Classification of feline intraocular neoplasms based on morphology, histochemical staining, and immunohistochemical labeling

The objectives of this study were to evaluate morphologic, histochemical, and immunohistochemical characteristics of well-differentiated and anaplastic intraocular neoplasms of cats, and to develop a diagnostic algorithm for, and investigate the association of ruptured lenses with these neoplasms. Seventy-five feline globes with intraocular neoplasms were stained with hematoxylin and eosin and examined by light microscopy. Morphologic diagnoses included 33 intraocular sarcomas, 17 diffuse iris melanomas, 15 lymphosarcomas, three ciliary adenomas, one metastatic carcinoma, and six undifferentiated intraocular neoplasms. Sections of these globes were then stained with periodic acid Schiff (PAS), and immunohistochemical (IHC) labels for various cellular markers. Histochemical staining and IHC labeling confirmed cellular differentiation in 73/75 neoplasms but was discordant with morphologic diagnoses in 8/75. These included four neoplasms morphologically diagnosed as lymphosarcomas but which expressed differentiation antigens consistent with melanoma (n = 3) or ciliary adenocarcinoma (n = 1), and four tumors morphologically diagnosed as intraocular sarcomas that expressed differentiation antigens for melanoma (n = 2), metastatic carcinoma (n = 1), or remained undifferentiated (n = 1). Immunohistochemical labeling suggested a diagnosis in 5/6 morphologically undifferentiated neoplasms including one intraocular sarcoma, two diffuse iridal melanomas, and two ciliary adenocarcinomas. Based upon morphologic, histochemical, and IHC characterization, ruptured lens capsules were detected in 28/30 intraocular sarcomas, 3/24 diffuse iris melanomas and 1/11 lymphosarcomas, but not in ciliary epithelial neoplasms, metastatic carcinomas, or undifferentiated intraocular neoplasms. An algorithm is provided that facilitates stain and IHC label selection for differentiating anaplastic intraocular feline neoplasms.     

Feline conjunctival melanoma: histopathological characteristics and clinical outcomes

Purpose  We report on the histopathology and clinical features of 21 cases of feline conjunctival melanoma.
Methods  A total of 18 cases are from the COPLOW collection and three cases from Antech Diagnostics. We tabulated the location of the tumor, pigmentation, cell shape, mitotic index and presence of multinucleated tumor cells. Surveys were sent to referring ophthalmologists to obtain further information about each case.
Results  The mean age of the cats was 12.4 years. A total of 11 cases were neutered males, six spayed females, and one each of intact female and male. Thirteen of the 21 cases were located on the bulbar conjunctiva, three on third eyelid only, three on palpebral conjunctiva. Sixteen tumors were pigmented while five were amelanotic. Seventeen of the cases consisted of round cell only while four cases were mixed populations of round and spindle cell. Fourteen of the cases contained multinucleated cells. The mitotic index ranged from 0 to 45 mitotic figures/10 HPF. Of the 13 cases with adequate follow-up information, four showed local recurrence while three reported metastasis. Eight cats had died at the time of the survey. Survival time post-diagnosis ranged from 0.5 to 36 months. Two cases had metastasized to the submandibular lymph nodes and in a third case, an abdominal mass was detected.
Conclusions  Feline conjunctival melanoma is most frequently found on the bulbar conjunctiva, are mostly round cells and suggest that conjunctival melanoma in cats has a poorer long term prognosis than the same neoplasm in dogs.     

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.     

