choroidal melanoma presented as glaucoma - cazalot - rev med vet 2008

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Revue Méd. Vét., 2008, 159, 2, 74-78 Introduction Although relatively rare, uveal melanomas are the most common primary intraocular tumours in dogs, and usually develop from the iris and/or ciliary body [7, 25]. Melanocytic tumours arising from the choroid are far less common, occurring at approximately 5% the frequency of anterior uveal melanomas, and are generally considered benign [5, 10]. By contrast, choroidal melanoma is the most common primary ocular malignant neoplasm among adult humans. It represents 85% of all uveal melanomas, and carries a 25-40% mortality rate [11, 20]. Most of these tumours are discovered during a routine examination of the fundus or following visual symptoms, and they typically appear like a dark grey-colored and elevated lesion [18]. Canine choroidal melanomas may also present like a retro- lental brown pigmented mass visualized during funduscopic examination [5, 14], but in most cases they are not discove- red until secondary ocular disease occurs, such as visual impairment [2], chronic uveitis [5], retinal detachment [4], retrobulbar expansion [14], intraocular haemorrhage [4], or glaucoma [4]. The present paper describes the original clinical presentation of a choroidal melanoma in a dog. SUMMARY Melanocytic tumours of the choroid are uncommonly diagnosed in dogs. The authors report the clinical findings on a 7-year-old intact male mixed- breed dog that was referred to the Veterinary School of Toulouse for evaluation of vision loss and presumptive glaucoma in the right eye. On examination, corneal oedema, areflexive mydriasis, and cataract were found on this eye. Intraocular pressure (IOP) was 46 mm Hg. As opacification of ocular media precluded adequate visualization of the posterior segment, ultrasonic examination was performed and revealed findings compatible with total retinal detachment and the presence of a surelevated lesion at the posterior pole of the vitreous cavity. A definite diagnosis of the disease pro- cess was not made, and the glaucoma was treated medically. Despite medical treatment, the condition worsened and the dog was reexamined two months later because the eye had become painful. IOP in the right eye was 64 mm Hg, and B-scans images showed that the lesion of the posterior pole had significantly enlarged in size. The eye was enucleated, and when the globe was cut in half after fixation, a heavily pigmented mass arising from the choroid of the parapapillary area was observed. Cellular morphology of the melanocytic lesion was compatible with a benign choroidal melanoma. Two years postoperatively, the owner reported no signs of either local recurrence or metastatic disease. We discuss the findings in our case and 22 others previously reported in dogs since 1984, and compare the clinical and histo- pathologic features to those described for choroidal melanomas in humans. Keywords: melanoma, retinal detachment, choroid, glau- coma, dog. RÉSUMÉ Mélanome de la choroïde se manifestant par un glaucome chez un chien : présentation du cas et revue de la littérature Les tumeurs mélaniques de la choroïde sont peu fréquentes chez le chien. Les auteurs rapportent l’observation clinique faite sur un chien croisé de 7 ans, présenté à l’Ecole Nationale Vétérinaire de Toulouse pour perte de la vision et suspicion de glaucome sur l’œil droit. Lors de l’examen, un œdème cornéen, une mydriase et une cataracte furent observés sur cet œil. La pression intraoculaire (PIO) était de 46 mm Hg. L’opacification des milieux transparents empêchant la vision du segment postérieur, une échographie fut réalisée, et montra l’existence d’un décollement total de la rétine et la présence d’une lésion en surélévation au pôle postérieur de la cavité vitréenne. Le diagnostic de certitude de ces lésions ne fut pas établi, et le glaucome fut traité médi- calement. Malgré ce traitement le glaucome continua de progresser, et l’animal fut à nouveau examiné deux mois plus tard car l’œil était devenu douloureux. La PIO était de 64 mm Hg, et l’échographie montra une augmentation significative de la taille de la lésion intraoculaire. L’énucléation fut réalisée et après hémisection du globe fixé, une masse fortement pigmentée fut observée en région péripapillaire. L’examen histo- pathologique conclut à un diagnostic de mélanome bénin de la choroïde. Deux ans après la chirurgie, le propriétaire n’a pas noté de récidive locale, ni d’extension métastatique ou d’apparition d’un glaucome sur l’œil adelphe. Les caractères cliniques et histopathologiques de ce cas et des 22 cas rapportés chez le chien depuis 1984 sont discutés et comparés à ceux décrits pour les mélanomes de la choroïde de l’homme. Mots-clés : mélanome, décollement de rétine, choroïde, glaucome, chien. Choroidal melanoma presented as glaucoma in a dog: case report and review of the literature G. CAZALOT 1 , I. RAYMOND-LETRON 2 , A. REGNIER 2* 1 Clinique Vétérinaire La Borde Rouge, 150, rue E. Rostand, 31200 Toulouse - FRANCE 2 Département des Sciences Cliniques, Ecole Nationale Vétérinaire, 23 chemin des Capelles BP 87614, 31076 Toulouse Cedex 3 - FRANCE *Corresponding author: E-mail: [email protected]

