Multiple Meningiomas in Three Dogs
Three dogs with seizures were diagnosed with multiple intracranial meningiomas. Two of the three dogs were golden retrievers, and ages ranged from 9 to 11 years. Treatment consisted of surgery and radiation (n=2) or chemotherapy (n=1). In all three cases, the masses were two distinct tumors as determined by imaging, surgery, or necropsy. In two dogs, the meningiomas had the same histological pattern, while in one dog the histological subtypes were different.
Introduction
Meningiomas are the most common intracranial tumors in dogs, with an incidence ranging from 30% to 39% for all intracranial tumors.1,2 They have been reported in dogs <6 months and up to 14 years of age, but most occur in dogs >7 years of age.2–4 Dolichocephalic breeds and females have a higher incidence, with a male-to-female ratio of 0.6.2,3 These tumors are encountered most frequently in humans, dogs, cats, and rats, and they are rare in other domestic species (e.g., horse, cow, sheep).3,5
One case of multiple meningiomas in a dog has been previously reported in a retrospective pathological study.4 A single report of a dog with concurrent oligodendroglioma and meningioma also exists.6 Multiple meningiomas are common in the cat, occurring in approximately 17% of meningioma cases.5,7,8 This paper presents the signalment, clinical signs, magnetic resonance imaging (MRI) findings, treatment, and histopathological findings of three dogs with multiple intracranial meningiomas.
Case Reports
Case No. 1
An 11-year-old, spayed female golden retriever [see Table] was referred to Tufts University Cummings School of Veterinary Medicine for generalized, major-motor seizures of 1 week’s duration. The physical examination revealed a right-sided Horner’s syndrome and mild proprioceptive deficits in the right pelvic limb. Complete blood count (CBC), serum biochemical analysis, and urinalysis were normal. Three thoracic radiographic views were normal, and the Horner’s syndrome resolved spontaneously over the course of 2 weeks.
Magnetic resonance imaging was performed using a 1.0-Tesla MR unit.a A left fronto-olfactory falcine mass and a right frontoparietal mass were detected [Figures 1A, 1B]. Both masses were sessile with broad attachments to the falx and dura, respectively. They were isointense to gray matter on T1-weighted spin-echo images, and they were hyperintense on T2-weighted images. On the post-contrast T1-weighted images (i.e., following intravenous administration of gadopentetate dimeglumineb), the masses enhanced strongly and homogenously. Dural tail signs (i.e., enhancement of the dura contiguous with and tapering away from the masses) were seen. The tumors were separate, and no connections were seen. Mild edema was noted around the fronto-olfactory mass. No edema was noted with the frontoparietal mass. Based on the imaging findings, a tentative diagnosis of multiple meningiomas was made. Other differential diagnoses included lymphosarcoma and dural metastases.
The dog was started on phenobarbitalc (2.0 mg/kg per os [PO] q 12 hours) and potassium bromided (30 mg/kg PO q 24 hours). A craniotomy was performed, and the two masses were surgically resected. Histopathology of the surgical biopsies revealed two meningiomas with similar histological patterns. Both tumors were composed of fronds of spindle cells supported by a sparsely vascular, fibrillar, eosinophilic stroma. The cells were spindle-shaped, polygonal, or stellate; they had indistinct borders; and they were arranged in sheets or bundles [Figure 2A]. They contained large, oval, central nuclei; finely stippled and marginated chromatin; and small amounts of fairly granular, pale eosinophilic cytoplasm. Mild anisocytosis and anisokaryosis were seen, but no mitoses were detected in 10 high-power fields (hpf) [Figures 2A, 2B]. Scattered throughout the masses were regions of mild neutrophilic inflammation and occasional mineralized foci (i.e., psammoma bodies). The histological diagnosis for both masses was transitional meningioma.