Ocular effects of topical 0.03% bimatoprost solution in normotensive feline eyes

OBJECTIVE: The current study was undertaken to evaluate the effects of topically applied bimatoprost, an ocular hypotensive lipid, on intraocular pressure (IOP) and pupil size (PS) in healthy cats. ANIMAL STUDIED: Nine European Shorthair cats free from clinically relevant ocular abnormalities were used in the study. PROCEDURES: Pretreatment baseline measurements of IOP and PS were obtained bilaterally at 8 am, 2 pm, and 8 pm for five consecutive days (days 1 to 5). Then the cats received one drop twice daily (10 am and 6 pm) of bimatoprost ophthalmic solution 0.03% (Lumigantrade mark, Allergan Inc., Irvine, CA USA), in one randomly selected eye and one drop of artificial tears in the fellow eye (control eye) for 5 days (days 6 to 10). Values for IOP and PS were obtained under the same conditions as in the pretreatment phase. The potential for ocular irritation following bimatoprost application was also evaluated. RESULTS: During the pretreatment period, the mean IOP and mean PS were not significantly different between the eyes subsequently treated with bimatoprost and those subsequently determined as controls. During the treatment period, the mean IOP in bimatoprost-treated eyes was not significantly lower than in control eyes (14.2+/-2.3 vs. 14.5+/-2.8 mmHg). Mean IOP in control eyes was not significantly changed at any time during the study period. A marked reduction of PS was seen in all bimatoprost-treated eyes, but no other clinically relevant side effects were observed. CONCLUSION: Twice daily topical applications of bimatoprost produced miosis but had no significant effect on IOP in healthy cats.     

Melanocytic neoplasia in the cat

Clinical features and histopathological details from 13 cases of melanocytic neoplasia in the cat are presented. The series includes cases of intraocular melanoma (n=5), limbal melanoma (n=2), dermal melanoma (n=5) and one case of metastatic melanoma for which a primary site was not identified. In the case of the intraocular tumours, there was apparent correlation between the degree of cellular pleomorphism, the mitotic rate and the extent of local infiltration. Such an association was not identified for the melanomas arising from the limbus or skin.     

Hypofractionated radiation therapy of oral melanoma in five cats

Five cats with melanoma involving the oral cavity were treated with hypofractionated radiation therapy (RT). Cobalt photons were used to administer three fractions of 8.0 Gray (Gy) for a total dose of 24 Gy. Four cats received radiation on days 0, 7, and 21 and one cat received radiation on days 0, 7, and 13. One of the cats received additional irradiation following the initial treatment course. Two cats received chemotherapy. Their age ranged from 11 to 15 years with a median age of 12 years. Three cats had a response to radiation, including one complete response and two partial responses. All five cats were euthanized due to progression of disease, with one cat having evidence of metastatic disease at the time of euthanasia. The median survival time for the five cats was 146 days (range 66-224 days) from the start of RT. The results of this study suggest that oral melanoma in cats may be responsive to hypofractionated RT, but response does not seem to be durable.     

Equine Melanocytic Tumors: A Retrospective Study of 53 Horses (1988 to 1991)

A study of 57 cutaneous melanocytic tumors from 53 horses revealed 4 distinct clinical syndromes: melanocytic nevus, dermal melanoma, dermal melanomatosis, and anaplastic malignant melanoma. Melanocytic nevus and anaplastic melanoma each had histopathologic features that distinguished them from dermal melanoma and dermal melanomatosis. Dermal melanoma and dermal melanomatosis were histologically similar but could be differentiated by their clinical features. Melanocytic nevi were diagnosed in 29 horses with an average age of 5 years; they were solitary, superficial masses that occurred in both grey and nongrey horses, and in which surgical excision was generally curative. Dermal melanomas were diagnosed in 20 horses with an average age of 13 years; all horses of known coat color were grey. Eight horses with an average age of 7 years had 1 or 2 discrete dermal melanomas. Follow-up information was available for 6 horses; metastases occurred in 2 horses, and surgical excision was apparently curative in 4 horses. Dermal melanomatosis was diagnosed in 12 grey horses with an average age of 17 years; all 6 of these horses evaluated had internal metastases. In 2 aged nongrey horses with anaplastic malignant melanoma, the tumors metastasized within 1 year of diagnosis. Two tumors with features of both melanocytic nevus and dermal melanoma remained unclassified.     

Feline non-ocular melanoma: a retrospective study of 23 cases (1991-1999).

