Prevalence, Anatomical Distribution, and Risk Factors of Adipocytic Tumors and Xanthomas in Psittaciformes: 1096 Cases (1998-2018).

Adipocytic tumors are mesenchymal tumors that are commonly reported in psittacine birds; however, large-scale studies evaluating their prevalence and associated risk factors are lacking. A retrospective study of adipocytic tumors in psittacine birds was performed by reviewing pathology submissions from the University of California, Davis-Drury Reavill Pathology Database, containing 26 013 submissions from psittacine birds (1998-2018). Age, sex, genus, anatomic distribution, and pathological diagnosis were collected for each case when available. The prevalence, risk factors, and association with other lipid-accumulation disorders were reported. A total of 450 cases of lipoma, 129 cases of myelolipoma, 35 cases of hemangiolipoma, 31 cases of liposarcoma, and 451 cases of xanthoma were identified. The prevalence of adipocytic tumors and xanthomas on necropsy was 1.3% (158/11 737, 95% confidence interval [CI]: 1.1-1.6). Adipocytic tumors were identified in 27 genera. Amazona (odds ratio [OR] = 1.93, 95% CI: 1.24-2.99, p = 0.004), Myiopsitta (OR = 2.3, 95% CI: 1.0-5.2, p = 0.041), Melopsittacus (OR = 3.4, 95% CI: 2.1-5.5, p < 0.001), and Agapornis (OR = 3.5, 95% CI: 2.0-6.1, p < 0.001) had significantly higher odds of developing adipocytic tumors compared with other genera, whereas Ara had significantly lower odds (OR = 0.5, 95% CI: 0.3-0.9, p = 0.030). Age was also a significant risk factor for many types of adipocytic tumors. There was no significant association between general adipocytic tumor formation and atherosclerosis or hepatic lipidosis. Xanthomas were associated with atherosclerosis (OR = 1.88, 95% CI: 1.01-3.51, p = 0.048), but not hepatic lipidosis (p = 0.503). On necropsy, the trunk and air sacs were the most common sites of xanthoma formation, whereas the trunk and liver were the most common sites of lipoma and myelolipoma formation, respectively.

Antemortem Diagnosis and Successful Long-term Management of Disseminated Intracoelomic Xanthogranulomatous Disease in an Eclectus Parrot (Eclectus roratus).

A 12-year-old male eclectus parrot (Eclectus roratus) was referred for evaluation of coelomic distention. Computed tomography and blood work revealed coelomic effusion with free coelomic mineral-attenuating material and elevations in the bile acids and aspartate aminotransferase activity, respectively. Coelomic effusion was consistent with macrophagic inflammation with abundant intracellular lipids. Initial treatment with meloxicam resulted in minimal patient improvement. Disseminated xanthogranulomatous inflammation was suspected based on imaging and diagnostic laboratory results, which were consistent with those previously reported. Biopsy samples of liver tissue and intracoelomic masses confirmed this diagnosis. Treatment was initiated with prednisolone 1 mg/kg/d for 6 months, followed by 0.5 mg/kg/d for 3 months. Clinical improvement was assessed based on owner evaluation, plasma bile acid concentrations, and repeated computed tomographic scans. After 2 months of treatment, the owner reported improved behavior and appetite; this persisted throughout treatment and when the bird was reexamined 17 months following the cessation of steroid therapy. Bile acid concentrations were normal 10 months after the prednisolone therapy was discontinued. Diagnostic imaging showed minimal coelomic effusion 10 months after the last prednisolone dose was administered, with improved ventilation of the air sacs and static to improved dystrophic mineral foci. This report describes the antemortem diagnosis and treatment of disseminated coelomic xanthogranulomatous disease in a psittacine species, with an observed measurable therapeutic response.

HYPERLIPIDEMIA AND XANTHOMATOSIS IN YELLOW-FOOTED ROCK WALLABIES (PETROGALE XANTHOPUS) UNDER MANAGED CARE.

