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C-B01 - Pullorum disease - heart - chicken

HD: Heart: The ventricular and septal walls are diffusely and transmurally thickened 2-4 times
normal by large numbers of macrophages and few lymphocytes and heterophils that separate and
replace cardiac myocytes. Similar inflammatory cells infiltrate the endocardium and epicardial
adipose tissue and multifocally form irregular tags and nodules that protrude from the epicardial
surface. Macrophages often have large vesiculate nuclei and foamy, pale eosinophilic cytoplasm.
Remaining cardiac myocytes are often pale and vacuolated (degeneration), or fragmented with loss
of cross striations and pyknosis (necrosis). Multifocally, arteriolar walls are disrupted and replaced
by intensely eosinophilic fibrillar material (fibrin), necrotic debris, and few degenerate
inflammatory cells (necrotizing vasculitis).
MDX: Morphologic Diagnosis: Heart: Pancarditis, histiocytic, diffuse, severe, with necrotizing
vasculitis, and myocardial degeneration and necrosis, Rhode Island Red, chicken, avian.
EDX: Myocardial salmonellosis
Cause: Salmonella enterica subsp. enterica Pullorum-Gallinarum
CS: Bacillary white diarrhea; White diarrhea
DDX:
For gross lesions:
Marek’s disease (Gallid herpesvirus 2) and Avian leukosis virus (Avian retrovirus): Similar white
nodules in the heart and other viscera
Salmonella arizonae: Acute or chronic egg-transmitted infection; primarily in turkeys with highest
mortality in the first 3-4 weeks of life
Paratyphoid disease: Caused by any of the non-host adapted Salmonellae, especially S.
typhimurium and S. enteritidis
Septicemic or localized coliform, staphylococcal, streptococcal and Pasteurella multocida infections
Mycoplasma synoviae, Staphylococcus aureus, Pasteurella multocida and Erysipelothrix
rhusiopathiae cause similar synovitis.

C-B02 - Streptococcus pneumoniae - heart - guinea pig

HD: Heart: Diffusely adherent to the epicardium is a variably-thick mat of fibrin which contains
numerous viable and degenerate heterophils, moderate numbers of erythrocytes, eosinophilic
cellular and karyorrhectic debris (necrosis), and fewer scattered lymphocytes, plasma cells and
macrophages. The underlying epicardium is diffusely edematous and expanded by fibrin, many
neutrophils, lymphocytes, plasma cells, and macrophages, few fibroblasts, and many perpendicular,
evenly spaced, small caliber blood vessels with plump endothelial cells (granulation tissue). This
inflammatory infiltrate extends into the superficial myocardium and separates and surrounds
myocytes. Diffusely blood vessels are congested and lymphatics are ectatic. There is focal mild
chondromatous metaplasia within the tunica media of a large muscular artery.
MDX: Heart: Epicarditis and subepicardial myocarditis, fibrinosuppurative, chronic, diffuse, severe,
with gram-positive diplococci, Guinea pig, rodent.
EDX: Pneumococcal epicarditis and myocarditis
Cause: Streptococcus pneumoniae
DDX:
Pericarditis in the guinea pig: S. zooepidemicus, Salmonella sp., Klebsiella pneumoniae, and
Pasteurella multocida

C-F01 - Coccidioidomycosis - pericardium – dog MG543

HD: Pericardium: Diffusely the pericardium is expanded up to 4mm thick by multiple granulomas
that are up to 500um in diameter and consist of numerous epithelioid macrophages and rare foreign
body-type multinucleate giant cells surrounded by plasma cells, lymphocytes, reactive fibroblasts
and collagen. Multifocally granulomas contain round fungal spherules up to 60um in diameter,
with a 4-5um thick double contour hyaline wall, that are filled with granular to flocculent,
basophilic material or occasionally few 5-8um round endospores. Granulomas are separated and
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surrounded by fibrous connective tissue and varying numbers of lymphocytes, plasma cells,
degenerative neutrophils, and macrophages admixed with small amounts of hemorrhage, fibrin and
edema. Diffusely the pleural surface is expanded by granulation tissue and a superficial layer of
eosinophilic fibrillar to beaded material (fibrin) with entrapped inflammatory cells and necrotic
debris.
MD: Pericardium: Pericarditis, granulomatous, diffuse, severe, with fibrinous pleuritis, and
numerous fungal spherules, consistent with Coccidioides immitis, breed unspecified, canine.
ED: Pericardial coccidioidomycosis
Cause: Coccidioides immitis
CS: San Joaquin Valley Fever
DDX:
Dimorphic fungal infections:
Blastomyces dermatitidis
Cryptococcus neoformans
Histoplasma capsulatum
Organisms that reproduce by endosporulation:
Coccidioides immitis
Rhinosporidium seeberi
Prototheca sp.
Chlorella sp.
Batrachochytrium dendrobatidis

C-M01 - Dystrophic cardiac calcinosis (DCC) - heart – mouse Balb/c adult

HD: Heart: Multifocally and extensively within the myocardium and particularly within the
subepicardial right ventricular wall, there is cellular disruption and fragmentation with loss of
sarcoplasmic detail (degeneration), or pyknotic or karyolytic nuclei (necrosis). Separating,
surrounding, and replacing degenerate and necrotic cardiac myofibers, there is abundant
basophilic granular material (mineral) and increased collagen (fibrosis). There are scattered
lymphocytes and plasma cells within the areas of mineralization and multiple areas of osseous
metaplasia. Occasionally, adjacent cardiomyocytes have large vesiculate nuclei.
MDX: Heart, myocardium: Mineralization, degeneration, and necrosis, multifocal, moderate, with
fibrosis, Balb/c mouse, rodent.
CS: Dystrophic mineralization

C-M02 - Rhabdomyomatosis - heart - guinea pig MG593

HD: Heart: Within the interventricular septum, there is a focally extensive, well-circumscribed,
3x2mm, subendocardial nodule composed of myocytes with cytoplasm markedly distended by a
single, clear, up to 120 um diameter vacuole (glycogen). The small amount of remaining cytoplasm
and the compressed nucleus are displaced to the periphery. In rare cells, the nucleus is centrally
located and surrounded by radiating finely fibrillar eosinophilic processes (spider cells).
Multifocally, few peripheral myocytes are hypereosinophilic and fragmented with pyknotic or
absent nuclei (necrosis). Multifocally admixed within vacuolated myocytes are rare lymphocytes.
MDX: Heart, myofibers: Vacuolar change, glycogen-type, multifocal, moderate
(rhabdomyomatosis), Guinea pig, rodent.
Condition Synonyms: Cardiac rhabdomyoma
GD: All ages, as young as 3 weeks, suggesting congenital condition. Hamartoma or malformation
rather than a true neoplasm
DDX: Mesenchymoma (Rare benign cardiac neoplasm in guinea pigs, most often in the right atrium
Composed of mesenchymal tissue: adipose, angiomatous, cartilaginous, osseous, hematopoietic,
myxomatous tissue and smooth muscle)

C-M03 - Endocardial fibroelastosis (EFE) - heart – cat (Siamese) MG573

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HD: Heart: Diffusely the endocardium is uniformly thickened up to 250 um (20x normal) by
abundant fibrocytes, fewer fibroblasts, and many layers of collagen and elastic fibers. Superficially,
fibers are thin, loosely and randomly arranged, and separated by increased clear space and
myxomatous material. Fibers within the deeper layers are thicker, more tightly packed, and
parallel. Multifocally the connective tissue extends minimally into the underlying myocardium,
rarely surrounding and isolating myofibers and Purkinje fibers.
MDX: Heart, endocardium: Fibroelastosis, diffuse, marked, Siamese, feline.
GD: Rare, congential, primarily affects Burmese and Siamese cats, leads to congestive heart failure.
Primary endocardial fibroelastosis: Diffuse endocardial thickening without other significant cardiac
lesions; uncommon, congenital; hereditary
Secondary endocardial fibroelastosis: Diffuse endocardial thickening secondary to other cardiac
conditions (i.e. myocardial inflammation, necrosis, degeneration)
Pathogenesis: Unknown. Degeneration of entrapped Purkinje fibers (left bundle branch) may lead to
cardiac conduction abnormalities.
Additional Diagnostic Tests: Masson’s trichrome for collagen; Elastica Van Gieson (EVG) for
elastic fibers
DDX: 1. Secondary EFE: Gross or histological evidence of a primary cause (congenital, infectious,
or inflammatory); 2. Postinfectious myocardial fibrosis
CP: Reported in dogs, horses, cattle, sheep, pigs, and chickens.

C-M04 - Polyarteritis nodosa - mesenteric arteries – rat MG162

HD: Small intestine and mesentery: Diffusely the walls of mesenteric arteries are markedly
thickened and are transmurally disrupted by high numbers of neutrophils with lymphocytes and
fewer plasma cells. Arterial lumina are often narrowed and occluded by organizing fibrin
thrombi. The subendothelial tunica intima is disrupted and markedly expanded by thick bands of
deeply eosinophilic hyaline to fibrinoid material admixed with cellular and karyorrhectic
debris (necrosis). The tunica media is expanded and disrupted by reactive fibroblasts, collagen,
numerous small caliber blood vessels, and clear space (edema) and infiltrated by numerous viable
and degenerate neutrophils, fewer macrophages, lymphocytes, plasma cells, rare multinucleated
giant cells, eosinophils and necrotic debris. Similar inflammatory cells extend into the tunic
adventitia, disrupting elastic fibers, and into surrounding connective tissue. Multifocally, there is
moderate atrophy of mesenteric fat.
MDX: Arteries, mesenteric: Arteritis, proliferative and necrotizing, chronic-active, diffuse, severe,
with thrombosis, Sprague-Dawley rat, rodent.
CS: Periarteritis, panarteritis nodosa, polyangitis
GD: most often occurs in aging rats, with a higher incidence in males. Most often in the muscular
medium sized arteries of the mesentery, pancreas, pancreaticoduodenal artery, and testis, but also
seen in hepatic, coronary, uterine, cerebral, adrenal, and renal arteries. Most often in Sprague-
Dawley, sporadic in all species of domestic animals.
Pathogenesis: Unknown. Thought to be an immune complex-mediated disease similar to the type III
hypersensitivity-immune complex deposition in vessel walls
CP: Metazoan parasites: Strongylus vulgaris, Dirofilaria immitis, Schistosoma sp., Elaeophora
schneideri, Onchocerca armillata / Viruses: Equine viral arteritis (arterivirus, Arteriviridae), Border
disease (pestivirus, Flaviviridae), Classical swine fever (pestivirus, Flaviviridae), African swine
fever (Asfarviridae), Malignant catarrhal fever (alcelaphine herpesvirus-1 or ovine herpesvirus-2) /
Bacterial diseases: Salmonella, Erysipelothrix, beta-hemolytic Streptococcus, Rickettsia rickettsii /
Fungi: Aspergillus, Mucoraceae
Canine juvenile polyarteritis syndrome ("Beagle pain syndrome"): Small to medium sized muscular
arteries of heart, cranial mediastinum and cervical spinal meninges, intimal and medial fibrosis,
rupture of elastic laminae, perivasculitis; splenic, renal and hepatic amyloidosis

C-M05 - Atherosclerosis - heart – dog MG599

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HD: Heart: Diffusely the large elastic and muscular coronary arteries have thickened walls with
narrowed to occluded lumina. There is extensive disruption of the internal elastic lamina and the
tunica intima and tunica media are moderately to severely thickened, disorganized, and expanded
by numerous acicular clefts (cholesterol) mixed with amphophilic granular cell debris and
mineral. Multifocally there are moderate numbers of histiocytic cells with abundant
microvacuolated cytoplasm (foam cells), and fewer lymphocytes and plasma cells. The tunica
adventitia is expanded by low numbers of lymphocytes, plasma cells and occasional macrophages
that extend into adjacent fibroadipose tissue.
MDX: Heart, coronary arteries: Atherosclerosis, diffuse, severe, with mineralization, Labrador
Retriever, canine.
GD: Vascular degenerative diseases in animals are classified into three groups:
Atherosclerosis refers to lesions composed of lipid, fibrous tissue and calcium deposits in vessel
walls; called “atheromas” or fibrofatty plaques. Affects elastic arteries (aorta, carotid, iliac) and
large and medium-sized muscular arteries. Hypothyroid or diabetic dogs; infrequent in domestic
animals, common in humans
Arteriosclerosis (literally “hardening of the arteries”) is characterized by intimal fibrosis of large
elastic arteries; abdominal aorta is most commonly affected. Age-related; affects many species but
rarely causes clinical signs.
Arterial medial calcification; frequent in animals; involves elastic and muscular arteries. Elastic
arteries: Characterized by mineral deposits on elastic fibers of the tunica media. Muscular arteries:
Mineral deposits form a complete ring of mineralization in the tunica media. Causes include:
ingestion of calcinogenic plants, vitamin D toxicosis, renal insufficiency; Johne’s Disease in cattle

C-M06 - Mulberry heart disease - heart – pig MG601

HD: Heart: Multifocally affecting 30 percent of the myocardium, there is necrosis and hemorrhage,
with multifocal to coalescing areas of myofiber loss and stromal collapse. Occasionally, myocytes
are fragmented, karyorrhectic and hypereosinophilic with loss of cross striations and pyknosis
(necrosis) or are swollen with vacuolated sarcoplasm (degeneration). Multifocally necrotic
myofibers contain basophilic granular material (mineral). There are moderate numbers of
fibroblasts within areas of necrosis. There is mild to moderate hemorrhage mixed with moderate
numbers of macrophages, often containing hemosiderin, lymphocytes, and occasional eosinophils.
Multifocally, the tunica media and intima of the myocardial vessels are disrupted and
hypereosinophilic (necrosis). Viable blood vessels are lined by reactive endothelium and are
surrounded by increased clear space (edema) and few eosinophils and lymphocytes.
MDX: Heart, myocardium: Degeneration and necrosis, multifocal to coalescing, moderate, with
vasculitis, lymphohistiocytic myocarditis, mineralization, and hemorrhage, crossbreed, porcine.
EDX: Vitamine E/Selenium deficiency cardiopathy
Cause: Vitamine E/Selenium deficiency
DDX myocardial necrosis: Encephalomyocarditis virus (Picornaviridae, genus Cardiovirus): Acute
death and myocardial necrosis / Foot and mouth disease (Picornaviridae, genus Aphthovirus):
Usually have typical vesiculoulcerative lesions / Swine vesicular disease (Picornaviridae, genus
Enterovirus): Characteristic vesicles / Gossypol toxicosis / Monensin toxicosis
CP: Other manifestations of vitamin E/selenium deficiency in pigs: Hepatosis dietetica, skeletal and
cardiac muscle necrosis, steatitis, hemolytic anemia, exudative diathesis.
Most species develop skeletal and cardiac muscle necrosis
Additional vitamin E/Se deficiency diseases in other species:
Ruminants: Hemolytic or destructive anemia
Lambs: Reported skeletal muscle degeneration, necrosis, and hepatic lipidosis caused by responsive
vitamin E deficiency only
Horses: Steatitis (yellow fat disease); possible cause of lower motor neuron disease
Dogs: Steatitis; "brown dog gut" (intestinal lipofuscinosis; ceroid), pigmentary retinal degeneration;
encephalomalacia; neuronal necrosis; axonal degeneration
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Cats: Steatitis
Poultry: Exudative diathesis; leukoencephalomalacia (cherry cerebellum); decreased egg
production and hatchability; aspermatogenesis; enlarged hocks; dystrophy of gizzard musculature
Brown pelicans: Vitamin E deficiency causes skeletal muscle and myocardial degeneration and
necrosis due to rancid feed
Fishing birds as herons, pelicans: Vitamin E deficiency causes pansteatitis
Rabbits: Cataracts; steatitis
Rats and mice: Hepatosis dietetica; fetal resorption; neuronal necrosis and axonal degeneration
Guinea Pigs: Testicular degeneration, aspermatogenesis
Non-human primates: Muscular dystrophy; hemolytic or destructive anemia; pigmentary retinal
degeneration; additionally, pyogranulomatous pansteatitis in marmosets
Humans: Dietary hypovitaminosis E is rare; most cases are secondary to diseases (e.g. fat
malabsorption due to cystic fibrosis of the pancreas, cholestasis) that interfere with vit E absorption.

C-M07A - Aotus cardiomyopathy - heart - Owl monkey

HD: Heart, ventricle: Multifocally, affecting approximately 40% of the myocardium, there is
moderate to marked loss of cardiomyocytes with replacement by fibrous connective tissue
(fibrosis). Remaining myocytes are variably sized; with increased diameter (hypertrophy),
shrunken, individualized, and surrounded by fibrous connective tissue (atrophy), contain pale
granular or vacuolated sarcoplasm (degeneration), or are shrunken with hypereosinophilic
sarcoplasm and pyknotic nuclei (necrosis). Multifocally, within the subepicardial connective tissue
and myocardium, there are low numbers of lymphocytes, plasma cells, macrophages, and rare
neutrophils, ectatic lymphatics (edema), and scattered small foci of hemorrhage. Many myocytes
contain variable amounts of golden-brown perinuclear pigment (lipofuscin).
MDX: Heart: Fibrosis, multifocal, marked, with myocyte degeneration and necrosis, Owl monkey
(Aotus sp.), nonhuman primate.
GD: Cardiomyopathy is a very common cause of morbidity and mortality in Aotus monkeys. The
pathogenesis of Aotus cardiomyopathy is unknown.

C-M07B - Aotus cardiomyopathy - lung, lymph node - Owl monkey

HD: 1. Lung: Diffusely alveolar lumina contain variable numbers of macrophages with
vacuolated cytoplasm or hemosiderin pigment (“heart failure cells”) and few extravasated
erythrocytes. Multifocally alveolar septa are thickened up to 4 times normal by congestion and
eosinophilic finely beaded material (fibrin). 2. Lymph node, site not specified: Diffusely,
subcapsular and medullary sinuses contain many erythrocytes (draining hemorrhage) and
increased numbers of macrophages that exhibit erythrophagocytosis and hemosiderosis.
MDX: 1. Lung: Alveolar histiocytosis, diffuse, moderate, with hemosiderosis and congestion, Owl
monkey (Aotus sp.), nonhuman primate. 2. Lymph node, site not specified: Draining hemorrhage.

C-M07C - Aotus cardiomyopathy - liver - Owl monkey

HD: Liver: Diffusely, there are coalescing areas of marked centrilobular congestion and necrosis,
with variable retention of architecture, that occasionally extend to the portal areas. There is
hepatocellular loss with marked dilation of sinusoids, individualized hepatocytes that are
degenerate or necrotic and admixed with small amounts of cellular debris; or there is replacement of
normal architecture by hemorrhage and fibrin. Remaining hepatocytes contain few to many
variably sized, clear discrete vacuoles (lipid-type vacuolar change). Multifocally portal areas
contain small amounts of clear space and ectatic lymphatics filled with an eosinophilic
proteinaceous material (edema), and hepatocytes and Kupffer cells contain a brown to black
globular pigment.
MDX: Liver: Necrosis, centrilobular, diffuse, severe, with congestion, hemorrhage, and lipid-type
vacuolar change, Owl monkey (Aotus sp.), nonhuman primate.
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C-M08 - Myocardial epithelial inclusions - heart – ox-1wk old MG256

HD: Heart: Subjacent to the endocardium, extending into the myocardium, and within one of the
papillary muscles are two expansile, unencapsulated, well demarcated masses up to 0.75 cm x 1.5
cm that separate, surround, isolate and replace individual cardiomyocytes and Purkinje fibers. The
masses are composed of multiple variably sized tubules that measure up to 2.5 mm diameter and are
lined by one to multiple layers of squamous to cuboidal epithelium. Between the tubules, there are
multifocal small nests of similar epithelial cells and abundant collagenous connective tissue. The
interstitial tissue subjacent to the endocardium is mildly separated by clear space (edema).
MDX: Heart, myocardium: Epithelial inclusions, multifocal, Holstein, bovine.
GD: Bovine myocardial epithelial inclusions are congenital masses that do not proliferate,
metastasize, or undergo malignant transformation. Can be considered a choristoma; may be
endodermal rests misplaced during organogenesis.

C-M09 - Endomyocarditis (EMC) - heart - cat

HD: Heart: Diffusely the endocardium of the left ventricle is expanded up to five times normal by
abundant eosinophilic beaded to fibrillar material (fibrin) and clear space (edema), admixed with
moderate numbers of fibroblasts, neutrophils, lymphocytes, plasma cells, macrophages,
eosinophilic cellular and karyorrhectic debris (necrosis), and hemorrhage. Multifocally,
inflammatory cells infiltrate the underlying myocardium, expand the interstitium, and separate,
surround, and replace cardiomyocytes that are occasionally vacuolated or shrunken with
hypereosinophilic sarcoplasm and pyknotic nuclei (degeneration and necrosis).
MDX: Heart, left ventricle: Endocarditis, fibrinous, subacute, diffuse, moderate, with necrosis,
edema, hemorrhage, and mild multifocal myocarditis, Domestic shorthair cat, feline.
EDX: Idiopathic endocarditis
Cause: Unknown
GD: Endomyocarditis (EMC) is a relatively common, but unique disease in cats, which is often
fatal, because of inflammation of the left ventricular outflow tract. Common in cats less than 4
years.
DDX:
For cardiac disease in cats:
Left ventricular endocardial fibrosis (LVEF) or restrictive cardiomyopathy (RCM): Older cats;
marked endocardial fibrosis; may be a sequela of EMC
Dilated (congestive) cardiomyopathy: Bilateral enlargement of all heart chambers associated with
dietary taurine deficiency in cats; carnitine deficiency in dogs
Hypertrophic cardiomyopathy
Marked hypertrophy of the ventricles, especially the left ventricle
Cardiomyocyte hypertrophy and disarray of sarcomeres
Hereditary in Persian cats
Hyperthyroidism
Concentric, usually bilateral, ventricular hypertrophy
Enlarged thyroid glands
Endocardial fibroelastosis: Young Burmese, Siamese
Aortic stenosis, hypertension
Systemic reactive angioendotheliomatosis: Intraluminal proliferation of spindle cells within vessels
often involving the heart with resultant myocardial dysfunction
CP: EMC is unique to cats.
Ulcerative endocarditis: Distinct ulcerative lesion in the left atrium of dogs, associated with acute
renal insufficiency
Valvular endocarditis:
Horses: Strongylus vulgaris larval migration
Bovine: Arcanobacter pyogenes
Pigs: Streptococcus sp. and Erysipelothrix rhusiopathiae
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Dogs and Cats: Streptococcus sp. and E. coli

Cardiomyopathies:
In dogs, the most commonly recognized cardiomyopathy is the dilated or congestive form in giant
and large-breed dogs. HCM is much less common than the dilated form.
In cattle, cardiomyopathies have been described in certain breeds (Japanese black cattle, Australian
polled Herefords and Holstein-Friesian); inheritance is autosomal recessive
Dilated and hypertrophic cardiomyopathies have been described in pigs.
An inherited cardiomyopathy exists in certain strains of Syrian hamsters causing atrial thrombosis.

C-M10 - Hypertrophic cardiomyopathy - heart – cat MG589

HD: Heart: The left ventricular free wall and interventricular septum are up to 8 mm thick and the
right ventricular wall is 2 mm thick. Multifocally in the myocardium of the left ventricular free
wall, papillary muscle, and interventricular septum, there is loss of cardiomyocytes with
replacement by moderate amounts of collagen and rare adipocytes. Adjacent myofibers are often
pale, vacuolated and fragmented (degenerate). Diffusely cardiomyocytes are enlarged 2-3 times
normal, with abundant eosinophilic fibrillar cytoplasm and a large vesicular central nucleus
(hypertrophy). Multifocally cardiomyocytes are irregularly arranged in right-angle branching
or radiating "pinwheel" patterns (myofiber disarray). Multifocally and segmentally, the tunica
media of intramyocardial vessels is mildly expanded by fibrillar eosinophilic material and
hypertrophic smooth muscle cells (arteriolar hypertrophy). Multifocally the endocardium is mildly
thickened by fibrous connective tissue.
MDX: Heart, myocardium: Fibrosis, multifocal, moderate, with myofiber hypertrophy, disarray,
degeneration and loss, Domestic Shorthair, feline.
GD:
Cardiomyopathy is subdivided into dilated, hypertrophic, and restrictive
Hypertrophic cardiomyopathy is characterized by ventricular hypertrophy without ventricular
dilatation that is not attributable to other cardiac, vascular, or systemic disease. Affected cats are
usually middle-aged males.
Pathogenesis:
Hypertrophic cardiomyopathy (HCM)
Diastolic disorder: Decreased compliance of the ventricular myocardium with normal systolic
myocardial contractile function > decreased filling of ventricle during diastole (decreased preload)
> decreased cardiac output (CO)
Concentric cardiac hypertrophy: Increase in mass of ventricle without increase in end-diastolic
volume; occurs in hyperthyroid cats (symmetrical or asymmetrical hypertrophy, hypertrophied
myofibers without myofiber disarray in most cases)
Hypertrophic cardiomyopathy is a heterogeneous disease with many phenotypes. The cause is not
known but there is a familial occurrence in cats and in humans there is a strong genetic link.
Regardless of the cause the end result is myocardial infarction with scarring. The most widely
accepted mechanism is that of myocardial ischemia as a result of coronary vessel hypertophy with
resultant luminal narrowing. Coronary vessel spasm, increase of cardiac muscle mass beyond the
ability of the vasculature to supply blood, thromboembolism of the coronary arteries, mutations in
genes encoding various sarcometic proteins and mitochondrial genes, and apoptosis have also been
suggested.
In addition to myocardial hypertrophy, nerve conduction within the heart is also altered in
hypertrophic cardiomyopathy. There is marked degeneration and fibrous replacement of the
atrioventricular conduction system involving the branching portion of the AV bundle and the upper
portion of the left bundle branch which leads to AV block and death.
Maine coon cats: Autosomal dominant, suspected sarcomeric gene defect similar to that occurring
in familial hypertrophic cardiomyopathy in humans (animal model)
Also heritable in Persian cats
Dystrophin-deficient cats: X-linked recessive dystrophin deficiency, animal model for Duchenne
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muscular dystrophy and Becker muscular dystrophy

