Pineoblastoma

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

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.

Gallery

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  _{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

Gallery

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  _{Pathology specimen of a pineoblastoma (HE stain, x200 magnification).}

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  _{Paraffin sections show fragments of a densely hypercellular tumor. Tumor cells have small round, oval, and angulated hyperchromatic nuclei and delicate processes which show strong immunostaining for neurofilament protein (NFP). Tumor cells are arranged in diffuse sheets. Prominent Homer-Wright rosettes are observed in several areas. Scattered mitotic figures are identified. No areas of necrosis are observed.}

Immunohistochemistry

Pineoblastoma is demonstrated by positivity to tumor markers such as:

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

Gallery

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  _{Immunohistochemical stain of a pineoblastoma demonstrating positivity to neurofilament.}

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  _{Immunohistochemical stain of a pineoblastoma demonstrating positivity to GFAP.}

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

When evaluating a patient for pineoblastoma, you should take a detailed history of the presenting symptom (onset, duration, and progression), other associated symptoms, and a thorough family and past medical history review.

Symptoms

• 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 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 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

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.

Gallery

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  _{Pineal calcification: exploded calcification of tumors of pineal cell origin, whereas engulfed calcification by germinomas.}

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  _{Single head CT image demonstrates a soft tissue mass in the region of the pineal gland with eccentric calcification (anterior) and evidence of hydrocephalus.}

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  _{Pre-contrast CT scan demonstrating moderate internal obstructive hydrocephalus, due to a large, partially calcified, dense mass which appears to be centered upon the pineal gland. The quadrigeminal plate appears anteriorly displaced and the aqueduct obliterated. It does not appear to have an intimate relationship with the tentorium.}

• 

  _{Axial brain CT image demonstrating a large hyperdense lobulated mass in the pineal region with peripheral foci of calcification and associated hydrocephalus. A VP shunt has recently been inserted (note the small amount of pneumocephalus). Hyperdense material is observed coating the frontal horns of the lateral ventricle and filling the floor of the third ventricle.}

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

Gallery

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  _{MRI image of pineoblastoma demonstrating restricted diffusion on DWI.}

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  _{Sagittal T1 with contrast CT image of pineoblastoma demonstrating an enhancing mass in the region of the pineal gland is present. A tongue of tissue is observed extending inferiorly through the aqueduct, obstructing it, and resulting in hydrocephalus with transependymal edema.}

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  _{Axial T1 with contrast demonstrating an irregular heterogenous enhancing pineal mass with several tiny cystic foci and eccentric coarse calcifications. There is moderate mass effect on the adjacent tectum and vermis, with loss of definition and possible parenchymal invasion on the left. There is associated aqueduct compression with moderate hydrocephalus.}

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  _{Axial T2-weighted MRI image demonstrating a lesion that is hyperintense.}

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

Gallery

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  _{MR spectroscopy of the lesion demonstrating elevation of the choline and lipid lactate peaks and depression of the neural markers; N-acetyl aspartate (NAA) and creatine (Cr).}

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.
• 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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