Pleomorphic xanthoastrocytoma. Immunohistochemical methods for differentiation from fibrous histiocytomas with similar morphology

Three cases of primary intracranial tumours fulfilling the clinical and histological criteria of pleomorphic xanthoastrocytoma are presented. As is typical, they occurred in young people, aged 15, 17, and 22 years, and were composed of lipid-laden pleomorphic cells with frequent bizarre multinucleated forms and a prominent reticulin network. However, subsequent immunohistochemistry, further histological review, and clinical follow-up suggest that these tumours were different entities. In one case the tumour cells were negative for GFAP but positive with a panel of histiocytic markers. The lesion, which extended rapidly and caused death within 6 months, was assumed to be a true meningeal fibrous histiocytoma. The remaining two cases were positive for glial fibrillary acidic protein (GFAP) and S100 protein. One of these was mitotically active, contained areas of necrosis and vascular proliferation, and also led rapidly to death. This, we concluded, was a glioblastoma. The third case showed little mitotic activity and the patient remains well; this is probably a true pleomorphic xanthoastrocytoma. These results indicate that tumours with light-microscopic appearance of pleomorphic xanthoastrocytoma require detailed immunohistochemical investigation. Only those lesions with low mitotic activity and undoubted evidence of glial origin should be accepted as true pleomorphic xanthoastrocytoma. Extensive necrosis in a tumour with GFAP-positive, lipid-rich cells indicates a lipidised glioblastoma, while positive histiocytic immunocytochemistry should suggest a fibrous histiocytoma.     

Pleomorphic xanthoastrocytoma: some observations

The authors describe 3 cases of cerebral pleomorphic xanthoastrocytoma, one of which has an unusual neuroradiological appearance, and review the clinical and prognostic features of the 96 cases reported in the literature. Pleomorphic xanthoastrocytoma is a neuroectodermal tumor that affects young patients, in a superficial or supratentorial site, most frequently at the temporal level. It is difficult to formulate a differential diagnosis with other neuroectodermal tumors or with meningioma on the basis et neuroradiological appearance, as demonstrated by one of the cases reported here. The prognosis of this tumor is very good, regardless of the type of treatment performed, although both relapse and, more rarely, malignant tumor evolution are possible.     

Arteriovenous malformation associated with pleomorphic xanthoastrocytoma

Summary A case of a left temporo-occipital arteriovenous malformation associated with a pleomorphic xanthoastrocytoma is described. The patient had the vascular lesion with a stable right hemiparesis for many years prior to his recent clinical deterioration. Correlation is made with nine previously reported cases of angiogliomas. With the close proximity and temporal correlation of the two components of this lesion, as well as pathological evidence, the authors propose that angioglioma may be the product of reactive glial proliferation and transformation secondary to a pre-existing vascular malformation and hemorrhage.     

Pleomorphic xanthoastrocytoma with 18-year survival. Case report

The authors present a case of right parietal pleomorphic xanthoastrocytoma that occurred in a 24-year-old man. The patient was originally operated on in 1966, and at that time the diagnosis of monstrocellular sarcoma was made. The patient is still alive and totally symptom-free. A careful reevaluation of the microscopic findings, including positive glial fibrillary acidic protein staining, led to the definite diagnosis of pleomorphic xanthoastrocytoma.     

Pleomorphic xanthoastrocytoma: report of two cases

Two cases of pleomorphic xanthoastrocytoma are presented to draw attention to this relatively benign variant of glioma. The circumscribed tumors, each with a cystic component, were located superficially, one in the mesial right temporal lobe and one in the right temporoparietal region. The patients were aged 12 and 14 years, and it is now almost 7 years since the onset of symptoms in the 12-year-old boy. The optimal plan of management is discussed.     

