Pineoblastoma

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Sujit Routray, M.D. [2]

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Synonyms and keywords: Pineoblastomas; Pinealoblastoma; Pinealoblastomas; PB; Pineal parenchymal tumor; Pineal gland tumor; Brain tumor

Overview

Pineoblastoma is a rare, malignant pineal parenchymal tumor. It is a supratentorial midline primitive neuroectodermal tumor. It is considered as a WHO grade IV tumor according to the WHO classification of tumors of the central nervous system.

Pathophysiology

Pathogenesis

Pineoblastoma originates from the neuroectodermal cells. It is the least differentiated pineal gland tumors, with pineocytoma and pineal parenchymal tumour with intermediate differentiation representing better differentiated tumors along the same spectrum.

Associated Conditions

• Pineoblastoma may occur in patients with hereditary uni- or bilateral retinoblastoma.
• When retinoblastoma patients present with pineoblastoma, this is characterized as "trilateral retinoblastoma".

Gross Pathology

On gross pathology, pineoblastoma is characterized by solid, large poorly defined masses.

_{An autopsy specimen showing a rather large pineal tumor. It was a pineoblastoma composed of highly cellular sheets of anaplastic cells with irregular hyperchromatic nuclei and brisk mitotic activity – resembling medulloblastoma and retinoblastoma.}

Microscopic Pathology

On microscopic histopathological analysis, pineoblastoma is characterized by:

• Hypercellular appearance
• Tightly packed small round blue cells (high nuclear to cytoplasmic ratio)
• Oval and angulated hyperchromatic nuclei with atypia
• Mitoses
• Homer-wright & Flexner-Winterstein rosettes
• Fleurettes

Immunohistochemistry

Pineoblastoma is demonstrated by positivity to tumor markers such as:

• GFAP
• Neurofilament
• Synaptophysin
• MIB-1
• Ki-67

Differentiating Pineoblastoma from other Diseases

Pineoblastoma must be differentiated from:

• Pineocytoma
• Pineal parenchymal tumor with intermediate differentiation
• Papillary tumor of the pineal region
• Pineal germinoma
• Pineal embryonal carcinoma
• Pineal choriocarcinoma
• Pineal yolk sac carcinoma (endodermal sinus tumor)
• Pineal teratoma
• Pineal cyst
• Astrocytoma of the pineal gland
• Meningioma near pineal gland
• Pineal metastasis
• Cavernoma in pineal region
• Aneurysm in pineal region

Epidemiology and Demographics

Prevalence

• Pineoblastoma constitutes approximately 0.1% of the intracranial neoplasms.
• Pineoblastoma together with germ cell tumors are the most common pineal tumors in children.

Age

Pineoblastoma is a disease that tends to affect children and young adults.

Gender

Pineoblastoma affects men and women equally.

Natural History, Complications and Prognosis

Natural History

• Pineoblastoma is the most agressive pineal parenchymal tumor.
• If left untreated, patients with pineoblastoma may progress to develop seizures, obstructive hydrocephalus, local recurrence, and CSF metastasis.

Complications

Common complications of pineoblastoma include:

• Obstructive hydrocephalus
• Local recurrence
• CSF metastasis

Prognosis

Prognosis is generally poor, and the 5-year survival rate of patients with pineoblastoma is approximately 58%.

History and Symptoms

History

The clinical presentation of pineoblastoma is mainly from the obstructive hydrocephalus secondary to compression of the tectum of the midbrain and obstruction of the aqueduct.

Symptoms

• Symptoms of pineoblastoma include:

• Headaches
• Nausea
• Vomiting
• Seizures
• Tinnitus
• Hearing loss
• Sleepiness
• Irritability
• Personality changes
• Double vision
• Trouble coordinating motor movements
• Difficulty walking
• Slowed growth

Physical Examination

• Compression of the superior colliculi can lead to a characteristic upward gaze palsy, known as Parinaud syndrome.
• Common physical examination findings of pineoblastoma include:

HEENT

• Bulging soft spots (fontanelles)
• Eyes that are constantly looking down (sunsetting sign)
• Deficiency in upward-gaze
• Pupillary light-near dissociation (pupils respond to near stimuli but not light)
• Convergence-retraction nystagmus
• Papilledema

Neurological

• Mental retardation
• Muscle spasms
• Loss of bladder control
• Ataxia
• Cranioneuropathies

• VI^th nerve palsy

Laboratory Diagnosis

There are no specific laboratory findings for pineocytoma. However, the following findings are of significant

• Both serum and CSF should be assayed for alpha-fetoprotein and beta human chorionic gonadotropin (beta-hCG) to help diagnose a germ cell tumor.
• Immunohistochemistry may be of value in detecting these markers or placental alkaline phosphatase.

CT

• Head CT scan may be diagnostic of pineoblastoma.
• Findings on CT scan suggestive of pineoblastoma include a mass with a solid component that tends to be slightly hyperdense compared to adjacent brain due to high cellularity. Calcification is present that is peripherally disperse or "exploded", similar to pineocytoma.

