Pigmented Pleomorphic Xanthoastrocytoma

Report of a Rare Case With Review of the Literature

Mehar Chand Sharma, MD; Rina Arora, MD; Navin Khanna, MD; Virender Pal Singh, MCh; Chitra Sarkar, MD

We describe a rare case of melanotic pleomorphic xan- MATERIALS AND METHODS

thoastrocytoma in a 32-year-old man who presented with
partial complex seizures. Radiologically, the mass was lo-
cated in the medial temporal lobe and was solid and cystic.
Microscopic examination revealed features of a pleomor-
phic xanthoastrocytoma with some heavily pigmented
cells. The pigment was demonstrated to be melanosomal
melanin, which was confirmed by special stains, immu-
nohistochemistry, and electron microscopy.
(Arch Pathol Lab Med. 2001;125:808811)
The surgical specimen was fixed in 10% buffered formalin, rou-
tinely processed, and embedded in paraffin. Five-micrometer-
thick sections were cut and the following stains were performed:
hematoxylin-eosin, Gomori silver impregnation for reticulin, Fon-
tana-Masson for melanin, potassium permanganate bleach for
melanin, periodic acidSchiff, and acid-fast stain. Immunohisto-
chemical staining was done using the avidin-biotin conjugate
complex immunoperoxidase method for glial fibrillary acidic pro-
tein (dilution 1:500), synaptophysin (1:50), neuron-specific eno-
lase (1:100), S100 protein (1:100), HMB-45 (dilution 1:50), neu-

M elanotic tumors of the central nervous system include

ependymomas,1,2 choroid plexus papillomas35 and
carcinomas,6,7 medulloblastomas,810 primitive pineal tu-
rofilament (dilution 1:50), and MIB-1 (dilution 1:20). All antibod-
ies were obtained from M/s Dakopatts (Glostrup, Denmark).
For electron microscopic examination, small fragments of for-
mors,1113 and medulloepitheliomas.14 The nonneuroepi- malin-prefixed tumor tissue were fixed in 2.5% glutaraldehyde
thelial pigmented intracranial tumors reported in the lit- and postfixed with 1% osmium tetroxide. The sections were em-
erature are schwannoma, meningioma, melanoma, and bedded in epoxy resin, and ultrathin sections were cut from the
melanocytoma.15 In many of these tumors the pigment was selected areas. Sections were stained with uranyl acetate and lead
melanin,2,714 whereas in others it was neuromelanin.36 citrate and were studied under a Philips CM-10 electron micro-
However, melanotic astrocytomas have been described scope.
only recently. One case each of pigmented ganglioglio-
ma,16 pilocytic astrocytoma,17 and pleomorphic xanthoas-
trocytoma18 have been reported to date. We present a case
of melanotic pleomorphic xanthoastrocytoma and discuss
its histogenesis.
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 an-
tiepileptic 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 T2-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.

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 sarkarch@medinst.ernet.in).
808 Arch Pathol Lab MedVol 125, June 2001
Figure 1. Magnetic resonance imaging scan (coronal plane) of head
showing a solid and cystic mass lesion in the left temporal lobe. On
contrast injection, the solid part of the lesion shows homogeneous in-
tense enhancement.
Pigmented Pleomorphic XanthoastrocytomaSharma et al
 Clinical Features of Pigmented Astrocytic Tumors
Age, Duration of
Source, y y/Sex Clinical Features Symptoms, y Diagnosis Nature of Pigment
Soffer et al, 1992
16
17/F Epilepsy 5 Ganglioglioma Melanin
Vajtai et al,17 1996 41/F Psychomotor seizures 24 Pilocytic astrocytoma Neuromelanin
Kanzawa et al,18 1997 47/M Psychomotor seizures 8 Pleomorphic xanthoastrocytoma Melanin
Present case 32/M Partial complex seizures 2 Pleomorphic xanthoastrocytoma Melanin

Figure 2. A, Photomicrographs showing sheets of oval to polygonal cells with marked cellular pleomorphism; some of the cells are multinucleated
giant cells and show intranuclear (arrow) cytoplasmic inclusions (hematoxylin-eosin, original magnification 3200). B, Higher magnification dem-
onstrating abundant foamy cytoplasm (hematoxylin-eosin, original magnification 3200). C, Spindle cell areas with sweeping pattern. Some of
these cells contained abundant brownish-black pigment (hematoxylin-eosin, original magnification 3100). D, Silver impregnation stains showing
reticulin-rich areas (original magnification 3100). E, Tumor cells are positive for glial fibrillary acidic protein (original magnification 3200).

