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Subedited by Dr Phil Tucak
Ocean was a 17-week-old female Australian cattle dog who presented to a specialist veterinary ophthalmology clinic in Perth with a history of having a strange appearance to the right eye for the past two days. She was otherwise feeling well and eating normally. There was no known history of trauma, toxin exposure or travel outside of the Perth area.
Two weeks prior to the referral, Ocean was evaluated at the primary care veterinary hospital for lethargy, vomiting, diarrhoea and inappetence. Examination revealed pyrexia (40.2C) and a palpable caudal abdominal abnormality, with nausea exhibited upon palpation. She later developed lameness with right stifle pain evident. Ocean’s eyes were unremarkable at that time.
Blood work revealed a neutropaenia (0.34 x 109/L, reference range [rr] 2.95-11.64), monocytosis (5.97 x 109/L, rr 1.05-5.1), hyperglobulinaemia (39g/L, rr 23-38), and thrombocytopaenia (55L/uL, rr 148-484). Her C-reactive protein (CRP) level was elevated at 99mg/L (rr 0-10). An in-house blood smear showed band neutrophils and platelet clumping.
A SNAP parvovirus test was negative. Abdominal radiographs were unremarkable. Ocean was treated with intravenous fluids, buprenorphine, metoclopramide, ondansetron, amoxicillin-clavulanate and metronidazole. By day 3, her pyrexia, gastrointestinal signs, and lameness had resolved, and she was feeling and eating better. She was discharged on day 3 with oral amoxicillin-clavulanate and metronidazole.
Ocean was rechecked at the primary care veterinary hospital four and 10 days later. At the first recheck, the neutropaenia was persistent, but the CRP had improved to 25mg/L (rr 0-10). At the second recheck, Ocean’s owner reported she was back to normal other than vomiting once that day. She had finished oral antibiotics two days prior and was no longer on any medication.
Physical examination including ophthalmic examination was unremarkable. Her blood work had normalised including CRP and leukogram. Shortly after the second recheck, the owner noticed an abnormal appearance to Ocean’s right eye, and the dog was then referred to the specialist veterinary ophthalmology clinic.
On initial examination at the ophthalmology clinic, Ocean was bright, alert and visual in both eyes but mildly to moderately blepharospastic with bilateral third eyelid elevation and mild mucoid discharges. Pupillary light reflexes (PLR) were bilaterally positive but reduced. There was bilateral moderate diffuse conjunctival hyperaemia with mild chemosis. There was mild aqueous flare with trace cells in the anterior chamber.
Both irises were medium brown with masses present. In the right eye, there was a large, smooth, pink to tan mass with specks of brown involving the 1-7 o’clock iris, causing dyscoria and tall ovoid pupil. The mass was raised enough to be occupying the majority of the medial anterior chamber and limited the views of the lens, vitreous and retina, which were otherwise unremarkable.
There were two masses in the left eye—a smooth, raised, light brown mass involving the 7-9:30 o’clock mid to peripheral iris and a smooth, raised, brown mass involving the 3-6 o’clock peripheral two-thirds of the iris. The lens, vitreous and retina in the left eye could be visualised and were unremarkable. Intraocular pressures (IOP) in both eyes were normal at 10mmHg. Physical examination was unremarkable including the peripheral lymph nodes.
Ocean was diagnosed with anterior uveitis and iris masses in both eyes. Causes of bilateral uveitis in a young dog include infectious (bacterial, Cryptococcus, Toxoplasma, Neospora), neoplastic and inflammatory (systemic histiocytosis) diseases. Other infectious causes of uveitis exist but were thought to be unlikely based on lack of any travel history.
Differential diagnoses for iris masses include fungal granuloma, inflammatory masses (histiocytic disease) and primary or metastatic tumours. Common iris or ciliary body tumours in dogs include melanoma, melanocytoma, adenoma, adenocarcinoma, and lymphoma. Less common types include haemangioma, haemangiosarcoma, leimyosarcoma, myxoid leiomyoma, medulloepithelioma, and histiocytic sarcoma.
Uveal melanocytoma can be seen in dogs younger than two years old, but iris or ciliary body tumours in puppies are otherwise rare. Ocean had a recent history of systemic illness, and the concern was that the ocular disease was related to the recent systemic illness.
A repeat blood panel was recommended along with an infectious disease panel to rule out obvious infectious causes of uveitis. Complete blood count, serum chemistry panel and serology for Toxoplasma, Neospora, and Cryptococcus were submitted. In the meantime, Ocean was placed on topical prednisolone acetate (Prednefrin Forte, both eyes QID) to treat uveitis.
