- Author: Jeffrey N Bruce, MD; Chief Editor: Brian H Kopell, MD more...
The pineal gland develops during the second month of gestation as a diverticulum in the diencephalic roof of the third ventricle. It is flanked by the posterior and habenular commissures in the rostral portion of the midbrain directly below the splenium of the corpus callosum. The velum interpositum is found rostral and dorsal to the pineal gland and contains the internal cerebral veins, which join to form the vein of Galen.
Pineal region tumors are derived from cells located in and around the pineal gland. The principle cell of the pineal gland is the pineal parenchymal cell or pinocyte. This cell is a specialized neuron related to retinal rods and cones. The pinocyte is surrounded by a stroma of fibrillary astrocytes, which interact with adjoining blood vessels to form part of the blood-pial barrier.
The pineal gland is richly innervated with sympathetic noradrenergic input from a pathway that originates in the retina and courses through the suprachiasmatic nucleus of the hypothalamus and the superior cervical ganglion. Upon stimulation, the pineal gland converts the sympathetic input into hormonal output by producing melatonin, which has regulatory effects upon hormones such as luteinizing hormone and follicle-stimulating hormone.
The pineal gland is a neuroendocrine transducer that synchronizes hormonal release with phases of the light-dark cycle by means of its sympathetic input. However, the exact relationship between the pineal gland and human circadian rhythm remains unclear and is an active area of investigation.
Some images of pineal tumors are below.
History of the Procedure
In the early part of the 20th century, pineal region surgery had poor outcomes, with operative mortality rates approaching 90%. From Horsley's initial attempt at removing a pineal mass in 1910 through the development of the lateral transventricular approach in 1931 by Van Wagenan, primitive anesthetic technique and the lack of an operating microscope hindered pineal region surgery.
In 1948, Torkildsen argued for abandoning aggressive surgical resection in favor of cerebrospinal fluid (CSF) diversion followed by empiric radiotherapy. If the patient did not respond to radiation, a surgical procedure to remove radioresistant tumor was performed. The algorithm of CSF diversion, radiation, and observation sometimes was successful; however, patients with benign lesions were exposed to unnecessary and ineffective radiation.
Modification of this treatment strategy led to the radiation test heralded by Japanese clinicians whose patient population had an inordinately high percentage of radiosensitive germinomas. According to this protocol, patients were administered small doses of radiation, and their cases were followed radiologically. Pineal tumors that decreased in size were presumed to be radiosensitive, and a full course of radiation was instituted. Patients not responding to radiotherapy underwent surgical exploration. Despite the low dose of radiation initially used, significant long-term morbidity remained associated with this strategy, particularly in children.
The advent of microsurgical techniques and stereotactic procedures in the later part of the 20th century has obviated the need for empiric radiotherapy without tissue diagnosis. Therapeutic decision-making now is based on tumor histology rather than radiation responsiveness. Currently, initial surgical management for tissue diagnosis, and possible resection, is the standard of care for most children with pineal region tumors.
Initial management of patients with pineal region tumors should be directed at treating hydrocephalus and establishing a diagnosis. Preoperative evaluation should include (1) high-resolution MRI of the head with gadolinium; (2) measurement of serum and CSF markers, if available; (3) cytologic examination of CSF, if available; (4) evaluation of pituitary function if endocrine abnormalities are suspected; and (5) visual field examination if suprasellar extension of the tumor is noted on MRI. The ultimate management goal should be to refine adjuvant therapy based on tumor pathology.
Pineal region tumors make up 0.4-1.0% of intracranial tumors in adults and 3.0-8.0% of brain tumors in children. Most children are aged 10-20 years at presentation, with the average age at presentation being 13 years. Adults typically are older than 30 years at presentation. A complete differential diagnosis for masses in the pineal region also should include vascular anomalies, as well as metastatic tumor.
Tumors of the pineal region have a varied histology that generally can be divided into germ cell and non–germ cell derivatives. Most tumors are a result of displaced embryonic tissue, malignant transformation of pineal parenchymal cells, or transformation of surrounding astroglia. No specific genetic mutations have been associated with sporadic pineal region tumors.
The pathophysiology of pineal region tumors is mostly a result of anatomic compression of adjacent structures, although local infiltration of neural structures can lead to symptoms in cases of highly invasive tumors. In some cases, neuroendocrine dysfunction is precipitated by specific factors secreted by the tumor. The clinical correlates of this pathophysiology are described in the following section on clinical presentation.
