260 O. W. Sakowitz et al. Acute haemorrhage into a microcystic meningioma leading to cerebral herniation O. W. SAKOWITZ1, I. HARTING2, P. KOHLHOF3, A. W. UNTERBERG1 & H. H. STEINER1 Br J Neurosurg Downloaded from informahealthcare.com by University of Melbourne on 10/29/14 For personal use only. 1 Departments of Neurosurgery, 2Neuroradiology and 3Neuropathology, University of Heidelberg, Germany Abstract Low-grade (WHO level I) meningiomas are slow-growing, benign tumours typically presenting with unspecific symptoms (e.g. headache), seizures, cranial nerve compression and neuropsychological symptoms determined by location and size of the lesion. Haemorrhagic onset and sequelae are rare, and have been described infrequently. This is a case of a 50-year-old male presenting with signs of tentorial herniation secondary to hyperacute intratumoural haemorrhage (ITH) into a previously undiagnosed meningioma. Emergency surgical decompression and exstirpation of the lesion helped to achieve a favourable outcome. ITH has been described in all including benign intracranial neoplasms. Factors associated with a higher risk for haemorrhage in meningiomas are discussed. Though haemorrhages associated with meningiomas have been reported, ITH into low-grade meningiomas leading to herniation remains a rarity. Bearers of known lesions and their treating physicians who opt for conservative or delayed treatment should be aware of this remote complication. Keywords: herniation, intratumoural haemorrhage, low-grade meningioma Introduction Intratumoural haemorrhage (ITH) is a rare complication of meningiomas that can occur spontaneously,1,2 after embolization,3,4 stereotactic radiation5 and perioperatively.6 Extratumoural types of haemorrhage, e.g. subdural, subarachnoid, intraparenchymal and intraventricular, have also been described.7 – 9 We present briefly a case of hyperacute ITH into a previously undiagnosed convexity meningioma leading to symptoms of cerebral herniation. Factors associated with haemorrhage in meningiomas and implications for treatment will also be discussed. Case report A 50-year-old previously healthy male presented to the emergency room of the University of Heidelberg neurosurgical department. The patient was found in bed, unresponsive and hypertensive with anisocoria and gaze-deviation to the left. Brief neurological examination revealed a comatose patient with laboured spontaneous respirations. Pupils were fixed and dilated on the right, with sluggish reaction to light on the left. Best motor response was decorticate posturing (Glasgow coma scale score 4). Analgesic sedation (pentobarbital/ fentanyl) and intubation for airway protection was carried out promptly. Cranial computed tomography (CCT) revealed a large, right frontal spaceoccupying lesion with intratumoural haemorrhage. Strong contrast enhancement of the extra-axial, dura-based lesion with hyperostosis of the adjacent calvarium was characteristic of a meningioma. There was obvious midline shift of approximately 2 cm and effacement of basal cisterns with tentorial herniation and impending foraminal herniation (Fig. 1). During imaging the patient developed bilaterally fixed and dilated pupils and prompt transfer to the operating room was arranged for emergency decompression. A right frontal craniotomy and dural incision was carried out along the non-infiltrated margins of the tumour. This was carefully enlarged along the superior sagittal sinus, where the tumour was partially mobilized in a blunt fashion. After complete microsurgical preparation, the 8 6 10 6 10 cm tumour node was removed without major cortical adhesions. The underlying cortical surface was pulsatile, but remained clearly depressed. After watertight duroplasty with galea-periosteum and removal of reactive hyperostoses, the bone flap was reimplanted and secured with titanium clamps. Correspondence: O. W. Sakowitz, Department of Neurosurgery, University of Heidelberg, Im Neuenheimer Feld 400, D-69120 Heidelberg, Germany. Tel: + 49 6221 56-36172. Fax: + 49 6221 56-5534. E-mail oliver.sakowitz@med.uni-heidelberg.de Received for publication 13 October 2004. Accepted 22 February 2005. DOI: 10.1080/02688690500208734 Br J Neurosurg Downloaded from informahealthcare.com by University of Melbourne on 10/29/14 For personal use only. Spontaneous haemorrhage into a microcystic meningioma 261 FIG. 1. Unenhanced (left) and enhanced (right) CT demonstrating extra-axial localization, hyperostosis of the adjacent calvarium and intense contrast enhancement of the haemorrhagic right frontal lesion. Pupils were checked, and found diminished in size and reactive to light. Postoperatively all sedatives and analgesics were discontinued, the patient regained consciousness promptly without obvious focal-neurological