Vet Times The website for the veterinary profession https://www.vettimes.co.uk FELINE DIFFUSE IRIDAL MELANOMA Author : JAMES OLIVER Categories : Vets Date : June 3, 2013 JAMES OLIVER looks at several clinical indicators of FDIM that help justify enucleation, as early treatment is associated with longer life expectancy PRIMARY intraocular tumours generally carry a much poorer prognosis in the cat than in the dog. This is because they tend to be both locally invasive and have high metastatic potential. Early diagnosis and treatment of primary intraocular neoplasia is, therefore, of paramount importance in the cat and is associated with an increased life expectancy. The most common primary intraocular tumours in cats are diffuse iridal melanoma and intraocular sarcoma. This article will focus on feline diffuse iridal melanoma (FDIM). Presentation FDIM usually presents as progressive pigmentation of the anterior iris surface. The average age of affected cats is 9.4 years and there appears to be no breed or gender predilection (Dubielzig et al, 2010). The pigmentation may develop at one site only or simultaneously in several regions of the iris. Where the pigmentation is strictly confined to the surface of the iris, as determined by ). histopathology, a diagnosis of iris melanosis is provided (Figure 1 Iris melanosis can, however, progress and undergo malignant transformation to FDIM, therefore 1 / 23
acting as a precursor lesion. The exact aetiology of this transformation is unknown. One study (Stiles et al, 1999) suggested an association between FDIM and FeLV/ feline syncytial virus infection. However, a later study failed to confirm this (Cullen et al, 2002). The rate of progression of iris melanosis/fdim is highly variable. Areas of benign pigmentation (melanosis) may remain static for the entire life of the cat or can progress to advanced uveal melanoma in a relatively short space of time. Once neoplastic cells begin to invade the anterior stroma of the iris, the disease is designated as early FDIM. As progression continues, and deeper and larger areas of the iris become affected, changes in pupil shape and motility occur. Neoplastic cells divide to further infiltrate the iris stroma, which becomes thicker and the surface loses its smooth appearance (Figures 2 and 3). However, FDIM is not always distributed diffusely within the iris. In some cases, FDIM exists as a solid localised mass or as masses within the iris (Figure 4a) and, in other cases, the tumour originates within the ciliary body or even, less commonly, the choroid. As progression continues, the iridocorneal angle becomes involved and secondary glaucoma may develop (Figure 5). Some cases of FDIM do not appear pigmented clinically and these amelanotic variants may be mistaken for other forms of neoplasia, such as adenocarcinoma or lymphoma, or as an inflammatory pathology. An uncommonly reported variant of FDIM is feline atypical melanoma. In this form, the tumours are distributed throughout the uvea and, although they may involve the iris, they are not centred on it. Most cases of feline atypical melanoma are associated with aggregates of tumour cells on the retinal pigment epithelium, which progress to fill the subretinal space and extend into the neurosensory retina (Dubielzig et al, 2010). Diagnosis Diagnosis of FDIM on the basis of clinical examination alone can be very difficult, especially in early cases. This is because the distinction between iris melanosis and FDIM requires histopathological evaluation. Incisional biopsies of the feline iris are rarely taken owing to the risk of iatrogenic damage to the eye and, therefore, a clinical diagnosis of suspected FDIM relies on close monitoring of early lesions and the detection of clinical indicators that suggest progression. Signs to look out for, and that may help justify enucleation, include: progressive and continued increase in the number and size of pigmented regions (Figure 6); 2 / 23
the presence of raised pigmented lesions on the iris surface (Figure 4a); changes in pupil shape and mobility (Figure 6); involvement of the iridocorneal angle (best assessed by gonioscopy; Figure 4b); pigment dispersion pigment may become deposited on the anterior lens capsule, corneal endothelium and within the pectinate ligament or pigmented cells may be free floating within the anterior chamber (Figure 7); and elevations in intraocular pressure. Histopathology As discussed, in some cats with iris melanosis, a morphological change occurs at the time the pigmented foci expand and infiltrate the iris stroma and eventually the iridocorneal angle (Dubielzig and Lindley, 1993; Figures 2, 3 and 8). The cells