The clinical syndromes associated with pineal region tumors relate directly to normal pineal anatomy, as well as tumor histology.
Mass lesions in the pineal region that compress adjacent structures result in typical clinical syndromes. One of the most common presentations is headache, nausea, and vomiting caused by aqueductal compression and resultant obstructive hydrocephalus. Untreated, hydrocephalus may lead progressively to lethargy, obtundation, and death.
Compromise of the superior colliculus, either through direct compression or through tumor invasion, results in a syndrome of vertical gaze palsy that can be associated with pupillary or oculomotor nerve paresis. This eponymic syndrome was first described by the French ophthalmologist Henri Parinaud in the late 1800s and has become virtually pathognomonic for lesions involving the quadrigeminal plate.
Further compression of the periaqueductal gray region may cause mydriasis, convergence spasm, pupillary inequality, and convergence or refractory nystagmus. Impairment of downgaze becomes more pronounced with tumors involving the ventral midbrain. Patients also can present with motor impairment, such as ataxia and dysmetria, resulting from compromise of cerebellar efferent fibers within the superior cerebellar peduncle.
Children with pineal region tumors can present with endocrine malfunction. Hydrocephalus or concurrent suprasellar tumors can cause diabetes insipidus. More specific endocrine syndromes can arise from secretion of hormones by germ cell tumors. Pseudoprecocious puberty caused by beta human chorionic gonadotropin (bhCG) can be observed with germ cell tumors in either the pineal or suprasellar region. In a large series of patients with germ cell tumors and suprasellar involvement, 93% of girls older than 12 years had secondary amenorrhea and 33% of patients younger than 15 years had growth arrest.
Pineal apoplexy, bleeding into the tumor area, has been described as a rare presenting feature of pineal region tumors. Hemorrhage into a vascular-rich pineal tumor can occur preoperatively and is a well-described postoperative complication.
Indications for neurosurgical intervention relate to the severity and chronicity of clinical presentation. The symptoms of pineal region tumors can be as varied as their diverse histology. Prodromal periods can last from weeks to years. Therefore, a rigorous and uniform preoperative workup is a requisite for all patients thought to harbor a pineal region tumor.
Any endocrine abnormalities should be investigated prior to surgery. Patients presenting with signs and symptoms of raised intracranial pressure must receive a head CT scan or an MRI to assess the need for emergent management. Subsequent nonemergent workup of a patient with a pineal region tumor can be divided into radiologic and laboratory studies.
In their 1954 pineal tumor study, Ringertz and colleagues defined the pineal region as being bound by the splenium of the corpus callosum and tela choroidea dorsally, the quadrigeminal plate and midbrain tectum ventrally, the posterior aspect of the third ventricle rostrally, and the cerebellar vermis caudally. As discussed in the subsequent section on treatment of these lesions, important anatomic considerations include the presence of deep venous structures.
Relatively few contraindications specifically preclude the surgical treatment of pineal region tumors. Medical clearance for general anesthesia is a requisite, as well as preoperative evaluation of neck motion (ie, tolerance of flexion) prior to planning a supracerebellar/infratentorial approach.
In a study of 35 consecutive patients from 7 academic centers of the Rare Cancer Network diagnosed between 1988 and 2006 (median age, 36 yr), median disease-free survival was 82 month. Age younger than 36 years was an unfavorable prognostic factor, and patients with metastases at diagnosis had poorer survival. Histological subtypes were pineoblastoma in 21 patients, pineocytoma in 8 patients, and pineocytoma with intermediate differentiation in 6 patients.
In a study of medical records of 31 patients with pineoblastoma (female, 67.7%; median age, 18.2 yr), median overall survival was found to be 8.7 years, with 2-, 5-, and 10- year actuarial rates of 89.5%, 69.4%, and 48.6%, respectively. Median disease-free survival was 10 years, with 2-, 5-, and 10- year actuarial rates of 84.3%, 62.6%, and 55.7%.
In another study of patients with pineoblastoma, the overall survival rate was 54% (175 of 299 patients) at a mean follow-up of 31 ± 1.9 months (range, 1-159 months). A markedly worse prognosis was demonstrated for children aged 5 years or younger compared with older patients (5-year survival rate: 15% for children aged ≤ 5 yr vs 57% for children aged ≥ 5 yr). A failure to achieve gross total resection markedly worsened patient survival.
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