Intraocular osteosarcoma in a dog

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Intraocular osteosarcoma in a dog A 10-year-old German shepherd dog was presented with unilateral uveitis and hyphaema. Treatment was unsuccessful and the eye was enucleated. Intraocular osteosarcoma was diagnosed by histological examination.

R. R. O. M. VAN DE SANDT, M. H. BOEVÉ, F. C. STADES, M. J. L. KIK† AND J. KIRPENSTEIJN* Journal of Small Animal Practice (2004) 45, 372–374

Ophthalmology Section, and *Soft Tissue Surgery Section, Department of Clinical Sciences of Companion Animals, and †Department of Veterinary Pathology, Faculty of Veterinary Medicine, Utrecht University, The Netherlands R. van de Sandt’s current address is Diergeneeskundig Specialisten Centrum Den Haag, Private Referral Clinic, Regentesselaan, 190 2562 EH The Hague, The Netherlands

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INTRODUCTION Intraocular neoplasms are relatively rare in dogs. Both primary and secondary uveal neoplasms can occur, with a typical unilateral presentation (Dubielzig 1990, Miller and Dubielzig 1996, Collins and Moore 1999). Anterior uveal melanomas, mainly benign, are the most frequent primary intraocular neoplasms in dogs, with the iris and ciliary body being the most common sites of tumour origin. Nodular growth is typical. The incidence of confirmed haematogenous metastasis is low (4 per cent); however, spread along ocular vessels and nerves, or via direct penetration of the sclera or cornea, can occur (Dubielzig 1990, Miller and Dubielzig 1996, Collins and Moore 1999, Pfeiffer and others 1999). Tumours of the ciliary body epithelium are the second most common primary intraocular tumours in dogs (Dubielzig 1990, Miller and Dubielzig 1996, Collins and Moore 1999). They are recognised as space-occupying masses visible through the pupil or by extension through the iris. These tumours may be benign or malignant. The ciliary body carcinomas have a low potential for metastasis and the metastases occur late in the course of the disease. Only a few other primary tumours, such as haemangioma of the iris and ciliary body, and iridal haemangiosarcoma or leiomyosarcoma, have been reported. Ocular inflammation, glaucoma and hyphaema are common sequelae of any intraocular neoplasm (Dubielzig 1990, Miller and Dubielzig 1996, Collins and Moore 1999, Pfeiffer and others 1999). Numerous malignant tumours have been reported to metastasise to the highly

vascular uveal tract, causing secondary uveal neoplasms (Dubielzig 1990, Miller and Dubielzig 1996, Collins and Moore 1999). Intraocular malignant lymphoma is the most common tumour type observed. Bilateral ocular involvement is characteristic and concurrent systemic disease is often present. Anterior uveitis is the most common clinical sign of malignant lymphoma and diffuse uveal infiltration with neoplastic lymphocytes is the typical histological feature. Other types of neoplasms may also invade the eye by local extension from the ocular adnexa, cornea, orbit, paranasal sinuses or nasal cavity (Dubielzig 1990, Miller and Dubielzig 1996, Collins and Moore 1999). Osteosarcoma, a tumour common in the dog, is a highly malignant neoplasm of bone. It is characterised by the formation of osteoid by neoplastic cells and is the primary bone tumour most frequently seen in dogs (osteosarcomas account for 85 per cent of all reported bone tumours). The vast majority of osteosarcomas (75 per cent) occur in the metaphyseal region of bones of the appendicular skeleton. The remaining 25 per cent are observed in the axial skeleton or extraskeletally (O’Brien and others 1993). Primary ocular osteosarcoma has not previously been described in dogs. Patnaik (1990) described one dog with an osteosarcoma in the eye but it is unclear whether this was a primary or a secondary tumour. Another study reported two other ocular osteosarcomas, but specific details were not described (Langenbach and others 1998). This case report describes a primary osteoblastic osteosarcoma in a dog.

