Original article
The coexistence of pleomorphic xanthoastrocytoma and arteriovenous malformation. A case report

Introduction

The association between vascular malformations and cerebral gliomas is unusual, especially if both such lesions occur separately. Most frequently the lesion consists of mixed elements of glial and vascular origin and is determined as angiogliomas [13,19,25,30,41]. The coexistence of vascular malformation with PXA is extremely rare, especially in the context of these two patterns occurring within the same tumour mass. The particular pattern of PXA with angiogliomatous features has been reported [22] but only one case report refers to the true coincidence of PXA and AVM [28]. We present a 36-year-old woman with PXA of parasagittal localization in the right occipital lobe, which was accompanied by vascular changes fulfilling the morphological criteria of AVM. The extremely rare coexistence of pleomorphic xanthoastrocytoma and arteriovenous malformation (AVM) seems to be of very interest, especially when both such lesions occur as separate parts of one tumour.

Case report

A 36-year-old woman was admitted to the Neurosurgical Department. She had been suffering from headaches, dizziness and vertigo for two years. In neurological examination, left hemianopsia was detected. Magnetic resonance of the brain showed a tumour mass of 3.5 × 3.0 × 2.5 cm, which was partially solid and partially cystic, localized parasagittaly in the front of the right occipital lobe, with no features of oedema and mass effect (Figs. 1A, B). The contrast enhancement in the solid part of the tumour was detected. The solid tumour zone touched closely the cerebral falx. The patient underwent right craniotomy and a gross total resection of the lesion was achieved. The postoperative course was uneventful.

Material and methods

The resected tissue was fixed in 10% formalin, embedded in paraffin and stained with haematoxylin-eosin (H&E) and Gomori’s method. Immunohistochemical studies were performed on paraffin-embedded specimens according to the labelled avidin-biotin complex method (ABC) with DAB as chromogen, using antibodies against glial fibrillary acidic protein (GFAP), synaptophysin and MIB-1 antigen (all antibodies from Dako).

Neuropathological examination



The surgical specimens consisted of two parts of different histopathological pattern. The neoplastic infiltration was seen in the superficial layers of the cerebral cortex with massive involvement of the leptomeninges (Fig. 2A). The main solid tumour mass, developing in the superficial cortex, showed typical PXA morphology with a moderate cellular polymorphism and varying degree of cytoplasmic lipidization (Figs. 2B-D). The eosinophilic granular bodies and perivascular lymphocytes could be occasionally seen. Focally, the elongated cells exhibited fascicular architecture. The dense reticulin fibers investing the small clusters of neoplastic cells predominated in the superficial part of the tumour (Fig. 2E). The subset of tumour cells stained positively for glial fibrillary acidic protein (GFAP), however the immunoreactivity was rather patchy and weak (Fig. 2F). Individual pleomorphic cells were immunopositive for synaptophysin. MIB-1 labelling index was low, up to 2%.

In the superficial part of the tumour and in the subarachnoid space, a number of abnormal blood vessels with various degree of hyalinization was seen (Fig. 3A). The vascular changes included abnormal, enlarged, often irregular vessels with asymmetrically thickened walls (Figs. 3B, C). The lesion exhibited morphology of arteriovenous malformation and consisted of arteries and veins of different calibre with local attenuation of the walls accompanied by small capillary channels embedded in brain parenchyma (Fig. 3D). The brain tissue surrounding the vascular conglomerates showed reactive fibrous gliosis and presence of hemosiderin deposits.