transform from small angular cells to rounded cells with a round nucleus and a prominent nucleolus. It is this change that represents the transition to early FDIM. As neoplastic progression continues, the cell type may further change. The majority of cases retain a round or polygonal cell morphology, but other reported cell types include spindle cells, balloon cells (large melanocytes with vacuolated cytoplasm), giant cells and anaplastic variants (Dubielzig et al, 2010; Figures 9, 10 and 11 ). Prognosis The prognosis of FDIM is variable and is directly associated with level of progression of disease. This is best assessed histopathologically and survival in cats with enucleation owing to FDIM has been the subject of a study (Kalishman et al, 1998). Cats in which neoplastic cells are confined to the iris and there is moderate spread into the iridocorneal angle have survival times similar to control cats. Poor prognostic indicators, which are associated with shorter survival times, include: high mitotic index (Duncan et al, 1991); involvement of the posterior iris epithelium and ciliary body (Kalishman et al 1998); and presence of neoplastic cells within the scleral venous plexus (Kalishman et al, 1998) 3 / 23
Once neoplastic cells have reached the scleral venous plexus, metastasis is highly likely. Metastasis can occur as late as one to three years after enucleation. The rate of metastasis is unknown, but may be as high as 63 per cent (Stiles and Townsend, 2007). Metastasis usually occurs to abdominal organs, such as the kidneys and liver, but reports of metastasis to lung and bone have also been reported (Dubielzig et al, 2010; Planellas et al, 2010). Treatment Treatment of FDIM is almost completely confined to enucleation. The dilemma for the clinician, however, is when to advise this. Some ophthalmologists advocate removal of eyes as soon as there is progression of pigmented lesions while others wait until glaucoma develops. As mentioned, however, survival is linked to extent of progression and early enucleation has been reported as important to avoid premature death due to presumed metastasis (Kalishman et al, 1998). All cats undergoing enucleation should receive a complete physical examination and thoracoabdominal imaging beforehand in attempt to rule out metastatic disease. Diode laser energy has been used to treat uveal cysts in cats, but there are no reports on use of this therapy in cases of FDIM. In dogs, a vaccine is licensed in the US as a treatment for malignant melanoma and there is no reason why this could not be used in cases of malignant uveal melanoma in this species (Oncept, Merial). The vaccine is not, however, licensed for use in the cat and there are no reports of its use in cases of FDIM. Differential diagnosis As discussed, the main differential diagnosis for FDIM is iris melanosis but definitive diagnosis requires histopathological examination. Other important differential diagnoses include uveal cysts, other forms of neoplasia, uveitis and other causes of glaucoma when this is present. Uveal cysts Uveal cysts are less common in cats than in dogs. They arise from the posterior pigmented epithelium of the iris, the iris pupillary margin or the ciliary processes (Figure 12). They may remain attached at their site of origin or bud off and move anteriorly into the anterior chamber. Uveal cysts only require treatment if their presence is associated with visual deficits or disease of other intraocular structures such as the lens. In these circumstances, photoablation with a diode laser can be considered. 4 / 23
Other forms of intraocular neoplasia The less common amelanotic variant of FDIM may have the appearance of other forms of intraocular neoplasia. Intraocular sarcoma is the second most common primary intraocular neoplasia in cats and adenocarcinoma is sometimes encountered. Lymphoma is the most common metastatic neoplasm, usu ally originating from primary tumours of the abdominal organs. Intraocular lymphoma is usually very exfoliative and cytology of aqueocentesis aspirates diagnostic. Uveitis Pigmentary uveitis as reported in the golden retriever and great Dane is not reported in the cat. The amelanotic variant of FDIM may be associated with uveitis. Common causes of uveitis in the cat include idiopathic, infectious (most commonly FIV, FeLV and FIP in the UK) and neoplastic. Other causes of glaucoma When FDIM is very advanced and secondary glaucoma has developed, it can be very difficult to establish the primary ocular disease on clinical examination alone. Primary glaucoma is much rarer in the cat than in the dog and most cases are secondary. Secondary glaucoma is most common as a result of chronic anterior uveitis, which is usually idiopathic. Other causes include lensassociated (cataract, lens luxation), intraocular neoplasia, hyphaema (systemic hypertension, coagulopathies) and feline aqueous humour misdirection syndrome. Summary FDIM is a fairly common primary intraocular neoplasm and usually occurs following malignant transformation of melanosis of the iris surface. Clinical diagnosis of FDIM is fraught with difficulties. Definitive diagnosis requires histopathology, which is almost always performed on enucleated globes. Several clinical indicators can increase one s suspicion of FDIM and help justify enucleation as early treatment is associated with longer life expectancy. 