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

• Anaplastic PXA
• APXA (Anaplastic Pleomorphic Xanthoastrocytoma)

What is Anaplastic Pleomorphic Xanthoastrocytoma? (Definition/Background Information)

• An Anaplastic Pleomorphic Xanthoastrocytoma (APXA) 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
• Anaplastic Pleomorphic Xanthoastrocytoma is an extremely rare brain tumor that arises from the star-shaped glial cells called astrocytes (a type of brain cells). The tumor is a type of glioma or astrocytic neoplasm. It is referred to as the aggressive and malignant variant of pleomorphic xanthoastrocytoma (PXA). According to research, between 9-20% of the Anaplastic Pleomorphic Xanthoastrocytomas develop from the malignant transformations of PXAs
• Anaplastic Pleomorphic Xanthoastrocytomas are categorized as WHO grade III brain tumors. Grade III tumors are high-grade, malignant and more infiltrative than lower-grade tumors; they have a tendency to recur as an even higher grade tumor following treatment. In a majority of cases, the tumor is diagnosed in children and young adults. APXA commonly originates in the cerebrum of the brain, especially in the temporal and parietal lobe. Per WHO, the tumor is part of a group designated “other astrocytic tumors”
• The cause of formation of Anaplastic Pleomorphic Xanthoastrocytoma 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 some cases, the risk factors for tumor formation include the presence of certain genetic disorders such as neurofibromatosis and familial melanoma-astrocytoma syndrome
• The signs and symptoms of Anaplastic Pleomorphic Xanthoastrocytoma depend on the location of the tumor. Individuals may experience headaches, nausea and vomiting, weakness in different parts of the body, vision and speech disturbances. Epileptic seizures are noted in many individuals. Large-sized tumors may compress adjacent brain tissue resulting in complications. APXA may also undergo further transformations to develop into higher-grade malignant tumors
• The treatment modalities for Anaplastic Pleomorphic Xanthoastrocytoma may include surgery, radiation therapy, and rarely, chemotherapy. The overall prognosis is determined by a wide variety of factors, such as age of the individual, tumor size, overall health status, and one’s response to treatment, since it is a malignant tumor. In general, the prognosis is unfavorable

Who gets Anaplastic Pleomorphic Xanthoastrocytoma? (Age and Sex Distribution)

• Anaplastic Pleomorphic Xanthoastrocytomas constitute much less than 1% of all brain tumors, and is an extremely uncommon tumor type
• These tumors generally develop in children and young adults. Most cases are observed in the age groups 1-10 years and 21-30 years
• Occasionally, they may be seen in older individuals
• Both and males and females are affected, and no preference is noted
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Anaplastic Pleomorphic Xanthoastrocytoma? (Predisposing Factors)

The following predisposing factors are associated with Anaplastic Pleomorphic Xanthoastrocytoma:

• Presence of pleomorphic xanthoastrocytoma (PXA)
• Hereditary cancer syndromes that include:
  • Familial melanoma-astrocytoma syndrome
  • Neurofibromatosis types 1 or 2 (NF1 or NF2)
• A family history of the above genetic conditions may place one at a higher risk for tumor development
• A higher incidence of tumor formation is noted in children and young adults

Typically, 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
  • Nevoid basal cell carcinoma syndrome
  • 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 Anaplastic Pleomorphic Xanthoastrocytoma? (Etiology)

The exact cause of development of Anaplastic Pleomorphic Xanthoastrocytoma (APXA) is not well-understood. The tumor is known to develop sporadically or spontaneously in the brain. Research scientists believe that the cause may involve a combination of several factors including genetic, environmental, and occupational factors.

• In some individuals, grade II pleomorphic xanthoastrocytomas may undergo anaplastic changes over time, to develop into Anaplastic Pleomorphic Xanthoastrocytomas that are grade III malignant tumors. On tissue biopsy studies, such tumor shows more cytologic anaplastic features
• In a large number of cases, BRAF gene mutations are observed. It is said that the BRAF-V600E gene mutation is noted in many APXA tumors
• APXA is also associated with genetic conditions such as neurofibromatosis and melanoma-astrocytoma syndrome

In general, it is known that cancers 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 Anaplastic Pleomorphic Xanthoastrocytoma?

The signs and symptoms of brain tumors 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 Anaplastic Pleomorphic Xanthoastrocytoma (APXA) primarily depend on the location and size of the tumor in the brain. APXA most commonly occurs in the superficial meningocerebral location (cerebrum) with a preference for the temporal and parietal lobes; it is also seen in the cerebral cortex. Occasionally, the tumor may arise from the ventricles of the brain (fluid-filled spaces).

