What are the other Names for this Condition? (Also known as/Synonyms)

• EVN (Extraventricular Neurocytoma)
• Cerebral Neurocytoma

What is Extraventricular Neurocytoma? (Definition/Background Information)

• An Extraventricular Neurocytoma (EVN) is a form of brain tumor. A brain tumor may be described as a mass of abnormally growing cells arising from the brain tissue (brain parenchyma and meninges) or the spinal cord (central spine). The brain along-with the spinal cord constitute the central nervous system (CNS) of the body
• Broadly, brain tumors are classified as benign (non-cancerous) and malignant. Malignant tumors are cancerous and can spread or metastasize to other regions of the body. They generally exhibit rapid growth and, in some cases, may present symptoms during the early stages of development
• The World Health Organization (WHO) classifies central nervous system tumors according to their grade and histological subtypes. A tumor subtype is determined by a pathologist after examining a tissue biopsy of the tumor under the microscope. This WHO classification system is used by healthcare professionals all over the world in diagnosing and treating these tumors
• Central neurocytoma (CNC) is a relatively benign neuroepithelial tumor that typically involves the ventricular system of the brain. On extremely rare occasions, a neurocytoma may arise outside the ventricles, but within the brain tissue or spinal cord. In such cases, it is known as an Extraventricular Neurocytoma. Some of the extraventricular locations include the cerebral hemispheres (most commonly), the brainstem, and cerebellum
• Per WHO, the tumor is part of a group designated as “neuronal and mixed neuronal glial tumors”. The tumor develops from the nerve cells. The brain is made of two main cell types - the nerve cells (neurons) and glial cells (non-neuronal cells). The nerve cells communicate with each other and relay information (electric signals or nerve impulses) from the peripheral nervous system (PNS) to the CNS. The glial cells support the nerve cells, but do not take part in the transmission of electrical signals
• Extraventricular Neurocytoma is a WHO grade II brain tumor, meaning that it is a low-grade tumor. The grade II tumors grow faster than grade I tumors, which are the most benign of the brain tumors. Grade II tumors tend to be minimally infiltrative into the surrounding brain tissue but have the possibility to recur as a higher grade tumor following treatment. It is less likely to grow and spread than malignant tumors
• Extraventricular Neurocytoma is found across a wide age range, from children to adults. The cause of formation of the tumor is not well-established. It is reported that a combination of several factors may play a role in their formation, including genetic, environmental, and lifestyle-related. In general, the risk factors for brain tumors may include the presence of certain genetic disorders, exposure to ionized radiation, viral infections, and head trauma
• The signs and symptoms of Extraventricular Neurocytoma depend on the location of the tumor. Individuals may experience headaches, weakness in different parts of the body, convulsions, vision and speech disturbances. Large-sized tumors may compress adjacent brain tissue resulting in complications. Complications from an acute hemorrhage in the brain can be life-threatening and fatal
• The treatments for Extraventricular Neurocytoma may primarily involve surgery; post-operative treatment with radiation therapy is recommended for partial tumor resections. The prognosis for individuals with EVN depend on a wide variety of factors, including the size of the tumor and overall health status of the individual. The prognosis is usually good with early diagnosis and adequate treatment

Who gets Extraventricular Neurocytoma? (Age and Sex Distribution)

• Extraventricular Neurocytoma is an extremely uncommon tumor that may be diagnosed in both children (rarely) and adults; an age range of 5 to 76 years is observed (median age is 34 years)
• Both males and females may be affected, and no gender preference is known
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Extraventricular Neurocytoma? (Predisposing Factors)

No clearly identified risk factors are reported for Extraventricular Neurocytomas.

In general, the following factors may increase one’s risk for brain tumors:

• Advancing age is an important risk factor; although, some tumors are common among children
• In general, males are at a higher risk for brain tumors than females
• Positive family history: It is reported that certain genetic (hereditary) factors are responsible for the formation of certain brain tumors. Such hereditary conditions include:
  • Li-Fraumeni syndrome
  • Neurofibromatosis types 1 and 2 (NF1 and NF2)
  • Tuberous sclerosis
  • Turcot syndrome
  • Von Hippel-Lindau disease
• Environmental factors such as ionized radiation exposure (both high-dose and low-dose)
• Individuals who have undergone radiation therapy for other cancers involving the head and neck region are at an increased risk
• Viral infections involving pathogens, such as Epstein-Barr virus (EBV) and cytomegalovirus (CMV), have been implicated
• Exposure to certain chemicals, pesticides, or products, either at work or at home
• Some reports indicate that the use of mobile phones may increase one’s risk due to exposure to electromagnetic waves. However, the scientific research community is presently divided on this factor
• Head injuries
• History of seizures
• Hormonal factors: Studies have shown a correlation between hormones and some types of brain tumors
• Intake of N-nitroso compounds, either in one’s diet (such as cured meat) or via vitamin supplements may increase one’s risk

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Extraventricular Neurocytoma? (Etiology)

The exact cause of development of Extraventricular Neurocytoma (EVN) is not well-understood. Research scientists believe that the cause may involve a combination of several factors including genetic, environmental, and occupational factors.

