JPC SYSTEMIC PATHOLOGY
Signalment (JPC #1925204): Military working dog
HISTORY: This dog was experiencing seizures. At necropsy a large meningeal mass was observed over the cerebrum.
HISTOPATHOLOGIC DESCRIPTION: Brain, meninges (per contributor): Extending to multiple cut borders is an expansile, poorly circumscribed, densely cellular neoplasm composed of interlacing streams and whorls of spindle to polygonal cells supported by a thin fibrovascular stroma interspersed with thicker bands of fibrovascular tissue. Neoplastic cells have variably distinct borders with small to moderate amounts of eosinophilic fibrillar cytoplasm. Nuclei are oval to elongate and vesiculate or contain finely stippled chromatin with one distinct nucleolus. Mitotic figures average less than 1 per 10 HPF. Scattered throughout the neoplasm are low numbers of lymphocytes, plasma cells, neutrophils, and rare macrophages with intracytoplasmic pale brown vacuolated material (hemosiderin). Multifocally, there are several variably sized foci of necrosis admixed with fibrin, hemorrhage, and edema.
MORPHOLOGIC DIAGNOSIS: Brain, meninges (per contributor): Meningioma, breed unspecified, canine.
· Meningiomas are derived from meningothelial (arachnoidal cap) cells which line the arachnoid villi; a unique form (granular cell tumor or meningioma) is thought to derive in common with cells of nerve sheaths and other neural crest mesenchyme
· Meningiomas are slow growing, discrete, expansile neoplasms arising anywhere along the meninges including those surrounding the optic nerve, usually in close association with the dura, that compress but rarely invade the brain
· Meningiomas are the most common type of intracranial primary tumor in the dog (40% of all primary tumors) and cat (60%), and are rare in other species (reported in horses, cattle, sheep, and pigs)
- 82% of meningiomas are intracranial, 15% intraspinal, and 2-3% retrobulbar
o Canine meningiomas are classified according to the human WHO system (2007); incidence is 56% grade I, 46% grade II, and 1% grade III
- In contrast, extracranial meningiomas (paranasal region and orbit) are typically anaplastic and locally aggressive
- Increased prevalence with age
- Golden retrievers and boxers are predisposed
- Pulmonary metastasis is rare
- Higher grade meningiomas tend to have increased numbers of infiltrating macrophages
TYPICAL CLINICAL FINDINGS:
· Neurologic signs depend on location, rate of growth, and degree of brain swelling and herniation; signs are caused by compression of the underlying nervous tissue
· Signs usually progress over weeks to months and include circling, propulsive gait, vision loss, seizures and cranial nerve deficits such as vestibular signs
· Feline meningiomas may be clinically silent in up to 20% of cases
TYPICAL GROSS FINDINGS:
· Solitary, globular, ovoid or tuberous, sometimes plaque-like, well circumscribed, gray to yellow, firm, sometimes gritty masses with a broad-based or pedunculated attachment to the meninges
· 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, but commonly affect the cerebral convexity and basilar meninges; in cats can also arise from the tela choroidea of the third ventricle; 82% of canine meningiomas are intracranial, 15% intraspinal, and 3% retrobulbar
· Hyperostosis of overlying bone may be present
· Cats may have multiple meningiomas (17% of cases)
· Granular cell tumors (granular cell meningiomas) are firm, well-demarcated, and unencapsulated or involve thickened meninges
TYPICAL LIGHT MICROSCOPIC FINDINGS:
· Key histologic features commonly seen are whorl formation, psammoma bodies, nuclear cytoplasmic invaginations, and intranuclear longitudinal bands; other common features include hemorrhage, foci of necrosis, and infiltrates of neutrophils
· Canine grade I mengiomas:
o Meningotheliomatous (epithelioid) meningioma: Diffusely cellular, cells in sheets or lobules of different size 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 cytoplasmic invaginations; most commonly Grade I subtype along with transitional subtype; may have areas of chondroid, osseous, or myxoid, differentiation or xanthomatous tissue
o Psammomatous meningioma: Similar general features to meningotheliomatous meningioma, 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 derived possibly from cells, stroma, or a blood vessel
o Fibrous (fibroblastic) meningioma: Bundles of spindle cells with collagen deposition
o 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; not uncommon to have focal neutrophil accumulations; may have areas of chondroid, osseous, or myxoid, differentiation or xanthomatous tissue
o 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
o Microcystic meningioma: Cells have elongated processes and cytoplasmic and interstitial vacuolation
o 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: Any grade I with evidence of brain invasion, at least 4 mitoses per 10 HPF, or 3 of the following 5 features: loss of architectural pattern replaced by cell sheeting, small cell formation with a high N/C ratio, nuclear atypia or macronuclei, hypercellularity, spontaneous necrosis
· Chordoid meningioma: Forms cords and trabeculae of eosinophilic epithelioid cells in a basophilic matrix
o Atypical meningioma: Are hypercellular with small cells in a sheet-like pattern, with necrotic areas, loss of whorls and fascicles, and more than 4 mitotic figures per 10 HPF
o Clear cell meningioma: Rare; sheets of polygonal cells with clear cyplasm containing PAS-positive, nondiastase-resistant (glycogen) staining
· Canine grade III meningiomas:
o Papillary meningioma: Meningothelial cells arranged in papillary structures supported by fibrovascular cores; rare in dogs
o 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
o Rhabdoid: Discohesive cells with a large vesiculate nucleus and intracytoplasmic paranuclear eosinophilic globular inclusion-like bodies
· Canine other meningiomas:
