Metastatic atypical meningioma 69
Metastatic atypical meningioma: case report and review of the literature Katharine J. Drummond MBBS FRACS, Richard G. Bittar MBBS, Michael R. Fearnside MS FRACS Department of Neurosurgery, The Westmead Centre, Sydney, Australia
Summary Extracranial metastasis of an intracranial meningioma is rare. We discuss the clinical, radiological and histopathological presentation of an elderly man with pulmonary metastases from a recurrent meningioma of atypical histology, and review the literature pertaining to this phenomenon. © 2000 Harcourt Publishers Ltd Journal of of Clinical Clinical Neuroscience Neuroscience (2000) (2000) 77 (1), (1), 69–72 69–72 © © 2000 2000 Harcourt Harcourt Publishers Publishers Ltd Ltd Journal DOI: DOI: 10.1054/ 10.1054/ jocn.1998.0153, jocn.1998.0153, available available online online at at http://www.idealibrary.com http://www.idealibrary.com on
Keywords: meningioma, metastasis, neoplasm, lung Received 2 September 1998 Accepted 20 October 1998
Correspondence to: R. G. Bittar, Department of Neurosurgery, Westmead Hospital, Hawkesbury Road, Westmead, NSW. 2145, Australia. Tel.: 2 9845 5555; E-mail: [email protected]
INTRODUCTION The diagnosis of meningioma is generally favourable, being associated with the potential for cure with good quality of life. However, reviews of large groups of patients reveal that this optimistic view is not entirely justified. Quality and length of survival may be reduced by neurological deficits, seizures and tumour recurrence and depend on such factors as tumour size, location, degree of tumour excision, histology and the preoperative condition of the patient. The invasive nature of many meningiomas precludes curative resection, reducing the duration of survival and quality of life after surgery for this ‘benign’ tumour. In this context we report the case of a 66 year old man with an invasive and recurring meningioma with metastases to the lungs. CASE REPORT The patient, a 66 year old man, was admitted to The Westmead Centre in 1983 for investigation of a gradually enlarging, painless right frontal skull mass, noticed 6 months earlier. This was associated with depressed mood and paranoid ideation, but with no headaches or other neurological symptoms or signs. Past history included heavy alcohol intake and electroconvulsive therapy 40 years prior for depression. Skull X-rays revealed a right frontoparietal bony erosion, and a computed tomography (CT) scan was consistent with a large right frontoparietal convexity meningioma with skull erosion and overlying soft tissue invasion. The tumour crossed the midline and produced significant mass effect. Angiography revealed vascular supply exclusively from the right middle meningeal artery, and a patent superior sagittal sinus. Chest X-rays were normal. The patient underwent a right frontoparietal craniotomy and excision of the tumour and associated dura and skull. A ‘mat’ © 2000 Harcourt Publishers Ltd
of tumour between the layers of the dura as it approached the superior sagittal sinus was observed, and it was not clear if this had been entirely excised or if there was tumour in the sinus. Postoperatively, the patient made a good neurological recovery. Histopathology revealed a predominantly meningothelial meningioma with marked invasion of skull, soft tissue and dural veins. Invasion of tumour beyond the margins of resection was observed. Regions of hypercellularity, pleomorphism and necrosis were consistent with a diagnosis of atypical meningioma (Fig. 1). A methylmethacrylate cranioplasty was performed 3 months later and suspected tumour was found in the bony margins of the defect. Excision to microscopically normal bone was undertaken and the histopathology of these fragments revealed features of bony sclerosis and fibrous tissue in the marrow spaces suggestive, but not diagnostic, of meningioma. Postoperative radiotherapy 60 Gy in 30 fractions was delivered to the excision site, with wide margins. The patient remained neurologically well for 8 years postoperatively. He developed hypertension and non-insulin-dependent diabetes mellitus, and required regular antipsychotic medication. A CT scan 1 year postoperatively showed no tumour recurrence. In 1991 (age 75) he was readmitted with headache, mild left hemiparesis, and a right proptosis. CT and magnetic resonance imaging (MRI) scans revealed a 4 cm recurrence of the tumour based on the right sphenoid wing and anterior cranial fossa with a moderate extension into the right orbit (Fig 2). Angiography