Pineocytoma

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

Synonyms and keywords: Pineocytomas; Pinealocytoma; Pinealocytomas; PC; Pineal gland tumor; Brain tumor

Overview

Pineocytoma is a benign, slowly growing pineal parenchymal tumor. The pineal gland, in the brain secretes melatonin which regulates sleep cycle . Pineocytomas most often occur in adults as a solid mass, although they may appear to have fluid-filled (cystic) spaces on images of the brain. Signs and symptoms of pineocytomas include headaches, nausea, , vision abnormalities, and Parinaud syndrome. Pineocytomas are usually slow-growing and rarely spread to other parts of the body. Treatment includes surgery to remove the pineocytoma; most of these tumors do not regrow (recur) after surgery.

Classification

The 2007 WHO classification of central nervous system tumors divides pineal gland tumors into four groups [16]:

• Pineocytoma (grade I)
• Pineal parenchymal tumors of intermediate differentiation (grade II or III)
• Papillary tumor of the pineal region (grade II or III)
• Pineoblastoma (grade IV)

Pathophysiology

Gross Pathology

On gross pathology, pineocytoma is characterized by solid, sometimes with focal areas of cystic change, gray, well-circumscribed mass with or without hemorrhage.

Microscopic Pathology

On microscopic histopathological analysis, pineocytoma is characterized by:

• Cytologically benign cells (uniform size of nuclei, regular nuclear membrane, light chromatin)
• Pineocytomatous/neurocytic rosette, which is an irregular circular/flower-like arrangement of cells with a large meshwork of fibers (neuropil) at the centre

According to the WHO classification of tumors of the central nervous system, pineocytoma is classified into a WHO grade I tumor.

Immunohistochemistry

Pineocytoma is demonstrated by positivity to tumor markers such as:

• Synaptophysin
• Neuron-specific enolase
• GFAP
• Chromogranin A
• PLAP
• Ki-67
• Beta tubulin III

Gallery

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  _{Intermediate magnification micrograph of a pineocytoma. HPS stain.}

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  _{High magnification micrograph of a pineocytoma. HPS stain.}

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  _{Very high magnification micrograph of a pineocytoma. HPS stain.}

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  _{The tumor cells are diffusely positive for synaptophysin and neurofilament.}

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  _{Positivity to Ki-67. The Ki-67 index is 2-3%.}

Differentiating Pineocytoma from other Diseases

Pineocytoma must be differentiated from:

• Pineal parenchymal tumor with intermediate differentiation
• Papillary tumor of the pineal region
• Pineoblastoma
• 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

Prevalence

• Pineocytoma constitutes approximately 45% of the pineal parenchymal tumors.
• Pineocytoma constitutes approximately 0.4 - 1% of the intracranial neoplasms.

Age

• Pineocytoma is a rare disease that tends to affect all age groups, most commonly in the second decade of life.
• Pineal tumors are more common in children aged 1 to 12 years where these constitute about 3 percent of brain tumors [2].

Gender

• Pineal tumors are substantially more common in males.
• In those with germ cell tumors, the male predominance was approximately 12:1.

Demographics

• In Europe and North America, pineal tumors account for less than 1 percent of all primary brain tumors.

Race

• Pineal tumors are more common in Asian countries than in Western countries.
• This increased frequency is due largely to an increase in germ cell tumors, which comprise 70 to 80 percent of all pineal region tumors in Japan and Korea.

Natural History, Complication and Prognosis

Natural History

If left untreated, patients with pineocytoma may progress to develop seizures, obstructive hydrocephalus, local recurrence, and CSF metastasis.

Complications

Common complications of pineocytoma include:

• Obstructive hydrocephalus
• Local recurrence
• CSF metastasis
• Distant metastasis (most commonly, lung)

Prognosis

• Prognosis is generally excellent, and the 5-year survival rate of patients with pineocytoma is approximately 86%.
• Pineocytoma has the most favorable prognosis among all the pineal gland tumors.
• Clark et al. after performing a systematic review of the literature reported that the 1- and 5-year progression free survival (PFS) rates for patients that underwent resection versus the biopsy group were 97% and 90%, and 89% and 75% respectively. The 1- and 5-year PFS rates for the gross total resection group versus the group undergoing subtotal resection combined with radiation therapy were 100% and 94%, and 100% and 84% respectively.

