Surgical excision of iridociliary tumors using a postero-anterior cyclo-iridectomy and thermocautery in two dogs.

OBJECTIVE: To report the surgical excision of an iridociliary adenoma and iridal melanocytoma using a postero-anterior cyclo-iridectomy in two dogs. PROCEDURE: A 7 year old neutered male English springer spaniel (case 1) and a 7 year old neutered male Labrador mix (case 2) were presented for evaluation of an intrairidal mass OS. RESULTS: Complete ophthalmic examination revealed a large, dorsonasal, well-demarcated, intrairidal mass OS. A tan to pink intrairidal mass extending into the iridocorneal angle (case 1) and a pigmented intrairidal mass (case 2) were present. B-mode ultrasonography showed a focal, soft tissue, homogenous mass within the uvea adjacent to and contacting the lens. Neither pars plana involvement nor vitreal extension was present. A postero-anterior cyclo-iridectomy was performed through a polyhedral scleral flap. Thermocautery was used to complete the cyclo-iridectomy (case 1) and partial iridectomy (case 2) to excise the mass en bloc. Histopathology revealed a completely excised iridociliary adenoma (case 1) and iris melanocytoma (case 2). The surgery sites healed without complication. Mild uveitis (cases 1 and 2), scant vitreal hemorrhage (case 1), and mild hyphema (case 2) were present three days postoperatively but had resolved ten days postoperatively. The patients remain visual twenty-two months (case 1) and seven months (case 2) postoperatively with a normal intraocular examination other than an iridal defect and mild dorsonasal lens capsular opacities. CONCLUSIONS: The surgical approach described in these cases is utilized in physician-based medicine. This approach and the use of thermocautery provide a viable surgical option for excision of large iridociliary tumors in dogs.

Iris biopsy to investigate feline iris hyperpigmentation.

OBJECTIVE: To evaluate the benefit of iris biopsy in cats with iris hyperpigmentation to differentiate melanosis from early feline diffuse iris melanoma (FDIM). METHODS: The medical records of cats with unilateral iris hyperpigmentation that had undergone iris biopsy between February 2013 and September 2016 at Willows Veterinary Centre & Referral Service were reviewed. RESULTS: Seven cats with unilateral iris hyperpigmentation were included in this retrospective study. The biopsy procedure was performed under general anesthesia (n = 7) with neuromuscular blockade (n = 6) following pre-operative topical miotic therapy (n = 5). One to six biopsy samples per eye were harvested from areas of hyperpigmentation. The samples were partial thickness (n = 4 eyes) and full thickness (n = 3 eyes). Complications were minor: mild intra-operative hemorrhage (n = 4), fibrin clot (n = 2), corneal ulcer (n = 1), post-operative ocular hypertension (n = 1), dyscoria (n = 1), and pseudopolycoria (n = 2). The first biopsy was diagnostic in six cats; a repeat biopsy was necessary in one cat. Histopathology was consistent with melanosis in five cats and with early FDIM in two cats. Screening for signs of metastatic disease (thoracic computed tomography and abdominal ultrasonography) was negative in the two cats with a preliminary diagnosis of early FDIM. Subsequent enucleation and histopathology confirmed the initial diagnosis in both cases. CONCLUSIONS: Iris biopsy in cats with iris hyperpigmentation can be beneficial to differentiate melanosis from early FDIM and thereby help to justify the decision for early enucleation.

Protein expression of KIT, BRAF, GNA11, GNAQ and RASSF1 in feline diffuse iris melanomas.

Feline iris melanoma, the most common feline intraocular tumour, has a reported metastatic rate of 19-63%. However, there is a lack of knowledge about its molecular biology. Previous studies have reported that feline iris melanomas do not harbour mutations comparable to common mutations found in their human counterpart. Nevertheless, there are differences in the gene expression patterns. The aim of this study was to investigate the protein expression of B-RAF oncogene serine/threonine kinase (BRAF), G protein subunit alpha q (GNAQ) and 11 (GNA11), KIT proto-oncogene receptor tyrosine kinase (KIT), and Ras association family member 1 (RASSF1) in feline iris melanomas. Fifty-seven formalin-fixed paraffin embedded (FFPE) iris melanomas and 25 FFPE eyes without ocular abnormalities were stained with antibodies against the respective proteins using immunofluorescence. Averaged pixel intensities/µm2 and percentage of stained area from total tissue area were measured and the results were compared. Compared to the control group, iris melanomas showed overexpression of BRAF, GNAQ, GNA11 and KIT. The higher expression of BRAF, GNAQ, GNA11 and KIT in feline iris melanomas suggest that these proteins may play a key role in the development of feline iris melanomas and KIT may present a possible target for future therapies in cats with feline iris melanomas.

Circulating cell-free DNA does not harbour a diagnostic benefit in cats with feline diffuse iris melanomas.