Low plasma vitamin B-12 concentrations correlate with severity of HCM; low B-12 and arginine
correlate with presence of arterial thromboembolism.
Dilated cardiomyopathy (DCM)
Systolic disorder: Decreased contractility + increased afterload > decreased CO
Eccentric cardiac hypertrophy: Increase in myocardial mass with increase in ventricular volume
(Ventricular wall is usually normal or thin.)
Linked to taurine deficiency; pathogenesis obscure
Restrictive cardiomyopathy (RCM)
Impaired diastolic relaxation with reduced ventricular filling (decreased preload) > decreased CO
Rare, usually in older male cats
Excessive moderator bands in the left ventricle; trabecula septomarginalis (moderator band)
normally only in the right ventricle
Burmese cats: Congenital endocardial fibroelastosis
Typical Gross Findings:
HCM
Symmetric hypertrophy of ventricles (especially the left ventricle), occasional asymmetric
ventricular septal thickening, papillary muscle hypertrophy, narrowing of the ventricular lumen and
dilation of the left atrium (concentric hypertrophy)
Atrial thrombosis with thromboembolism of caudal aorta (saddle thrombus)
DCM
Dilation of the heart chambers, most often the left ventricle. Walls maybe thin or thick (eccentric
hypertrophy)
Thickened opaque endocardium, expanded atrioventricular rings, and atrial thrombosis
Pulmonary edema; pleural effusion; ascites; chronic passive hepatic congestion; left or bilateral
congestive heart failure
RCM
Severe ventricular endomyocardial fibrosis and thickening with atrial enlargement
Mural thrombosis; left or bilateral congestive heart failure
Typical Light Microscopic Findings:
HCM: 1) the histologic gold standard is myofiber disarray; 2) myofiber hypertrophy; 3) myofiber
loss with replacement fibrosis; 4) thick-walled, intramural, coronary arteries with a narrowed
lumen.
DCM: Myocardial and interstitial fibrosis; myofiber hypertrophy without myofiber disarray;
myofiber degeneration, necrosis, atrophy and loss
RCM: Endomyocardial replacement with granulation tissue and fibrosis
Differential Diagnosis:
Vascular or metabolic diseases: Hyperthyroidism, hypertension, aortic stenosis, PDA, patent
foramen ovale, ventricular septal defects, etc.
Hypertrophic muscular dystrophy: Dystrophin abnormality; concentric myocardial hypertrophy
predominantly left ventricle; mineralization
Excessive moderator bands: Left ventricle; left sided heart failure
Endocardial fibroelastosis: Burmese, Siamese cats
Endomyocarditis: Young cats
Comparative Pathology:
Dogs:
Usually DCM, young to middle-aged giant and large-breed dogs, especially Doberman Pinscher,
Boxers, Portuguese Water Dogs, Dalmatians
There are two distinct histologic forms: 1) the cardiomyopathy of Boxers and of Doberman
Pinschers, corresponding to the “fatty infiltration-degenerative” type of DCM; 2) the form detected
in many giant, large- and medium-sized breeds, which can be classified as the “attenuated wavy
fiber” type of DCM.
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English Cocker Spaniel: Early HCM > DCM late in life; taurine deficiency in some canine cases
Cattle: Usually DCM, autosomal recessive; right sided heart failure in young to mature Holsteins;
sudden death in Japanese Blacks and Polled Hereford calves (associated with curly coat)
Pigs: HCM and DCM
Syrian hamsters: Hereditary dystrophic cardiomyopathy; dilated ventricles with mineralization
Mice: Transgenic mice expressing mutant tropomyosin, an essential sarcomere component, develop
ventricular hypertrophy, fibrosis and atrial enlargement one month after birth; death occurs between
4-5 months.
Ferret: Secondary generalized dilatative cardiomyopathy, hepatosplenomegaly, hydrothorax

C-N01 - Endocardial schwannoma - heart - rat

HD: Heart: Diffusely, expanding the subendocardium of the left ventricle, occasionally infiltrating
adjacent myocardium, and multifocally expanding the atrium and aortic valve, is an unencapsulated,
poorly circumscribed, variably dense cellular neoplasm composed of spindle cells arranged in
short interlacing streams, bundles and whorls, with frequent nuclear regimentation. The
neoplastic cells are surrounded and separated by variable amounts of eosinophilic finely fibrillar
matrix. Neoplastic cells have indistinct borders, a small amount of eosinophilic fibrillar to
vacuolated cytoplasm, and variably sized, oval to elongate, vesiculate nuclei that contain one
variably distinct basophilic nucleolus. Multifocally, elongate nuclei have a central band of
chromatin that spans the greater diameter of the nucleus (Anitschkow type nuclei). There are
occasional larger polygonal and multinucleate neoplastic cells. Mitoses average 5-6 per HPF and
are occasionally bizarre. Multifocal cardiomyoctes adjacent to or entrapped within the neoplasm
are pale, swollen, and vacuolated (degeneration).
MDX: Heart: Schwannoma, endocardial, breed unspecified, rat, rodent.
CS: Endocardial sarcoma, endomyocardial neurofibromatosis, neurinoma, neurilemoma,
endocardial mesenchymal tumor, Anitschkow cell sarcoma, neurosarcoma
GD: Most common primary cardiac tumor of the rat. Metastasis rare, mostly to lung and liver
Pathogenesis: Cell of origin unknown; Schwann cell origin suspected based on histologic features
and positive immunohistochemistry for S-100 protein and neuron specific enolase
Typical Light Microscopic Findings:Biphasic population of neoplastic cells: Superficial cells:
Ovoid with large dense oval nuclei, prominent nucleoli, and finely vacuolated cytoplasm: Deep
cells: Spindled and separated by collagen, forming whorls (Antoni type A) and herring bone
patterns. Anitschkow cells: Neoplastic cells with a central band of heterochromatin that spans the
greater diameter of the nucleus. Occasionally, there may be giant nuclei, multinucleate cells, areas
of loosely arranged neoplastic cells (Antoni type B), and palisaded elongated nuclei (Verocay
bodies)
DDX: Intramural schwannoma: Well circumscribed, discrete nodules
Fibroma/fibrosarcoma, myxoma, rhabdomyoma/sarcoma, hemangioma/sarcoma

C-N02 - Hemangiosarcoma - heart – dog 593

HD: Heart, right atrium: Expanding the myocardium and replacing 95% of the cardiac myocytes,
there is a loosely cellular, poorly circumscribed, infiltrative neoplasm. Neoplastic cells form
irregularly sized blood-filled vascular channels, often wrap collagen bundles, or rarely are
arranged in streams and bundles in more solid areas. Neoplastic cells are spindle with variably
distinct cell borders and a moderate amount of eosinophilic fibrillar cytoplasm. Nuclei are
irregularly oval to elongate and bulge into the vascular channels, have coarsely clumped chromatin
and up to 2 distinct nucleoli. Mitotic rate averages 3-5 per high power field. There is marked
anisokaryosis, anisocytosis, cellular pleomorphism, and single cell necrosis. At the periphery of the
neoplasm, cardiac myocytes are surrounded by neoplastic cells and are degenerate (swollen and
pale) or necrotic (shrunken and hypereosinophilic with pyknotic nuclei) and there are large areas of
necrosis and few fibrin thrombi. There are scattered aggregates of lymphocytes, plasma cells,
hemosiderin-laden macrophages, and degenerate and non-degenerate neutrophils
 10

MDX: Heart, right atrium: Hemangiosarcoma, breed not specified, canine.

GD: Typical Light Microscopic Findings:
Spindle to polygonal to ovoid neoplastic cells that usually form vascular channels, spaces, or small
clefts somewhere in the tumor / Pleomorphic, hyperchromatic nuclei that often bulge into the
lumina of vascular channels / Frequent mitotic figures; hemorrhage and necrosis; collagen wrapping
Large solid areas may be difficult to distinguish from poorly differentiated sarcomas. / Additional
Diagnostic Tests: Factor VIII-related antigen for endothelial cells
DDX:
Hemangioma: Well circumscribed neoplasm, vascular spaces are lined by a single layer of uniform
endothelial cells and are filled with erythrocytes; there are different variants based on the size and
appearance of vascular spaces
Vascular hamartoma: An improper proliferation of normal blood vessels; endothelial cells are
surrounded by tunica media and tunica adventitia
Kaposi-like vascular tumor: Well circumscribed neoplasm with angular slit-like vascular spaces
with few erythrocytes surrounded by large cavernous vascular spaces, lymphocytes, and a thick
fibrous capsule (This tumor is named for its similar histologic appearance to the human Kaposi
sarcoma and has NO association with human herpes virus 8 or immunosuppression)
Lymphangiosarcoma: Vascular channels containing few erythrocytes
Aortic body tumor (chemodectoma): White, firm mass at the base of the heart
Neoplasm arising in ectopic thyroid or parathyroid tissue
Rhabdomyoma/rhabdomyosarcoma: Gray nodules that often project into cardiac chambers; rare in
all species
Malignant lymphoma: White, fleshy mass that resembles deposits of fat
Pericardial mesothelioma
Schwannoma: Seen in cattle as single or multiple white nodules

C-P01 - Spirocerca lupi infection - aorta – dog MG598/ 606/07

HD: Aorta: The tunica intima is thickened multifocally and expanded up to 3 times normal by
plaque-like accumulations of collagen (fibrosis) and low numbers of plasma cells. Multifocally the
intima is necrotic with accumulations of amorphous, eosinophilic material (fibrin), eosinophilic
cellular and karyorrhectic debris, few neutrophils and hemorrhage. The tunica media and adventitia
are disrupted by multifocal to coalescing tracts composed of central necrotic cellular debris,
hemorrhage, and variable numbers of macrophages which are often hemosiderin-laden, neutrophils,
lymphocytes, and abundant fibrin (larval migration tracts). Multifocally within the tunica media,
there are cross sections of larval nematodes up to 300 um in diameter, with a smooth cuticle,
coelomyarian-polymyarian musculature, prominent stalked lateral chords, brightly
eosinophilic material in the pseudocoelom, and a large intestine lined by uninucleate epithelial
cells with a prominent, tall brush border. Focally, there is osseous metaplasia within the tunica
media.
MDX: Aorta: Arteritis, necrotizing, subacute, diffuse, severe, with larval nematodes and focal
osseous metaplasia, breed unspecified, canine.
ED: Aortic spirocercosis
Cause: Spirocerca lupi
GD: Tropical and subtropical areas / Intermediate host: Dung beetles / Spirally coiled nematodes,
pink to red
DDX:
Gongylonema pulchrum: Spirurid with broad host range; favors esophagus and stomach; does not
form nodules; small thread-like worms present in the mucosa
Dirofilaria immitis : Adults are filarid nematodes found normally within the heart or vascular
lumina

C-P02 - Strongylus vulgaris infection - artery – horse MG607

 11

HD: Artery, mesenteric: Diffusely expanding and replacing the endothelium and internal elastic
lamina is a variably thick band of eosinophilic granular to beaded fibrillar material
(thrombus) admixed with high numbers of eosinophils and plasma cells with fewer neutrophils,
lymphocytes, macrophages, hemorrhage, and abundant cellular and karyorrhectic debris (necrosis).
Lesser numbers of inflammatory cells infiltrate the subendothelial connective tissue tunica intima,
and the tunica media, which is moderately thickened up to 4 times normal by fibrin and necrotic
debris. Within the thrombus are multiple cross and tangential sections of larval nematodes up to
220 um in diameter with a smooth 6 um thick cuticle, platymyarian-meromyarian
musculature, prominent lateral cords, pseudocoelom, and a large, central intestine lined by
few multinucleated cells with a prominent brush border. Within the tunicae media and
adventitia, low numbers of lymphocytes and eosinophils surround vessels.
MDX: Artery, mesenteric: Arteritis, transmural, proliferative and necrotizing, eosinophilic and
lymphoplasmacytic, chronic, diffuse, severe, with an organizing thrombus, and subendothelial
larval strongyles, breed not specified, equine.
ED: Strongylid arteritis
Cause: Strongylus vulgaris
CS: Strongylosis, strongylidosis, true strongyles, large strongyles
DDX:
Small strongyles (cyathostomes): Synchronous emergence may cause hemorrhagic enteritis,
hypoalbuminemia and weight loss; they are generally nonpathogenic.
S. edentatus: The larvae migrate via the portal system to the liver and eventually return to the cecum
where they mature into adults
S. equinus: Migrate through peritoneal cavity to liver, then pancreas; re-enter the cecum/right
ventral colon by direct penetration
CP:
Strongylus, Triodontophorus, Oesophagosdontus, Craterostomum in equids
Vascular parasites
Schistosomiasis (Schistosoma, Heterobilharzia, Orientobilharzia): Blood flukes of mammals and
birds
Onchocerca sp.: In the wall of the aorta of cattle, buffalo and goats
Dirofilaria immitis: Heartworm of dogs and, less commonly, domestic and wild cats, wild canids,
sea lions, muskrats, and horses
Brugia sp.: Tropical parasite of dogs and cats

C-P03 - Dirofilaria immitis infection - lung – dog MG547, 582

HD: Lung: Focally, a pulmonary artery is moderately dilated and there is thickening of the tunica
intima by abundant fibrous connective tissue that extends from the tunica intima, contains few
lymphocytes and plasma cells, and forms frond-like proliferations into the lumen. Within the lumen
there are multiple cross sections of adult male and female 1 mm diameter nematodes with a thin
eosinophilic cuticle; prominent lateral cords that possess an internal lateral cuticular ridge;
tall coelomyarian/polymyarian musculature; a small intestine lined by few multinucleate
epithelial cells; and paired uteri or a single gonad. Multifocally there are nodular aggregates of
epithelioid macrophages surrounded by neutrophils, eosinophils, fibrous connective tissue and few
lymphocytes and plasma cells (granulomas). Within bronchi and bronchioles there are numerous
eosinophils, neutrophils, lymphocytes, eosinophilic fibrillar material (fibrin) and erythrocytes.
Often there are peribronchial/bronchiolar and perivascular eosinophils, macrophages, and fewer
plasma cells and lymphocytes. Alveolar septa are diffusely thickened by low numbers of similar
inflammatory cells and increased fibrous connective tissue.
MDX: 1. Lung, artery: Endarteritis, proliferative and villous, chronic, focally extensive,
moderate, with intraarterial male and female nematodes, etiology consistent with Dirofilaria
immitis, breed unspecified, canine.
2. Lung: Pneumonia, eosinophilic, histiocytic, and lymphoplasmacytic, multifocal, moderate, with
 12

multiple granulomas.
ED: Pulmonary dirofilariasis
Cause: Dirofilaria immitis
CS: Heartworm disease
GD: Heartworm disease is primarily a pulmonary vascular disease. Fibrovascular proliferations
grossly produce a shaggy or roughened appearance to the intima, which is pathognomonic for
heartworm disease. Antigen stimulation from parasites may lead to immune complex
glomerulonephritis.
DDX:
Dipetalonema reconditum is nonpathogenic cutaneous parasite that produces microfilaria
Angiostrongylus vasorum is a parasite of the pulmonary arteries of dogs and foxes that cause a
proliferative endarteritis. The eggs that lodge in small vessels cause more severe damage.
CP: Cats: Infection of cats by D. immitis is common in endemic areas and is an important clinical
entity.

C-P04 - Cysticercosis - heart - ox

HD: Heart: Focally expanding the myocardium, is a 3 x 3 mm parasitic cyst containing a cross-
section of a larval cestode (cysticercus) surrounded by a 4 mm thick fibrous capsule.
Bounding the cyst there is abundant eosinophilic cellular and karyorrhectic debris (necrosis),
numerous epithelioid macrophages, and fewer lymphocytes, plasma cells, and eosinophils, which is
further surrounded by dense collagen. The encysted larval cestode has a 4 um thick, eosinophilic
tegument; a lacy, fibrillar, eosinophilic parenchyma; numerous 5 um diameter, basophilic,
round, calcareous corpuscles; and a central scolex with two muscular suckers. Replacing
approximately 50 percent of one section, is a focally extensive area of dense fibrous connective
tissue admixed with numerous lymphocytes, plasma cells and macrophages and few eosinophils and
neutrophils. There are occasional foreign-body type multinucleate giant cells and mineral. Cardiac
myocytes adjacent to these fibrous areas are either hypereosinophilic, and fragmented with pyknosis
or karyolysis (necrotic) or vacuolated and swollen (degenerate), and myofibers are often separated
by eosinophilic, fibrillar to beaded material (fibrin) and increased clear space (edema). Multifocally,
random cardiac myocytes contain thin-walled, 100 X 200 um protozoal cysts containing abundant 3
X 5 um, basophilic, crescent-shaped bradyzoites (sarcocysts).
MD: 1. Heart: Myocarditis, granulomatous and eosinophilic, multifocal, severe, with cardiomyocyte
degeneration and necrosis and an intralesional cysticercus, breed unspecified, bovine.
2. Heart, cardiomyocytes: Sarcocysts, intracellular, few.
ED: Myocardial cysticercosis and sarcocystosis
Cause: Cysticercus bovis
GD: Preferentially infects heart and masticatory muscles, although cysts also occur in liver, lungs
and lymph nodes. The adult stage, Taenia saginata, is the most common and longest tapeworm in
humans. A cysticercus is a fluid-filled, thin-walled, muscular cyst, with an invaginated scolex and
neck.
DDX:
T. solium: Pork tapeworm; metacestode C. cellulosae. Unlike T. saginata, humans can be both
definitive and intermediate hosts for T. solium. Cysticerci often develop in cerebral or ocular
locations and can be fatal.
Echinococcosis granulosus: Hydatid disease. Larval stages form unilocular hydatid cysts that
localize in the lung, liver and other organs. Thick outer membrane, encasing a germinal membrane
that contains brood capsules (hydatid sand) that are free or connected to the membrane by a stalk;
brood capsules with many ovoid, hooklet-laden scolices. Hydatid cysts are usually surrounded by
mononuclear cells, eosinophils, giant cells and fibrosis; in humans most cysts are located in the
liver.

C-P05 - Acanthamoeba sp. infection - heart – dog MG384

 13

HD: Heart: Multifocally the myocardial architecture is disrupted by large amounts of eosinophilic
cellular and karyorrhectic debris (necrosis), moderate numbers of viable and degenerate neutrophils,
fewer macrophages, hemorrhage, fibrin and edema. Multifocally, many cardiomyocytes are
fragmented and hypereosinophilic with loss of cross striations (myocardiocyte necrosis). Within
areas of inflammation and necrosis, there are scattered, 10-20 um diameter, irregularly round
amoebic trophozoites with abundant granular amphophilic cytoplasm, a single 7 um eccentric
magenta nucleus and a 1-2 um dense basophilic nucleolus surrounded by a thin, clear rim.
Cysts are smaller, irregular in shape and have a thick 1-2 um, wavy outer wall. The
endocardium is thickened up to 3 times normal by edema, hemorrhage, fibrin, and low numbers of
lymphocytes, neutrophils, and macrophages.
MD: Heart: Myocarditis, necrohemorrhagic, subacute, multifocal, marked, with amoebic
trophozoites and cysts, breed unspecified, canine.
ED: Myocardial acanthamebiasis
Cause: Acanthamoeba sp.
GD: Small free living amebas of different genera, such as Acanthamoeba, Naegleria, Balamuthia,
and Sappinia. Trophozoites resemble macrophages and are 10-30 um in diameter with an eccentric
nucleus and eosinophilic cytoplasm containing glycogen vacuoles and occasional ingested
erythrocytes. Cysts are generally rare and are more prevalent in CNS lesions than in extraneural
lesions. Additional Diagnostic Tests: Organisms are PAS positive. Cysts can be demonstrated with
silver stains.
DDX:
Trophozoites of Acanthamoeba and Naegleria are indistinguishable by light microscopy.
Naegleria generally does not produce cysts in tissue and is often associated with acute neurologic
infections.
Balamuthia: Slightly larger and more pleomorphic trophozoites than other amebas; often multiple
nucleoli

C-P06 - Chagas' disease - heart – dog MG593

HD: Heart: Diffusely and transmurally, cardiac myocytes are separated, surrounded, and replaced
by high numbers of lymphocytes, plasma cells, and macrophages and fewer neutrophils and
fibroblasts with multifocal areas that contain an eosinophilic beaded to finely fibrillar material
(fibrin), and increased clear space along with ectatic lymphatics (edema). Up to 80 percent of
remaining cardiac myocytes range from degenerate characterized by cells that are swollen, pale and
vacuolated to necrotic characterized by cells that are shrunken, angulated with pyknosis or
karyolysis, loss of cross striations and a hypereosinophilic often fragmented sarcoplasm.
Multifocally, individual myofibers contain variably sized, intracytoplasmic oval to elongate
pseudocysts (up to 60 x 125um), with numerous 2-4 um round to oval protozoal amastigotes
with a distinct basophilic nucleus and a rod-shaped kinetoplast oriented parallel to the
nucleus. The endocardium and epicardium have similar, but less severe, changes.
MD: Heart: Pancarditis, necrotizing, chronic-active, diffuse, severe, with many intramyocyte
protozoal amastigotes, breed not specified, canine.
ED: Trypanosomal myocarditis
Cause: Trypanosoma cruzi
CS: American trypanosomiasis
GD: T. cruzi is a hemoflagellate protozoan (Class Zoomastigophorea, Family Trypanosomatidae)
that causes fatal chronic myocarditis in both dogs and humans. Transmitted by “kissing” or assassin
bugs (Triatoma sp.); nocturnal feeders, short flying distances, inhabit animal bedding and human
dwellings. Three morphologic forms: Trypomastigotes (blood form); amastigotes (intracellular
form); epimastigotes (form found in the vector). Trypomastigotes: Host blood and insect hindgut;
undulating membrane running the entire length of the organism and a free flagellum. Amastigote
(“leishmanial form”): Intracellular; within pseudocysts primarily in muscle, especially heart muscle;
round to oval, 1.5-4 um in diameter, contain a nucleus, and a rod-like kinetoplast parallel to the
 14

nucleus; no free flagellum or undulating membrane

DDX:
Toxoplasma/Neospora: No kinetoplast
Leishmania: Larger kinetoplast perpendicular to the nucleus (parallel in T. cruzi); no trypomastigote
form
Sarcocystis sp.: No kinetoplast
Histoplasma capsulatum: Intracellular yeast; no kinetoplast
Other Trypanosoma sp.: No tissue amastigote form

C-V01 - Canine parvoviral type 2 infection - heart – dog – 5wk MG593

HD: Myocardium: Multifocally there is cardiomyocyte loss and replacement with loosely arranged,
edematous collagen and small numbers of lymphocytes and rare plasma cells. Adjacent
cardiomyocytes are occasionally swollen or vacuolated (degeneration); or rarely are shrunken and
fragmented, with loss of cross striations and hypereosinophilic sarcoplasm (necrosis). Occasionally
cardiomyocyte nuclei contain a 5-10 um intranuclear inclusion body that is either basophilic
and completely fills the nucleus, or is eosinophilic and surrounded by a 1-2 um clear halo and
marginated chromatin. Diffusely the endomysial fibrous connective tissue is mildly expanded
by clear space and finely fibrillar material (edema).
MDX: Heart: Myocarditis, lymphoplasmacytic, chronic, multifocal, mild, with myocardiocyte
degeneration, necrosis and loss, and intranuclear inclusion bodies, Labrador Retriever, canine.
ED: Parvoviral myocarditis
Cause: Canine parvovirus type 2 (CPV-2)
GD: Multisystemic necrotizing vasculitis. Basophilic intranuclear inclusion bodies in heart, kidney,
liver, lung, intestinal tract, vascular endothelium. Lymphoid depletion
DDX:
Myocardial necrosis in puppies:
Canine distemper virus (Paramyxoviridae, Morbillivirus): Purely degenerative; eosinophilic
intracytoplasmic and intranuclear inclusion bodies
Canine herpes virus: Inflammatory exudate; intranuclear inclusions
CP:
Canine parvovirus type 1 (Minute virus of canines): Sporadic cause of respiratory disease, mild
enteritis or myocarditis in 1-3 week old pups; enterocyte hyperplasia with intranuclear inclusions in
villus epithelium, no crypt lesions
Feline parvovirus (feline panleukopenia): Intrauterine infection results in cerebellar hypoplasia;
panleukopenia and enteritis in postnatal kittens and cats
Porcine parvovirus: Subclinical in adults; important cause of reproductive failure and the SMEDI
syndrome: Stillborn, mummification, embryonic death, infertility
Rodent parvoviruses - Most cause subclinical infections:
Kilham’s rat virus (RV), Rat parvovirus, H-1 virus: Cerebellar hypoplasia, hemorrhagic
encephalopathy, focal hepatic necrosis, peritesticular hemorrhage; amphophilic intranuclear
inclusion bodies in hepatocytes, endothelial cells and bile duct epithelium
Minute virus of mice (infant mice) - cerebellar hypoplasia; Mouse parvovirus (adult mice) - tropism
for T lymphocytes resulting in immune modulation
Hamster parvovirus - Epizootic occurrence in weanling/suckling hamsters, high mortality; facial
and dental malformations, domed calvaria; testicular atrophy; multifocal hemorrhage and necrosis;
multifocal cerebral mineralization
Mink enteritis virus - Closely related to feline parvovirus; panleukopenia, enteritis
Aleutian Mink Disease (AMD) - Results in rapidly life-threatening immune-mediated
glomerulonephritis, vasculitis, and hypergammaglobulinemia in mink. In ferrets AMD is a more
protracted disease (two years or more) characterized by hypergammaglobulinemia and immune
complex glomerulonephritis; prominent plasmacytic infiltrates in numerous organs especially renal
interstitium, hepatic portal areas and splenic red pulp where a nearly pure population of plasma cells
 15

expands the red pulp

Duck parvovirus: Muscovy ducklings; hepatitis, myocarditis; closely related to adeno-associated
virus 2
Goose parvovirus: Lethal disease of young goslings and Muscovy ducks; hepatitis, myocarditis;
inclusion bodies in liver, spleen, myocardium, thymus, thyroid gland, intestines

C-V02 - Encephalomyocarditis virus infection - heart – pig MG593

HD: Heart, ventricle: Multifocally disrupting the epicardium, myocardium, and endocardium and
surrounding, separating, isolating and replacing cardiac myocytes are high numbers of lymphocytes,
plasma cells, and macrophages, moderate amounts of clear space (edema), eosinophilic fibrillar
material (fibrin), and basophilic granular material (mineral). Within affected areas, cardiac
myocytes are swollen with vacuolated sarcoplasm (degeneration) or shrunken with
hypereosinophilic sarcoplasm, loss of cross striations, and pyknosis (necrosis). Occasionally
myocytes contain multiple nuclei that form rows.
MDX: Heart: Pancarditis, lymphocytic, plasmacytic and histiocytic, multifocal, severe, with
myocardial necrosis, breed unspecified, porcine.
EDX: Picornaviral myocarditis
Cause: Encephalomyocarditis virus (EMCV)
GD: Family Picornaviridae; genus Cardiovirus. Viral strains may produce either encephalitis or
myocarditis. Rats and mice are reservoir hosts, with clinically inapparent disease and shedding of
virus in urine and feces. The host range includes primates, swine, mice, raccoons and other
mammals with swine most susceptible (up to 100 percent mortality in suckling pigs).
DDX:
Myocarditis in pigs:
Foot and mouth disease (picorna/aphthovirus): Gross and microscopic cardiac lesions may be
indistinguishable from EMCV.
Parvovirus in pigs can induce a nonsuppurative myocarditis
Vitamin E/Se deficiency (Mulberry Heart Disease)
Edema:
Edema disease (E. coli)

C-V03 - Epizootic Hemorrhagic Disease (EHD) of Deer - heart - deer

HD: Heart: Affecting approximately 60 percent of the myocardium, epicardium and endocardium
are multifocal areas of necrosis, hemorrhage and inflammation. Multifocally, myocytes are
fragmented and granular; nuclei and cross striations are absent (necrosis). Myocytes multifocally
have thick, irregular, hypereosinophilic, segmental bands (contraction bands). Moderate numbers of
degenerate neutrophils and fewer macrophages separate, surround and occasionally replace
myocytes. Occasionally, the tunica intima of blood vessels is disrupted and replaced by cellular and
karyorrhectic debris, mild hemorrhage, fibrin, and few neutrophils (vasculitis). There is multifocal
mesothelial cell hypertrophy.
MDX: Heart: Pancarditis, necrotizing, multifocal, moderate, with necrotizing vasculitis, and
hemorrhage, White-tailed deer (Odocoileus virginianus), cervid.
EDX: Orbiviral myocarditis
Cause: Cervid orbivus 1 and 2
GD: Arthropod-borne virus which causes fatal hemorrhagic disease, particularly in White-tailed
deer, also mule deer, pronghorn antelope and cattle. Reoviridae family: Nonenveloped, linear
dsRNA. 2 serotypes: EHDV-1 and EHDV-2 are enzootic in the US. In deer herds: All ages
susceptible; morbidity-90%, mortality 60%; clinically resembles acute bluetongue in sheep.
Typical Gross Findings: Hemorrhage at the base of the pulmonary artery (from vasa vasorum).
Widespread hemorrhage and edema. Erosions/ulcers dental pad, tongue, palate, rumen, reticulum
and omasum. Hemorrhage of the rumen pillars
Typical Light Microscopic Findings: Widespread hemorrhage, edema, necrosis and thrombosis.
 16

Arterioles and venules most markedly affected

DDX:
Bluetongue (Orbivirus): Identical lesions
Adenovirus: Black-tailed and white-tailed deer, other cervids: Pulmonary edema, systemic
vasculitis, intranuclear inclusions in endothelial cells
Other veterinary orbiviral diseases:
Ibaraki disease: Cattle in Japan infected with EHDV-2, killed 4,000 in 1959
African horse sickness: Acute pulmonary edema and death; periorbital and nuchal ligament edema,
hydropericardium
Equine encephalosis: Limited to South Africa, alternating hyperexcitability and depression,
abortion

C-V04 - West Nile virus infection - heart - Chilean flamingo

HD: Heart: Multifocally infiltrating over 50% of cardiomyocytes, Purkinje fibers, and the
epicardium are coalescing aggregates of many lymphocytes, plasma cells and macrophages. The
majority of cardiomyoctes are shrunken, hyalinized with loss of cross striations, pyknosis or
karyolysis, and are surrounded by eosinophilic cellular and karyorrhectic debris (necrosis). Rare
cardiomyocytes are pale, swollen and vacuolated (degenerate). Diffusely similar inflammatory cells
infiltrate the epicardial adipose tissue and nerves.
MDX: Heart: Pancarditis, necrotizing, lymphoplasmacytic and histiocytic, multifocal to coalescing,
moderate, Chilean flamingo (Phoenicopterus chilensis), avian.
EDX: Flaviviral myocarditis
Cause: West Nile virus
GD: Cellular targets include CNS (cerebellum) and PNS; cardiomyocytes; macrophages and
monocytes; multiple epithelial cell types; oocytes; fibrous connective tissues.
DDX:
Exotic Newcastle's disease (Paramyxoviridae; Rubulavirus) or highly pathogenic avian influenza
(Orthomyxoviridae; Influenzavirus A): Both cause mortality in chickens and turkeys; however,
WNV is seldom a fatal infection in these species
Eastern equine encephalitis (Togaviridae; Alphavirus): Arbovirus known to be pathogenic for birds

D-B01 - Salmonella enteritidis infection - Liver - Guinea pig

HD: Liver: Multifocally there are random, variably sized (up to 2mm diameter) areas of
coagulative and lytic necrosis, which are frequently bordered by a variable number of
lymphocytes, macrophages, neutrophils, and plasma cells (paratyphoid nodules) as well as
hemorrhage. There is rare erythrophagocytosis. Multifocally there are moderate numbers of portal
and periportal lymphocytes and plasma cells, with fewer neutrophils and macrophages. Diffusely
remaining hepatocytes contain clear cytoplasmic vacuoles (vacuolar change, lipid-type).
Multifocally the capsule is irregular and expanded up to two times normal by variable numbers of
neutrophils, lymphocytes, plasma cells, and macrophages.
MDX: Liver: Hepatitis, necrotizing, multifocal, random, with nodular lymphohistiocytic and
neutrophilic hepatitis (paratyphoid nodules), diffuse lymphoplasmacytic portal hepatitis, and lipid-
type vacuolar change, guinea pig (Cavia porcellus), rodent.

