Intraocular tumours are a relatively frequent disease in both the canine and feline species. They mostly occur in anterior uveal structures. Intraocular tumours can be primary or metastatic; the former are usually unilateral while the latter may be unilateral or bilateral. Clinically they can present with the signs typical of an organized primary tumour, or with non-specific signs of uveitis [4], or with a combination of both. Frequently, in the presence of ocular tumours, the clinical signs of complications of uveitis are present, such as haemorrhages, retinal detachment and glaucoma. In the metastatic forms of ocular neoplasms systemic signs of the primary malignancy may also be present.
PRIMARY INTRAOCULAR TUMOURS
- Melanoma
- Carcinoma and adenocarcinoma
- Carvernous haemangioma of the iris
- Leiomyosarcoma
- Haemangiosarcoma of the iris
- Haemangioma of the ciliary body
- Spindle-cell tumours
- Leiomyoma
- Osteosarcoma
- Peripheral nerve sheath tumours
- Chondrosarcoma
- Malignant teratoid medulloepithelioma
Melanoma is the most common intraocular tumour, with carcinomas and adenocarcinomas of the ciliary bodies taking second place in terms of frequency.
Uveal melanomas
Uveal melanomas are commonly divided into benign melanomas, or melanocytomas, and malignant melanomas. The criteria for differentiating between benign and malignant tumours have not been completely defined in the field of ophthalmology. In the past, attempts were made to define malignancy based on the histopathological appearance of cell morphology, mitotic index, tumour invasiveness, macroscopic presentation, size and presence of necrotic areas; however, some studies have shown a total lack of correlation between the mitotic index, invasiveness, size of the tumour and survival of the patient. The current trend is to consider a neoformation as malignant when the mitotic index is greater than four mitotic figures per ten high-power fields (40 x), although there is no confirmation that this corresponds to an equally malignant biological behaviour of the tumour in terms of metastasisation.
Uveal melanomas usually include limbal or epibulbar melanocytoma, anterior uveal melanoma, which may involve the iris or the ciliary body, and choroid melanoma. From a statistical point of view 96% of melanomas occur in the anterior uvea, against the 4% which occur in the choroid.
Limbal or epibulbar melanocytoma
Limbal or epibulbar melanocytoma is a benign tumour which originates from limbal melanocytes. The origin is initially scleral but for practical purposes it is often included among the intraocular melanomas. According to some authors the incidence of this tumour is 10% of all intraocular melanocytic tumours.
Clinically, the tumour is manifested by a perilimbal pigmented lesion (non-pigmented/amelanotic forms have also been described), prevalently in the dorsal portion and more frequently in the lateral quadrant of the sclera (Fig. 1). The neoformation may have well defined or irregular margins, and may be slightly elevated. The nearby cornea is often involved, appearing pigmented, and in some cases corneal lipid degeneration may appear adjacent to the pigmentation. The breeds most commonly affected are the German Shepherd and Retrievers (Golden and Labrador). The age of onset has a first peak in young, 2-4-year old animals, and in these subjects the tumour may be aggressive and infiltrate deeply to involve the iridocorneal angle and the ciliary bodies. There is a second peak incidence in 7- to 11-year old subjects, in which tumour growth seems slower and less invasive, especially in very old animals. The diagnosis may be made on clinical, instrumental (gonioscopy and high resolution ultrasonography) and histopathological grounds. In terms of prognosis, it is extremely important to differentiate these tumours from intraocular tumours with exophytic growth through the sclera and from conjunctival neoplasms. Being a benign tumour, only extremely rare cases of metastases have been reported. The treatment of choice is surgical resection, combined with cryotherapy, radiotherapy or laser photocoagulation. Surgical resection has often been followed by various types of grafts to reconstruct the scleral wall.
Anterior uveal melanoma
Anterior uveal melanoma may originate from both the iris and the ciliary body, and when the signs are complex it is not always possible to determine the exact origin of the tumour. Clinically, in the iris the tumour has a pigmented, nodular appearance, while in the ciliary body, although a pigmented neoformation may be observed, given that the tumour is a space-occupying lesion in many cases the complications resulting from the primary lesion (keratitis, corneal oedema, uveitis, hyphaema, glaucoma, retinal detachment and lens subluxation) are seen before the tumour itself (Fig. 2). Amelanotic forms have been described and suggested to be more anaplastic and, therefore, more malignant than the pigmented tumours.
The more commonly affected breeds are the German Shepherd, Schnauzer, Cocker Spaniel and Retrievers. A possible genetic transmission in Retrievers has also been suggested. No gender predisposition has been found. The mean age at diagnosis is around 9 years old, with clinical cases reported in animals ranging from 2 months to 17 years old.
