Multiple meningiomas: A clinical, surgical, and cytogenetic analysis

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Multiple Meningiomas: A Clinical, Surgical, and Cytogenetic Analysis G i o r g i o B u t t i , M . D . , R o b e r t o Assietti, M . D . , R o s a r i o C a s a l o n e , M . D . , and Pietro Paoletti, M . D . Dipartimento di Chirurgia-Neurochirurgia, Universit~ di Pavia, Pavia; and Laboratorio di Citogenetica, Ospedale di Circolo, Varese, Italy

Butti G, Assietti R, Casalone R, Paoletti P. Multiple meningiomas: a clinical, surgical, and cytogenetic analysis. Surg Neurol 1989;31:255-60.

Eight cases of multiple meningiomas were found in our 13-year series of 148 operated meningiomas. The relative frequency, 5.4%, of multiple meningiomas observed is compared with that in the literature. The clinical presentation, surgical results, and diagnostic tools are discussed. Cytogenetic analysis was performed in five patients (eight neoplastic specimens). No specific abnormality for multiple meningiomas was found, but our results point out the different origin of each tumor and exclude cell migration through the subarachnoid space as a pathogenetic factor in multiple meningiomas. KEY WORDS:

Multiple meningiomas; Chromosome analysis;

Meningiomas

"Multiple meningiomas" were first described in 1889 by Anfimow and Blumenau [3]. In 1938 Cushing and Eisenhardt [8] used the term multiple meningiomas to refer to a condition in which at least two tumors were present in different sites in a patient without signs of neurofibromatosis, regardless of the chronology of their appearance. Before the introduction of computer tomography (CT) scanning, the frequency of multiple meningiomas reported by almost all authors ranged from 1% to 3% of all meningiomas [1,2,8,12,17,19,22,33,37,40] with the exception of Horrax [15] who reported an incidence of 6.7%. Since the introduction of CT scanning, incidences ranging between 4.4% [30] and 10.5% [11] have been reported. Extensive studies performed on the karyotype of human brain tumors prove that chromosome abnormalAddress reprint requests to: G. Butti, M.D., Dipartimento di Chirurgia-Neurochirurgia, Universit~ di Pavia, Policlinico S. Matteo, 27100 Pavia, Italy. Received April 22, 1988; accepted August 29, 1988.

© 1989 by Elsevier Science Publishing Co., Inc.

ities are not randomly distributed in neoplastic cells and that there is an exceedingly high incidence of abnormalities involving chromosome 22 in meningiomas [6,36,43]. In this article we report the clinical, surgical, and cytogenetic aspects of eight patients whose diagnosis was multiple meningiomas. Materials and Methods We reviewed the clinical and surgical records of 148 cases of meningioma operated on during a period of 13 years at the Neurosurgical Institute of the University of Pavia and found eight cases of multiple meningiomas (incidence: 5.4%; Table 1). The multiplicity was detected during the first neuroradiologic examination in three cases and at different times in the other five. The completeness of surgical removal of the tumors was estimated according to the grading system proposed by Simpson [35] (Table 2). Specimens obtained at operation from five patients (eight tumors) were utilized for chromosome analysis performed after short-term cell culture. For karyotypic analysis, a fragment of tumor was rinsed in Ham's F-10 culture medium containing antibiotics and supplemented with 20% fetal calf serum, and then finely minced with scissors. The fragments and disaggregated cells were introduced into 25-cm 2 culture flasks. Two milliliters of the same culture medium was regularly replaced every 3 days. When growth areas were observed around the fragments, they were removed with a Pasteur pipette. The remaining cells were cultured until they reached a nearly confluent growth and a number of mitoses were detected under microscopic observation. Colcemid (0.01 wg/mL) was then added to the culture medium 3 hours before processing. The cells were removed by trypsinization, treated in hypotonic solution (0.075 M KCI) for 7 minutes, and fixed in a methanol/acetic mixture (3:1). Chromosome spreads were air dried. 0090-3019/89/$3.50

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Table 1. Clinical and Surgical Data of Eight Patients with Multiple Meningiomas Case 1

Sex Male

Age (yr)