EDX: Hepatic salmonellosis

Cause: Salmonella enteritidis
DDX:
Differential diagnosis for hepatic necrosis in a guinea pig
Clostridial enterotoxemia (C. perfringens, C. difficile): Acute fatal necrotizing typhlitis
Yersiniosis (Y. pseudotuberculosis): Large colonies of bacteria
Tyzzer’s disease (Clostridium piliforme): Portal necrosis; focal to segmental cecal mucosal
necrosis; characteristic appearance of intracellular bacteria best demonstrated with Warthin-Starry
 17

or Giemsa stains
Pneumococcal septicemia (Streptococcus pneumoniae): Acute fibrinous bronchopneumonia;
fibrinopurulent pleuritis, pericarditis, peritonitis, and consolidated lung lobes

D-B02 - Clostridium perfringens type C infection - small intestine – horse- 4d old MG366
HD: Small intestine: Transmurally, but most prominent in the submucosa, there is marked
hemorrhage, increased clear space and ectatic lymphatics (edema), congested vessels, and fibrin.
Multifocally, there are areas of lytic necrosis within the mucosa and areas of coagulative necrosis in
the lamina propria with multifocal loss of epithelium cells. The necrotic, denuded villi are often
lined by a dense layer of 1-2 x 3-7 um bacilli which are also present individually and in colonies
within the lamina propria. Multifocally, the tunica media of submucosal small and medium-sized
blood vessels are occasionally expanded and disrupted by fibrin, edema, karyorrhectic debris and
hemorrhage (vasculitis).
MDX: Small intestine: Enteritis, hemorrhagic and fibrinonecrotic, acute, transmural, diffuse,
marked, with vasculitis, edema, and large numbers of bacilli, Thoroughbred, equine.
EDX: Clostridial enteritis
Cause: Clostridium perfringens type C
DDX:
Bacterial equine enteric disease:
Salmonellosis - Gram negative bacilli, peracute septicemia in foals; acute fibrinonecrotic
ileotyphlocolitis and catarrhal enteritis in horses; chronic necroulcerative typhlocolitis (button ulcer
lesions in pigs)
Rhodococcus equi - Gram positive bacillus; pyogranulomatous and necroulcerative typhlocolitis;
pyogranulomatous mesenteric lymphadenitis in foals
Clostridium perfringens type A - Gram positive bacillus; unproven association with Colitis X
Clostridium perfringens type B - Gram positive bacillus; hemorrhagic enteritis in foals
Clostridium difficile - Gram positive bacillus; pseudomembranous typhlocolitis in horses;
enterocolitis in foals
Clostridium piliforme (Tyzzer's disease) - Gram negative bacillus; hepatic necrosis; segmental
ileotyphlitis/ileocolitis; myocardial necrosis
CP:
Clostridium perfringens - Types, toxins and diseases
Toxin
Type Diseases
Alpha Beta Epsilon Iota
Gas gangrene
Food Borne Illness humans
Necrotic enteritis - Chickens
A ++ - - - Gastroenteritis - Ferrets
Yellow lamb disease - enterotoxemia, western
US
Colitis X in horses - unproven association
Lamb dysentery
B + ++ + - Hemorrhagic enteritis - calves, foals, guinea pigs
- UK, S. Africa, Middle East
Enterotoxic hemorrhagic enteritis - neonatal
C + ++ - - foals, lambs, goats, cattle, pigs
Struck - Adult sheep, UK
D + - ++ - Overeating disease/ pulpy kidney - Sheep, cattle,
 18

goats
Focal symmetric encephalomalacia - Sheep
Enterotoxemia - calves, lambs. guinea pigs,
E + - - ++
rabbits

D-B03 - Ulcerative enteritis - small intestine - quail

HD: Small intestine: There is extensive loss of mucosal crypts and villi and replacement by a
coagulum of abundant fibrin, necrotic debris, and many colonies of 1x4 um bacilli that occasionally
contain 1 um, oval, subterminal spores. There are many macrophages, lymphocytes and few
heterophils admixed with the fibrinonecrotic debris, forming a diphtheritic membrane. Adjacent
villi are multifocally eroded and ulcerated and remaining mucosal and crypt epithelial cells are
often brightly eosinophilic, angular and shrunken with pyknotic nuclei (necrosis) or swollen and
microvacuolated (degeneration). Many heterophils, macrophages, lymphocytes, and plasma cells,
erythrocytes, fibrin and edema expand the remaining lamina propria and extend through the tunica
muscularis into the serosa. Multifocally, adventitial vessels are markedly congested.
MDX: Small intestine: Enteritis, ulcerative and necrotizing, subacute, diffuse, severe, with colonies
of bacilli, Quail, avian.
EDX: Clostridial enteritis
Cause: Clostridium colinum
CS: Quail disease
GD: Sudden death in young captive game birds, turkeys and chickens; does not affect water fowl
Mortality varies with species (10% in chickens, up to 100% in quail)
Additional typical Light Microscopic Findings: Liver: Centrilobular or diffuse, pinpoint coagulative
hepatic necrosis with abundant bacteria. Spleen: Variable splenic necrosis in quail
DDX:
Coccidiosis: Often seen with, or confused with, ulcerative enteritis; does not cause focal liver
necrosis or an enlarged hemorrhagic spleen
Hemorrhagic enteritis in turkey poults (avian adenovirus type 2): Intranuclear inclusion bodies (can
also be seen in inclusion body hepatitis (avian adenovirus type 1)
Necrotic enteritis Clostridium perfringens: No liver lesions, quail are not affected
Histomonas meleagridis: Produces caseous cecal cores and necrotic targetoid hepatic lesions;
histological examination of liver and spleen will usually reveal histomonads
Heterakis gallinarum: Cecal worm; necrotic lesions in the ceca and liver

D-B04 - Braxy - abomasum – ox MG334

HD: Abomasum: Diffusely and transmurally, the abomasum is markedly expanded by eosinophilic
finely fibrillar material (fibrin), increased clear space and lymphangiectasia (edema), and moderate
numbers of neutrophils that infiltrate the lamina propria and submucosa, and extend into the tunica
muscularis and serosa. The mucosa is multifocally eroded, with loss of distinct architecture and
replacement by karyorrhetic debris, and moderate hemorrhage. Multifocally, there is vasculitis
characterized by disruption of the endothelium and infiltration of neutrophils within the tunica
media. There is diffuse moderate congestion.
MDX: Abomasum: Abomasitis, necrohemorrhagic, acute, transmural, diffuse, moderate, with
submucosal edema, and vasculitis, breed unspecified, bovine.
EDX: Clostridial abomasitis
Cause: Clostridium septicum
CS: bradsot
GD: Vasculitis, thrombosis and hemorrhage
DDX: For abomasitis:
Mycotic abomasitis (Mucor sp., Aspergillus sp., Rhizopus sp.): Also causes necrotizing and
hemorrhagic abomasitis with vasculitis and submucosal hemorrhage and edema; fungal hyphae
 19

evident with PAS and GMS stains

Viral abomasitis: Rarely limited to the abomasum; not emphysematous
Rinderpest (Morbillivirus, Paramyxoviridae): Syncytia, intranuclear and intracytoplasmic inclusion
bodies
Malignant catarrhal fever (Alcelaphine herpesvirus and ovine herpesvirus 2): Lymphocytic and
lymphoblastic vasculitis
Infectious bovine rhinotracheitis (Bovine herpesvirus 1): Multifocal necrosis in the digestive system
with intranuclear inclusion bodies
Bovine viral diarrhea virus/mucosal disease (Pestivirus, Flaviviridae): May cause abomasal
necrosis, hemorrhage and thrombosis
Bluetongue (Orbivirus, Reoviridae): May cause abomasal necrosis, hemorrhage and thrombosis
Black disease (Clostridium novyi): Similar abomasal lesions with necrotizing hepatitis; usually
related to migration of Fasciola hepatica
Enterotoxemia (Clostridium perfringens type A): Similar lesions in neonatal calves in the western
US with ruminal tympany and abomasitis
Toxins (arsenic, thallium, phosphorus, zinc) cause hemorrhage, necrosis, and ulcers throughout the
gastrointestinal tract

D-B05 - Hepatic necrobacillosis - liver – sheep – 6d old MG431

HD: Liver: There are multifocal, random, 1-3 mm diameter, discrete areas of coagulative necrosis
characterized by retention of tissue architecture, swollen hypereosinophilic hepatocytes, loss of
cellular detail, eosinophilic cellular and karyorrhectic debris, and rare basophilic granular material
(mineral). Within and along the periphery of the necrotic foci, there are numerous radiating
colonies of extracellular filamentous bacilli. The adjacent sinusoids are mildly expanded by clear
space and contain rare lymphocytes and neutrophils. Occasionally adjacent vessels have focal
disruption of their walls with necrotic debris, fibrin, and invasion of filamentous organisms into the
vessel lumina.
MDX: Liver: Necrosis, coagulative, multifocal, random, with vascular fibrinoid necrosis, and
intralesional filamentous bacilli, etiology consistent with Fusobacterium necrophorum, crossbred
sheep, ovine.
EDX: Hepatic fusobacteriosis
Cause: Fusobacterium necrophorum
DDX:
Sheep and cattle: Multifocal random hepatic necrosis (hepatocellular necrosis)
Infectious necrotic hepatitis (Black Disease): Clostridium novyi; associated with migration tracts of
Fasciola hepatica; necrotic lesions similar but often linear.
Bacillary hemoglobinuria: Clostridium hemolyticum; also associated with migration tracts of
Fasciola hepatica; icterus, hemoglobinemia, hemoglobinuria
Arcanobacter pyogenes (often isolated with F. necrophorum), Staphylococcus, and Streptococcus
can cause hepatic abscesses.
Mycotic hepatitis (Mucor, Rhizopus): Damage to ruminal mucosa (ruminal acidosis) allows ruminal
microflora to enter the portal circulation.

D-B06 - Tyzzer's disease - liver – horse – 3wk old MG433

HD: Liver: Effacing 80% of the normal architecture are multifocal to coalescing areas of lytic
necrosis characterized by replacement with eosinophilic cellular and karyorrhectic debris,
occasionally with central dropout, admixed with fibrin, hemorrhage, large numbers of viable and
degenerate neutrophils, fewer macrophages, and entrapped individualized hepatocytes.
Surrounding hepatocytes are swollen with pale, vacuolated cytoplasm (degeneration) or are
shrunken, hypereosinophilic with pyknotic nuclei (necrosis). Peripheral, less affected hepatocytes
often contain numerous, pale, filamentous (1x15um) bacilli. Periportal areas and the
subcapsular space (capsule of Glisson) are expanded up to three times normal by ectatic
 20

lymphatic vessels (edema), hemorrhage, fibrin, and low numbers of lymphocytes, plasma cells,
macrophages, and rare neutrophils. Multifocally, sinusoids are congested. Liver (Warthin Starry
Technique pH 4.0): There are many argyrophilic, filamentous bacilli within hepatocytes at the
periphery of necrotic areas. Bacilli occur in parallel and perpendicular sheaves and bundles as
well as singly. Occasionally bacilli are free within necrotic debris.
MDX: Liver: Hepatitis, necrotizing, subacute, multifocal to coalescing, severe, with intracellular
bacilli, breed not specified, equine.
EDX: Clostridial hepatitis
Cause: Clostridium piliforme
GD: Necrotizing enterocolitis, described in foals and other species. Foci of myocardial necrosis.
DDX:
For random necrotizing hepatitis in foals:
Equine Herpesvirus I: Hepatic necrosis, concurrent interstitial pneumonia, intranuclear inclusion
bodies in hepatocytes
Salmonella sp. or E. coli septicemia: Watery, foul smelling diarrhea, joint lesions, pneumonia and/or
meningitis (with Salmonella).
Sleepy Foal Disease (Actinobacillus equuli): Multifocal hepatitis, severe enteritis, embolic nephritis

D-B07 - Bacillary dysentery - colon - Rhesus monkey - juv.

HD: Colon: Diffusely, there is partial to full thickness mucosal necrosis and loss with replacement
by abundant hemorrhage, eosinophilic cellular and karyorrhectic debris, few degenerate neutrophils,
and scattered colonies of many minute bacteria. Occasionally remaining intestinal crypts are
ectatic, lined by attenuated epithelium, and contain sloughed epithelial cells admixed with
degenerate neutrophils (crypt abscesses). Diffusely, the submucosa is moderately expanded by
increased clear space with ectatic lymphatics (edema), eosinophilic fibrillar material (fibrin), and
congestion admixed with moderate numbers of degenerate neutrophils. Multifocally, blood vessels
in the lamina propria and submucosa are variably occluded by finely fibrillar to consolidated
eosinophilic material admixed with few degenerate inflammatory cells (fibrin thrombi). The
submucosal lymphoid tissue contains decreased numbers of lymphocytes admixed with necrotic
debris (lymphoid depletion).
MDX: Colon: Colitis, necrohemorrhagic, acute, diffuse, severe, with fibrin thrombi, congestion, and
edema, Rhesus monkey (Macaca mulatta), nonhuman primate.
EDX: Colonic shigellosis
Cause: Shigella sp.
GD: Shigella sp. cause severe hemorrhagic enteritis (dysentery) in non human primates and
humans. Four species: S. dysenteriae, S. flexneri, S. boydii, and S. sonnei. S. flexneri is most
common; S. dysenteriae is the most pathogenic. Few organisms are required to cause disease.
Affects terminal ileum, colon and rectum. Necrohemorrhagic periodontitis/gingivitis may be present
in macaques.
DDX:
For gross and microscopic findings:
Campylobacter jejuni affects both small and large intestine; lesions are less severe than those of
Shigella sp.
Salmonella enteritidis or typhimurium causes necrotizing, suppurative enterocolitis and can cause
septicemia.
Yersinia enterocolitica and Y. pseudotuberculosis produce submucosal microabscesses with large
colonies of bacteria.
Enteropathogenic E. coli causes hemorrhagic gastroenteritis and ulcerative colitis.
Balantidium coli can cause ulcerative colitis.

D-B09 - Paratuberculosis - small intestine, mesentery, adipose tissue – ox MG372

HD: Small intestine: The intestine is diffusely thickened and the mucosa is thrown into prominent
 21

rugose folds. Expanding the submucosa and lamina propria and separating and isolating crypts,
there are dense sheets of large macrophages with abundant, finely granular eosinophilic
cytoplasm and an eccentric oval nucleus, mixed with fewer lymphocytes, plasma cells and rare
neutrophils and foreign-body type multinucleated giant cell macrophages. Diffusely within
crypt epithelium there is increased cytoplasmic basophilia, a high nuclear to cytoplasmic
ratio, vesicular nuclei, and piling up of cells 3-5 deep, with mitotic figures high in the mucosa
(regeneration). Villi are diffusely blunted or absent. Submucosal and serosal lymphatics are mildly
ectatic. Within the tunica muscularis and serosa, there are low to moderate numbers of perivascular
lymphocytes, and serosal adipocytes are diffusely atrophied. Acid fast: Small intestine:
Macrophages contain large numbers of 0.3 x 2 um acid fast bacilli.
MDX: 1. Small intestine: Enteritis, granulomatous, diffuse, marked, with villus atrophy, edema, and
numerous intrahistiocytic acid-fast bacilli, Angus cross, bovine. 2. Mesentery, adipose tissue:
Atrophy, diffuse, severe
EDX: Mycobacterial enteritis
Cause: Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis)
CS: Johne's disease
GD: Mesenteric lymph nodes - granulomatous lymphadenitis. Thymus - lymphoid depletion
DDX:
Chronic diarrhea in adult cattle
M. bovis - usually fewer organisms; nodule formation; fibrosis; necrosis; calcification
Bovine viral diarrhea (Bovine Pestivirus, Flaviviridae) - diarrhea with mucosal and Peyer's patch
erosions
Salmonellosis - generally acute; Gram negative bacteria; not acid fast
Secondary copper deficiency (chronic molybdenum poisoning) - generally regional; affects multiple
animals;
Intestinal parasites (coccidiosis, gastrointestinal helminthiasis) - fecal examination for eggs or
oocysts
Malnutrition; neoplasia (lymphosarcoma; chronic reticulopericarditis)

D-B10 - Avian mycobacteriosis - liver - quail

HD: Liver: Effacing over 90% of normal architecture and multifocally elevating the overlying
capsule are numerous, varisized, up to 1 mm diameter, granulomas composed of a central core of
abundant eosinophilic cellular and karyorrhectic debris (caseous necrosis), admixed with abundant
1 X 1-3 um bacilli. Surrounding the necrotic core are numerous epithelioid macrophages and fewer
multinucleated giant cells that often contain intracytoplasmic bacilli. The macrophages are further
surrounded by abundant fibrous connective tissue and numerous lymphocytes and plasma cells.
Diffusely between nodules, there is loss of hepatocytes with replacement by abundant fibrosis,
increased numbers of small bile ducts (biliary hyperplasia) and many lymphocytes and plasma cells
admixed with epithelioid macrophages and fewer multinucleated giant cells with intracytoplasmic
bacilli. (Acid-fast): Liver: Necrotic areas, macrophages, and multinucleated giant cells contain
abundant acid-fast 1 x 1-3 um bacilli.
MDX: Liver: Granulomas, numerous, with chronic diffuse severe lymphoplasmacytic and
histiocytic hepatitis, moderate bile duct hyperplasia, and acid-fast bacilli, etiology consistent with
Mycobacterium sp., Coturnix quail (Coturnix coturnix), avian.
EDX: Hepatic mycobacteriosis
Cause: Mycobacterium avium-intracellulare complex (MAIC)
CS: Avian tuberculosis
DDX:
Neoplasia
Fowl cholera (Pasteurella multocida): Gram negative bacilli; not acid-fast.
Fowl typhoid (Salmonella gallinarum): Most characteristic lesions are in heart and gizzard; Gram
negative bacilli; not acid-fast.
 22

Escherichia coli: Coligranulomas - granulomas in liver and intestinal tract; not acid-fast.

D-B11 - Yersinia enterocolitica infection - colon, liver - African green monkey

HD: Colon: Multifocally, there is well-demarcated coagulative necrosis of the mucosa characterized
by loss of differential cell staining with retention of cellular architecture. There are multifocal,
transmural, colonies of coccobacilli up to 250 um wide that extend into the mesentery and are
admixed with moderate numbers of viable and degenerate neutrophils, macrophages, lymphocytes,
and fewer plasma cells, along with fibrin, hemorrhage, edema, congestion, and eosinophilic cellular
and karyorrhectic debris (lytic necrosis). Vessels often contain bacterial emboli and the tunica media
is disrupted by previously described inflammatory cells.
Liver: Multifocally and randomly affecting 10% of the parenchyma there are well demarcated areas
of necrosis characterized by loss of normal hepatic architecture and replacement by eosinophilic
cellular and karyorrhectic debris, admixed with low numbers of degenerate neutrophils, fibrin, and
large, up to 200 um wide, colonies of coccobacilli. Randomly in the sinusoids, there are bacterial
colonies and few viable and degenerate neutrophils and macrophages.
Morphologic Diagnosis: 1. Colon: Colitis, necrotizing, segmental, transmural, subacute,
multifocal, severe, with peritonitis and large colonies of intralesional and intravascular coccobacilli,
African green monkey (Cercopithecus aethiops), nonhuman primate.
2. Liver: Hepatitis, necrotizing, acute, multifocal, random, moderate, with numerous large colonies
of coccobacilli
Etiologic Diagnosis: Colonic, hepatic, and peritoneal yersiniosis
Cause: Yersinia enterocolitica
General Discussion:
Y. enterocolitica is a gram negative, intracellular, nonmotile, coccobacillus that causes enterocolitis,
mesenteric lymphadenitis, hepatitis, and less commonly septicemia in many mammals including
rodents, lagomorphs, domestic animals (swine, sheep, cattle, horses, dogs, and cats), new and old
world primates, and some prosimians and apes.
Three major pathogenic species of Yersinia: Y. enterocolitica, Y. pseudotuberculosis and Y. pestis
Birds and rodents are reservoirs; infections are more common in outdoor housed primate colonies
and during wet weather.
Y. enterocolitica can replicate at refrigeration temperatures; it is an important foodborne pathogen.
Pathogenesis:
Transmission is fecal-oral.
Bacteria invade enterocytes, causing necrosis and subsequently enter the lamina propria of the distal
ileum, cecum, and colon.
Bacteria multiply in Peyer's patches; necrosis eventually causes mucosal ulceration. Extension to
the mesenteric lymph nodes may occur. If septicemia develops, suppurative lesions may occur in
various organs (liver, spleen, lungs, meninges).
Typical Gross Findings:
Multifocal to diffuse, often transmural, hemorrhage and necrosis of the small and large intestine
(ulcerative enterocolitis)
Hepatomegaly and splenomegaly with multifocal necrosis or abscesses
Mesenteric lymphadenopathy
Typical Light Microscopic Findings:
Intestine: Multifocal mucosal necrosis, ulcers, hemorrhage, marked neutrophilic inflammation, and
large bacterial colonies
Liver and spleen: Random, multifocal necrosis with neutrophilic inflammation and large, lobulated
bacterial colonies
Differential Diagnosis:
Bacteria That Form Large Colonies in Tissue (YAACSS):
Y. pseudotuberculosis affects a wide range of species including primates. Acute septicemia;
granulomatous nodules in the spleen, liver, lymph nodes, and lung occur in the chronic form. In
 23

primates, there is acute, severe, fibrinonecrotic enteritis and mesenteric lymphadenitis with necrosis
in the liver, lung, and spleen. It can cause abortions in cattle, sheep, and goats. Histologically there
is a necrotic core with suppuration surrounded by large numbers of epithelioid macrophages but no
giant cell macrophages. Differentiation from Y. enterocolitica requires culture.
Y. pestis (Plague): Transmission occurs by direct contact with infected carcasses or bodily
excretions or by flea bites. The organism enters through mucous membranes or broken skin.
Bacteria are killed in neutrophils but can survive and replicate within macrophages, with spread to
regional lymph nodes and/or bacteremia. Bacteria use host derived proteins to produce an envelope
that is resistant to host phagocytosis, allowing rapid replication and causing sudden death.
Actinomyces sp. (gm +), Actinobacillus sp. (gm -), Corynebacterium sp. (gm +), Staphylococcus sp.
(gm +) and Streptococcus sp. (gm+)
Gross and Microscopic Lesions in Primates:
Shigella sp. (gm -) (S. dysenteriae, S. flexneri, S. boydii, S. sonnei): Lesions limited to large
intestine; colonic edema, hemorrhage and ulcers +/- pseudomembrane; no large bacterial colonies
Campylobacter sp. (C. jejuni, C. coli): Similar to shigellosis but also affect small intestine; necrosis,
edema, hemorrhage, villus blunting and fusion.
Salmonella sp. (gm -) (S. typhimurium, S. dublin, S. enteriditis, S. stanley): Fibrinonecrotic
enteritis, typhlitis and colitis; no large colonies
Comparative Pathology:
Y. ruckeri: Causes “Red Mouth”, a hemorrhagic inflammation of the perioral subcutis of freshwater
fish (esp. rainbow trout)

