Canine and Feline Meningiomas: Diagnosis,Treatment, and Prognosis

CE Email comments/questions to [email protected], fax 800-556-3288, or log on to www.VetLearn.com Meningiomas are the most common primary tumor of the central nervous system in dogs and cats. Meningiomas are usually histologically benign; however, their biologic behavior may be malignant. Differences between canine and feline meningiomas include histopathologic appearance, prognosis, and therapy. Meningiomas in cats are often fibrotic and usually do not infiltrate the brain tissue; their surgical removal is easier compared with that in dogs, radiation therapy may not be necessary in cats after complete gross tumor resection, and the long-term prognosis is better than that in dogs. This article reviews the origin, histologic subtypes, therapeutic response, and outcome of meningiomas in dogs and cats. HISTOLOGIC CLASSIFICATION Canine and feline meningiomas are classified as meningothelial, fibroblastic, transitional, psammomatous, angioblastic, papillary, granular cell, myxoid, or anaplastic. Mild nuclear pleomorphism, rare mitosis among cells, absence of tumor infiltration in the neuroparenchyma, and extensive hemorrhage and necrosis are histologic features of benign meningiomas. In contrast, malignant meningiomas have high numbers of cells undergoing mitosis, necrosis, loss of normal cell architecture, and, rarely, metastasis. Meningiomas in dogs and cats are usually histologically benign, but their biologic behavior may be malignant. According to immunohistochemical studies used to evaluate hormonal receptors, meningiomas in dogs and cats have a high number of cells that express intranuclear progesterone receptors and a low to absent number of cells that express estrogen receptors. Two separate studies using two different proliferative index markers, PFPCNA and December 2004 951 COMPENDIUM Canine and Feline Meningiomas: Diagnosis,Treatment, and Prognosis P. Filippo Adamo, DVM, DECVN Lisa Forrest, VMD, DACVR (Radiology, Radiation Oncology) Richard Dubielzig, DVM, DACVP University of Wisconsin–Madison Ki67, respectively, showed an inverse correlation between progesterone receptor expression and tumor behavior. High progesterone receptor expression is more common in benign meningioma, whereas decreased or absent progesterone receptor expression seems to be more common in malignant meningiomas. Tumors with a high PFPCNA index were 9.1 times as likely to recur as were tumors with a low PFPCNA index. INCIDENCE, PREDISPOSITION, LOCALIZATION, AND HISTOLOGIC FEATURES Canine Cerebral Meningiomas In dogs, intracranial meningiomas account for 33% to 49% of all primary brain tumors and are the most common central nervous system (CNS) tumor in this species. Intracranial meningiomas can develop in dogs 16 months to 14 years of age (mean age: 9 years); occurrence has been reported in dogs older than 7 years of age in 95% of cases, and dolichocephalic breeds, especially German shepherds and collies, are more frequently affected. In another study, such breed predisposition was not reported. In dogs with intracranial meningiomas, a female sex predisposition has been reported, with a male:female ratio of 0.6, which is similar to that among humans with these tumors. In dogs, most intracranial meningiomas are located over the cerebral convexities and below the brain stem; other locations include the midline attached to the falx cerebri, or the tentorium cerebelli or an intraventricular location associated with a choroid plexus. On gross examination, meningiomas in dogs are usually more friable and red compared with meningiomas in cats. In contrast to histologic findings in meningiomas of humans and cats, many meningiomas in dogs have areas of focal necrosis with pools of neutrophils, and some have been invaded along the perivascular spaces around the veins and arteries of the CNS. Attachment of meningiomas to the dura or leptomeninges may be broad (sessile), narrow (pedunculated), or total (meningioma en plaque). Ultrastructurally, canine meningiomas have extensive folds in the cytoplasm and desmosomal junctions, as do human meningiomas. Immunohistochemically, canine meningiomas commonly express vimentin-intermediate filaments. Cystic meningiomas are occasionally reported in dogs. Cystic meningioma accounts for 2% to 4% of all intracranial meningiomas in humans, and it is even less common in dogs. Meningioma cysts can be peritumoral or intratumoral. Intratumoral cyst formation can be due to ischemic necrosis and aggregation of microcytes. Peritumoral cyst formation can be due to development of peritumoral edema or secondary dilation of the subarachnoid cavity being compressed by the tumor. Active secretion from the tumor may also be a factor in cyst formation. Feline Cerebral Meningiomas In cats, intracranial meningiomas are the most common primary intracranial tumor and account for 56% of neoplasms of the CNS in this species. These tumors develop mainly in geriatric patients (i.e., older than 10 years of age). Development of meningiomas in young cats (i.e., younger than 3 years of age) has been associated with mucopolysaccharidosis type 1. There is no breed predisposition for development of meningiomas; among affected cats, domestic shorthaired and longhaired cats are overrepresented, although meningiomas are also reported in Siamese, Persians, and Maine coons. There is a slight predominance of males among cats with meningiomas. Cerebral meningiomas in cats are located mainly in the rostral fossa, particularly on