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

• DNET (Dysembryoplastic Neuroepithelial Tumor)
• DNT (Dysembryoplastic Neuroepithelial Tumor)

What is Dysembryoplastic Neuroepithelial Tumor? (Definition/Background Information)

• Dysembryoplastic Neuroepithelial Tumor (DNET) is a type 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
• Dysembryoplastic Neuroepithelial Tumor is a benign and slow-growing brain tumor that usually occurs in children and teens. A majority of the tumors are observed in the supratentorial region of the cerebral cortex (the outer folded area of the cerebrum). Per WHO, DNET tumor is part of a group designated as “neuronal and mixed neuronal glial tumors”
• 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. Dysembryoplastic Neuroepithelial Tumor is described as a mixed glioneuronal tumor
• DNET is a WHO grade I brain tumor, meaning that is designated as “low-grade”. Grade I tumors are the most benign of the tumors. They are slow-growing and are not known to infiltrate into the surrounding tissues. They offer a very high chance for surgery to be curative; and thus, have the best prognosis among all brain tumors with long-term survival being noted
• The cause of formation of Dysembryoplastic Neuroepithelial 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. The risk factors may include the presence of certain genetic disorders such as Noonan syndrome
• The signs and symptoms of Dysembryoplastic Neuroepithelial Tumor depends on the location of the tumor and may include headaches, weakness in arms or legs, and vision and speech problems. In a majority, persistent seizures are noted. DNET may be also associated with memory loss and personality changes; complications may develop during/from the treatment too
• The treatments for Dysembryoplastic Neuroepithelial Tumor may primarily involve surgery and radiation therapy. The prognosis for individuals with Dysembryoplastic Neuroepithelial Tumor depend on a wide variety of factors, including the size of the tumor and overall health status of the individual. In a majority, the overall prognosis is excellent with complete surgical removal of the tumor, since it is a WHO grade I benign tumor

Who gets Dysembryoplastic Neuroepithelial Tumor? (Age and Sex Distribution)

• Dysembryoplastic Neuroepithelial Tumors are rare pediatric tumors that account for only 1% of all neuroepithelial tumors
• The tumor is largely diagnosed in individuals under the age of 20 years; children, teenagers, and young adults are affected. It is rarely observed beyond this age group
• Both males and females are affected, although a slight male predominance is observed
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Dysembryoplastic Neuroepithelial Tumor? (Predisposing Factors)

The following predisposing factors are associated with Dysembryoplastic Neuroepithelial Tumor:

• Noonan syndrome: An inherited disorder that causes an abnormal development of various parts of the body. It is considered as a type of dwarfism
• A family history of the above genetic condition may place one at a higher risk for tumor development
• A higher incidence of tumor cases are reported in young children and adolescents

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 or 2 (NF1 or 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 Dysembryoplastic Neuroepithelial Tumor? (Etiology)

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

The tumor specimen is known to present variable architecture - when observed by a pathologist under the microscope. Based on this, three histological forms of DNET are described:

• Dysembryoplastic Neuroepithelial Tumor, simple pattern: In this histological subtype, only specific glioneuronal element (SGNE) is noted. SGNE refers to patterns of axon bundles that are surrounded by oligodendrocyte-like cells, positioned at 90 degrees to the cortical surface above
• Dysembryoplastic Neuroepithelial Tumor, complex pattern: In this subtype, specific glioneuronal element is noted with multiple glial nodules
• Dysembryoplastic Neuroepithelial Tumor, non-specific pattern: In this subtype, no specific glioneuronal element is noted

Molecular studies on DNET have provided the following observations:

• Absence of IDH and TP53 gene mutations
• Chromosomes 1p or 19q codeletions are not present
• Mutations correlating with the associated genetic disorder, such as Noonan syndrome, if any present, may be identified

The lack of involvement of IDH gene, TP53 gene, and 1p/19q codeletions is useful in differentiating DNET from other brain tumors such as low-grade astrocytomas and oligodendrogliomas.

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 Dysembryoplastic Neuroepithelial Tumor?

The signs and symptoms of Dysembryoplastic Neuroepithelial Tumor (DNET) 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 of DNETs primarily depend on the location and size of the tumor. Many tumors arise from the supratentorial cerebral cortex; and of this, 50-65% are noted in the temporal lobe and 20% in the frontal lobe. Other less common sites in the brain include the brainstem, the basal ganglia at the base of forebrain, the septum pellucidum at the midline of the brain, and the cerebellum.