D-B12 - Psittacosis - liver - Amazon parrot

Histopathologic Description: Liver: Multifocally there are random irregularly round, up to 1 mm
diameter areas of necrosis characterized by complete loss of hepatic architecture and replacement
by eosinophilic cellular and karyorrhectic debris (lytic necrosis), often surrounded by epithelioid
macrophages and multinucleated giant cells (granuloma), and fewer lymphocytes and plasma cells.
Remaining foci are characterized by retention of hepatic cord architecture with loss of differential
staining (coagulative necrosis). Multifocally, few random hepatocytes and Kupffer cells contain
intracytoplasmic gray granular material (bacteria). Diffusely sinusoids are expanded by
macrophages, heterophils and lymphocytes. Multifocally hepatocytes are mildly vacuolated and
contain small aggregates of brown, granular pigment (bile and/or hemosiderin). Bile ducts are
prominent, mildly ectatic, and lined by hyperplastic epithelium characterized by piling up, mild
anisokaryosis and increased mitotic activity.
Morphologic Diagnosis: Liver: Hepatitis, necrotizing, multifocal to coalescing, moderate, with
multiple granulomas, mild bile duct hyperplasia, and intrahepatocellular bacteria, Yellow Nape
Amazon parrot (Ochrocephala auropalliate), avian.
Etiologic Diagnosis: Hepatic chlamydophilosis
Cause: Chlamydophila psittaci
General Discussion:
C. psittaci has 8 known fairly host specific serovars: 6 in birds (A-F) and 2 in mammals (WC and
M56). Elementary body (EB): infectious form that enters the cell. Reticulate body (RB):
intracellular, metabolically active, replicating form that synthesizes DNA, RNA, and protein, and
divides by binary fission. Intermediate body (IB): has morphologic characteristics between EB and
RB. Tropism for columnar epithelial cells lining mucous membranes
Pathogenesis: Inhalation or ingestion of contaminated feather dust or feces > multiply in lung, air
sacs and pericardial sac within 4 hours > bacteremia within 48 hours > portals of exit (cloaca &
nasal turbinates). The reproductive cycle: EBs attach to host cell membrane at coated pit >
internalization into host cell via invagination of the host cell membrane > inhibition of phagosome -
lysosome fusion > differentiation into RB > binary fission > reorganization, through IBs, into new
EBs > release from host cell (cell lysis or exocytosis)
Typical Light Microscopic Findings: Liver: Multifocal coagulative necrosis - acute infection
 24

Granulomas and bile duct hyperplasia - more chronic infection. Kupffer cell hyperplasia.
Intrahepatocellular bacteria. Spleen: Histiocytosis, lymphoid depletion, plasmacytosis, multifocal
necrosis. Air sacs: Fibrinous exudate with heterophils and macrophages, some of which contain
bacteria. Inclusion body-like microcolonies may be seen in affected cells of many organs,
particularly in serosal membranes
Differential Diagnosis:
Hepatic necrosis in psittacine birds:
Pacheco's disease (alphaherpesvirus): Intranuclear hepatocellular inclusions
Polyomavirus (Budgie Fledging Disease): Glassy intranuclear inclusions
Salmonellosis (Salmonella sp.) and colibacillosis (E. coli): Hepatocellular necrosis with
necrogranulomas
Reoviral hepatitis: Hepatocellular necrosis without inclusion bodies
Lead toxicosis: Eosinophilic, acid-fast, intranuclear inclusions
Mycobacteriosis (MAIC): Acid-fast, intracellular bacilli
In poultry, similar signs and lesions may be caused by the following diseases:
Fowl cholera (Pasteurella multocida)
Mycoplasmosis: M. gallisepticum (chronic respiratory disease/infectious sinusitis of turkeys); M.
meleagridis (air sacculitis)
Colibacillosis
Salmonellosis - S. typhimurium (paratyphoid); S. pullorum (Pullorum disease); S. gallinarum (fowl
typhoid)
Adenovirus - eg. hemorrhagic enteritis of turkeys
Comparative Pathology:
Ruminants: C. psittaci serovar WC: sporadic bovine encephalomyelitis, pneumonia, polyarthritis of
calves, conjunctivitis, and sporadic abortion; most cases of abortions in ruminants due to
Chlamydophila abortus, including ovine enzootic abortion (necrotizing placentitis in ewe, hepatic
necrosis in fetus)
Cats: C. psittaci or more often C. felis; conjunctivitis, pneumonia
Guinea Pigs: Guinea Pig Inclusion Conjunctivitis (GPIC); can also cause rhinitis and genital tract
infections
Mice: Mouse pneumonitis (focal interstitial pneumonia and bronchitis) and experimental genital
infection resolution of infection and milder clinical signs associated with pronounced PMN
response and increased numbers of CD8+ T cells
Swine: Polyarthritis, pericarditis, pseudomembranous enteritis, epididymitis, orchitis, accessory sex
gland infections, and perinatal mortality
Koalas (C. pneumoniae): Multiple organs including the eye, respiratory tract, and intestinal and
reproductive systems, may result in sterility or death
Humans: Zoonotic disease; wide spectrum of illnesses, ranging from inapparent to severe systemic
disease with pneumonia

D-B13 - Enterotoxigenic colibacillosis - small intestine - pig

Signalment: A 2-day-old piglet
Histopathologic Description: Small intestine: Multifocally, there is mild blunting of intestinal villi.
Within crypts and along villi, there are small aggregates of 1x2 um bacilli that are often adjacent to
enterocytes that are mildly attenuated and occasionally have a loss of cellular detail with nuclear
pyknosis or loss (necrosis). The lamina propria is mildly expanded by few neutrophils, large
granular leukocytes and eosinophils and many cells exhibiting karyolysis and necrosis. The
intestinal lumen contains variably sized aggregates of sloughed enterocytes admixed with small
amounts of eosinophilic cellular and karyorrhectic debris and abundant bacilli. Rarely, crypts
contain necrotic cellular debris and few neutrophils (crypt abscess). Capillaries within the lamina
propria are mildly congested.
Morphologic Diagnosis: Small intestine: Enteritis, acute, multifocal, mild, with villus blunting,
 25

villus tip necrosis, and numerous superficial bacilli, breed not specified, porcine.
Etiologic Diagnosis: Enteric colibacillosis
Cause: Escherichia coli
General Discussion:
Classification based on specific pathogenic mechanisms (toxins, adhesins, invasiveness, etc.) and
varies among bacteriologists:
1. Enterotoxigenic E. coli (ETEC)
2. Enteropathogenic E. coli (EPEC)
Attaching and effacing E. coli (AEEC)
3. Enterohemorrhagic E. coli (EHEC)
4. Shiga-toxin producing E. coli (STEC)
Verocytotoxic E. coli (VTEC)
5. Necrotoxigenic E. coli (NTEC)
6. Enteroinvasive E. coli (EIEC)
7. Enteroaggregative E. coli (EAggEC)
Typical Light Microscopic Findings:
Bacteria adherent to brush borders of villi or limited to the crypts of Lieberkühn. Typically no
damage to enterocytes within the first 24-hours. Mild villus blunting or fusion; villus height:crypt
depth ratio reduced from the 7:1 found in normal pigs to 4:1 in infected pigs. Usually no
inflammation or erosions; few neutrophils, lymphocytes, and macrophages in the lamina propria;
congestion; rarely hemorrhage into the lumen
Differential Diagnosis:
Diarrhea in young piglets
Transmissible gastroenteritis (TGE) virus (Coronavirus): Diarrhea in piglets <10 days old; marked
atrophy of small intestinal villi; villus epithelial cell lysis
Isospora sp.: Diarrhea in piglets 5-15 days old; fibrinonecrotic pseudomembrane without blood;
organism within the cytoplasm of villus and crypt enterocytes
Rotavirus: Diarrhea in piglets > 10 days old; enterocyte sloughing, with replacement by cuboidal to
squamoid cells; villus blunting and fusion
Clostridium perfringens type C: <8 days old; whole litter affected; necrohemorrhagic enteritis
Salmonella sp.: Ulcerated Peyer’s patches covered with a necrotic pseudomembrane; colonic
“button ulcers”
Comparative Pathology:
Pigs: Edema disease (ED) from STEC in weaners and growers causing neurologic signs, edema and
vascular necrosis; postweaning E. coli diarrhea (PWECD) caused by ETEC in recently weaned pigs
Cattle: The most common Gram-negative cause of mastitis in dairy cattle; endotoxin-mediated and,
in severe cases, may lead to shock and death; EHEC (O157:H7) contaminant in meat products
important cause of food-borne illness
Calves
Less than 5 days old: ETEC; profuse yellow watery diarrhea, severe dehydration, weakness, weight
loss and high mortality
Less than 4 weeks old: EHEC; diarrhea and dysentery with blood; generalized systemic infection
(septicemic colibacillosis); usually follows colostrum deprivation; survivors with polyarthritis,
meningitis, or interstitial nephritis (white-spotted kidney)
Lambs: 2-8-days-old: enteric and septicemic forms; enteric form caused by enteropathogenic, non-
invasive strains; signs similar to calves
Foals: Diarrhea in foals common but usually mild, transient and not caused by infectious agents;
common cause of foal septemia
Dogs: ETEC and EPEC strains associated with gastro-intestinal disease in young dogs;
asymptomatic carriers of human pathogenic STEC strains and O157:H7
Poultry: Acute septicemia, fibrinopurulent serositis and coligranuloma (Hjarre’s disease); in newly
hatched chicks omphalitis and mushy-yolk disease
 26

Rabbits: Highly susceptible to AEEC; mortality exceeding 50% in weanlings

Extra-intestinal lesions in animals: Urinary tract infections, prostatitis, pyometra, abortion, mastitis,
bacteremia/septemia
Humans: ETEC is the most common cause of traveler’s diarrhea; EHEC (O157:H7) causes food-
borne illness and hemorrhagic colitis and hemolytic uremic syndrome.

D-B14 - Tularemia - liver - beaver

Histopathologic Description: Liver: Effacing approximately 40% of the hepatic architecture are
random, variably sized (up to 1mm diameter) areas of necrosis characterized by eosinophilic
cellular debris and degenerate neutrophils. Adjacent hepatocytes are individualized, and contain
granular, yellow-brown or green-brown cytoplasmic pigment (hemosiderin or bile). Multiple central
veins and portal vessels have disruption of the tunica media and endothelium with replacement by
necrotic debris and degenerate neutrophils (vasculitis). Occasionally, fibrin thrombi occlude vessels.
Multifocally, portal areas are expanded by low numbers of lymphocytes, plasma cells and
macrophages.
Morphologic Diagnosis: Liver: Hepatitis, necrotizing, acute, random, multifocal to coalescing,
moderate, with necrotizing vasculitis, and fibrin thrombi, beaver (Castor canadensis), rodent.
Etiologic Diagnosis: Hepatic francisellosis
Cause: Francisella tularensis
Condition Synonyms: Rabbit fever, O'Hara's disease, Deerfly fever
General Discussion:
Highly infectious zoonotic disease; endemic worldwide; most prevalent in the western US
Primarily causes disease in rodents and lagomorphs; reported in over 125 species of mammals,
birds, reptiles and fish
Transmitted by ticks (Dermacentor, Ixodes, Amblyomma) which pass the infection transtadially and
transovarially, and act as reservoir; and other arthropods (mosquitoes, deerfly)
Small, pleomorphic, gram-negative, facultative, intracellular coccobacillus
Typical Gross Findings:
Numerous pinpoint to small white foci in the enlarged liver, spleen, lymph nodes and kidneys, less
commonly in the heart and lung with occasional caseous granuloma formation
Hemorrhagic enteritis with ulcerations of the Peyer's patches has been reported
Pneumonia reported in dogs and swine
Typical Light Microscopic Findings:
Liver, lymph node, spleen, kidneys: Multifocal to coalescing areas of caseous to lytic necrosis,
surrounded by a few lymphocytes, neutrophils and macrophages
Vasculitis and thrombosis
+/- Lymphoid necrosis
Differential Diagnosis:
For necrotizing hepatitis in rodents:
Tyzzer's disease (Clostridium piliforme): Intracellular gram-negative bacillus; multifocal necrosis in
the liver, spleen and intestine; intracellular bacilli stain with Warthin-Starry 4.0 and similar silver
stains
Salmonella sp.: Gram-negative bacilli; "paratyphoid nodules" (multifocal to coalescing areas of
necrosis that progress to microgranulomas
Listeria monocytogenes: Gram-positive coccobacillus; multifocal necrosis in the liver +/- other
organs with septicemia; differentiate with a gram stain
Toxoplasma gondii: Multifocal coagulative necrosis in the liver and other organs, with intralesional
tachyzoites
Yersinia pseudotuberculosis and Yersinia enterocolitica: Multifocal hepatic necrosis with large
lobulated colonies of gram-negative coccobacilli
Mouse Hepatitis Virus (Coronavirus): Multifocal hepatic necrosis with syncytia
D-B15A - Intestinal adenomatosis complex of swine - ileum - pig
 27

Histopathologic Description: Ileum: Multifocally, the mucosa is expanded by polypoid projections

up to 3x5 mm composed of haphazardly arranged, cystic, branching and/or tortuous glands. The
glands are lined by hyperplastic columnar epithelial cells up to 4-5 cells thick with amphophilic,
vacuolated cytoplasm, vesicular nuclei, and increased mitotic figures. There is a marked decrease in
goblet cells. Crypts are variably lined by attenuated to hyperplastic epithelium and contain abundant
eosinophilic cellular and nuclear debris, degenerate neutrophils, and sloughed epithelial cells (crypt
abscesses). Diffusely, villi in the areas between the polypoid areas are blunted and fused with mild
multifocal loss of epithelium. Multifocally, the lamina propria is mildly expanded by moderately
increased numbers of lymphocytes, plasma cells, few neutrophils and macrophages, and rare
eosinophils.
Morphologic Diagnosis: Ileum: Enteritis, proliferative, subacute, multifocal, moderate, with crypt
abscesses, breed unspecified, porcine.
Etiologic Diagnosis: Lawsonial enteritis
Cause: Lawsonia intracellularis
Condition Synonyms: porcine proliferative enteropathy, porcine intestinal adenomatosis, intestinal
adenomatosis complex of swine, necrotic enteritis, regional ileitis, proliferative ileitis, proliferative
hemorrhagic enteropathy, intestinal adenoma of swine
General Discussion:
L. intracellularis is an obligate intracellular curved gram-negative bacterium that colonizes
enterocytes in the ileum, cecum, and colon of several species and causes proliferative enteritis.
Pigs and hamsters are the most commonly affected.
Most common and important spontaneous disease of hamsters; primarily in weanlings
Porcine proliferative enteropathy encompasses four histomorphologically distinct syndromes:
Porcine Intestinal Adenomatosis (PIA), Necrotic Enteritis (NE), Regional Ileitis (RI), and
Proliferative Hemorrhagic Enteropathy (PHE).
PIA is a persistent uncomplicated condition in young growing animals. If the animal is subjected to
additional insult, PIA can progress to NE. In those that survive NE, lesions often fibrose and
progress to RI.
PHE occurs in pigs > 4 months old; this may be an acute manifestation of PIA.

Pathogenesis:
Predilection for crypt cells within the ileum, cecum and proximal colon.

Typical Gross Findings:

Pigs:
PIA: Multifocal nodular or ridgelike thickenings, congestion of the ileal mucosa, hypertrophy of the
tunica muscularis
NE: Yellow/brown, blood tinged necrotic mucosa
RI: Thickened intestine “hosepipe gut”; may result in stricture
PHE: Abundant fluid blood, intestinal clots and fibrin casts within lumen and no discernible points
of hemorrhage; thickened edematous ileum with a cerebriform pattern; pale skin
Ferrets: Palpable segmental colonic thickening with prominent longitudinal folds
Hamsters: Ileum (+/- jejunum) thick and dilated; well-demarcated from normal mucosa; possibly
ileocecal obstruction; serosal adhesions
Typical Light Microscopic Findings:
Pigs:
PIA: Nodular or polypoid masses; expansion, elongation, and branching of crypts; numerous
mitoses; absent goblet cells; crypt abscesses; open or vesiculate nuclei with basophilic cytoplasm;
atrophy of surrounding villi
NE: Coagulative necrosis of adenomatous epithelium with inflammation
RI: Replacement of damaged mucosa by granulation tissue; smooth muscle hypertrophy.
PHE: Congestion of mucosal vessels; moderate inflammation; thrombi; necrosis of mucosa; luminal
 28

hemorrhage
Granulomatous enteritis and lympadenitis: marked granulomatous infiltrate consisting of histiocytes
and multinucleated giant cells in Peyers patches and regional lymph nodes; rare.
Ferrets: Colonic epithelial hyperplasia; reduced goblet cells; variable inflammation; lesions
predominantly in colon (unlike most other species)
Hamsters: Lesions are similar to ferrets; in late stages, the epithelial cells may herniate through the
muscularis mucosa, causing pyogranulomatous inflammation. Recovered animals have ileocecal
fibrosis and stenosis.
Differential Diagnosis:
For hemorrhagic enteritis in pigs:
Clostridium perfringens type C
Swine dysentery (Brachyspira hyodysenteriae): Large bowel; less severe; argyrophilic spirochetes
in mucus layer
Escherichia coli in post weanling pigs
Acute enteric salmonellosis
Intestinal hemorrhage syndrome: Affects all areas of the intestine; associated with abdominal
distention and tympany as a result of torsion
Esophagogastric ulceration: Sudden death; ulcers evident grossly.
Ferrets: For hemorrhagic or green tinged diarrhea
Epizootic catarrhal enteritis (coronavirus) - Catarrhal mucoid green diarrhea (affects the small
intestine)
Hamsters: For hemorrhagic enteritis
Proliferative lesions have been described in the cecum and colon with intracellular organisms
unrelated to Lawsonia.
Tyzzer's disease (Clostridium piliforme): Diarrhea in adult hamsters; hepatic necrosis; no
proliferative lesions
Intestinal adenocarcinoma: more chaotic cell proliferation; +/- metastasis

D-B15B - Proliferative colitis - colon - ferret

HD: Colon: Multifocally, the mucosa is thickened 2-4 times normal by deep, often tortuous glands
lined by hyperplastic epithelium. Crypt epithelium is hyperplastic characterized by plump, cuboidal
to columnar, cells with basophilic cytoplasm that pile up to 4-5 cells layers thick, with numerous
mitotic figures present at all levels. There is a marked decrease in goblet cells. Multifocally, crypts
are dilated, lined by attenuated epithelium, and contain numerous nondegenerate and degenerate
neutrophils, sloughed epithelial cells, cellular and nuclear debris (crypt abscesses). The lamina
propria and submucosa are mildly expanded by moderate numbers of lymphocytes, plasma cells,
neutrophils and macrophages.
Colon (Warthin-Starry): Affected mucosal and glandular epithelial cells contain many silver-
positive curved bacilli, measuring 1x5um, that concentrate in the apical cytoplasm of the cells.
Morphologic Diagnosis: Colon: Colitis, proliferative, subacute, multifocal, moderate, with crypt
abscesses, and agyrophilic intracellular bacilli, etiology consistent with Lawsonia intracellularis,
sable ferret (Mustela putorius furo), mustelid.
Etiologic Diagnosis: Lawsonial colitis
Cause: Lawsonia intracellularis
Condition Synonyms: Proliferative bowel disease

D-B15C - Proliferative ileitis - small intestine - hamster

HD: Small intestine and attached mesentery: Diffusely the mucosa is thickened 2-4 times normal
with deep, often tortuous glands and irregularly thickened, blunted, and fused villi. Affecting
approximately 70% of the mucosa, there is extensive transmural coagulative necrosis characterized
by retention of tissue architecture with loss of cellular detail, cytoplasmic hypereosinophilia,
nuclear pyknosis and karyolysis, and small amounts of cellular debris surrounded by a band of
 29

nondegenerate and degenerate neutrophils as well as necrotic debris and abundant basophilic
granular material (mineral) within muscular tunics and mildly expanding the serosa and mesentery.
Within the necrotic areas there are numerous mixed bacteria (fecal bacteria). In the remaining
mucosa, crypts and villi are lined by closely packed, tall columnar epithelial cells with amphophilic
to basophilic cytoplasm, and increased mitotic figures (hyperplasia) with decreased numbers of
goblet cells. There is scattered individual cell necrosis, and rarely crypts are ectatic and contain
necrotic and cellular debris (crypt abscesses). There is focal crypt herniation into the submucosa
and tunica muscularis. Within the lamina propria and submucosa there are mildly increased
numbers of neutrophils, macrophages, rare lymphocytes, plasma cells and moderately congested
vessels. The attached mesentery is diffusely expanded by clear space (edema) and moderate
numbers of neutrophils, lymphocytes, and macrophages.
Morphologic Diagnosis: Small intestine and attached mesentery: Enteritis, proliferative, subacute,
diffuse, severe, with focally extensive transmural necrosis, and mild subacute serositis, hamster
(Mesocricetus auratus), rodent.
Etiologic Diagnosis: Lawsonial enteritis
Cause: Lawsonia intracellularis
Condition Synonyms: Wet tail, hamster enteritis, transmissible ileal hyperplasia of hamsters

D-B16 - Swine dysentery - colon - pig

Histopathologic Description: Colon: Diffusely the mucosa is expanded up to three times normal
with elongated crypts. There are multifocal to coalescing areas of necrosis within the superficial
mucosa that occasionally extend deep into the crypts. Admixed with the necrotic debris are
moderate numbers of degenerate neutrophils, fibrin, and numerous 6 um long bacteria. There are
rare crypt abscesses and abundant mucus. Superficial mucosal vessels adjacent to the necrotic areas
often contain fibrin thrombi. Focally there is crypt herniation into a submucosal lymphoid nodule.
Multifocally, there is moderate congestion.
Morphologic Diagnosis: Colon: Colitis, proliferative and necrotizing, subacute, diffuse, moderate,
with excessive mucus, crypt abscesses, and numerous bacteria, Yorkshire crossbred, porcine.
Etiologic Diagnosis: Brachyspiral colitis
Cause: Brachyspira hyodysenteriae
Condition Synonyms: Vibrionic dysentery, bloody scours, bloody dysentery, black scours,
mucohemorrhagic diarrhea
General Discussion:
Acute to chronic contagious disease, mainly of weaned pigs (7-16 weeks) but more common in
fattening than in breeding units
Gram-negative, strongly beta hemolytic, oxygen tolerant, anaerobic, loosely coiled, motile
spirochete, 6-8.5 micron long and 320-380 nm in diameter
Mice are a reservoir host for infection.
Asymptomatic carrier pigs are the most important mode of transmission from farm to farm.
Mechanical vectors include boots, coveralls, vehicles, migratory animals and birds.
Typical Gross Findings:
Lesions in the large intestine, not small intestine, often sharp line of demarcation at the ileocecal
junction. Fibrinonecrotic pseudomembranous colitis with a granular, hyperemic mucosa in
advanced cases. Opaque spots (enlarged submucosal glands) visible through the colonic serosa.
Mucus, fibrin and blood in the lumen in chronic cases. Congestion of the gastric mucosa and
pericardial serous effusion
Typical Light Microscopic Findings:
Elongated hyperplastic crypts, may be dilated and contain necrotic debris and abundant mucus
Significant lesions limited to cecum, colon, rectum.
Early - discrete necrosis of the superficial mucosa with a fibrinocellular exudate
Fibrin thrombi in the vessels of the superficial lamina propria
 30

Transmural edema
Mucosal and submucosal thickening from vascular congestion and extravasation of fluids and
electrolytes
Additional Diagnostic Tests:
Silver stains demonstrate spirochetes in superficial erosions and crypt lumina.
Differential Diagnosis:
Porcine colonic spirochetosis: caused by the weakly beta-hemolytic intestinal spirochetes (WBHIS);
mild diarrhea and reduced growth rate in weanling pigs (5-12 weeks)
Coliform gastroenteritis: deep red gastric venous infarcts; flaccid small intestine and enlarged
mesenteric lymph nodes
Salmonellosis:
S. typhimurium: yellow watery diarrhea; acute enterocolitis with pseudodiphtheritic membrane;
lesions in colon and rectum.
S. choleraesuis: primarily septicemia with enteritis
Classical swine fever (swine pestivirus): Sudden death; weak pigs; anorexia; watery diarrhea;
hypertrophy and ulceration of mucosa of stomach, cecum and colon; colonic button ulcers
Trichuris suis: Concurrent infections are possible, which can cause bloody diarrhea.
Acute hemorrhagic proliferative enteropathy (Lawsonia intracellularis) : affects terminal ileum and
colon, rapidly fatal with severe hemorrhagic diarrhea.
Gastric ulceration: Melena rather than frank blood

D-B17 - Bacillary hemoglobinuria - liver - ox

Histopathologic Description: Liver: Multifocally, there are areas of lytic necrosis interspersed
among diffuse coagulative necrosis disrupting and multifocally effacing hepatic architecture. The
areas of lytic necrosis are characterized by eosinophilic cellular and karyorrhectic debris admixed
with moderate numbers of degenerate neutrophils, with lesser macrophages and few lymphocytes
and plasma cells, hemorrhage and fibrin. The inflammatory cells, hemorrhage, and fibrin extend
into areas where sinusoids are moderately expanded but hepatic cord architecture is retained.
Hepatocytes in these areas are shrunken with pale eosinophilic cytoplasm with loss of cellular detail
and absent, pale or pyknotic nuclei (coagulative necrosis). Peripheral to the areas of lytic necrosis
there are multifocal individual and colonies of 1x7um bacilli. There are ectatic lymphatics (edema)
that occasionally contain fibrin and multifocal variably sized up to 1mm in diameter areas of clear
space (emphysematous change).
Morphologic Diagnosis: Liver: Necrosis, diffuse, extensive, with multifocal acute moderate
hepatitis, emphysema, and numerous bacilli, Holstein, bovine.
Etiologic Diagnosis: Clostridial hepatitis
Cause: Clostridium hemolyticum
Condition Synonyms: Red water disease, hemorrhagic disease or infectious icterohemoglobinuria.
General Discussion:
Bacillary hemoglobinuria is an acute, highly fatal disease of sheep and cattle that occur in regions in
which liver fluke (Fasciola hepatica) infections also occur.
Typical Light Microscopic Findings:
Hepatic necrosis
Thrombi in hepatic venules, intestines, and other abdominal organs
Mottled kidneys due to hemoglobinuric nephrosis
Bacilli are present singly or in short chains in tissue and have distinctive subterminal spores that
bulge.
Differential Diagnosis:
Other diseases causing hemoglobinuria and hematuria in cattle
Acute leptospirosis causes intravascular hemolytic anemia and hemoglobinuria
Hypophosphatemic hemolytic anemia (postparturient hemoglobinuria): This is common in dairy
 31

cows 3 to 8 weeks following parturition. Erythrocytes require phosphorus for the synthesis of ATP
(Embden-Meyerhof pathway), which is essential for membrane function and integrity.
Babesia bovis (Texas or red water fever): Fever, intravascular hemolysis, hemoglobinuria;
intracytoplasmic paired pyriform protozoa
Hemolytic anemia associated with Brassica sp. (rape or kale): Anemia results from dimethyl
disulfide produced by ruminal bacteria from plant breakdown.
Bracken fern (enzootic hematuria): Hemorrhagic cystitis; neoplasia in chronic cases
Other bacteria: Cl hemolyticum, Cl novyi, Cl perfringens, E coli.
Oxidants: Acetaminophen, Copper, Onions, Propylene glycol, Red maple, Phenothiazine
Immune mediated: Autoimmune hemolytic anemia (horses, cattle)
Comparative Pathology:
Bacillary hemoglobinuria:
Also occurs in sheep, can be experimentally induced in rabbits, and has been diagnosed in a free
ranging elk calf following similar undiagnosed deaths
Black disease, or infectious necrotic hepatitis, occurs mostly in sheep and cattle, but occasionally in
horses and pigs, and is caused by Clostridium novyi (usually type B).
Pathogenesis is very similar to bacillary hemoglobinuria: Hepatic necrosis (immature fluke
migration) > decreased oxygen tension > germination of dormant spores > toxin production

