Conference 20 - 2015 Case: 04 20160406

Signalment:

7-year-old neutered female Maltese, dog (Canis familiaris)The animal presented signs of exophthalmos in the right eye, with mucopurulent discharge, for over half a year. Computed tomography scan revealed an irregular, retrobulbar, space-occupying mass with osteolytic lesion. A retrobulbar tumor was highly suspected. After five months of follow-up, the patient was presented for enucleation to relieve the discomfort, poor condition of right eye, and blindness. Right eye transconjunctival exenteration was performed and submitted for histopathological examinations.

Gross Description:

The submitted specimens included (1) the right eye and periorbital mass, (2) right eyelids, (3) third eyelids, and (4) the mass in deep orbit. The periorbital mass, which was solitary, firm, yellowish, and space-occupying, en-compassed and surrounded the globe. On cross section, the mass was multilobulated, leading to deformation of eyeball, but the delineation of eyeball was still identified. There was also a solitary, firm, and brownish tissue of irregular shape and with uneven surface along with the globe. Pieces of the eyelid displayed a firm and solitary appearance, partially containing haired skin coat. The third eyelid with an uneven surface was meaty, brownish, solitary and firm. The tissues obtained from the deep orbit comprised several solitary and firm tissues of variable shape and size. Submitted specimens were trimmed and selected for histopathological examination.

Histopathologic Description:

The periorbital mass, which is located behind the globe, is unencapsulated and poorly demarcated, and is causing the deformation of globe. The neoplastic cells are arranged in islands, small lobules and tight whorls or bundles, and are separated by a delicate fibrous stroma. These tumor cells have epithelioid appearance with ample eosinophilic cytoplasm, fairly distinct cell margins, and large open-faced nucleoli. Mitoses are rare. Islands of chondroid and osseous metaplasia, and varied size of vacuolation resembling adipose tissue, are present in the tumor area. The neoplasm invades the peripheral adipose tissues and extra-ocular muscles. Tumor cells infiltrate the lamina propria of the bulbar conjunctiva and partially replace the outer sclera. Multifocal necrosis is remarkable in the tumor area, but may be rare in the tissue of the submitted slide. Aggregations of lymphocytes and hemorrhage are also noted at the marginal area of the tumor. Retinal detachment, with remarkable hypertrophy of retinal pigment epithelium and degeneration of ganglion cells, is noted. Edema is present in the conjunctival epithelia. At the area behind the globe, the tumor cells encompassed an obscure nerve bundle with degenerative changes, suggestive of an orbital nerve.

By tissue immunohistochemistry tumor cells are immunopositive for vimentin, S-100 and neuron-specific enolase (NSE), and are immunonegative for cytokeratin (CK), desmin, glial fibrillary acidic protein (GFAP), Melan-A, and neurofilament (-).

The epithelia of eyelid and third eyelid demonstrate severe hyperplasia, and the lamina propria displays extensive plas-macytic infiltration and hemorrhage. The tissues from the deep mass display numerous aggregates of lymphocytes, edema, hemorrhage, and necrosis, with presence of suspected neoplastic cells as described.

Morphologic Diagnosis:

Orbit: Orbital meningioma, excisional biopsy, right eye, dog

Lab Results:

N/A

Condition:

Orbital meningioma

Contributor Comment:

Although meningiomas are common tumors in the central nervous system of dogs, orbital meningioma is rare. 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 outside the optic nerve sheath.³ Orbital meningiomas in dogs and humans usually grow slowly, compress the peripheral connective tissues, and may involve bilateral optic nerves with rare ex-tracranial metastasis.^3,6,7 On imm-unohistochemistry, they may show variable positivity for S-100 and vimentin, but are generally negative for cytokeratin.³ It is reported that an orbital meningioma with extracranial metastasis to the lung and heart in a dog demonstrated intracytoplasmic PAS+ granules.⁷

The histological features of meningiomas can be classified as meningotheliomatous, fibromatous, psamommatous or transitional pattern. In a study from the Comparative Ocular Pathology Laboratory of Wisconsin,³ in 22 canine orbital meningiomas collected from 1981-1997, most of them were meningotheliomatous with rare fibromatous foci. The tumors characteristically have large epithelial-like neoplastic cells with nuclei containing disperse chromatin and prominent nucleoli. Psammoma bodies, which are commonly found in intracranial meningiomas, were not found in this study. In addition, islands of bone and cartilage metaplasia, which are very rare in the intracranial menin-giomas, are very commonly present.³ Metaplasia is very rare in human and canine meningiomas, but is more common in the orbital meningioma, which can be a diagnostic aid for both histologic and ultrasound analysis.³ In the present case, the histology findings are very similar to the Wisconsins study; nevertheless, prominent local invasion suggesting malignancy is noted in our case.

In the present case, due to the overlapping expression of neural markers, the diagnosis should rely on histologic findings of classic chondroid and osseous metaplasia with myxomatous changes. It's reported that canine meningiomas reveal variable positive results for neural markers, such as S-100 and NSE.² Correlated to the location, morphology, and IHC results, the differential diagnosis should include an epithelioid variant of malignant peripheral nerve sheath tumor. The orbital meningioma classically shows that epithelioid tumor cells envelope the optic nerve, expand into the peripheral adipose and loose connective tissues with myxomatous stroma, and chondroid and osseous metaplasia is present.⁶ In the veterinary literature, epithelioid malignant PNST involving multiple organs with a mixture of spindle and epithelioid cells histologically has been reported.⁴

JPC Diagnosis:

Eye, extraocular tissues: Orbital meningioma.