The following genetic abnormalities are observed:

• There are no mutations on the IDH genes
• Chromosome 1p/19q codeletion is noted

The above features are important in distinguishing between an Extraventricular Neurocytoma and an oligodendroglioma.

In general, it is known that tumors form when normal, healthy cells begin transforming into abnormal cells - these cancer cells grow and divide uncontrollably (and lose their ability to die), resulting in the formation of a mass or a tumor.

What are the Signs and Symptoms of Extraventricular Neurocytoma?

The signs and symptoms of Extraventricular Neurocytoma (EVN) may be significantly different from one individual to another. It may be mild or severe, depending on several factors. The onset of symptoms and speed of progression of the tumor can vary. In many individuals, tumors that grow slowly and remain asymptomatic, are only diagnosed during certain radiological imaging studies of the head and neck region, which are performed for unrelated health conditions.

The signs and symptoms primarily depend on the location and size of the tumor. It may occur anywhere in the brain parenchyma (brain tissue) or spinal cord, outside of the ventricular system. These tumors may be referred to as the extraventricular version of central neurocytomas.

• Most of the tumors involve the cerebral hemispheres (usually frontal lobe)
• Other locations in the brain include the following areas:
  • Amygdala
  • Brainstem
  • Cerebellum
  • Pons
  • Region of the pineal gland
  • Retina
  • Thalamus
• Spinal cord

The signs and symptoms may include:

• Symptoms due to tumor mass effect
• Headaches that may increase in intensity and be persistent
• Lack of coordination
• Unsteadiness and loss of balance (vertigo)
• Nausea and vomiting
• Numbness and tingling sensation
• Muscle weakness; loss of strength in the arms of legs
• Visual impairment such as blurred vision, double vision or poor eyesight
• Neck pain
• Hearing impairment or hearing loss
• Speech problems
• If the cranial nerves are involved, it may lead to cranial nerve palsies
• Insomnia or loss of sleep, or excessive sleepiness (usually during daytime)
• Tremors
• Seizures or convulsions that may be any of the following types
  • Myoclonic seizures
  • Grand mal (tonic-clonic) seizures
  • Sensory seizures
  • Complex partial seizures
• Dizziness and fainting
• Confusion
• Changes in one’s behavior; personality changes
• Mental impairment
• Memory loss
• Involvement of the spinal cord may lead to:
  • Back pain and/or chest pain
  • Pain in the arms and legs, depending on the nerves that are compressed by the tumor
  • Severe cases may result in loss of bowel and bladder control

Large tumors can cause significant signs and symptoms. Most of the cases represent single tumors; but occasionally, multiple tumors can be detected growing simultaneously in the brain or spinal cord region, particularly in individuals with genetic disorders. The associated symptoms of the underlying condition, if any present, may be noted.

How is Extraventricular Neurocytoma Diagnosed?

Extraventricular Neurocytomas may remain undiagnosed for prolonged periods, if they are asymptomatic. If the tumors develop slowly, then it may also contribute to a delayed detection and diagnosis of these tumors. The tumors are detected when there is a sudden worsening of symptoms prompting the healthcare provider to perform radiological studies of the brain and/or spinal cord.

Due to its similarity to other brain tumors and relative rarity of Extraventricular Neurocytoma (EVN), it is known to be frequently misdiagnosed, particularly as oligodendroglioma. The diagnosis of EVN may involve the following tests and examinations:

