Pigmented Pleomorphic Xanthoastrocytoma: Report of a Rare Case With Review of the Literature.
REPORT OF A CASE
The patient was a 32-year-old man with a 2-year history of seizures. The seizures were partial complex in nature, and their frequency varied from once a week to once every 3 to 4 days. The patient had a history of perinatal asphyxia. General physical examination revealed no abnormalities. He was treated with antiepileptic medications, but his seizure control was poor.
Hematologic parameters and serum chemistry panels revealed no abnormalities. A comprehensive neuropsychologic battery and a 72-hour video electroencephalogram showed no abnormalities. Radiographs of the chest and head were normal. Imaging studies demonstrated a cystic lesion with a solid enhancing area, which on [T.sub.2]-weighted imaging demonstrated hyperintensity (Figure 1). A radiologic diagnosis of a ganglioglioma was entertained. The patient was operated on through a left Falconer flap craniotomy, and a medial temporal lobectomy was performed. Postoperative follow-up was uneventful with good seizure control.
MATERIALS AND METHODS
The surgical specimen was fixed in 10% buffered formalin, routinely processed, and embedded in paraffin. Five-micrometer-thick sections were cut and the following stains were performed: hematoxylin-eosin, Gomori silver impregnation for reticulin, Fontana-Masson for melanin, potassium permanganate bleach for melanin, periodic acid-Schiff, and acid-fast stain. Immunohisto-chemical staining was done using the avidin-biotin conjugate complex immunoperoxidase method for glial fibrillary acidic protein (dilution 1:500), synaptophysin (1:50), neuron-specific enolase (1:100), S100 protein (1:100), HMB-45 (dilution 1:50), neurofilament (dilution 1:50), and MIB-1 (dilution 1:20). All antibodies were obtained from M/s Dakopatts (Glostrup, Denmark).
For electron microscopic examination, small fragments of formalin-prefixed tumor tissue were fixed in 2.5% glutaraldehyde and postfixed with 1% osmium tetroxide. The sections were embedded in epoxy resin, and ultrathin sections were cut from the selected areas. Sections were stained with uranyl acetate and lead citrate and were studied under a Philips CM-10 electron microscope.
The pleomorphic tumor demonstrated a variety of cellular patterns, including sheets of oval to polygonal cells with marked cellular pleomorphism (Figure 2, A), some with foamy cytoplasm (Figure 2, B), some with clustered nuclei with indistinct cytoplasmic borders, and others with intranuclear cytoplasmic inclusions. Separate areas of spindle cells arranged in a sweeping pattern were also present (Figure 2, C). Some of these cells contained brownish-black pigment in the cytoplasm. This pigment bleached with potassium permanganate and stained black with Fontana-Masson stain. This pigment was non-acid fast and negative for periodic acid-Schiff, thereby ruling out the possibility of lipofuscin and neuromelanin. No mitosis, necrosis, or endothelial proliferation was seen. The tumor was reticulin rich (Figure 2, D). Immunohistochemical staining revealed these cells to be positive for glial fibrillary acidic protein (Figure 2, E) and S100 in both areas, but negative for neurofilament and synaptophysin. This pigment did not stain with HMB-45. MIB-1 labeling index was less than 1%.
The tumor was diagnosed as a pigmented (melaninproducing) pleomorphic xanthoastrocytoma. The pigment was determined to be melanin. The melanosomal melanin nature of this pigment was further confirmed by electron microscopy, which revealed electron-dense, round to oval granules with no discernible internal structures (stage IV melanosomes). Less mature melanosomes (stage III) with electron-dense striations and melanosomal complexes were also seen (Figure 3). Some of these cells revealed a poorly developed external basal lamina and abundant intracellular intermediate filaments.
This unusual tumor was composed of large pleomorphic glial cells and spindle cells with melanin pigment. Both components were positive for glial fibrillary acidic protein. This pigment was determined to be melanosomal melanin. The differential diagnoses considered in this case were pleomorphic xanthoastrocytoma and ganglioglioma. The latter was excluded in the absence of synaptophysin and neurofilament positivity. Electron microscopy revealed no neurosecretory granules or presynaptic vesicles. Therefore, a final diagnosis of melanotic pleomorphic xanthoastrocytoma was made.