Uveal melanoma may metastasise to the vertebrae, brain, liver, heart, lungs, spleen and to the contralateral eye. It has been calculated that from 4 to 6% of these melanomas may be potentially metastatic.
Choroidal melanoma
Choroidal melanoma is a rare clinical entity in the dog. It has been estimated to account for 5-6% of all melanin-producing tumours. Clinically, it may present as a flat, well-defined, pigmented neoformation in the posterior segment mostly originating from the peripapillary region around the optic nerve. The initial clinical signs, however, are often complicated by the presence of uveitis, glaucoma, haemorrhages and retinal detachment. The site of origin is the choroidal tissue, but there is often secondary involvement of the adjacent retina. From a statistical point of view there is no typical age of onset and cases have been reported in animals ranging from 13 months to 6 or 7 years old. There is no breed predisposition, although there is a predominance of Beagles and Labradors among the cases reported in the literature.
Choroidal melanomas are rarely metastatic, although some cases of infiltration with extension through the sclera and along the optic nerve have been described. In terms of diagnosis, if the abovementioned complications are not present, the diagnosis can be made by indirect ophthalmoscopy. If the fundus of the eye cannot be seen because of haemorrhage, uveitis [4] or vitreous opacity, the diagnosis is delayed, and in such cases ultrasonography can help to identify the lesion together with other intraocular alterations. Given the often benign nature of this tumour in the initial stages, if no other complications are present, it may be decided simply to follow the evolution of the disease without intervening. However, in the presence of severe intraocular lesions, enucleation of the eye is suggested.
Adenomas and adenocarcinomas
Adenomas and adenocarcinomas are the second most frequent primary tumours in the dog, with an incidence of around 50% compared to uveal melanomas. Frequently they occur as isolated, non-pigmented, pinkish, papillary and non-invasive masses which prolapse at the pupil, behind the iris (Fig. 3). In other cases the tumours can be more aggressive, projecting to the iridocorneal angle or to the periphery of the iris. In some subjects they can appear pigmented. Histologically they can originate from the pigmented or non-pigmented epithelium of the iris and of the ciliary body. As regards growth, adenocarcinomas appear to be more aggressive, with a prevalently exophytic type of growth, in contrast to adenomas, which tend to have endophytic, more contained growth. Some authors have proposed a classification into non-invasive adenomas, invasive adenomas affecting the uveal stroma but not the sclera, invasive adenocarcinomas affecting the sclera (non-metastatic or partially metastatic) and finally pleomorphic adenocarcinomas which tend to metastasise to the vascular system and to the orbit.
In the past, the breeds considered most affected were the American Cocker Spaniel and the German Shepherd, while currently the incidence is higher in Golden and Labrador Retrievers. The mean age of onset reported in the literature is between 6.7 to 9 years old, with adenomas having an earlier onset.
These tumours may originate from the pigmented and non-pigmented epithelium of the iris and ciliary body. In terms of diagnostic procedures, needle biopsies are often not useful and may potentially trigger metastatic dissemination. Treatment is enucleation of the eye, as excision or evisceration, with the goal of then inserting a prosthetic eyeball, may give rise to local relapses.
Malignant teratoid medulloepithelioma
Medulloepithelioma is a congenital tumour which is rare in the dog. The tissue of origin of this tumour is the primitive neurectoderm, an embryonic, non-differentiated tissue. The tumour usually occurs in the ciliary body, but it can extend and involve the posterior segment and the retina. Clinically, it is a papillary, or “bunch of grapes” neoformation, with whitish or whitish-grey masses that invade the posterior chamber. In some subjects the anterior chamber may also be affected by small, nodular formations. Hyphaema, uveitis [4] and glaucoma may also be present. Although the tumour is benign, a few extremely rare cases of metastasisation have been reported. The treatment of choice is surgical resection, combined with cryotherapy, radiotherapy and laser photocoagulation. Surgical resection has often been followed by grafts of various types to reconstruct the scleral wall. In terms of prognosis, it is extremely important to differentiate these tumours from intraocular tumours with exophytic growth through the sclera and from conjunctival neoplasms.
INTRAOCULAR METASTATIC NEOPLASMS
The exact incidence of metastatic ocular neoplasms in the dog is not known. The reasons for this are that: (i) autopsies are not always carried out in animals affected by tumours involving other organs which died of natural causes or were euthanized, (ii) histopathological evaluation of the eyeballs is not carried out in subjects affected by systemic neoplasms, and (iii) subjects with tumours in other organs do not undergo a specialist ophthalmologic examination, and the diagnosis of an intraocular tumour secondary to a primary neoplasm is, therefore, missed.
