Brain Tumors in Dogs and Cats
Cancer affecting the brain is not uncommon in older dogs and cats, although the need for advanced imaging of the brain (such as magnetic resonance imaging, or MRI) in order to detect a brain tumor means that they frequently go undiagnosed. There is also a concerning trend for brain tumors to arise in young dogs of certain breeds, such as the Boxer or the Boston terrier. Developing a brain tumor has serious implications and many owners feel helpless when such a diagnosis is made for their pet. However, these tumors vary widely in their level of malignancy and some can be treated effectively. Unfortunately, there is still a lot that we do not yet know about how different types of brain tumor behave in dogs and cats, and this can make it difficult to advise owners as to the best form of treatment for their pet. This web page provides information on what we do know about the diagnosis, treatment and prognosis of different types of brain tumor and describes ongoing research efforts at North Carolina State University College of Veterinary Medicine.
What is a brain tumor?
Strictly speaking, the term brain tumor simply means a mass in the brain. However, it is commonly used to describe a cancerous (or neoplastic) mass inside the cranial cavity (figure 1). Brain tumors may be primary, arising from the cells of the brain and its lining (figure 2), or secondary, arising elsewhere and spreading to the brain.
Figure 1: Illustrations of the major cell types that give rise to brain tumors in dogs and cats.
Figure 2: The image on the left shows how the brain is divided into supra and infratentorial regions. The different divisions of the brain are shown in the image on the right.
Primary brain tumors seen in dogs and cats include meningioma, glioma, choroid plexus papilloma, pituitary adenoma or adenocarcinoma, and others.
Meningioma – This is the most common primary brain tumor in dogs and cats (and in humans). It arises from the arachnoid mater of the meninges (the membranes that line the brain, figure 2) 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. Figure 3 is a MRI of a meningioma. These tumors occur more commonly in long nosed (doliochocephalic) breeds of dog, such as the Golden retriever. Meningiomas are usually relatively slow growing and amenable to treatment, although more malignant forms do occur.
Figure 3: Sagittal MRI of the brain of an 8 year old female German Shepherd dog. The dog presented to its veterinarian because she had a seizure. The image of the left is a T1 weighted image after intravenous contrast agent has been adminstered. The contrast agent leaks out of abnormal blood vessels, such as those found in tumors, causing the tumor to ‘light up’ on MR images. The tumor can be seen as a lighter colored (contrast enhanced), well encapsulated mass in the olfactory bulb and frontal cortex of the brain (arrowhead). This appearance is typical of a meningioma and this diagnosis was confirmed when the tumor was removed surgically. The image on the right is a T2 weighted image of the same dog. On this type of image, fluid shows up white and it shows clearly how fluid (edema) tends to accumulate around a tumor (arrows). This dog was treated by surgical removal of the tumor followed by radiation, and is currently doing well.
Glioma – These tumors arise from the supporting cells of the brain (figure 2) 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. Figure 4 shows a MRI of a glioma. Gliomas can range in malignancy from low grade and slow growing, to high grade, poorly differentiated malignant tumors (known as glioblastoma multiforme).
Figure 4: Transverse T1 weighted MRI of a 6 year female old Boxer. This dog developed increased thirst, a change in personality and seizures. A large cystic tumor is present in the thalamus. Intravenous contrast agent has been administered highlighting the tumor (arrow). The tumor itself has produced fluid making a cyst (*) within the brain. The location of the tumor, within the substance of the brain, rather than on the surface, makes a glioma the most likely diagnosis. A CT guided biopsy was performed both to obtain a diagnosis, and to remove the excess free fluid from the cystic structure. The biopsy diagnosis was an oligodendroglioma (a type of glioma) and the excess fluid was removed without problem. The dog is currently being treated with chemotherapy.
Choroid plexus papilloma – Tumors of the choroid plexus (figure 2) are relatively common in dogs. 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. Figure 5 shows a CT scan of one of these tumors.
Figure 5: Transverse contrast enhanced CT image of the brain of a 5-year-old male mixed breed dog. There is a large contrast enhancing mass (arrow) lying in one of the lateral ventricles causing obstruction of cerebrospinal fluid drainage. As a result, the other lateral ventricle (V) is dilated. A sample of the tumor was taken by CT guided biopsy and confirmed the diagnosis of choroid plexus papilloma.
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 and cause hyperadrenocorticism (Cushing’s disease). Usually they do not cause any other neurologic signs and remain outside the actual cranial cavity. In some cases, however, they expand rapidly and compress the overlying brain. These tumors are known as pituitary macroadenomas (figure 6), 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.
Figure 6: Transverse contrast enhanced CT image of the brain of a 7-year-old male Labrador Retriever who developed non-specific pain and profound depression. A large contrast enhancing mass can be seen lying on the floor of the cranial cavity and compressing the overlying brain (arrow). The location and appearance of the mass is consistent with a pituitary mass. The diagnosis of a pituitary adenocarcinoma was confirmed at necropsy.
Others – There are many other forms of brain tumors that can be encountered more rarely.
Secondary brain tumors
Secondary tumors represent spread (metastasis) of another tumor to the brain from elsewhere in the body. Examples of tumors that may spread to the brain include hemangiosarcoma, mammary carcinoma and melanoma. These tumors carry a very poor prognosis because they have already spread through the body. It is routine practice to take radiographs of the thorax and even to ultrasound the abdomen to check there is no evidence of cancer elsewhere in the body whenever a diagnosis of a brain tumor has been made or is suspected.
