Brain Tumors in Dogs

Definition

A brain tumor is any intracranial tumor created by abnormal and uncontrolled cell division, normally either found in the brain itself, in the cranial nerves, in the brain envelopes (meninges), skull, or pituitary and pineal gland.  Primary brain tumors (those arising form the cells of the brain and it’s lining) in dogs include meningioma, glioma, choroid plexus papilloma, pituitary adenoma or adenocarcinoma, and others.

Secondary or metastatic brain tumors originate from malignant tumors (cancers) located primarily in other organs and metastasize (spread) to the brain.  These include hemangiosarcoma, mammary carcinoma and melanoma. These tumors carry a very poor prognosis because they have already spread through the body.

Brain tumors are not uncommon in older dogs; however, there is an increasing incidence of brain tumors occurring in younger dogs. Brain tumors vary widely in their level of malignancy and some can be treated quite effectively. The most common forms of brain tumors are outlined below.

Causes
While there are no definitively identified causes of brain tumors in dogs, we can probably learn from the suspected causes of brain tumors in humans.

These include:

·    Genetic syndromes
·    Radiation exposure
·    Immunological Factors – several large studies have reported that gliomas are less likely to occur in people with allergies and in people who have had infections with common viruses such as that which causes chicken pox.
·    Serious head injuries
·    Pesticides
·    Solvents
·    Electromagnetic fields
·    Nitrosamines that may be created in the digestion of processed meats such as hot dogs, bacon, ham, and sausages.

Risk Factors

Adult dogs of several related brachycephalic (short-nose) breeds such as Boxers, English Bulldogs, and Boston Terriers, are often cited as having the highest incidence of brain tumors among domestic animals. These breeds are especially prone to glial tumors, including unclassified gliomas.  A more recent study of 97 dogs indicated that Golden Retrievers also have a high incidence of brain tumors, especially meningiomas.

Age also appears to be a risk factor, with 95% of canine meningiomas occurring in dogs over 7 years old.

Symptoms

The symptoms associate with brain tumors vary widely but are generally caused by compressing of or invasion into the brain. The onset of symptoms may occur very suddenly or may progress slowly over time.

Typical signs include:  unsteadiness or staggering, forgetting commands or failure to recognize familiar people, unexplained aggressiveness or puppy-like behavior, development of obsessive behaviors, loss of bladder control, change in appetite, loss of hearing or sight, seizures, labored breathing, or whimpering or head shaking, loss of bladder control, change in appetite, loss of hearing or sight, seizures, labored breathing, or whimpering or head shaking.

The resulting symptoms of a brain tumor relate directly to the area of the brain affected by the tumor and are not specific to the tumor itself: any disease affecting that area of the brain could produce similar signs. Clinical signs typically associated with each area of the brain are listed below:

The Forebrain – The forebrain is responsible for “thinking,” behavior, and final integration of sensory information. Tumors in the forebrain are associated with the following symptoms:

·    Behavioral abnormalities such as loss of learned behavior or depression
·    Increased or decreased appetite and thirst
·    Constant pacing or circling,
·    Decreased awareness and vision on one side of the body causing mis-judgement of openings to doorways and bumping of one side of the body.
·    Sometimes affected animals behave as if they are in pain.
·    Seizures are a classic sign of forebrain disease and in fact, new onset of seizures is the most common presenting sign of animals with tumors of the forebrain. These seizures can occur alongside any of the other signs listed above, or may occur as the only abnormality. Whenever a dog or cat that is greater than five or six years of age has a new onset of seizures, a brain tumor is a possible differential and ruled out by a full diagnostic workup.

The Brainstem – The brainstem plays various vital roles including regulation of motor function (the ability to walk), the level of wakefulness, and the respiratory and cardiovascular systems. The sense of balance originates in the brain stem. The brain stem is also the source of the nerves that control movement of and sensation to the face, the eyes, the throat, larynx and tongue, and the muscles of mastication. Tumors in the brainstem can be rapidly fatal if, for example, they affect the control of breathing, but typically the first signs of brainstem disease are a loss of balance (vestibular signs), and weakness on one side of the body. There can be a wide variety of additional signs such as difficulty swallowing, change in voice and inability to move the eyes. Further progression of the signs can result in paralysis, coma and death.