Twenty-five days after surgery, radiation therapy using a linear acceleratore and a total dose of 48 Gy delivered in 16 fractions (on a Monday through Friday schedule) was performed. Treatment with prednisonef (1 mg/kg PO q 24 hours) was initiated at the time of radiation treatment. After surgery and radiation therapy, the dog was dull and weak in the pelvic limbs, but these signs disappeared over 3 months. Four weeks following radiation therapy, prednisone was tapered and eventually stopped 8 weeks later. Hypertension and proteinuria were diagnosed 3 months after radiation treatment. The dog was euthanized 18 months after diagnosis [see Table] because of increased seizure activity, decreased appetite, and difficulty ambulating. A postmortem examination and histopathology were performed. Diffuse membranous to membranoproliferative glomerulopathy, with tubular ectasia and tubular hyaline casts was detected in the kidneys, and a cortical adenoma was found in the right adrenal gland. In the brain, gliosis and myelin degeneration were seen at the surgical sites, but there was no evidence of tumor.
Case No. 2
A 9-year-old, spayed female rottweiler [see Table] was referred for recent onset of multiple major-motor seizures that occurred over a 16-hour period. Physical and neurological examinations were normal. Thoracic radiographs taken by the referring veterinarian, a serum biochemical profile, a CBC, and urinalysis were all normal.
On MRI, a large, left fronto-olfactory mass and a smaller, sessile, left frontoparietal falcine mass were discovered [Figures 3A, 3B]. The rostral mass caused a severe midline shift to the right and infiltrated the nasal cavity through the cribiform plate. It was slightly hypointense to gray matter and contained focal hypointensities on T1-weighted spinecho images. The mass was hyperintense on T2-weighted images. On post-contrast images, the mass showed moderate heterogeneous enhancement in a ring-like pattern. The foci of hypointensity on the T1-weighted images did not enhance and were thought to represent cysts. Minimal peritumoral edema was noted. The frontoparietal mass was slightly hypointense to gray matter on T1-weighted images, and hyperintense on T2-weighted images. On post-contrast images, it enhanced strongly and homogenously. No peritumoral edema was noted. Based on the imaging findings, a tentative diagnosis of multiple meningiomas was made. Other differential diagnoses included lymphosarcoma and dural metastases, as well as esthesioneuroblastoma and nasal adenocarcinoma for the rostral mass.
The dog was treated with phenobarbital (2.1 mg/kg PO q 12 hours) and potassium bromide (30 mg/kg PO q 24 hours) for the seizures. Prednisone (1 mg/kg PO q 24 hours) was initiated to decrease peritumoral edema. Lomustineg (85 mg/m2 PO q 4 weeks for five treatments) was begun for its antineoplastic properties. Trimethoprim-sulfadiazineh (20 mg/kg PO q 12 hours) was given for 10 days following each dose of lomustine to prophylactically treat expected myelosuppression. The dog tolerated all medications well.
Six months after diagnosis, multiple major-motor seizures recurred. Examination at that time showed generalized weakness and right-sided postural reaction deficits. The phenobarbital was increased to 3.2 mg/kg PO q 12 hours. The dog was euthanized 7 months after diagnosis because of increased seizures, weakness, and dullness.
A postmortem examination was performed. Two intracranial masses were found that were similar histologically. The larger mass was sessile, and the smaller mass was somewhat papillary. Both masses had a prominent, radially oriented, finely vascular, collagenous stroma. Neoplastic cells were arranged between bands of stroma in solid nests or in whorls (rarely) around small, mineralized foci (i.e., psammoma bodies) [Figures 4A, 4B]. At the apex of the masses, neoplastic cells were arranged in broader, cribriform to microcystic sheets. The cells were plump or spindle-shaped, with indistinct borders. They contained large, central, open-faced nuclei; a single small nucleolus; and moderate amounts of faintly vacuolated, pale grey cytoplasm. Moderate anisocytosis and anisokaryosis were seen, but mitoses were not evident. The tumors were spatially distinct masses and were histologically diagnosed as psammomatous meningiomas.
Case No. 3
A 9-year-old, castrated male golden retriever [see Table] was presented after a major-motor seizure of 3 to 5 minutes’ duration. On physical and neurological examinations, no significant abnormalities were noted. A serum biochemical analysis, CBC, and urinalysis were normal. No abnormalities were detected on thoracic or abdominal radiography.