Histology

Date of surgery ~

Grade b

Site

Initial symptoms

49

M M M

6/1969 6/1969 2/1976

1 1 2

C FR L C FR L FX MED L

Aphasia Hemiparesis Hemiparesis Hypoesthesia Bone bulging Bone bulging Hemiparesis Aphasia Hemiparesis Hemiparesis Behavioral disturbances Visual deficits Paraparesis Visual deficits Hypoesthesia Anosmia Behavioral disturbances Behavioral disturbances None None Hemianopia Hemianopia None Visual disturbances Exophthalmus None

42

2

Male

70 73

F M

9/1975 1/1978

1 2

FX ANT L C FR L

3

Male

57

M

10/1981

1

C PR L

62

M

10/1986

1

C FR L

56 57 39 54 55 46

12/1979 3/1980 5/1968 1/1983 5/ 1984 12/1983 12/1983 4/1987 4/1987 12 / 1984 3/1985 8/1986 4/1984

2 1 1 1 2 2 1 2 1 2 1 4

SW L D4/D5 C OC L C PR R OG FX ANT FX ANT FX TE C OC R TU TU C FR L SW L

5/1987

1

C OC L

4

Female

Male

51

Female

53 43

M P M M F F F F M M M M M

5

Female

6

Female

46

M

52 7

8

Abbreviations: M, meningothelial;F, fibroblastic;P, psammomatous;C, convexity;FX, falx; SW, sphenoid wing; D, dorsal; OG, olfactorygroove; TE, tentorial; TU, tuberculum seUae;FR, frontal; PR, parietal; OC occipital;R, right; L, left; ANT, anterior; MED, medial. Date on which each tumor was removed; same dates indicate removal of different tumors during the same operation. bDegree of radical removal according to Simpson [35].

At this stage, QFQ- and, in two cases, GTG-banding techniques were applied [7]. Karyotypes were determined by microscopic analysis and by arranging photographed metaphases. A clone was defined when at least two metaphases with the same structural rearrangement or at least three metaphases with the same numerical abnormality were found. The constitutional karyotype was determined in lymphocyte cultures. The karyotype was found normal in all patients.

deficits followed by visual disturbances; seizures were not the first sign of the disease in any case. The histologic subtypes of the removed tumors were different in three patients (cases 2, 4, and 5). Patient 4 carried an intracranial and a spinal meningioma which is a rarely reported association [9,13,46]. The longest

Degree of Radical Removal According to Simpson [35] (Partially Modified)

T a b l e 2.

Grade

I:

Grade

II:

Results Clinical and surgical data of our patients are summarized in Table 1. The male:female ratio was 1:1 and the average age at the first operation was 51 years (range 39 to 70). No patient carried stigmata of neurofibromatosis. Years before the operation, case 8 suffered from a significant cranial trauma at the site of meningioma growth. The average duration of symptoms was 7.3 months (range 1 to 17). The second tumor was diagnosed before the appearance of clinical signs by means of routine follow-up CT in three cases (cases 6, 7, and 8). The most common initial symptoms were motor

Grade III:

Grade IV: Grade V:

Macroscopically complete removal of the tumor with excision of its dural attachment and of any abnormal bone. Such an operation entails resection of the sinus where the tumor arises from its wall Macroscopically complete removal of the tumor and of its visible extension with coagulation of its dural attachment Macroscopically complete removal of the intradural tumor without resection or coagulation of its dural attachment or, alternatively, of its extradural extension (e.g., an invaded sinus or hyperostotic bone) Partial removal, leaving intradural tumor in situ Decompression, with or without biopsy

Multiple Meningiomas

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Table 3. CytogeneticFindings Date of

No. of

Case

surgery

Site*

Karyotype

metaphases

5

1/1983 5/1984 12/1983 4/1987 3/1985

C PR R OG FX ANT FX TE TU

46,XX Scattered abnormalities (see Table 4 A) 45,XX,-22 46,XX t(1;7; 14)(q25;q32;q22), t(18;22)(q12;ql 1),+ random losses 46,XY,t(1;7; 14)(q25;q32; q22),t(18;22)(q12;ql 1) Scattered abnormalities (see Table 4 B)

12

6 7

8/1986

C FR L

10 10 23 19

° For abbreviations see Table 1.

