J Neurosurg (Pediatrics 3) 102:322–325, 2005

Pineal region giant cell astrocytoma associated with tuberous
sclerosis
Case report
SHERVIN R. DASHTI, M.D., PH.D., SHENANDOAH ROBINSON, M.D., MARK RODGERS, M.D.,
AND ALAN R. COHEN, M.D.
Division of Pediatric Neurosurgery, Rainbow Babies and Childrens Hospital; and Departments of
Neurosurgery and Pathology, University Hospitals of Cleveland, Case Western Reserve University School
of Medicine, Cleveland, Ohio

PTuberous sclerosis complex is a genetic disorder characterized by the development of hamartomas in multiple organs
including the brain, skin, eye, kidney, and heart. Neurological features include seizures and mental retardation. Cortical
tubers and subependymal nodules are the characteristic intracranial lesions of tuberous sclerosis. Subependymal giant cell
astrocytomas, typically located adjacent to the foramen of Monro, can enlarge and cause symptomatic ventricular obstruction.
The authors describe the case of a 3-year-old boy with a history of tuberous sclerosis and retinal lesions who presented
with an enlarging enhancing pineal region mass. Via an infratentorial supracerebellar approach, the mass was removed
using both the operative microscope and a rigid neuroendoscope. Pathological examination showed a giant cell astrocytoma. To the authors’ knowledge, this is the first reported case of tuberous sclerosis associated with a giant cell astrocytoma of the pineal region. Diagnostic considerations are discussed.
KEY WORDS • tuberous sclerosis • subependymal giant cell astrocytoma • pineal gland •
brain neoplasm • phakomatosis • pediatric neurosurgery

T

UBEROUS sclerosis complex is a genetic disorder char-

acterized by the development of hamartomas in multiple organs, including the brain, skin, eye, kidney,
and heart.10 Its prevalence is estimated to range from
one/6000 to one/170,000 live births. The disorder is inherited in an autosomal-dominant manner with a penetrance of
approximately 80%, but its expression is extremely variable.10 This disease is caused by various mutations in
genes coding for the proteins hamartin (TSC1) or tuberin
(TSC2).13 The loci for the tuberous sclerosis genes have
been mapped to chromosomes 9q34 (TSC1) and 16p13
(TSC2).4,13 Tuberin has been shown to be a tumor-suppressor protein, which forms stable complexes with hamartin in
vitro and in vivo.14 Complex formation, which is necessary
for tuberin’s tumor-suppressor function, requires phosphorylation at tyrosine and serine residues.1
Neurological features of tuberous sclerosis include seizures and mental retardation. Ophthalmological manifestations of TSC include retinal hamartomas, which occur in

more than 40% of all patients with TSC.9 Cortical tubers
and subependymal nodules are pathognomonic intracranial
features of TSC.11 Subependymal nodules are periventricular hamartomas measuring up to 10 mm in diameter
and are composed of abnormal glial or vascular tissue.
Multiple nodules usually appear along the striothalamic
zone of the lateral ventricles and resemble candle drippings.10 These lesions may increase in number and calcify
as an individual ages.6
A unique tumor, the SEGA develops in some patients
with TSC, presumably due to transformation of subependymal nodules.11 The SEGA is most commonly situated in the
lateral ventricles adjacent to the foramen of Monro. Occasionally SEGAs can occur at sites remote from the foramen
of Monro. We report the unusual case of an SEGA presenting as a pineal region tumor and discuss the importance
of considering atypical presentations of SEGA in the setting of tuberous sclerosis.5
Case Report

Abbreviations used in this paper: MR = magnetic resonance;
SEGA = subependymal giant cell astrocytoma; TSC = tuberous
sclerosis complex.

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Presentation and History. This 3-year-old boy presented
with a history of tuberous sclerosis. Surveillance MR imagJ. Neurosurg: Pediatrics / Volume 102 / April, 2005

Pineal giant cell astrocytoma associated with tuberous sclerosis
weighted sequences (Fig. 1). This mass was shown to enlarge slightly on follow-up MR images. There was no evidence of surrounding parenchymal edema or hydrocephalus.
Operation. The tumor was removed via an infratentorial supracerebellar approach by using both the operative
microscope and a rigid neuroendoscope inserted through a
small posterior fossa craniotomy. The lesion appeared as a
rounded mass just deep to the precentral cerebellar vein. It
possessed a yellowish covering with multiple small vessels over the surface. The central portion of the tumor appeared reddish gray and moderately vascular. Gross-total
resection of the mass was achieved.
Histopathological Examination. Microscopically, the diagnosis was SEGA. There were eosinophilic uninucleated
giant cells with both hemosidrin and melanin pigmentation
(Fig. 2). Immunohistochemical evaluation demonstrated
predominant neurofilament reactivity, with a minor population of spindle-shaped glial fibrillary acidic protein–positive tumor cells.
Postoperative Course. Postoperative MR imaging revealed gross-total resection of the tumor. Currently, 1.5
years after surgery, the patient is neurologically intact
without MR imaging evidence of recurrent tumor (Fig. 3).