• Complete physical examination and a thorough medical history
• Assessment of the presenting signs and symptoms
• Neurological, motor skills, and cognitive assessment:
  • Checking intellectual ability, memory, mental health and function, language skills, judgment and reasoning, coordination and balance, reflexes, sensory perceptions (space, sight, hearing, touch)
  • The healthcare provider/neurologist may use the Karnofsky Performance Scale in order to assess the neurological functioning of the individual’s central nervous system (CNS)
• Electroencephalography (EEG)
• Electromyography with nerve conductivity tests
• Imaging studies that may be performed include:
  • X-ray of the head and neck region
  • Computerized tomography (CT) scan of the head and neck region; CT scan with contrast agent
  • Magnetic resonance imaging (MRI) scan of the central nervous system; MRI with contrast agents such as gadolinium
  • Cerebral angiographic studies or MR angiography: An angiogram involves injecting dye into the bloodstream, which makes the blood vessels to appear visually on X-rays. The X-ray may show a tumor in the brain or the blood vessels leading into the tumor
  • Magnetic resonance spectroscopy: This radiological technique is used to study the chemical profile of the tumor. It is often performed with and compared to corresponding MRI scan images of the affected region
  • Positron emission tomography (PET scan): A PET scan is a nuclear medicine imaging technique that uses three-dimensional images to show how tissue and organs are functioning. It may be performed to detect any malignancy, and if there is a metastasis (spread) of the tumor to other regions
• Cerebrospinal fluid analysis, where a spinal tap or lumbar puncture procedure may be performed: This diagnostic test is used to remove a sample of cerebrospinal fluid (CSF) from the spaces in and around the brain and spinal cord. The sample is removed from the lower spinal cord using a thin needle, and it is then checked for the presence of cancer cells
• Molecular testing to identify genetic mutations

Tissue biopsy: A biopsy of the affected region (brain or spinal cord) is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy sample under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy sample under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis.

There are two ways to perform a biopsy:

• First, a biopsy can be performed as part of a surgical procedure to remove the brain tumor
• Second, a stereotactic needle biopsy can be performed when the tumor is deep within the brain or located in a sensitive area. In this procedure, the surgeon drills a small hole (called a burr hole) into the skull. A thin needle, guided by CT or MRI scanning, is then inserted through the hole to help in the removal of tissue

A differential diagnosis to eliminate other conditions or tumor types may be considered, before arriving at a definitive diagnosis. 

Radiological differential diagnosis may include:

• Diffuse leptomeningeal glioneuronal tumor (DLGNT)
• Ganglioglioma and gangliocytoma
• Gemistocytic astrocytoma
• Oligodendroglioma
• Papillary glioneuronal tumor (PGNT)
• Pilocytic astrocytoma
• Pleomorphic xanthoastrocytoma (PXA)
• Rosette-forming glioneuronal tumor (RGNT)

Pathological differential diagnosis may include:

• Ependymoma
• Meningioma of the sellar region
• Oligodendroglioma
• Primitive neuroectodermal tumor (PNET)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Extraventricular Neurocytoma?

The possible complications associated with Extraventricular Neurocytoma include:

• Emotional and mental stress for both the patient and the caretakers, due to the diagnosis and during treatment of a brain tumor
• Large undetected tumors can severely affect brain function and be disabling or even life-threatening, due to mass effect/compression of surrounding tissue
• In the brain, large tumors may also press against the skull (or other) bones causing it to expand, causing severe complications
• Trouble with concentration
• Tumors involving the retina may cause blindness
• Severe loss of memory
• Dementia including personality changes causing a reduced quality of life
• Bleeding in the brain (brain hemorrhage)
• Paralysis and coma
• Peritumoral brain edema (PTBE): Presence of fluid around the tumor region in the brain resulting in severe symptoms and complications
• Complications due to an underlying genetic disorder, if any present

Complications may arise from surgery, radiation therapy, or other treatment modalities. These may lead to long-term side effects, particularly in children and older adults.

Surgical complications:

• Damage to the muscles, vital nerves, and blood vessels, during surgery to remove the tumor; injury to unaffected brain tissue during surgery
• Post-surgical infection at the wound site is a potential complication
• Post-operative bleeding in the brain can be a major complication
• Sometimes, removing the tumor can worsen the signs and symptoms in some individuals
• Recurrence of the tumor after surgery may be observed

Chemotherapy side effects depend on the type of chemotherapy medication used and may include:

• Nausea and vomiting
• Hair loss
• Mouth sores
• Loss of appetite
• Diarrhea
• Fatigue
• Increased risk for infections
• Easy bruising
• Infertility

Radiation therapy can cause short-term side effects. It depends on the type used and may include:

• Nausea and vomiting
• Hair loss
• Dryness of mouth; loss of taste
• Headaches
• Fatigue
• Skin color changes; usually darkening of skin on the face and neck may be noted
• Speech and hearing difficulties
• Memory issues
• Seizures

Long-term side effects of radiation therapy (seen after 6 months or beyond) may include loss of memory, impaired brain function, and appearance of symptoms that mimic stroke.

Radiation and chemotherapy may increase the chance of developing other brain and spinal cord tumors/cancers.

