Ocular and multicentric lymphoma in a young racehorse

A 6-year-old thoroughbred gelding was presented with a history of blepharospasm and opacity in the OS of 1 weeks' duration. Ophthalmic examination findings were consistent with acute uveitis in the OS, and traditional treatment was initiated with systemic antibiotics and anti-inflammatory drugs, topical mydriatics, and corticosteroids. During the total treatment period of 4 weeks response to treatment was weak and the horse developed further problems such as cellulitis of the right hind limb with fever and eventually weight loss and dependent edema. Blood work was indicative of liver disease. Abdominal sonography revealed severe splenomegaly and slight hepatomegaly, and a liver biopsy confirmed malignant T-cell lymphoma. The horse was euthanized due to deteriorating general condition and subsequently underwent postmortem examination. Necropsy and histologic examination revealed a multicentric lymphoma with involvement of spleen, mesenteric lymph nodes, and OU.
The findings in this case demonstrate that the differential diagnosis of intraocular and systemic lymphoma should be considered in any horse presenting with anterior uveitis, especially when uveitis is unresponsive to treatment and when additional systemic signs of illness such as lethargy, fever, weight loss, or dependent edema arise.
Cytological examination of aqueous humor may provide a rapid diagnosis of intraocular lymphoma in eyes with clinical uveitis.     

Ocular manifestations of systemic disease in cats

Systemic feline diseases (parasitic, bacterial, fungal, viral, neoplastic, metabolic, vascular, and immune-mediated) are often associated with ocular symptoms. An ocular examination is an important diagnostic tool and should be part of any physical examination. Conversely, cats afflicted with systemic disease require periodic ocular examinations for prognostic information and to prevent vision threatening complications. Typical feline systemic diseases encountered by the practicing clinician are presented with their commonly associated ocular signs.     

Feline uveitis: diagnosis and treatment

Uveitis is the inflammation of any or all parts of the vascular tunic of the eye; the vascular tunic includes the iris, the ciliary body, and choroid. A good knowledge base, up-to-date reference materials, and good instruments will improve the diagnosis of uveitis. Feline uveitis can be caused by numerous infectious agents in addition to neoplasia and less likely trauma. The infectious causes most commonly associated with feline uveitis include feline leukemia virus, feline immunodeficiency virus, feline infectious peritonitis, systemic fungal infections, toxoplasmosis, and bartonellosis. Neoplastic causes of uveitis can be primary or secondary. Iris melanoma is the most common primary uveal neoplasia and trauma-associated sarcoma is the second most common primary uveal neoplasia. Treatment for the clinical signs of anterior uveitis include topical steroidal or non-steroidal anti-inflammatory agents, parasympatholytic agents for ciliary spasm, to keep the pupil dilated, and to prevent posterior synechia. Posterior uveitis should be treated with systemic medications that will address the underlying cause. Enucleation of blind, painful eyes not responsive to medications is a means to alleviate the animal's discomfort and to further diagnose the underlying cause.     

Ocular penetration of oral doxycycline in the horse

OBJECTIVE: To investigate intraocular penetration of orally administered doxycycline in the normal equine eye and to compare intraocular and serum doxycycline concentrations. Procedures Six mares were administered doxycycline at 10 mg/kg every 12 h by nasogastric tube for 5 days. Blood, aqueous, and vitreous samples were collected on days 1 and 5. All samples were assayed for doxycycline concentrations. Aqueous and vitreous samples were also assayed for protein quantitation. RESULTS: Doxycycline was rapidly absorbed after the first dose (T(max) value of 1.42 +/- 1.28 h); and elimination of doxycycline occurred slowly (median t(1/2) = 10.88 h). Doxycycline could not be detected in the aqueous on days 1 and 5, nor could it be detected in the vitreous on day 1. On day 5, the mean vitreous doxycycline concentration was 0.17 +/- 0.04 microg/mL at 2 h after drug administration. CONCLUSIONS: Repeated oral administration of doxycycline in the horse resulted in steady state serum concentrations of < 1 microg/mL; however, it did not result in appreciable concentrations of drug in the aqueous and vitreous in normal eyes.     

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.     

