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.

Pathology:

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 blood vessels. 

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.

Other rarer tumors include meningioma, ependymoma, paraganglioma, melanoma, hemangioma, hemangiopericytoma, craniopharyngioma.

Rare Cysts include pineal cyst, arachnoid cyst, epidermoid and dermoid, lipoma and metastases.

Pineal Cyst:

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.

Pineal parenchymal neoplasms (pinealomas):

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.

Pineocytoma is a better differentiated variant of pineal tumors and occurs mostly in adult life. 

Usually 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 pinoeblastoma (the so-called 'ganglioglioma' of the pineal), but the nuclear: cytoplasmic ratio is much higher in this tumor, and the mitoses are evident.

Pineoblastoma is the 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. 

It 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.

Clinical features:

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.

Dorsal midbrain compression or infiltration can cause lid retraction (Collier's sign) or ptosis.

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.

Endocrine disturbance is rare due to tumor spread to hypothalamus.

Imaging:

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 masses.

Teratomas are of mixed signal intensity, frequently with calcification. They may also have cystic components and fat.

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.

Tumor markers:

CSF analysis, whenever possible, should be carried out. It is most valuable in germ cell tumors, which constitutes about

70% of the pineal tumors. Expression of embryonal proteins, such as, alpha fetoprotein (AFB), and beta HCG are indicative

of malignant germ cell elements. Other biological markers for germ cell tumors include, Lactic dehydrogenase isoenzymes

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 purposes. 

Management:

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 dissemination.

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 stereotactic biopsy or open surgery.

Germinoma is an exception. Detection of Placental Alkaline Phosphatase (PLAP) is diagnostic of germinomas, and obviates biopsy.

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 microsurgical techniques.

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 complication.

Germinomas are highly radiosenstive. A long term survival of greater than 90% is reported with radiotherapy. The 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 cases.

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 complications. Stereotactic radiosurgery 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 recommended.

Chemotherapy is, 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.