D-B18A - Helicobacter infection - stomach - Rhesus monkey

HD: Stomach: Multifocally there is marked loss of parietal and chief cells lining gastric pits and
glands and replacement by high numbers of mucous neck cells (mucous neck cell hyperplasia). The
lamina propria contains small clusters of plasma cells and lymphocytes that expand and surround
gastric glands and extend into the submucosa. Occasionally gastric glands are mildly dilated, lined
by attenuated epithelium, and contain few neutrophils and eosinophilic cellular and karyorrhectic
debris (glandular abscess). There is occasional individual epithelial cell necrosis and rare spiral
shaped bacilli adhered to the epithelium.
Morphologic Diagnosis: Stomach: Parietal and chief cell loss, chronic, multifocal, marked, with
mucous neck cell hyperplasia, mild lymphoplasmacytic gastritis, and rare epithelial-associated
spiral shaped bacilli, Rhesus macaque (Macaca mulatta), nonhuman primate.
Etiologic Diagnosis: Helicobacter gastritis
Cause: Helicobacter pylori
General Discussion:
Helicobacter sp. are gram negative, microaerophilic, curved to spiral motile bacilli with sheathed
flagella. Cause of lymphoplasmacytic gastritis in several animal species and peptic ulcers and
gastric neoplasia in humans. Associated with gastric lymphoma and carcinoma in ferrets. Causes
chronic active hepatitis in mice.
Mice: Helicobacter hepaticus will persist indefinitely in the bile canaliculi. Also causes proliferative
typhlocolitis and rectal prolapse in immunocompromised mice.
Typical Light Microscopic Findings:
Pathologic findings vary from absence of lesions to severe gastritis. Lymphoplasmacytic gastritis
with erosion, ulceration, mucosal hypertrophy, dilated glands, and necrosis of individual glands
+/- hyperplasia and metaplasia of superficial glands. Focal infiltration by neutrophils and
eosinophils may also occur. H. mustelae and H. pylori are 2-5 um long, loosely spiraled, "gull
wing" bacilli and are most commonly found in antral glands. H. felis and H. heilmannii are 7-15 um
long, more tightly spiraled bacilli and most common in fundic glands
Mice: H. hepaticus causes acute, focal, non-suppurative, necrotizing hepatitis; progresses to chronic
active hepatitis with minimal necrosis and is associated with gallbladder mucosal erosion and
ulceration
Differential Diagnosis:
Gross lesions:
 32

Chronic NSAID administration

Catarrhal or hemorrhagic gastritis caused by infectious or toxic agents;
Lack characteristic spiral shaped bacteria
Differential diagnosis for rectal prolapse in mice:
Helicobacter hepaticus
Citrobacter rodentium - Transmissible Murine Colonic Hyperplasia (TMCH)
Syphacea obvelata, Aspicularis tetraptera - cecal pinworms of mice
Microscopic lesions:
For H. hepaticus in mice: Mouse Hepatitis Virus (MHV) infection, coronavirus; however, MHV
infection results in virus-induced syncytia formation and acute hepatic necrosis but does not
typically result in biliary hyperplasia
Comparative Pathology:
H. pylori: Man (50%) assoc with chronic active gastritis, peptic ulcer, gastric adenocarcinoma and
mucosa-associated lymphoid tissue lymphoma; non-human primates and felines
H. mustelae: Ferrets (found in 99% of sick and healthy ferrets); animal model for study of gastritis,
ulcers, and carcinogenesis
H. muridarium; H. bilis; H. rodentium; H. ganmani; H. typhlonius; H. muricola; H. rappini: Mice,
rats
H. hepaticus: Mice; alters the pathogenicity of mouse hepatitis virus in co-infections
H. felis: Dogs, cats
H. acynonix: Cheetah
H. nemestrinae: Pigtailed macaque
H. heilmannii-like organisms: Non-human primates, dogs, cats
H. pullorum: Chickens
H. mesocricetorum; H. aurati: Syrian hamsters; animal model of IBD and potentially IBD related
cancer

D-B18B - Helicobacter infection - stomach - ferret

Histopathologic Description: 1. Stomach: Multifocally nodular aggregates of lymphocytes and
plasma cells expand the lamina propria, surround and separate gastric glands and extend into the
muscularis mucosa and submucosa. Rarely, ectatic glands are lined by attenuated epithelial cells
and contain few neutrophils and eosinophilic cellular and karyorrhectic debris (pit abscesses). There
are lightly basophilic spiral shaped bacilli mixed with a layer of mucous, scattered erythrocytes and
occasional neutrophils multifocally adhered to the epithelium. Warthin Starry 4.0: Numerous
agyrophilic 1x3um gently curved bacilli are present on the mucosal surface.
2. Liver: Diffusly, many lymphocytes and plasma cells infiltrate portal triads. Rarely, periportal
connective tissue extends between adjacent lobules (bridging fibrosis). Multifocally, there is
scattered yellow-brown globular material within Kupffer cells and hepatocytes (hemosiderin).
Multifocally, there is fatty change.
3. Spleen: Diffusely, there is scattered extramedullary hematopoiesis and intra and extracellular
brown, globular material (hemosiderin/bile).
Morphologic Diagnosis:
1. Stomach: Gastritis, lymphoplasmacytic, multifocal, moderate, with superficial argyrophilic
curved bacilli, etiology consistent with Helicobacter sp., ferret (Mustela putorius furo), mustelid.
2. Liver: Hepatitis, portal, lymphoplasmacytic, multifocal, mild with mild fibrosis.
3. Spleen: Extramedullary hematopoiesis, diffuse, mild.
Etiologic Diagnosis: Helicobacter gastritis
Cause: Helicobacter mustelae

D-B18C - Helicobacter infection - liver - mouse

Histopathologic Description: Liver: Multifocally there are moderate portal and periportal infiltrates
 33

of lymphocytes, plasma cells and neutrophils, as well as markedly increased numbers of small
caliber bile ducts lined by cuboidal epithelium with vesicular nuclei (bile duct hyperplasia). Rarely,
bile ducts are lined by attenuated epithelium and contain sloughed cellular and proteinaceous debris.
Multifocally hepatocytes have abundant eosinophilic to markedly vacuolated cytoplasm and an
extremely large nucleus up to 25um in diameter, clumped chromatin and up to eight prominent
magenta nucleoli (hepatocytomegaly and karyomegaly). Hepatocyte nuclei frequently contain
inclusion body-like cytoplasmic invaginations. Multifocally hepatocytes are swollen and have
microvacuolated cytoplasm (degeneration) or are randomly hypereosinophilic, angular and
shrunken with pyknosis (necrosis).
Morphologic Diagnosis: Liver: Cholangiohepatitis, lymphoplasmacytic and neutrophilic,
multifocal, moderate, with marked bile duct hyperplasia, hepatocytomegaly, karyomegaly, and
random hepatocellular degeneration and necrosis, ICR mouse, rodent.
Etiologic Diagnosis: Helicobacter hepatitis
Cause: Helicobacter hepaticus

D-F02 - Zygomycetes infection - rumen - ox

Histopathologic Description: Rumen: Extending from the mucosa into the tunica muscularis is a
focally extensive area of coagulative necrosis (infarct), characterized by retention of tissue
architecture, loss of cellular detail, and nuclear pyknosis or loss. The infarcted area is bounded by a
5 mm wide band of degenerate and nondegenerate neutrophils, macrophages, lymphocytes, plasma
cells, and eosinophilic cellular and karyorrhectic debris. Multifocally, vessel walls are transmurally
disrupted by fibrin with moderate numbers of nondegenerate and degenerate neutrophils admixed
with nuclear and cellular debris (necrotizing vasculitis), and vessels often contain fibrin thrombi,
and fungal hyphae. Within the infarct and extending into adjacent tissues, there are moderate
numbers of nonseptate 5-15 um wide, occasionally folded, fungal hyphae with non-parallel walls,
non-dichotomous, irregular or right angle branching, and bulbous dilatations. The epithelium
adjacent to the infarct is thickened up to 3 times normal with prominent anastomosing rete ridges
(epidermal hyperplasia) and aggregates of nondegenerate and degenerate neutrophils
(microabscesses). The lamina propria, submucosa, and serosa are expanded by increase in clear
space and ectatic lymphatics (edema) along with fibrin. In the tunica muscularis, myocytes are often
hypereosinophilic, vacuolated, and fragmented with pyknotic or absent nuclei (degeneration and
necrosis). At the mucosal/ submucosal interface there are small colonies of basophilic 1-2 um
diameter bacilli.
Morphologic Diagnosis: Rumen: Rumenitis, necrotizing, acute, focally extensive, severe, with
necrotizing vasculitis, infarction, fibrin thrombi, and numerous nonseptate fungal hyphae, breed
unspecified, bovine.
Etiologic Diagnosis: Ruminal zygomycosis
Cause: Zygomycetes sp.
Typical Light Microscopic Findings:
Necrotizing vasculitis, thrombosis, infarctions and hemorrhagic necrosis. Diffuse
pyogranulomatous inflammation (+/- transmural) with coagulative necrosis and multinucleated
giant cells. Chronic cases: Granulomatous inflammation in the deep mucosa. Fibrinous exudate;
varying leukocytic inflammation. Pauciseptate, thin-walled 3-25 um wide hyphae with non-parallel
walls, non-dichotomous, irregular, often right angle, branching and focal bulbous dilatations.
Hyphae in necrotic/infarcted areas and within blood vessels (angiotropic)
Liver: Necrotizing thrombophlebitis of portal radicles with disseminated infections
Differential Diagnosis:
Mycotic rumenitis
Aspergillus fumigatus (Class Hyphomycetes):
Hyphae are 3-6 microns wide, septate, with parallel walls and acute angle, dichotomous branching.
Angioinvasive.
 34

Candida albicans (Class Blastomycetes, Family Cryptococcaceae): Masses of branching, septate

hyphae, with pseudohyphae, and round to oval budding yeasts (blastospores). 3-5 microns in
diameter. Typically an infection of squamous epithelium in young animals (“thrush”)
Fusobacterium necrophorum: Usually superficial; affects papillated areas of ventral sac and
occasionally rumenal pillars; less hemorrhagic
Comparative Pathology:
Zygomycetes sp.
Dogs: Ulcerative and granulomatous stomatitis, gastritis, and enteritis, lymphadenopathy with
calcification, encephalitis, pneumonia, cutaneous nodules
Horses: Lips and pharynx, nostrils, nasal mucosa
Candida sp.:
Calves: Disseminated candidiasis
Pigs: Often invades the parakeratotic material on the squamous gastric mucosa. May be inapparent
Young pigs: “Thrush” (candidiasis of the oral cavity)
Foals: Gastroesophageal candidiasis, usually involves squamous epithelium, associated with
ulceration near margo plicatus
Aspergillus sp.:
Cats: Mycotic ileitis and colitis; may be a sequel to panleukopenia; hemorrhagic and necrotizing
lesions with a prominent cellular response; often disseminates to lung
Dogs: Disseminated mycotic enteritis with canine parvoviral enteritis (rare)
Pythium sp. (Kingdom Protista, Phylum Oomycetes):
Tropical and sub-tropical areas; enteric disease in dogs; cutaneous disease in horses

D-F03 - Prototheca sp. infection - colon - dog

Histopathologic Description: Colon: Transmurally, there are many extracellular and intrahistiocytic,
round to oval, 8-20 um diameter algae that have a clear 2-4 um thick wall, and contain either central
granular amphophilic material or multiple (2-8 or more) wedge-shaped endospores admixed with
moderate numbers of macrophages and plasma cells, and rare lymphocytes and neutrophils. The
submucosa is expanded to twice normal thickness by algae and inflammatory cells, which also
moderately expand the lamina propria, rarely infiltrate the tunica muscularis and multifocally
disrupt serosa and attached mesentery. Occasionally, the mucosal epithelium is disrupted by cellular
and karyorrhectic debris. Submucosal vessels are congested. The algal cell wall is PAS positive.
Morphologic Diagnosis: Colon: Colitis, histiocytic and plasmacytic, transmural, diffuse, moderate,
with mesenteric steatitis and many extracellular and intrahistiocytic algae, etiology consistent with
Prototheca sp., Vizsla, canine.
Etiologic Diagnosis: Protothecal colitis.
Cause: Prototheca sp.
General Discussion:
Achlorophyllous (colorless), unicellular, ubiquitous saprophytic algae that reproduces asexually by
internal septation (endosporulation) and causes disseminated infections in dogs (intestine and eye
are most common sites in dogs)
Only P. zopfii & P. wickerhamii are pathogenic; both have been reported in dogs. P. wickerhamii:
(2-12 um) with compact round or cuboidal endospores. P. zopfii: (10-25 um) oval with larger, round
to polyhedral endospores.
Differential Diagnosis:
Organisms that reproduce by endosporulation:
Chlorella sp.: Algal organism reported in cattle, sheep, and beaver; granulomatous and necrotizing
lesions with similar organisms containing intracytoplasmic starch granules and chloroplasts, which
are PAS positive and anisotropic in unstained and H & E sections and evident on EM; green
discoloration of unfixed tissue grossly
Coccidioides immitis: Larger (10 60 um), with many endospores per sporangium
Rhinosporidium seeberi: Nasal mucosa; large, mature sporangia 100-350 um diameter with
 35

numerous round, mature endospores 7-9 um diameter

Batrachochytrium dendrobatidis: Thalli with discharge papillae in the epidermis of amphibians
Granulomatous colitis in dogs:
Histoplasma capsulatum.: Ulcerative, granulomatous transmural colitis
Trichuris vulpis (whipworms): Presence of intraluminal nematodes; usually affects cecum and
proximal ascending colon; evolves into a granulomatous transmural condition
Mycobacterium sp. (M. bovis, M. tuberculosis)
Leishmania sp.: Heavy mucosal infiltrate of macrophages
Fungi resembling Prototheca sp. histologically:
Phaeohyphomycosis: Pigmented brown fungi with septate hyphae
Blastomyces dermatitidis: Broad-based budding yeast 5-20 um in diameter with refractile, double-
contoured wall and no mucinous capsule
Cryptococcus neoformans: Budding yeast with a wide 2-6 um, clear mucinous capsule, which
contains acid mucopolysaccharide
Sporothrix schenkii: Pleomorphic yeast; cause granulomatous dermatitis in cats
Comparative Pathology:
Cats: Mostly cutaneous; single or multiple small gray-white or tan subcutaneous nodules on
extremities; usually confined to dermis and subcutis +/- regional lymph nodes; dense infiltrations of
macrophages and giant cells without discrete granulomas
Bovine: Bovine mammary gland nodular (granulomatous) mastitis; enlarged and pale
supramammary lymph node; giant cells and eosinophils common
Salmon: Renal granulomatous disease

D-F04 - Pythiosis - small intestine - dog

Histopathologic Description: Small intestine: Focally disrupting and replacing 60% of the mucosa,
submucosa, and tunica muscularis are multiple coalescing granulomas that expand the intestinal
wall up to 4 times normal. Granulomas are characterized by a central area of necrotic debris,
degenerate eosinophils and neutrophils, surrounded by numerous epithelioid macrophages,
eosinophils, neutrophils and fewer multinucleated giant cells (both Langhans and foreign body
type) with up to 15 nuclei, that are further surrounded by haphazardly arranged hypertrophied
fibroblasts and fibrous connective tissue admixed with previously described inflammatory cells.
Within the central core of granulomas there are occasional poorly discernible hyphae. Eosinophils,
neutrophils, and macrophages with variable numbers of fibroblasts and fibrous connective tissue
separate, surround, and replace collagen bundles and muscle fibers of the adjacent submucosa,
overlying extant lamina propria, and underlying extant tunica muscularis, extending transmurally
and expanding the serosa. Villi are often blunted and fused. Multifocally within the remaining
section, the lamina propria and submucosa contain moderate numbers of eosinophils, neutrophils,
and macrophages and there is a single, 400 um, granuloma in the submucosa.
GMS: Scattered throughout the tissue, but primarily within the center of granulomas, there are
small to moderate numbers of GMS-positive hyphae that are 4-7um wide, have nonparallel walls,
non-dichotomous branching, and rare septations.
Morphologic Diagnosis: Small intestine: Granulomas, multiple, with rare intralesional hyphae, and
a focally extensive marked transmural eosinophilic and granulomatous enteritis, breed not specified,
canine.
Etiologic Diagnosis: Enteric pythiosis
Cause: Pythium insidiosum
Condition Synonyms: Oomycosis
General Discussion:
A chronic, progressive cutaneous, GI, or multisystemic granulomatous disease of horses, dogs,
cattle, cats, sheep, and humans in tropical, subtropical, and temperate climates. Only Pythium
insidiosum is pathogenic in mammals. Identified as a member of the class Oomycetes, Pythium is a
water mold with broad, irregularly branching, rarely septate hyphae with thick, nonparallel walls.
 36

Water molds differ from true fungi in the composition of their cell wall and plasma membrane, and
in the production of motile, biflagellate zoospores.
The only other oomycete recognized to cause disease in mammals is Lagenidium; Saprolegnia sp. is
an oomycete in fish.
Two forms in the dog:
GI form - most common
Subcutaneous form
Disseminated disease may develop from either the cutaneous or GI form but is rare.
Typical Light Microscopic Findings:
Eosinophilic granulomatous to pyogranulomatous inflammation and/or granulomas associated with
numerous multinucleated giant cells and epithelioid macrophages. Organisms found in areas of
necrosis have broad, irregularly branching, rarely septate hyphae (range 2-7um diameter) with
thick, nonparallel walls
Differential Diagnosis:
Histologic appearance - pyogranulomatous and eosinophilic inflammation with hyphae:
Lagenidium sp. - oomycete
Lesions may be more generalized (great vessels, sublumbar and inguinal lymph nodes, lung, and
cranial mediastinum). Hyphae have larger diameter than Pythium sp. (range 7-25um).
Zygomycetes - hyphal wall surrounded by a band of eosinophilic material (eosinophilic sleeve)
Conidiobolus coronatus - diameter range 5-13um; eosinophilic sleeve 5-10um wide
Basidiobolus ranarum - diameter range 5-20um; eosinophilic sleeve up to 25um wide

D-M01A - Feline oral eosinophilic granuloma - oral mucosa - cat

Histopathologic Description: Oral mucosa (per contributor): The subepithelial connective tissue is
expanded by a diffuse inflammatory infiltrate centered around multifocal to coalescing scattered,
sharply-delineated eosinophilic foci that are up to 250 um. These foci consist of fragmented,
intensely eosinophilic material (degenerate collagen), mixed with a small amount of basophilic
debris, surrounded by a rim of macrophages and foreign body giant cells. The surrounding
connective tissue is expanded by many eosinophils, fewer neutrophils, macrophages, mast cells,
lymphocytes, plasma cells and fibroblasts. Lymphatics are mildly dilated, and blood vessels are
often lined by reactive endothelial cells. Occasionally mucosal epithelial cells are pale and swollen
(hydropic degeneration), or are separated by clear space (spongiosis).
Morphologic Diagnosis: Oral mucosa: Stomatitis, eosinophilic and granulomatous, diffuse,
moderate, with collagen degeneration, breed unspecified, feline.
General Discussion:
Feline eosinophilic granuloma complex includes lesions affecting the skin, mucocutaneous
junctions and oral cavity of cats. There is no breed or sex predilection. It encompasses the following
distinct clinical entities:
Eosinophilic granuloma: subdivided into oral eosinophilic granuloma and linear granuloma.
Indolent ulcer
Eosinophilic plaque
Canine eosinophilic granulomas are rare, nodular to plaque-like lesions in the oral cavity or rarely
the skin, primarily affecting young (<3 years old) male Siberian huskies and Cavalier King Charles
spaniels.
Pathogenesis:
Cause unknown
Typical Gross Findings:
Feline eosinophilic granuloma
Feline oral eosinophilic granuloma: Single or multiple firm, ulcerated raised nodules on the ventral
tongue, soft palate, and frenulum.
Feline linear granuloma: Linear, well-demarcated, pinkish-yellow, elevated, firm lesion on the
caudal or medial thighs.
 37

Feline eosinophilic granuloma – pink-yellow swelling of chin, “fat chin”. May also occur on paws
and cause swelling of pads.
Feline eosinophilic plaque: Alopecic and erosive to ulcerative erythematous, singular to multiple
plaques located on the abdomen, perianal, and medial thigh regions.
Indolent ulcer: Erosive to ulcerative lesion on upper lip or adjacent to the upper canine tooth.
Canine eosinophilic granuloma:
Oral: Well-demarcated, yellow to greenish-brown, vegetative, granulomatous plaques on the ventral
and lateral surfaces of the tongue or palatine mucosa. Ulceration is common.
Cutaneous: Multiple papules, nodules and plaques, usually on the abdomen, flanks and prepuce, or
solitary lesions in the external ear canal
Oral and cutaneous lesions rarely coexist
Typical Light Microscopic Findings:
Eosinophilic granuloma: Nodular to diffuse granulomatous inflammation, with numerous
eosinophils, surrounding degenerate collagen (flame figures); eosinophilic folliculitis or
furunculosis (in cutaneous lesions), giant cells. Overlying epithelium may be hyperplastic and/or
ulcerated.
Eosinophilic plaque: Severe acanthosis, spongiosis, eosinophilic exoctyosis. Epidermal and
follicular mucinosis is common. Eosinophils may extend to panniculus. Ulceration.
Indolent Ulcer: Eosinophilic inflammation with fewer neutrophils and variable fibrosis and rarely
eosinophilic “flame figures”.
Dogs: Oral eosinophilic granulomas are often ulcerated, have eosinophils, fewer lymphocytes,
macrophages, and plasma cells, submucosal edema, and variable fibrovascular proliferation with
endothelial swelling. In Cavalier King Charles Spaniels, degranulating eosinophils may be absent
and there may be mild flame figure formation; in Siberian Huskies, flame figures are prominent.
Differential Diagnosis:
For gross lesions in the oral cavity of cats:
Neoplasia (squamous cell carcinoma)
Ulceration (fungal, bacterial, viral)
Feline plasma cell gingivitis-pharyngitis: Typically raised erythematous, proliferative lesions,
mainly in the glossopalatine arches (often bilateral)
For gross lesions in the oral cavity of dogs:
Oral eosinophilic granulomas are visually distinctive, have marked breed predilections, and hence
have few differential diagnoses but consider the following:
Granulomas (fungal, bacterial)
Neoplasia (mast cell tumor, lymphoma, squamous cell carcinoma, melanoma, plasmocytoma)
Comparative Pathology:
Equine nodular collagenolytic granuloma (nodular necrobiosis): Nonpruritic nodules over withers,
back and neck.
Oral, nasal, and cutaneous eosinophilic granulomas are reported in Black rhinoceros.

D-M01B - Canine oral eosinophilic granuloma - oral mucosa - dog

Histopathologic Description: Oral mucosa (per contributor): There is a polypoid lesion covered by
an extensively ulcerated mucosa. Within the mass, there are multifocal to coalescing nodular
aggregates of eosinophils and macrophages that palisade around degenerate, fragmented, and
sometimes hyalinized bundles of collagen. These foci are surrounded by abundant eosinophils,
macrophages, neutrophils, lymphocytes and mast cells. The stroma is expanded by hypertrophic
fibroblasts separated by pale basophilic fibrillar matrix, ectatic lymphatics, and many small caliber
parallel blood vessels lined by hypertrophic endothelium (granulation tissue). There are a few
neutrophils transmigrating the remaining mucosa.
Morphologic Diagnosis: Oral mucosa (per contributor): Stomatitis, eosinophilic and granulomatous,
focally extensive, severe, with collagen degeneration and ulceration, Siberian Husky, canine.
 38

D-M02 - Eosinophilic enteritis - small intestine - horse

Small intestine: Multifocally villi are blunted and fused with mucosal ulceration. Many eosinophils,
macrophages, and fewer lymphocytes and plasma cells diffusely infiltrate the lamina propria,
admixed with many erythrocytes and small amounts of eosinophilic cellular, pyknotic, and
karyorrhectic debris (necrosis). Multifocally lacteals are dilated with increased numbers of
lymphocytes. The submucosa is thickened 4-5 times by many eosinophils, macrophages,
lymphocytes, neutrophils, plump fibroblasts and collagen. The submucosal glands are mildly dilated
and frequently filled with or obscured by nodular aggregates of degenerate eosinophils, eosinophilic
cellular and karyorrhectic debris, and fibrillar basophilic material (mucin). Multifocally dense
aggregates of brightly eosinophilic debris are surrounded by epithelioid macrophages, eosinophils,
rare multinucleate giant cells, and concentric rings of collagen (eosinophilic granulomas).
Multifocally in the submucosa there are areas of hemorrhage, mildly dilated lymphatics, fibrin, and
edema. The lumen contains focally extensive accumulations of fibrin admixed with sloughed
epithelial cells and cellular debris.
Morphologic Diagnosis: Small intestine, mucosa and submucosa: Enteritis, eosinophilic and
histiocytic, diffuse, severe, with eosinophilic granulomas, Quarter horse, equine.
General Discussion:
Equine inflammatory bowel diseases (IBDs) in which no cause has been identified include
granulomatous enteritis (GE), multisystemic eosinophilic epitheliotropic disease (MEED),
lymphocytic-plasmacytic enterocolitis (LPE), and idiopathic eosinophilic enterocolitis (EC).
In some papers, EC and MEED describe IBD in which eosinophils infiltrate the intestine and other
organs. In other papers, EC describes IBD with intestinal eosinophilic infiltrates only. Affected
horses with EC (lesions confined to the intestinal tract) have different clinical signs and a better
prognosis for survival than other forms of IBD.
Chronic eosinophilic enteritis of horses is considered to be part of MEED with eosinophils
infiltrating many organs (gastrointestinal tract, liver, pancreas, mesenteric lymph nodes, spleen,
bronchial epithelium, oral cavity and skin).
Peripheral eosinophilia is absent.
Pathogenesis:
Unknown specific cause
Typical Light Microscopic Findings:
Gastrointestinal tract
Diffuse infiltration of enteric tunics by eosinophils, macrophages, mast cells, and fewer
lymphocytes and plasma cells
Eosinophilic granulomas - central core of eosinophils surrounded by macrophages, giant cells, and
fibrosis
Villus atrophy, lamina propria fibroplasia, muscularis hypertrophy
Skin - perivascular dermatitis, epidermal acanthosis, hyperkeratosis, ulceration, exudation
Differential Diagnosis:
For eosinophilic enteritis - Inflammatory bowel disease, pythiosis, parasite migration (strongyles),
other chronic enteritides
Comparative Pathology:
Multisystemic eosinophilic disease (hypereosinophilic syndrome - HES) - reported in dogs, cats,
ferrets and humans; usually with peripheral eosinophilia
Feline enteric eosinophilic syndrome is often progressive and fatal.