Vestibular disease symptom include:

·    Head tilt
·    Leaning and falling to the side of the head tilt
·    Drunken gait with loss of balance (ataxia)
·    Circling to the side of the head tilt.
·    Involuntary flicking of the eyes (nystagmus)
·    Loss of appetite, vomiting.
·    Abnormal eye position (strabismus)

The Cerebellum – The cerebellum controls coordination of movements and interacts closely with the vestibular system to control balance and posture.

Signs of cerebellar disease include:

·    Uncoordinated gait characterized by dramatic goosestepping (hypermetria)
·    Head tremors that are worst when the animal is intent on something (for example, food) but disappear when the animal is relaxed (intention tremors)
·    Swaying of the trunk
·    Wide based stance
·    Sometimes there can be vestibular signs such as a head tilt
·    The animal’s strength remains normal.

Diagnosis

Astrocytomas are probably the most common neuroectodermal brain tumor in dogs. They are usually found in adult dogs, but they have been reported in dogs less than 6 months old as well. They are common in brachycephalic (short nose) breeds but can be seen in any breed. The cells tend to be arranged around blood vessels.

Choroid plexus papilloma are common tumors in dogs, with reported frequency similar to that of glioblastomas (~12% of neuroglial tumors). Due to their cell of origin, they tend to arise within the ventricular system and can block drainage of CSF, thus a small tumor can cause very severe neurologic signs. These tumors are reddish, papillary growths that may bleed. Histologically, they are well defined, grow by expansion, and have a granular papillary appearance. In both benign and malignant variants of choroid plexus papillomas, dissemination to other areas of the brain or spinal cord via the CSF pathways may occur following exfoliation. Obstructive hydrocephalus may occur. Meningeal carcinomatosis may follow spread of the tumor in the subarachnoid space. Choroid plexus tumors are seen as well-defined, hyperdense masses with marked, uniform contrast enhancement on CT scans. Marked enhancement, potentially including hemorrhage and mineralization, is also seen with MRI. Choroid plexus papillomas have no apparent predilection for brachycephalic.

Ependymomas originate from the epithelium lining the ventricles and central canal of the spinal cord. They are rare, but have been reported most frequently in brachycephalic breeds. The gray to reddish, soft, lobular masses tend to invade the ventricular system and meninges, which may result in obstructive hydrocephalus. Mestastases within the CSF system may be observed. Ependymomas of the fourth ventricle may encircle the brain stem. Both epithelial and fibrillary varieties have been described.

Gangliocytomas are rare intracranial tumors reported in adult dogs of several breeds. Histologic findings include mature, neuronal-like cells with multiple processes, a central nucleus, and a nucleolus. Neuroblast-like immature cells may also be seen, and occasionally, newly formed myelin sheaths. They seem to be seen most often in the cerebellum.

Suprasellar germ cell tumors are located dorsal to the sella turcica at the base of the brain. They are often intimately associated with the pituitary gland, which may be trapped within or replaced by the germ cell tumor. They are thought to result from extensive migration of germ cells during embryogenesis. Neurologic signs may be acute in onset and may include lethargy; depression; bradycardia; dilated, non-responsive pupils; ptosis; visual deficits; and blindness. Affected animals are usually 3-5 yr old; Doberman Pinschers may be at higher risk than other breeds. Some germ cell tumors have been misdiagnosed as pituitary tumors or craniopharyngiomas.

Glioblastoma multiforme, considered to be equated with the more malignant forms of astrocytomas, has been reported with varying frequency in dogs. In one study, the incidence was 12% of 215 neuroglial tumors. Most are large and found in the cerebrum. They are locally invasive and destructive, well vascularized, and often contain necrotic zones. Glioblastomas and are most common in brachycephalic breeds.

Glioma – These tumors arise from the supporting cells of the brain and include astrocytomas, oligodendrogliomas, glioblastoma multiforme and ependymomas. They are common in certain breeds of dog, in particular breeds with short noses (brachycephalic breeds) such as the Boxer, the Boston terrier, and the French and English bulldog. Gliomas can range in malignancy from low grade and slow growing, to high grade, poorly differentiated malignant tumors (known as glioblastoma multiforme).