Non-ocular melanoma is considered to be a rare neoplasm in cats; however, more than 150 cases have been reported in the literature since 1961. The objective of this study was to characterise this tumour better by evaluating case outcome and survival data for cats with melanoma and to compare clinical and histopathological findings with those of previous reports. Twenty-three feline non-ocular melanomas were identified, the most common locations being the nose, digit and pinna. Cats with digital melanomas had survival rates similar to their canine counterparts. Histological assignation of benignity, malignancy or junctional activity was not found to be an accurate predictor of clinical behaviour. Melanoma should be considered as a differential diagnosis for cats presenting with pigmented or non-pigmented masses and histopathology is essential for definitive diagnosis, as other tumours may clinically appear quite similar. Regular follow-up examinations are recommended indefinitely for benign or malignant feline melanomas.     

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.     

Circadian rhythm of intraocular pressure in cats

OBJECTIVE: To evaluate the rhythm of intraocular pressure (IOP) in healthy domestic cats with no evidence of ocular disease and to analyze the influence of photoperiod, age, gender and ocular diseases on diurnal-nocturnal variations of cat IOP. ANIMALS: All animals were Domestic Short-haired cats; 30 were without systemic or ocular diseases, classified as follows: 12 male intact adult cats, five intact adult female, five adult spayed female, and eight male cats; the latter were less than 1 year of age. In addition, five adult cats with uveitis and three adult cats with secondary glaucoma were included. PROCEDURE: IOP was assessed with a Tono-Pen XL at 3-h intervals over a 24-h period in 12 healthy adult male cats kept under a photoperiod of 12-h light/12-h darkness for 2 weeks. Eight animals from the same group were then kept under constant darkness for 48 h, and IOP was measured at 3-h intervals for the following 24 h. In addition, IOP was assessed at 3 p.m. and 9 p.m. in five intact females, five spayed females, and in eight young cats, as well as in five adult cats with uveitis and three glaucomatous cats. RESULTS: Consistent, daily variations in IOP were observed in animals exposed to a light-dark cycle, with maximal values during the night. In cats exposed to constant darkness, maximal values of IOP were observed at subjective night. Differences of IOP values between 3 p.m. and 9 p.m. (diurnal-nocturnal variations) persisted in intact females, spayed females, and young animals, as well as in uveitic and glaucomatous eyes. CONCLUSIONS: The present results indicate a daily rhythm of cat IOP, which appears to persist in constant darkness, suggesting some level of endogenous circadian control. In addition, daily variations of cat IOP seem to be independent of gender, age, or ocular diseases (particularly uveitis and glaucoma).     

Metastatic malignant melanoma in a prehensile-tailed porcupine (Coendou prehensilis)

A 14-yr-old male, prehensile-tailed porcupine (Coendou prehensilis) presented for an ulcerated, bleeding lesion of the right flank. The wound presented similar to a bite wound and was treated with antibiotics. After 2 mo, the lesion had increased in size and was nonhealing, so surgical excision was elected. Histopathology diagnosed this lesion as a malignant melanoma with incomplete margins. Radiographs showed no evidence of pulmonary metastasis. At 6 mo, another skin lesion was removed and was diagnosed as malignant melanoma with clean surgical margins. At 8 mo, another four dermal masses were surgically excised and, again, these were melanomas that were completely excised. The animal was euthanized approximately 15 mo after initial presentation due to continued growth of dermal masses, dyspnea, and decreased appetite. Necropsy and histopathology revealed metastatic melanoma present in skin, kidneys, and lung.     

Malignant melanoma of the conjunctiva in a cat

A conjunctival melanoma was diagnosed in an adult domestic cat. The neoplasm was excised without further complications. It is important to differentiate conjunctival melanoma from other types of pigmented ocular neoplasia. In man, conjunctival melanomas are often malignant tumors with potential for metastatic behavior. Although this neoplasm had histologic features of malignancy, no evidence of local recurrence or metastasis has been apparent during the 11-month follow-up period.     

