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An unusual case of malignant pilocytic astrocytoma

occurring in the eye
Alessandra Canesso & Marina Gardiman &
Roberto Salmaso & Rita Alaggio & Vito Ninfo
Received: 18 September 2005 / Accepted: 10 April 2006 / Published online: 20 May 2006
# Springer-Verlag 2006
Abstract Pilocytic astrocytoma is a central nervous system
neoplasia that arises during pediatric age. Only few cases
have been documented in patients older than 50 years old.
It is a low-grade lesion that can rarely undergo malignant
changes presenting the histologic features of a high-grade
glioma. We report a case of a pilocytic astrocytoma arising
in the eyeball of a 53-year-old man affected by glaucoma
that underwent malignant evolution.
Keywords Pilocytic astrocytoma
Pilocytic astrocytoma is a low-grade neoplasia of the
central nervous system that occurs in pediatric age without
any sexual distinction. Some cases have also been detected
in young adults and only rarely after fifth decade [14].
It is located more frequently in the cerebellum, where it
grows as a quite well-restricted mass, often cystic with
mural nodule. Other possible locations are the chiasmatic
hypothalamic region, the optic nerve and, rarely, the
cerebral emispheres and the spinal cord.
Its typical imaging shows hypointensive images in T1
sequences and hyperintensive images in T2 sequences with
enhancement of the tumoral nodule after administration of
contrast material [4].
Its clinical course is generally favorable. Even after a
subtotal resection, its growth is slow and leptomeningeal
spread is rare. Some cases have been reported, however, in
which pilocytic astrocytoma underwent malignant evolu-
tion presenting the histologic features of high-grade
malignant glioma, including palisading necrosis, vascular
proliferation, and mitotic index increase [14].
We report a case of a pilocytic astrocytoma with
histologic features of malignancy occurring in the eyeball
of a 53-year-old man with a clinical history of glaucoma.
Case report
Clinical history
A 53-year-old man underwent an enucleation and an
endoprosthesis implant for a glaucoma of the right eye.
He had undergone a surgical operation for a congenital
cataract when he was 6 years old and another one for
glaucoma at the age of 45.
There are no previous tumor diagnosis
Surgical specimen showed deformed eyeball with diffuse
increased consistency and scleral darkening; crystalline lens
was entirely embebbed in a relatively friable yellowish
mass. On cut surface, the tumor occupied the whole
posterior chamber of the eye replacing the vitreous body
and infiltrating the optic nerve and the iris that appeared
No preoperative RMN of the facial bones was carried out,
while postoperative RMN, with and without administration
of contrast material, revealed that the extrinsic muscle
structures and part of the optic nerve were normal and there
Virchows Arch (2006) 449:248252
DOI 10.1007/s00428-006-0224-3
A. Canesso (*)
M. Gardiman
R. Salmaso
R. Alaggio
V. Ninfo
Section of Pathology, Department of Oncological and Surgical
Sciences, University of Padova,
Via Gabelli 61,
Padova 35100, Italy
were no signs of chiasma alteration. Sixteen months after the
operation, the patient is alive and free of disease.
The material obtained from the eyeball was fixed in
formalin, embedded in paraffin and stained with hematox-
ylin and eosin using standard methods. The following
immunohistochemical stainings were performed: MIB-1
(Neomarkers, dilution 1:20), glial fibrillary acidic protein
(GFAP) (Novocastra, dilution 1:100), S100 protein (Neo-
markers, dilution 1:1,200), HMB-45 (Novocastra, dilution
1:60), AE1/AE3 (Neomarkers, dilution 1:500), and p53
(Novocastra, dilution 1:100).
Microscopically, the lesion showed different areas: typical
features of pilocytic astrocytoma associated with foci of
necrosis with pseudopalisading (Fig. 1). Areas of pilocityc
astrocytoma were focally evident and characterized by the
classic byfasic pattern formed by compact piloid tissue
intermingled with calcification and microcysts (Fig. 2a).
Rosenthal fibers were prominent in solid areas, whereas
granular bodies were easily detected in the cystic compo-
nent (Fig. 2b).
Most of the tumor was composed by highly cellular
areas of spindle cells with oval hyperchromatic and
pleomorphic nuclei; in this areas, more than one mitosis/
10 HPF were detected (average two mitosis/10 HPF) as
well as vascular proliferation and necrosis with pseudo-
palisading (Fig. 3). Vascular proliferation was characterized
by medium-sized vascular channels with multilayered
endothelial cells around foci of necrosis. Typical glomer-
uloid vasculature of pylocitic astrocytoma was not present.
The immunohistochemical stainings showed a strong
and diffuse positivity for S-100 protein, GFAP, and p53
especially in the compact fibrillar areas (Figs. 4 and 5).
Mib-1 highlighted the different proliferative rate in the area
of classic pilocytic astrocytoma (6.97%) and in area of
malignant transformation (19.52%) (evaluation with Roche
Image Analysis System) (Fig. 4).
Fig. 2 Typical features of pilocytic astrocytoma: calcification (a) and microcystic areas with granular bodies (arrow, b). H&E, 12; 15
Fig. 1 Tumor shows a typical area of pilocytic astrocytoma (on the
left) composed of spindle cells arranged in fascicles with calcifications
associated with foci of necrosis with pseudopalisading (on the upper
right). H&E, 3
Virchows Arch (2006) 449:248252 249
Cytokeratins and HMB-45 were negative. Our final
diagnosis was pilocytic astrocytoma with malignant trans-
A wide range of neoplasia occur in the orbit such as soft
tissue tumor, lymphoid tumor, metastatic tumor, glioma,
and meningioma.
