JPC SYSTEMIC PATHOLOGY
NERVOUS SYSTEM
February 2023
N-N07
SLIDE A: Signalment (JPC #4044171-00): 8-year-old intact male Belgian Malinois military working dog
HISTORY: This dog was euthanized following progressively worsening neurologic signs in conjunction with a left midbrain mass seen on computed tomography (CT). At necropsy, the ventral midbrain had an irregular surface and the lateral ventricles were dilated.
HISTOPATHOLOGIC DESCRIPTION: Brainstem and meninges: Expanding the meninges and focally infiltrating the adjacent brainstem is well demarcated, unenceapsulated, multinodular, densely cellular neoplasm composed of polygonal cells arranged in whorls and lobules separated by moderate fibrovascular stroma. Neoplastic cells have indistinct cell borders, a scant to moderate amount of eosinophilic finely granular cytoplasm, an oval to elongate nucleus with finely stippled chromatin and up to 2 prominent nucleoli. Anisocytosis and anisokaryosis are mild and there are 2 mitotic figures per 2.37mm2. Throughout the neoplasm are multifocal variably sized areas of necrosis composed of eosinophilic cellular and karyorrhectic debris admixed with basophilic fragmented material (mineral), mild hemorrhage, fibrin, edema, and few infiltrating neutrophils, macrophages, lymphocytes, and plasma cells. Within the adjacent brainstem, there are minimal vacuolization of the white and gray matter (spongiosis) and low numbers of lymphocytes, plasma cells, and foamy macrophages with pale granular cytoplasm expanding Virchow-Robins space.
Cerebellum: Essentially normal tissue.
MORPHOLOGIC DIAGNOSIS: Brainstem and meninges: Meningioma, transitional, Belgian Malinois, canine.
SLIDE B: Signalment (JPC #3086729-00): 7-year-old neutered male German shepherd dog military working dog
HISTORY: This dog was euthanized following a history of neurologic signs in conjunction with an extramedullary right frontal cerebral cortex mass seen on magnetic resonance imaging (MRI). At necropsy, an irregularly shaped mass was observed in the right frontal cerebral cortex adjacent to the interhemispheric fissure which had extended throughout the cortex and was adhered to the calvarium.
HISTOPATHOLOGIC DESCRIPTION: Cerebrum (per contributor): Extending to all margins of this tissue section is a densely cellular, multilobulated neoplasm composed of spindle cells arranged in whorls, frequently surrounding eosinophilic hyaline material to deeply basophilic mineralized foci (psammoma bodies) on a delicate fibrous stroma. Neoplastic cells have indistinct cell borders, a moderate amount of eosinophilic finely granular cytoplasm, an oval to elongate nucleus with finely stippled chromatin and up to 2 prominent nucleoli. Anisocytosis and anisokaryosis are mild and there is <1 mitotic figures per 2.37mm2. Scattered throughout the neoplasm are rare neoplastic cells that are shrunken with hypereosinophilic cytoplasm and pyknotic nucleus (single cell necrosis), increased clear space (edema), and scant hemorrhage.
MORPHOLOGIC DIAGNOSIS: Cerebrum (per contributor): Meningioma, psammomatous, Belgian Malinois, canine.