showed prominent tumour staining with external carotid artery injection and minimal internal carotid artery supply. The lesion was embolised preoperatively and excised with gross macroscopic removal of tumour and involved bone. The tumour involved the skull around the previous craniotomy as well as the sphenoid wing, anterior clinoid process, optic canal and floor of the anterior cranial fossa. Fascia lata was used to repair the dura and orbital roof and an acrylic cranioplasty was performed. Histopathology revealed partly meningothelial and partly fibroblastic meningioma. It had a more bland and less cellular appearance than the previous specimen with fewer features of atypia. Postoperatively, he had a persistent mild left hemiparesis, and other psychiatric problems. Marked frontal lobe and memory deficits were present. Three years later, the patient presented with progressive right proptosis and left hemiparesis. An MRI scan demonstrated multicentric tumour recurrence in both the roof of the right orbit and right ethmoid air cells. A chest X-ray revealed a 3–4 cm coin lesion in the apical segment of the right lower lobe (Fig 3), with features of previous asbestos exposure and congestive cardiac failure. In retrospect, the coin lesion, although smaller, was present on a chest X-ray in 1993. A thoracic CT scan revealed multiple masses in the right lung and fine needle aspiration biopsy was consistent with meningioma (Fig 4). There was no suggestion of malignancy and the small tissue fragments displayed prominent whorl formation. An abdominal CT scan revealed calcific lesions of uncertain nature in the liver and spleen. The patient declined further operative treatment and returned home. He died 6 months later after a period of progressive drowsiness, left hemiparesis and worsening seizures. DISCUSSION We have presented the case of an elderly man with pulmonary metastases from an invasive and recurrent intracranial meningioma of atypical histology. Reports of metastatic meningioma are scattered throughout the literature, furnishing examples of the rare phenomenon of metastatic involvement of extracranial sites including the lungs,2,3 liver,4 and skeletal system.5 This case provides an opportunity to review the literature regarding metastatic meningioma, in the light of the recent reclassification of meningeal tumours and contemporary knowledge of tumour biology. Journal of Clinical Neuroscience (2000) 7(1)
70 Drummond et al.
Fig. 1 Histopathology of tissue from the initial resection revealed an atypical meningioma, with hypercellularity and pleomorphism (light microscopy, haematoxylin and eosin. X 400).
Fig. 2 Magnetic resonance imaging (sagittal plane) revealed recurrent meningioma invading the right orbit.
Fig. 3 Chest radiograph demonstrating a 3–4 cm coin lesion in the right lower lobe.
A literature review regarding metastatic meningioma highlights the advances in histopathology and changes in tumour classification which have occurred over the last few decades. However, the absence of a longstanding, uniform, and well defined histopathological classification has diminished the utility of many of these publications in analysing this clinicopathological entity. Three main problems are evident: i) the failure to discriminate between extracranial meningioma metastases and other extracerebral tumours in patients with meningiomas; ii) the absence of a reliable distinction between benign and malignant histopathology; and iii) the previous inclusion of haemangiopericytomas as ‘angioblastic’ meningiomas. Inadequate histological documentation and verification cast doubt over the true diagnosis of dozens of cases previously reported as metastatic meningioma.6–8 In 1960, Kruse9 could find only 22 acceptably documented reports. In some cases, meningeal metastases from extracerebral tumours were wrongly assumed to be meningioma with extracranial metastases.6,7 Many series do not separate histologically benign and malignant meningioma when analysing their patient group.7,8,10 In some reports, the two tumour types are described and analysed together. In others, the distinction is not considered, making much of the literature unreliable.11 Furthermore, the criteria on which malignant classification is based in older reports are often different to those used more recently and described below.11–14
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Fig. 4 Fine needle aspiration cytology of the pulmonary lesion was consistent with meningioma (light microscopy, haematoxylin and eosin) X 640.