A variety of melanotic brain tumors have been described in the literature, including ependymoma, choroid plexus papilloma and carcinoma, medulloblastoma, medulloepithelioma, schwannoma, meningioma, melanocytoma, and melanoma. Melanotic astrocytic tumors have been reported only recently (Table). Vajtai et al described a temporal lobe astrocytoma in a 41-year-old woman with a long history of epilepsy (since the age of 17 years), which on microscopic examination turned out to be a pigmented pilocytic astrocytoma. However, the pigment was neuromelanin. Kanzawa et al reported a melanotic astrocytoma in a 47-year-old man who also presented with complex partial seizure and whose tumor was located in the temporal lobe. Pigment in this case was melanosomal melanin. Softer et al described a partly solid and cystic ganglioglioma in a 17-year-old girl who presented with a 5-year history of epilepsy. The lesion was composed of ganglionic and astrocytic components. The astrocytic component was like pleomorphic xanthoastrocytoma and contained melanosomal melanin pigment.
Clinical Features of Pigmented Astrocytic Tumors Age Duration of Source, y y/Sex Clinical Features Symptoms, y Soffer et al, 1992 17/F Epilepsy 5 Vajtai et al, 1996 41/F Psychomotor seizures 24 Kanzawa et al, 1997 47/M Psychomotor seizures 8 Present case 32/M Partial complex seizures 2 Diagnosis Nature of Source, y Pigment Softer et al, 1992 Ganglioglioma Melanin Vajtai et al, 1996 Pilocytic astrocytoma Neuromelanin Kanzawa et al, 1997 Pleomorphic xanthoastrocytoma Melanin Present case Pleomorphic xanthoastrocytoma Melanin
The common features of the tumor in our case and those described in the literature include presentation with epilepsy (partial complex seizure), temporal lobe location, mixed solid cystic appearance, and benign histology with low proliferative indices. Interestingly, the tumor described in this article was located in the medial temporal lobe, which is an unusual site for pleomorphic xanthoastrocytoma.
In the intracranial lesions, the various possibilities considered for brownish-black pigment are melanin, neuromelanin, and lipofuscin. The pigment in our case was determined to be melanosomal melanin because it stained black with Fontana-Masson and bleached with potassium permanganate. Lack of staining with periodic acid-Schiff and acid-fast stains and the presence of melanosomes in various stages of maturation on electron microscopic examination ruled out the latter possibilities. Neuromelanin is produced and stored by neurons involved in catecholamine synthesis. The possibility that this pigment represented lipofuscin, which is of wear-and-tear origin, is ruled out by electron microscopic examination. The presence of various stages of melanogenesis indicates synthesis of melanin by these tumor cells.
Melanin production is an active process, and its presence indicates melanosomal activity. Production of melanosomal melanin in tissues of central neuroepithelial origin is developmentally restricted in humans to the fetal pineal gland and to the pigmented layers of the retina. Astrocytes are not involved in either of these synthetic modalities.
Until recently, melanosomal melanogenesis was considered as evidence for a neural crest derivation of the pigment-forming cells. However, there is a growing body of evidence, mainly from experimental studies, suggesting that central neuroepithelial cell derivatives are also capable of melanosomal production.[19,20] Shuangshoti et al described deep brown pigment in astrocytes in a patient with melanosis of the central nervous system. Freide reported the occurrence of melanin in astrocytes of the striatum, pallidum, and substantia nigra of 2 elderly women who died following debilitating joint disease.
The melanotic pigmentation of otherwise normal astrocytes and ependymal cells has occasionally been reported as an incidental finding in the dentate nucleus, lining of glioependymal cysts, and in the filum terminale.[2,23] Melanosis of cerebellar and brainstem astrocytes has been described in systemic degenerative processes.
Melanocytes and neuroglial elements have a common origin from primitive neuroectodermal tissue from "toti-potent" neural crest stemlike cells. Therefore, our unusual case further supports the hypothesis that melanosomal melanogenesis can occur in neoplastic astrocytic cells in humans.
The authors thank Rajeshwar Khadia for performing the immunohistochemical stains and Mr Kamal Gulati for his secretarial assistance.
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Accepted for publication November 14, 2000.
From the Departments of Pathology (Drs Sharma, Arora, and Sarkar), Neuroradiology (Dr Khanna), and Neurosurgery (Dr Singh), All India Institute of Medical Sciences, New Delhi, India.
Reprints: Chitra Sarkar, MD, Department of Pathology, All India Institute of Medical Sciences, New Delhi 110029, India (e-mail: sarkarcs@ hotmail.com or email@example.com).