OBJECTIVES: Feline diffuse iris melanoma (FDIM) is the most common malignant primary intraocular tumour in cats, with reported metastases rates between 19% and 63%. Currently, the only available diagnostic tool for a tentative diagnosis is histopathological examination of the enucleated eye. Therefore, the veterinary ophthalmologist is often faced with the dilemma of whether to enucleate an oftentimes visual eye or to continue monitoring, with the risk of metastases developing. In the past, cell-free DNA (cfDNA) gained more attention in human medicine, especially in the field of oncology. Prior studies have shown the use of cfDNA as diagnostic or prognostic markers in canine and human cancer patients. Therefore, the aim of this study was to investigate cfDNA concentration and integrity in cats with FDIMs compared with cats with benign iris naevi and without ocular abnormalities. METHODS: cfDNA from plasma of cats with iris melanoma (n = 34), iris naevus (n = 30) and without ocular abnormalities (n = 32) were extracted. Primer and probes for feline amyloid beta precursor protein ( APP) and beta actin ( ACTB) were designed for amplicons of various lengths and quantitative PCRs of extracted cfDNA were performed to measure cfDNA concentration and integrity of the plasma samples. Differences of cfDNA concentrations and integrity levels between the three groups (iris melanoma, iris naevi and controls) were analysed using the Mann-Whitney U-test. RESULTS: cfDNA concentration and integrity analysis revealed no significant differences between the cats with iris melanoma, iris naevus or the control group ( P >0.01). Cats with metastases showed similar cfDNA concentration and integrity to cats without metastases. CONCLUSIONS AND RELEVANCE: cfDNA concentration and integrity seem to be insufficient as a diagnostic or prognostic marker in cats with FDIMs.

Four cases of iridociliary tumors in domestic rabbits (Oryctolagus Cuniculus).

Spontaneously occurring ocular neoplasia is rarely reported in rabbits. This case series presents four cases of rabbits diagnosed with iridociliary tumors, which have not been previously reported in this species. Major pathological findings include epithelial tumors affecting the anterior uvea with variable pigmentation and basement membrane formation. Follow-up information was only available for two cases, but neither showed evidence of metastasis, suggesting that the prognosis for these tumors in rabbits, as in other species, may be very good.

Iridociliary adenocarcinoma with oncocytic change in a dog.

An intraocular mass lesion was found in the left eyeball in a spayed female Pembroke Welsh Corgi dog. The surgically resected left eyeball was pathologically examined. Histologically, the mass lesion consisted of proliferation of the atypical cuboidal or columnar epithelial cells, arranging in papillary, tubular or solid form. In addition, some neoplastic cells showed oncocytic change characterized as large oval cells with numerous eosinophilic intracytoplasmic granules. Cytoplasm of the oncocytic cells showed dark blue granules by phosphotungstic acid-hematoxylin stain. Immunohistochemically, the oncocytic cells were intensely positive for cytochrome C. Based on these findings, the ocular mass was diagnosed as iridociliary adenocarcinoma with oncocytic change. The findings indicate that the oncocytic changes of the neoplastic epithelial cells might be caused by mitochondrial accumulation.

Histologic and immunohistochemical predictors of clinical behavior for feline diffuse iris melanoma.

OBJECTIVE: To determine histologic and immunohistochemical predictors of metastasis of feline diffuse iris melanoma (FDIM). ANIMALS: Globes from 47 client-owned cats enucleated for FDIM between January 1985 and December 2013. PROCEDURES: Hematoxylin and eosin-stained sections were evaluated for neoplastic invasiveness and cell morphology, necrosis within the neoplasm, inflammation, and glaucoma. Sections were immunolabeled with antibodies against melan-A, PNL2, E-cadherin, or B-Raf, and label intensity, percentage of labeled cells, and label homogeneity were semi-quantitatively graded. Medical records were evaluated, and referring veterinarians and clients were contacted to determine whether cats developed metastasis following enucleation. The log-rank test or Cox proportional hazards model was used to determine associations between histologic or immunohistochemical parameters and metastasis. RESULTS: Metastasis was suspected or confirmed in 9/47 (19%) cats. Extrascleral extension, necrosis within the neoplasm, a mitotic index of >7 mitoses in 10 high-power (×400) fields, choroidal invasion, and increased E-cadherin and melan-A label intensity were each associated with increased rate of metastasis. PNL2 label homogeneity was associated with decreased rate of metastasis. Decreased PNL2 label intensity and an increasing percentage of neoplastic cells labeled for melan-A each approached significance for increased rate of metastasis. CONCLUSIONS: We report four histologic and three immunohistochemical parameters helpful in determining cats at risk of metastasis of FDIM. Further studies should determine if B-Raf mutations identified in human malignant melanomas are found in cats with FDIM and assess benefits of adjunctive therapy following enucleation of eyes with FDIM bearing poor prognostic indicators.