Despite these difficulties, Celli et al.15 reviewed the literature and felt that only 11 cases of histologically verified benign metastatic meningioma had been reported, from more than 100 cases. In 1994, Tominaga et al.16 stated that 60% of 113 reported patients with metastases were from histopathologically benign meningiomas. Unfortunately, the determination of malignancy in meningiomas is imprecise. With extracerebral tumours, the usual proof of malignancy with extracerebral tumours is the presence of distant metastases. However, these are unusual even for histologically very anaplastic meningiomas, with an incidence possibly as low as 0.1%.17 Further, meningiomas with benign histological characteristics occasionally produce secondary deposits. Malignancy in meningiomas, as with other intracranial tumours, is described in terms of histological grade rather than the presence of metastasis.18 The intermediate grade ‘atypical’, meningioma, is defined by the presence of more than one of the following: frequent mitoses, increased cellularity, high nuclear to cytoplasmic ratio, prominent nucleoli, loss of tumour architecture (e.g. whorl formation) and microscopic foci of necrosis, but not in such a degree to warrant the diagnosis of malignancy.19 These features
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Metastatic atypical meningioma 71
were seen in the initial specimen of the case reported here, but were less evident in the recurrence and were absent in the metastatic lesion (this may be due to the small tissue sample obtained by fine needle aspiration). Frank malignancy, the histopathological features of which were not observed in any specimens from our patient, involves a progression of the above features with obvious malignant cytology, high mitotic index and conspicuous necrosis. Invasion of the brain is variably associated with malignancy but invasion of other structures such as calvarial bone and scalp, as in our case, is not.19–21 Malignancy and atypia are associated with a higher rate of recurrence and metastasis,18,22–25 and, unlike this particular case, meningiomas tend to become more histologically atypical with each recurrence.22,25,26 When a histologically ‘benign’ meningioma metastasizes, the classifications become confused, and our inadequate knowledge of the factors responsible for such behaviour of this heterogeneous group of tumours becomes evident. The radiographic presence of the long-standing pulmonary lesion, together with the failure of histopathological progression towards malignancy, suggests that the metastatic process in this case was not intimately associated with malignant transformation of the primary tumour. The relatively recent WHO reclassification of most ‘angioblastic’ meningiomas as haemangiopericytoma,19,21,27 has further clouded the interpretation of older reports of metastatic meningiomas. Many such reports include tumours defined as metastatic ‘angioblastic meningiomas’,10,28–30 however, the exact nature of these tumours is difficult to determine in retrospect. Where haemagiopericytoma is used as a classification, it is often not separated as a non-meningiomatous tumour in the analysis.11,31,32 This is important as haemangiopericytoma is an aggressive tumour with a higher propensity to recurrence and metastasis than meningiomas.20,27 Despite the above limitations, important information can be gleaned from previous reports. Metastatic meningioma is a rare occurrence which is more common in men, despite the overall female preponderance of the primary disease.8,10,15,22 This may be related to the higher incidence of haemangiopericytoma in males,20 which are often included in reports of metastasising meningioma. No particular histological subtype is known to predispose to metastasis.33,34 Parasagittal and falcine locations may give rise to metastases more frequently,10,15,22 however, this is controversial.33 Pulmonary and pleural metastases are the most common (60%), followed by deposits in the liver and other abdominal viscera, lymph nodes (especially cervical and mediastinal), vertebrae and other bones.7–10,13–16,23,26,30,33,35–39 Metastases via the CSF pathways are extremely rare, even for malignant menigioma.12 Metastases are often asymptomatic and rarely a cause of death.7,9,20,23,37 The interval between diagnosis of the primary and the metastasis is variable but may be decades.9,16 The likely routes of extracranial metastasis are venous and lymphatic.8–10,13,16 Meningiomas commonly invade dural venous sinuses and cranial veins and from there can travel to the pulmonary circulation, the azygous