interval between the appearance of two neoplasms is 16 years (case 5), but longer intervals have been reported [13]. Eighteen operations were performed to resect all the meningiomas: two tumors were resected during the same operation in three patients, whereas the tuberculum sellae meningioma of patient 7 required two operations to be completely removed. The resection of the sphenoid wing meningioma of patient 8 was largely incomplete (grade 4); all the other tumors were radically resected (grade 1 or 2). Patients 1, 5, and 8 developed a recurrence at the site of the first resected tumor after 15, 14, and 2 years, respectively. There was no operative mortality in this group of patients. Chromosome analysis revealed a

normal karyotype m cases 3 and 8, in which only one tumor was analyzed. In three other cases (cases 5, 6, 7), two different tumors were cytogenetically analyzed from each patient. The results are reported in Table 3. In case 5 one tumor had a normal diploid chromosome number. The modal chromosome number of the other tumor was 46, and 10 of the 11 metaphases with a diploid chromosome number showed a 46,XX karyotype (Table 4 A). However, we found a large variation in karyotypic abnormalities in eight cells with the presence of various nonclonal rearrangements. Case 6 presented a 4 5 , X X , - 2 2 karyotype in one tumor and a normal karyotype in the other. In case 7 the specimen obtained at the second operation for the tuberculum sellae meningioma pre-

Table 4. Detailed Karyotypic Findings of Cases 5 (A) and 7 (B) Karyotype A. Case 5 49,XX,+ 3,+6,+8,+9,+ 10,+ 11 , - 12,- 14,- 16,- 16,+ 17,del(22)(q 11) 46,XX,del(6)(q21 ), 17q + 4 5 , X X , - 3 , - 7 , - 17,Dq+,+marl,+mar2 45,XX,-8,del(2)(p 13 ?),del(5)(p 12),del(6)(q 12 ?) 4 5 , X X , - 9 , - 14,- 15,+mar3,+mar4 4 5 , X X , - 10,t(1;7)(p32;q36) 4 4 , X X , - 1 , - 2 , - 10,- 12,+mar5,+mar6 4 0 , X X , - 8 , - 8 , - 12,- 16,- 18,- 22 4 0 , X , - 8 , - 8 , - 9 , - 12,- 15 46,XX B. Case 7 46,Y, - X, - 11, + der(X)(Xqter- Xp22:: ?), + mar 1 46,XY,- 5,+mar2 46,XY,- 1,- 11,+ der(11)(1 l q t e r - 1 l p l 5:: l q 2 3 - 1 qter),+mar3 46,XY,inv(7)(p 12;q35),t(14; 14 ?)(q33;q22) 46,Y,t(1 ;X)(q22 ?;q24 ?) 45,XY,- 5,-6,-21,+mar4,+mar5,t(1;11)(q23;pl 5) 45,XY,- 14,t(1;16)(q32;q24) 4 5 , X Y , - 9 , - 11,+mar6 45,XY,- 12,del(9)(q22) 46,XY

No. of metaphases 1 1 1 1 1 1

1 1 1

10

2 2 1 1 1 1 1 1 1

13

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sented the translocations t(1; 7; 14) and t(18; 22). The karyotypic finding of the meningioma from the occipital convexity of the same patient was similar to that observed in case 5 (Table 4 B). Thirteen metaphases showed a 46,XY karyotype and 11 metaphases showed the presence of various clonal, der(11), der(X), - 5 , mar 3, and nonclonal rearrangements.

Discussion The 5.4% incidence of multiple meningiomas encountered in our series is higher than the 2.4% of Geuna et al [12]. It is interesting to note that these two series share similar ethnic characteristics and cover a similar period of time. In fact, both studies include patients operated on before and after the introduction of the CT scan. The difference in incidence observed in the two series can be explained by the fact that our patients operated on for meningioma are followed up with CT scanning at least once every 2 years. These scheduled controls sometimes led us to operate on patients without clinical signs related to new meningiomas. However, the incidence in our series is in the range of other series studied with CT only (from 4.4% [20] to 5.9% [30]), but our values do not reach the 8.9% and 10.5% reported by Lusins and Nakagawa [21] and Federico et al [11] (Table 5), respectively. Data reported in recent years point out that the introduction of the CT scan has made the diagnosis of small lesions, not detectable with previous techniques,