Pleomorphic xanthoastrocytoma. Report of four cases

Four cases of pleomorphic xanthoastrocytoma (PXA), a low-grade leptomeningeal glioma with a reported favorable prognosis affecting young patients, are reported together with a discussion and review of management and prognosis. A literature review has confirmed a favorable prognosis in at least 50% of patients with this disorder. Seventeen of 35 reported patients are still alive and often seizure-free for a mean period of 7.4 years (range 2 to 18 years) after diagnosis. Five patients have died within 2 years and four between 9 and 25 years after diagnosis of PXA. In some cases in which death followed shortly after diagnosis, there may have been histological confusion between PXA and a malignant glioma with heavily lipidized tumor cells. Nonetheless, transformation of PXA into a malignant astrocytoma or glioblastoma with eventual death may occur many years after initial diagnosis. From the currently reported cases it does not appear possible on clinicopathological grounds to predict which patients will have a favorable prognosis. Optimal management of PXA seems to be primary surgical resection with later surgery for residual or recurrent tumor. The role of radiotherapy in the management of PXA is at this time uncertain.     

Pleomorphic xanthoastrocytoma (Kepes): a case report

A case of tumor to be diagnosed as pleomorphic xanthoastrocytoma (Kepes) is reported. This patient was a 34-year-old female with a 6-year history of TIA. Neurological examination on admission showed no abnormalities except for bilateral choked disc. Plain CT scan revealed a well-defined low density area with a small high density region in the right temporal lobe. The small high density region and a part of peripheral portion of low density area were moderately enhanced with contrast media. At operation there was a cyst containing xanthochromic fluid at 1.5 cm depth from the cerebral surface. Temporal lobectomy and subtotal removal of tumor (5gr) were performed. The patient received postoperative radiation therapy (5960 rad). She has been doing extremely well for these 5 years following craniotomy and has no deficits except for the left upper quadrant hemianopsia which appeared immediately after surgery. There cannot be observed any symptoms or signs suggesting tumor recurrence. Histologically the tumor cells displayed marked pleomorphism. However, either necrosis or mitosis were very hard to find. The tumor cells were surrounded by a dense network of reticulin fibers. Electron-microscopically the tumor cells were occasionally filled with glial fibrils, and lipid granules were seen. Immunoperoxidase technique revealed both glial fibrillary acidic protein (GFAP) and S-100 protein in the cytoplasm of tumor cells, suggesting of neuroectodermal origin. Although this patient is older than previously reported cases (age 3 to 32), the histological findings as well as the good postoperative course indicate that this case may fulfill the criteria of pleomorphic xanthoastrocytoma first proposed by Kepes et al.     

Pleomorphic xanthoastrocytoma of the spinal cord. Case report

The authors present clinical, radiological, and pathological features in a patient with a pleomorphic xanthoastrocytoma (PXA) of the spinal cord. To their knowledge, this is only the second report of a spinal cord PXA. In addition they provide a review of the literature on these tumors.     

Pleomorphic xanthoastrocytoma of the cerebellum: illustrated review

Summary Although rarely, the usually benign, supratentorial, grade II astrocytic tumour pleomorphic xanthoastrocytoma (PXA) may arise from the cerebellum. A review of the published cases of these PXAs is made including the authors own case of a 40 years-old man with a right cerebellopontine angle tumour, which recurred after a gross total resection.The major clinical and histopathological features of cerebellar PXAs are discussed, and factors playing a role in their biological behaviour, like post-surgical medical treatment, genetics and extent of leptomeningeal seeding are stressed.     

Eighteen-year survival of a patient with malignant pleomorphic xanthoastrocytoma associated with von Recklinghausen neurofibromatosis

The authors report the first adult case of pleomorphic xanthoastrocytoma associated with neurofibromatosis-1. A 40-year-old man with history of neurofibromatosis-1 underwent total removal of a right temporo-parietal superficial glioma followed by radiation therapy. Eighteen years after surgery, the patient remained well with no tumour recurrence, which prompted review of the surgical material. The diagnosis of pleomorphic xanthoastrocytoma was then made though the tumour exhibited malignant features histologically, with marked necrosis. This extremely good clinical outcome suggest that some astrocytoma tumours in patients with neurofibromatosis might be associated with a favourable prognosis.     