Soft tissue tumor are infrequent; the list includes fibrous
histiocytoma (the most commonly diagnosed mesenchymal
lesion at this anatomic site) hemangioma, hemangiopericy-
toma and solitary fibrous tumor, giant cell angiofibroma,
rhabdomyosarcoma, particularly in childhood, and a variety
of soft tissue lesions [5, 10].
Lymphoid tumors generally develop in the course of a
previously recognized non-Hodgkins malignant lymphoma or
leukemia [10]. Direct spread from adjacent structures can occur
with primary intraocular tumors such as retinoblastoma or
Fig. 3 Areas of necrosis with peripheral palisading mimicking glioblastoma multiforme (right) and rich vascular proliferation (left). H&E, 12
Fig. 4 Strong and diffuse positivity for GFAP (left). Mib 1 staining highlights the different proliferative rate in the area of classical pilocytic
astrocytoma (upper right) and in area of malignant transformation (down) (6; 25)
250 Virchows Arch (2006) 449:248252
uveal malignant melanoma. Hematogenous metastases to the
orbit may be seen: carcinoma of the breast, bronchus, kidney
or prostate in adults, and neuroblastoma in children [10].
Most optic gliomas are low grade pilocytic astrocytoma
[8]. Typically make their presence with minimal exophtal-
mos, optic nerve atrophy or papilledema. Generally, these
tumors can be adequately managed by surgical [10].
Pilocytic astrocytoma is a slowly growing neoplasia
defined a low-grade malignancy in WHO classification [14]
characterized by rare leptomeningeal spread and recurrences
after an incomplete resection. Transformation into high-
grade astrocytoma is even a rarer occurrence. Only few cases
of cerebellar [13, 7, 12] and chiasmatichypothalamic [6,
9, 15] pilocytic astrocytomas had recurrences within 4 to
48 years after the original diagnosis manifesting the
histologic features and the clinical behavior of glioblastoma
multiforme or anaplastic astrocytoma.
All initial lesions occurred during pediatric age and were
treated by surgical excision and/or radiation therapy. The
histologic examination showed neoplasias with the typical
features of pilocytic astrocytoma, e.g., solid areas alternat-
ing with microcystic areas, spindle-shaped monomorphous
cells, eosinophilic granular bodies, and Rosenthal fibers.
Recurrent lesions occurred in the same locations as the
initial ones, except one reported by Yukitaka et al. [13], but
their morphological features only partly reminded those of
a low-grade astrocytoma [15]; this was due to their high-
cellular polymorphism, endothelial proliferation, brisk
mitotic index, and palisading necrosis. Only one case
showed areas formed by small cells mixed with others
typical features of pilocytic astrocytoma, which were
considered as anaplastic astrocytoma [9].
In most cases, the authors linked the malignant evolution of
the low-grade initial lesions to radiation therapy that can be
also involved in the development of some other types of
tumors such as meningiomas, astrocytomas, and fibrosarcomas
[12]; on the other hand, malignant evolution seems almost
unlikely in patients who did not receive any radiation therapy.
The case described herein can be included in those reported
by literature because it shows the features of pilocytic
astrocytoma, such as the typical cellularity located in some
areas of the neoplasia, eosinophile granular bodies, Rosenthal
fibers, and calcification as well as palisading necrosis,
vascular endothelial proliferation, and nuclear abnormalities.
These last morphological findings are in favor of the
diagnosis of malignancy. Vascular proliferation is common
in pilocytic astrocytoma and numerous eosinophilic hyaline
droplets were described in glioblastoma multiforme [11].
In our case, vascular proliferation was characterized by
medium-sized vascular channels with multilayered endothe-
lial cells around foci of necrosis. Typical glomeruloid
vasculature of pylocitic astrocytoma was not present.
Eosinophilic granular bodies are an important diagnostic
feature of several neoplasms including ganglion cell
tumors, pleomorphic xanthoastrocytoma, and pilocytic
astrocytoma [14]. Sasaki et al. [11] reported a case of
glioblastoma multiforme with unusual histological features
in a 79-year-old woman. In the tumor, there were marked
nuclear atypism, frequent mitotic figures, small areas of
necrosis with pseudopalisading, microvascular prolifera-
tion, and numerous eosinophilic round bodies within the
cytoplasm of large neoplastic cells. Nevertheless, there are
no areas of low-grade astrocytoma.
For these reasons, we concluded for a diagnosis of
malignant pilocytic astrocytoma and not for glioblastoma
multiforme despite the presence of vascular proliferation
and presence of eosinophile granular bodies.
The difference from the cases reported by literature lies
in the fact that neoplasia underwent malignant evolution
even though this was not induced by typical factors such as
radiation therapy.
We can hypothesize that the only symptom was treated by
surgery but not the growing neoplastic mass that was
overlooked and remained in the eyeball. Longstanding tumor
mass with an inadequate treatment can have induced malignant
transformation in an otherwise typical pilocytic astrocytoma.
In conclusion, if this kind of low-grade lesions are not
diagnosed because their locations allow them to grow
without manifesting clear symptoms, in time, they can
undergo malignant transformation even in absence of an
history of radiation therapy.
Acknowledgement Special thanks to Ms. Elena Leonardi for the
linguistic revision of this text.
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Fig. 5 Positivity for p53 in compact fibrillar areas (40)
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