The worldwide incidence
of pineal tumor is about 1%. In Japan, Korea and China, it is more common,
constituting about 3 to 8% of all brain tumors, and about 10% of all
pediatric brain tumors.
Histogenesis of tumors
of the pineal gland is related to the development of this organ. In late
fetal life as well as in early infancy, sections of the pineal present a
mosaic appearance produced by aggregation into groups of large cells with
large nuclei, with intervening bands of smaller lymphocyte like cells with
small dense nuclei. These are immature forms of larger cells and
disappear in childhood. In adult life the gland is lobulated from the
intersection of parenchymal cells by connective tissue strands bearing
In the commonest tumor
of the pineal, now called ‘germinoma’ and considered as a
‘maldevelopmental tumor’, there is a recapitulation of the fetal
architecture of the pineal gland.
Most pineal tumors
originate infratentorially, and grow into posterior third ventricle, and
later into thalamus or posteriorly over the dorsal surface of the
quadrigeminal plate. Malignant tumors can invade the midbrain and
thalamus, which determines the resectability. The different cell types
account for the diverse pathology of pineal region tumors.
Pineal tumors may be
classifieds as follows.
Tumors of pineal parenchymal cells
neuronal, glial or/and retinoblastic differentiation
normal differentiation only
astrocytic differentiation only
divergent neuronal and astrocytic differentiation
Germ cell tumors
Embryonal carcinoma, yolk sac tumor
germ cell neoplasm
C. Tumors of glial cell origin
Other rarer tumors include
melanoma, hemangioma, hemangiopericytoma,
Cysts include pineal cyst,
arachnoid cyst, epidermoid and dermoid,
lipoma and metastases.
These benign pineal cysts are considered as
normal variants of the pineal gland. They consist of cystic structures
surrounded by normal pineal parenchyma. They are usually asymptomatic and
incidental radiological finding as a rim enhancing lesion compressing the
gland. Very occasionally, they may result in aquedect stenosis and require
intervention. Pineal cysts were visualized in 4.3% of normal patients in
one MR study as areas of high signal on intermediate T2-weighted images.
They are rare, constituting approximately 15%
to 32% of all tumors in the pineal region. Neoplasms of the pineal
parenchymal cell are referred to as pineoblastomas or pineocytomas
depending on the cellularity and cytologic characters of the tumors.
Otherwise, these two sub varieties are comparable in respect to the age
of the patient and the gross appearance of the tumor. Thus they both
occur more frequently in late childhood or early adulthood.
is a better
differentiated variant of pineal tumors and occurs mostly in adult life.
well-circumscribed but may disseminate along the CSF pathways.
The pineocytoma consists
of small round cells set in a fibrillary background. The cells may form
Homer-Wright (neuroblastoma) rosettes, similar cells are found in
so-called 'ganglioglioma' of the pineal),
but the nuclear: cytoplasmic ratio is much higher in this tumor, and the
mitoses are evident.
least differentiated pineal parenchymal neoplasm. This tumor tends to
occur during the first or second decades of life. It is highly malignant
and represents a true primitive neuroectodermal tumor. Usually replaces
the tissue of pineal gland.
It is pink, white or
grey, smooth or granular when cut, sometimes cystic and frequently
hemorrhagic or necrotic.
bears a histological resemblance to
medulloblastoma, the cells being primitive with scanty cytoplasm and
relatively large nuclei rich in chromatin. An attempt at rosette formation
may be seen. The appearance may, in places, resemble a germinoma. The
centre of the rosette may not reveal argyrophilic filaments, which are
more readily seen in the rosettes of the pineocytoma.
On account of their
vascularity these tumors tend to bleed and the blood pigment seeping out
of the tumor may be detected in the CSF in the spinal theca. Tumor cells
may also be detected in the spinal fluid in along the meninges.
Germ cell tumors:
Tumors of glial cell origin:
True gliomas of
the pineal gland are almost exclusively astrocytomas of varying grades of
malignancy. Being generally extensive, their precise source of origin is
difficult to determine and they might even originate from the corpora
quadrigemina. Small non-neoplastic glial cysts of the pineal may be found
incidentally at autopsy in the elderly.
Among the very rare
pineal neoplasms may be mentioned ganglioglioma and chemodectoma.
Clinically, there are
features of hydrocephalus, such as, headache, vomiting, and papilledema.
Upward gaze paresis,
convergence or retraction nystagmus, and disturbed light reflex (Parinaud's
syndrome) is a characteristic sign due to midbrain compression at the
level of superior colliculus. Further compression, down gaze or horizontal
gaze can result.
compression or infiltration can cause lid retraction (Collier's sign)
Less commonly, 4th nerve
palsies with diplopia and head tilt can occur.
Ataxia and dysmetria can
result due to interference of superior cerebellar peduncles.
Rarely, there may be
hearing disturbances due to disturbance of inferior colliculi.
is rare due to tumor spread to hypothalamus.
CT and MRI typically
reveals a homogenously enhancing mass in most cases, depending on the
pathology. MRI delineates
pineal region masses better than CT, showing the relationships of the
tumor to the posterior third ventricle, vein of Galen, and aqueduct.
Pineal germinomas and primary pineal tumors
are most often isointense with the brain on T1- and T2-weighted images. A
few lesions exhibit long T1 and T2, which may correlate with embryonal
cell elements. These tumors are well defined and enhance to a moderate
degree, usually without central necrosis, cystic change, or hemorrhage.