Discussion

Pleomorphic xanthoastrocytoma (PXA) was first described by Kepes and co-authors in 1979 [27]. It is a rare, low-grade astrocytic tumour, corresponding to WHO grade II that generally affects children and young adults [26,37,39,43]. This tumour develops predominantly at superficial cortical regions with partial occupation of the leptomeninges, more preferably within the temporal lobe [6,10,27]. PXA usually appears as a highly cellular astrocytic tumour composed of cells of varying size and shape [26,27,34]. The significant cellular pleomorphism includes spindle cells, mononucleated and multinucleated giant cells and lipid-rich vacuolated ones accompanied by eosinophilic granular cell bodies and reticulin fibers. Necrosis is usually absent. A small number of lymphocytes and plasma cells infiltrations are common. Immunohistochemical studies demonstrate diffuse positivity for glial fibrillary acidic protein (GFAP), vimentin and S-100 protein and occasionally neuronal markers expression [14]. About 70% of cases show positive staining for CD34. PXA belongs to grade II of the WHO histological classification of CNS tumours and therefore is considered as a relatively benign lesion with a favourable prognosis [12]. Most cases show typical pathologic features, nevertheless occasionally the tumour undergoes malignant transformation and behaves more aggressively [7,31,33,44]. Nevertheless, the patients with PXA with anaplastic features have a significantly better overall survival than patients with other malignant gliomas [36]. PXAs may recur and demonstrate aggressive clinical behaviour with a mortality rate between 15% and 20%. Such tumours are usually less pleomorphic and more diffusely infiltrative. The mitotic index and extent of resection appear to be the main predictors of recurrence-free time and overall survival rates. The basic treatment of PXA is its total surgical removal whereas the efficacy of adjuvant radiotherapy or chemotherapy has not been clearly defined [34,42]. In rare cases with evidence of dissemination the repeated stereotactic irradiation might be considered.

The primary brain tumours may be accompanied by vascular malformations and such rare coincidence involves mostly gliomas and meningiomas [2,4,13,16,19,20,23,24,29].

Vascular malformations consisting of abnormal arteries and veins are usually congenital. They can occur at any age, but most often between 20 and 40 years of age. Clinical symptoms of AVM depend on its location. Most frequently, AVM presents with headaches and seizures but at least 15% occur asymptomatic. More than 50% of AVMs present with intracranial haemorrhages that account for about 2% of all haemorrhagic strokes each year [1,8,9,11,21]. AVM-specific treatment may involve endovascular embolization, neurosurgery or radiation therapy [5]. Grading schemes were initially developed as a means to predict the surgical risk during obliteration [17,40]. The most commonly used grading scale is the system described by Spetzler and Martin [38].

The association between vascular malformation and cerebral gliomas is unusual. The lesions, consisting of mixed tumours of glial and vascular origin, particularly of cavernous or arteriovenous type, have been often defined as angiogliomas [3,13,19,25,30,41]. The term “angioglioma” is confusing and according to some authors should not be used to determine the true coincidence of vascular and neoplastic glial lesions. However, the term “angioglioma” appears to be valid for rare cases of the low-grade glioma with a distinct vascular pathology. It has been mostly used for highly vascular low-grade gliomas associated with a favourable prognosis [30,32,35]. The pathogenetic suggestions consider such angiogliomatic lesions as a result of reactive astroglial neoplastic proliferation secondary to a pre-existing vascular malformation and/or haemorrhages. Microscopically, the hemosiderin-laden macrophages and reactive gliosis could be observed in the vicinity of the lesion. It is important not to confuse such angiogliomatic lesion with high-grade gliomas displaying malignant neovascularity.

The coexistence of clearly demarcated glioma and vascular malformation is rarely identified [4]. Vascular malformations might be associated with different glial components including benign and anaplastic astrocytoma, oligodendroglioma, mixed oligo-astrocytoma or glioblastoma [4,13,15,16,18,20,35,45]. The majority of vascular pathology in coexistence with gliomas consists of arteriovenous malformation (AVM), less often cavernous angioma. Only a few reports describe the coexistence of PXA and AVM [28]. The current case presents the lesion of two separate components of PXA and AVM, that are closely related and form a common tumour mass. The pathogenesis of such coexistence, being the two parts of one tumour, remains still unclear, and further studies of a series of patients are needed.

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