deficits. He was extubated without problems. No tumour residual or haemorrhage were demonstrated on repeat computed tomography (CT) the following day. Retrospectively the patient recalled occasional headaches, but no circumstances of seizure activity, nausea or vomiting in the past 2 – 3 months. No history of head trauma or previous exposure to radiation was elicitable. Past medical and surgical history, family history, medications and detailed review of systems were non-contributory. Haematological studies for occult bleeding diastheses was completed without pathological findings. Histopathological examination was confirmative of a microcystic meningioma with haemorrhagic infiltration (WHO level I; Fig. 2). A pseudomeningocele resolved with repetitive percutaneous drainage. The patient was discharged home in excellent condition on hospital day 9. Discussion Meningiomas comprise approximately 20% of all primary intracranial neoplasms.10 The microcystic variant originally termed ‘humid’ due to its succulent and spongy macroscopic appearance is rare and accounts for 1.6% of all intracranial meningiomas.11,12 According to the literature, the overall rate of haemorrhage in intracranial neoplasms ranges from 1.5 to 5.4%, metastases and gliomas being the most frequently involved.13,14 Meningiomas with haemorrhagic onset are rare, with incidences ranging from 0.5 to 2.4% of all meningeal neoplasms.1,14 – 16 Most cases of haemorrhage associated with meningiomas are extratumoural and subarachnoid, whereas subdural, intracerebral and intratumoural haemorrhage are reported less frequently.7 – 9 To the best of our knowledge (MEDLINEsearch) no other instance of a microcystic meningioma with haemorrhagic onset has been described in the English literature since its inclusion in the WHO classification in 1993.17 Microscopically, this variant has a stellate appearance through numerous cells with processes due to microcystic dilatation of the intercellular spaces. This pseudo-astrocytic appearance may be mistaken for astrocytoma.12 The largest series of histologically proven microcystic meningiomas comprises a total of 11 cases, none of them associated with haemorrhage. The preoperative magnetic resonance (MR) signal characteristics (T1 very low and T2 very high) and enhancing pattern (either homogeneous or peripheral rim enhancement) were reviewed and found to be misleading in 4/11 cases (i.e. interpreted as either glioma or metastasis).18 In accordance with its spongy consistency, the computed tomography (CT) appearance of microcystic meningiomas is hypodense, almost mimicking brain oedema. Contrast enhancement, however, is marked in the majority of cases.19 Br J Neurosurg Downloaded from informahealthcare.com by University of Melbourne on 10/29/14 For personal use only. 262 O. W. Sakowitz et al. FIG. 2. Histopathological findings. (A) Haematoxylin-eosin stain shows a microcystic meningioma with haemorrhage ( 6 100). (B) MIB-1 labelling index is low ( 5 5%), even in areas adjacent to haemorrhage ( 6 100). (C,D) CD31 staining shows a dense capillary network with prominent CD31 expression in areas surrounding haemorrhage (C, 6 100) and a less dense vascularization in other tumour areas with an only slight endothelial expression of CD31 (D, 6 100). Approximately 50% of all meningiomas grow along the calvarium, half of them parasagittally originating from the falx cerebri. Meningiomas are thought to arise from arachnoidal cells of the leptomeninges. Subtypes are histopathologically described as meningotheliomatous, metaplastic, fibroblastic, transitional, psammomatous, secretory, angiomatous, lymphoplasmacyte-rich and microcystic. According to the WHO-classification11 these are all slow-growing, benign lesions (WHO level I). Nevertheless, aggressive growth into the adjacent bone and brain tissue is occasionally observed. Semibenign (atypical, clear-cell and chordoid) and semi-malignant (papillary, rhabdoid and anaplastic) variants with infiltrative growth, high rates of recurrence and metastasis do exist. Based on larger series of meningiomas with haemorrhagic onset both location and histological subtype are unrelated to the risk of bleeding.2,8,9 An increased rate of haemorrhage, however, was reported in ‘angioblastic and malignant’ meningiomas.7 Besides their invasive properties, vascularization and the propensity to cause oedema are clinically important characteristics of meningiomas. Menin- giomas are well vascularized tumours, as demonstrated by the ‘tumour blush’ on angiography. Increased vascularity of meningiomas as a predisposing risk factor for ITH, however, has been controversial.2,15,20 Vascularity of meningiomas apparently depends on paracrine mechanisms of tumour cells. Both vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) and (putatively) endothelins (ETs) have been shown to correlate with vascularity.21 Interestingly, VPF/VEGF is also proposed as a major factor in the formation of peritumoural brain oedema and cystic changes observed in certain meningioma subtypes.21 The given subtype of a microcystic meningioma is known to be highly vascularized and has been associated high expression of VPF/VEGF and its respective receptor.22 Others, however, have found VPF/VEGF not to be correlated with vascularity, but with higher malignancy grades.23 In this case, immunolabelling of the endothelial cell marker CD31 was performed in the operative specimen to assess vascularity of the tumour.15 A dense capillary network with prominent CD31 expression was demonstrated in areas adjacent to Spontaneous haemorrhage into a microcystic meningioma Br J Neurosurg Downloaded from informahealthcare.com by University of Melbourne on 10/29/14 For personal use only. the haemorrhage, whereas other tumour areas exhibited only slight endothelial expression of CD31. Immunohistochemistry of proliferation antigens like Ki-67 can be used to determine the ‘growth fraction’ of a population of cells. MIB-1 is the monoclonal antibody developed against the Ki-67 antigen. The Ki-67 antigen-expressing fraction (‘MIB-1 labelling index’) is therefore a surrogate of the mitotic rate within tumours. In our case, the MIB-1 labelling index was 5 5%, which is considered indicative of benign behaviour.24 Pathophysiological mechanisms underlying ITH are currently not well understood. Yet, several factors associated with haemorrhage in meningiomas have been described: . . . . . . The extent of vascularization, as an independent factor involved in haemorrhagic onset meningiomas, is still under debate, as discussed above. Atypical vessels, fragility and arachnoidal infiltration, seen in semi-benign or semi-malignant variants, seem to be associated with ITH more often.15 Endothelial proliferation and tumour necrosis have been proposed risk factors of haemorrhagic transformation.7,20 Macroscopic cysts are thought to result from ischaemic necrosis and/or ITH. They are frequently associated with the microcystic variant found in this case.21 Venous congestion secondary to infiltration and/ or compression of dural sinuses and bridging veins may lead to a higher propensity to bleed.25 Additionally, association with cerebrovascular malformations has been described and may be an independent factor for ITH in meningiomas.26 Haemorrhagic diastheses are putative precipitating factors,6 as are others (e.g. trauma, stress, hypertension), and are likely to increase the risk for ITH in any of the other circumstances.2 In the case presented above, a benign, microcystic variant meningioma was previously undiagnosed. Intraoperatively, no cerebrovascular abnormality was found nor was a bleeding diasthesis diagnosed subsequently. Therefore, we assume that an intrinsic vessel abnormality or ischaemic portion of the tumour gave rise to ITH. According to imaging characteristics this space-occupying lesion was large enough to critically impair intracranial compliance. Then, even small volumes of ITH could have caused a sudden increase in intracranial pressure with resultant compensatory arterial hypertension. This, in turn, would exacerbate any ongoing haemorrhage, finally leading to cerebral herniation. Despite sustained symptoms of cerebral herniation the patient achieved a good outcome. This could be tentatively explained by adaptation of the cerebral circulation to a slow-growing lesion and tapered loss of intracranial compliance, respectively. Then timing of operative 263 decompression is certainly critical in every spaceoccupying lesion with symptoms of intracranial hypertension. Conclusion Haemorrhagic onset meningiomas remain rare and pathophysiology is still incompletely understood. Prevention and outcome of ITH highly depend on early diagnosis and adequate treatment. Even in cases of hyperacute ITH, patients may achieve a good outcome if rapid and radical evacuation is undertaken. Bearers of known lesions and their treating physicians who opt for conservative or delayed treatment should be aware of this remote complication. References 1 Modesti LM, Binet EF, Collins GH. Meningiomas causing spontaneous intracranial hematomas. J Neurosurg 1976;45: 437 – 41. 2 Martinez-Lage JF, Poza M, Martinez M, Esteban JA, Antunez MC, Sola J. Meningiomas with haemorrhagic onset. Acta Neurochir (Wien) 1991;110:129 – 32. 3 Kallmes DF, Evans AJ, Kaptain GJ, et al. Hemorrhagic complications in embolization of a meningioma: case report and review of the literature. Neuroradiology 1997;39:877 – 80. 4 Yu SC, Boet R, Wong GK, Lam WW, Poon WS. 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