Xanthomas are localized lipid deposits in organs with associated granulomatous inflammation. Xanthomatosis is a rare condition in both human and veterinary medicine and is often linked to inherited or acquired dyslipidemias. Three female yellow-footed rock wallabies (Petrogale xanthopus) at a single institution were diagnosed via biopsy with cutaneous xanthomas secondary to hypertriglyceridemia and hypercholesterolemia, and an additional two female yellow-footed rock wallabies were diagnosed with xanthomas at a second institution. All cases presented with cutaneous masses at the haired skin and paw pad junctions of the extremities, and/or mucocutaneous junctions of the face or urogenital tract. The clinically affected individuals were overconditioned or obese, had lipemic serum, and had elevations in blood cholesterol and triglyceride levels. When full lipid panels were performed, inverse high- and low-density lipoprotein fractions were observed. Six other individuals at the first institution had identical husbandry but were of more appropriate body condition, were normolipidemic, and had no xanthomas. One of the affected animals was also concurrently diagnosed with hepatic lipidosis via liver biopsy. Pedigree review and evaluation for underlying endocrine diseases such as hypothyroidism were performed. Because all affected animals were found to be related, a genetic predisposition is possible but requires further investigation. Consideration for the predisposition of some individuals for obesity, hyperlipidemia, and subsequent xanthoma formation should be factored in the husbandry and medical management of this species.

A clinicopathological study of 17 cases of ocular surface xanthogranuloma in dogs.

OBJECTIVE: To evaluate the clinical, histopathological, and immunohistochemical features of 17 cases of ocular surface xanthogranuloma (OSX) in dogs. METHODS: Archived records from the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) were searched for cases of canine OSX. Cases were evaluated for lipid-laden macrophages and Touton giant cells. Seventeen cases matching those criteria were identified (1993-2018). Clinical and epidemiological data were collected from the submission forms and additional follow-up survey. RESULTS: Ocular surface xanthogranuloma in dogs presented as small bland nodules. OSX commonly occurred at the limbus (8/17) or cornea (4/17). Three of 17 affected animals were less than 1-year-old and the average age was 6.9 years (range 0.7-14 years). Fourteen of 17 cases did not report any lipid or metabolic abnormalities. Histologically, lesions were composed mainly of dense sheets of vacuolated lipid-laden macrophages and Touton giant cells with scant additional inflammatory cells and an intact overlying epithelium. No recurrence was noted in cases where complete surgical resection was achieved, and medical treatment either pre or post-resection led to only partial resolution. CONCLUSIONS: Xanthogranulomas are histiocytic lesions characterized by abundant lipid-laden macrophages. The authors use the term, ocular surface xanthogranuloma, to describe nodules with rigidly defined cellular characteristics. Although these lesions share characteristics with human limbal xanthogranulomas, further investigation is needed to suggest the different subsets that have been reported in the medical literature. Complete surgical excision is the most effective treatment for OSX in dogs, and intralesional triamcinolone and topical steroids can be useful adjunctive therapies to surgery.

Imaging features of disseminated xanthogranulomatous inflammation in eclectus parrots (Eclectus roratus).

Xanthogranulomatous disease is a rare condition, which can be caused by infection, inflammation, hemorrhage, immunologic disease, or inherited lysosomal disorders. It is characterized by non-intracellular lipid and cholesterol deposits among an inflammatory infiltrate of vacuolated macrophages and giant cells. The diagnosis of xanthogranulomatous disease is challenging, with nonspecific imaging findings often misinterpreted as aggressive neoplastic processes in humans. In this retrospective case series study, we describe the diagnostic imaging characteristics of a disseminated xanthogranulomatous condition identified in five eclectus parrots (Eclectus roratus). Decreased serosal detail and celomic distension were present in all three birds radiographed, with multifocal variably sized celomic mineralization (3/3 birds), and extracelomic mineralized masses (1/3 birds). Celomic effusion with foci of celomic mineralization and hepatomegaly were identified in all birds (3/3) imaged with ultrasound. Finally, a mineralized mural ventricular mass was present in one of three patients imaged with CT, multifocal celomic mineralization with moderate to severe celomic effusion in two of three patients, diffuse severe proventricular and intestinal dilation in all three patients, and atherosclerosis of the major arterial trunks in all three patients. Veterinary radiologists should be aware of this inflammatory condition in birds, especially in eclectus parrots, and should be able to recognize the imaging features of xanthogranulomatous inflammation.

Scleral and corneal xanthomatous inflammation in a gray mouse lemur (Microcebus murinus).

Bilateral multifocal corneal opacity was detected in a 4.5-year-old male captive gray mouse lemur (Microcebus murinus) without other clinical ocular changes. Histopathological examination revealed a severe diffuse granulomatous scleritis and focal keratitis with intralesional cholesterol, consistent with xanthomatous inflammation. This is the first report of xanthomatous inflammation in a gray mouse lemur. This condition may be the result of systemic factors (lipid metabolism disorders) and/or local predisposing factors such as hemorrhage or inflammation. The pathogenesis in this case could not be fully determined. Further studies on lemurs are required for a better understanding of their lipid metabolism, as well as for diagnosing and evaluating the incidence of xanthomatous inflammation in these species.