easier, and has allowed neurosurgeons to estimate the true incidence of multiple meningiomas. The opinion that frequency of multiple meningiomas should be about 8% to 10% is supported by autopsy studies of Nakasu et al [29], and Wood et al [41] in which respective incidences of 8.2% and 10% are reported. The high incidence reported by Wood et al could be explained by the high average age (69.8 years) of their cases. In fact, aging seems to be related to a high occurrence of symptomatic meningiomas [29] and to their multiplicity [10]. In our series there is no difference in incidence of multiple meningiomas between males and females in contrast to the reports of almost all other authors who found a clear preponderance in females [12,17,20,34,38]. It is thought [40] that multiple meningiomas are the result of the regrowth of an incompletely resected neoplasm. We think that tumors arising in the same or proximal site of a previously completely resected tumor must be considered recurrences and not defined as "multiple meningiomas." Two out of three recurrences observed among the 20 resected tumors occurred after a Simpson's grade 1 resection. Those were local recurrences. The long recurrence-free time suggests that those tumors might have grown from some neoplastic foci in the dura mater around the insertion zone of the meningioma as shown by Borovich and Doron [4]. We agree with these authors' statement that a grade 0 (removal of about 4 cm of dura mater around the periphery of the attachment of the meningioma) should be added to Simpson's scale

Table 5. Incidenceof Multiple Meningiomas No. of multiple Author

Year

No. of meningiomas

meningiomas

%

C u s h i n g and Eisenhardt [8] a H o r r a x [15] * Vestergaard [38] * Mufson and Davidoff [28]* W o o d et al [41] d Abthai [1] ~ Ischbeck and K u s k e [17]* Stowsand [37] * Sheehy a Ekong et al [10] ~ Lusins and Nakagawa [21]b N a s h e r et al [30] b G e u n a et al [12]' Sheehy and Crockard [34] b Federico et al [11] b LocateUi et al [20] ~ N a k a s u et al [29] d Present report ~

1938 1939 1944 1944 1957 1975 1975 1975 1977 1978 1981 1981 1983 1983 1984 1987 1987 1989

259 60 187 58 100 351 714 108 517 80 168 84 372 49 104 227 231 148

3 4 5 2 16 12 11 1 6 1 15 5 9 4 11 10 19 8

1.0 6.7 2.7 3.4 16.0 3.4 1.5 0.9 1.2 1.2 8.9 5.9 2.4 8.1 10.5 4.4 8.2 5.4

* Pre-CT. b post-CT. "Pre- and post-CT, d Autopsy.

Multiple Meningiomas

[5]. T h e third recurrence was clearly a progression of the incompletely r e m o v e d meningioma invading the bone o f the orbital wall. N o n e o f our patients had family histories o f m e n i n g i o m a and few cases on this account have been reported [24]. Irradiation o f the skull has been reported to be a cause o f single [3 9] and multiple meningiomas [ 16], but the records o f all our patients were negative in this regard. In 1967 Zang and Singer [43] observed the frequent absence o f a g r o u p G c h r o m o s o m e during their research on the karyotype of meningiomas. M o r e recently other authors [23,45] have stated that the absent chromosome was the 22nd. Even if m o n o s o m y or rearrangements o f c h r o m o s o m e 22 are typical o f meningiomas [6], other aberrations involving c h r o m o s o m e 1, 8, 14, 17, 20, X, and Y have been described [18, 25,26,31,36,44]. T h e presence of "oncogenes" located on the same c h r o m o s o m e bands involved in chromosome rearrangements o f different tumors strongly supports a biological role for n o n r a n d o m chromosomal aberrations in tumors [32]. T h e incidence of karyotype abnormalities seems to be different a m o n g racial and geographical groups. Abnormalities are present in 9 6 . 3 % o f meningiomas in a Swedish population, in 56.6% in a G e r m a n one, and in 71% in a Japanese one [27,42]; we found an incidence o f 4 5 . 1 % [6]. Differences are reported by the type o f abnormality: m o n o s o m y o f c h r o m o s o m e 8 was observed in 6 5 % of Swedish cases, in 3.3% of G e r m a n cases, and none in Japanese cases or in our own cases [6,25,42]. We studied the karyotype o f multiple meningiomas because this pathological condition affords the opportunity o f comparing the g e n o t y p e of tumors with similar histologic patterns belonging to the same person and located in the same anatomical compartment. In three cases (cases 5, 6, 7) we obtained specimens from two meningiomas o f the same patient. It is relevant that in all these cases the karyotype was different from tumor to t u m o r o f the same patient. This observation, connected with that o f cases 2, 4, 5, in which the histologic subtypes of the two tumors were different, supports the view that the second t u m o r does not originate from the first through cellular desquamation in the subarachnoid space [14,32]. W e have not observed aberrations that could be considered typical of multiple meningiomas and no correlation was found between histologic subtype and genomic abnormalities. We think that further studies are needed to elucidate these aspects. At the m o m e n t it can be pointed out that CT scanning has increased the n u m b e r of multiple meningiomas diagnosed. W e have observed that these neoplasms are not biologically m o r e aggressive than the