On MRI, a sessile, left frontal falcine mass [Figure 5A] and a plaque-like, left occipital mass [Figure 5B] were seen. The frontal mass was slightly hypointense to gray matter on T1-weighted images, and it was isointense on T2-weighted images. On post-contrast images, the mass enhanced strongly and heterogeneously. Moderate peritumoral edema was evident. The occipital mass was isointense on T1-weighted images and had mixed intensity (hyper- and isointense) on T2-weighted images. On post-contrast images, it enhanced strongly and uniformly. A dural tail sign and mild peritumoral edema were present with the occipital mass. Based on the imaging findings, a tentative diagnosis of multiple meningiomas was made. Other differential diagnoses included lymphosarcoma and dural metastases.
Craniectomy and surgical resection were performed. Histopathology of the tissue removed at the time of surgery showed the frontal lobe mass had areas of densely packed neoplastic cells that formed whorls or sheets. The cells were round, oval, or polygonal with indistinct borders; they had scant to moderate eosinophilic cytoplasm; and each had a single round or oval, open-faced nucleus. Whorls were surrounded and separated by interlacing fascicles of elongated or spindle-shaped cells, with finely stippled chromatin [Figure 6A]. Mitoses were not seen. Extensive foci of necrosis and neutrophilic infiltrates were interspersed with sheets of lymphocytes. Neoplastic cells extended to all margins of the specimen.
The occipital lobe mass was composed of densely packed neoplastic cells that formed interlacing whorls and streams [Figure 6B]. The cells were mildly pleomorphic; they were round, oval, or elongated in shape; they had indistinct borders and scant to moderate eosinophilic cytoplasm; and each had a single round or oval, hyperchromatic nucleus [Figure 6B]. Mitoses were not seen. Whorls frequently contained laminated hyaline and mineralized material (i.e., psammoma bodies). Neoplastic cells extended to all margins of the specimen and were confluent with a portion of the meninges. The histological diagnoses were a frontal lobe transitional meningioma and an occipital lobe psammomatous meningioma.
Postoperatively, the dog was treated with phenobarbital (2.1 mg/kg PO q 12 hours) for the seizures. Enrofloxacini (5 mg/kg PO q 12 hours) was also administered for 4 weeks. Thirty days after surgery, radiation therapy was performed using a linear accelerator and a total dose of 48 Gy delivered in 16 fractions (on a Monday through Friday schedule). Prednisone (1 mg/kg PO q 24 hours) was initiated at the time of radiation treatment. After radiation treatment, the dog was mentally dull and quiet, but mentation improved over 2 months. Four weeks following radiation therapy, prednisone was slowly tapered and eventually stopped 8 weeks later. The dog had one major-motor seizure 4 months following surgery, and potassium bromide (30 mg/kg PO q 24 hours) was started. Five months following surgery, a second MRI showed minimal meningeal enhancement at both surgical sites, with no obvious tumor regrowth. Ten months after surgery, the dog remains neurologically normal and has had no seizures.
Discussion
Meningiomas occur most commonly in dolichocephalic breeds of dogs, such as the German shepherd dog, collie, and golden retriever.4,9 They also commonly occur in boxers, poodles, terriers, and mixed-breed dogs.4,9 Two of the three dogs in this report were golden retrievers. Meningiomas are reportedly more common among mature or older dogs, which was also true of the dogs in this study.2,5 A report of 97 brain tumors found that 95% of affected dogs were >5 years of age at the time of diagnosis.10 In two prior reports of canine intracranial meningiomas, the mean ages of affected dogs were 10.5 and 11.0 years.1,4 In humans with multiple intracranial meningiomas, the reported mean age is 50 years (range 29 to 72 years).11,12
The ratio of male to female dogs was 0.6 in one study of intracranial meningiomas.3 Other case studies have shown that meningiomas occurred in approximately equal numbers in male and female dogs.4 Two of the three dogs in this study were female. Multiple meningiomas are more common in women, with humans having a male to female ratio of 0.4.13
Clinical signs attributed to brain tumors vary depending on their location, growth rate, and secondary effects. Seizures and behavioral changes are common in older dogs with brain tumors.1,5,10 All three cases in the present study were presented for seizures. Humans with multiple meningiomas often have progressive, focal neurological deficits; headache; or seizures.12,13 The first two dogs in this report were euthanized because of progression of neurological signs, including seizures. Necropsy findings from case no. 1 reported inflammation and degeneration at the surgical sites but no recurrence of the tumors. It was unclear why this dog had progressive seizures and weakness.