How is Extraventricular Neurocytoma Treated?

The treatment modality for Extraventricular Neurocytoma is chosen, depending on the size, location, and stage of the tumor, tumor growth rate, age and health status of the individual. Often, a multidisciplinary team of specialists including neurologists, oncologists, surgeons, radiation therapy experts, and other healthcare professionals are involved in managing the condition.

The treatment measures for Extraventricular Neurocytoma may include:

• Symptomatic treatment may involve the use of antiseizure medications, painkillers, steroids (to reduce inflammation), and administration of anti-depressants

Surgical treatment: Surgery to remove the entire tumor or just part of the tumor depends on several factors including the risk assessment by a neurosurgeon, with respect to the potential injury to nearby brain tissues. It is also considered based on the location, size, and overall health of the individual. A complete removal of the tumor can result in a cure in many patients. Although, in many cases, removal of the tumor offers a lot of surgical challenges to the healthcare providers, due to the complexity of the tumor site involved.

• Craniotomy: It is a surgical procedure wherein a tiny hole is created in the cranium to access and remove the tumor. The main goal of surgery is to remove as much tumor as possible without damaging the surrounding brain tissue
• In some individuals, the tumor is partially removed, so as not to cause brain damage, resulting in unwanted additional symptoms. A partial removal is usually considered in slow-growing grade I benign tumors
• Microsurgery: The surgery is performed using microsurgical techniques, which can help minimize damage to the accompanying nerve. Since the tumor mostly affects the covering around the nerves, it can be completely removed without affecting the nerve in most cases. The following techniques may be employed:
  • Subtotal removal; when the tumor is incompletely removed
  • Near total removal; when most of the tumor is removed and there is very little tumor remnants
  • Total tumor removal; when the tumor is removed completely
• In some cases, embolization of the tumor may be performed, in order to shrink the tumor size, before major invasive procedures are undertaken. In embolization, the blood supply to the tumor is cut-off, resulting in its shrinkage. This also helps reduce blood loss during a surgical resection
• Radiosurgery for individuals who cannot undergo surgery or have recurrent tumors
• Post-operative care is important: One must maintain minimum activity levels, until the surgical wound heals

Surgical procedures to remove brain tumors carry risks, including infection, possible damage to healthy brain tissue, swelling, or possible fluid build-up in the brain.

Radiation therapy: There are a variety of radiation therapy methods that can be used to treat the tumors. Radiation therapy is performed either after removal of the tumor (to destroy any remaining meningioma cells), or in individuals where surgical removal procedure is not an option. Radiation therapy is helpful to reduce the rate of recurrence. It is also recommended for individuals where the tumor is removed partially. Radiation therapy is considered for Extraventricular Neurocytomas based on the tumor locations and incomplete surgical removals.

The types of radiation therapy include:

• Standard external radiation beam therapy using a beam of high-energy X-rays; it is the most common form of radiation therapy used to treat cancers
• 3-dimensional conformal radiation therapy, where 3-d images of the tumor are created using radiological imaging scans to help design appropriate radiation therapy beam size and angles
• Intensity modulated radiotherapy (IMRT): It is a procedure that uses computer-controlled linear accelerators to deliver precise radiation to a malignant tumor
• Stereotactic radiosurgery using Gamma Knife or CyberKnife technique
• Proton radiation therapy: It is a form of external beam therapy using high-energy proton beams to destroy the tumor cells
• Fractionated radiation therapy: It is a good option for individuals whose tumors are too large for radiosurgery, or if the tumor is in a sensitive location. In this therapy, small doses of radiation are administered for a certain set period

Some individuals may experience a few side effects, while others may experience none. These may include fatigue, headaches, hair loss, and scalp irritation. Radiation therapy beams may affect the pituitary gland causing it to dysfunction (bringing about hormonal changes in the body).

Chemotherapy: The response of the tumor to chemotherapy is an important consideration while using this treatment modality. Chemotherapy may not be recommended as a treatment option for treating some tumors.

• Chemotherapy may be beneficial in individuals diagnosed with higher grade tumors. Whether to use chemotherapy as a treatment modality is determined by healthcare provider on case-by-case basis
• Chemotherapy may be administered for those tumors that cannot be effectively treated by surgery or radiation therapy. The administration of some drugs may slow the rate of growth of the tumor

The following chemotherapy agents and methods have been used in higher grade tumors with varying beneficial results:

• Immunotherapy to stimulate an affected individual’s immune system
• Somatostatin analogs which prevent the release of growth hormones
• Hydroxyurea, epidermal growth factor receptor inhibitors, platelet-derived growth factor receptor inhibitors, and vascular endothelial growth factor inhibitors

There are side effects for chemotherapy, which depends upon the type and dose of drugs administered. The common chemotherapy side effects include nausea, vomiting, hair loss, loss of appetite, headache, fever, chills, and weakness.