o Granular cell meningioma: Resemble granular cell tumors elsewhere; solid sheets of large, oval to polygonal cells with abundant granular, eosinophilic cytoplasm containing distinctive PAS positive, diastase resistant intracytoplasmic granules
· Feline meningiomas: More uniform appearance than canine, with whorls of elongate cells, collagen deposition, focal elongate linear mineralization, often prominent necrosis, and cholesterol clefts; not amenable to WHO classification
· EM is the most definitive diagnostic technique; most meningiomas have numerous very long, interdigitating, parallel-layered cytoplasmic processes with normal and abnormal gap and desmosomal junctions
· Granular cell meningiomas (granular cell tumors) intracytoplasmic granules appear to be derived from autophagic lysosomes
ADDITIONAL DIAGNOSTIC TESTS:
· Cytologic examination of stereotactic biopsy of smear preparations is diagnostically very accurate irrespective of histologic classification, with clumps and individualized cells with a round nucleus and variably wispy, elongate eosinophilic cytoplasm; nuclei may exhibit characteristic intranuclear cytoplasmic invaginations or basophilic longitudinal nuclear folds, and can be pathognomonic particularly when whorls or psammomatous bodies are present; neutrophils are a prominent component of some meningiomas
o Positive: Vimentin, E-cadherin, NSE, S-100
o Negative: GFAP, synaptophysin
o Variable: Cytokeratin, claudin-1 (Schwannomas are Claudin-1 negative), PR, CD34, N-cadherin, DCX (doublecortin)
o Canine meningiomas: Early loss of tumor suppressor genes NF2, 4.1B, and TSLC1
o Anaplastic meningiomas: Overexpression of doublecortin and nuclear β-catenin
o VEGF expression in meningiomas is low; meningiomas possessing high levels of VEGF expression had shorter survival in one study
o MMP-9 +/- MMP-2 is expressed in canine intracranial meningiomas (but is not predictive of the formation of peritumoral edema); increased expression in cats
o Cox-2 positive in dogs
o Increased merlin expression (protein product of NF2 tumor suppressor gene) in all meningiomas
o Granular cell meningioma (granular cell tumor): S-100, ubiquitin, and α-1-antitrypsin positive; GFAP, leukocyte, and macrophage marker negative
· Carcinomatosis of the meninges vs. meningothelial and transitional meningioma: Vimentin immunoreactivity of meningiomas, strong cytokeratin immunoreactivity of carcinomatosis
· Supracellar germ cell tumor vs. meningioma (gross ddx): Alpha fetoprotein, placental alkaline phosphatase, c-KIT, and OCT4 immunoreactivity of supracellar germ cell tumors
· Ependymoma, astroblastoma, and choroid plexus tumor vs. papillary meningioma: GFAP immunoreactivity of ependymoma and astroblastoma, strong cytokeratin immunoreactivity for choroid plexus tumor
· Hemangiopericytoma vs. highly vascular meningioma: Both contain endothelial cells, pericytes, and stromal cells
· Fibrous dysplasia vs. psammomatous meningioma: Fibrous dysplasia has thin trabeculae of woven bone that may form rounded islands of mineralized osteoid resembling psammoma bodies
· Schwannomas arising from cranial nerves vs meningioma: Schwannomas are composed of collagen-producing fibroblasts and schwann cells arranged in whorls and palisading arrays
· Gemistocytic and anaplastic astrocytoma vs. granular cell meningioma: Astrocytic neoplasms lack PAS-positive granules and have more invasive growth
· Choroid plexus cholesteatomas in horses vs meningioma (gross ddx): Cholesteatomas are composed of granulomas with central acicular cholesterol clefts
· Angiomatous meningiomas must be differentiated from meningoangiomatosis – a vascular malformation within the intracranial leptomeninges with a proliferation of meningothelial cells around blood vessels
· Primary fibrosarcomas of the meninges are rare
· Meningiomas are the most common primary CNS tumor in the spinal canal of dogs, most occurring from C1-C4 with decreasing frequency caudally
· Paranasal meningioma, a rare variant, arises from meningeal arachnoid cells that are trapped within or outside bone during skull development; reported in horses and dogs; in dogs appears similar to intracranial meningioma but tends to behave more invasively
· Optic nerve meningioma
o General discussion: Reported only in dogs; probably arises from meningeal rests of arachnoid cells that project through the dura mater of the optic nerve into the orbital connective tissue
o Typical gross findings: Creates a conical soft tissue mass that surrounds the optic nerve with occasional limited extension into the choroid or posterior vitreous through the optic nerve but more often infiltrates into the muscle and fat of the orbit
o Typical light microscopic findings: Most commonly large stellate mesenchymal cells that can be confused with epithelial cells with abundant glassy eosinophilic cytoplasm that may or may not form a characteristic swirling pattern typical of meningiomas; commonly have myxoid, chondroid, or osseous metaplasia
· Cutaneous meningiomas are extremely rare in dogs (case reports of 4 dogs total), and are congenital from ectopic arachnoid cells that have become trapped in the dermis during development; adult-onset and presumed to derive from nests of arachnoid cells along nerves of sensory organs that are displaced after the nerves penetrate the dura, or as direct extension or metastasis from intracranial neoplasm
· Meningiomas are rare in domestic animals other than cats and dogs, but have been reported in the horse, cow, and sheep
· Case reports in a Scottish wildcat hybrid, a Bengal tiger, a baboon,
· Meningiomas have been experimentally induced in dogs with methylcholanthrene, Rouse sarcoma virus, and perinatal X-ray irradiation and in cattle with bovine papillomavirus
· Meningiomas in rats are subclassified as fibroblastic, meningothelial (syncytial), granular cell, and psammomatous
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