Mast cell tumor destruction by deionized water

In a controlled study, malignant murine P815 mastocytoma cells exposed in vitro to distilled and deionized water died as a result of progressive swelling, degranulation, and membrane rupture. A 90% mean cell death occurred when cells obtained directly from culture were exposed to deionized water for 2 minutes. Of 6 cryopreserved malignant murine cell lines, which included Cloudman S91 melanoma, CMT-93 rectum carcinoma, MMT-06052 mammary carcinoma, and S-180 Sarcoma, only P815 mastocytoma and YAC-1 lymphoma were significantly (P less than 0.05) affected by hypotonic shock; Cloudman S91 melanoma cells were the most resistant. Mastocytoma cells were selectively killed by hypotonic solution, and lymphoma cells were also killed by isotonic saline solution. Local mast cell tumor (MCT) recurrence and percentage survival were evaluated in 12 cats (21 MCT) and 54 dogs (85 MCT) subjected to surgery alone or local infiltration of deionized water as an adjunct to surgery. Of all 16 incompletely excised MCT in cats, there was no local recurrence following injection. Four mast cell tumors (2 cats) regressed after being injected in situ. In dogs with clinical stage-I MCT, local recurrence was detected in 50% (5/10), but with injection after incomplete excision, local MCT recurrence was significantly (P less than 0.05) less (6.6%, 1/15). Percentage recurrence was significantly (P less than 0.05) less and survival significantly greater when incompletely excised grade-II MCT were injected. Mean follow-up period after surgery in cats and dogs was 35 and 23.4 months, respectively.     

Epidemiologic analysis of oral and pharyngeal cancer in dogs, cats, horses, and cattle.

Four hundred sixty-nine oral-pharyngeal malignancies diagnosed in dogs, cats, horses, and cattle and submitted to the Viterinary Medical Data Program between March 1, 1964, and Dec 31, 1974, were analyzed. Of these cases, 84% were in dogs. The most frequent oral-pharyngeal cancer in dogs was melanoma; in cats and horses, it was squamous cell carcinoma. In dogs, the risk of developing melanoma increased more with age than did the risk of developing squamous cell carcinoma and fibrosarcoma. Male dogs had significantly greater risk of developing fibrosarcomas and melanomas than did female dogs. The German Shorthaired Pointer, Weimaraner, Golden Retriever, Boxer, and Cocker Spaniel breeds had significantly higher risk and Dachshunds and Beagles had significantly lower risk, as compared with all breeds combined. There was no significant difference between observed and expected numbers of tonsillar carcinomas diagnosed at veterinary colleges located in small urban areas (less than 50,000 persons) as compared with large urban populations (greater than 500,000).     

Treatment of oral squamous cell carcinoma with accelerated radiation therapy and concomitant carboplatin in cats

Background: Feline oral squamous cell carcinoma (SCC) carries a very poor prognosis with traditional treatments. Hypothesis/Objectives: To examine the effectiveness of adding carboplatin to a previously published accelerated radiation protocol in the treatments of oral SCC in cats. Animals: Thirty‐one cases of oral SCC in cats. Tumor sites included lingual (n = 9), mandible (n = 10), maxilla (n = 7), tonsil (n = 4), and cheek (n = 1). Methods: Prospective trial using a planned radiation protocol consisting of 14 fractions of 3.5 Gy given within a 9‐day period with the addition of carboplatin given at 90–100 mg/m² on day 1 and day 4.5. Treatments were twice daily with a 6‐hour delay between treatments. All cats presenting with oral SCC without evidence of distant metastasis were eligible. Results: Median survival for all cats was 163 days (range 53–770 days) with a mean of 319 ± 53 days with significant predictors of survival being site (P= .004) and whether there was a complete response at 30 days (P= .001). Cats with tumors of tonsil origin or cheek responded best to therapy and were long‐term survivors with a mean survival of 724 days and the median had not been reached because of continued survival of 4 cats. Conclusions and Clinical Importance: This protocol offers an aggressive yet tolerable treatment of oral SCC in cats that might offer improved survival as compared with previously reported treatments. The long‐term survival of cats with tonsillar SCC has not been reported previously.     