Subcutaneous xanthomatosis in a great white pelican (Pelecanus onocrotalus).

A great white pelican (Pelecanus onocrotalus) was referred for assessment of a subacute-onset, nonpainful swelling located in the pectoral region. Physical examination revealed a firm, round, well-circumscribed subcutaneous mass approximately 10 cm in diameter. Cytological evaluation of a fine needle aspirate of the mass was consistent with a mesenchymal tumor. The mass was excised, and a diagnosis of xanthomatosis was made based on histopathologic results. Avian xanthomatosis is a nonneoplastic condition of unknown etiology. Possible causes of this condition include trauma, metabolic or nutritional disorders. Similar lesions were not observed in the nine conspecifics that were fed the same diet and housed in the same enclosure. To our knowledge, this is the first report of xanthomatosis in the family Pelecanidae.

A case of xanthoma in a Saanen goat.

This report describes a case of a subcutaneous xanthoma of the sacral region in a 2-year-old female Saanen goat. The tan-coloured mass was 8.5 cm × 4.0 cm × 0.5 cm in size. Yellow-white areas were present across the cut surface. Histopathologically, the mass was composed of foamy macrophages, numerous giant cells, abundant lipid material and cholesterol clefts. The structure consisted of lobular areas surrounded by a stroma. Tissue sections were negative for bacteria, fungi and mycobacteria. Frozen tissue from the mass stained positively with Oil Red O, confirming lipid accumulation in both the extracellular spaces and the large foamy macrophages. Immunohistochemically, the mass was positive for vimentin, proliferating cell nuclear antigen and CD68, but negative for smooth muscle actin, glial fibrillary acidic protein and S100 protein antibodies. As the animal was presented dead, it was not possible to analyse blood lipid levels. To the authors' knowledge, this is the first report of a xanthoma in a goat.

Cerebral xanthomatosis in three green water dragons (Physignathus cocincinus).

Cerebral xanthomatosis was diagnosed in three female green water dragons (Physignathus cocincinus), all of which presented with progressive neurologic signs. No antemortem evidence for xanthomatosis was identified, but on postmortem examination cholesterol granulomas, composed of cholesterol clefts surrounded by macrophages and multinucleated giant cells, were found in the forebrain of each animal and were associated with significant displacement and pressure on the adjacent brain. Although the cause of xanthomatosis in these animals is unknown, nutrition and trauma may be involved in the pathogenesis of this condition. Cerebrum, cholesterol, green water dragon, Physignathus cocincinus, xanthoma.

Xanthogranulomatous Pituitary Adenoma in a Dog with Typical Hyperadrenocorticism.

Xanthogranuloma of the sellar region has been reported in both humans and animals. The lesion is rare, and its aetiology and pathogenesis are not fully understood. The association of sellar xanthogranuloma with an adenoma, known as xanthogranulomatous pituitary adenoma (XPA), is an extremely rare condition in humans and is usually associated with anterior pituitary insufficiencies, headache, vomiting and visual deficits. We present the first report of XPA in an animal. A 7-year-old male neutered Labrador Retriever was presented for investigation of progressive lethargy, vomiting and hyporexia, having been previously diagnosed with chronic kidney disease, pituitary-dependent hyperadrenocorticism and hypoparathyroidism. The dog was euthanized due to lack of response to medical treatment and post-mortem examination revealed XPA. Although rare, xanthogranulomatous lesions should be considered in patients with pituitary disease.

Multiple atypical mucosal xanthomas in a dog similar to human verruciform xanthoma.

A case of atypical mucosal xanthomas in a 14-year-old Shi-Tzu dog is reported. Grossly, 1-6-mm granular plaques or slightly elevated papillary nodules were found in the oral cavity (dorsal and ventral sides of the tongue, inner upper lip) and in the upper digestive tract (esophagus, stomach). Microscopically, subepithelial aggregates of large foamy cells were found in strong association with papillary epithelial hyperplasia. By immunohistochemistry, the majority of these cells tested positive for lysozyme and ACM1. The cells had cytoplasmic lipid content that stained positively with oil red O. These findings confirmed a monocyte/macrophage lineage. On the basis of macroscopic observations, microscopic changes, and the absence of a clinical metabolic defect, the condition in this dog appears similar to that of humans with oral verruciform xanthoma. The pathogenesis of these xanthomas in the dog remains obscure, although this condition appears to affect people and dogs with an Asian origin.