Combined oligodendroglioma/pleomorphic xanthoastrocytoma: a probable collision tumor: case report

OBJECTIVE AND IMPORTANCE: We report the first case of combined oligodendroglioma and pleomorphic xanthoastrocytoma. CLINICAL PRESENTATION: A female college student and competitive cross-country runner presented to the Mayo Clinic at age 18 years with complaints of progressive headache and visual disturbances. Neuroimaging revealed a heavily calcified left parieto-occipital mass with focal enhancement and remodeling of the overlying calvarium. INTERVENTION: A histological examination of the nearly gross total resection specimen disclosed a low-grade oligodendroglioma discretely abutting a superficially situated focus of pleomorphic xanthoastrocytoma. Ten months thereafter, a recurrence was suspected on the basis of the detection of a new focus of nodular enhancement. This lesion stabilized after radiation therapy, and the patient is well, without apparent residual disease 2.8 years after surgery. CONCLUSION: This unique neoplasm is presumed to represent a collision tumor, its biological behavior being similar to that of oligodendroglioma alone. However, the possibility of an unusual, mixed oligoastrocytoma with pleomorphic xanthoastrocytoma as the astrocytic component cannot be excluded entirely. Potentially, both components have the capacity for recurrence and anaplastic transformation.     

Distinctive pleomorphic xanthoastrocytoma-like tumor with exclusive abortive or aberrant neuronal differentiation and repeated recurrence--case report

A 9-year-old girl with a 1-month history of generalized seizure presented with a distinctive tumor resembling pleomorphic xanthoastrocytoma. Neuroimagings showed a right frontotemporal lobe tumor. Histological examination of the resected tumor indicated similarity to pleomorphic xanthoastrocytoma without staining for glial fibrillary acidic protein. The neuronal immunoreactivity and ultrastructural features showed two discrepancies: Numerous cytoplasmic processes containing rich structures suspected to be microtubules and neurofilaments were present, but neurofilament protein 70 kd/200 kd staining was negative; and many tumor cells showed synaptophysin staining, but no synaptic structures or vesicles were observed. She suffered recurrence 14 months after the first surgery. The specimen from the second operation revealed no malignant transformation with a MIB-1 labeling index of 1.9%. Only 2 months after the second operation, there was a second recurrence. Irradiation was administered (60.2 Gy). Twenty-eight months later, no tumor progression was seen. This tumor was an unconventional type with "abortive" or "aberrant" neuronal differentiation or an extreme variant of pleomorphic xanthoastrocytoma.     

Multicentric pleomorphic xanthoastrocytoma in a patient with neurofibromatosis type 1. Case report and review of the literature

The authors report an unusual case of multicentric pleomorphic xanthoastrocytoma (PXA) in a 36-year-old woman with neurofibromatosis Type 1 (NF1). Both lesions were diagnosed as PXA but demonstrated different neuroimaging features and very different outcomes. Although the occipital lesion was cured surgically, the cerebellar tumor recurred three times and underwent malignant transformation into an anaplastic oligodendroglioma. The authors discuss the causes of PXA and suggest that it could originate from common bipotential precursor cells with two phenotypes.     

Intrasellar pleomorphic xanthoastrocytoma: case report

OBJECTIVE AND IMPORTANCE: A patient with a primary intrasellar pleomorphic xanthoastrocytoma is described. CLINICAL PRESENTATION: A 78-year-old woman experienced slowly progressing bilateral visual disturbance. Analysis of magnetic resonance imaging scans indicated a well-enhanced tumor occupying intra- and suprasellar spaces with displacement of the pituitary gland anteriorly. INTERVENTION: Partial resection of the tumor via the transsphenoidal route brought about improvement of the patient's visual disturbance. The tumor was conspicuously pleomorphic and composed of plump to spindle-shaped large and bizarre cells with single or multiple nuclei and lipid-laden foamy cytoplasm. The neoplastic cells were positive for glial fibrillary acidic protein, S-100 protein, and vimentin. The MIB-1 antibody labeling index was very low (<1%) CONCLUSION: Pleomorphic xanthoastrocytoma should be included in the differential diagnosis of tumors arising in the posterior hypophysis.     

