C O N F E R E N C E 18 6 February 2019
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Joint Pathology Center Veterinary Pathology Services WEDNESDAY SLIDE CONFERENCE 2018-2019 C o n f e r e n c e 18 6 February 2019 Conference Moderator: Andrew Cartoceti, DVM, DACVP Staff Pathologist National Zoologic Park Washington DC, 20008 CASE I: 13-161654 (JPC 4048673). Signalment: 25 year-old, female intact Congo African Grey Parrot (Psittacus erithacus erithacus) History: This parrot was a permanent resident of a pet shop collection and was fed a diet of pellets, seeds, apples, and peanuts. The previous medical history included a Presentation, parrot: The arteries are thickened and yellow and there is marked hepatomegaly. (Photo courtesy prolapsed oviduct in May of 2013 with egg of Cornell University – Animal Health and Diagnostic retention, but the bird was otherwise healthy. Center, 240 Farrier Road, Ithaca, NY 14850) The bird was presented to the referring veterinarian in November of 2013 for a recent The coelomic cavity contains multiple onset of lethargy, anorexia, and feather aggregates of dark red gelatinous material picking. On presentation, blood work that cover the viscera. The spleen is abnormalities included increased bile acids uniformly enlarged measuring 4.7 x4.5 cm and hyperproteinemia (absolute values were and diffusely mottled white to light tan to red. not provided). The liver is enlarged with rounded margins and the parenchyma is diffusely mottled Gross Pathology: Both brachiocephalic green to black to tan with dozens of random arteries are prominent, diffusely yellow, hard 0.1 cm round white foci (necrosis, and do not collapse. On section, the luminal presumptive). surface is expanded by a locally extensive 1mm thick, rough, yellow plaque (atherosclerosis). 1 Laboratory results: University of Miami – intima and media contain numerous small Avian and Wildlife Laboratory aggregates of granular amorphous deeply o Increased beta and gamma basophilic material (mineral). In cross globulins on electrophoresis section the arteriolar lumen is occluded up to consistent with acute 60% by a confluent mass composed of a inflammation and active deeper region of large foam cells, acicular humoral immune response clear clefts (cholesterol), large clear spaces o High titer (1:25) for (fatty infiltration), multifocal aggregates of Chlamydophila psittaci mineral, and islands of chondroid matrix covered by a thin variably present endothelial Microscopic Description: lining (atheroma). HEART (not submitted): Randomly scattered throughout the parenchyma are small foci of LIVER (not submitted): Randomly scattered cardiomyocyte loss with replacement by throughout the hepatic parenchyma large foamy macrophages and lymphocytes. coalescing areas of hepatocyte loss with the remaining hepatocytes being pale VESSEL, NOS: Arteries: Diffusely the eosinophilic with loss of nuclear detail tunica intima and media is disorganized with (necrosis). Admixed within these foci are the tunica media expanded by abundant foam small numbers of macrophages with fewer cells creating an irregular luminal surface. plasma cells and lymphocytes and rare Occasionally the tunica media contains heterophils. Surrounding hepatocytes contain multifocal clear acicular clefts (cholesterol) fine granular golden brown cytoplasmic that are variably surrounded by foamy pigment (lipofuscin). The remaining macrophages and includes locally extensive hepatocytes show moderate anisocytosis and regions of cellular loss with replacement by anisokaryosis, with occasional binucleate large clear spaces (fatty infiltrate) and several cells. foci of chondroid metaplasia. The tunica SPLEEN (not submitted): Diffusely expanding the red pulp are large coalescing aggregates of foamy macrophages admixed with few degenerate and non-degenerate heterophils. Contributor’s Morphologic Diagnoses: Arteries: Severe, diffuse, chronic atherosclerosis Heart: Mild, multifocal, lymphohistocytic myocarditis Liver: Severe, multifocal to coalescing, chronic, hepatocellular necrosis with granulomatous, lymphoplasmacytic Heart and great arteries, parrot: The arteries are hepatitis thickened, do not collapse under their own weight and yellow and there is marked hepatomegaly. (Photo courtesy Spleen: Severe, multifocal, chronic, of Cornell University – Animal Health and Diagnostic granulomatous splenitis Center, 240 Farrier Road, Ithaca, NY 14850) 2 injury hypothesis. Here the principle inciting cause is endothelial damage, secondary to endothelial dysfunction and oxidative stress that creates a local atherogenic environment2, 5. Endothelial dysfunction is characterized by a chronic state of endothelial cell activation leading to increased production of procoagulative and proinflammatory factors.2 In a recent study endothelial cell changes