Brain tumors cause signs by compressing or invading the brain. The resulting signs relate directly to the area of the brain affected and are not specific to a tumor: any disease affecting that area of the brain could produce similar signs. As a general rule, brain tumors cause progressive signs in older animals. Signs may start very suddenly or quite insidiously, and they can wax and wane in severity.
The Forebrain – The forebrain is responsible for “thinking,” behavior, and final integration of sensory information. Tumors in the forebrain may therefore cause:
- Behavioral abnormalities such as loss of learned behavior and depression
- Increased or decreased appetite and thirst
- Constant pacing or circling
- Decreased awareness and vision on one side of the body, causing misjudgement 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 (figure 7). 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.
Figure 7: This is Kasey, a 10-year-old female Golden retriever. She has lost muscle mass on one side of her head (arrow) due to a trigeminal nerve root tumor. The trigeminal nerve provides sensation to the face and motor function to the muscles of mastication. Growth of the tumor gradually compresses the nerve causing the loss of muscle mass and loss of sensation. Eventually the tumor gets large enough to compress the brain. Kasey lived happily for 15 months with no special treatment of her tumor.
Vestibular signs 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 and 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 (i.e., 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
A brain tumor should be suspected whenever there is new onset of neurological signs in an animal older than 5 years. It is important to understand, that with rare exceptions, brain tumors are tumors of the soft tissues of the brain and they cannot be seen on radiographs of the skull. The brain can be imaged using magnetic resonance imaging (MRI) or computed tomographic (CT) scans. The following diagnostic steps are recommended:
- 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
- Thoracic radiographs to check there is no evidence of spread (metastasis) of cancer to the lungs (a common site of metastasis)
- CT or MRI of the brain. This has to be done under general anesthesia. As a general rule, MRI shows the brain in more detail than CT and is the test of choice when assessing for brain tumors. However, it is a more expensive test and less widely available. CT images will identify most meningiomas and choroid plexus papillomas but can fail to identify gliomas. CT images also have a lot of artifact when trying to assess the brainstem and cerebellum. We therefore strongly recommend an MRI if the animal has signs of brainstem or cerebellar disease, or if it is a breed of dog that is predisposed to gliomas, such as the Boston Terrier.
- Tumor type can be suspected from the appearance of the mass on 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 (figure 8). 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.
Figure 8: A transverse contrast enhanced CT image of the brain of a male cat. There is a contrast enhancing lesion in the area of the cerebellum (arrow) that was found to be the result of a fungal infection of the brain.
The options for treating brain tumors include surgical removal, radiation therapy, chemotherapy, and palliative treatment of the symptoms. Unfortunately, we have relatively little data to present on the outcome of tumors because it is common for owners to decide not to treat their pet, or because pets are treated with radiation therapy or chemotherapy without ever determining the tumor type. This mentality is changing as CT guided biopsies become more routinely offered, and one of our research aims is to generate a large data base of how different tumors respond to different types of treatment, and what happens if they are not treated at all (see research).
Brain tumors present unique problems related to their location and the tissue that they affect. Firstly they arise in the restricted space of the cranial cavity (Figure 1). The cranial cavity is formed by the bones of the skull and encloses and protects the brain. While a delicate structure like the brain must be protected in this way, it means there is no room for anything else within the cavity and when a tumor grows, it compresses the surrounding brain. Secondly, brain tissue cannot regenerate, and therefore removal of normal brain tissue surrounding a tumor can have unacceptable repercussions for the patient.
Surgical Removal – The aim 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 life saving 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, their location close to the floor of the cranial cavity, and because 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 – We do know that radiation will slow the rate of growth of most types of brain tumor. The full dose of radiation is administered in fractions, the number and timing of which vary between veterinary institutions. At NCSU, we administer 16 small doses of radiation on consecutive days (with breaks for the weekend). 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 (Figure 9), 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 is usually in the region of $3000-4000. Radiation is currently the treatment of choice for gliomas.
Figure 9: This is Siah, a 10-year-old female Labrador Retriever who has undergone surgery and radiation of a meningioma. Her coat has changed color in the radiation field, but she has not suffered any other side effects from her treatment.
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 is 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 therefore, 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.
Pallative Treatment – If none of the above therapies are an option, it is possible to treat the signs caused by a brain tumor. For example, any dog with a brain tumor that has seizures will be placed on an anti-epileptic drug such as Phenobarbital. 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. This response is often short lived as the tumor itself is not being treated by this drug, but can certainly give owners and pets some good quality time.
Prognosis –It is important to understand that most brain tumors can be treated but not cured. Thus the major aim of treatment is to extend a good quality of life for as long as possible. Another critical point is to understand exactly what is meant when data on efficacy of treatment is presented. Useful terms include:
- Median. Used in the context of survival, a median survival of three months means that 50% of the animals are alive at three months, but 50% have died. It does not give any information of the range of survival of individuals from within the group. For example, individual animals may have survived for only a day to several years. A median survival is very useful to allow comparison between different types of treatment.
- Survival means just that: how long an animal stayed alive, usually from time of diagnosis, but it could also mean from time of treatment, or from time the owner first noticed signs of a problem. It does not give any information on what the animal’s quality of life was during that time.
- Progression free survival is the time the animal survived without progression of the clinical signs. This gives a better idea of the quality of life.
It is fair to say that we have little solid data on the outcome of different tumor types. There are several studies looking at the effectiveness of radiation for treating brain tumors, but in most instances, the actual tumor type was not known. As a general rule, however, 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, particularly meningiomas in cats. 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)