and hemiazygous system, and the vertebral venous plexus, accounting for the major sites of metastasis.40 The very rare metastases to long bones are more difficult to explain but may be arterial.41 Meningiomas gain access to the lymphatic system if they involve the skull and scalp or lymphatics around the cranial nerves for instance in the cavernous sinus.10,13,42 Surgery was initially thought to predispose to metastasis, allowing tumour cells access to the blood and lymphatic circulation.16 Their occurrence in the absence of surgery,7–10,14,15,18,33 as well as the preoperative involvement of many meningiomas in the venous system, making the role of surgery unclear. The mechanism of metastasis and the features of a particular tumour which predispose it to metastasis are poorly understood. High proliferative potential, as revealed by mitotic rate,
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bromodeoxyuridine (BRDU) labelling index, proliferating cell nuclear antigen labelling indices or MIB-1 monoclonal antibody staining of the Ki67 nuclear protein, has been suggested to predispose to metastasis.15,22,34 High MIB-1 and BRDU proliferation indices have indeed been related to atypical and malignant histology and time to recurrence in meningiomas,22,43–46 however, the relationship to metastasis is unclear. It appears likely that proliferative potential is more closely related to the rate of tumour growth and time to recurrence than to the process of traversing the basement membrane and surviving in blood or lymphatic vessels, evading host defences, implanting at a distant site and establishing a blood supply (as would be necessary for meningioma metastasis). The ability to metastasise may be dependent upon coexistent but different characteristics of the tumour biology than those conferring rapid growth and ‘malignancy’. The ability of meningiomas to invade widely into adjacent tissues has been extensively discussed by other authors, largely in relation to postoperative recurrence, which is difficult to predict on the basis of tumour histology.24,43 The high rate of recurrence, even after Simpson Grade 1 excision,47 has been ascribed both to regional multicentricity48 and to the invasive nature of meningiomas (and consequently probable incomplete excision). It is not clear whether the tendency to invade locally is related to the ability to metastasise, however, in some series of metastatic meningiomas there is a preponderance of invasive tumours.15 It seems logical that those characteristics which permit invasion of local tissues, such as cell migration and the ability to breakdown vascular basement membrane and interstitial extracellular matrix, would be useful to promote metastasis. These characteristics are variably present in meningiomas. Confrontation of meningioma monolayer cultures with spheroids of cultured embryonic chick heart showed a great variability between individual meningiomas to invade and progressively replace the embryonic tissue which did not always correlate with histological malignancy.49 Metastatic potential has been correlated with the ability to degrade the basement membrane for more than a decade.50 More recently, the interplay of matrix metalloproteinases and their inhibitors,51,52 and other proteases such as urokinase- and tissuetype plasminogen activator and their inhibitors,53 have been shown to be important in tumour metastasis and invasion. There is evidence that increases or decreases in the production of these enzymes or their induction in surrounding tissues may be important in meningioma invasion54 and possibly, therefore, metastasis. The poor expression of CD44 (a cell adhesion molecule and receptor for hyaluronic acid thought to be important for tumour invasion and metastasis) on meningioma cells lacking any atypical or malignant features may partly explain their usual inability to invade and metastasise.55 Conversely, the same authors demonstrated increased CD44 expression in invasive gliomas. Other factors are also likely to be important, such as vascular endothelial growth factor, which has been shown to be related to tumour angiogenesis and metastasis in a number of human cancers and which is overexpressed in some meningiomas.56 In relation to the case reported, some of the problematic features of patients with meningiomas are highlighted. This man had a highly invasive tumour, of atypical histology on at least one specimen, which recurred despite repeated gross macroscopic surgical excision and adjuvant radiotherapy. The histopathology of the lung metastasis had no atypical features, as opposed to that of the cranial lesions, particularly the first, a phenomenon that has been previously reported.26 The relationship of the invasive potential of the tumour and the pulmonary and possibly abdominal metastases is unclear, but as suggested above, the two features may be related. The location of the tumour, patient gender and site of the metastases