Ophthalmic diagnostic tests and ocular findings in healthy adult cockatiels (Nymphicus hollandicus)

Cockatiels (Nymphicus hollandicus) are a common companion psittacine for which little ophthalmic data has been gathered. The goal of this study was to establish normal ocular parameters in healthy cockatiels and evaluate whether intraocular pressure (IOP) varies by restraint method. Twenty-five cockatiels free of ophthalmic disease underwent complete ophthalmic examination including slit-lamp biomicroscopy, indirect ophthalmoscopy, and measurement of palpebral fissure diameter, tear production by absorbent paper point tear test (PPTT) and rebound tonometry. IOP measurements were obtained with birds held in two different body positions (vertical and dorsal recumbency). Cockatiel eyes are atapetal, anangiotic, and possess robust filoplumes, brown irises, pleated pecten, and circular pupil. There was no significant difference for horizontal palpebral fissure diameter, vertical palpebral fissure diameter, PPTT or IOP when comparing dorsal to vertical recumbency. For all eyes (50 eyes from 25 cockatiels), the mean (range) of horizontal palpebral fissures was 5.45 (5.0–6.0) mm, PPTT was 9.39 (6–14) mm/15s, and IOP (both recumbencies) was 13 (8.0–24.0) mm Hg. Described data can be used to improve diagnosis and management of ocular alterations in this species.     

Malignant melanoma in pleural effusion in a 14-year-old cat

CASE DETAILS: A 14-year-old female cat presented with signs of respiratory distress. Pleural fluid was found on radiographic assessment. Cytologic evaluation of the fluid revealed malignant melanocytosis. The cat had a previous history of a recurrent malignant melanoma near the base of the right ear. Due to declining clinical condition, the cat was euthanized. CLINICAL SIGNIFICANCE: Cutaneous malignant melanomas (or melanosarcomas) are uncommon neoplasms in cats, and knowledge is limited. As far as the authors are aware, there are no previous reports in the veterinary literature of malignant melanocytes being identified in pleural effusion in cats, as they have in dogs. This report suggests that, despite conflicting information in the literature regarding the clinical behavior of cutaneous melanomas in cats, these tumors are capable of recurrence and metastasis. Aggressive treatment may be necessary even, as in this case, if the tumor is well differentiated on histopathology.     

Intraocular pressure measurements obtained as part of a comprehensive geriatric health examination from cats seven years of age or older.

OBJECTIVE: To determine intraocular pressure (IOP) in cats > or = 7 years of age undergoing a routine comprehensive geriatric health examination. DESIGN: Prospective study. ANIMALS: 538 cats (1,068 eyes). PROCEDURE: IOP was measured by applanation tonometry following instillation of 0.5% proparacaine. RESULTS: Mean +/- SD IOP for all eyes was 12.3 +/- 4.0 mm Hg (range, 4 to 31 mm Hg). Mean age was 12.3 +/- 2.9 years. Intraocular pressure did not vary significantly cross-sectionally with age. However, in 78 cats, IOP was measured more than once, and follow-up measurements were significantly less than initial measurements (mean time between measurements, 9.4 +/- 3.0 months). The most useful tonometric criteria for identifying ocular abnormalities on the basis of IOP was an IOP > or = 25 mm Hg (mean + 3 SD) or a difference in IOP between eyes > or = 12 mm Hg. Eight cats met these criteria, and 5 of these cats had ophthalmic abnormalities. Low IOP was a nonspecific indicator of the presence of ocular abnormalities, as 111 cats had an IOP < or = 8 mm Hg, but only 2 had uveitis. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that IOP measurements can be a useful addition to a comprehensive geriatric health examination in cats > or = 7 years of age, especially when combined with an ophthalmic examination. Cats without ocular abnormalities that have lOP > or = 25 mm Hg or a > or = 12 mm Hg difference in IOP between eyes should have tonometry repeated or be referred to an ophthalmologist for further evaluation before beginning antiglaucoma treatment.