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Page 1: Choroidal melanoma presented as glaucoma - CAZALOT - Rev Med Vet 2008

Revue Méd. Vét., 2008, 159, 2, 74-78

IntroductionAlthough relatively rare, uveal melanomas are the most

common primary intraocular tumours in dogs, and usuallydevelop from the iris and/or ciliary body [7, 25].Melanocytic tumours arising from the choroid are far lesscommon, occurring at approximately 5% the frequency ofanterior uveal melanomas, and are generally consideredbenign [5, 10]. By contrast, choroidal melanoma is the mostcommon primary ocular malignant neoplasm among adulthumans. It represents 85% of all uveal melanomas, andcarries a 25-40% mortality rate [11, 20]. Most of these

tumours are discovered during a routine examination of thefundus or following visual symptoms, and they typicallyappear like a dark grey-colored and elevated lesion [18].Canine choroidal melanomas may also present like a retro-lental brown pigmented mass visualized during funduscopicexamination [5, 14], but in most cases they are not discove-red until secondary ocular disease occurs, such as visualimpairment [2], chronic uveitis [5], retinal detachment [4],retrobulbar expansion [14], intraocular haemorrhage [4], orglaucoma [4].

The present paper describes the original clinical presentationof a choroidal melanoma in a dog.

SSUUMMMMAARRYY

Melanocytic tumours of the choroid are uncommonly diagnosed in dogs.The authors report the clinical findings on a 7-year-old intact male mixed-breed dog that was referred to the Veterinary School of Toulouse forevaluation of vision loss and presumptive glaucoma in the right eye. Onexamination, corneal oedema, areflexive mydriasis, and cataract were foundon this eye. Intraocular pressure (IOP) was 46 mm Hg. As opacification ofocular media precluded adequate visualization of the posterior segment,ultrasonic examination was performed and revealed findings compatiblewith total retinal detachment and the presence of a surelevated lesion at theposterior pole of the vitreous cavity. A definite diagnosis of the disease pro-cess was not made, and the glaucoma was treated medically. Despite medicaltreatment, the condition worsened and the dog was reexamined two monthslater because the eye had become painful. IOP in the right eye was 64 mmHg, and B-scans images showed that the lesion of the posterior pole hadsignificantly enlarged in size. The eye was enucleated, and when the globewas cut in half after fixation, a heavily pigmented mass arising from thechoroid of the parapapillary area was observed. Cellular morphology of themelanocytic lesion was compatible with a benign choroidal melanoma. Twoyears postoperatively, the owner reported no signs of either local recurrenceor metastatic disease. We discuss the findings in our case and 22 otherspreviously reported in dogs since 1984, and compare the clinical and histo-pathologic features to those described for choroidal melanomas in humans.

Keywords: melanoma, retinal detachment, choroid, glau-coma, dog.

RRÉÉSSUUMMÉÉ

Mélanome de la choroïde se manifestant par un glaucome chez unchien : présentation du cas et revue de la littérature

Les tumeurs mélaniques de la choroïde sont peu fréquentes chez le chien.Les auteurs rapportent l’observation clinique faite sur un chien croisé de 7ans, présenté à l’Ecole Nationale Vétérinaire de Toulouse pour perte de lavision et suspicion de glaucome sur l’œil droit. Lors de l’examen, un œdèmecornéen, une mydriase et une cataracte furent observés sur cet œil. La pressionintraoculaire (PIO) était de 46 mm Hg. L’opacification des milieux transparentsempêchant la vision du segment postérieur, une échographie fut réalisée, etmontra l’existence d’un décollement total de la rétine et la présence d’unelésion en surélévation au pôle postérieur de la cavité vitréenne. Le diagnosticde certitude de ces lésions ne fut pas établi, et le glaucome fut traité médi-calement. Malgré ce traitement le glaucome continua de progresser, etl’animal fut à nouveau examiné deux mois plus tard car l’œil était devenudouloureux. La PIO était de 64 mm Hg, et l’échographie montra uneaugmentation significative de la taille de la lésion intraoculaire.L’énucléation fut réalisée et après hémisection du globe fixé, une massefortement pigmentée fut observée en région péripapillaire. L’examen histo-pathologique conclut à un diagnostic de mélanome bénin de la choroïde.Deux ans après la chirurgie, le propriétaire n’a pas noté de récidive locale,ni d’extension métastatique ou d’apparition d’un glaucome sur l’œiladelphe. Les caractères cliniques et histopathologiques de ce cas et des 22cas rapportés chez le chien depuis 1984 sont discutés et comparés à ceuxdécrits pour les mélanomes de la choroïde de l’homme.