History and Symptoms

History

When evaluating a patient for pineocytoma, 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 pineocytoma is mainly from the obstructive hydrocephalus secondary to compression of the tectum of the midbrain and obstruction of the aqueduct.
  • Pineal tumors cause neurologic dysfunction by direct invasion, compression, or obstruction of cerebrospinal fluid (CSF) flow.
  • The rate of tumor growth determines the rapidity of symptom onset and is an important prognostic factor.
• Pineal gland tumors share some common clinical and radiographic features based upon their anatomic location. Symptoms of pineocytoma include:

• Hydrocephalus is common, manifested by headaches, lethargy, and signs of increased intracranial pressure.
• Progressive local tumor growth may result in cranial neuropathies or hypothalamic dysfunction.
  • 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 pineocytoma 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

Neurological

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

CT

• Head CT scan may be diagnostic of pineocytoma.
• Findings on CT scan suggestive of pineocytoma include a mass of intermediate density similar to the adjacent brain with peripheral calcifications.

Gallery

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  _{Different patterns of pineal calcification: Exploded calcification of tumors of pineal cell origin and engulfed calcification by germinomas.}

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  _{Single image following biopsy and third ventriculostomy demonstrates a pineal region soft tissue mass. A small amount of blood is seen in the occipital horn on the right. Ventricles remain dilated.}

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  _{A 14 X 13 mm (axial) soft tissue density mass in the pineal region with eccentric peripheral calcification demonstrated. The ventricles are prominent, out of keeping with the degree of sulcal prominence, indicating mild to moderate obstructive hydrocephalus due to the lesion partially obstructing the upper margin of the cerebral aqueduct. Periventricular hypoattenuation is in keeping with chronic small vessel ischaemia +/- transependymal CSF accumulation.}

MRI

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

MRI component	Findings
T1	Isointense to brain parenchyma
T2	Solid components are isointense to brain parenchyma Areas of cystic change Sometimes the majority of the tumor is cystic
T1 with gadolinium contrast	Solid components vividly enhance

Gallery

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  _{A large and ill-defined mass is present in the region of the pineal gland, demonstrating contrast enhancement.}

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  _{Axial T2 demonstrating a circular mass centered in pineal region measures 12 x 11 x 9 mm and demonstrates homogeneous enhancement (on volumetric sequence for stereotaxis), peripheral calcification, and diffusion restriction. It has mass effect on the adjacent structures with stenosis of the cerebral aqueduct (some flow still present on cine imaging) and associated non-communicating hydrocephalus affecting the lateral ventricles and 3rd ventricle. Foramina of Monroe are patent. No other suspicious enhancing lesion, including of the leptomeninges. No suprasellar/sellar mass in non-dedicated study.}

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  _{T2 MRI image demonstrating a well circumscribed mass is located in the region of the pineal gland. It is a little heterogeneous with multiple small regions of cyst formation (on T2) most marked anteriorly, probably at the site of biopsy.}

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  _{Axial T1 with contrast demonstrating a large enhancing mass is present in the pineal region compressing the tectum and resulting in obstructive hydrocephalus.}

Treatment

• The mainstay of therapy for pineocytoma is surgery (gross total or subtotal resection).
• The treatment of PPTs must be guided by the histologic subtype.

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

• Successful treatment of pineocytomas requires surgery with or without RT, while the best results with pineoblastomas are seen with multimodality approaches that include chemotherapy.
• The main goal of open surgery on pineocytoma 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.
• Radiotherapy administration to subtotally resected tumor is not associated with an increase in either tumor control or survival.
• Stereotactically guided iodine-125 seed implantation has been proposed as a potential alternative to microsurgery in de novo diagnosed pineocytomas, since it was proven efficient and safe.
• Patients with pineocytoma 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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