Clinical and histopathological classification of feline intraocular lymphoma

This retrospective study aimed to describe and classify cats with intraocular lymphoma, determine the proportion of cases with presumed solitary ocular lymphoma (PSOL) compared with ocular manifestations of multicentric disease and assess the clinical outcomes of these patients. One hundred seventy‐two cases identified through biopsy submissions were reviewed histologically; 163 of these cases were subtyped according to the WHO classification system. Cases were categorized as having PSOL or ocular lymphoma with suspected systemic involvement (SSI) based on submission forms and follow‐up data. The majority of cases exhibited concurrent uveitis (75%) and secondary glaucoma (58%). Diffuse large B‐cell lymphoma was the most common subtype (n = 86; 53%), followed by peripheral T‐cell lymphoma (n = 44; 27%). Other subtypes included anaplastic large T‐ (n = 8; 5%) and B‐cell (n = 4; 2.5%) lymphomas, and 15 cases (9%) were negative for all immunohistochemical markers. In sixty‐nine cases (40%), adequate clinical data and sufficient survival data were obtained to distinguish PSOL from SSI. PSOL comprised the majority of cases (64%), while 36% had SSI. When covarying for age at diagnosis, the median survival time was significantly higher (P = 0.003) for cases of PSOL (154 days) versus those with SSI (69 days); hazards ratio of 0.47 for PSOL (95% CI: 0.241‐0.937). The subtype of lymphoma did not affect survival time. Cats with PSOL represent a greater proportion of the disease population, and this subset of cats with intraocular lymphoma has a better clinical outcome.     

Atypical primary ocular melanoma in cats

The clinical and pathologic features of six cases of atypical primary ocular melanoma in cats are described. In contrast to diffuse iris melanomas, these atypical tumors originated multifocally from any portion of the uvea and in five of the six cases were very advanced at the time of clinical presentation. Two of the advanced cases involved primarily the ciliary body, while three others showed extensive involvement of the choroid. Histologically, these tumors consisted primarily of round, heavily pigmented cells lacking the anaplastic nuclear features characteristic of advanced diffuse iris melanomas. The advanced stage of the tumors at presentation may have been due to either the posterior uveal origin of these tumors or to more rapid progression. Additional cases with long-term follow-up need to be studied in order to accurately assess the biological behaviour of these tumors.     

Onchocerca lupi causing ocular disease in two cats

Although canine ocular onchocerciasis has been well described as an emerging pathogen of dogs in Europe and North America over the past 20 years, there are no previous reports of feline ocular onchocerciasis. This report details the clinical, histopathologic, and molecular diagnosis of two domestic short hair cats residing in the United States infected with Onchocerca lupi causing episcleritis and orbital cellulitis. The results of this report suggest that O. lupi is a newly recognized disease of domestic cats.     

Mutation analysis and gene expression profiling of ocular melanomas in cats

Feline ocular melanomas show a high malignant behaviour, but adjunctive therapies are non‐existent. The aim of this pilot study was to determine, whether feline ocular melanomas harbour mutations comparable to mutations in human melanomas and to evaluate the gene expression status of genes known to be involved in initiation and progression of human melanomas. Mutation hotspot regions of several genes of feline ocular melanomas were analysed by DNA sequencing and RNA expression levels of the respective genes and others were evaluated by quantitative real‐time polymerase chain reaction (RT‐qPCR). Common mutations found in human melanomas are not present in feline tumours. Gene expression analysis revealed a significant upregulation of KIT and LTA4H, as well as a downregulation of GNAQ, GNA11, BRAF and RASSF1 in feline ocular melanomas. As KIT seems to harbour a potential as target gene in human uveal melanomas, future studies should further investigate the potential of KIT as target for adjunctive therapy in feline ocular melanomas.     