Mots-clés : mélanome, décollement de rétine, choroïde,glaucome, chien.

Choroidal melanoma presented as glaucomain a dog: case report and review of theliterature

G. CAZALOT1, I. RAYMOND-LETRON2, A. REGNIER2*

1 Clinique Vétérinaire La Borde Rouge, 150, rue E. Rostand, 31200 Toulouse - FRANCE2 Département des Sciences Cliniques, Ecole Nationale Vétérinaire, 23 chemin des Capelles BP 87614, 31076 Toulouse Cedex 3 - FRANCE

*Corresponding author: E-mail: [email protected]

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CHOROIDAL MELANOMA IN A DOG 75

Case reportA 7-year-old intact male mixed-breed dog was referred to

the National Veterinary School of Toulouse for evaluation ofa slowly progressive enlargement associated with vision losson the right eye. Two weeks prior to referral, a presumptivediagnosis of glaucoma had been made by a local practitioner,and the eye had been treated with timolol maleate eye drops.At presentation, the dog was clinically normal. Ophthalmicassessment revealed a red buphthalmic but painless righteye. The unilateral blindness was confirmed by loss of themenace response. Direct and consensual pupillary lightreflexes of the right eye were negative and resulted in anareflexive mydriasis. On the left eye, the absence of consensuallight reflex confirmed a severe ocular or pre-chiasmaticlesion on the right side. Subepithelial corneal oedema, slightaqueous flare and a dense leucocoria were also observed onthe right eye. The presence of a polar haemorrhage wassuspected in the retrolental area. Intraocular pressures eva-luated by applanation tonometry (Tonopen XL®, Mentor)were 46 mm Hg and 16 mm Hg in the right and left eyerespectively. As opacification of the lens precluded adequatevizualisation of the posterior segment, ultrasound examinationwas performed using a 10 MHz probe. On transverse B-scans, two retrolental highly echogenic convex lines formeda funnel-shaped image connected to a conical echodenselesion protruding into the vitreous cavity at the posterior pole(Figures 1 and 2). The mass lesion appeared to have a maximalthickness of approximately 6 mm. Nasal and temporal fluidspaces posterior to the funnel-shaped structure were filledwith lower-amplitude echoes uniformly distributed (Figure2). Cataract was identified in the lens cortex (Figure 2).Examination of the left eye, including gonioscopy withBarkan’s lens, did not reveal any abnormalities. The resultsof complete blood count and blood chemistry were withinnormal limits for a 7-year-old dog. Thus, diagnosis of secon-dary glaucoma was confirmed for the right eye, but thedisease process was not clearly defined. Differential diagno-ses for posterior segment abnormalities included 6-gradepersistent hyperplasic primary vitreous (PHPV) with largeBergmeister’s papilla linked by the hyaloid artery to apersistent retrolental vascular tunic, total retinal detachment