Hamartomas are formed by disorderly overgrowth of tissues normally present at a site. They are focal malformations resembling neoplasms and have been reported only rarely in dogs, usually as a subclinical finding.

Hematogenous metastatic brain tumors commonly originate from extracranial sites. In dogs, they often develop from carcinomas of the mammary glands, thyroid, bronchopulmonary epithelium, kidneys, chemoreceptor cells, nasal mucosa, squamous epithelium of the skin, prostate, pancreas, adrenal cortex, and salivary glands. Common sarcoma metastases in dogs include fibrosarcomas, hemangiosarcomas, lymphosarcomas, and melanoblastomas. Brain metastases may accompany intramedullary spinal cord metastasis in dogs with lymphosarcomas or hemangiosarcomas. Most CNS lymphomas, especially in dogs, are one part of a multicentric disease, with extensive infiltration of the choroid plexus and leptomeninges a common finding. Neoplastic angioendotheliomatosis in dogs is thought to be an angiotropic lymphoma, possibly of the B-cell line. Extraneural tumor cells sometimes localize in the meninges (eg, meningeal carcinomatosis), often in association with intestinal carcinoma or mammary adenocarcinoma.
Intracranial intra-arachnoid cysts have been reported in dogs. These rare malformation tumors seem to develop most often in the quadrigeminal cistern. Of the 6 dogs in one report, 3 were 1 yr old, 4 were males, and 5 of the 6 dogs weighed 11 kg. One dog had additional developmental anomalies (abnormal corpus callosum and block vertebrae). On CT scans and MRI the cysts were extra-axial, had sharply defined margins, contained fluid isodense to CSF, and did not show contrast enhancement.

Malformation tumors, including epidermoid and dermoid cysts and teratomas, originate from heterotopic tissue and are rare tumors in dogs. They typically lie close to embryonal lines of closure. Epidermoid and dermoid cysts result from inclusion of epithelial components of embryonal tissue at the time of closure of the neural tube. They reportedly have a predilection for young dogs (e.g, 3-24 mo old), although cysts have been found in older dogs.

Malignant histiocytosis, which has focal and diffuse forms, is rarely reported in dogs.

Medulloblastomas are highly malignant, uncommon neuroectodermal canine tumors that almost always develop in the cerebellum. The tumors tend to bulge into the fourth ventricle, often replacing part of the cerebellar vermis and compressing the midbrain rostrally and the brain stem ventrally. They may infiltrate the meninges, metastasize within the CSF pathways, and cause obstructive hydrocephalus. While most cases are seen in young dogs, a cerebellar medulloblastoma with multiple differentiation was recently noted in a 4-yr-old Border Collie.

Meningioangiomatosis is a rare, benign malformation of CNS blood vessels, characterized by proliferation of the vessels and spindle-shaped, perivascular meningothelial cells in the cerebral cortex and brain stem of juvenile and adult dogs.

Meningioma is the most common primary brain tumor in dogs (and in humans) probably the cause of most seizures in dogs over 6 years old.  These tumors can also occur in dogs under 6 months old.  It arises from the arachnoid mater of the meninges (the membranes that line the skull and vertebral column, effectively surrounding the central nervous system which consists of the brain and spinal cord) rather than the cells of the brain itself. As such, meningiomas are not strictly brain tumors, but tend to be grouped with them because they arise within the cranial cavity and compress or invade the brain. These tumors occur more commonly in long nosed (doliochocephalic) breeds of dog, such as the Golden retriever and collie.

Meningiomas are usually relatively slow growing and amenable to treatment, although more malignant forms do occur.  Because the meningioma is a tumor of the meninges (the outer membranes) these tumors grow from the skull inward. This makes them much more surgically accessible (depending on their size).

Meningiomas rarely metastasize outside the brain, but may extend into paranasal regions and lungs or be seen as primary extracranial masses as a result of embryonic displacement of arachnoid cells or meningocytes. The reason they are a problem is that there is a limited amount of space within the skull. The brain and its bath of cerebrospinal fluid takes up almost all the room and when a tumor begins to grow, the brain tissue is compressed. Inflammation can result leading to more swelling and soon nerves of the brain are damaged.
Meningeal sarcomatosis are sarcomas which cause diffuse thickening of the meninges; extensive hemorrhages are common. These rare tumors tend to infiltrate nervous tissue and run along blood vessels. Cell types include lymphoid, plasmacytoid, mature plasma cells, immunoblastic cells, and multinucleate giant cells.