Ocean was rechecked two days later at the ophthalmology clinic. Her owner reported that Ocean had been lethargic and sleeping more in the last two days and had developed a cloudiness of the right eye. Her appetite was normal. At this point, blood work had shown low-normal haematocrit at 37% (rr 37-55), mild hypoglobulinaemia (24g/L, rr 28-44), mild hyperphosphataemia (2.37 mmol/L, rr 0.8-2.2) and increased CRP (50.4 mg/dl, rr <10.0). Cryptococcus latex agglutination test was negative. Toxoplasma and Neospora titres were still pending.
On ophthalmic examination, Ocean had developed glaucoma in the right eye with an IOP of 49mmHg. She was blind in the right eye with negative menace response, dazzle reflex and PLR. There was mild diffuse corneal oedema secondary to glaucoma. The iris mass in the right eye was largely unchanged, but there was now fibrin over the mass. The left eye’s examination was unchanged from two days prior. IOP was 10mmHg, and she was visual in the left eye.
Physical examination revealed the right mandibular lymph node to be firm and enlarged. The remainder of the peripheral lymph nodes were unremarkable. The left vulva was severely thickened with two 5mm by 7mm papules, and there was a 3mm by 5mm papule on the skin above the left vulva. The anus was severely hyperaemic and diffusely thickened, especially dorsally. No obvious mass or lymphadenomegaly was palpable on rectal examination.
Under brief sedation, fine needle aspirates (FNA) of the bilateral iris masses and right mandibular lymph node were obtained, and the smears were submitted for pathologist review. Ocean was continued on prednisolone acetate (both eyes QID), and topical brinzolamide (Azopt, right eye TID) was added to treat glaucoma. In-house review of FNA smears was suspicious for lymphoma, so a referral letter was sent to a local veterinary oncology specialist. Subsequent pathologist review of the cytology from both iris and lymph node revealed a population of large lymphocytes consistent with lymphoma.
A week later, Ocean was evaluated by specialist veterinary oncologist Dr Jessica Finlay. By that time, Neospora titre had returned and was positive at 1:16; whilst there is no correlation between magnitude of the titre and clinical status, this result was not considered high enough to be the cause of Ocean’s disease.
Toxoplasma titres were still pending. Bilateral mandibular lymph nodes were found to be moderately enlarged, but the other peripheral lymph nodes remained normal on palpation. There were also several well-circumscribed, raised, erythemic lesions (<10mm diameter) on the caudal ventral abdomen. Because paediatric lymphoma is rare, further diagnostic tests were recommended to support the diagnosis. Immunocytochemistry, PCR for Antigen Receptor Rearrangements (PARR) and/or flow cytometry were considered to confirm phenotype and clonality. Immunocytochemistry was requested. Repeat Neospora titres were declined. While Toxoplasma titres were pending, Ocean was started on oral clindamycin (150mg BID).
Immunocytochemistry was consistent with B-cell lymphoma (95% Pax-5 positive). Toxoplasma IgG and IgM were negative (<1:16). Treatment options for B-cell lymphoma were discussed, including multi- and single-agent protocols, palliative intent chemotherapy and prednisolone alone. Ocean’s owner considered the options but indicated they were unlikely to pursue definitive chemotherapy. Oral prednisolone 25mg (1.7mg/kg) PO q24h was commenced, but Ocean’s condition deteriorated. The pet owner elected humane euthanasia about four weeks after the ocular signs started.
Paediatric (<12 month) neoplasia is rare in veterinary medicine. Cutaneous histiocytoma are most commonly diagnosed; however, other haematopoietic neoplasms such as mast cell tumour and lymphoma have been the most commonly reported neoplasms in dogs <12 month old (Keller JAAHA 1992, Kessler BMTW 1997). The response and outcome for dogs <12 month with lymphoma has not been reported, but it is assumed to respond and behave similarly to the adult disease. In children, paediatric neoplasia is similarly uncommon, but lymphoproliferative neoplasma (leukaemia and lymphoma) are common. With thanks to Dr. Jessica Finlay for her input into this case study.
Dr Taemi Horikawa DVM, DACVO, MANZCVS
Dr Taemi Horikawa is a veterinary ophthalmology specialist currently practising at Perth Animal Eye Hospital.
Dr Horikawa has special interests in anterior segment imaging and glaucoma surgeries and is thrilled to be able to offer her experiences in ultrasound biomicroscopy, Ahmed gonioshunts and endoscopic cyclophotocoagulation to the WA veterinary community.
Prior to being convinced by her now-husband to relocate to his native-land Perth in 2018, Dr Horikawa completed her veterinary education at UC Davis, followed by a small animal rotating internship and a three-year comparative ophthalmology residency.
After her board certification, Dr Horikawa practised in Northern California, where she also enjoyed opportunities to provide ophthalmic care to local rescue groups and teach interns.