with subretinal haemorrhages, uveal neoplasm with retinaland/or choroidal detachment and hypertensive haemorrhagicendophthalmitis with posterior inflammatory cataract. Theowner refused any further diagnostic procedure and rejectedsuggested surgical treatments for the glaucoma. Thus, theeye was treated with topical applications of a timolol-dorzo-lamide fixed combination and dexamethasone alcohol eyedrops. In spite of the treatment the glaucoma worsened, andthe dog was reexamined two months later because the righteye had become painful. A severe blepharospasm was notedin association with conjunctival and episcleral hyperhemia,deep peripheral corneal vascularization and stromal oedema.The intraocular pressures were 64 mm Hg and 15 mm Hg inthe right and left eyes, respectively. On B-scan images, thefunnel-shaped echogenic structure was still present, but theconical lesion at the posterior pole had enlarged in size andchanged into a roundish mass which connected to the para-papillary area (Figure 3). The mass was largely protrudinginto the vitreous cavity and was acoustically heterogenous(Figures 3 and 4). The base of the tumour with lesser reflec-tivity determined indentation of the surrounding normalchoroidal outline (Figures 3 and 4). A slowly progressivetumour was strongly suspected, and as there was no evidenceof metastatic dissemination on thoracic radiographs,enucleation of the right eye was recommended and perfor-med. When the fixated globe was sagitally cut in half, grossexamination revealed a heavily pigmented mass arising fromthe parapapillary area and invading into the optic disc. Thetumour was protruding into the vitreous cavity, and caudallyextended to the optic nerve head adjacent to the globe(Figure 5). A massive haemorrhagic exsudate filled the ocularcavities. Histologically, the tumour was a well-delineatedsubretinal melanocytic proliferation, tapering off peripherallyinto the choroidal tissue without scleral infiltration but breakingthe optic disc and protruding as a second mass into the opticnerve head. This tumour was composed of a majority of largeplump polyhedral heavily pigmented cells associated withsome polyhedral to spindle less pigmented cells (Figure 6).Nuclei were central, round, small and regular in shape withclear chromatin and central nucleolus. No mitotic figureswere seen. There was no histologic evidence of involvementof the anterior uvea and orbital portion of the optic nerve

FIGURE 1: B-scan ultrasonogram showing two retrolental convex linesconnected to a conical mass protruding into the vitreous cavity inthe vicinity of the papilla.

FIGURE.2: B-scan ultrasonogram (horizontal image) showing the funnelshape aspect delineated by the two convex lines. Cataract is presentin the lens cortex (white arrows).

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76 CAZALOT (G.) AND COLLABORATORS

removed with the globe. A severe exudative haemorrhagicanterior and posterior uveitis characterized by lymphocyticand plasma cell multifocal infiltrates was present, and wasassociated with a fibrino-haemorrhagic clot surrounding thelens. Other associated lesions included: cataract formation,complete retinal detachment and degeneration with cycliticmembrane formation over the posterior lens capsule andciliary processes. Numerous large pigment laden cells wereseen in the exudate. The histologic diagnosis was primarychoroidal melanoma with cytologic features suggestive ofbenign biological behaviour. Two years after diagnosis, theowner contacted by telephone reported no signs of localrecurrence oorr metastatic disease. No signs of glaucoma wereobserved on the fellow eye.

DiscussionEven if melanomas are the most common intraocular

tumours in dogs, choroidal origin has been estimated to beno more than 4% to 5% [10]. We reviewed the veterinaryliterature from 1984 to 2006 and found only 22 cases thatwere histopathologically proven [1, 2, 4-6, 12-15, 19, 24].

The demographic data available for 21 of these dogs indica-te that the median age of dogs with choroidal melanoma is 7years (range, 13 months to 14 years), and that there is nosexual preponderance; ten dogs were female, from which 6were spayed, and 11 were males. Nine breeds of dogs wererepresented with Golden and Labrador Retrievers (n = 7),mixed-breed-dogs (n = 5), and Beagles (n = 3) being themost common. This may represent a breed-related suscepti-bility for retrievers.

Clinically, canine choroidal melanomas may present asraised, darkly pigmented lesions of the fundus identified atroutine ophthalmologic examination [1, 6, 24]. In othercases, the choroidal mass cannot be detected until it resultsin secondary changes manifesting like vision impairment,globe enlargement, and/or ocular pain [16]. These clinicalsigns may be associated with intraocular haemorrhage, uveitis,retinal detachment, or secondary glaucoma as in the currentcase [12-14, 19]. In man, most choroidal melanomas aredetected during routine funduscopic examination. Patientsmay be completely asymptomatic or present with visual fielddefects [11]. Association between choroidal melanomas andsecondary glaucoma has also been reported in humans byseveral authors who observed that tumours presenting a large

FIGURE 3: Ultrasonographic features of the choroidal mass two monthsafter initial presentation. There was obvious enlargement of thelesion.

FIGURE. 4 : B-scan ultrasonogram demonstrating that the choroidalmass was acoustically heterogenous with lesser reflectivity at itsbase compared with its anterior part and surrounding high-reflec-tive normal choroid.

FIGURE 5: Longitudinal histological section of the eye showing thatthe choroidal mass infiltrated the parapapillary area and the opticdisc, and caudally extended beyond the optic nerve head (C: cor-nea; L: lens).