Outcome of iridociliary epithelial tumour biopsies in dogs: a retrospective study.

To evaluate the outcome of eyes with a confirmed iridociliary epithelial tumour (ICET) following biopsy. Forty-two specimens were selected from the Comparative Ocular Pathology Laboratory of Wisconsin database, including 11 globes enucleated following ICET biopsy and 31 iridociliary biopsies with a confirmed ICET. Histopathology was performed for all specimens. When identified, the corneal surgical wound was examined in enucleated globes. Tumour type and margins were determined for biopsy specimens and follow-up was obtained when possible. Biopsies were performed for diagnosis, debulking or excision. 30/31 biopsies had dirty margins, and iridociliary adenomas were indistinguishable from adenocarcinomas by biopsy. Upon biopsy submission 5/23 biopsies were reported as incisional and 18/23 as excisional. Follow-up information was obtained for 14/18 of those reported as excisional. 8/14 had documented recurrence within 5.0±5.6 months and 6/14 had no recurrence at 21.5±13.6 months postoperatively. Three enucleated globes were diagnosed with iridociliary adenocarcinomas and eight with iridociliary adenomas. The corneal surgical wound was sampled in 8/11 globes. There was a synechia to the surgical wound in 3/8 globes, and in 3/8 globes there were neoplastic cells within or adjacent to the surgical wound. The postoperative success of ICET excision is highly variable; complete excision is rarely achieved and recurrence is common. Biopsy effects on ocular tissues may result in synechia and other surgical complications. ICET can be diagnosed by biopsy, but adenomas are indistinguishable from adenocarcinomas.

Canine ocular tumors following ciliary body ablation with intravitreal gentamicin.

Iridociliary tumors are the second most common primary ocular tumor in dogs and are usually benign. A review of the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) database in 2009 suggested a potential correlation between malignant iridociliary epithelial tumors and ciliary body ablation by intravitreal gentamicin injection for the treatment of glaucoma. The purpose of this case series was to determine whether there is evidence of such a correlation in the COPLOW collection. Mining of the COPLOW database revealed that a significant number (39.5%) of canine globes with a history of ciliary body ablation were subsequently diagnosed with primary ocular tumors at enucleation, most commonly iridociliary epithelial tumors and melanocytic tumors. It is possible that neoplasia was present but unrecognized at the time of ciliary body ablation. These tumors had a higher than expected incidence of malignancy. These cases underscore the importance of reserving ciliary body ablation with gentamicin for disease-free eyes.

Canine pre-iridal fibrovascular membranes: morphologic and immunohistochemical investigations.

OBJECTIVE: Pathologic intraocular neovascularization is a key component of many canine ophthalmic diseases such as uveitis, retinal detachment, intraocular neoplasms, and corneal perforation. The purpose of this study was to evaluate the structure of pre-iridal fibrovascular membranes (PIFMs) associated with several different disease processes and to identify specific factors associated with their development in the canine eye. PROCEDURE: This study examined 36 enucleated canine eyes with the diagnosis of PIFM and one of the following: lens-induced uveitis, retinal detachment, iridociliary adenoma, corneal perforation, severe hyphema, or vitreal gliovascular membranes (canine ocular gliovascular syndrome, COGS). Three histologic stains and six immunohistochemical stains were performed in all 36 PIFM eyes and four histologically normal eyes, including: hematoxylin and eosin, alcian blue periodic acid schiff (PAS), Masson's trichrome, platelet endothelial cell adhesion molecule-1 (CD31), smooth muscle actin, vimentin, laminin, vascular endothelial growth factor (VEGF), and cyclooxygenase-2 (COX-2). RESULTS: Pre-iridal fibrovascular membrane extracellular matrix staining was consistent with collagen and mucins in all cases and positive for laminin in most cases. All PIFMs contained CD31-positive vessels and predominantly lymphoplasmacytic inflammation. Both PIFM vessels and spindle cells were positive for laminin, vimentin, smooth muscle actin, VEGF, and COX-2. Secondary intraocular pathology and immunohistochemical staining of other intraocular structures are also reported. CONCLUSIONS: Pre-iridal fibrovascular membrane morphology and immunohistochemical characteristics were similar across six canine disease processes, suggesting analogous pathophysiologic mechanisms. COX-2 and VEGF were identified using immunohistochemistry and may play a role in PIFM development.

Ocular myxoid leiomyosarcoma in a cat.

