Diagnosis and Treatment of Brain Tumors
Richard A. LeCouteur, BVSc, PhD, Diplomate ACVIM (Neurology), DECVN
University of California
Davis, California, USA
Primary brain tumors appear to be relatively uncommon in most domestic species, however this is not the case in dogs and cats. Although a broad spectrum of primary tumor types occurs in dogs, meningiomas and gliomas appear to occur most frequently. Most primary brain tumors are solitary, but multiple primary brain tumors have been reported. Secondary or metastatic tumors appear to be less common and may result from local extension (e.g., nasal adenocarcinoma) or metastases from primary tumors elsewhere. Skull tumors may affect the brain by local extension.
Although brain tumors occur in dogs of all breeds, either sex and any age, the incidence increases over 5 years of age, and with certain breeds. Glial cell tumors and pituitary tumors occur commonly in brachycephalic breeds, whereas meningiomas occur most frequently in dolichocephalic breeds. Breeds such as the Boxer, golden retriever, Doberman pinscher, Scottish terrier, and old English sheepdog are reported to develop intracranial tumors more commonly than other breeds.
Cerebral meningioma is the most frequently reported primary brain tumor of cats and accounts for almost 10% of all nonhematopoietic neoplasms. Primary tumors other than meningiomas appear to be less common in cats than in dogs or people. Meningiomas in cats may occur without neurologic signs. Multiple meningiomas occur relatively commonly in cats. Secondary tumors reported to occur in the brain of cats include pituitary macroadenomas macrocarcinomas, and metastatic carcinomas. Local extension in cats may be either from squamous cell carcinoma of the middle ear cavity or from nasal adenocarcinoma.
Primary brain tumors originate from cells normally found within the brain and meninges, while secondary tumors are metastasis from a primary tumor located outside the nervous system, or by local invasion from adjacent non- neural tissues (e.g., bone). Pituitary gland neoplasms and tumors arising from cranial nerves are considered secondary brain tumors.
The terms benign and malignant must be used carefullywhen referringto a brain neoplasm. Cytologic malignancy is a morphologic assessment of anaplasia, while biologic malignancy is the likelihood that a tumor will kill the animal. Most cytologically malignant brain tumors are also biologically malignant, despite current treatments. Cytologically benign brain tumors may be biologically malignant due to various secondary effects such as increased intracranial pressure (ICP). Although a canine meningioma may be classified as benign, it may be locally invasive and have poor demarcation from normal brain tissue. Meningiomas in cats are almost always well defined with a clear demarcation between normal and affected brain tissue and appear to grow more slowly than canine meningiomas.
Brain tumors cause cerebral dysfunction through infiltration of normal brain tissue, compression of adjacent structures, disruption of cerebral circulation and local necrosis. Secondary effects of brain tumors include hydrocephalus, increased ICP, cerebral edema and brain herniation. Primary brain tumors often are slow growing and the brain adapts to the slow increase in ICP. During this period of compensation there may be a history of vague signs and subtle behavior changes. Even with a slowly progressive tumor, clinical signs may progress rapidly when compensatory mechanisms have been exhausted. Rapidly growing tumors do not permit the same degree of compensation and a sudden onset of severe neurologic dysfunction may occur in the absence of premonitory signs.
History and Clinical Signs
Neurologic signs resulting from a brain tumor depend primarily on the location, size and rate of growth of the mass. Many dogs or cats will have a long history of "vague" signs, such as not wishing to be handled, hiding during the day, decreased frequency of purring or diminished activity levels. Frequently focal or generalized seizures occur.
Focal neurological signs are usually indicative of a fairly well developed mass lesion. Neoplasms involving the brain stem may result in cranial nerve deficits. Weakness and sensory abnormalities are often seen with a lesion in the cerebral frontoparietal regions or their deeper pathways. Visual deficits involve the visual pathways from the occipital lobe of the cerebrum to the optic nerve. Hearing loss involves the cerebellomedullary region, the brain stem, or temporal lobes of the cerebrum. Decreased ability to smell may be seen with lesions of the cribriform plate, olfactory or temporal lobes of the cerebrum, or other rhinencephalic connections. Difficulties with balance or gait suggest cerebellar or vestibular involvement.
Secondary effects of brain tumors include increased ICP and by the time these effects occur a large tumor and significant cerebral edema is present. Clinical signs include alterations in behavior (e.g., lethargy, irritability), circling, head pressing, compulsive walking, altered states of consciousness, or associated locomotor disturbances. Unfortunately, the majority of cats or dogs with a brain tumor will be presented to a veterinarian with problems related to the secondary effects of a tumor.