Therapy for Australian cats with lymphosarcoma

OBJECTIVE: To determine the response of Australian cats with lymphosarcoma to chemotherapy and/or surgery in relation to patient and tumour characteristics, haematological and serum biochemical values and retroviral status. DESIGN: Prospective study of 61 client-owned cats with naturally-occurring lymphosarcoma subjected to multi-agent chemotherapy and/or surgery. PROCEDURE: An accepted chemotherapy protocol utilising l-asparaginase, vincristine, cyclophosphamide, doxorubicin, methotrexate and prednisolone was modified and used to treat 60 cats with lymphosarcoma. Clinical findings were recorded before and during therapy. As far as practical, cases were followed to death, euthanasia or apparent cure. Owner satisfaction with the results of chemotherapy was determined using a questionnaire sent after the completion of chemotherapy. RESULTS: One cat, with lymphosarcoma limited to a single mandibular lymph node, was treated using surgery alone and was cured. The other 60 cats were treated using multi-agent chemotherapy, although seven cats with localised intestinal, ocular and subcutaneous lesions had these lesions partially (2 intestinal lesions) or completely (2 eyes, 2 intestinal lesions and a cluster of regional lymph nodes) resected prior to starting chemotherapy. The median survival time for these 60 cats was 116 days. Of the 60 cats, 48 rapidly went into complete remission following the administration of 1-asparaginase, vincristine and prednisolone (complete remission rate 80%) and these cats had a median survival of 187 days. Three cats were censored from further analysis as their long-term survival data were uninterpretable because they died of causes unrelated to lymphosarcoma or were prematurely lost to follow-up. Twenty cats were classed as 'long-term survivors' based on survival time in excess of one year and at least 14 were 'cured' based on the absence of physical evidence of lymphosarcoma 2-years after initiating treatment. In other words, of the 48 cats that reached complete remission, in excess of 29% were 'cured'. Despite detailed analysis, few meaningful prognostic indicators based on patient or tumour characteristics were identified, although long-term survivors were more likely to be less than 4-years (P= 0.04) and to have tumours of the T-cell phenotype (P= 0.06). Excluding the one FeLV ELISA-positive cat with mediastinal LSA, 7 of 9 cats less than 4 years-of-age were long-term survivors (median survival time >1271 days). There was a strong association between achieving complete remission and long-term survival (P = 0.003). On the basis of 27 replies to a questionnaire, owners were generally very satisfied with the response to chemotherapy, irrespective of the survival time of the individual patient. Eighty five percent of owners expressed complete satisfaction with their decision to pursue chemotherapy and 70% believed their cat's health status improved during the first 2-weeks of treatment. Importantly, 78% of owners considered that chemotherapy required a very substantial time commitment on their part. CONCLUSIONS: It was possible to cure approximately one quarter of cats with lymphosarcoma using sequential multi-agent chemotherapy and/or surgery. FeLV-negative cats younger than 4 years (typically with mediastinal lymphosarcoma) had a particularly favourable prognosis. The decision to embark on chemotherapy should be based on the results of induction chemotherapy with l-asparaginase, vincristine and prednisolone, as the response to this was a good predictor of long-term survival. Cats surviving the first 16 weeks of chemotherapy generally enjoyed robust remissions (in excess of 1 year) or were cured of their malignancy.     

Hypoadrenocorticism as the primary manifestation of lymphoma in two cats

Hypoadrenocorticism secondary to bilateral lymphomatous invasion of adrenocortical tissue was diagnosed in 2 adult castrated domestic shorthair cats. In both cats, findings during initial physical examination (ie, lethargy, anorexia, weight loss, and severe weakness) were consistent with severe hypoadrenocorticism. Hyperkalemia, hyponatremia, and azotemia were also detected, which were consistent with hypoadrenocorticism. Hypoadrenocorticism was documented on the basis of finding low baseline and ACTH-stimulated serum cortisol concentrations. The cats initially responded well to treatment, but both owners chose to have the cat euthanatized. Multicentric lymphoma with infiltration and destruction of the adrenal glands was confirmed during necropsy.     

Evaluation of P-glycoprotein expression in feline lymphoma and correlation with clinical outcome

P-glycoprotein (Pgp) is a transmembrane protein pump involved in drug resistance in canine and human lymphoma. There are no published clinical studies evaluating Pgp expression in feline lymphoma. The purpose of this study is to evaluate the level of Pgp expression in feline lymphoma and correlate it with clinical outcome. Two human Pgp monoclonal antibodies, C219 and C494, were used to detect Pgp expression in tissue samples from 63 cats with lymphoma. Demographic results appear comparable to recently published feline lymphoma studies. The Kaplan–Meier median remission and survival times were 164 and 571 days, respectively. Fourteen cats had positive expression of Pgp using MAb C219, and 40 were positive with C494. Variables statistically associated with survival included bone marrow involvement, stage, substage, and use of radiation therapy as a part of treatment. Pgp expression as assessed by MAb C219 and C494 is not predictive of remission or survival time in cats with lymphoma.     