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is typical for that previously reported. Over the course of 11 years the primary tumour caused a marked deterioration in his quality of life and was almost certainly the eventual cause of death. The cell biology being investigated in relation to invasion by other intracranial tumours, such as gliomas, and invasion and metastasis by extracranial tumours may hold the key to the invasive nature of meningiomas and their rare metastases, regardless of histological type and grade. ACKNOWLEDGEMENTS The authors thank Dr MF Gonzales (Neuropathologist, Royal Melbourne Hospital, Melbourne) and Dr THK Ng (Neuropathologist, The Westmead Centre, Sydney) for reviewing the histopathology. REFERENCES 1. Chan RC, Thompson GB. Morbidity, mortality, and quality of life following surgery for intracranial meningiomas. J Neurosurg 1984;60:52–60. 2. Tworek JA, Mikhail AA, Blaivas M. Meningioma: local recurrence and pulmonary metastasis diagnosed by fine needle aspiration. Acta Cytol 1997;41:946–947. 3. Shin MS, Holman WL, Herrera GA, Ho K-J. Extensive pulmonary metastasis of an intracranial meningioma with repeated recurrence: radiographic and pathologic features. South Med J 1996;89:313–318. 4. Ferguson JM, Flinn J. Intracranial meningioma with hepatic metastases and hypoglycaemia treated by selective hepatic arterial chemo-embolization. Australas Radiol 1995;39:97–99. 5. Palmer JD, Cook PL, Ellison DW. Extracranial osseous metastases from intracranial meningioma. Br J Neurosurg 1994;8:215–218. 6. Abbott KH, Love JG. Metastasizing intracranial meningiomas. Ann Surg 1943;118:343–352. 7. Christensen E, Kiaer W, Winblad S. Meningeal tumours with extracerebral metastases. Br J Cancer 1949;3:485–493. 8. Glasauer FE, Yuan RHP. Intracranial tumours with extracranial metastases. Case report and review of the literature. J Neurosurg 1963;20:474–493. 9. Kruse F. Menigeal tumours with extracranial metastasis. A clinicopathological report of 2 cases. Neurology 1960;10:197–201. 10. Shuangshoti S, Hongsaprabhas C, Netsky MG. Metastasizing meningioma. Cancer 1970;26:832–841. 11. Thomas HG, Dolman CL, Berry K. Malignant meningioma: clinical and pathological features. J Neurosurg 1981;55:929–934. 12. Ludwin SK, Conley FK. Malignant meningioma metastasizing through the cerebrospinal pathways. J Neurol Neurosurg Psychiatry 1975;38:136–142. 13. Vlachos J, Prose PH. Meningioma with extracranial metastases. Cancer 1958;11:439–445. 14. Miller DC, Ojemann RG, Proppe KH, McGinnis BD, Grillo HC. Benign metastasizing meningioma. J Neurosurg 1985;62:763–766. 15. Celli P, Palma L, Domenicucci M, Scarpinati M. Histologically benign recurrent menigioma metastasizing to the parotid gland: case report and review of the literature. Neurosurgery 1992;31:1113–1116. 16. Tominaga T, Koshu K, Narita N, Yoshimoto T. Metastatic maningioma to the second cervical vertebral body: a case report. Neurosurgery 1994;43:538–540. 17. Strang RR, Tovi D, Nordenstam H. Meningioma with intracerebral, cerebellar and vsceral metastases. J Neurosurg 1964;21:1098–1102. 18. Alvarez F, Roda JM, Romero MP, Morales C, Sarmiento MA, Blazquez MG. Malignant and atypical menigiomas: a reappraisal of clinical, histological, and computed tomographic features. Neurosurgery 1987;20:688–694. 19. Kleihues P, Burger PC, Scheithauer BW. Histological typing of tumours of the central nervous system. World Health Organisation. 2nd ed. Berlin: Springer Verlag, 1993:33–42. 20. Russell DS, Rubenstein LJ. Pathology of Tumours of the Nervous System. 5th ed. London: Williams and Wilkins, 1989. 21. Gonzales MF. Classification and pathogenesis of brain tumours. In: Kaye AH, Laws ER (eds) Brain Tumours. Edinburgh: Churchill Livingstone, 1995:31–45. 22. Ohta M, Iwaki T, Kitamoto T, Takeshita I, Tateishi J, Fukui M. MIB-1 staining index and scoring of histological features in meningioma. Cancer 1994;74:3176–3189. 23. Leighton SEJ, Rees GL, McDonald B, Alun-Jones T. Metastatic meningioma in the neck. J Laryngol Otol 1991;105:229–231. 24. De la Monte SM, Flickinger J, Linggood RM. Histopathological features predicting recurrence of meningiomas following subtotal resection. Am J Surg Pathol 1986;10:836–843.
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