5 / 23
References Cullen C L, Haines D M, Jackson M L et al (2002). Lack of detection of feline leukemia and feline sarcoma viruses in diffuse iris melanomas of cats by immunohistochemistry and polymerase chain reaction, Journal of Veterinary Diagnostic Investigation 14(4): 340-343. Dubielzig R R, Ketring K, McLellan G J and Albert D M (2010). The uvea. In Veterinary Ocular Pathology: A Comparative Review (1st edn): Saunders Elsevier, Oxford 285-292. Dubielzig R R and Lindley D M (1993). The transition from iris freckle to diffuse iris melanoma in cats: a histopathological study, Proc Am Coll Vet Ophthalmol 24: 56-57 Duncan D E and Pfeiffer R L (1991). Morphology and prognostic indicators of anterior melanomas in cats, Prog Vet Comp Ophthalmol 1: 25-32 Kalishman J B, Chappell R J, Flood L A and Dubielzig R R (1998). A matched observational study of survival in cats with enucleation due to diffuse iris melanoma, Veterinary Ophthalmology 1(1): 25-29. Planellas M, Pastor J, Torres M D, Peña T and Leiva M (2010). Unusual presentation of a metastatic uveal melanoma in a cat, Veterinary Ophthalmology 13(6): 391-394. Semin M, Serra F, Mahe V et al (2011). Choroidal melanocytoma in a cat, Veterinary Ophthalmology 14(3): 205-208. Stiles J, Bienzle D, Buyumihci and Johnson E C (1999). Use of nested polymerase chain reaction (PCR) for detection of retroviruses from formalin-fixed, paraffin-embedded uveal melanomas in cats, Veterinary Ophthalmology 2(2): 113-116. Stiles J and Townsend W (2007). Feline ophthalmology. In Gelatt K N (ed): Veterinary Ophthalmology (4th edn) Blackwell Publishing, Oxford, 1,124. 6 / 23
Figure 10 (far left). Photomicrograph of FDIM within the iris. Pleomorphism and mitotic figures. Images: ANIMAL HEALTH TRUST. 7 / 23
Figure 11 (left). FDIM within the ciliary body. Images: ANIMAL HEALTH TRUST. 8 / 23
Figure 12. Uveal cysts arising from the pupillary margin. Images: ANIMAL HEALTH TRUST. 9 / 23
Figure 1. Three cases of presumed iris melanosis or freckles. These lesions can represent a precursor to feline diffuse iridal melanoma. Images: ANIMAL HEALTH TRUST 10 / 23
Figure 1. Three cases of presumed iris melanosis or freckles. These lesions can represent a precursor to feline diffuse iridal melanoma. 11 / 23
Images: ANIMAL HEALTH TRUST 12 / 23
Figure 1. Three cases of presumed iris melanosis or freckles. These lesions can represent a precursor to feline diffuse iridal melanoma. Images: ANIMAL HEALTH TRUST 13 / 23
Figure 2. Low magnification photomicrograph of FDIM in an eight-year-old domestic shorthaired. The iris is typically diffusely affected. Images: KAREN DUNN 14 / 23
Figure 3. Photomicrograph of FDIM. Pigmented neoplastic cells are found on the iris surface and throughout the iris stroma. In addition, a carpet of neoplastic round cells is present on the posterior pigmented iris epithelium. Images: KAREN DUNN 15 / 23
Figure 4a. FDIM variant a distinct pigmented mass is present within the lateral iris. Images: JAMES OLIVER 16 / 23
Figure 4b. Gonioscopy of the same eye as in Figure 4a. Images: JAMES OLIVER 17 / 23
Figure 5. Secondary glaucoma caused by aggressive FDIM. Note the scleral invasion which has led to globe rupture. Images: ANIMAL HEALTH TRUST. 18 / 23
Figure 6. FDIM in a five-year-old domestic shorthaired cat. Note the subtle pupil distortion at the one to 3 o clock position associated with ectropion uveae. Images: ANIMAL HEALTH TRUST. 19 / 23
Figure 7. FDIM in a four-year-old domestic shorthaired cat. Note pigment deposition on the anterior lens capsule and corneal endothelium. Images: ANIMAL HEALTH TRUST. 20 / 23
Figure 8 (far left). Low magnification photomicrograph of FDIM. The iris and iridocorneal angle are involved in this case. Images: ANIMAL HEALTH TRUST. 21 / 23
Figure 9 (left). Photomicrograph of FDIM within the iris. Round, polygonal and spindle cells are present along with several mitotic figures. Images: ANIMAL HEALTH TRUST. 22 / 23
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