CASE HISTORY A 10-year-old German shepherd dog was referred to the ophthalmology section of the Department of Clinical Sciences of Companion Animals at Utrecht University. The dog had a two-week history of hyphaema and blepharospasm of the right eye. The referring veterinarian had initi-

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FIG 1. The eye showing the lobulated tumour in the iris and ciliary body. Haematoxylin and eosin (H&E)

FIG 2. Histology of the tumour showing the osteoid-forming osteoblastic cells. H&E
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ated treatment with dexamethasone-gentamicin-polymyxin eye drops (Helgritin PD; Sanofi) without obvious clinical improvement. Three years prior to the ocular problem, the dog had had a soft tissue swelling at the base of the tail. Fine needle aspiration biopsy had been performed and the tumour was diagnosed JOURNAL OF SMALL ANIMAL PRACTICE

to be a sarcoma. The referring veterinarian surgically removed the tumour, but histological examination was not performed. The tumour did not recur. No other abnormalities were noted upon thorough physical examination. An ophthalmic examination was performed using a hand-held slitlamp bio-

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microscope and indirect ophthalmoscopy. Examination of the right eye showed pronounced scleral hyperaemia, a diffuse corneal oedema, hyphaema of the ventral anterior chamber and a severe swelling of the dorsal (visible) part of the iris, causing a reduced anterior chamber depth. Fundoscopy was not possible because the pupil was invisible. Examination of the left eye revealed no abnormalities. A tentative diagnosis of hyphaema and uveitis in the right eye was made. After unsuccessful treatment of the right eye with dexamethasone eye drops (four times daily) and oral prednisolone (initial dose 2 mg/kg), enucleation was performed because an intraocular neoplasm was suspected. Clinical signs of metastatic disease were not observed before or after the surgical therapy, and thoracic radiography was unremarkable. The enucleated eye was fixed in 0·1M phosphate buffered 10 per cent formalin (pH 7·3) and examined by a pathologist using light microscopy. For the examination, the eye was cut in a horizontal plane and embedded in paraffin. Sections were cut at 5 µm and stained with haematoxylin and eosin. The globe was macroscopically enlarged (2·5
2 cm) (Fig 1). In the area of the lens and the ciliary body, a lobulated grey tumour (1 cm diameter) with a firm consistency was visible. Histological examination showed that the tumour was located in the iris and ciliary body, and was composed of osteoidforming osteoblastic cells with minimal calcification (Fig 2). The nuclei were highly pleiomorphic and the number of mitoses in three randomly chosen high power fields was 30. There were signs of haemorrhage in the vitreous humour. The cornea was vascularised and had focally round nuclear cell infiltrations. Subepithelial lymphoplasmacellular infiltrations were observed in the conjunctiva. Based on the histological findings, intraocular osteoblastic osteosarcoma was diagnosed. Lack of owner compliance meant that additional chemotherapy was not administered. The dog was euthanased two years 373

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later because of unrelated problems. A postmortem examination was not performed.

DISCUSSION In this report, an extraskeletal osteosarcoma located in the eye of a dog is described. The age and histological type of this osteosarcoma corresponded with previous reports (Patnaik 1990, Langenbach and others 1998, Kirpensteijn and others 2002). Extraskeletal osteosarcomas are rare mesenchymal, osteoid-producing neoplasms of soft tissues and visceral organs, without primary periosteal or bone involvement. In a large retrospective study (Langenbach and others 1998), only 0·13 per cent of all submitted biopsies and 12·6 per cent of all osteosarcomas were diagnosed as extraskeletal osteosarcomas. Of the two subcategories, 36 per cent were soft tissue osteosarcomas and were located in the gastrointestinal tract, subcutaneous tissues, spleen, urinary tract, liver, skin, muscle, eye and thyroid gland, while 64 per cent were mammary gland osteosarcomas. The soft tissue osteosarcomas occurred in older dogs (median age 10 years) with no apparent sex predilection. Predisposed breeds were beagles and rottweilers. Patnaik (1990) reported a mean age in dogs with soft tissue osteosarcomas of 11 years and a male to female ratio of 1:3. In a study by Kuntz and others (1998), the mean age of dogs with soft tissue osteosarcomas was 11·5 years. Patnaik (1990) reported an osteosarcoma in the eye of a dog. Clinical findings were chronic glaucoma, corneal opacity and panophthalmitis. Gross pathology showed firm and necrotic tissue that replaced the right eye but no exact details were given. Histological examination revealed the presence of osteoblastic osteosarcoma. The size and extraocular extension of the tumour and presence of metastasis at the time of the diagnosis were not described. It remains unclear whether