FIGURE 6: Photomicrograph of a section showing large, heavily pig-mented and roughly circular cells (Type I cells), and less pigmen-ted polyhedral to spindle cells (Type II cells). Notice the absence ofmitotic figures (Bleached, H. & E. x 200).

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CHOROIDAL MELANOMA IN A DOG 77

volume, mainly those accompanied by total retinal detachmentwere more frequently associated with secondary glaucoma[3, 8, 17, 21, 23]. This observation may apply to the presentcase too.

A diagnosis of choroidal melanoma is based on history,ophthalmic examination, and results of supplementary testssuch as ocular ultrasonography, computed tomography,magnetic resonance imaging, and cytological puncture.Differential diagnoses for the mass may include neoplasia,infectious granuloma (i.e. blastomycosis in endemic areas),parasitic granuloma (i.e. Dirofilaria or Toxocara), hemato-ma, abscess or cyst [4, 19]. In human beings the differentialdiagnosis includes various lesions, such as choroidal nevus,exudative haemorrhagic chorioretinopathy, congenitalhypertrophy of the retinal pigment epithelium, circumscribedchoroidal hemangioma, and age-related macular degeneration[22]. B-scan ultrasonography will help confirm the clinicaldiagnosis by demonstrating a mass lesion located at theposterior pole of the globe. In the present case, the base ofthe choroidal tumour had low internal reflectivity comparedwith surrounding normal high-reflective choroid. This ultra-sonographic finding resembled choroidal excavation whichis reported in 65% of the human choroidal melanomas [9].Color Doppler is used in human beings to provide furthersupport for diagnosis, and might be of value in dogs. Thepresence of blood flow was observed in the interior of 39/44cases of human choroidal melanomas, but was not identifiedin benign lesions [17]. In complement to ultrasonography,computed tomography or magnetic resonance imaging mayhelp evaluate extraocular involvement of the tumour [11,14].

Typically choroidal melanomas are slowly expansive.They disrupt the overlying pigmented epithelium, rupturethrough the Bruch’s membrane, and eventually develop insidethe vitreous cavity [18]. Canine choroidal melanomas usuallyshow similar gross appearance consisting of a well-delineatedheavily pigmented subretinal lesion with tapering edges [6,16]. The pigmented mass may surround and/or encroach theoptic disc, as observed in our case [2, 6, 13, 14]. Expansioninto the sclera and retrobulbar tissues is not an uncommonoccurrence [10]. Amelanotic choroidal melanomas exist butare very rare in dogs [16].

Histologically, canine choroidal melanomas have commonfeatures with choroidal nevus and melanocytomas in humans[6], but a small percentage assumes features of malignantspindle cell tumours [5]. Other microscopic changes mayinclude detachment and atrophy of the retina, neovascularglaucoma, uveitis, preiridal fibrovascular membranes, andcataract formation [5, 16]. In our case the tumour was mostlycomposed of plump pigment laden polyhedral cells with noevidence of mitosis, corresponding to Type 1 cells, as definedby Collinson and Peiffer [5]. A few Type 2 cells correspondingto plump spindle cells were also present. Thus, this case showedhistologic features previously reported in canine choroidalmelanomas classified "melanocytoma".

Enucleation is the treatment option when the eye is painful,or when the lesion progresses or causes secondary changes [7,16, 25]. When the eye is comfortable, enucleation should bediscussed because of the benign characteristics previously

reported, and a continuous monitoring of the mass is thealternative to evaluate for its enlargement or other secondarychanges [13, 14]. In some cases no clinical signs appearedfor several years without any treatment [24]. Radiotherapy iscurrently the popular treatment for choroidal melanoma inhumans. Enucleation is used for patients with a blind, painfuleye or when the tumour exceeds 40% of the ocular volume[11]. There is no evidence that chemotherapy is helpful in themanagement of these tumours. In man, prognosis after anytreatment depends on the size of the tumour, the patient’sage, the cell type and the extrascleral extension [11]. Therisks for metastasis include increasing tumour size and poorlydefined margins. Choroidal melanomas carry approximately a46% of metastasis by blood way that can occur within 15years of evolution. By contrast, choroidal melanomas in dogsseem to metastasize at a very low rate, as there is only onereport of metastatic canine choroidal melanoma [12].

In conclusion, glaucoma may be the initial feature ofchoroidal melanoma and the present case illustrates the factthat every glaucomatous blind eye with opaque media requiresultrasonographic and, if enucleated, histopathologic exami-nation.

AcknowledgementsThe authors are grateful to Françoise Michaud for revising

the english prose style.

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