Pineal region tumors: A diverse pathology in the seat of the soul

Results: A total of 14 cases were operated during the study period. The mean age was 12 years (4-50 years) with male preponderance (64%). Most of these patients had clinical features of raised intracranial pressure due to obstructive hydrocephalus followed by oculomotor sign in the form of Perinaud syndrome and endocrine dysfunction. Most common histopathology was Pineoblastoma in our study (4 out of 14).


Original Article Introduction
Tumors of the pineal region represent a diverse collection of tumors which may involve not only the pineal gland itself but also posterior portion of the third ventricle, tectum and aqueduct of the midbrain. The histological heterogeneity of the variety of cell types which present in this area. According pineal region tumors include four principal groups [1][2][3][4] 1. Germ cell tumors 2. Pineal parenchymal tumors 3. Gliomas 4. Tumous of other histology (meningiomas, PNET, neurocytomas, haemangioblastomas, cavernomas and metastasis) Pineal region tumors account for 0.4-1% of all primary brain tumors and approximately two third of these tumors are malignant. 1,3,5,6 The clinical course of pineal region tumors depends on tumor histology. The rate of tumor growth determines the rapidity of symptom onset. In cases of malignant tumors, rapid progression of the disease occurs within several months or even weeks. In contrast, benign tumors such as tectal gliomas many not change their size over many years. Pineal tumors cause neurogenic dysfunction by direct invasion, compression or obstruction of cerebrospinal nausea, vomiting, dizziness due to compression of the cerebral aqueduct, resulting in obstructive hydrocephalus. Perinaud syndrome which includes vertical gaze palsy is the most common of the oculomotor symptoms that results

Results
Fourteen cases were operated during the study period. The mean age was 12 years (range 4-50 years). The tumors were most common in the paediatric population (6) and young adults (4). Male had preponderance (64%) verses female (36%). Most of these patients had clinical features of raised intracranial pressure due to obstructive hydrocephalus in 13 cases (93%) followed by oculomotor sign in the form dysfunction in four patients (29%). Hydrocephalus was typically triventricular.
All these patients were investigated with both contrast CT scan and MRI of the brain. Figure 1 and Figure 2 show typical pictures of a pineal region tumor in CT and MRI respectively. One patient also needed CT cerebral angiography to evaluate the relationship of tumor with surrounding blood vessels.         Out of the 14 cases, 12 were operated in semi sitting position, while two cases were operated in three quarter prone position (Figure 3). All the cases were operated by using infratentorial supracerebellar approach (Figure 4-7). Total excision of the tumor was achieved in 12(86%) of the cases. All patients had postoperative CT scan of the brain to evaluate the extent of surgical resection and presence of any other complications like pneumocephalus ( Figure  8). Postoperative period was uneventful for all cases and there was no mortality. All patients had favorable Glasgow Outcome Scale.