D-M03 - Chronic hypertrophic gastritis - stomach - dog

Histopathologic Description: Stomach, fundus: In one section, the gastric mucosa is diffusely and
markedly thickened (up to three times normal) and thrown into exaggerated rugal folds supported
by a submucosa thickened by abundant fibrous connective tissue. The thickened mucosa contains
 39

elongated gastric glands. Multifocally surface and neck mucus cells extend deep into the gastric
glands, replacing parietal cells. Occasionally nodular aggregates of lymphocytes and plasma cells
expand the lamina propria. The second section is within normal limits.
Morphologic Diagnosis: Stomach, mucosa: Hyperplasia, focally extensive, moderate, with mild
lymphoplasmacytic gastritis, German Shepherd Dog, canine.
Condition Synonyms: Idiopathic or giant hypertrophic gastritis; gastric polyposis; pseudotumoral
gastritis; hyperrugosity of the stomach; adenomatous hyperplasia; nodular mucosa; hypertrophic
gastropathy; giant rugal hypertrophy; Menetrier's Disease
General Discussion:
An idiopathic condition of dogs producing marked gastric rugal hypertrophy and mucosal gland
hyperplasia in the body of the stomach. The Basenji, Beagle, Boxer and Bull terrier are predisposed,
often presenting with a protein-losing gastropathy similar to Menetrier’s disease in humans.
Typical Light Microscopic Findings: Hyperplastic mucosa, may include secondary folds of
muscularis mucosa. Mucus cell metaplasia that gradually replaces parietal cells. Cystic dilatation of
mucous glands may be present. Lymphocytes and plasma cells expand the lamina propria at the
base of glands.
Differential Diagnosis:
For thickened gastric mucosa in dogs:
Chronic hypertrophic pyloric gastropathy: Involves pylorus; associated with small breed dogs
Adenomatous polyps: Raised, sessile or pedunculated polypoid masses
Zollinger-Ellison Syndrome: Fundic mucosal hypertrophy secondary to increased gastrin secretion
from pancreatic islet cell tumor or gastrinoma
Infiltrating lymphoid tumors: Monomorphic population of lymphocytes
Leiomyoma: Usually well demarcated; absence of both inflammatory infiltrate and mucosal
hypertrophy
Comparative Pathology:
Causes of hypertrophic/proliferative gastritis:
Non-human primates: Nochtia nochti
Cattle: Ostertagiasis (Ostertagia ostertagi)
Sheep: Ostertagia circumcincta
Horse: Trichostrongylus axei; Habronema sp.
Pig: Hyostrongylus rubidus
Cat: Ollulanus tricuspis
Snakes: Cryptosporidium infection causes hypertrophy, edema, and thickening of gastric mucosa;
replacement of granular cells by cuboidal and columnar cells resembling mucous neck cells; cystic
changes in gastric glands and focal mucosal necrosis

D-M04 - Mucoid enteropathy - ileum - rabbit

Histopathologic Description: Ileum (per contributor): Over 95% of the mucosal epithelium is
composed of goblet cells (hyperplasia) that diffusely and markedly distort the villi, replace
enterocytes, expand the crypts and compress the adjacent lamina propria. Multifocally the lamina
propria contains low numbers of heterophils, macrophages, lymphocytes, and plasma cells.
Multifocally within crypts and the intestinal lumen, there are low numbers of sloughed and necrotic
epithelial cells and previously described inflammatory cells, and abundant amphophilic fibrillar
material (mucus).
Morphologic Diagnosis: Ileum (per contributor): Hyperplasia, goblet cell, diffuse, severe, with
minimal subacute enteritis, New Zealand White rabbit, lagomorph.
General Discussion:
A common, worldwide, noninflammatory, subacute enteric condition that affects weanling rabbits
between 7-14 weeks of age
Pathogenesis:
Cause is unknown.
 40

Typical Gross Findings:

Colon distended with clear, gelatinous mucus. Cecum may contain mucus or fluid. Colonic
constipation or cecal impaction are common. Small intestines generally contain watery, bile-stained
contents.
Typical Light Microscopic Findings:
Goblet cell hyperplasia may be present throughout the gastrointestinal tract and is most severe and
consistent in the ileum and colon. The absence of inflammation is characteristic.

D-M05 - Intestinal emphysema - small intestine - pig

Histopathologic Description: Small intestine: Diffusely the submucosa is markedly expanded by
multiple, often coalescing, clear cystic spaces up to 2 mm in diameter, which are lined by a
discontinuous layer of flattened endothelium (lymphatics). The cysts are separated by a thin to
moderate collagenous stroma that multifocally is infiltrated by moderate numbers of lymphocytes,
plasma cells, macrophages, eosinophils and occasional, small aggregates of multinucleated giant
cells of both the Langhans and foreign body types. Eosinophils and lymphocytes multifocally
infiltrate the tunica muscularis and, in conjunction with edema, expand the subserosa. Lymphatics
within the tunica muscularis and serosa are also moderately ectatic. Focally a lymphatic within the
subserosa contains an aggregate of eosinophilic material and degenerate leukocytes.
Morphologic Diagnosis: Small intestine: Emphysema, submucosal, diffuse, severe, with multifocal
transmural lymphangiectasia and granulomatous and eosinophilic inflammation, breed not
specified, pig, porcine
Cause: Unknown
Condition Synonyms: Pneumatosis cystiodes intestinalis; emphysema intestinalis
General Discussion:
Gas-filled cystic spaces in the intestinal wall
Rare, incidental finding in healthy swine at slaughter
Typical Light Microscopic Findings:
Gas-filled cystic structures are dilated lymphatics of the lamina propria, submucosa, tunica
muscularis, subserosa, mesentery, or mesenteric lymph nodes.
A mixed to granulomatous inflammatory reaction may be evident in the walls of the cyst-like
structures; macrophages can contain vacuoles (gas).
Differential Diagnosis:
Fluid-filled lymphatics (edema or lymphatic obstruction)
Empty parasitic cysts
Congenital anomalies (remnant cysts of reproductive origins)
Comparative Pathology:
Sheep: Occasionally occurs with enterotoxemia
Human: Usually asymptomatic incidental finding
Rabbit: Experimentally induced through nutritional factors.

D-M06 - Equine serum hepatitis - liver - horse

History: The animal was vaccinated 2 weeks prior to death for tetanus, EEE, and WEE. Clinical
findings included blindness, incoordination, constipation, head pressing, icterus, AST=1800,
bilirubin=12, BSP more than 15 min.
Histopathologic Description: Liver: Diffusely the hepatic cord architecture is disrupted by loss of
centrilobular and midzonal hepatocytes with stromal collapse. Remaining hepatocytes in these areas
are shrunken and often individualized and contain pale, vacuolated cytoplasm (degeneration), or
condensed eosinophilic cytoplasm with pyknotic nuclei or karyorrhectic debris (necrosis). Hepatic
cords are disrupted and separated by multifocal areas of hemorrhage, moderate numbers of
macrophages and Kupffer cells that sometimes contain phagocytosed erythrocytes and minimal
amounts of globular brown pigment (hemosiderin), and scattered lymphocytes and plasma cells.
Remaining hepatic cords surrounding portal areas are mildly disrupted and hepatocytes contain
 41

mildly vacuolated cytoplasm. Portal areas are mildly expanded by clear space (edema) and contain
slightly increased amounts of collagen (fibrosis), few lymphocytes, plasma cells, macrophages, and
rare neutrophils.
Morphologic Diagnosis: Liver: Hepatocellular degeneration, necrosis and loss, centrilobular and
midzonal, diffuse, severe, with stromal collapse, and mild multifocal subacute hepatitis, Appaloosa,
equine.
Cause: Unknown
Condition Synonyms: Theiler's disease, post-vaccinal hepatitis, X-disease, acute yellow atrophy of
horses, idiopathic acute hepatic disease
General Discussion:
Most common cause of acute hepatic failure in horses. Generally occurs 40-70 (range of 27-165)
days after receiving injections of equine-origin biologics, including tetanus antitoxin, equine
encephalomyelitis antiserum, pregnant mare serum gonadotropin, African horse sickness antiserum,
anthrax antiserum, plasma. Mortality is 50% -90% in horses that develop clinical signs.
Sporadically occurs in horses that have not received equine biological products; there are reports of
in-contact non-treated horses developing the disease. Higher incidence in horses > 1yr
Typical Light Microscopic Findings:
Subacute to chronic hepatocyte degeneration and necrosis (not acute like the clinical disease)
Severe fatty change affecting most hepatocytes; may coalesce and form fatty cysts; dilated
sinusoids and condensed reticulin framework
Bile pigment may accumulate in hepatocytes and Kupffer cells. Diffuse mild fibroplasia primarily
in portal areas
Differential Diagnosis:
Equine hepatic necrosis
Pyrrolizidine alkaloid toxicity: Chronic; individual hepatocyte necrosis; megalocytosis;
centrilobular fibrosis; bile duct proliferation and fibrosis
Equine infectious anemia (equine lentivirus): Subacute; centrilobular fatty degeneration and
hepatocellular loss; increased numbers of sinusoidal Kupffer cells; portal infiltration by
lymphocytes and plasma cells very characteristic
Acute toxic hepatitis (mycotoxins, i.e. aflatoxin): Usually centrilobular necrosis with minimal
inflammation; biliary hyperplasia; fibrosis with chronicity; +/- photosensitization
NOTE: Serum sickness is a different condition, a generalized type III hypersensitivity reaction. The
classic example is the acute or "single shot" serum sickness which was formerly seen in people
given large doses of equine-origin antisera. About 10 days later, these people developed generalized
vasculitis with erythema, edema, and urticaria of the skin, neutropenia, joint swelling and
proteinuria (due to immune complex glomerulonephritis). Acute and chronic forms may occur in
animals that are continuously antigenemic, i.e. in feline leukemia virus infection and canine
dirofilariasis.

D-M07 - Lymphocytic portal hepatitis - liver - cat

Histopathologic Description: Liver: Diffusely, markedly expanding and bridging portal areas are
high numbers of lymphocytes and fewer plasma cells, neutrophils, macrophages, and fibroblasts
that separate and surround bile ducts, compress adjacent lobules and rarely infiltrate adjacent
sinusoids, separating, surrounding and replacing individual necrotic hepatocytes (piecemeal
necrosis). Diffusely, there are increased numbers of branched and tortuous small bile ducts (biliary
hyperplasia) and occasionally, portal lymphocytes form follicular nodules. Centrilobular
hepatocytes and Kupffer cells often contain moderate amounts of granular to globular yellow-brown
pigment (hemosiderin or bile). The capsule is diffusely and markedly expanded by moderate
amounts of clear space (edema) and few previously described inflammatory cells.
Morphologic Diagnosis: Liver: Hepatitis, portal and periportal, lymphocytic, chronic, diffuse,
severe, with biliary hyperplasia and multifocal piecemeal necrosis, breed unspecified, feline
Cause: Unknown
 42

General Discussion:
Inflammatory liver diseases are the second most common type of liver disease in cats (after hepatic
lipidosis).
Two histologically distinct feline inflammatory liver diseases:
Lymphocytic portal hepatitis
Cholangiohepatitis: acute and chronic forms
Mild lymphocytic portal hepatitis is common in older cats (>10 years) and may be an aging change
or a subclinical form of this slowly progressive disease
Pathogenesis:
Unknown
Immune mediated etiology is suspected because of intense lymphocytic inflammation. Not
associated with inflammatory bowel disease or pancreatitis
Typical Gross Findings:
Hepatomegaly, with exaggerated lobular pattern
Chronic cases: Portal fibrosis
Typical Light Microscopic Findings:
Subacute:
Portal tracts expanded by lymphocytes with few macrophages and neutrophils
Bile duct proliferation, may be remarkable
No cholangitis, no periportal necrosis, no bile duct degeneration
Chronic:
Portal fibrosis with bile duct proliferation
Minimal extension into the periportal hepatic parenchyma
Differential Diagnosis:
Acute Cholangiohepatitis (Suppurative Cholangiohepatitis):
Neutrophils within walls or lumina of bile ducts; biliary epithelial degeneration
Disruption of limiting plate; extension of inflammation into parenchyma; periportal hepatocellular
necrosis
May be secondary to an ascending biliary infection
Hemogram: usually neutrophilia with left shift
Chronic Cholangiohepatitis (lymphoplasmacytic/nonsuppurative cholangitis or cholangiohepatitis):
More common in young cats (<4 years) and Persians
Generally thought to be advanced stage of acute cholangiohepatitis
Mixed inflammation (equal numbers of neutrophils and lymphocytes) in portal areas and in bile
ducts, with bile duct degeneration
Marked bile duct proliferation
Periportal hepatocellular necrosis
Bridging fibrosis, leading to pseudolobule formation and cirrhosis
Hepatomegaly, pronounced nodularity of capsule, lobular fibrosis, and nodular hyperplasia
Severe form called “sclerosing cholangitis”; small bile ducts are replaced by periductal “onion skin”
concentric fibrosis.
Hyperglobulinemia
Commonly associated with pancreatitis and inflammatory bowel disease
Malignant Lymphoma:
No polymorphonuclear infiltrate (though may contain eosinophils); concentric layers of cells and
collagen around the bile ducts; less intense biliary hyperplasia; often bridges limiting plate

Comparative Pathology:
Dogs and Man: Chronic active hepatitis has similar hepatocellular piecemeal necrosis and
destruction of the limiting plate as in chronic cholangiohepatitis. This is caused by Hepatitis B virus
in humans.
D-M08 - Uremic gastropathy - stomach - dog
 43

Histopathologic Description: Stomach: Diffusely, but primarily affecting the middle and deep
mucosa, there is necrosis and loss of the glandular epithelium. Gastric glands are torturous, ectatic,
and often lined by, or contain sloughed, individualized, rounded chief and parietal cells with
pyknosis and karyorrhexis (necrosis). Chief cells lining the glands are attenuated and have
decreased cytoplasmic basophilia. There is granular to globular basophilic material (mineral) within
epithelial cell cytoplasm and surrounding cells. The lamina propria is expanded by abundant fibrous
connective tissue that surrounds and widely separates glands. Multifocally capillaries are ectatic and
some contain fibrin thrombi. The lamina propria contains few plasma cells, lymphocytes,
macrophages and occasional neutrophils and mast cells. There is multifocal mucosal hemorrhage.
The submucosa is segmentally expanded up to three times normal by loosely arranged collagen
separated by clear spaces and ectatic lymphatics (edema), and moderate numbers of neutrophils,
lymphocytes, plasma cells and macrophages. Within submucosal arteries the endothelium is
multifocally disrupted and the tunica media contains cellular and nuclear debris, fibrin and mineral
(vasculitis and mineralization). Multiple submucosal vessels contain thrombi.
Morphologic Diagnosis: Stomach: Gastritis, necrotizing, chronic, diffuse, moderate, with vasculitis,
mucosal and vascular mineralization, thrombi, hemorrhage, and edema, Pomeranian, canine.
General Discussion:
Uremia is a systemic toxicosis caused by renal failure and affects multiple organ systems. Severity
of lesions depends on the duration of the uremic state (few lesions with acute renal failure, many
with chronic renal failure).
Pathogenesis:
Lesions associated with uremia are secondary to:
Damage to endothelial cells (pulmonary edema, fibrinous pericarditis, atrial and aortic thrombosis,
stomatitis and gastritis)
Altered calcium-phosphorous metabolism (soft tissue mineralization, fibrous osteodystrophy, and
parathyroid hyperplasia)
Ammonia secretion (gastritis and stomatitis)
Decreased erythropoietin and increased erythrocyte fragility (anemia)
Typical Gross Findings:
Gastrointestinal:
Ulcerative, necrotizing stomatitis and glossitis (esp. underside of tongue)
Ulcerative and hemorrhagic gastritis - dogs and cats
Ulcerative and hemorrhagic colitis - horses and cattle
Hemorrhagic lymphadenopathy
Cardiovascular:
Fibrinous pericarditis
Atrial and aortic thrombosis
Respiratory:
Subpleural intercostal mineralization
Solid, gritty, pale (pumice) lungs
Pulmonary edema and hyperemia
Skeletal: Fibrous osteodystrophy
Typical Light Microscopic Findings:
Gastric mucosal necrosis with erosion and ulceration
Atrophy of gastric glands with fibrosis and mineralization
Submucosal arteriopathy (myocyte necrosis, hypertrophy, mineralization, and thrombosis); limited
to the body and fundus
Shrunken, agranular, atrophic chief cells
Swollen and fragmented parietal cells
Comparative Pathology:
Cats: Similar to dogs
Cattle: Colitis is common, stomach and proximal intestine are edematous.
 44

Horses: Uremic gastritis occurs occasionally (ddx: cantharidin toxicosis).

D-M09 - Vitamin A deficiency - esophagus - chicken

Histopathologic Description:
Esophagus: Diffusely the submucosal glands are markedly ectatic, up to 2 mm in diameter, and the
lining epithelium is replaced by a keratinizing stratified squamous epithelium (squamous
metaplasia). The glandular lumina are filled with eosinophilic lamellations of keratin, admixed with
moderate numbers of pale basophilic coccobacilli, low to moderate numbers of necrotic heterophils,
and occasional foci of mineralization. Multifocally the glands are surrounded by a dense band of
lymphocytes with fewer plasma cells, macrophages, and heterophils. Few lymphocytes, plasma
cells and neutrophils are present within the lamina propria.
Morphologic Diagnosis: Esophagus, submucosal glands: Squamous metaplasia and ectasia,
diffuse, severe, with moderate periglandular lymphoplasmacytic esophagitis, White Leghorn
chicken, avian.
Cause: Vitamin A deficiency (Hypovitaminosis A)
General Discussion:
In poultry, Vit A is essential for optimal growth, vision and integrity of mucous membranes.
Therefore, epithelial linings composed of mucous membranes like the alimentary, urinary, genital,
and respiratory systems are most often affected.
Typical Gross Findings:
Small white nodules (1-3 mm) often with a central depression in nasal passages, mouth, esophagus,
pharynx and often into the crop
Seromucoid watery masses fill turbinates and may cause facial swelling. The paranasal sinuses,
trachea and bronchi may be lined by a delicate pseudomembrane.
Other lesions: bone deformities, keratinization of the tongue, corneal opacity
Typical Light Microscopic Findings:
First histologic lesion is atrophy and deciliation of respiratory cells +/- necrosis > squamous
metaplasia
Bone lesions: Decreased endosteal and periosteal osteoblasts > impaired bone growth, bone
remodeling, and thin cortex
Differential Diagnosis:
Oral lesions
Fowl pox (avian poxvirus): Raised nodules with necrotic centers in oropharynx and esophagus
Trichomoniasis (Trichomonas gallinae): Caseous proliferative lesions in buccal cavity, pharynx,
esophagus, crop, especially in pigeons and raptors
Thrush (Candida albicans): Crop mucosa is thickened with white circular, raised plaques.
Mucoid oronasal discharge and facial swelling
Infectious coryza (Hemophilus paragallinarum): Profuse nasal discharge (“wet beak”)
Infectious bronchitis (coronavirus): Swollen sinuses, catarrhal nasal and ocular discharge, caseous
exudate in lower trachea and bronchi
Neurologic signs:
Ataxia in severe deficiency may resemble Vitamin E deficiency; differentiation is by histologic
examination of the brain.
Comparative Pathology:
Reptiles: Common in turtles and tortoises, rare in snakes; squamous metaplasia of respiratory and
digestive mucous membranes; bilaterally swollen conjunctiva from metaplasia of orbital gland
epithelium; respiratory disease
Dogs: Hyperkeratosis of sebaceous gland ducts; vitamin A-responsive dermatosis (Cocker Spaniel);
deafness from changes in internal auditory meatus
Cattle, swine, sheep, and goats:
Night blindness; excessive lacrimation; neurologic disorders; increased cerebral spinal fluid
pressure; corneal changes; skeletal abnormalities; reproductive disorders (infertility and abortion,
 45

particularly in swine); faded hair and seborrheic skin diseases

In male calves stenosis of the optic foramen > atrophy of the optic nerve and blindness
The pathognomonic lesion in cattle is squamous metaplasia of the parotid gland.
Cats: Experimental (rare) loss of vision; ocular exudate; weakness; incoordination;
bronchopneumonia; subpleural pulmonary cysts lined with squamous epithelium; corneal
ulceration; squamous metaplasia of the conjunctiva, salivary glands, uterus, and respiratory tract
Fish: Poor growth; ascites; edema; exophthalmos; hemorrhagic kidneys
Guinea pigs and rats: There is inadequate differentiation and organization of odontoblasts leading to
irregular dentin formation and enamel hypoplasia.

D-M10 - Hepatosis dietetica - liver - pig

HD: Liver: There is massive necrosis affecting approximately 40% of the hepatic lobules
characterized by retention of lobular architecture but with variable disruption of hepatocellular
cords, loss of central veins, hepatocellular drop-out, and hemorrhage. Within necrotic lobules,
hepatocytes are individualized, hypereosinophilic, angular and shrunken with karyolytic to pyknotic
nuclei (necrosis) and occasionally have finely granular, basophilic cytoplasm (mineralization).
Multifocally, less affected lobules have small foci of necrosis. Portal areas are moderately expanded
by edema, fibrin and hemorrhage and frequently contain low to moderate numbers of lymphocytes,
plasma cells, neutrophils, macrophages, reactive fibroblasts and fewer eosinophils. Multifocally the
capsule is indented overlying areas of fibrosis and stromal collapse.
Lymph node: Multifocally scattered throughout the sinuses, cortex and medulla there is moderate
amounts of hemorrhage and fibrin. Diffusely there are numerous cells undergoing apoptosis.
Morphologic Diagnosis: 1. Liver: Necrosis, massive, multifocal, with moderate
lymphoplasmacytic, neutrophilic, and histiocytic portal hepatitis, fibrosis, and stromal collapse,
breed not specified, pig, porcine.
2. Lymph node: Draining hemorrhage, acute, multifocal, mild.
Cause: Vitamin E/selenium deficiency
General Discussion:
A disease of young, rapidly growing pigs with inadequate dietary protein, vitamin E and/or
selenium
In nutritionally predisposed pigs, it may be precipitated by stressful conditions
Deficiencies cause multisystemic disease in many species
Vitamin E and selenium act synergistically to prevent oxidative damage to cell membranes;
deficiency of one or both may lead to necrosis of tissues
Pathogenesis:
Vitamin E is absorbed from the intestine, transported in blood within chylomicrons and low density
lipoproteins, stored primarily in liver, muscle, and fat and scavenges free radicals, particularly in
membranes
Selenium is a cofactor in the enzyme glutathione peroxidase (reduces hydroxyl radicals and H2O2)
Liver: Vit E/Selenium def. > unknown stimulus or trigger > generation of free radicals >
degradation of lipoprotein membranes of hepatocyte cytoplasmic organelles > hepatocellular
necrosis
Muscle: Oxidative damage to myocyte membrane > massive influx of Ca++ into the cytosol and
accumulation in mitochondria > decreased energy production > necrosis (white muscle disease)
Heart: Oxidative damage to endothelium > thoracic/pericardial transudate, pulmonary edema, and
myocardial hemorrhage > ischemic necrosis of cardiomyocyte (mulberry heart disease)
Adipose tissue: Excessive peroxidation of fatty acids > free radical tissue damage > neutrophilic,
then granulomatous inflammation (steatitis)
Typical Gross Findings:
Massive hepatic necrosis
Pale streaks on the myocardium, often with intramural and subendocardial hemorrhages and
pulmonary edema
 46

Yellow fat
Typical Light Microscopic Findings:
Liver: Massive coagulative necrosis and stromal collapse; usually not all lobes affected (hepatosis
dietetica)
Muscle: Myocyte degeneration and necrosis, hemorrhage, edema, and usually calcification
(nutritional muscular dystrophy and mulberry heart disease)
Arterioles: Fibrinoid necrosis common in small arterioles in many tissues (mesentery, intestines,
skeletal and cardiac muscle)
Fat: Steatitis (yellow fat disease)
Differential Diagnosis:
Differentials for toxic hepatic necrosis
Gossypol toxicosis: Uniformly distributed submassive hepatocellular necrosis, myocardial
degeneration and necrosis
Xanthium sp. (cocklebur) toxicosis: Similar to gossypol without cardiac lesions
Cresol toxicosis: Centrilobular hepatic necrosis, without cardiac lesions
Iron dextran toxicosis: Suckling pigs with marginal vitamin E/selenium levels; apparently due to
iron-catalyzed lipid peroxidation in hepatocytes and skeletal muscle; cardiac toxicity from increased
potassium released into the circulation
Comparative Pathology:
Sheep: Nutritional muscular dystrophy; infertility (embryonic death); periodontal disease;
unthriftiness; poor wool production; slowed growth
Cattle: Nutritional muscular dystrophy; liver necrosis; retained placenta; chronic low-grade or
subclinical mastitis associated with inadequate selenium
Horses: Skeletal and cardiac myopathy in foals; equine motor neuron disease (EMND) and
associated retinal degeneration; steatitis
Dogs: Cardiac and skeletal myopathy; intestinal lipofuscinosis (“brown dog gut”), actually due to
an accumulation of ceroid pigment in the myocytes of the tunica muscularis; can also see retinal
degeneration and steatitis
Cats, mink, foals, pigs, piscivorous birds: Nutritional panniculitis +/- muscle degeneration due to
accumulation of ceroid (diets high in fish meal or other highly unsaturated fats and a vitamin E
deficiency); in cats, globules of extracellular ceroid in interstitial tissue or ingested by macrophages
and giant cells.
Chickens: Skeletal myopathy (thighs>breasts), encephalomalacia in chicks , encephalomalacia in
chicks ("crazy chick disease"); exudative diathesis; decreased egg production and hatchability,
pancreatic necrosis
Turkeys: Encephalomalacia with hemorrhage (cherry red cerebellum); muscular dystrophy of
gizzard; enlarged hocks
Ducks, non-human primates, rainbow trout: Skeletal myopathy
Rats and mice: Muscular dystrophy; liver necrosis; infertility
Hamsters: Spontaneous Hemorrhagic Necrosis (SHN) of the central nervous system of fetal
hamsters; symmetrical, subependymal vascular degeneration with edema and hemorrhage into
adjacent neuropil
Guinea pig: Nutritional muscular dystrophy; testicular degeneration
Humans: Dietary deficiencies are rare; most cases involve decreased vitamin E absorption:
manifestations include spinocerebellar degeneration, skeletal muscle changes, and hemolytic
anemia in infants

D-M11 - Hepatic lipidosis - liver - donkey

HD: Liver: Diffusely the hepatocytes are markedly enlarged by a discrete clear cytoplasmic vacuole
(lipid) that flattens and displaces the nucleus to the periphery (vacuolar degeneration, lipid type).
Multifocally, vacuoles of adjacent hepatocytes coalesce. There are few hepatocytes that are
shrunken, hypereosinophilic and pyknotic (necrosis). Diffusely sinusoids are collapsed. Portal areas
 47

contain few lymphocytes and plasma cells, admixed with rare neutrophils. The capsule is mildly
thickened by fibrous connective tissue, and the liver has a rounded contour.
Morphologic Diagnosis: Liver, hepatocytes: Vacuolar change, lipid-type, diffuse, severe, breed
unspecified, donkey (Equus asinus), equine.
Condition Synonyms: Hyperlipemia syndrome, equine hyperlipidemia
General Discussion:
Hepatic lipidosis is the abnormal accumulation of triglycerides within hepatocytes and most often
affects ponies (Shetland ponies are predisposed), donkeys, miniature horses, cattle, cats and sheep
that are pregnant, obese or lactating, and is a characteristic finding in rabbits with gastric
trichobezoar
Pathogenesis:
Hepatic lipidosis occurs when triglycerides, neutral fats and cholesterol accumulate faster than
metabolic degradation or release as lipoproteins; these excess lipids are deposited as intra
hepatocellular droplets.
VLDL is the primary lipoprotein in the blood of hyperlipemic ponies.
Hepatic lipidosis can occur as the result of one of five mechanisms:
Excessive delivery of free fatty acids either from the gut or from adipose tissue
Increased mobilization of fat is the most common cause of lipidosis in domestic animals
Decreased beta-oxidation of fatty acids to ketones and other substances because the mitochondrial
injury (toxins, hypoxia)
Impaired synthesis of apoprotein (CCL4 toxicity, aflatoxicosis)
Impaired combination of triglycerides and protein from lipoprotein (uncommon)
Impaired secretion of lipoproteins from the hepatocyte (uncommon)
Insulin resistance is a proposed underlying cause in ponies. Increased steroid hormones interfere
with insulin function; stress (increased cortisol) and increased progesterone during pregnancy may
exacerbate the problem. Insulin resistance results in increased lipolysis and free fatty acids, leading
to hypertriglyceridemia.
Special stains: Oil red-O, Sudan IV
Differential Diagnosis:
Hyperlipidemia and fatty liver may occur with endocrinopathies: diabetes mellitus, hypothyroidism,
hyperadrenocorticism.
Hepatotoxins usually cause necrosis in addition to fatty change.
Comparative Pathology:
Feline fatty liver syndrome is an idiopathic syndrome of hepatic lipidosis that typically affects
obese and anorectic cats. These cats develop hepatic failure, icterus and hepatic encephalopathy.
White liver disease of sheep and goats is caused by dietary deficiencies of Vitamin B12 and cobalt.
Hepatic lipidosis and ceroid deposition start in the centrilobular areas. Anemia and icterus are
common.
Ketosis results from impaired carbohydrate and volatile fatty acid metabolism. In pregnant and
lactating ruminants, the continual demand for glucose and amino acids may result in ketosis when
fat metabolism becomes excessive.
Bovine fatty liver syndrome (physiologic fatty liver/fat cow syndrome) occurs most often in obese,
periparturient dairy cattle and rarely beef cattle and is precipitated by an event that causes anorexia.
Pregnant bison: Hepatic lipidosis is similar to beef cattle.
Camelids: Hepatic lipidosis may be induced by anorexia, weight loss or experimentally by severe
feed restriction and an increased metabolic demand.
Watanabe rabbit: single-gene defect in the gene encoding for low-density lipoprotein receptor;
develop hypercholesterolemia on a low-cholesterol diet
Fatal fasting syndrome of obese macaques: Usually older, obese females that are stressed and
anorectic. Hepatic lipidosis is accompanied by renal tubular fatty change, subcutaneous and
intracavitary fat necrosis and pancreatic acinar degeneration
Pregnancy toxemia: Periparturient disease in ruminants, camelids, rodents, ferrets and mink; due to
 48

negative energy balance and mobilization of fatty acids. Hepatic pathways for oxidation of fatty
acids and VLDL formation are overwhelmed, and fat accumulates in the liver.
Fatty liver is normal in neonates of species in which the milk is rich in fat.
Hepatic lipidosis is a characteristic finding in rabbits with gastric trichobezoar (hairballs)