Arch Pathol Lab MedVol 125, June 2001 Pigmented Pleomorphic XanthoastrocytomaSharma et al 809

Figure 3. Electron micrograph showing melanosomes in various stag-
es of development (original magnification 33400). Inset, Stage III me-
lanosomas with internal striations (original magnification 315 500).
PATHOLOGIC FINDINGS
The pleomorphic tumor demonstrated a variety of cel-
lular 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 brown-
ish-black pigment in the cytoplasm. This pigment
bleached with potassium permanganate and stained black
with Fontana-Masson stain. This pigment was nonacid
fast and negative for periodic acidSchiff, thereby ruling
out the possibility of lipofuscin and neuromelanin. No mi-
tosis, necrosis, or endothelial proliferation was seen. The
tumor was reticulin rich (Figure 2, D). Immunohistochem-
ical staining revealed these cells to be positive for glial
fibrillary acidic protein (Figure 2, E) and S100 in both ar-
eas, 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 (melanin-
producing) 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 in-
tracellular intermediate filaments.
COMMENT
This unusual tumor was composed of large pleomor-
phic 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.
810 Arch Pathol Lab MedVol 125, June 2001
The latter was excluded in the absence of synaptophysin
and neurofilament positivity. Electron microscopy re-
vealed no neurosecretory granules or presynaptic vesicles.
Therefore, a final diagnosis of melanotic pleomorphic xan-
thoastrocytoma was made.
A variety of melanotic brain tumors have been de-
scribed in the literature, including ependymoma, choroid
plexus papilloma and carcinoma, medulloblastoma, med-
ulloepithelioma, schwannoma, meningioma, melanocyto-
ma, and melanoma. Melanotic astrocytic tumors have been
reported only recently (Table). Vajtai et al17 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 pig-
mented pilocytic astrocytoma. However, the pigment was
neuromelanin. Kanzawa et al18 reported a melanotic astro-
cytoma 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. Soffer et al16 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 com-
ponent was like pleomorphic xanthoastrocytoma and con-
tained melanosomal melanin pigment.
The common features of the tumor in our case and those
described in the literature include presentation with epi-
lepsy (partial complex seizure), temporal lobe location,
mixed solid cystic appearance, and benign histology with
low proliferative indices. Interestingly, the tumor de-
scribed in this article was located in the medial temporal
lobe, which is an unusual site for pleomorphic xanthoas-
trocytoma.
In the intracranial lesions, the various possibilities con-
sidered for brownish-black pigment are melanin, neuro-
melanin, and lipofuscin. The pigment in our case was de-
termined to be melanosomal melanin because it stained
black with Fontana-Masson and bleached with potassium
permanganate. Lack of staining with periodic acidSchiff
and acid-fast stains and the presence of melanosomes in
various stages of maturation on electron microscopic ex-
amination ruled out the latter possibilities. Neuromelanin
is produced and stored by neurons involved in catechol-
amine synthesis. The possibility that this pigment repre-
sented lipofuscin, which is of wear-and-tear origin, is
ruled out by electron microscopic examination. The pres-
ence of various stages of melanogenesis indicates synthe-
sis of melanin by these tumor cells.
Melanin production is an active process, and its pres-
ence indicates melanosomal activity. Production of mela-
nosomal melanin in tissues of central neuroepithelial ori-
gin is developmentally restricted in humans to the fetal
pineal gland and to the pigmented layers of the retina.2
Astrocytes are not involved in either of these synthetic
modalities.
Until recently, melanosomal melanogenesis was consid-
ered as evidence for a neural crest derivation of the pig-
ment-forming cells. However, there is a growing body of
evidence, mainly from experimental studies, suggesting
that central neuroepithelial cell derivatives are also capa-
ble of melanosomal production.19,20 Shuangshoti et al21 de-
scribed deep brown pigment in astrocytes in a patient
with melanosis of the central nervous system. Freide22 re-
ported the occurrence of melanin in astrocytes of the stri-
Pigmented Pleomorphic XanthoastrocytomaSharma et al
atum, pallidum, and substantia nigra of 2 elderly women
who died following debilitating joint disease.
The melanotic pigmentation of otherwise normal astro-
cytes 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 Mela-
nosis of cerebellar and brainstem astrocytes has been de-
scribed in systemic degenerative processes.24
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 im-
munohistochemical stains and Mr Kamal Gulati for his secretar-
ial assistance.
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