Meningiomas can appear very similar on plain
scan, but their intense enhancement may set them apart from other lesions.
Gliomas infiltrate the tectum and posterior
walls of the third ventricle. They tend to be poorly circumscribed. Edema
is not a consistent finding, and enhancement is variable. Larger gliomas
in the splenium of the corpus callosum may present as pineal region
Teratomas are of mixed signal intensity,
frequently with calcification. They may also have cystic components and
Arachnoid cysts, epidermoid and dermoid
tumors can usually be distinguished from other pineal region tumors by
their increased signal on T2-weighted images.
MR venography may be more
useful to study the displacement of deep venous system, which is very
important in deciding the surgical approach, is well shown in MRI.
Meningiomas from the velum interpositum and epidermoids or other tumors
from the corpus callosum displace the deep venous system ventrally and
inferiorly which may give a 'clue'.
Staging with neuroaxis
imaging and if possible, CSF analysis, is recommended.
CSF analysis, whenever possible, should be
carried out. It is most valuable in germ cell tumors, which constitutes
70% of the pineal tumors. Expression of
embryonal proteins, such as, alpha fetoprotein (AFB), and beta HCG are
of malignant germ cell elements. Other
biological markers for germ cell tumors include, Lactic dehydrogenase
and placental Alkaline Phosphatase (PLAP).
Pineal parenchymatous cell tumor markers
include, melatonin, and S antigen; they are more valuable in follow ups
and to study the response to treatment, and not reliable for diagnostic
The pineal tumors are
invariably, aggressive. Gross total removal, although ideal, is
technically difficult. The main
aim of management is to get a tissue diagnosis for further therapy, and
reestablish the CSF drainage pathway. The
hydrocephalus is usually
managed with shunt surgery, although it carries a potential risk of tumor
In the past, the pineal tumors were
irradiated with out a tissue diagnosis, and surgery was performed in
unresponsive cases, as favored by the Japanese. With a good response,
germinoma, (which constitutes about 70% of pineal tumors, and found more
frequently in Japan) was presumed.
Nowadays, a tissue diagnosis is recommended
before radiotherapy, either by
biopsy or open surgery.
Germinoma is an exception. Detection of
Placental Alkaline Phosphatase (PLAP) is diagnostic of germinomas, and
Stereotactic biopsy, shunt for the
hydrocephalus, and CSF studies at the time of shunt surgery, followed by
radiotherapy in malignant lesions is widely accepted, despite the
recent surgical tools and
The aim of surgery is to get a tissue biopsy,
and reestablish CSF drainage. Advocates of surgery claim, that only open
surgery can provide adequate tissue for a detailed biopsy studies, and
that surgery can provide a 'cure' in benign lesions. In addition, with the
recent advances in surgery, and anesthesia, the pineal tumors, which was
once a 'no go area' in the past, can be satisfactorily excised. Successful
tumor excision may obviate a shunt. An extraventricular drainage at tumor
surgery is increasingly practiced.
The surgical approaches can be divided
into, supratentorial, infratentorial and a combined supra and
infratentorial approach. Surgeon's familiarity largely decides the
approach, more than the tumor extensions.
Supratentorial approaches include, parietal
interhemispheric (as described by Dandy), and occipital
transtentorial approach (as described by Horrax, and later modified
by Poppen and others). It provides a wide exposure, and is best
suited for tumors extending supratentorially or laterally into the trigone
of the lateral ventricle; however, it is difficult to remove the tumor
that lies below the convergence of the deep venous system.
Infratentorial supracerebellar approach was
described by Krausse, and later popularized by Stein. It is
midline approach suitable for midline tumors that grow into the third
ventricle, and posterior fossa. The deep venous system caps the dorsal
aspects of the tumor, and remains away at surgery; however, the exposure
provides only a limited access to the lateral extensions of the tumor,
and the tumor above the deep venous system.
Complications: Pineal region surgery
is a microsurgical challenge, despite all new surgical tools. In expert
hands, severe permanent morbidity should be rare. Transient worsening of
extraocular problems, and gait, hemiparesis due to brain stem retraction,
visual field deficits due to occipital lobe lobe retraction, may occur.
Disconnection syndromes due to corpus callosum incisions have been
reported. Hemorrhage into the residual tumor bed is the most devastating
Germinomas are highly radiosenstive. A long
term survival of greater than 90% is reported with
recommended dose is 5500cGy given in 180cGy daily fractions, with 4000cGy
to the ventricular system, and an additional 1500cGy to the tumor bed.
Nongerminomas are less responsive with 5 years survival in about 40% of
Radiotherapy may be withheld following total
excision of benign lesions, such as pineocytoma; but they need close
follow ups. Combined radiotherapy and chemotherapy is being studied to
reduce the radiation dose in view of the reported delayed post radiation
is increasingly being used in pineal tumors with satisfying results; long
term follow up is awaited.
Staging with neuroaxis
imaging and CSF analysis, when possible, is recommended. Post
operative craniospinal radiation in tumors prone for dissemination
is recommended. Currently, prophylactic craniospinal radiation is not
effective in children with malignant pineal tumors. Many consider this as
the first line of therapy instead of radiotherapy in children under 3
years of age. It has a definite role in recurrences. The agents include,
carboplatin, etoposide, and bleomycin, cyclophosphamide Vinblastine,
losfamide in various combinations and cycles.