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other meningiomas and that they may have a worse prognosis owing to the higher n u m b e r o f operations required to resect all the tumors. We believe that multiple meningiomas will be a very good field for investigation of c h r o m o s o m e abnormalities in solid tumors. This research will possibly help our understanding o f the mechanism o f d e v e l o p m e n t and spread of meningiomas.

References 1. Abthai H. Proceedings: multiple meningiomas. Acta Neurochir 1980;31:279. 2. Andrioli GC, Rigobello L, Iob I, Casentini L. Multiple meningiomas. Neurochirurgia 1981;24:67-9. 3. AnfimowJ, Blumenau L. Ein Fall: multipler Geschwulste in der Schadelh6hle. Neurol Zentralbl 1889;8:585. 4. Borovich B, Doron Y. Recurrence of intracranial meningiomas: the role played by regional multicentricity. J Neurosurg 1986; 64:58-63. 5. Borovich B, Doron Y, Brown J, Guilburd JN, Zaaroor N, Goldsher D, Lemberger A, Gruszkiewicz J, Feinsod M. Recurrence of intracranial meningiomas: the role played by regional multicentricity. 2: clinical and radiological aspects. J Neurosurg 1986;65:168-71. 6. Casalone R, Granata P, Simi P, Tarantino E, Butti G, Buonaguidi R, Faggionato F, Knerich R, Solero L. Recessive cancer genes in meningiomas? An analysis of 31 cases. Cancer Genet Cytogenet 1987;27:145-59. 7. Casperson T, Lomakka G, Zech L. The 24 fluorescence patterns of human metaphase chromosome--distinguishing characteristics and variability. Hereditas 1971;67:89-102. 8. Cushing H, Eisenhardt L. Meningiomas: their classification, regional behavior, life history, and surgical end results. Springfield, Ill.: Charles C Thomas, 1938. 9. Distelmaier P, Lins E, Kolberg T. Multiple meningiomas: two patients with spinal and intracranial meningioma. Radiological diagnosis. Neurochirurgia 1976;19:114-7. 10. Ekong CEU, Kenneth BS, Paine WE, Rozdilsky B. Multiple meningiomas. Surg Neurol 1978;9:181-4. 11. Federico F, D'Aprile P, Lorusso A, Belsanti M, Carella A. Multiple meningiomas diagnosed by computed tomography. ItalJ Neurol Sci 1984;5:295-8. 12. Geuna E, Papadg G, Regalia F, Arrigoni M. Multiple meningiomas: report of nine cases. Acta Neurochir 1983;68:33-43. 13. Harish Z, Schiffer J, Rap A, Reif RM. Intracranial and spinal multiple meningiomas appearing after an interval of 22 years. Neurochirurgia 1985;28:25-7. 14. Hoffman GT, Earle KM. Meningiomas with malignant transformation and implantation in the subarachnoid space. J Neurosurg 1960; 17:486-92. 15. Horrax G. Meningiomas of the brain. Arch Neurol Psychiatry 1939;41:147-57. 16. Iacono RP, Apuzzo MLJ, Davis RL, Tsai FY. Multiple meningiomas followingradiation therapy for medulloblastoma:case report. J Neurosurg 1981;55:282-6. 17. Ischbeck H, Kuske V. Proceedings: multiple meningiomas. Acta Neurochir 1975;31:278-9. 18. KatsuyamaJ, Paenhausen R, Herz F, Gavizoda P, Hirano A, Koss LG. Chromosome abnormalities in meningiomas. Cancer Genet Cytogenet 1986;22:63-8.