the cerebral falx or in the transverse fissure. Microscopically, these tumors in cats are much more stereotyped than those in dogs; most are meningotheliomatous or psammomatous, and many have cholesterol deposits. Intracranial meningiomas in cats and humans share similarities; these tumors are often fibrotic and benign and do not usually infiltrate brain tissue. Multiple meningiomas reportedly occur in 14% to 17% of affected cats and as much as 20% of affected COMPENDIUM December 2004 Canine and Feline Meningiomas 952 CE In dogs, the main initial clinical sign associated with forebrain meningiomas is seizures. In contrast, the most common initial clinical signs in cats are lethargy and behavior changes. humans. Calvaria hyperostosis in cats has been reported in 50% of cases. Spinal Meningiomas Spinal meningiomas in dogs and cats have been reported sporadically. In dogs, about 14% of CNS meningiomas reportedly involve the spinal cord (27% in the cervical spinal cord, 47% in the thoracic cord, and 27% in the lumbar cord), whereas in cats, only 4% of all CNS meningiomas reportedly occur in the spinal cord. Other studies in dogs also report that spinal meningiomas were mainly located in the cervical area. In one study of spinal meningiomas in 13 dogs, 10 were located in the cervical region and three were found in the lumbar area. Four of these meningiomas invaded the spinal cord. An extensive spinal meningioma from the cervical to the lumbosacral spine has been reported in a 5-month-old dog. In dogs with spinal meningiomas, there is no breed predisposition, the mean age at diagnosis is 9.5 years (range: 5 to 14 years of age), and there is a male:female predominance of 2:1. These data contrast sharply with what is reported in humans, in whom spinal meningiomas demonstrate a distinct female predilection, ranging from 4:1 to 19:1. Spinal meningiomas in cats have rarely been reported. Orbital Meningiomas in Dogs Orbital meningiomas can arise from secondary extension of an intracranial neoplasm along the optic nerve or, as in the case of primary orbital tumors, from neoplastic transformation of arachnoid cap cells surrounding the intraorbital optic nerve cells within the optic nerve sheath. In dogs and humans, primary orbital meningiomas are generally thought to be slow growing and benign, but intraocular invasion and malignant variants with extracranial metastasis have been reported. In a study of 22 cases, poodles, poodle crosses, Samoyeds, Samoyed crosses, German shepherds, and German shepherd crosses were the only breeds affected. In the same study, the mean age at the time of diagnosis was 9 years (range: 3 to 7 years of age), and a male sex predisposition with a male:female ratio of 2:1 was also evident. Although not highly invasive, canine orbital meningiomas are difficult to remove, and local regrowth or extension through the optic foramen leading to blindness is a common complication. Histologically, canine orbital meningiomas often have multiple foci of myxomatous, chondromatous, or osseous metaplasia, a distinctive feature in these tumors. Paranasal Meningioma Paranasal meningiomas have been reported in 10 dogs. These meningiomas may occur as primary extracranial masses as a result of embryonic displacement of arachnoid cells or meningocytes. Paranasal meningiomas differ from intracranial meningiomas mainly because paranasal meningiomas are more anaplastic, malignant, and aggressive. CLINICAL SIGNS Intracranial Meningiomas Slow tumor growth accounts for the typically insidious and progressive onset of neurologic dysfunction. Clinical signs depend on the location and size of the tumor. If affected animals are not treated with primary therapy, survival time is usually short once neurologic deficits are observed. In one study, dogs with seizures and/or behavioral abnormalities developed demonstrable neurologic deficits within 3 months; once these deficits were detected, the clinical course was short (mean time from deficits to necropsy: less than 2 weeks). Forebrain Meningiomas Unilateral forebrain (diencephalon–cerebral hemispheres) meningiomas may be associated with any of the classic clinical signs seen in patients with any unilateral December 2004 COMPENDIUM Canine and Feline Meningiomas 953 CE Once neurologic deficits have been detected in dogs with meningiomas of the brain, survival time is short if animals are not treated with primary therapy, which includes surgical excision, radiation therapy, or a combination of the two. forebrain disease, including change in mental status, behavior changes, circling (usually toward the side of the lesion), central blindness (amaurosis), contralateral menace deficit with normal pupillary light reflexes and palpebral reflexes, contralateral decreased conscious proprioception, and contralateral facial sensation deficit. Papilledema (often bilateral) may also be present and is considered to arise from a generalized increase in intracranial pressure (ICP). The cause of circling secondary to cerebral disease is unknown; however, thalamic dysfunction is believed to be involved. Circling and visual abnormalities are also probably part of hemineglect or hemiinattention syndrome. Dogs with this syndrome are slightly to moderately obtunded; have the tendency to walk in circles; and have unique, unilateral disturbances in response to somatosensory, auditory, and visual stimuli and in eating and drinking behavior. The anatomic basis for hemineglect syndrome is hypothesized to be located in a corticolimbic-reticular loop, which helps