The signs and symptoms may include:

• The tumors are infiltrative and aggressive
• Headaches that may increase in intensity and be persistent
• 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)
• Damage to peripheral nerves
• Tremors
• Seizures or convulsions that may be any of the following types: Seizures are the most common symptoms observed
  • Myoclonic seizures
  • Grand mal (tonic-clonic) seizures
  • Sensory seizures
  • Complex partial seizures
• Increased intracranial pressure may be observed if there is obstruction of the cerebrospinal fluid (CSF) drainage, when the ventricular system is affected. This may result in nausea, vomiting, headaches, and 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 tumors are single; 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 Anaplastic Pleomorphic Xanthoastrocytoma Diagnosed?

The tumors may be detected when there is a sudden worsening of the symptoms prompting the healthcare provider to perform radiological studies of the brain and/or spinal cord. However, reports inform that it is very difficult to diagnose Anaplastic Pleomorphic Xanthoastrocytoma, unless the healthcare provider has a high degree of suspicion for this specific tumor type.

The diagnosis of Anaplastic Pleomorphic Xanthoastrocytoma may involve the following tests and examinations:

• Complete physical examination with thorough evaluation of the individual’s medical history (including family history of any genetic disorder)
• 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 head and neck
  • Computerized tomography (CT) scan of the head and neck region; CT with contrast - the scans may reveal calcifications
  • Magnetic resonance imaging (MRI) scan of the central nervous system (brain and spine); 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, if necessary

Tissue biopsy: A biopsy of the affected region 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 (both radiological and pathological) to eliminate other conditions or tumor types may be considered, before arriving at a definitive diagnosis. These may include:

• Ganglioglioma
• Giant cell glioblastoma
• Glioblastoma
• Malignant fibrous histiocytoma
• Pilocytic astrocytoma

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 Anaplastic Pleomorphic Xanthoastrocytoma?

The possible complications associated with Anaplastic Pleomorphic Xanthoastrocytoma (APXA) include:

• Emotional and mental stress for both the patients and the caretakers, due to the diagnosis and treatment of a brain tumor
• Hydrocephalus: When the tumor obstructs the free flow of cerebrospinal fluid in the brain, it can cause a condition known as hydrocephalus. This can result in lethargy, irritability, nausea and vomiting, loss of balance, seizures, urinary incontinence, and growth delays, among other symptoms
• Large undetected tumors can severely affect brain function and be disabling or even life-threatening, due to mass effect/compression of surrounding tissue
• 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
• Occasionally, APXA may undergo malignant transformations to develop into a glioblastoma, which is an even higher grade (grade IV) and more aggressive tumor
• Malignant tumors may spread (metastasize) to other sites of the body leading to severe 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; malignant tumors often have very high recurrence rates

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 Anaplastic Pleomorphic Xanthoastrocytoma Treated?

The treatment modality for brain tumor is chosen, depending on the type, 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 Anaplastic Pleomorphic Xanthoastrocytoma may include:

• Symptomatic treatment may involve the use of antiseizure medications, painkillers, steroids (to reduce inflammation), and administration of anti-depressants
• Placement of ventriculoperitoneal (VP) shunt: It is an invasive procedure that involves the use of a medical device called a VP shunt. The device is placed in the ventricles of the brain to treat hydrocephalus, and thus helps relieve excess CSF pressure on the brain

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.

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 is reportedly not an effective modality in treating Anaplastic Pleomorphic Xanthoastrocytoma. However, the healthcare provider will determine if chemotherapy should be considered as a treatment option on a case-by-case basis.

• 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 certain advanced stage tumors, 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 Anaplastic Pleomorphic Xanthoastrocytoma be Prevented?

Presently, there are no specific methods or guidelines to prevent the formation of Anaplastic Pleomorphic Xanthoastrocytoma. 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 and 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 to minimize the risk for head/body injury

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 Anaplastic Pleomorphic Xanthoastrocytoma? (Outcomes/Resolutions)

The prognosis of Anaplastic Pleomorphic Xanthoastrocytoma (APXA) may vary from one individual to another and is dependent on a set of factors.

• The prognosis of Anaplastic Pleomorphic Xanthoastrocytoma is generally poorer than pleomorphic xanthoastrocytoma, which is the benign variant of APXA. The 5-year survival is between 40% to 50% for individuals with APXA
• In case of transformation of APXA to even higher-grade tumors, such as glioblastomas; then, the overall prognosis is much worse

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
• Stage of tumor: With lower-stage tumors, when the tumor is confined to site of origin, the prognosis is usually excellent with appropriate therapy. In higher-stage tumors, such as tumors with metastasis, the prognosis is poor
• 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
• Metastatic spread: Spread of the malignancy to other body sites portrays a poorer prognosis
• 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
• Progression of the condition makes the outcome worse
• Functional neurologic status based on neurological evaluation of the patient: A higher score on the Karnofsky Performance Scale may indicate more favorable outcomes

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 Anaplastic Pleomorphic Xanthoastrocytoma:

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

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