GENERAL DISCUSSION:
- Meningioma(s) are the most common type of intracranial primary tumor in the cat (60%) and in dogs (~50%, especially golden retrievers and boxers), but are very rare in horses and ruminants
- Arise from meningothelial cells (arachnoidal cap cells) within the outer layer of the arachnoid mater and arachnoid villi, usually in close association to the dura
- They are expansile and compressing, but rarely invade the brain
TYPICAL CLINICAL FINDINGS:
- 7-14 year old dogs; >10 year old cats
- Neurologic signs (e.g. seizures, vestibular signs) depend on location, rate of growth, and degree of brain swelling and herniation; signs are caused by compression of the underlying nervous tissue
- In cats, may be subclinical (mass incidentally found at necropsy)
TYPICAL GROSS FINDINGS:
- Globular, ovoid to tuberous to plaque-like, well circumscribed, firm; on cut surface are gray to yellow and sometimes gritty
- May be single or multiple (multiple common in cats [17-19%])
- Cause compression atrophy of subjacent nervous tissue
- In cats, they are more easily separated from the underlying brain parenchyma than in dogs which are more interdigitated
- Can be located anywhere in the meninges (brain or spinal cord), but commonly affect the cerebral convexity, basilar meninges, and in cats, the tela choroidea of the third ventricle; spinal cord overall less common, but have predilection for cervical region (C1 especially); 82% of canine meningiomas are intracranial, 15% intraspinal, and 3% retrobulbar
- Hyperostosis of overlying bone may be present
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Meningiomas are classified according to their predominant pattern; depending on the subtype, can have mesenchymal and/or epithelial-like features with spindle cells within a collagenous stroma and/or polygonal cells with visible intercellular junctions and occasional secretory activity
- Transitional, meningothelial, psammomatous, fibrous, and atypical subtypes are most common in the dog; meningothelial or transitional with frequent psammoma bodies are most common in the cat
- May also see hemorrhage, foci of necrosis, and infiltrates of neutrophils; their significance in tumor progression is unknown
- Canine grade I mengiomas: 56% incidence; depending on how vascularized the meningioma is, it may be difficult to differentiate from hemangioma
- Meningotheliomatous (epithelioid) meningioma: Diffusely cellular, cells in sheets or variably sized lobules separated by thin collagenous septa; cells are large with abundant finely granular pale cytoplasm and indistinct cell borders; nuclei are spherical or ovoid and may have intranuclear cytoplasmic invaginations (pseudoinclusions); most common Grade I subtype along with transitional subtype
- Psammomatous meningioma: Similar general features to meningotheliomatous subtype, but cells are arranged in whorls with lamellar hyaline tissue in the center of the whorls that tends to mineralize (psammoma bodies) as the hyaline focus expands; hyaline material is derived possibly from cells, stroma, or a blood vessel
- Fibrous (fibroblastic) meningioma: Bundles of spindle cells with collagen deposition
- Transitional (mixed type) meningioma: Has features of both epithelioid and fibroblastic with formation of whorls and psammoma bodies; most common Grade I subtype along with meningotheliomatous (epithelioid) subtype
- Angiomatous (angioblastic) meningioma: Highly vascular with prominent endothelial cells in formed vessels and lining vascular clefts surrounded by spindle cells, similar in appearance to hemangiopericytoma
- Microcystic meningioma: Cells have elongated processes and cytoplasmic and interstitial vacuolation
- Myxoid meningioma: Similar to myxoma elsewhere; vacuolated cells separated by abundant myxoid matrix that is PAS, Alcian blue, and mucicarmine positive
- Canine grade II meningiomas: 46% incidence;
- Choroid meningioma: Forms cords and trabeculae of eosinophilic epithelioid cells in a basophilic matrix.
- Atypical meningioma: Hypercellularity with loss of whorls and fascicles with necrotic areas and more than 4 mitotic figures per 10 HPF
- Canine grade III meningiomas: rare (1% incidence)
- Papillary meningioma: Meningothelial cells arranged in papillary structures supported by fibrovascular cores; rare in dogs
- Anaplastic (malignant) meningioma: Distinct features of malignancy including more than 20 mitotic figures per 10 HPF and/or obviously malignant cytologic characteristics such as resemblance to carcinoma, sarcoma, or melanoma
- Rhabdoid: Discohesive sheets of polygonal cells with a large vesiculate nucleus, abundant eosinophilic cytoplasm, and intracytoplasmic paranuclear eosinophilic hyaline inclusion-like bodies
- Other canine meningomas:
