Pineal germinoma

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

Synonyms and keywords: Pineal gland germinoma; Pineal germinomas; Germinoma of the pineal gland; Pineal dysgerminoma; Pineal dysgerminomas; Pineal gland tumor; Brain tumor

Overview

Pineal germinoma is the most common tumor of the pineal gland accounting for 50% of all tumors and the majority (80%) of intracranial germ cell tumors. Pineal germinoma is a type of germ cell tumor. It refers to a tumor in the pineal gland that has a histology identical to two other tumors, i.e. dysgerminoma in the ovary and seminoma in the testis.

Pathophysiology

Pathogenesis

• Pineal germinoma is a malignant neoplasm of the germinal tissue of the pineal region.
• Germinomas are thought to originate from an error of development, when certain primordial germ cells fail to migrate properly. Germinomas lack histologic differentiation, whereas nongerminomatous germ cell tumors display a variety of differentiation. Like other germ cell tumors, germinomas can undergo malignant transformation.

Associated Pathology

• Pineal germinoma may be associated with Down syndrome.

Gross Pathology

• On gross pathology, pineal germinoma is characterized by a mass whose external surface is smooth and bosselated (knobby) and the interior is soft, fleshy, and either cream-coloured, gray, pink, or tan.

Microscopic Pathology

• On histopathological analysis, pineal germinoma is characterized by uniform large, round cells with vesicular nuclei and clear or finely granular cytoplasm that is eosinophilic. Typically, the stroma contains lymphocytes and approximately 20% of patients have sarcoid-like granulomas.

Immunohistochemistry

Pineal germinoma is demonstrated by positivity to tumor markers such as:

• CD117
• PLAP
• β-HCG

Differentiating Pineal Germinoma from other Diseases

Pineal germinoma must be differentiated from:

• Pineocytoma
• Pineal parenchymal tumor with intermediate differentiation
• Papillary tumor of the pineal region
• Pineoblastoma
• Pineal embryonal carcinoma
• Pineal choriocarcinoma
• Pineal yolk sac carcinoma
• 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

Pineal germinoma is the most common tumor of the pineal gland, but accounts for less than 1% of all the intracranial tumors. Pineal germinoma accounts for 50% of all the pineal gland tumors and the majority (80%) of the intracranial germ cell tumors.

Age

Pineal germinoma is a disease that tends to affect the children and young adult population. Most patients are 20 years or younger at the time of diagnosis.

Gender

Males are more commonly affected with pineal germinoma than females. The male to female ratio is approximately 13 to 1.

Natural History, Complications and Prognosis

Natural History

If left untreated, patients with pineal germinoma may progress to develop seizures, obstructive hydrocephalus, and CSF metastasis.

Complications

Common complications of pineal germinoma include:

• Obstructive hydrocephalus
• Leptomeningeal spread

Prognosis

• Prognosis is generally excellent, and the 5-year survival rate of patients with pineal germinoma is approximately 90%.
• Multifocal or disseminated lesions are associated with poorer prognosis.
• Pineal germinoma usually presents with negative biological markers. The prognosis of patients with beta-human chorionic gonadotropin (β-HCG )secreting germinoma has been suggested to be worse than that of patients with pure germinoma.

History and Symptoms

History

• When evaluating a patient for pineal germinoma, 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 pineal germinoma is mainly from the obstructive hydrocephalus secondary to compression of the tectum of the midbrain and obstruction of the aqueduct.
• Symptoms of pineal germinoma include:

• Headaches
• Nausea
• Vomiting
• Seizures
• Hearing loss
• Sleepiness
• Irritability
• Slowed speech
• Fatigue
• Loss of appetite
• Hair loss
• Presyncopal episodes
• 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 pineal germinoma 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
• Hemiparesis
• Loss of bladder control
• Ataxia
• Tremor
• Dysmetria
• Pronator drift

CT

• Head CT scan may be diagnostic of pineal germinoma.
• Findings on CT scan suggestive of pineal germinoma include:

• Obstructive hydrocephalus

• Large midline mass in the pineal region

• Hyperdense compared to normal brain
• Vivid contrast enhancement
• Calcification: usually representing "engulfed" pineal calcification

MRI

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

MRI component	Findings
T1	Isointense to adjacent brain
T2	Isointense to adjacent brain
T1 with gadolinium contrast [T1 C+ (Gd)]	Vivid homogenous enhancement
Diffuse weighted imaging [DWI]	Restricted diffusion due to high cellularity

Gallery

• 

  _{Sagittal MRI with contrast demonstrating a large enhancing mass centered on the pineal region. It is heterogeneous with areas of cystic change. There is marked compression of the tectum with resulting obstructive hydrocephalus. A little surrounding edema is also present.}

Treatment

• The mainstay of therapy for pineal germinoma is radiotherapy, since it is highly radiosensitive.
• In children, there is an attempt to reduce the toxicity of radiation therapy by the use of chemotherapy in combination with reduced dose radiation to decrease the volume of normal tissue irradiated by stereotactic radiotherapy.
• The various chemotherapeutic agents that may be used for the treatment of pineal germinoma include:
  • Cisplatin
  • Etoposide
  • Carboplatin
  • Bleomycin

Management Options for Pineal Gland Tumors
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 are 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

• Patients with pineal germinoma may 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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