Oligodendrogliomas are common tumors in dogs, particularly in brachycephalic breeds. Most grow by infiltration and destroy invaded tissue.
Pituitary adenoma or adenocarcinoma – The pituitary gland lies beneath the forebrain and is connected by a stalk to an area of the brain called the hypothalamus. Pituitary tumors (adenomas) are common in dogs, with an apparent predilection for brachycephalic breeds. They cause hyperadrenocorticism (Cushing’s disease). Usually they do not cause any other neurologic signs and remain outside the actual cranial cavity. However, in some cases they expand rapidly and compress the overlying brain. These tumors are known as pituitary macroadenomas, or adenocarcinomas (if more malignant). There are several other more unusual tumor types that may be seen in this area such as the suprasellar germ cell tumor.

Primary skeletal tumors do not typically cause neurologic signs. Multilobular osteochondroma originates in the flat bones of the skull, usually in older medium- or large-breed dogs and appears as a firm, fixed mass. It may erode the cranium and compress, rather than infiltrate, underlying brain tissues. Radiographically, the tumor contains nodular or stippled areas of mineralization, resulting in a characteristic “popcorn ball” appearance. Local recurrence and metastasis are common. Vertebral osteochondroma is the spinal cord counterpart.

Vascular malformations are considered developmental lesions rather than true neoplasms and are uncommon in dogs. They may be located in the cingulate gyrus, pyriform-hippocampal area of the temporal lobe, basal ganglia, cerebellum, occipital lobe, or septum pellucidum and fornix and comprise variable combinations of arteries, veins, and capillaries. The vessels tend to be dilated, sinusoidal in
Whenever there are neurological changes in a dog, especially in those older than 5 years, a veterinarian should be consulted to rule out a brain tumor.

Diagnosis

Whenever there are neurological changes in a dog, especially in those older than 5 years, a veterinarian should be consulted to rule out a brain tumor. To accurately assess your dog’s condition, the following diagnostic methods will likely be performed by your veterinarian:
Complete physical and neurological examination to identify any other health problems and to localize the neurological signs to a particular area of the brain.

Routine blood work to rule out a systemic problem and assess the anesthetic risk better able to identify fluid build up, swelling, cysts, bleeding ad other subtle soft tissue changes inside the brain and therefore an MRI is a better able to identify fluid build up, swelling, cysts, bleeding ad other subtle soft tissue changes inside the brain and therefore an MRI is a better tool, especially if the dog has signs of brain stem or cerebellar disease, or if it is a breed of dog that is predisposed to gliomas, such as the Boston terrier.

A specific tumor type can be suspected from its appearance on a CT or MRI, but can only be definitively identified by taking a sample of the tumor, either at surgery or by biopsy. Indeed, masses caused by infections (for example abscesses or fungal granulomas) can look like brain tumors on brain images . It is therefore vital that a sample of the tumor is taken and examined with a microscope to identify the cell types involved. Not only will this identify the tumor type, but it will also grade the malignancy of the tumor. Many neurologists, particularly those working in university teaching hospitals, routinely perform CT guided biopsies of tumors.

Treatment

Brain tissue cannot regenerate, and therefore removal of normal brain tissue surrounding a tumor can have unacceptable repercussions for the patient.

Surgery
The goal of surgical removal of a brain tumor is either to cure the disease by complete removal (which only occurs rarely) or to alleviate the clinical signs by decompressing the brain. This can be lifesaving if the mass is very large. Brain tumors can be removed surgically if they are located in a site that can be reached safely. There are two considerations for this, firstly, how close is the tumor to the surface of the brain and secondly, how close is the tumor to critical areas of the brain. Tumors of the brainstem pose problems on both of these fronts. They are difficult to access, because of the thick bone surrounding them, and their location close to the floor of the cranial cavity, and the brainstem does not have much redundancy of function so damaging it could be fatal. In contrast, there is much more functional redundancy in the forebrain: you can resect certain parts of the forebrain without long-term effects. Meningiomas tend to be located on the surface of the brain and are therefore the best candidates for surgical removal. Gliomas are more difficult to remove because they lie deep within the substance of the brain.