Conjunctival xanthoma in a blue and gold macaw (Ara ararauna).

A 17-year-old female blue and gold macaw (Ara ararauna) presented for evaluation of a discreet, conjunctival mass of the OD. No other abnormalities were found on ophthalmic or physical examination. A heterophilic leukocytosis was present on the complete blood count, and elevated aspartate aminotransferase activity, creatinine kinase activity and cholesterol were present on the plasma biochemistry panel. Surgical removal of the mass was complete and no recurrence has occurred by six months after excision. Reduction of dietary fats was recommended to reduce serum cholesterol levels and reduce the likelihood of future occurrence of xanthomas in this bird.

Unique cytologic and histologic features of a suspected cutaneous xanthoma in a dog.

A 4-year-old spayed female American Staffordshire Terrier presented to the U-Vet Animal Hospital, Werribee, Australia, with a cutaneous mass that had been slowly growing over 12 months. Cytologic evaluation showed cohesive to individualized, vacuolated spindled cells often arranged in a perivascular pattern. The mass was completely excised, and the histopathologic examination demonstrated sheets of vacuolated spindled to round cells expanding the full thickness of the dermis. The cells demonstrated both Iba1 and CD18 antibody binding, leading to an initial interpretation of histiocytic sarcoma. Given the discordance with the clinical presentation, further immunohistochemistry (IHC) was performed. The cells demonstrated strong CD204 antibody binding and did not bind E-cadherin antibody, consistent with a dermal macrophage origin. Ki-67 antibody binding was regionally variable from <5% to 25%, with more regions that had low Ki-67 expression. A fasted serum biochemistry panel revealed hypertriglyceridemia and persistent hypercholesterolemia. Based on clinical, microscopic, biochemical, and IHC results, the final interpretation was an indolent dermal histiocytic proliferation of macrophage origin, with a preference for cutaneous xanthoma or reactive dermal fibrohistiocytoma.

Dietary cholesterol-induced xanthomatosis in atherosclerosis-susceptible Japanese quail (Cotunix japonica).

Japanese quail of a strain (SUS) susceptible to dietary cholesterol-induced atherosclerosis were fed a diet supplemented with cholesterol (0.5% w/w) for 4, 8 or 12 weeks. Plasma cholesterol increased significantly from 240-1550 mg/dl at 4 weeks and remained at that concentration for 8 and 12 weeks on the same diet. Plasma triglycerides (TGs) increased from 112-384 mg/dl after 4 weeks but showed no significant increases thereafter. Striking eruptive xanthomatous lesions were noticed on the feet of 50% of these birds at 4 weeks, and the percentage of birds affected increased to 85 after 12 weeks on the cholesterol-supplemented diet. This is the first report of xanthomatosis in birds. These birds had also developed atherosclerotic plaques in the aorta and brachiocephalic arteries by 4 weeks. There was no significant correlation between xanthoma scores and plasma cholesterol and TG concentrations at any of the three sampling periods (4, 8 and 12 weeks of cholesterol feeding). There was, however, a significant negative correlation (r = -0.61) between xanthoma scores and atherosclerotic plaque scores at 4 weeks. The correlation became non-significant at later stages of cholesterol exposure. Similarities between mammalian and SUS Japanese quail xanthomatosis may make the SUS quail a useful model for the study of this disorder.

The pathology of an inherited hyperlipoproteinaemia of cats.

The gross and histological features of congenital lipoprotein lipase deficiency are described in eight cats. The main histological features could be directly related to the presence of the chylomicronaemia. They consisted of lipid accumulation within clear vacuoles or ceroid accumulation within residual bodies in parenchymatous organs such as the liver, spleen, lymph nodes, kidney and adrenal gland. Xanthomata were seen in various sites, probably arising either from frank haemorrhage or the leakage of lipid-rich plasma perivascularly. As in human lipoprotein lipase deficiency there was no evidence of the formation of atherosclerotic plaques. Focal degenerative changes were, however, present within arteries and this may indicate blood vessel weakness and explain the tendency to haemorrhage and xanthomata/granulomata formation. The degeneration and fibrous replacement of glomeruli and nephrons possibly arises from pressure necrosis of adjacent xanthomata and alterations in renal blood flow.