A case of myxoid leiomyosarcoma likely of iris dilator muscle origin in the enucleated eye of a 6-year-old domestic short haired cat is reported. The poorly demarcated mass expanded the iris, partially filled the globe and extended into the optic nerve. The mass was composed of spindle cells separated by abundant matrix positive for mucopolysaccharides with alcian blue. The neoplastic cells were immunoreactive for smooth muscle actin (SMA), S100 and vimentin, and negative for cytokeratin, Melan-A, glial fibrillary protein (GFAP) and desmin. There was no evidence of recurrence or metastasis 6 months after enucleation.

[Intraocular hemorrhage in a goat with thrombocytopenia and metastasis of an adenocarcinoma in the iris]. / Intraokuläre Blutung bei einer Ziege mit Thrombozytopenie und Karzinommetastase in der Iris.

This case report describes the findings in a 10-year-old goat with metastasis of an adenocarcinoma in the iris. Two weeks before admission, the owner had noticed blepharospasm of the left eye. Clinical examination by the referring veterinarian revealed unilateral intraocular hemorrhage. The goat was referred to our clinic for further work-up. The rectal temperature was 40 degrees C. The most important haematological result was severe thrombocytopenia. There was mild corneal oedema of the left eye. Approximately 75 per cent of the anterior chamber was filled with non-coagulated blood. The fluid in the anterior chamber dorsal to the blood was cloudy, and the corpora nigra could not be seen clearly. All other internal parts of the eye could not be seen. Ultrasonography of the left eye confirmed cloudiness of the anterior chamber and revealed moderate thickening of the iris. The right prescapular lymph node was markedly enlarged. Cytological examination of a fine needle aspirate of the lymph node showed a mixed population of neoplastic cells. Based on immunohistochemical evaluation of the cells metastasis of a carcinoma was diagnosed. The goat was subjected to euthanasia, and a postmortem examination was carried out. The anterior chamber of the left eye contained blood, and the iris was thicker than normal and adhered to the posterior surface of the cornea. There were neoplastic alterations in the iris, the oesophagus, the lung lobes, the liver, the kidney and in the prescapular, retropharyngeal, mediastinal and hepatic lymph nodes. Histologically, a diagnosis of carcinoma was confirmed, but the origin of the tumour could not be determined.

Surgical management of a progressive iris melanocytoma in a Mustang.

CASE DESCRIPTION: A 7-year-old gray Mustang gelding weighing 454 kg was presented for evaluation of a brown mass within the left eye (OS) of 1 year's duration with recent enlargement. CLINICAL FINDINGS: A nonpainful, 8 mm diameter, brown, vascularized mass was identified in the anterior chamber of the OS. Ocular B-scan ultrasound confirmed iris involvement and corneal endothelial contact. Histopathology confirmed the presumptive diagnosis of a uveal melanocytic neoplasm, and revealed 1-3 mitotic figures per high power (400x) field. TREATMENT AND OUTCOME: The mass was removed via sector iridectomy without complications, but without complete margins. Three cutaneous melanocytomas noted 1.5 months postoperatively were completely excised. No tumor regrowth was noted 15 months postoperatively, supporting a diagnosis of melanocytoma for the iridal mass. CLINICAL RELEVANCE: Sector iridectomy is a reasonable treatment option for uncomplicated iridal melanocytomas in horses. Mitotic index and presence of cutaneous melanocytic neoplasms may be irrelevant to the prognosis of equine iridal melanocytic neoplasms.

Myxoid leiomyoma of the iris in a dog.

A leiomyoma of the iris is described in an 11-year-old Yorkshire Terrier. This is a rare primary intraocular tumor in dogs and we describe the clinical presentation, gross findings and histopathologic characteristics of this tumor. The diagnosis was made on the basis of light microscopy and immunohistochemical staining using antidesmin antibodies, which is specific for myogenic tissues. An unusual feature of the tumor was the presence of myxoid change. To our knowledge myxoid change has not been previously described in a primary intraocular leiomyoma.

Lack of detection of feline leukemia and feline sarcoma viruses in diffuse iris melanomas of cats by immunohistochemistry and polymerase chain reaction.

Diffuse iris melanoma was confirmed by light-microscopic examination in 10 formalin-fixed, paraffin-embedded globes from 10 cats. To determine if feline leukemia virus or a replication defective feline leukemia virus, feline sarcoma virus, was present in these anterior uveal melanomas, immunohistochemistry and polymerase chain reaction for feline leukemia virus were utilized. Immunohistochemical staining for feline leukemia virus glycoprotein 70 was performed on all 10 tumors using an avidin-biotin complex technique. The DNA was extracted from each specimen and a 166-base pair region of the feline leukemia virus long terminal repeat was targeted by polymerase chain reaction. Immunohistochemical staining for feline leukemia virus glycoprotein 70 and polymerase chain reaction amplification of a feline leukemia virus long terminal repeat region were negative in all cases. Feline leukemia virus/feline sarcoma virus was not detected in any neoplasms and therefore was unlikely to play a role in the tumorigenesis of these feline diffuse iris melanomas.