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this was an intraocular tumour (primary or secondary) or a tumour of orbital origin invading the eyeball or replacing the eye. Recurrence of the tumour and metastasis to the lymph nodes implied that the tumour had invaded extraocular tissues. Langenbach and others (1998) also mentioned the location of two soft tissue osteosarcomas near or in the eye without giving any further information. The present case describes a primary canine intraocular osteosarcoma without clinical or radiographic signs of metastasis. Extraskeletal osteosarcomas are highly malignant tumours with local infiltration and a high incidence (64 per cent) of distant metastasis (Patnaik 1990). In cases with soft tissue osteosarcomas, local recurrence of the osteosarcoma is the most common cause of death (Langenbach and others 1998). The prognosis for survival of dogs with extraskeletal osteosarcomas appears to be worse than for dogs with skeletal osteosarcomas (Kuntz and others 1998, Langenbach and others 1998). In this case, there were no signs of recurrence or metastasis of the intraocular osteosarcoma. The dog’s survival of more than two years after tumour resection may have been due to the absence of tumour extension beyond the ocular globe, allowing complete removal without risk of local recurrence. The reason for this may be that the eye is a ‘closed’, highly independent system, which might prevent early development of metastasis. On the other hand, most diagnoses of intraocular tumours are made in combination with ocular inflammation. During ocular inflammation, the bloodeye barrier is impaired and the uveal tract will become more vascularised. This will facilitate local spread or distant metastasis. It would be interesting to study the vessel density of intraocular osteosarcomas since there is a relationship between this density and tumour progression in canine osteosarcomas (Coomber and others 1998). The behaviour of intraocular osteosarcomas would suggest a low vessel density tumour.

The presence of a soft tissue sarcoma near the base of the tail three years prior to the intraocular osteosarcoma could suggest a possible relationship between the two tumours. However, this relationship seems unlikely, given the osteosarcoma in the eye occurred three years later and that there were no other signs of metastatic disease anywere else in the body. If the soft tissue sarcoma near the base of the tail was in fact an osteosarcoma and no chemotherapy was given after the tumour resection, a survival rate of less than 10 per cent at one year would be likely (O’Brien and others 1993, Kirpensteijn and others 2002). Evaluation of future cases will be necessary to determine if intraocular osteosarcomas are different from other osteosarcomas. Early resection of intraocular osteosarcomas, to prevent the tumour from extending through the globe, will most likely decrease the chance of recurrence and the presence of metastasis.ll References COLLINS, B. K. & MOORE, C. P. (1999) Diseases and surgery of the canine anterior uvea. In: Veterinary Ophthalmology. 3rd edn. Ed K. N. Gelatt. Lippincott, Williams and Wilkins, Philadelphia. pp 781-788 COOMBER, B. L., DENTON, J., SYLVESTRE, A. & KRUTH, S. (1998) Blood vessel density in canine osteosarcoma. Canadian Journal of Veterinary Research 62, 199-204 DUBIELZIG, R. R. (1990) Ocular neoplasia in small animals. Veterinary Clinics of North America: Small Animal Practice 20, 837-848 KIRPENSTEIJN, J., KIK, M. J. L., RUTTEMAN, G. R. & TESKE, E. (2002) Prognostic significance of a new histologic grading system for osteosarcoma. Veterinary Pathology 39, 240-246 KUNTZ, C. A., DERNELL, W. S., POWERS, B. E. & WITHROW, S. (1998) Extraskeletal osteosarcomas in dogs: 14 cases. Journal of the American Animal Hospital Association 34, 26-30 LANGENBACH, A., ANDERSON, M. A., DAMBACH, D. M., SORENMO, K. U. & SCHOFER, F. D. (1998) Extraskeletal osteosarcomas in dogs: a retrospective study of 169 cases (1986-1996). Journal of the American Animal Hospital Association 34, 113-120 MILLER, P. E. & DUBIELZIG, R. R. (1996) Ocular tumours. In: Small Animal Clinical Oncology. 2nd edn. Eds S. J. Withrow and E. G. MacEwen. W. B. Saunders, Philadelphia. pp 423-431 O’BRIEN, M. G., STRAW, R. C. & WITHROW, S. J. (1993) Recent advances in the treatment of canine appendicular osteosarcoma. Compendium on Continuing Education for the Practising Veterinarian 15, 939-946 PATNAIK, A. K. (1990) Canine extraskeletal osteosarcoma and chondrosarcoma: a clinicopathologic study of 14 cases. Veterinary Pathology 27, 46-55 PFEIFFER, R. L., WILCOCK, B. P., DUBIELZIG, R. R., RENDER, J. A. & WHITELEY, H. E. (1999) Fundamentals of veterinary ophthalmic pathology. In: Veterinary Ophthalmology. 3rd edn. Ed K. N. Gelatt. Lippincott, Williams and Wilkins, Philadelphia. pp 416-422

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