The commonly observed signs and symptoms include:

• The most prominent symptom is persistent convulsions
• Usually neurological deficits are not observed
• Chronic headaches
• Nausea and vomiting
• Numbness and tingling sensation
• Muscle weakness; loss of strength in the arms of legs
• Neck pain
• Visual impairment such as blurred vision, double vision or poor eyesight
• Hearing impairment or hearing loss
• Speech problems
• 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
• Lack of coordination; unsteadiness and loss of balance (vertigo)
• Dizziness and fainting
• Confusion
• Changes in one’s behavior; personality changes
• Mental impairment
• Memory loss

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 Dysembryoplastic Neuroepithelial Tumor Diagnosed?

A majority of Dysembryoplastic Neuroepithelial Tumors may remain undiagnosed for prolonged periods, if they are asymptomatic and generally slow-growing. The slow development of symptoms may 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. Occasionally, recurrent epileptic seizures and young age of the individual may prompt the healthcare provider to suspect the presence of these tumors.

The diagnosis of Dysembryoplastic Neuroepithelial Tumors 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, if necessary

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:

• Ganglioglioma
• Neuroepithelial cyst
• Pleomorphic xanthoastrocytoma (PXA)
• Taylor cortical dysplasia

Pathological differential diagnosis may include:

• Diffuse low-grade astrocytoma, IDH mutated
• Metastatic cancers to the brain
• Oligodendroglioma, IDH mutated and 1p19q co-deleted
• Additional consideration in children:
  • Desmoplastic infantile astrocytoma
  • Ganglioglioma

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 Dysembryoplastic Neuroepithelial Tumor?

The possible complications associated with Dysembryoplastic Neuroepithelial Tumor (DNET) 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
• Severe loss of memory
• Dementia including personality changes causing a reduced quality of life
• Peritumoral brain edema (PTBE): Presence of fluid around the tumor region in the brain resulting in severe symptoms and complications
• Rarely, the low-grade tumors can transform into high-grade malignancies by undergoing anaplastic transformations. Such tumors are called anaplastic DNETs and these can present additional complications and treatment challenges
• 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
• Sometimes, removing the tumor can worsen the signs and symptoms in some individuals
• Recurrence of the tumor after surgery may be observed; the recurrence rate for DNET is usually low

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 Dysembryoplastic Neuroepithelial Tumor Treated?

The treatment modality for Dysembryoplastic Neuroepithelial Tumor is chosen, depending on the size, location, and stage of the tumor, tumor growth rate, age and health status of the individual. Tumors that are small and slow-growing usually may be observed and no treatment necessitated, based on the healthcare provider’s assessment, specifically on a case-by-case basis. 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 Dysembryoplastic Neuroepithelial Tumor may include:

• Wait and watch approach by the healthcare provider:
  • Observation of the tumors is often recommended in individuals with small-sized tumors, slow-growing tumors, tumors with no significant signs and symptoms, elderly patients, individuals where treatment, such as surgery, may be too risky, and individuals, who do not prefer surgical treatment for a variety of reasons (opting out of surgery through personal preference)
  • Recurring brain scans may be taken to observe the rate of tumor growth; if the tumor is small and growing slowly, then there may be no need for invasive procedures
• 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
• Osteoplastic laminotomy: It is a minimally-invasive procedure to treat spinal cord tumors. The technique also helps minimize post-operative complications and provides increased spinal stability. If necessary, osteoplastic laminotomy may be followed up by a spinal column reconstruction procedure
• Laminectomy: An invasive procedure that is performed to relieve compression on the spinal cord or spinal nerves, caused by the tumors, by widening the spinal canal through removal of the laminae (part of the vertebra)
• 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.

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 Dysembryoplastic Neuroepithelial Tumor be Prevented?

Presently, there are no specific methods or guidelines to prevent the formation of Dysembryoplastic Neuroepithelial Tumor. 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 Dysembryoplastic Neuroepithelial Tumor? (Outcomes/Resolutions)

The prognosis of Dysembryoplastic Neuroepithelial Tumor (DNET) may vary considerably from one individual to another and is dependent on a set of factors.

• The prognosis is generally favorable to excellent in individuals with DNET following surgery, as these are low-grade tumors
• The tumor is known to cause drug-resistant epilepsy. In many cases, a partial to complete tumor resection can result in seizure control
• In the rare case of malignant transformations to high-grade tumors, the prognosis can significantly worsen

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 Dysembryoplastic Neuroepithelial Tumor:

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

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