Approximately 82% of canine meningiomas are intracranial, 15% are found in the spinal canal, and 3% occur in the retrobulbar space.9 Canine intracranial meningiomas are common in the region of the olfactory bulb and frontal lobes.9 They may also occur in basal locations, over the cerebral and cerebellar convexities, adjacent to the falx cerebri and tentorium cerebelli, and in the pontocerebellar angle.14 All of the tumors in this report were located in the supratentorial region. In a prior study of 97 canine brain tumors, 47% of the tumors located in this region were meningiomas.10 In another review of 22 intracranial canine meningiomas, 15 were located in the supratentorial region.15 All three dogs in the study reported here had a tumor at the rostral aspect of the frontal lobes. The second tumor was in the frontoparietal region in two dogs and in the occipital lobe in one dog. In two of the three dogs in this study, the tumors affected only one hemisphere.
On MRI, canine meningiomas are usually hypointense or isointense to gray matter on T1-weighted spin-echo images, and they are hyperintense or isointense on T2-weighted spin-echo images.15–17 They are usually broad-based, occur along the falx or dura, and are rounded or plaque-like.15 Hyperostosis of the adjacent skull bones may be present, and surrounding edema is variable.15–17 Peritumoral cysts or fluid accumulations have been reported in ≤31% of meningiomas, and extension of the tumor through the cribiform plate has been described in ≤18%.15,16 Following contrast administration, meningiomas typically are strongly enhancing, although the pattern of enhancement can vary.15–17 A dural tail sign has been reported in 60% of meningiomas in dogs and cats, but it is not specific for meningiomas.16–18 Although a definitive diagnosis cannot be made based solely on MRI findings, the presence of an intracranial mass in a peripheral location (with a typical shape, intensity, enhancement pattern, and dural tail sign) is strongly suggestive of a meningioma.17,19 All three cases presented in this paper had MRI findings similar to those described above. Three of the six tumors had prominent dural tail signs. Five of the tumors had no or mild peritumoral edema. One tumor had a cystic component and extended through the cribriform plate into the nasal cavity. None of the tumors caused hyperostosis. In Figure 1B, the slight hypointensity adjacent to the meningioma was not thought to be hyperostosis, as it was not visible on the adjacent images. The hypointensity was thought to be related to a difference in the shape of the left frontal sinus compared to the right, as well as to silhouetting from air in the frontal sinus. The apparent thickening of the left occipital bone in Figure 5B was also not present on the adjacent images. Hyperostosis was considered less likely in case no. 3, because intradiploic fat was still present.
The recognized histological growth patterns of meningiomas in dogs are meningothelial, fibroblastic, transitional, angioblastic, psammomatous, papillary, microcystic, myxoid, and atypical.2,3,5,9 More than one histological pattern may be present within a single tumor.8 In humans, histological patterns in multiple meningiomas parallel those reported in single meningiomas.11,12 In a report of 14 people with multiple meningiomas, 11 (79%) had histologically similar tumors.11 In case no. 1 of the current study, both meningiomas exhibited transitional growth patterns, while both meningiomas in case no. 2 exhibited psammomatous growth patterns. In case no. 3, the frontal lobe meningioma was transitional, and the occipital lobe meningioma was psammomatous.
Median survival times for dogs with single intracranial meningiomas have been 16.5 months for dogs that had tumor resection followed by radiation therapy, 7 months for dogs treated with surgery alone, and 2.5 months for dogs not treated.1,20 In the three cases presented here, survival times were similar to those of prior reports. Survival times in these three cases were also similar to those in humans, where survival times and recurrence rates are similar for both single and multiple meningiomas.11,12
Conclusion
Three dogs with seizures were diagnosed with multiple intracranial meningiomas. Two of the dogs were golden retrievers, and all were older dogs. Two of the dogs were treated with surgical resection and radiation therapy. Recovery and subsequent survival times were comparable to those reported for solitary intracranial meningiomas. Further study of multiple intracranial meningiomas in dogs is necessary to determine the age of onset, breed and sex predilection, and common tumor locations, as well as to accurately determine the best treatment and prognosis for these tumors.