Radiation Therapy

Radiation will slow the rate of growth of most types of brain tumor.  There are many different schedules used for radiation treatments: some weekly, some daily, some on alternate days.  Radiation can be done instead of surgery or in combination with surgery and what protocols yield the longest survival times is not clear. Currently, the philosophy on treatment is that a combination of surgery plus radiation yields the best results for dogs.

The full dose of radiation is administered in fractions, the number and timing of which vary between veterinary institutions. Because the brain cannot tolerate large doses of radiation, the total dose is limited and side effects are usually minimal. It is common to see a change in hair color in the area irradiated, and other side effects depend on the area that is being irradiated. For example, if the ear is included in the radiation field, there may be some irritation of the ear canal (rather like an ear infection) that will resolve once the course of radiation is completed. In order to complete a course of radiation safely, the animal must be healthy enough to have a general anesthetic for each dose of radiation. Therefore, if the animal has a very large mass, it is preferable to surgically remove as much of it as possible first, thus decompressing the brain and enabling the animal to survive the course of radiation. The cost of radiation varies geographically, but you can expect to pay several thousands of dollars for this treatment.  Radiation is currently the treatment of choice for gliomas.

Chemotherapy

The brain is protected from circulating substances in the blood by a barrier called the blood brain barrier (BBB) and this barrier limits the effectiveness of chemotherapeutic agents. As a result, chemotherapy has not been advocated all that often for treatment of canine and feline brain tumors and we have very little if any data on the efficacy of such drugs in our patients. However, some drugs, such as the alkylating agents lomustine (CCNU), carmustine (BCNU) and a more recently developed drug, temozolomide, can cross the BBB and may be effective when treating gliomas. Recently, temozolomide has shown to be effective for this purpose in people although there are no data in dogs as yet. Chemotherapy is a reasonable alternative when treating a glioma if radiation is not an option. Drugs like CCNU can be administered once every three weeks in tablet form at home, by the owner. There are dose limiting side effects on the liver and bone marrow and so these must be monitored closely by the attending veterinarian while receiving treatment. Recently, drugs such as 5-hydroxyurea have been used to treat meningiomas, but as yet there are no data on the efficacy of this approach.

Palliative Treatment

If none of the above therapies are an option, it is possible to treat the symptoms caused by a brain tumor.  For seizures caused by brain tumors, dogs can be place on an anti-seizure drug such as Phenobarbital or potassium bromide. Tumors tend to cause the accumulation of fluid (edema) around them and this can be treated with a corticosteroid such as prednisone. As many of the clinical signs can be due to the edema, some animals show a dramatic improvement within 24 hours of starting treatment with prednisone.  In one study of dogs with meningioma, the tumor’s blood volume decreased by 21% within 24 hours of beginning prednisone. This response is often short lived as the tumor itself is not being treated by this drug, but can certainly give dogs some good quality time.

Prognosis

Unfortunately, most brain tumors cannot be cured, but many can be treated. The primary goal of treatment is to extend a good quality of life for as long as possible.

There is little solid data on the outcome of different tumor types because many dog owners do not have the necessary diagnostic testing performed to determine the exact type of tumor that afflicts their dog. However, there are several studies looking at the effectiveness of radiation for treating brain tumors. As a general rule, median survivals of around a year are obtained when a brain tumor is irradiated. Better survivals may be obtained when treating meningiomas with surgery followed by radiation.  There are some general guidelines that can be applied to individual animals when considering prognosis:

·    The more severe the signs, the worse the outcome
·    The larger the tumor the worse the outcome
·    Supratentorial tumors (tumors of the forebrain) have a better prognosis than infratentorial tumors (tumors of the brainstem and cerebellum).
·    Radiation therapy does prolong lifespan in most cases
·    Meningiomas have a better outcome than tumors that lie within the brain (e.g. gliomas)

Disclaimer: The information contained in this article is intended solely for informational purposes and not for the purpose of rendering medical or veterinary advice.