MRI

• Brain MRI may be diagnostic of pineoblastoma.
• Features on MRI suggestive of pineoblastoma include:

MRI component	Findings
T1	Isointense to hypointense to adjacent brain
T2	Isointense to adjacent brain Areas of cyst formation or necrosis may be present
T1 with gadolinium contrast [T1 C+ (Gd)]	Vivid heterogenous enhancement
Diffuse weighted imaging/Apparent diffusion coefficient [DWI/ADC]	Restricted diffusion due to dense cellular packing ADC values are typically 400-800 mm2/s

Other Imaging Findings

Other imaging studies for pineoblastoma include magnetic resonance spectroscopy (MR spectroscopy), which demonstrates:

• Elevation of the choline and lipid lactate peaks
• Depression of the neural markers (N-acetyl aspartate (NAA) and creatine (Cr)
• Prominent glutamate and taurine peaks at 3.4 ppm with shot TE signal voxel MR spectroscopy

Other Diagnostic Studies

Stereotactic biopsy

• A direct, visually guided biopsy of the pineal gland mass with open or neuroendoscopic surgery has been preferred due to concerns about injury to the deep cerebral veins.
• An open procedure also allows CSF to be obtained for
  • Tumor marker studies
  • Permits direct visualization of the third ventricle for staging purposes
  • Sllows a third ventriculostomy to be performed for CSF diversion if needed.
• The diagnostic yield of stereotactic biopsy ranges from 94 to 100 percent.
• If the biopsy is nondiagnostic, equivocal, or suggests a benign tumor such as mature teratoma or meningioma, surgery is recommended to establish a definitive diagnosis or to identify focal areas of malignant disease

Treatment

• The predominant therapy for pineoblastoma is surgical resection. Adjunctive chemotherapy and radiation may be required.
• The main goal of open surgery on pineoblastoma is the complete tumor removal with minimal morbidity, whenever possible. However, even if gross total excision cannot be achieved, establishment of an accurate diagnosis, maximal cytoreduction, and restoration of the CSF pathway may be achieved.

Management Options of Penial Gland tumors
CSF diversion	The optimal surgical strategy to treat acute hydrocephalus in patients with pineal tumors is uncertain. CSF diversion (ventriculoperitoneal [VP] shunt or third ventriculostomy may be necessary in symptomatic patients, although debulking surgery may obviate the need for this procedure When CSF diversion is necessary, endoscopic third ventriculostomy can be carried out at the same time as the biopsy and is preferred over VP shunts, which can be complicated by infection, shunt malfunction, subdural hematoma, and rarely, tumor seeding
Surgical resection	Some series report long-term survival with surgery alone, even in patients with pineoblastomas. Indeed, for pineoblastomas, gross total surgical resection appears to correlate with improved survival. Patients with symptomatic recurrent pineocytomas should also be considered for surgical resection of the lesion
Radiation	Postoperative adjuvant RT is frequently (but not universally) recommended, and local control is dose-dependent. The incidence of leptomeningeal recurrence was significantly lower among patients receiving CSI compared with those who did not. The five-year survival rates were 86 and 49 percent for pineocytomas and non-pineocytoma PPTs, respectively. Adjuvant RT is not universally recommended after gross total resection of a pineocytoma
Stereotactic radiosurgery	Stereotactic radiosurgery (SRS) is emerging as a useful treatment alternative for pineocytomas, although experience is limited. The precise radiation fields that are defined by MRI or CT-computerized treatment planning minimize damage to the surrounding brain, and the risks of general anesthesia and craniotomy are avoided. SRS is increasingly being used to treat pineal region tumors, either as an additional therapy after conventional treatments or as a primary treatment. Due to the low rate of side effects, IRS may develop into an attractive alternative to microsurgery in de novo diagnosed pineocytomas. In malignant PPTs, IRS may be routinely applied in a multimodality treatment schedule supplementary to conventional irradiation.
Chemotherapy as part of multimodality therapy	The similarity of pineoblastomas to medulloblastomas in terms of their clinical behavior and tendency for leptomeningeal seeding has led to the use of similar chemotherapy regimens in patients with pineoblastoma as part of a multimodality approach. Chemotherapy has been used to delay radiation therapy in very young children, for whom the long-term neurocognitive and developmental side effects of craniospinal irradiation (CSI) are a major concern. The importance of radiation therapy as a component of the initial treatment of supratentorial primitive neuroectodermal tumors (PNETs) is also supported by the German HIT-SKK87 and HIT-SKK92 protocols, as well as the Canadian pediatric brain tumor protocol

• Gross total resection has been associated with improved survival, similar to treatment with craniospinal irradiation and multi-agent chemotherapy.
• Children under the age of 36 months with pineoblastoma should be treated with multi-agent chemotherapy for 12 to 24 months with the goal of delaying radiation past the age of 36 months. Craniospinal irradiation before this age of 3 has been associated with significant cognitive and neuroendocrine sequelae.
• Tate et al. summarized the existing literature on patients with pineoblastoma and found that children under 5 years of age and subtotal tumor resection markedly worsened patient survival. According to the Children's Oncology Group trials, these tumors require craniospinal irradiation (with local tumor doses of at least 50 Gy) and adjuvant chemotherapy. When carboplatin and vincristine were administered during craniospinal irradiation followed by 6 months of non-intensive non-cisplatin containing adjuvant chemotherapy, an 84% 2-years progression free survival was reported in pineoblastomas without evidence of dissemination at presentation.
• Patients with pineoblastoma will develop hydrocephalus in majority of the cases and they will require CSF diversion. Ventriculo-peritoneal (V-P) shunt placement is a viable option with low morbidity and mortality rate. However, shunt malfunction in this population is as high as 20%. In addition, tumor metastasis through a CSF shunt has been reported. Endoscopic third ventriculostomy (ETVC) is an alternative option, which also permits a biopsy of the tumor in the same procedure. Ahn et al. reported that the biopsy samples, obtained in the lateral ventricle or pineal region, were more favorable towards a successful diagnosis than those in the thalamus or tectal region. Neuroendoscopic biopsy procedures have been proven safe with low complication rates.

References

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