260

Surg Neurol 1989;31:255-60

19. Levin P, Gross SW, Malis LI, Kirshenbaum AH, Hollin SA. Multiple intracranial meningiomas. Surg Gynecol Obstet 1964; 119:1085-90. 20. Locatelli D, Bottoni A, Uggetti C, Gozzoli L. Multiple meningiomas evaluated by computed tomography. Neurochirurgia 1987;30:8-10. 21. Lusins JO, Nakagawa H. Multiple meningiomas evaluated by computed tomography. Neurosurgery 1981;9:137-41. 22. Luyendijk W. Meningiomes multiples et meningiomatoses. Acta Neurochir 1954;3:263-74. 23. Mark J, Levan G, Mitelman F. Identification by fluorescence of the G chromosome lost in human meningiomas. Hereditas 1972;71:163-8. 24. Memon MY. Multiple meningiomas without evidence of neurofibromatosis. Neurosurgery 1980;7:262-4. 25. Mitelman F. Catalog of chromosome aberrations in cancer. 2nd Ed. New York: Alan R. Liss, 1985. 26. Mitelman F. Clustering of breakpoints to specific chromosomal regions in human neoplasia. Hereditas 1986;104:113-9. 27. Mitelman F. Levan G. Clustering of aberrations to specific chromosomes in human neoplasms. III. Incidence and geographic distribution of chromosome aberrations in 856 cases. Hereditas 1978;89:207-32.

Butti et al

34. 35.

36.

37. 38. 39. 40. 41.

42.

28. Mufson JA, Davidoff LM. Multiple meningiomas: report of two cases. J Neurosurg 1944;1:45-7. 29. Nakasu S, Hirano A, Shimura T, LlenaJF. Incidental meningiomas in autopsy study. Surg Neurol 1987;27:319-22.

43.

30. Nasher HC, Grote W, Lohr E, Gerhardt L. Multiple meningiomas. Clinical and computer tomographic observations. Neuroradiology 1981;21:259-63.

44.

31. Rey JA, Bello JM, de Campos JM, Benitez T, Ayuso MC, Valcarel E. Chromosome studies in two human tumors. Cancer Genet Cytogenet 1983;10:159-65.

45.

32. Rowley D. Human oncogene locations and chromosome aberrations. Nature 1983;301:290-1. 33. Sharrer E, Brunngraber CV. l]ber multiple Meningeome: syn-

46.

dromgenetischer Beitrag zur Frage: Systemerkrankung oder Metastasierung? J Neurol 1974;207:227-46. Sheehy JP, Crockard HL. Multiple meningiomas: a long-term review. J Neurosurg 1983;59:1-5. Simpson D The recurrence of intracranial meningiomas after surgical treatment. J Neurol Neurosurg Psychiatry 1957;20: 22-39. Singer H, Zang KD. Cytologische and cytogenetische Untersuchungen an Hirntumoren. I. Die Chromosomenpathologie des menschlichen Meningioms. Humangenetik 1970;9:172-84. Stowsand D. Proceedings: multiple meningiomas. Acta Neurochir 1975;31:259-60. Vestergaard E. Multiple intracranial meningiomas. Acta Psychiatr Neurol Scand 1944;19:389-411. Waga S, Handa H. Radiation induced meningioma: with review of literature. Surg Neurol 1976;5:215-9. Waga S, Matsuda M, Handa H. Multiple meningiomas: report of four cases. J Neurosurg 1972;37:348-51. Wood MW, White RJ, Kernohan JW. One hundred intracranial meningiomas found incidentally at necroscopy. J Neuropathol Exp Neurol 1957;16:337-40. Yamada K, Kondo T, Yoshioka M, Dami H. Cytogenetic studies in twenty human brain tumors: association of No. 22 chromosome abnormalities with tumors of the brain. Cancer Genet Cytogenet 1980;2:293-303. Zang KD, Singer H. Chromosomal constitution of meningiomas. Nature 1967;216:84-5. Zankl H, Siedel H, Zang KD. Cytological and cytogenetical studies on brain tumors. V. Preferential loss of sex chromosomes in human meningiomas. Humangenetik 1975;27:119-28. Zankl H, Zang KD. Cytological and cytogenetical studies on brain tumors. IV. Identification of the missing G chromosome in human meningiomas as No. 22 by fluorescence technique. Humangenetik 1972;14:167-9. Zervas NT, Shintani A, Kallar B, Berry RG. Multiple meningiomas occupying separate neuraxial compartments. Case report. J Neurosurg 1970;33:216-20.