Magnetom Impact; Siemens, Erlangen, Germany
Magnevist; Berlex Laboratories, Wayne, NJ 07470
Phenobarbital; Westward Pharmaceutical Corporation, Eatontown, NJ 07724
Potassium bromide; Sigma-Aldrich Corporation, St. Louis, MO 63103
Mevatron 77; Siemens, Erlangen, Germany
Prednisone; Westward Pharmaceutical Corporation, Eatontown, NJ 07724
Lomustine; Bristol-Myers Squibb, New York, NY 10154
Tribressin; Pitman-Moore Company, Mundelein, IL 60060
Enrofloxacin; Bayer Healthcare, Shawnee Mission, KS 66201
Citation: Journal of the American Animal Hospital Association 43, 4; 10.5326/0430201
Citation: Journal of the American Animal Hospital Association 43, 4; 10.5326/0430201
Citation: Journal of the American Animal Hospital Association 43, 4; 10.5326/0430201
Citation: Journal of the American Animal Hospital Association 43, 4; 10.5326/0430201
Citation: Journal of the American Animal Hospital Association 43, 4; 10.5326/0430201
Citation: Journal of the American Animal Hospital Association 43, 4; 10.5326/0430201
Magnetic resonance images of an 11-year-old, spayed female golden retriever (case no. 1) with two intracranial transitional meningiomas. Both images are T1-weighted, transverse images (TR 644 ms, TE 15 ms) taken after administration of contrast medium. (A) Image is taken at the level of the frontal lobes. A strongly enhancing (white), sessile, left falcine mass (*) is causing a slight midline shift to the right. (B) Image is taken at the frontoparietal junction. A strongly enhancing (white) mass (×) is evident, with a broad attachment to the dura and dural tail signs (arrows). R=right; L=left.
High-magnification photomicrographs of surgical biopsy specimens of the masses removed from the dog in Figure 1. (A) The mass in the left frontal lobe was composed of plump or spindle-shaped cells arranged in sheets and whorls. (B) The mass in the right frontoparietal area had a similar appearance, with cells arranged in prominent whorls. Histopathological diagnosis for both masses was transitional meningioma. (Hematoxylin and eosin stain, bar=100 μm.)
Magnetic resonance images of a 9-year-old, spayed female rottweiler (case no. 2) with two intracranial psammomatous meningiomas. Both images are T1-weighted, transverse images (TR 644 ms, TE 15 ms) taken after administration of contrast medium. (A) Image is taken at the level of the frontal lobes. A heterogeneous, ring-enhancing, cystic, left-sided mass (*) is causing a marked midline shift to the right. Additional meningeal enhancement is noted along the deviated falx cerebri (arrow). (B) Image is taken at the level of the frontoparietal junction. A strongly enhancing, rounded, left falcine mass is present (×). A cystic structure associated with the mass described in A is present ventrally (arrowhead). R=right; L=left.
High-magnification photomicrographs of necropsy specimens from the dog in Figure 3 that were histologically diagnosed as psammomatous meningiomas. Both masses contained multiple, mineralized psammoma bodies (arrows). (A) Mass in the left frontal lobe. (B) Mass in the left frontoparietal area. (Hematoxylin and eosin stain, bar=100 μm.)
Magnetic resonance images of a 9-year-old, castrated male golden retriever (case no. 3) with a frontal lobe transitional meningioma (A) and an occipital lobe psammomatous meningioma (B). Both images are T1-weighted, transverse images (TR 644 ms, TE 15 ms) taken after administration of contrast medium. (A) Image is taken at the level of the frontal lobes. A heterogeneously enhancing, left falcine mass (*) is causing a mild midline shift to the right. (B) Image is taken at the level of the occipital lobes. A strongly enhancing, plaque-like mass (×) is noted on the left side. A dural tail sign is evident (arrows). R=right; L=left.
High-magnification photomicrographs of surgical biopsy specimens of the masses removed from the dog in Figure 5. Histologically, the masses were a frontal lobe transitional meningioma (A) and an occipital lobe psammomatous meningioma (B). (A) This section of the transitional meningioma shows lobules (*), whorls (×), and areas of necrosis (arrowheads). (B) Psammoma bodies (arrows) can be seen in this image of the left occipital meningioma. (Hematoxylin and eosin stain, bar=100 μm.)