FIG. 1. Preoperative sagittal (upper) and coronal (lower) T1weighted MR images revealing an enhancing pineal tumor.

ing had demonstrated an enlarging 2-cm enhancing mass in
the pineal region but no associated hydrocephalus. The
boy’s mother had a history of a seizure disorder. Fetal ultrasonography revealed cardiac tumors. At birth he was noted
to have microphthalmos and soon thereafter right-eye leukocoria, right-eye persistent primary hypertrophic vitreous,
and a left-eye retinal mass had been diagnosed.
Examination. On examination, a 1-cm-diameter hypopigmented macule on the left side of the lower back and a 2cm cutaneous hemangioma on the upper back were observed. Neurological examination showed otherwise
normal status. Brain MR imaging revealed multiple cortical tubers and subependymal nodules, as well as an enhancing 2-cm-diameter pineal region mass that was isointense
to gray matter on T1-weighted and hypointense on T2J. Neurosurg: Pediatrics / Volume 102 / April, 2005

Discussion
Cortical tubers and subependymal nodules are the most
commonly seen intracranial lesions in tuberous sclerosis.
In a minority of patients with TSC, the subependymal nodules undergo transformation to SEGAs. These tumors are
distinguished from other astrocytomas by the presence of
bizarre eosinophilic giant cells. The typical markers of
malignancy such as mitosis, atypia, and endothelial proliferation are often associated with a good outcome in patients with SEGA.11
In the present report we have described the case of a 3year-old boy with a history of tuberous sclerosis in whom
an asymptomatic enhancing pineal mass enlarged on follow-up imaging. Although SEGA is considered in the differential diagnosis in any patient with tuberous sclerosis
presenting with an enhancing intracranial mass, SEGAs
characteristically occur along the terminal sulcus near the
foramen of Monro. Although SEGAs may sometimes develop in other locations, they have never been reported in
the pineal region.5 In the Japanese-language literature, we
found one reported case of a pineal region tumor associated with tuberous sclerosis. That tumor, however, was a
mixed oligodendroglioma and fibrillary astrocytoma and
giant cells were absent.8
In the present case a diagnosis of primary persistent hyperplastic vitreous in the right eye and a noncalcified retinal tumor in the left eye had been diagnosed shortly after
birth. Tuberous sclerosis complex is associated with several ophthalmological manifestations, including retinal
hamartomas, which occur in more than 40% of all patients
with TSC.9 The retinal tumor in our patient was thought to
be an astrocytic hamartoma. The diagnosis of retinoblastoma had been considered, but the retinal tumor had
remained stable for 3 years and the nonprogressive nature
suggested that it was unlikely to be a retinoblastoma. The
finding of a pineal region tumor, however, did raise the
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S. R. Dashti, et al.

FIG. 2. Photomicrograph. The tumor consists of large cells with abundant eosinophilic cytoplasm and finely granular
chromatin, which resemble astrocytes. The pathological diagnosis was SEGA. H & E, original magnification 3 600.

possibility of trilateral retinoblastoma. Trilateral retinoblastoma is a well-recognized but rare syndrome that refers to bilateral retinoblastoma associated with a midline
intracranial tumor, usually in the pineal region.2,3 Moreover, there have been reported cases of a variant of trilateral retinoblastoma presenting with unilateral retinoblastoma, germline mutation, and midline intracranial
primitive neuroectodermal tumor.7,12,15,16 Trilateral retino-

blastoma is associated with a median survival of 8 months
after diagnosis.
Conclusions
We have reported the first case of an SEGA occurring
in the pineal region in a child with tuberous sclerosis. In
patients with tuberous sclerosis, SEGA should be includ-

FIG. 3. Postoperative sagittal (left) and coronal (right) T1-weighted MR images demonstrating no tumor recurrence.

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J. Neurosurg: Pediatrics / Volume 102 / April, 2005

Pineal giant cell astrocytoma associated with tuberous sclerosis
ed in the differential diagnosis of intracranial enhancing
mass lesions, even if they occur in atypical locations.
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Manuscript received November 10, 2003.
Accepted in final form November 9, 2004.
Address reprint requests to: Alan R. Cohen M.D., Division of
Pediatric Neurosurgery, Rainbow Babies and Childrens Hospital,
11100 Euclid Avenue, Cleveland, Ohio 44106-5036. email: alan.
cohen@uhhs.com.

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