Conference Comment:

Orbital meningiomas are generally regarded as slow growing and benign, but intraocular invasion may occur and metastasis has also been documented.Local recurrence is seen with intermediate frequency due in part to the difficulty in obtaining complete excision.The tumors are often found to be closely associated with the optic nerve and may appear to originate from the optic nerve sheath.⁶ Fine needle aspiration or diagnostic imaging may be included in the initial diagnostic process.The cytologic ap-pearance of meningioma cells upon aspiration may include round to polygonal to indistinctly shaped spindle cells which have moderate to abundant pale blue to grey cytoplasm, round to ovoid nuclei, mild anisokaryosis, a granular chromatin pattern, and small or indistinct nucleoli.^8,10 The features may be consistent with a mesenchymal neoplasm without prominent signs of malignancy, but may also present a diagnostic challenge due to the variable appearance of cells.Cells of the adjacent retina may also be obtained during aspiration and various components of the retina, including pigment epithelium, rods and cones, and nerve fibers, which have a distinctive cytologic appearance, should not be interpreted as part of the neoplasm.¹⁰ Central blindness has been found to develop in the opposite eye in some cases of orbital meningioma, which suggests infiltration of the tumor along the optic nerve to the level of the optic chiasm.⁶Aside from being reported in dogs and cats, orbital meningioma has also been reported in large animals, such as cattle, although much less commonly.⁹

The moderator discussed the classic appearance of orbital meningioma in dogs and suggested that in an orbital neoplasm composed of large polygonal to spindle cells containing areas of cartilaginous and osseous differentiation, meningioma should be the first consideration.The differential diagnosis for orbital tumors in the dog includes multilobular tumor of bone, a mesenchymal neoplasm which also contains areas of cartilage and bone; these tumors have a characteristic lobulated pattern, and lobules are surrounded by spindle cells embedded in a rich collagenous matrix.Soft tissue sarcoma is an additional consideration for an orbital spindle cell neoplasm containing abundant collagen; these tumors typically lack bone and cartilage; however, and in dogs, morphologically low-grade but biologically high-grade fibrosarcoma would be the primary concern. -Other considerations for orbital neoplasia include lymphoma, osteosarcoma, lacrimal or sa-livary gland adenocarcinoma, hem-angiosarcoma, liposarcoma (including hibernoma) and canine lobular orbital adenoma. Microscopically, the presence of osteoid would be the discriminating feature for osteosarcoma; and the presence of strap cells, rowed nuclei, and cross striations are characteristic features of rhab-domyosarcoma.³ Macroscopically, canine orbital multilobular adenoma has a discriminating appearance and texture that may help differentiate it from other neoplasms, including the presence of friable, translucent lobules with a delicate capsule and often found to be challenging to manipulate and remove during surgery.Histologically, multilobular adenoma consists of well-differentiated lacrimal or salivary gland tissue with the absence of ducts, and may have PAS positive material within the cytoplasm.⁵

References:

1. Adamo P, Forrest L, Dubielzig R: Canine and Feline Meningiomas: Diagnosis, Treatment, and Prognosis. Compendium. 2004; December(26):951-966.

2.Barnhart KF, Wojcieszyn J, Storts RW. Immunohistochemical staining patterns of canine meningiomas and correlation with published immunophenotypes. Vet Pathol. 2002;39:311-321.

3.Dubielzig RR, Ketring KL, McLellan GJ, Albert DM. Veterinary Ocular Pathology: A Comparative Review. Philadelphia, PA: Saunders Elsevier; 2010:126-141.

4.Garcia P, Sanchez B, Sanchez MA, Gonzalez M, Rollan E, Flores JM: Epithelioid malignant peripheral nerve sheath tumour in a dog. J Comp Pathol.2004;131: 87-91.

5.Headrick JF, Bentley E, Dubielzig RR.Canine lobular orbital adenoma: a report of 15 cases with distinctive features. Vet Ophthalmol. 2004; 7(1):47-51.

6.Mauldin EA, Deehr AJ, Hertzke D, Dubielzig RR. Canine orbital meningiomas: a review of 22 cases. Vet Ophthalmol. 2000; 3:11-16.

7.Perez V, Vidal E, Gonzalez N, Benavides J, et al. Orbital meningioma with a granular cell component in a dog, with extracranial metastasis. J Comp Pathol. 2005; 133: 212-217.

8. Regan DP, Kent M, Mathes R, Almy FS, et al.Clinicopathologic findings in a dog with a retrobulbar meningioma. J Vet Diag Invest. 2011; 23(4):857-862.

9. Reis Jr. JL, Kanamura CT, Machado GM, Franca RO, et al. Orbital (retrobulbar) meningioma in a Simmental cow. Vet Pathol. 2007; 44(4):504-507.

10. Tvedten H, Hillstrom A.Cytologic appearance of retinal cells included in a fine-needle aspirate of a meningioma around the optic nerve of a dog.Vet Clin Pathol. 2013; 42(2):234-237.