explain the association of the syndrome with lesions at widely separated locations. Visual abnormalities are generally attributed to pressure on the optic radiation as it ascends or to pressure on the occipital lobe of the cerebrum. In meningiomas involving the rostral cerebrum (e.g., olfactory and frontal lobes), the initial abnormalities may be restricted to seizures and behavioral changes, and meningiomas in the frontal and prefrontal lobe may be clinically silent. In dogs, the main initial clinical sign associated with forebrain meningiomas is seizure activity; in contrast, seizures in cats were reported in only 11% of cases (36 cats) in one study and in 29% (17 cats) in another study. In cats, the most common initial clinical signs seen with forebrain meningiomas are lethargy and behavioral changes. Brain Stem and Cerebellar Meningiomas Meningiomas that arise from the brain stem can result in cranial nerve deficits or hemior tetraparesis, and cerebellar meningiomas may cause dysmetria, circling, ataxia, and intention tremors. Meningiomas located in the cerebellopontine angle are often associated with clinical signs of paradoxical vestibular syndrome. However, in some cases, precise neuroanatomic localization can be obscured by the secondary effects induced by the tumor, such as cerebral edema, obstructive hydrocephalus, and brain herniation. COMPENDIUM December 2004 Canine and Feline Meningiomas 954 CE Figure 1. CT transverse section of a 16-year-old domestic shorthaired castrated cat with a parieto-occipital transitional meningioma. Note the large, partially mineralized mass in the right dorsal cerebrum, which is obliterating the right lateral ventricle. There is cortical bone thickening of the calvarium adjacent to the mass. On postcontrast images, there is evidence of marked deviation of the falx to the left and patchy contrast enhancement of the mass (arrows). At presentation, neurologic clinical signs included dullness, circling, pacing, left eye blindness, and a proprioceptive deficit on the left front limb, suggesting a focal right forebrain lesion.The tumor was surgically removed, and there were no clinical signs of recurrence at follow-up 2 years later. Precontrast CT transverse section. Postcontrast CT transverse section. Spinal Meningiomas According to tumor location, any of the four spinal cord syndromes (i.e., cervical, cervicothoracic, thoracolumbar, lumbosacral) can be anticipated. Common clinical signs associated with spinal meningiomas in dogs include mild to moderate spinal pain, weakness, or sensory or motor deficits from ataxia to nonambulatory states and urinary incontinence. Motor deficits are usually insidious and progressive, with a mean duration between onset of clinical signs and diagnosis of 5.8 months (range: 3 days to 14 months). Orbital Meningiomas Common clinical signs are usually indicative of a retrobulbar mass (i.e., exophthalmos, orbital swelling, prolapsed globe). Fundic abnormalities in the posterior segment may show papilledema, an abnormal optic disk, or retinal hemorrhage, and animals are often blind in the affected eye. DIAGNOSTIC WORKUP Intracranial Meningiomas History The history of CNS signs in middle-aged or older dogs or cats should raise the possibility of neoplasia. Neoplasia should be first on the differential list in animals older than 7 years of age with seizures and no other clinical signs. A progressive course and focal neurologic signs are initial clues to the presence of a brain tumor. Minimum Database A minimum database for a dog or cat with clinical signs of brain dysfunction should include a hemogram, serum chemistry panel, and urinalysis. Survey radiography of the thorax and an abdominal ultrasonographic examination can help rule out a primary tumor or malignancy elsewhere in the body. In one study, 55% of pathologically confirmed intracranial tumors were metastatic in origin. This same screening may reveal evidence of metastasis from a primary CNS neoplasm. Advanced Imaging Techniques Findings on computed tomography (CT) and magnetic resonance imaging (MRI) are often highly suggestive of intracranial meningioma. On CT and MRI, meningiomas usually present as a mass effect with distortion of brain symmetry. Meningiomas on CT are usually characterized by extensive contrast enhancement throughout the lesion (Figures 1 and 2); however, other intracranial neoplasms (e.g., choroid plexus tumor) and inflammatory diseases (e.g., granulomatous meningoencephalomyelitis) may have the same appearance. Calvaria hyperostosis is a common finding on CT scans in cats with intracranial meningiomas. Hyperostosis is associated with bone erosion caused by pressure atrophy of the calvaria, and subsequent bony thickening is associated with the presence of clumps of tumor cells in the medullary spaces. MRI is superior to CT in detecting many of the feaDecember 2004 COMPENDIUM Canine and Feline Meningiomas 955 CE The standard of care for intracranial and spinal meningiomas in dogs includes surgical excision when viable, followed by postoperative fractionated radiation therapy. Figure 2. Postcontrast CT transverse section of an olfactory bulb meningioma in a 12-year-old German shepherd mix. Seizure was the only neurologic complaint. Note the contrast-enhancing mass in the right dorsal frontal lobe (arrow).The peripheral location and uniform enhancement are typical of meningiomas.The tumor was surgically removed, and the dog was treated with phenobarbital.The dog died 1 year later because of an unrelated neurologic cause.