- Granular cell meningioma, a variant in dogs that resembles granular cell tumors elsewhere in the body; small, well circumscribed, non-encapsulated with large round cells with clear cytoplasm with variable numbers of intracytoplasmic PAS-positive acidophilic granules on a delicate stroma that individualizes cells or separates them into small groups; amyloid may be present in the stroma
- Feline meningiomas: More uniform appearance than canine, with whorls of elongate cells, collagen deposition, focal mineralization and cholesterol clefts; consistent with grade I tumors
ULTRASTRUCTURAL FINDINGS:
- EM is the most definitive diagnostic technique; meningothelial cells characteristically have numerous very long, interdigitating, parallel-layered cytoplasmic processes with normal and abnormal gap and desmosomal junctions
- Rhabdoid meningioma: presence of whorls of intermediate filaments that often entrap cell organelles (“gold standard” for diagnosis)
ADDITIONAL DIAGNOSTIC TESTS:
- CSF analysis (intercranial meningioma): in dogs, reported to be normal (29%), have increased total protein (ACD; 45%), or have increased total nucleated cell counts (pleocytosis, usually neutrophilic; 27%); pleocytosis was correlated with masses in the caudal portion of the cranial fossa
- CSF analysis (spinal meningioma): in dogs, 62% had mild pleocytosis and normal are variably elevated protein concentrations
- Cytology: highly variable depending on histologic subtype; individualized to dense aggregates of round to spindeloid cells with whispy to solid, eosinophilic cytoplasm, plump round to elongate nuclei draped around vessels and whorling around centralized mineralized material (psammoma bodies) +/- intranuclear cytoplasmic pseudoinclusions (not reliably seen) and neutrophils; cells may have eosinophilic secretory material that is PAS negative and Alician blue or mucicarmine positive
- Immunohistochemistry:
- Positive: Vimentin; sparse to moderate expression in cytokeratin, NSE, S-100; histologic pattern dependent expression in dogs for E-cadherin, N-cadherin, and CD34
- Negative: GFAP, synaptophysin, melan A
- Canine meningiomas have early loss of tumor suppressor genes NF2, 4.1B, and TSLC1; also overexpress osteopontin (OPN) regardless of histologic grade and express somatostatin receptor 2 (SSTR2)
- Anaplastic meningiomas: Overexpress doublecortin and nuclear β-catenin
DIFFERENTIAL DIAGNOSIS:
- Meningeal sarcomatosis: rare (dogs only) with diffuse infiltration of the leptomeninges by pleomorphic neoplastic mesenchymal cells; more common in the lumbar spinal region, but may span anywhere within the cerebrospinal axis (medulla to sacral cord); neoplastic cells are pleomorphic, large, irregularly round cells with abundant cytoplasm, large hyperchromatic nuclei, and a high mitotic rate; positive for vimentin +/- CD18, and actin; negative for lymphocyte markers, S100, cytokeratin, and GFAP
- Meningioangiomatosis: rare, benign hamartoma; forms plaques on the brain stem and cervical spinal cord composed of blood vessels cuffed by proliferating meningothelial cells with mixed degenerative and reactive changes that efface the subarachnoid spaces; reported in dogs, cattle, horses, and recently in a cat (Corbett, JVDI 2022)
- Other meningeal tumors: leiomyoma, leiomyosarcoma, hemangiopericytoma
- Other brain tumors; may be difficult to differentiate histologically depending on subtype
COMPARATIVE PATHOLOGY:
- Extracranial meningiomas, including paranasal and orbital, are often anaplastic and locally aggressive
- Paranasal meningioma, a rare variant, arises from meningeal arachnoid cells that are trapped within or outside bone during skull development; histologically similar to intracranial meningiomas; reported in horses and dogs
- Optic nerve (orbital, retrobulbar) meningioma, a rare variant, arises from meningeal rests of arachnoid cells that project through the dura mater of the optic nerve into the orbital connective tissue; has a distinctive gross and histologic appearance, creating a conical soft mass behind the eye surrounding the optic nerve with large stellate mesenchymal cells that can be confused with epithelial cells; neoplastic cells have abundant glassy eosinophilic cytoplasm +/- swirling pattern and myxoid, chondroid, and/or osseous metaplasia; metastasis and extension into the eye is rare; clinically see exophthalmos, vision loss, and optic nerve/retinal atrophy; reported in dogs only
- Nilgai Antelope: one report of a microcystic meningioma (Breuer, J Comp Pathol 2021)
- African pygmy hedgehog: one report of a ventricular meningoma; neoplastic cells were vimentin and cytokeratin positive (Thompson, JDVI 2020)
- Pet and aviary birds: occasionally seen
- NHPs: exceedingly rare
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