D-M12 - Canine necrotizing sialometaplasia - salivary gland - dog

HD: Salivary gland, mandibular: Affecting 50% of the normal tissue architecture, there is a well-
demarcated area of coagulative necrosis (infarct). The interlobular interstitium and capsule of the
affected area are minimally to greatly expanded by degenerate neutrophils, macrophages, and
multifocal hemorrhage. The capsule is also markedly thickened by granulation tissue characterized
by increase in fibrous connective tissue and varisize blood vessels. Within the interstitium and
peripherally, are increased numbers of ducts lined by multiple layers of epithelial cells (regenerative
hyperplasia) that are often vacuolated, or have prominent intercellular bridges and are luminally
attenuated and elongate (squamous metaplasia).
Morphologic Diagnosis: Salivary gland, mandibular: Coagulative necrosis (infarct), focally
extensive, with ductular hyperplasia and squamous metaplasia, breed unspecified, canine.
Condition Synonyms: Salivary gland infarction
Differential Diagnosis:
Grossly enlarged and hemorrhagic salivary gland:
Salivary neoplasia (adenocarcinoma, carcinoma, adenomas)
Sialoadenitis, sialocele, salivary mucocele

D-M13 - Congenital portosystemic shunt (PSS) - liver - dog

History: The animal presented for acute onset of ataxia, disorientation, vomiting, drooling,
collapse, and "blindness" one week earlier. A similar episode occurred again 1 week later.
HD: Liver: There is diffuse lobular atrophy characterized by small lobules, small hepatocytes, and
increased proximity of hypercellular portal triads. Central veins are often indistinct. Diffusely portal
triads contain multiple arterioles, bile ducts and mildly dilated lymphatics, however, portal veins are
inapparent. There is rare individualization and rounding of brightly eosinophilic hepatocytes that
contain karyorrhectic debris (individual cell necrosis). There are multifocal small aggregates of
viable and degenerate neutrophils and macrophages, with few lymphocytes, and nuclear and cellular
debris. Multifocally there is mild extramedullary hematopoiesis. Peripherally sinusoids are mildly
congested.
Morphologic Diagnosis: 1. Liver: Venous hypoplasia, portal and central, diffuse, severe, with
lobular atrophy, lymphangiectasia and hepatocellular hypoplasia, Golden Retriever, canine.
2. Liver: Hepatitis, neutrophilic and histiocytic, multifocal, mild.
General Discussion:
Congenital portosystemic shunts occur most commonly in purebred female dogs and mixed breed
male cats. Breeds at increased risk include Irish Wolfhound, Cairn Terriers, Miniature Schnauzers,
Yorkshire Terriers, Maltese, Australian Cattle Dogs, and Old English Sheepdogs, Golden and
Labrador Retrievers, and Persian and Himalayan cats.
Types of congenital shunts:
Intrahepatic: Failure of closure of the ductus venosus (large breeds)
Extrahepatic: Portal vein shunts to the caudal vena cava or azygous vein (small breed dogs and cats)
Arterioportal shunts: An uncommon condition in dogs only resulting from connections between the
hepatic artery and portal vein > portal hypertension > acquired portocaval shunts and ascites > liver
atrophy, loss of portal veins, proliferation of hepatic arterioles and neurologic signs
Congenital hypoplasia of the portal vein > portosystemic shunt (dogs)
Acquired portosystemic shunts are caused by prolonged portal hypertension often secondary to
chronic liver disease or chronic passive congestion. There are multiple extrahepatic shunts between
the portal vein and caudal vena cava. Ascites is present.
 49

Pathogenesis:
Abnormal vascular channels bypass the liver and shunt blood from the portal venous system
directly into the systemic circulation.
Hepatic hypoplasia due to lack of primary portal perfusion; hepatotrophic factors such as insulin,
glucagon, and amino acids bypass the liver and are diluted by the total blood volume; the
concentration in blood that reaches the liver is ineffective.
Elevated bile acids: Portosystemic shunts bypass the liver and deliver bile acids directly to the
systemic circulation. Bile acid removal by hepatocytes from the systemic circulation is less efficient
than uptake from the portal circulation.
Hyperammonemia: Ammonia is produced in the gastrointestinal tract by enteric microflora and is
transported to the liver via the portal circulation for conversion into urea. Shunting of blood from
the portal to the systemic circulation results in elevated blood ammonia levels.
Because of the decreased hepatic mass, there are fewer hepatocytes available to remove bile acids
or convert ammonia to urea.
Typical Clinical Findings:
Stunted growth, failure to gain weight
Hepatic encephalopathy: Depression, incoordination, coma and seizures
+/- polydipsia/polyuria (dogs)
Elevated postprandial serum bile acids, hypoalbuminemia, hypoglobulinemia, hypoglycemia,
decreased BUN, hypocholesterolemia, hyperammonemia with formation of ammonium biurate
crystals in alkaline urine
+/- leptocytes on cytology
Typical Gross Findings:
Microhepatica; usually with a single relatively large anomalous vessel
+/- renal, cystic or urethral ammonium biurate calculi
Typical Light Microscopic Findings:
Congenital shunts:
Lobular atrophy, small hepatocytes,
Portal areas: Reduplication of arterioles and small to absent portal veins
Acquired shunts:
Chronic inflammation, nodular regeneration, tortuous vessels, fibrosis
Differential Diagnosis:
For histologic features of congenital PSS:
Hepatic microvascular dysplasia (HMD)/Microvascular portal dysplasia (Congenital vascular
anomaly of dogs and cats): Microscopic, intrahepatic shunting of blood. Present with congenital
PSS or alone. Clinically similar to PSS but milder. Transcolonic scintigraphy needed to
differentiate. Cause unknown.
Acquired PSS. Arises from chronic liver disease secondary to chronic passive congestion, or
primary liver disease (e.g., hepatitis, therefore often has inflammation), leading to portal
hypertension. Ascites always present.
Comparative Pathology:
Shunts have been reported in cats, cattle and horses.

D-M14 - Gastric heteropy - jejunum - dog

HD: Jejunum: Multifocally replacing intestinal mucosa are foci of gastric mucosa, up to 1.5 mm
wide, which are fairly distinctly demarcated from adjacent intestinal mucosa. The gastric mucosa is
composed of tightly packed glandular structures, the lumina of which are lined by pyramidal to
cuboidal cells with basally positioned nuclei and apical, lightly eosinophilic, foamy cytoplasm
(Chief cells). Also lining glands, usually more peripherally, are round to polygonal cells with round
nuclei and abundant eosinophilic, granular cytoplasm (parietal cells). Villi overlying and
immediately adjacent to gastric mucosa are blunted and fused, and the lamina propria of these villi
are moderately expanded by increased numbers of mostly lymphocytes and macrophages with
 50

fewer neutrophils and plasma cells. Markedly increased numbers of goblet cells line the villi and
crypts in adjacent intestine.
Morphologic Diagnosis: Jejunum: Heterotopic fundic gastric mucosa, segmental, with goblet cell
hyperplasia, Beagle, canine.
Condition Synonyms: choristoma
General Discussion:
Extremely rare in animals but has been noted in the dog and cat
Choristoma is defined as normal mature tissue in an ectopic location
Differential Diagnosis:
Intestinal Masses (gross):
Intestinal neoplasms
Hyperplastic polyps
Inflammation (Pythiosis)

D-M15 - Acute pancreatic necrosis - pancreas - dog

Histopathologic Description: 1. Pancreas: Expanding the interlobular septa and capsule up to 10
times normal, replacing 30% of the pancreatic parenchyma, and extending into peripancreatic
adipose tissue are multifocal to coalescing areas of lytic necrosis characterized by loss of tissue
architecture and replacement by abundant eosinophilic cellular and karyorrhectic debris admixed
with moderate numbers of degenerate neutrophils, fewer macrophages, abundant fibrin,
hemorrhage, and increased clear space and mildly ectatic lymphatics (edema). At the interface of
the less affected lobules and areas of necrosis, acinar cells are swollen with pale eosinophilic,
vacuolated cytoplasm (degenerate) or are shrunken with pyknotic nuclei (necrotic). There is
coagulative necrosis of peripancreatic fat characterized by retention of tissue architecture, loss of
nuclei, and loss of cellular detail of the peripheral rim of cytoplasm. Occasionally, necrotic
adipocytes contain intracytoplasmic eosinophilic or basophilic wispy fibrillar material and acicular
clefts (cholesterol).
2. Lymph node: Within the subcapsular and medullary sinuses, there are high numbers of
erythrocytes (draining hemorrhage) and macrophages, often with light brown granular to globular
intracytoplasmic pigment (hemosiderin).
Morphologic Diagnosis: 1. Pancreas: Pancreatitis, necrosuppurative, acute, multifocal to
coalescing, severe, with hemorrhage and peripancreatic fat necrosis, breed not specified, canine.
2. Lymph node: Draining hemorrhage, diffuse, moderate, with sinus histiocytosis and
hemosiderosis.
General Discussion:
Important disease of dogs characterized by secretion of activated pancreatic enzymes that lead to
autodigestion of the pancreas and peripancreatic adipose tissue
May be acute fatal disease; repeated acute episodes lead to chronic fibrosing pancreatitis in some
survivors
Also known as acute pancreatitis
Pathogenesis:
The cause is unknown. Three proposed mechanisms: 1) obstruction of the ducts (e.g. parasites,
pancreatic calculi), 2) direct injury to acinar cells (e.g toxins [e.g. zinc, Cassia occidentalis, T-2],
trauma), 3) disturbances of enzyme trafficking within the cytoplasm of acinar cells (e.g.
corticosteroids).
Initiating event (high fat meal, abdominal trauma, toxin, corticosteroids) > pancreas releases
enzymes into pancreatic parenchyma > trypsinogen activated to trypsin which activates proelastase
and prophospholipase > digestion of pancreatic tissue and peripancreatic adipose tissue > release of
inflammatory mediators > inflammatory cells > amplification of the process. Trypsin also activates
prekallikrein causing involvement of the kinin system, complement, and clotting cascades which
leads to thrombosis, hemorrhage, and inflammatory cells.
Consumption of plasma protease inhibitors > free proteases > activation of kinin, coagulation,
 51

fibrinolytic, and complement cascade systems > DIC and shock

Less severe disease may result in repeated acute episodes or a chronic smoldering process >
ultimately destroys the exocrine and endocrine pancreas > pancreatic insufficiency and diabetes
mellitus
Typical Light Microscopic Findings:
Acute lesion: Coagulation necrosis at the periphery of affected pancreatic lobules with numerous
degenerating neutrophils, fibrinous exudate, edema, necrosis and inflammation of peripancreatic
adipose tissue; centrilobular tissue intact
Necrotic adipocytes with acidophilic, opaque, amorphous, or lacy intracytoplasmic substance, or
basophilic fibrillar or granular mineralized substance
Chronic lesion: Fibrosis and atrophy of remaining parenchymal remnants with random foci of
inflammation and necrosis
Liver may be involved.
Differential Diagnosis:
Gross – nodular exocrine hyperplasia, zinc toxicosis
Histologically – zinc toxicosis
Zinc toxicosis is a cause of pancreatic necrosis in dogs, calves, sheep, and waterfowl
Comparative Pathology:
Causes of pancreatitis:
Horses: Migrating strongyles
Calves, sheep, dogs: Zinc toxicosis, pancreatic calculi
Pigs: Cassia occidentalis (shrub in Southeastern US) intoxication; T-2 (trichothecene mycotoxin)
toxicosis
New World monkeys: Trichospirura leptostoma found in pancreatic ducts
Cats (types of pancreatitis):
Acute necrotizing form similar to dogs, with or without fibrosis
Suppurative pancreatitis involving inflammation rather than necrosis

D-M16 - Lymphangiectasia - small intestine - dog

History: This animal had a protein losing enteropathy. The small intestine and attached mesentery
were grossly thickened.
HD: Small intestine (multiple sections): Multifocally, affecting 30% of villi, villi are blunt or club-
shaped and are expanded by dilated lacteals up to 400 microns in diameter. Lymphatics in the
submucosa, tunica muscularis, and serosa are also moderately dilated. Lacteals and lymphatics
often contain abundant fibrin admixed with few erythrocytes. Randomly, obscuring and replacing
lymphatics in the tunica muscularis, serosa, and mesentery are varisized, up to 0.5 mm diameter
foci composed of many lipid-laden macrophages, fewer lymphocytes, plasma cells, and occasional
foreign-body type multinucleated giant cells that surround amorphous pale eosinophilic to clear
material (lipogranulomas). Multifocally, the tunica muscularis, serosa, and mesentery are expanded
by moderate numbers of lymphocytes and plasma cells and increased fibrous connective tissue
(fibrosis).
Morphologic Diagnosis: Small intestine: Lymphangiectasia, multifocal, moderate, with
granulomatous lymphangitis, Shetland Sheepdog, canine.
General Discussion:
Intestinal lymphangiectasia (IL) is the most commonly reported cause of malabsorption/protein-
losing enteropathy in the dog.
In the Lundehund and Soft Coated Wheaten Terrier, it is part of an inflammatory bowel syndrome.
Typical Light Microscopic Findings:
There is dilation of the lacteals and often lymphatics of the submucosa, muscularis, and mesentery;
lipid-laden macrophages may be present.
Blunt villi, with some hypertrophy of crypts
Possible mild increase in numbers of lymphocytes, plasma cells and eosinophils within the lamina
 52

propria
Lipogranulomas: collar of lipid-laden macrophages that surround centrally located amorphous lipid
material +/- cholesterol clefts
Comparative Pathology:
Secondary or acquired intestinal lymphangiectasia occurs in many animals such as nonhuman
primates, cats, cattle, swine, etc.
Soft Coated Wheaten Terriers have a familial predisposition for protein-losing nephropathy, protein-
losing enteropathy, or both. Intestinal lesions include inflammatory bowel disease,
lymphangiectasia, and lipogranulomatous lymphangitis; renal lesions include chronic
glomerulonephritis/glomerulosclerosis.

D-M17 - Canine chronic hepatitis (CCH) - liver - dog

History: This dog presented with anorexia, icterus and elevated ALT, ALKP and total bilirubin.
HD: Liver: Diffusely there is marked expansion and bridging of portal areas by large numbers of
neutrophils, lymphocytes, and macrophages, with fewer plasma cells and fibroblasts. Multifocally,
inflammatory cells disrupt the limiting plate and extend into the adjacent hepatic parenchyma
separating, surrounding, and replacing hepatocytes. Some of the hepatocytes in these areas are
swollen, with loss of cellular detail, and cytoplasm that is either vacuolated or contains eosinophilic
granular material and karyolytic, pyknotic, or karyorrhectic nuclei (degeneration and necrosis).
There are increased numbers of small bile ducts (biliary hyperplasia). The capsule is irregular with
previously described inflammatory cells replacing subcapsular hepatocytes. There are dilated
lymphatics (edema), and scattered macrophages and hepatocytes that contain golden brown
cytoplasmic globules (hemosiderin or bile). Focally compressing a large caliber vessel, there are
moderate numbers of fibroblasts admixed with collagen (fibrosis).
Liver (Rhodanine): Diffusely, macrophages and hepatocytes contain abundant red globular pigment
(copper).
Morphologic Diagnosis: Liver: Hepatitis, portal and periportal, histiocytic, lymphoplasmacytic
and neutrophilic, chronic, diffuse, moderate, with biliary hyperplasia, hepatic degeneration and
necrosis, and abundant hepatocellular and intrahistiocytic copper, Doberman Pinscher, canine.
Condition Synonyms: Canine chronic-active hepatitis, chronic progressive hepatitis, lobular
dissecting hepatitis
General Discussion:
CCH is a long term (4-6 months), persistent inflammation of the liver.
The cause is often unknown
The term "chronic active hepatitis" was previously used as a descriptor for this condition but
developed into a name for the condition. Recommendations have been made to discontinue the use
as a name of the condition because it is a descriptive term and is the name for the human condition
involving the Hepatitis B virus, which does not always correlate with the condition in dogs.
Certain dog breeds have a hereditary or familial predisposition for excessive accumulation of
copper in the liver that may cause the condition. Some authors suggest the elevated copper may be
the result of the CCH and not the cause of the condition.
Clinically normal dogs can have a wide range of hepatic copper concentrations and the majority of
dogs with chronic hepatitis do not have increased concentrations of hepatic copper.
Differential Diagnosis:
Causes of chronic hepatitis in dogs:
Unknown
Infectious agents
Infectious canine hepatitis virus (Canine adenovirus type 1) – basophilic intranuclear inclusion
bodies may be seen in the first ten days of infection
Leptospira infections – spiral bacteria, seen with Warthin-Starry stains
Canine acidophil cell hepatitis virus – acidophilic periportal hepatocytes
Copper accumulation
 53

Hereditary copper storage disease in Bedlington Terriers – mutation of the MURR1 gene that is
associated with copper excretion in hepatocytes.
Copper associated hepatitis (mechanisms unknown) – Skye Terrier, Dalmation, West Highland
White Terrier, Doberman Pinscher, Cocker Spaniel, and Labrador Retriever
Drug-associated - anticonvulsants, diethylcarbamazine/oxibendazole combination
Alpha-1-antitrypsin anomaly – English Cocker Spaniel
Autoimmunity
Comparative Pathology:
Feline – Copper-associated chronic hepatitis and cirrhosis (rare)

D-N01A - Fibromatous epulis - gingiva - dog

HD: Gingiva: Expanding the lamina propria, elevating the overlying hyperplastic mucosa, and
extending to cut borders is an unencapsulated neoplasm composed of loosely arranged streams of
evenly spaced spindle to stellate cells separated by an abundant collagen matrix within a well
vascularized stroma. Neoplastic cells have indistinct borders with scant to moderate amounts of
eosinophilic fibrillar cytoplasm. Nuclei are irregularly oval to elongate with moderately stippled
chromatin and an indistinct nucleolus. The mitotic rate is less than 1 per 10 high power fields.
Focally, neoplastic cells are within lacunae and are widely separated by a deeply eosinophilic
woven matrix (osteoid/dental hard substance). There are multiple small subepithelial and
perivascular accumulations of plasma cells, fewer lymphocytes and occasional neutrophils. The
overlying epithelium is moderately hyperplastic, forming anastomosing rete ridges up to 2 mm in
length. There is moderate acanthosis and spongiosis, and multifocally epithelial cells are markedly
vacuolated (intracellular edema). There is focal erosion. Multifocally within the mucosa, there is
neutrophilic exocytosis.
Morphologic Diagnosis: Gingiva: Fibromatous epulis of periodontal ligament origin, Boxer,
canine.
General Discussion:
Epulis is a nonspecific and clinical term for an inflammatory, hyperplastic, or neoplastic mass of the
gingiva that is common in dogs and infrequent in cats.
Nonneoplastic epulides include pyogenic granuloma, giant-cell epulis, and fibrous hyperplasia
(fibrous epulis).
Neoplastic epulides include fibromatous epulis of periodontal ligament origin, canine
acanthomatous ameloblastoma, and calcifying epithelial odontogenic tumor.
Fibromatous epulis of periodontal ligament origin (fibromatous epulis) is a tumor composed
primarily of periodontal ligament-type stroma.
Common, benign
Local excision curative
Canine acanthomatous ameloblastoma (acanthomatous epulis) is a tumor of odontogenic epithelium
without odontogenic mesenchyme.
Aggressively infiltrative, no metastatic potential
With surgical excision, clean margins mandatory
Recurrence common; recurrent tumors more aggressive and anaplastic, and can often recur as
squamous cell carcinoma
Typical Gross Findings:
Fibromatous epulis of periodontal ligament origin: Hard, pink, smooth, often lobulated mass that
are always adjacent to teeth. The mass may displace teeth, but it does not invade bone.
Canine acanthomatous ameloblastoma: Papillary to sessile mass most commonly found in the
mandibular incisor-premolar region and often associated with local invasion of alveolar bone.
Typical Light Microscopic Findings:
Fibromatous epulis of periodontal ligament origin: This is a periodontal ligament-type stromal
tumor consisting of regularly positioned stellate mesenchymal cells, smooth fibrillar collagen
matrix, and regularly positioned dilated and usually empty blood vessels. Localized deposition of
 54

collagen matrix is often seen and can have characteristics of osteoid/bone, cementum, or dentin.
Cords of odontogenic epithelium are frequently seen and are considered a secondary feature.
Characteristic features of periodontal ligament stroma:
Dense fibrillar collagen
Regularly positioned stellate mesenchymal cells
Regularly positioned, widely dilated, and usually empty blood vessels
Canine acanthomatous ameloblastoma: Sheets and cords of nonkeratinizing odontogenic epithelium
with prominent intercellular bridges and distinguishable peripheral palisading of epithelial cells that
have antibasilar nuclei; often infiltrates underlying bone but no evidence of distant metastasis; cyst
formation is a common feature
Neoplastic epithelium of odontogenic origin has the following characteristics:
Peripheral palisading of epithelial cells with antibasilar nuclei
Nucleus of palisading cells located at apical pole (antibasal)
Basilar epithelial cytoplasmic clearing
Nonbasilar epithelial cells (acanthocytes) have long intercellular bridges
Differential Diagnosis:
For oral/gingival mass:
Fibrous epulis (fibrous hyperplasia): This occurs secondary to localized chronic inflammation that
produces a mass of mature fibrous tissue often with a band of plasma cells adjacent to the overlying
hyperplastic epithelium. It is common in dogs and usually does not recur following surgical
excision. Diffuse gingival hypertrophy is familial in boxer dogs.
Pyogenic granuloma: Bright red or blue mass; vascular granulation tissue covered by gingival
epithelium; rare; usually does not recur
Giant cell epulis: Smooth and sessile or pedunculated; dense, well-vascularized stroma with
hemosiderin and numerous multinucleated giant cells with overlying hyperplastic epithelium;
associated with the site of tooth extraction; rare with little chance of recurrence
Calcifying epithelial odontogenic tumor: Unencapsulated, strands, nests, or masses of epithelium,
often mineralized, with trabeculae of osteoid/dentinoid and deposits of amyloid; rare; recurrence not
reported
Squamous cell carcinoma (SCC): In dogs it usually involves the gingiva or tonsils and locally
invades bone and metastasizes to regional lymph nodes (second most common oral tumor). SCC is
the most common oral malignancy in cats, and is usually located on the frenulum of the tongue.
Melanoma: It is the most common oral tumor of dogs; usually located on the gingiva, gums, buccal
mucosa, lips, and palate; up to 90% metastasize to regional lymph nodes or lungs
Fibrosarcoma: Occur on the gums of the upper molars and anterior half of the mandible; more
common in younger dogs; about 35% metastasize to regional lymph nodes or lungs; second most
common oral malignant neoplasm in cats
Comparative Pathology:
Cats: Epulides occur less frequently in cats as compared to dogs. However, with multiple epulides,
recurrence following excision is more common in cats than in dogs.
Human: Fibromatous epulis in dogs is similar to the rare peripheral odontogenic fibroma in humans.
Canine acanthomatous ameloblastoma in dogs resembles peripheral ameloblastoma in form but
intraosseous ameloblastoma in biologic behavior.

D-N01B - Acanthomatous ameloblastoma - gingiva - dog

HD: Gingiva: Expanding the lamina propria and multifocally extending from a hyperplastic
mucosa, is an unencapsulated, infiltrative, moderately cellular neoplasm composed of anastomosing
cords, ribbons, and trabeculae of well-differentiated squamous epithelial cells separated by an
abundant dense and well vascularized stroma. Neoplastic cells are polygonal with distinct cell
borders, moderate amounts of eosinophilic granular cytoplasm, and irregularly round to oval nuclei
that have finely stippled chromatin and 1-2 magenta nucleoli. The mitotic rate is less than 1 per 10
high power fields. Palisading neoplastic cells along the edge of trabeculae are cuboidal to columnar
 55

with antibasilar nuclei and frequently, basilar cytoplasmic clearing. There is prominent intercellular
bridging between nonbasilar neoplastic cells. Multifocally infiltrating the lamina propria are large
numbers of macrophages, fewer lymphocytes, plasma cells and neutrophils. Diffusely the
epithelium is hyperplastic with prominent rete ridge formation, acanthosis and spongiosis.
Multifocally within the mucosa, there is neutrophilic exocytosis. Focally there is an ulcer with
replacement by eosinophilic cellular and karyorrhectic debris, abundant viable and degenerate
neutrophils, fibrin, hemorrhage, and reactive fibroblasts.
Morphologic Diagnosis: Gingiva: Canine acanthomatous ameloblastoma, breed unspecified,
canine.