were appreciated in mild pre- atheroma lesions; giving further support to the hypothesis that endothelial damage precedes lipid deposition.5 A recent experimental model showed that type VIII Liver: The liver is enlarged, with a cobblestoned mottled collagen is up-regulated in artherosclerotic parenchyma. (Photo courtesy of Cornell University – lesions and allows for smooth muscle cell Animal Health and Diagnostic Center, 240 Farrier Road, Ithaca, NY 14850) proliferation and migration, which is important for fibrous cap formation.7 Contributor’s Comment: The histologic Currently the association between histologic features seen here are consistent with severity and clinical disease course is atherosclerosis of a grade IV out of VII, 5 unknown. As atherosclerosis in psittacines although grade varies between submitted represents a similar spontaneous disease sections. The changes in the liver and spleen progression to that seen in humans, a similar are seen with Chlamydophila psittaci grading scheme based on the American Heart infection, but other systemic bacterial Association’s human grading scheme has infections (e.g. Escherichia coli, Salmonella been purposed for better characterization and sp, Mycobacterium sp, Staphylococcus sp, future prognostication of disease. This and Streptococcus sp) can create similar scheme divides atherosclerotic lesions into changes. Antemortem testing for seven grades based on the light microscopic, Chlamydophila psittaci were consistent with an active infection. In this case the cause for coelomic hemorrhage remained unclear, as thrombotic events and vessel rupture are uncommon complications of atherosclerosis in the avian species. Atherosclerosis is a chronic inflammatory fibroproliferative disorder, which commonly causes spontaneous disease in psittacines, as well as numerous other avian species. Most notably the Japanese Quail (Coturnix coturnix japonica) and pigeon (Columa livia domestica) have been used as inducible Muscular artery, parrot. The tunica intima is effaced and experimental models for the human the tunica media is markedly expanded by a complex disease.2,3,11 The pathogenesis of disease has atheroma. (HE 20X). been largely explained by the response-to- 3 histochemical, and electron microscopic concurrent reproductive or hepatic disease, features, with grades greater then IV of VII and the genera Psittacus, Amazona, and being considered clinically significant.5 Nymphicus were found to increase the risk of development of severe atherosclerotic Several risk factors have been proposed for lesions.4 The synthesis and transport of the development of atherosclerosis in VLDLs and vitellogenin to the oocyte and psittacines. Diet has been implicated, as future egg yolk in response to estrogen may many animal models for experimental be the underlying pathogenesis for this disease are diet-inducible. In one study predisposition in female birds.2 As VLDLs increasing the cholesterol within the feed of have been shown to be pro-inflammatory.2 Quaker parrots (Myiopsitta monachus) by 1% Infectious agents have been implicated as induced clinically significant lesions within risk factors for lesion development. In one 4-6 months.6 With hypercholesterolemia, study there was a significant association lipoproteins themselves can allow for between Chlamydophilia psittaci antigen in activation of endothelial cells and leukocyte the blood and development of athero- adhesion. Oxidized lipoproteins act as strong sclerosis, however this correlation was not chemoattractants for monocytes. Once they appreciated in one large retrospective study. enter the vascular wall and transform, to However it is interesting to note that this macrophages, they express scavenger patient had concurrent histologic findings receptors that allow for uptake of additional and antemortem test findings consistent with low density lipoproteins (LDLs) and active Chlamydophila psittaci infection. simulation of smooth muscle cells to foam Marek’s disease (herpes virus infection) has cells 2. In addition increased age, female sex, Muscular artery, parrot. Higher magnification of the atherosclerotic plaque reveals a thick, often artifactually cleaved layer of foam cells, cholesterol clefts and abundant collagen (black arrows), mineral (yellow arrows), and at the periphery, foci of cartilaginous metaplasia. (HE 66X). 4 been shown in chickens to promote 2. Elastic artery, adventitial adipose tissue: atherosclerotic lesion formation.2 Atrophy, diffuse, severe. Underlying genetic factors can predispose a patient to endothelial dysfunction. In one JPC Comment: The contributor has study in White Carneau Pigeons there was a provided an excellent discussion of divergence in the genes responsible for atherosclerosis in psittacines and other avian cytoskeleton remodeling, proteasome