Clinical trials: In advanced stages of tumor progression, there may be some newer treatment options, currently on clinical trials, which can be considered for some patients depending on their respective risk factors.

Regular observation and periodic checkups to monitor the condition is strongly recommended following treatment. In order to avoid a relapse, or be prepared for a recurrence, the entire diagnosis, treatment process, drugs administered, healthcare recommendations post-treatment, etc. should be well-documented and follow-up measures initiated.

How can Extraventricular Neurocytoma be Prevented?

Presently, there are no specific methods or guidelines to prevent the formation of Extraventricular Neurocytoma. However, if it is associated with a genetic disorder, the following points may be considered:

• Genetic counseling and testing: If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Regular health check-ups might help those individuals with a history of the condition in the immediate family, in order to help diagnose the tumor early

In general, the factors that may help reduce the incidence of brain tumor may include:

• Reducing exposure to ionizing radiation
• Avoiding cigarette smoke inhalation
• Weight loss, in case one is obese or overweight; maintaining a good BMI
• Availing early treatment for infections
• Using safety gear including wearing helmets when playing sports or while riding two-wheelers
• Wearing seatbelts while driving automobiles

According to the U.S. Preventive Services Task Force (USPSTF), currently there is no standard testing protocols available for brain tumor.

Regular medical screening at periodic intervals with blood tests, scans, and physical examinations are mandatory. Often several years of active vigilance are crucial and necessary.

What is the Prognosis of Extraventricular Neurocytoma? (Outcomes/Resolutions)

The prognosis of Extraventricular Neurocytoma (EVN) may vary considerably from one individual to another and is dependent on a set of factors.

• In a majority of individuals, the prognosis is good with complete surgical removal of the tumor. In case of incomplete resections, adjuvant radiation therapy is provided with overall good outcomes
• Factors that adversely affect outcomes include older age of the individual, incomplete tumor excision, and atypical tumors that show increased cell proliferation rates

Some of the EVNs are known to be atypical in nature. Atypical Extraventricular Neurocytoma is an aggressive tumor with high mitotic activity, the presence of atypical features, such as necrosis (tissue death), and elevated tumor vascularity. Such atypical tumors display malignant behaviors, show increased tendency to spread via the CSF, and portend much poorer outcomes.

In general, the prognosis may depend upon several factors, which include: 

• Tumor histology or grade of the tumor: The lower the grade, the better is the prognosis
• Age of the individual: Older individuals generally have poorer prognosis than younger individuals
• Overall health of the individual: Individuals with overall excellent health have better prognosis compared with those with poor health
• The size of the tumor: Individuals with small-sized tumors fare better than those with large-sized tumors
• Location of the tumor is an important prognostic factor: Tumors at certain sites involving the central nervous system are more difficult to surgically excise and remove. They can also cause considerable neurological damage at certain sites in the brain and/or spinal cord. Tumors located near vital structures of the brain have poor prognosis
• Tumors that are slow-growing have better prognosis than rapidly-growing tumors
• Presence of certain genetic abnormalities may result in a rapid progression of tumor growth and development
• Sporadic tumors have generally better prognosis than syndromic tumors; tumors in a background of genetic disorders/syndromes may have additional complications
• The ease of accessibility and surgical resectability of the tumor (meaning, if the primary tumor can be removed completely). This is an important prognostic factor
• Extent of residual tumor in the body following a surgical resection: A complete surgical excision with entire tumor removal presents the best outcome. In some cases, large portions of the tumor may be removed; or, only a small portion for tissue biopsy
• Individuals with bulky disease may have a poorer prognosis
• Involvement of other vital organs may complicate the condition
• Whether the tumor is occurring for the first time or is a recurrent tumor. Recurring tumors have worse prognosis compared to tumors that do not recur 
• Response to treatment and absence of post-operative complications: Tumors that respond to treatment have better prognosis compared to tumors that do not respond to treatment
• Functional neurologic status based on neurological evaluation of the patient: A higher score on the Karnofsky Performance Scale may indicate a more favorable outcome

An early diagnosis and prompt treatment of the tumor generally yields better outcomes than a late diagnosis and delayed treatment.

Additional and Relevant Useful Information for Extraventricular Neurocytoma:

The following DoveMed website link is a useful resource for additional information:

https://www.dovemed.com/diseases-conditions/cancer/