On the basis of signalment, history, and the results of complete physical and neurologic examinations, it is possible to localize a problem to the brain and, in some cases, to determine the approximate location. Signs resulting from disease in a given location in the nervous system will be similar regardless of the exact cause and in order to eliminate other categories of disease it is essential to follow a logical diagnostic plan. A minimum database for these patients should include a hemogram, serum chemistry panel, urinalysis, and survey radiographs of the thorax and abdominal ultrasound. Although plain skull radiographs are of limited value in the diagnosis of a primary brain tumor they may be helpful in detecting neoplasms of the skull or nasal. Occasionally, lysis or hyperostosis of the skull may accompany a primary brain tumor (e.g., meningioma of cats), or there may be radiographically visible mineralization within a neoplasm. General anesthesia is necessary for precise positioning of the skull for radiographs.
Analysis of CSF is recommended as the results may help to rule out inflammatory diseases, and may support a diagnosis of a brain tumor. Care should be used in the collection of CSF, because frequently ICP is increased and pressure changes associated with CSF drainage may lead to brain herniation. Hyperventilation of the patient or administration of mannitol prior to CSF collection will help to decrease intracranial pressure. Increased CSF protein content and a normal to increased CSF white blood cell count are considered "typical" of a brain neoplasm although often CSF may be normal. Neoplastic cells may be present in CSF, particularly when sedimentation techniques are used for analysis.
Computed tomography (CT) and magnetic resonance (MR) imaging provide accurate information about the presence, location and size of intracranial neoplasms. MR images are superior to those of CT in certain brain regions (e.g., the brainstem), and the diagnostic specificity of MRI may eventually make biopsy of tumors prior to treatment unnecessary. Meningiomas may be difficult to detect on MR images, without contrast administration. A meningioma may have a "mottled" appearance and an interface is often visible between the tumor and the surrounding brain on T1- and T2-weighted images. This hypointense signal may indicate a compressed arachnoid plane between the tumor and the brain, and also compression of the draining venous plexus. Hypointense areas within the meningioma may indicate intratumoral mineralization. The "dural tail" sign, while not necessarily specific for a meningioma, is often associated with either neoplastic infiltration of meninges beyond the margin of the meningioma or hypervascularity of the dura mater. Ideally, an intracranial lesion should be biopsied prior to the institution of therapy, however biopsy is not always attempted for practical reasons such as cost and morbidity.
Non-neoplastic space-occupying lesions may mimic the CT or MR appearance of a neoplasm and occasionally a metastasis may resemble a primary brain tumor. Currently biopsy and/or surgical excision are the only methods available for the definitive diagnosis of brain tumor types. Biopsy methods described include ultrasound-guided biopsy, and CT-guided biopsy. The most recent advance in the biopsy of brain tumors has been the modification of a CT-guided stereotactic brain biopsy system (Pelorus Mark III Stereotactic System, Ohio Medical Instruments Company, Cincinnati, Ohio) for use in cats and dogs. This CT-guided stereotactic biopsy system provides a relatively rapid and extremely accurate means of tumor biopsy, with a low rate of complications.
Cytological evaluation of brain tumor biopsy specimens can be done within minutes of biopsy collection by means of crush preparations. Tissue samples are rapidly fixed in 95% alcohol and stained with hematoxylin and eosin. Accurate information using this rapid technique is generally available from both primary and metastatic nervous system tumors, and from non-neoplastic lesions. Air-dried slides of crush preparations may also be stained with Wrights stain and counter stained with Giemsa to provide additional information regarding cell types present in a mass.
The aims of therapy for a brain tumor are to eliminate the tumor or reduce its size and to control secondary effects (e.g., increased ICP or cerebral edema). Palliative therapy for animals with a brain tumor consists of glucocorticoids for edema reduction and, in some cases (e.g., lymphoma), for retardation of tumor growth. Should seizure therapy be needed, phenobarbital is the drug best suited for the control of generalized seizures.
Surgery has become an essential consideration in the management of intracranial neoplasms of cats or dogs. The precise location, size, and type of a neoplasm, determine the extent of removal. Meningiomas, particularly those located over the frontal lobes of the cerebrum, often may be completely removed, especially in cats and in cats long-term survival is excellent. In contrast, there is a significant morbidity and mortality associated with the surgical removal of caudal fossa and brainstem neoplasms. Partial removal of a brain neoplasm may relieve signs of cerebral dysfunction, provide a histologic diagnosis and may make an animal a better candidate for other therapy such as radiation. Surgical biopsy of a tumor must be approached with care to avoid seeding of tumor cells to normal tissue.
The use of radiation therapy for the treatment of primary brain tumors of dogs and cats is well established and it may be used either alone or in combination with other treatments. External beam, megavoltage irradiation currently is recommended for the therapy of brain tumors in dogs or cats. Although orthovoltage radiation has been used it is not optimal because of poor beam penetration, profile, and limited field configuration. Careful treatment planning by a radiation therapist is essential. The selection of a radiation dose is based on considerations such as tumor type, location, and tolerance of the surrounding normal tissues.
Richard A. LeCouteur, BVSc, PhD, Diplomate ACVIM (Neurology),