Since the eye lacks a lymphatic circulation, the spread of metastases is mostly haematogenous; metastases may also occur by contiguity or continuity with tumours originating from the ocular adnexae, cornea, orbit, paranasal sinuses, nasal cavity or the central nervous system. The most frequent intraocular metastatic neoplasm is lymphoma. There are also descriptions of metastatic melanomas originating from the oral cavity, the skin, the contralateral eye and from the nail bed. Other intraocular metastases are seminoma (a transmissible venereal tumour), carcinomas of the bladder, urethra and nasal cavities, rhabdomyosarcoma, sarcomas (osteosarcoma, chondrosarcoma), phaeochromocytoma, mammary adenocarcinoma and thyroid, parathyroid, renal, adrenal and pancreatic adenocarcinomas.
Metastatic tumours of the eyes are usually bilateral, although one eye may be more affected than the other. Clinical manifestations usually consist of non-specific signs of anterior uveitis, such as photophobia, blepharospasm, epiphora, pain, prolapse of the third eyelid, hyperaemia and conjunctival oedema, ciliary flush, corneal oedema, flare, keratic precipitates, hypopyon, hyphaema, rubeosis iridis, miosis and vitreal opacity, all associated with tumour infiltration or the neoplastic mass (Fig. 4). Not infrequently complications of an anterior uveitis may be present, including glaucoma. Metastases in the posterior segment are less frequent, and in such cases they are usually present together with an anterior tumour; clinically, posterior segment metastases are characterized by retinal and subretinal haemorrhages.
An intraocular localisation of multicentric lymphoma (stage V, according to the common classification for the clinical staging of canine lymphomas) is, after generalised lymphadenopathy, the most common sign of the disease. It has been estimated that about 37% of subjects with lymphoma have ocular involvement. The tumour is mostly bilateral and it more frequently involves the anterior uvea causing non-specific signs of uveitis. Not infrequently there is also a characteristic secondary involvement of the cornea with keratitis, characterized by oedema, deep vascularisation and perilimbal infiltration of neoplastic lymphocytes. Infiltration of the posterior uvea is possible, although less frequent, and in such case the clinical signs are retinal and subretinal haemorrhages, retinal detachment and papilloedema. Some authors have reported that the incidences of posterior uveitis, panuveitis and retinal haemorrhages in patients with multicentric lymphoma are 3%, 5% and 9%, respectively. In most cases all the above clinical symptoms usually coexist with the signs of anterior uveits.
The mean age at diagnosis varies between 6 and 9 years old. There is no gender predisposition, while according to some authors the incidence is apparently higher in some breeds, such as the Rottweiler and the Golden Retriever. Being a systemic disease, with ocular involvement, there may be clinical signs typical of a generalised disorder, such as anaemia, thrombocytopenia, disseminated intravascular coagulation and hyperviscosity syndrome.
Ocular involvement, in cases of lymphoma, is also important from a prognostic point of view, as some authors have reported a decreased survival in subjects with lymphoma with intraocular involvement. The diagnosis can be made by cytological studies of tapped aqueous humor.
There are reports of a special form of intravascular lymphoma (malignant angioendotheliomatosis) involving the eye, characterized by panophthalmitis, retinal detachment and localisation in the iris.
As regards treatment, the systemic therapy consists of the more common chemotherapeutic protocols for lymphoma, while topical treatments include corticosteroids, atropine and anti-glaucoma drugs if hypertension, as a complication of uveitis, is present.
Suggested readings
- Wilcock BP, Peiffer RL Jr. Morphology and behavior of primary ocular melanomas in 91 dogs. Vet Pathol. 1986 Jul;23(4):418-24.
- Dubielzig RR. Tumors of the eye. In:Tumors in Domestic Animals Meuten DJ, ed.749 –750. IowaState Press, Ames, IA, USA.2002
- Dubielzig RR, Steinberg H, Garvin H, Deehr AJ, Fischer B. Iridociliary epithelial tumors in 100 dogs and 17 cats: a morphological study.Vet Ophthalmol 1:223 –231,1999
- Barsotti G, Marchetti V, Abramo F. Primary conjunctival mast cell tumor in a Labrador Retriever. Vet Ophthalmol. 2007 Jan-Feb;10(1):60-4.
- Lim CC, Cullen CL, Grahn BH. Choroidal melanoma in the right eye with focal retinal detachment. Can Vet J. 2006 Jan;47(1):85-6.
- Heath S, Rankin AJ, Dubielzig RR.Primary ocular osteosarcoma in a dog. Vet Ophthalmol. 2003 Mar;6(1):85-7. Review.
- Giuliano EA, Chappell R, Fischer B, Dubielzig RR. A matched observational study of canine survival with primary intraocular melanocytic neoplasia. Vet Ophthalmol. 1999;2(3):185-190.
- Dubielzig RR, Ketring KL, McLellan GJ, Albert DM. Veterinary ocular pathology a comparative rewiew. Saunders Ed Elsevier 2010