous channels metastasis from meningiomas is extremely rare 1231.

%Patients 40 1

Figure 3. The histological types of multiple meningiomas. (A) mixed; (B) meningiotheliomatous; (C) jibromatous; (D) tramitional; (E) psammomatous; (F) syncytial; (G) angioblastic; (H) sarcomatous; (I) melanotic.

Review of Multiple Meningiomas

Surg Neural 1989;32:131-6

135

Radiotherapy has been implicated in the causation of multiple [36] and solitary [28f meningiomas. Case 2 received cranial radiotherapy and chemotherapy after the first operation. Although she developed further intracranial meningiomas, she also developed a spinal meningioma that could not be due to the radiotherapy. The presence of steroid receptors and possible hormonal manipulation to reduce recurrence and further growth of meningiomas is an attractive idea. However, studies of these receptors in multiple meningiomas are few because of the rarity of the disease. Neuss et al [34] studied four cases and found no receptors in one, and progesterone receptors of variable concentration in three.

13. Ekong CEU, Paine KWE, Surg Neurol 1978;9:181-4.

Conclusions

of the 20. Holliday III PO, Davis C, Angelo J. Multiple meningiomas cervical spinal cord associated with Klippel-Feil malformation and atlanto-occipital assimilation. Neurosurgery 1984;14:353-7.

Multiple meningiomas are not a specific disease entity and have no distinctive clinical, laboratory, or pathological features. Most of them represent one end of the spectrum of neurofibromatosis 2; laboratory confirmation of true multiple meningioma is not yet possible. These patients tolerate multiple operations remarkably well; therefore, they need to be followed very closely to detect any advance in their tumors as early as possible.

Rozdisky

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