A xanthomatous lesion resembling balloon cell melanoma of the iris and ciliary body of a dog.

A slow-growing xanthomatous tumour which diffusely infiltrated the iris and ciliary body of a dog was composed of large, pale, vacuolated cells which contained scattered fine pigment granules. Electron microscopy revealed coalescing vacuoles, lamellar membranous structures, and small groups of melanosomes in the cytoplasm, suggesting melanocytic origin. The lesion resembled balloon cell melanoma of the ciliary body of man. The behaviour of the tumour was benign. This is a clinical and pathological entity which has not been reported previously in the dog.

Hyperlipoproteinaemia associated with atherosclerosis and cutaneous xanthomatosis in a cat.

Bilateral uveitis and multiple xanthomas (fat deposits in the skin) are described in a 3.5-year-old ovariohysterectomized female Persian cat. The cat had been treated for 2 years with corticosteroids. Examinations included a routine blood chemistry profile, radiographic examination of the thorax and abdomen, histopathological examination of multiple skin punch biopsies, and analysis of blood lipid components by cellulose-acetate electrophoresis and by preparative ultracentrifugation studies. Total lipid values were 23 g/l. Ultracentrifugation studies indicated strongly elevated VLDL and LDL fractions and a decreased concentration of the HDL fraction. Because of sudden blindness the cat was euthanized at the request of the owner. Autopsy revealed massive atherosclerotic changes in the large abdominal vessels, the wall of the aorta, and the coronary vessels. Although the exact pathogenesis remains uncertain, these unusual findings might be explained by a primary hyperlipoproteinaemia, complicated by long-term use of corticosteroids.

Atypical multiple, papilliform, xanthomatous, cutaneous neoplasia in a goose (Anser anser).

An 18-month-old, male greylag goose was presented for assessment of multiple, semi-pedunculated cutaneous masses limited to non-feathered areas of skin. Initial biopsy and histopathology revealed a mesenchymal neoplasm suggestive of lipoblastomatosis or atypical xanthoma. Immunohistochemistry was unsuccessful in determining the tissue type of origin. Surgical resection of all masses was prevented by the mucocutaneous location of several masses. Chemotherapy using intralesion cisplatin was unsuccessful in resolving the masses but was well-tolerated by the goose. Serum lipid and lipoprotein analysis revealed a persistent hypercholesterolaemia and hypertriglyceridaemia without biochemical evidence of an underlying metabolic disease. The persistent hyperlipidaemia may have contributed to the formation of the masses identified in this case.

Cutaneous xanthomas with concurrent demodicosis and dermatophytosis in a cat.

Multiple cutaneous xanthomas, associated with fasting hyperlipidaemia, are described in a 9-month-old domestic long-haired cat. A severely pruritic, papular, and crusting dermatitis affecting the head and neck, initially diagnosed as lesions of the eosinophilic granuloma complex, progressively developed on the head and pinnae. Pruritus was controlled with administration of prednisolone and chlorambucil. Repeat histological examination confirmed the diagnosis of cutaneous xanthoma and concurrent mild demodicosis. Marked fasting hypercholesterolaemia, hypertriglyceridaemia and transient hyperglycaemia were subsequently confirmed. Treatment for hyperlipidaemia and xanthomas with a low-fat diet (Hill's Feline r/d) and the previously unreported treatment for feline demodicosis of daily oral milbemycin were commenced. Multiple pink, alopecic plaques and papules gradually regressed, however pruritus recurred if immunosuppressive treatment was reduced, and well-demarcated areas of alopecia developed on the head, limbs and trunk, despite negative skin scrapings for demodex mites. Fungal culture of hair samples yielded Microsporum canis. All cutaneous lesions resolved with the addition of griseofulvin to the treatment regimen. Concurrent corneal ulceration and keratoconjunctivitis sicca ultimately resolved with treatment, including topical cyclosporin. Diabetes mellitus developed 6 months after resolution of skin lesions. No cutaneous or ocular abnormalities were present 6 months later with continued low-fat diet and insulin administration, although transient recurrence of papules and pruritus occurred after inadvertent access to a fatty meal. An underlying primary hyperlipidaemia was suspected, causing pruritic xanthomas. This may represent the first report of concurrent cutaneous xanthomas, demodicosis and dermatophytosis in a cat.