Discussion
Pineal region tumors account for 0.4-1% of all primary brain tumors and approximately two third of these tumors are malignant. 1,3,5,6 They represent 3% of all pediatric intracranial neoplasms. 7 Pineal region masses include those that originate from the pineal gland, as well as those that arise from adjacent structures. Masses of the pineal region range from simple benign cysts to high-grade neoplasms.
The pineal gland ranges in size from 10-14 mm and is located within the midline above the tentorium and superior colliculi and below the splenium of the corpus callosum and vein of Galen. It develops as a diverticulum in the diencephalon roof of the third ventricle during the second month of gestation. The gland itself is attached to the posterior aspect of the third ventricle by the pineal stalk. The mature gland secretes melatonin, an endocrine hormone involved in multiple pathways, but most commonly known for its association with circadian rhythms. The pineal gland is composed of 95% pineocytes (specialized neurons related to retinal rods and cones) and 5% astrocytes. Unlike most intracranial structures, the gland is outside of the blood-brain barrier. 8 Small pineal masses may be asymptomatic, but as lesions increase in size, they compress adjacent structures and may become symptomatic. Poppen and Marino initially suggested three clinical phases to pineal region masses: 1) headaches with nausea and vomiting; 2) blurred vision, diplopia, changes in mental states, drowsiness, papillary changes, ataxia or dizziness, and paralysis of the extraocular muscles; 3) papilledema, weakness, and spasticity. 9 Two common syndromes associated with pineal region masses include the Sylvian aqueduct syndrome and Parinaud syndrome. These syndromes are similar and result from compression of the mesencephalon. Typical abnormalities of the pupil, and nystagmus retractorius. One dreaded complication of a pineal region mass is pineal apoplexy, which are sequelae of hemorrhage into a pineal cyst or tumor with sudden decrease in consciousness and headache. 10 Magnetic resonance imaging (MRI) is the most useful initial study to determine the relationship of pineal tumors to adjacent structures.
vary according to their histological nature. However, with the exception of germinomas which can be nowadays cured by low-dose radiotherapy and chemotherapy and only require a biopsy for diagnosis, surgery still plays a central role in the management of most of the other pineal region tumors, followed or not by adjuvant radiotherapy, successful removal of a pineal tumor was reported in 1913 and successfully use the infratentorial supracerebellar approach in three cases in 1926. 11 In the micro-surgical era Stein further developed and popularized this approach during the 1970s. 12 Finally the right suboccipital approach in 1971. 13 The infratentorial supracerebellar and the occipital transtentorial approaches are nowadays accepted as the main standard accesses to the pineal region.
Germ cell tumors are the most common, particularly germinoma, followed by pineal cell tumors, to include pineocytomas and pineoblastomas. 14 Germinoma and astrocytoma were the commonest histopathological tumors are as follows: Germinomas: Germinomas are the most common tumor in this region and are highly radiosensitive with expectations of 80 -90% long term survival when adequate ( > 55 Gy) radiation doses are given to the tumor and surrounding 15 Value of chemotherapy for germinomas is yet to be conclusively proven. Pediatric Oncology Group (POG) study demonstrated extensive spinal relapses using exclusive chemotherapy protocols. Therefore chemotherapy should children. 16 Combination chemoradioherapy for germinomas is interesting and showed encouraging results, especially in reducing the brain's overall radiation exposure. 17 Chemoradiation protocol is an alternative to radiation therapy alone and it is probably best advocated for higher

Non Germinomatous Germ Cell Tumors:
Nongerminomatous malignant germ cell tumors (NGGCT) including endodermal sinus tumors, choriocarcinomas and embryonal carcinomas carry a poor prognosis. Most are levels or on histological diagnosis from tissue biopsy. In NGGCT study, comparing upfront chemotherapy prior to radiotherapy with radiotherapy alone, resulted in 5-year survival rate of 65% vs. 30% respectively. 18 From this study, they concluded that these tumors are radiosensitive but still require adjuvant chemotherapy for optimal longterm survival.

Intermediate Grade Pineal Parenchymal Tumors and
Pineaoblastomas : Intermediate grade pineal parenchymal tumors and pineoblastomas are highly aggressive tumors. Various clinical trials including pineal and non-pineal PNET have universally advocated gross total resection and adjuvant radiation and/or chemotherapy for these tumors. 19,20 Improvement in chemotherapy regimens than four years and therefore avoiding the radiation complications.
Teratomas: Combination of radio and chemotherapy is the treatment of choice for mixed (mature and immature teratomas) and immature or malignant teratomas. Minimally invasive endoscopic biopsy is the preferred strategy to obtain the initial tumor tissues for actual diagnosis. Debulking surgery is reserved for large tumor to make it susceptible for adjuvant therapy and to reduce cranial radiation dose and therefore cranial toxicity. On the contrary, for patients with mature teratomas, the treatment of choice is surgical resection. 21 Gliomas: Astrocytomas arising in pineal gland are often cystic and complete surgical resection is achievable resulting in probable cure. 22 A large tumor, thought to be a normally treated with radical surgery to debulk the tumor followed by radiation therapy; radiosurgery, stereotactic radiotherapy or intraoperative radiotherapy. The role of adjuvant radiation therapy for benign gliomas is debated.
Benign Pineal Region Tumors: These include Meningiomas, Epidermoids, Pineocytomas, Pineal and Arachnoid Cysts. Benign pathology is associated with excellent prognosis with surgery. Aggressive open surgical treatment with the goal of gross total resection invariably results in long term remission and potential cure. Minimally invasive endoscopic surgery is sometimes the treatment of choice for benign cystic lesions such as epidermoid and symptomatic pineal cysts. Radiation therapy may have a role for inoperable benign tumors such as meningiomas or pineocytomas. This type of therapy is normally opted for elderly or patients with multiple medical problems

Conclusion
Pineal region tumors are most commonly seen in adolescent age group. Most common symptoms are features of raised intra cranial pressure due to hydrocephalus followed by Perinaud syndrome. Pineal region tumors consist of diverse histopathological variants.