A variant of cerebral glioma called pleomorphic xanthoastrocytoma: case report

A newly recognized type of cerebral astrocytoma has been described in the last 5 years among patients under the age of 30. The designation of pleomorphic xanthoastrocytoma has been suggested for this neoplasm on the basis of its unique histological features. These include abundant lipid droplets in the astrocytic cytoplasm. We report an additional case of this cerebral hemisphere astrocytoma, which (in common with 17 others reported before) occurred in a young patient. His postoperative course has been benign and he remains ambulatory and almost symptom-free 9 years after the initial tumor excision. The diagnosis of pleomorphic xanthoastrocytoma should be entertained in patients in whom a superficially placed intracerebral tumor (i.e., one that seems to be in contact with the meninges) develops during the juvenile years.     

Pleomorphic xanthoastrocytoma as a component of a cerebellar ganglioglioma: case report.

A 27-year old male patient underwent surgery for a cerebellar ganglioglioma in which a pleomorphic xanthoastrocytoma constituted the gliomatous element. Neither radiation nor chemotherapy was administered. The patient was well for 12 years and then he suffered a recurrence and underwent a gross total resection. Histological examination revealed a ganglioglioma with thrombosed blood vessels, areas of tumor necrosis, and scattered mitoses. These anaplastic changes, which were restricted to the glial component of the tumor, may herald a more aggressive clinical course. However, 11 months after the second operation, there have been no signs of tumor recurrence.     

Immunophenotype of pleomorphic xanthoastrocytoma

Pleomorphic xanthoastrocytoma (PXA) is an uncommon tumor, often seizure-associated and occurring in the temporal lobe of young adults. Although its cells are considered astrocytic in nature, recent studies suggest the presence of neuronal differentiation and a possible relationship to glioneuronal neoplasms. We immunostained 40 cases of PXA, including two composite PXA-gangliogliomas (PXA-GG), with a panel of glial (glial fibrillary acidic protein, S-100 protein) and neuronal markers (class III beta-tubulin, synaptophysin, neurofilament proteins, MAP2, and chromogranin A). Conventional PXAs demonstrated immunoreactivity for glial fibrillary acidic protein (100% of cases), S-100 protein (100%), class III beta-tubulin (73%), synaptophysin (38%), NF proteins (18 and 8%), and MAP2 (8%). Chromogranin A stain was absent in all conventional PXA cases. Neoplastic ganglion cells in both PXA-GGs stained with class III beta-tubulin, synaptophysin, and chromogranin A. Ultrastructural studies, performed in nine cases, demonstrated neuronal features including microtubules, dense core granules, and/or clear vesicles largely limited to cell processes (two PXAs) and in the cytoplasm (PXA component of one PXA-GG). Although the essential nature of PXA is clearly and uniformly glial, the significance of the limited neuronal differentiation is unclear, as it is the relationship between conventional PXA and PXA-GG. We found no evidence that the former is a precursor of the latter.     

Hugh Cairns, Dorothy Russell and the first pleomorphic xanthoastrocytoma?

The 40-year survival of a patient with an unusual astrocytoma, excised in 1930, has been re-evaluated by study of the original microfilmed records, histological slides and paraffin-wax embedded tissue blocks. The operation and neuropathological examination were carried out by Mr Hugh Cairns and Dr Dorothy Russell, in the very early days of neurosurgery. Review of the original tissue specimen with immunocytochemistry has revealed that the tumour was a pleomorphic xanthoastrocytoma, the earliest recorded example.     

Atypical pleomorphic xanthoastrocytoma

A 65-year-old man experienced an ictal episode. CT revealed a left capsulo-thalamic mass, and SPET showed hypoperfusion of the left cerebral emisphere. The lesion was subtotally removed, and postoperative radiotherapy was given. Pathological examination demonstrated an "atypical" pleomorphic xanthoastrocytoma. The patient died of massive regrowth of the tumor 22 months after surgery. This case is discussed in light of the pertinent literature.