Biphenotypic B‐cell lymphoma in 2 cats

The clinical and pathologic features of biphenotypic B‐cell lymphoma in 2 cats are reported. Clinical presentation varied from multiple cutaneous masses identified on the thigh in one cat to signs of lethargy from acute hemorrhage due to neoplastic infiltration of one kidney in the other. Cytology and histopathology confirmed round cell neoplasia in both cats and immunochemical staining demonstrated expression of both B‐ and T‐lymphocyte markers by the neoplastic cells in both animals. In PCR analysis of antigen receptor gene rearrangement, clonal rearrangement of B‐cell receptor genes and polyclonal T‐cell receptor gene rearrangement were demonstrated in both lymphomas. These findings were consistent with a diagnosis of B‐cell lymphoma with aberrant CD3 expression in both cases. Clinical progression of disease post diagnosis was rapid in both cats, suggesting a poor prognosis for this lymphoma type. Although bigenotypic receptor rearrangement of lymphoma cells appears relatively common, this is the first known report of actual biphenotypic lymphoma in cats.     

Conjunctival lymphoma: immunophenotype and outcome in five dogs and three cats

Conjunctival lymphoma is well documented in the medical literature, but veterinary reports are few. We report five cases of canine lymphoma, and three of feline in which the presenting sign was conjunctival involvement. All animals were in apparently good health at the time of presentation, and attended the referring clinic because of conjunctival disease. One dog showed generalized lymphadenopathy at presentation, although the ocular lesion was the reason for consultation, but all other patients were well with no detectable disease beyond the eye. All cats were presented for their ocular disease. All dogs were confirmed to have T‐cell tumors, although the histological appearance of these was variable. In contrast, all cats had B‐cell tumors. Referring clinicians and owners were contacted for follow‐up information. Three dogs had been euthanased within 6 months of diagnosis for deterioration of general health. The remaining two were alive and showed no signs of systemic disease. Two cats had good survival following diagnosis, the other died of lesions that may not be related.     

A matched observational study of survival in cats with enucleation due to diffuse iris melanoma

Although a small number of cases of feline diffuse iris melanoma have been documented to metastasize, the prognosis is not known. In this matched observational study, the survival time of 34 cats with enucleation due to histologically confirmed diffuse iris melanoma was recorded. These results are compared to the survival times of 83 age-matched control cats. Affected cats had enucleation between 2 and 10 years prior to the study. One group of control cats with eye disease had enucleation for either lymphoplasmacytic uveitis (27 cases), ocular trauma (seven cases), or endophthalmitis (four cases). In these control cats, enucleations were performed between 2 and 10 years prior to this study. Forty-five additional control cats presented for vaccination between 2 and 10 years prior to the study. The extent of diffuse iris melanoma at the time of enucleation in affected cats was graded according to the extent of involvement of ocular tissues and the invasiveness of the tumor. Affected cats have a significantly decreased survival compared with control cats and cats with extensive tumors at the time of enucleation have the lowest survival rates. Cats with tumors confined to the iris survive at the same rate as controls. These results suggests that early enucleation is important to avoid premature death, presumed to be due to cancer metastasis in cats with diffuse iris melanoma.     

A dexamethasone,melphalan, actinomycin‐D and cytarabine chemotherapy protocol as a rescue treatment for feline lymphoma

Nineteen cats with relapsed high‐grade/large‐cell lymphoma were treated with dexamethasone, melphalan, actinomycin‐D and cytarabine (DMAC). All cats had received Cyclophosphamide, Vincristine, Prednisolone (COP) as first‐line chemotherapy and most cats had received at least 2 prior rescue agents with 14 of 19 having received both epirubicin and lomustine. Five cats (26%) exhibited a response (defined as an improvement or resolution of tumour‐associated clinical signs/tumour volume, or complete/partial response) to chemotherapy though no patients received more than 2 cycles of DMAC. Most cats tolerated the protocol well though 3 patients exhibited Veterinary Cooperative Oncology Group (VCOG) grade 4 neutropenia and 1 patient exhibited grade 4 thrombocytopenia. The median progression‐free survival and overall survival from starting DMAC were 14 and 17 days respectively. There is still an unmet need for successful rescue chemotherapy protocol for cats with relapsed lymphoma. [Correction added on 02 November 2017, after first online publication: The expansion for the term DMAC was previously incorrect and has been corrected in this current version.]