D-N02 - Ameloblastic odontoma - gingiva - rhesus monkey

HD: Gingiva; alveolar bone; tooth: Expanding the lamina propria, elevating the overlying
moderately hyperplastic epithelium and a tooth, and disrupting alveolar bone, is an unencapsulated,
poorly circumscribed, infiltrative neoplasm composed of islands and lobules of neoplastic cells that
incompletely recapitulate dental elements. The islands are composed of palisades of tall columnar
cells (ameloblasts) on a fine fibrovascular stroma that often surround a central focus of loosely
arranged small spindle to stellate cells (stellate reticulum) on a pale myxomatous matrix.
Occasionally, islands have central cystic spaces up to 3 mm in diameter. The neoplastic ameloblasts
have distinct cell borders, moderate amounts of pale eosinophilic fibrillar cytoplasm, a pale, oval to
elongate, basillar nucleus, with finely stippled chromatin, and 1-2 distinct nucleoli. The neoplastic
stellate cells have distinct cell borders, scant eosinophilic fibrillar cytoplasm, and an oval to
elongate nucleus, with finely stippled chromatin and a variably distinct nucleolus. Multifocally,
adjacent to the ameloblasts are columnar cells (odontoblasts), which often blend into the underlying
mesenchymal tissue. The odontoblasts have distinct cell borders, small amounts of eosinophilic
granular cytoplasm, and an irregularly round to oval nucleus, with finely stippled chromatin and an
indistinct nucleolus. Mitoses are rare in all cell populations. There are multifocal aggregates of
eosinophilic homogenous to fibrillar material (dentin) often with prominent dentin tubules and
basophilic, amorphous, homogenous to lamellated material (mineral or enamel), occasionally lined
by neoplastic cells. The overlying gingival epithelium is expanded to 20 cell layers thick, with
prominent, often anastomosing rete ridges (gingival hyperplasia).
Morphologic Diagnosis: Gingiva; alveolar bone; tooth: Ameloblastic odontoma, rhesus monkey
(Macaca mulatta), non-human primate.
Condition Synonyms: Odontoameloblastoma; Ameloblastic fibro-odontoma
General Discussion:
Odontogenic tumors, including ameloblastic odontomas, are uncommon in animals.
Most tumors of dental tissues are benign, but they can be locally aggressive and displace/destroy
bone and teeth.
The term “odontoma” specifies induction of both dentin and enamel.
Classification:
Epithelial (not inductive):
Ameloblastoma/Keratinizing Ameloblastoma
Calcifying epithelial odontogenic tumor/Amyloid-Producing Odontogenic Tumor
Acanthomatous Epulis/Canine Acanthomatous Ameloblastoma
Mixed Epithelial and Mesenchymal (Inductive):
Ameloblastic odontoma/Ameloblastic Fibro-odontoma
Ameloblastic fibroma
Feline Inductive Odontogenic Tumor/Inductive Fibroameloblastoma
Complex odontoma
Compound odontoma
Tooth Development (Brachydont):
Develops from two embryonic tissues: Dental laminae that forms enamel cap and embryonic
mesenchyme that forms dentine, cementum, and pulp
 56

Odontogenic induction: Ameloblastic epithelium induces differentiation of dental papilla

mesenchyme into odontoblasts > odontoblasts form dentin > dentin induces ameloblasts >
ameloblasts form enamel. Ameloblasts disintegrate once tooth erupts; enamel is incapable of repair.
Odontoblasts remain viable for the life of the tooth.
In hypsodont (continuously erupting) teeth, ameloblasts continue producing enamel after eruption.
Pathogenesis:
Odontogenic tumors originate from dental epithelium.
Dental epithelium can induce maturation of undifferentiated mesenchyme of the dental papilla.
Differences between odontogenic tumors depend on the degree or extent of interaction between the
epithelium and mesenchyme.
Typical Gross Findings:
Firm, hard swelling on posterior jaw; more common in the mandible
May have a hard white material resembling teeth with the mass
May have multiloculated cysts on cut section
Typical Light Microscopic Findings:
Ameloblastic odontomas are the least differentiated of the odontomas.
Resembles ameloblastic fibroma, except enamel and dentin are present
Cords of epithelium resembling the enamel organ associated with spindle cells resembling dental
pulp
Structures may appear like normal or atypical tooth germs, with or without calcified dental tissue.
Differential Diagnosis:
Ameloblastoma (Adamantinoma):
No enamel, dentin, or cementum
Usually intraosseous, more often in mandible
Islands and irregular anastomosing cords of odontogenic epithelium with peripheral palisades of
polarized cuboidal to columnar cells (resembling inner enamel epithelium) enclosing stellate
reticulum
Basal lamina separates stellate reticulum from fibrous connective tissue.
May have keratinization or cysts
Stromal osteoid and bone may develop.
Acanthomatous form has broad sheets of epithelium with central acantholytic formation.
Calcifying epithelial odontogenic tumor:
Usually extraosseous
Interconnected cords and lobules of pleomorphic epithelial cells separated by a moderate
fibrovascular stroma
No basement membrane between epithelium and stroma
Amyloid may be present in the epithelium or stroma and is occasionally mineralized in concentric
rings (Liesegang rings).
Stellate reticulum and multinucleate cells may be present.
Ameloblastic fibroma:
No enamel, dentin, or cementum
Often in bone or soft tissue of maxilla
Similar to ameloblastoma, except a primitive mesenchymal stroma rather than mature fibrous
connective tissue
Both components are neoplastic.
Basal lamina between epithelium and mesenchyme
Complex odontoma:
All dental tissues are present, but in disorganized patterns.
Dentin is prominent.
Usually in maxilla
Compound odontoma:
Most differentiated of the odontomas
 57

Normal or near normal denticles containing dentin, pulp, and enamel

Little epithelial tissue
Both complex and compound odontomas are often referred to as hamartomas.
Comparative Pathology:
Ameloblastoma: More common in dogs and cattle than cats and horses; differentiate from
fibromatous epulis
Calcifying epithelial odontogenic tumor: Dogs, cats, and man
Ameloblastic fibroma: Rare in calves, occurs more often in young cats (feline inductive
odontogenic tumor)
Compound odontoma: Young dogs, adult horses, rodents, fish
Complex odontoma: Dogs, cows, non-human primates, and rodents (incisors)
Rats commonly present with odontogenic (dental) dysplasia secondary to trauma and/or fracture of
teeth; ameloblastomas, ameloblastic odontomas, and odontomas also occur.
Dentigerous cysts: Young horses; often near ear; an epithelium-lined cyst forming around tooth
remnants
Transgenic TG.AC (v-Ha-ras) mice have a high incidence of odontogenic tumors

D-N03 - Hepatocellular carcinoma - liver - woodchuck

HD: Liver: Effacing 60-70% of normal tissue architecture is an expansile, unencapsulated,
multilobulated neoplasm composed of cords, trabeculae (5-10 cell layers thick), and occasional
acini supported by a fine fibrovascular stroma. Neoplastic cells are polygonal, have variably distinct
cell borders, abundant eosinophilic granular to vacuolated cytoplasm and a round vesiculate nucleus
with one to two prominent magenta nucleoli. There is moderate anisocytosis, anisokaryosis and
multifocal cytomegalic cells that occasionally contain multiple nuclei. The mitotic rate averages 1
per 10HPF. Multifocally, there are areas of necrosis and cystic spaces filled with amorphous
eosinophilic material and hemorrhage. The adjacent compressed hepatic parenchyma contains
moderate to high numbers of portal and periportal lymphocytes, plasma cells and neutrophils that
bridge portal areas. There are numerous small bile ducts (hyperplasia) and numerous oval cells
(hyperplasia). Diffusely, hepatocytes contain microvacuolated, lacy cytoplasm (vacuolar change,
glycogen type). There is diffuse moderate congestion. Multifocally there are up to 2mm areas of
loss of differential staining with retention of hepatic architecture (coagulative necrosis).
Morphologic Diagnosis: 1. Liver: Hepatocellular carcinoma, woodchuck (Marmota monax),
rodent.
2. Liver: Hepatitis, portal, lymphoplasmacytic and neutrophilic, chronic, diffuse, moderate, with
biliary and oval cell hyperplasia, bridging fibrosis, and necrosis.
Etiologic Diagnosis: Hepadnaviral hepatitis and hepatocellular carcinoma.
Cause: Woodchuck hepadnovirus (Woodchuck hepatitis virus)
General Discussion:
Family Hepadnaviridae: DNA virus
Genus Orthohepadnavirus: Affects mammals
Genus Avihepadnavirus: Affects birds
Causes hepatitis in wild American woodchucks; strongly associated with the development of
hepatocellular carcinoma
Hepadnaviruses also cause hepatitis and increased incidence of hepatocellular carcinoma in other
species, including man and chimpanzees (human hepatitis B virus).
The woodchuck is a valuable animal model for studying the pathogenesis of viral hepatitis and viral
hepatocarcinogenicity.
Classifications of hepatocellular carcinoma
Trabecular
Most common form
More differentiated (closely resembles normal liver
Thickened trabeculae are frequent feature
 58

Adenoid
Crude acini formed by neoplastic hepatocytes
Neoplastic hepatocytes have no apparent pattern
Solid
Poorly differentiated and pleomorphic
Differential Diagnosis:
Hyperplastic and neoplastic lesions of hepatocyte origin in domestic animals:
Nodular hyperplasia: Middle-aged to old dogs, rare in swine; usually multiple, clearly
circumscribed, often fatty and pale with normal cords (1-2 cells thick) and recognizable portal areas
Regenerative nodules: Usually found in damaged, fibrotic livers, process occurs with significant
fibrosis and disruption of normal parenchyma
Hepatocellular adenoma: Trabecular, acinar, or solid patterns; clearly demarcated; sometimes
unencapsulated; usually single; loss of normal lobular architecture; compresses adjacent liver
without invasion
Hepatoblastoma: Rare benign neoplasm, usually in lambs; cells similar to fetal hepatocytes,
extramedullary hematopoiesis within mass
Comparative Pathology:
Hepatocellular carcinomas reported in humans, dogs, cats, cows, sheep, pigs, fowl, woodchucks,
and trout
Dog - most common lobe is left lateral liver lobe
Chronic inflammation and hepatitis virus are associated with hepatocellular carcinoma in humans,
ducks (DHBV), and woodchucks.
Viral or chemical (aflatoxin or nitrosamines) etiologies are suggested in laboratory and domestic
animals.
Hepadnaviruses cause hepatitis in man and chimpanzees (HBV), Beechey ground squirrels, tree
squirrels, ducks (Pekin and others) and herons.
In man, HBV infection produces a wide spectrum of hepatic disease, including fulminant hepatitis
and an asymptomatic carrier state.
There may be similar viruses in marsupials, rodents, dogs and cats.
WHV and HBV have also been associated with glomerulonephritis in woodchucks and humans,
respectively.

D-N04 - Mast cell tumor - small intestine - cat

HD: Small intestine: Focally elevating the mucosa, blunting and fusing the villi, expanding and
infiltrating the lamina propria, submucosa, tunica muscularis, separating, surrounding and replacing
smooth muscle bundles, and extending into the serosa is an 8 X 4 mm unencapsulated, poorly
circumscribed neoplasm arranged in sheets and cords of round to occasionally spindle cells.
Neoplastic cells have variably distinct cell borders, moderate amounts of pale eosinophilic, finely
granular cytoplasm, irregularly round central nuclei with finely-stippled chromatin and one variably
distinct nucleolus. Mitoses average 1 per 10 HPF. Diffusely, neoplastic cells are admixed with low
numbers of eosinophils and rare lymphocytes and plasma cells. Within the inner circular layer of the
tunica muscularis, there is a focally extensive area of hemorrhage.
Giemsa: Multifocally, cytoplasmic granules of neoplastic cells stain metachromatically (magenta).
Morphologic Diagnosis: Small intestine: Mast cell tumor, breed unspecified, feline.
General Discussion:
Feline mast cell tumors occur in two distinct forms:
Cutaneous: one or more tumors that originate in the skin; metastasize to regional lymph nodes or
viscera
Visceral: Arise in the internal organs without obvious cutaneous tumors
3rd most common primary feline intestinal tumor (after lymphoma and adenocarcinoma)
Most frequent in aged cats; rare in dogs
Primarily located in the small intestine; rarely in colon
 59

Metastasis occurs most often to mesenteric lymph nodes, followed by liver, spleen, and rarely the
lungs.
Mucosal ulceration is rare in feline primary intestinal mast cell tumors. This is thought to be
because of low cellular histamine levels. Ulceration may be present in feline systemic mast cell
tumors and large canine cutaneous mast cell tumors.
Typical Light Microscopic Findings:
Less well-differentiated than those of cutaneous tumors; well demarcated but not encapsulated
Arranged in whorls of spindled cells with indistinct cell borders or as compact nests of uniformly
polygonal cells, 10-20 um diameter with indistinct cell borders
Cytoplasm may be vacuolated, pale eosinophilic and granular, or clear; granules may be difficult to
identify even with special stains.
Eccentric, oval or indented, hyperchromatic nucleus; may have marginated chromatin or prominent
nucleolus; low mitotic rate
Often infiltrates among tunica muscularis cells; rarely effaces gut-associated lymphoid tissue; may
extend into lamina propria
Fibrosis is common; eosinophils are uncommon.
Additional Diagnostic Tests:
Metachromatic stains to highlight granules: Acid toluidine blue (pH 2.5); Giemsa; Wright-Giemsa
Differential Diagnosis:
For gross appearance of thickened intestines:
Lymphoma: Monomorphic population of small or large lymphocytes
Granulated round cell tumors (GRCT):
Large granular lymphocyte (LGL) lymphoma: Small intestinal intraepithelial lymphocyte;
immunoreactivity for CD3 epsilon, CD103, CD8 alpha alpha
Tumors of globule leukocytes: Thought to be either of mast cell or lymphoid origin; round, uniform
cells with fewer and larger eosinophilic granules which are indistinct with H&E, do not stain with
Alcian blue, Giemsa or PAS and are brown or black with PTAH
Eosinophilic inflammatory bowel disease: Usually high numbers of tissue, bone marrow, and blood
eosinophils; characteristic granules on EM
Adenocarcinoma: Usually form acini with mucin production
Intestinal carcinoid: Arise from neuroendocrine cells; arranged in nests and packets
Comparative Pathology:
Intestinal mast cell tumors are rare in other species; occasional cases have been reported in cattle
and dogs.

D-N05A - Adenocarcinoma - duodenum, pancreas - rhesus monkey

HD: Duodenum: Transmurally infiltrating and effacing the normal tissue architecture, compressing
the subjacent pancreas and extending into the duodenal lumen is a unencapsulated infiltrative
neoplasm composed of columnar to cuboidal cells arranged in tubules and acini supported on a
moderately dense fibrovascular stroma. Neoplastic cells have indistinct borders, a moderate amount
of eosinophilic cytoplasm, irregularly round nuclei with clumped chromatin and up to two distinct
nucleoli. Frequently neoplastic cells lack polarity, and pile up to 4 cell layers thick. The mitotic rate
is 4 per 10 HPF. Tubules are often surrounded by increased fibrous connective tissue (desmoplasia),
and filled with sloughed neoplastic cells, necrotic debris, and occasionally degenerate and non-
degenerate neutrophils. Scattered throughout the fibrous stroma there are aggregates of plasma cells
and lymphocytes. Focally within the pancreas there is marked decrease in zymogen granules, loss of
acinar cells (atrophy), and increased numbers of small pancreatic ducts (hyperplasia). Multifocally
within the pancreas there are small aggregates of lymphocytes and plasma cells. Frequently within
the adjacent non-neoplastic mucosa, there are ectatic lymphatics and increased clear space (edema).
Morphologic Diagnosis: 1. Duodenum: Adenocarcinoma, tubular, Rhesus monkey (Macaca
mulatta), nonhuman primate. 2. Pancreas: Atrophy, acinar, multifocal, chronic, moderate, with
ductular hyperplasia.
 60

Pathogenesis:
Arise from undifferentiated cells in the crypts of Lieberkuhn
Cotton-top tamarins (CTT)
Fifty percent of laboratory maintained CTT develop diffuse colitis; 25-40% develop multicentric
adenocarcinoma after 2-5 years of captivity.
Repeated inflammatory episodes cause distortion and atrophy of crypts and surface epithelium, and
adenocarcinoma arises from the distorted crypts.
Novel Helicobacter sp. isolated from CTT is a proposed cause through promoting inflammation and
hyperplasia in the GI epithelium.
Environmental factors, immune system disorders, Campylobacter sp., and genetics are also
proposed etiologies.
Sheep – Suspected to be caused by bracken fern or other dietary carcinogen
Cattle – Suspected to be related to bracken fern and/or papillomavirus
Typical Light Microscopic Findings:
Four types of adenocarcinoma based on the predominant cell type:
Papillary: Papillary projections usually covered by anaplastic epithelial cells with a high mitotic
rate; desmoplasia not a common feature
Tubular: Irregularly branching tubules lined by flattened to columnar cells; fibrovascular stroma
Mucinous: Anaplastic, pale epithelial cells that produce large lakes of mucin
Signet ring: Isolated or nests of cells with a large globule of mucin in the cytoplasm, and a
peripherally placed nucleus
Some classifications include a solid type composed of nests and sheets of anaplastic epithelial cells.
Cats and ruminants: +/- Osseous metaplasia and mineralization
Differential Diagnosis:
Hyperplastic polyp – Tubular or papillary proliferation resembling normal adjacent tissue; most
common in dogs and cattle
Adenoma – Similar pattern, but lacks malignant features (invasiveness, marked nuclear atypia, etc.)
and desmoplasia
Carcinoid (Tumors of neuroendocrine origin) – Nests ribbons and rosettes divided by a fine
fibrovascular stroma; granular to vacuolated cytoplasm; vesiculate nuclei with prominent nucleoli
Undifferentiated carcinoma (solid carcinoma, medullary carcinoma) – Nests of epithelial cells,
without glandular and papillary formation
Comparative Pathology:
Dogs – Most often in the rectum and colon; average age of 8-9 years old; boxers, collies, poodles
and German shepherd dogs predisposed
Cats - Rivals lymphoma as the most common intestinal tumor in cats; most frequently in the ileum,
rarely in the large intestine; average age of 10-11 years; Siamese predisposed
Ruminants, swine, and horses - Usually arise in small intestine, frequently scirrhous
Opossum – Gastrointestinal adenocarcinoma described with Paneth, enteroendocrine and goblet cell
differentiation
Syrian hamster - Gastric adenocarcinoma associated with helicobacter has been reported
Emerald tree boa - Intestinal adenocarcinoma with intraepithelial viral particles resembling type A
retroviral particles

D-N05B - Adenocarcinoma - colon - cotton-top tamarin

HD: Colon: Multifocally expanding and infiltrating the mucosa and submucosa is a moderately
cellular, unencapsulated, poorly circumscribed neoplasm composed of polygonal cells arranged in
disorganized tubules and supported by a fine fibrous stroma. Multifocally, surrounding neoplastic
cells there is increased amount of fibrous connective tissue (desmoplasia). Neoplastic have
indistinct cell borders and a small amount of lightly basophilic, granular to vacuolated cytoplasm.
Nuclei are oval with finely stippled chromatin and one prominent nucleolus. Mitoses average 2 per
10 high power fields, and there is moderate anisokaryosis. Occasional cells are rounded with
 61

abundant foamy amphophilic cytoplasm that peripheralizes the nucleus (signet ring cells).
Multifocal neoplastic tubules are dilated and contain a mixture of neutrophils, mucin, epithelial
cells, and cellular debris. Neoplastic cells often pile up. Subjacent lymphatics are ectatic (edema).
Diffusely within adjacent normal tissue, the mucosal epithelium is uneven with papillary
hyperplasia, and the lamina propria is moderately expanded by numerous previously described
inflammatory cells and ectatic lymphatics (edema). Multifocally crypts are mildly ectatic and
contain crypt abscesses.
Morphologic Diagnosis: 1. Colon: Adenocarcinoma, signet-ring, cotton-top tamarin (Saguinus
oedipus), nonhuman primate. 2. Colon: Colitis, proliferative, chronic-active, diffuse, moderate, with
crypt hyperplasia and crypt abscesses.

D-N06 - Anal sac gland adenocarcinoma - anal sac gland - dog

HD: Anal sac: Expanding the subepithelial connective tissue, compressing adjacent anal sac glands,
and infiltrating adjacent skeletal muscle is an unencapsulated, multilobulated, infiltrative neoplasm
composed of cells arranged in nests, packets, cords, and tubuloacinar structures separated and
supported by fine fibrovascular stroma. Neoplastic cells, which often form rosettes or rare
pseudorosettes, are polygonal to columnar with variably distinct cell borders and a moderate
amount of eosinophilic granular cytoplasm. Nuclei are often basilar and round to oval with coarsely
stippled chromatin, and up to two nucleoli. There is mild anisokaryosis. Mitoses average 2 per HPF
with occasional bizarre mitoses. Multifocally, neoplastic cells are within lymphatic vessels. There is
rare scattered single cell necrosis, occasional eosinophilic amorphous material (secretory product)
in tubuloacinar lumina, and scattered low numbers of lymphocytes, plasma cells, and hemosiderin-
laden macrophages in connective tissue stroma. Multifocally, similar inflammatory cells infiltrate
the subepithelial connective tissue of the anal sac, and remaining apocrine glands are moderately
ectatic.
Morphologic Diagnosis: Anal sac: Anal sac gland adenocarcinoma (Adenocarcinoma of the
apocrine glands of the anal sac), Shepherd-cross, canine.
General Discussion:
Most common malignant perineal neoplasm of dogs with higher incidence in old females and
neutered males; rare in cats
Arises from the anal sac glands (apocrine secretory epithelium) located on the ventral lateral aspect
of the anus as intradermal and subcutaneous masses.
Highly malignant: Highly invasive; commonly metastasizes to regional lymph nodes and then to
abdominal and thoracic viscera
Neoplastic cells produce parathyroid hormone-related protein (PTHrP) which results in
hypercalcemia and hypophosphatemia (humoral hypercalcemia of malignancy (HHM))
Typical Light Microscopic Findings:
Three patterns: One or more pattern can be seen in a single tumor
Solid type: Sheets of tumor cells, fine fibrovascular stroma
Rosette type: Rosette formation with basilar nuclei
Tubular type: Multiple tubular lumina containing eosinophilic secretions
Variable amounts of eosinophilic cytoplasm
Minimal to prominent desmoplastic response
Bland monomorphic population despite the malignant behavior
The stratified squamous lining of the anal sac is often highly melanized while the surrounding
tumor is white.
Differential Diagnosis:
Perianal neoplasia
Anal sac gland adenoma: Little mitotic activity; well encapsulated; rare
Hepatoid gland adenoma: Common in old intact male dogs; well organized trabeculae of polygonal
cells with abundant granular cytoplasm and peripheral reserve cells; little atypia
Hepatoid gland epithelioma: Mostly basaloid cells with mitotic activity but little atypia
 62

Hepatoid gland carcinoma: Pleomorphic basaloid cells and hepatoid cells with mitotic activity;
invasive growth
Sebaceous and apocrine tumors
Hypercalcemia (“HARDIONS”):
H Primary hyperparathyroidism
A Addison’s or Acidosis
R Renal Disease (Renal failure in horses; rare in dogs)
D Hypervitaminosis D, Calciferol rodenticides, Vitamin D glycoside plants (Solanum malacoxylon,
Cestrum diurnum, Trisetum flavescens)
I Immobilization
O Osteolytic lesion
N Neoplasm (lymphoma, multiple myeloma, metastatic bone tumors
S Spurious = Granulomatous disease, e.g. blastomycosis, hyperproteinemia and hemoconcentration
Comparative Pathology:
HHM has also been reported in cats and horses.
Anal sac gland carcinoma from dogs is used in nude mice models for the study of human HHM.

D-N07 - Carcinoid - cecum - dog

HD: Cecum: Infiltrating and replacing the tunica muscularis, is an unencapsulated, highly cellular
neoplasm arranged in small, closely packed nests and packets separated by a fine, fibrovascular
stroma. Neoplastic cells are polygonal with distinct borders and abundant lightly eosinophilic to
clear, occasionally granular, cytoplasm. Nuclei are round with finely stippled chromatin and 1-2
indistinct nucleoli. Mitotic figures average 2 per 10 HPF. Multifocally, neoplastic cells are widely
separated by aggregates of clear, acicular clefts (cholesterol), surrounded by low numbers of
macrophages, multinucleated giant cells, lymphocytes, and plasma cells further bound by a thin rim
of fibrous connective tissue (cholesterol granulomas) separated by clear space and ectatic
lymphatics (edema), fibrin, minimal hemorrhage and occasional hemosiderin-laden macrophages.
Multifocally, neoplastic cells infiltrate the tunica serosa and invaginate into the subendothelial space
of lymphatics and vessels. Within the mass, vessels multifocally contain fibrin thrombi that adhere
to the vessel walls and nearly occlude the lumen. Diffusely, edema, moderate numbers of
neutrophils and fewer macrophages, lymphocytes, and plasma cells expand the submucosa.
Morphologic Diagnosis: Cecum: Carcinoid, Bichon Frise, canine.
General Discussion:
Arise from neuroendocrine cells in a variety of organs, including the stomach and intestine
Rare tumor of domestic animals
Reported mainly in old dogs; rare in cats, cows and horses
Malignant, slow growing neoplasms that metastasize through hematogenous and lymphatic routes
In dogs the duodenum, colon, and rectum are the most frequent sites
Metastatic sites:
Canine: Lung, pleura, liver, pancreas, and local lymph nodes
Cats: Mesentery, omentum, and lymph nodes
Typical Light Microscopic Findings:
3 distinct histologic patterns:
Solid groups or nests of cells with palisading of peripheral cells along the stroma
Groups of rosettes or acinar-like structures
Anastomosing groups and rows of cells forming ribbons
All three patterns separated by fine fibrovascular stroma
Polygonal cells with abundant finely eosinophilic granular cytoplasm
Vesiculate nuclei and prominent nucleoli
Occasional amyloid; multinucleate giant cells
Differential Diagnosis:
Lymphoma: Positive for lymphocyte markers i.e. CD3, CD79a
 63

Adenoma/Carcinoma: May contain argyrophilic cells (exclude with neurendocrine markers i.e.
NSE, chromogranin, synaptophysin)
Plasma cell tumor: Round cells with plasmacytoid appearance i.e. eccentric nuclei with perinuclear
hoff, variation in chromatin pattern i.e. “clockface” or “cartwheel” nuclei, exclude with silver stains
i.e. Churukian-Schenk
Mast cell tumor: Round cells, granules stain with Toluidine Blue; C-kit positive
Leiomyoma/leiomyosarcoma: Spindle-shaped cells; positive for desmin, muscle specific actin and
smooth muscle actin
Comparative Pathology:
"Carcinoid Syndrome" in humans includes diarrhea, cyanosis, flushing of the skin,
bronchoconstriction, hypotension and right-sided valvular disease. The syndrome is caused by
tumor production of histamine and/or serotonin (5-HT)
In captivity, the multimammate rat (Praomys (Mastomys) natalensis) has a high prevalence of
carcinoids of the gastric epithelium
There is one report of a spontaneous gastric carcinoid in a Sprague-Dawley rat
Other reports in laboratory animals have been only after long-term treatment with various chemical
agents
Carcinoid tumors have also been reported in a mare with chronic colic, the colon of a cow, the
foregut in a domestic cat, three cases in the maxillary sinuses of horses, in a cynomolgus monkey,
and in an elephant

D-N08 - Gastric squamous cell carcinoma - stomach - horse

HD: Stomach: Expanding the lamina propria, submucosa and tunica muscularis is a multicentric,
infiltrative, unencapsulated, poorly circumscribed neoplasm composed of polygonal cells that form
packets and cords supported by a fine fibrovascular stroma. Neoplastic cells have distinct cell
borders, a moderate amount of granular to fibrillar, eosinophilic cytoplasm and exhibit prominent
intercellular bridging. Nuclei are round to oval, vesiculate and contain a single, prominent, magenta
nucleolus. There is marked anisokaryosis and anisocytosis. The mitotic rate averages 2 per HPF.
There is abundant desmoplasia characterized by large bands of anastomosing fibrous connective
tissue separating neoplastic lobules. Multifocally, neoplastic cells are shrunken and have
hypereosinophilic, concentrically arranged fibrillar cytoplasm (individual cell keratinization or
dyskeratosis). Multifocally, there are variably-sized accumulations of extracellular, eosinophilic,
homogenous to vacuolated and often lamellated material (keratin pearls). Multifocally, neoplastic
cells invade into blood vessels. Multifocally, within the stroma, there are areas of hemorrhage and
edema.
Morphologic Diagnosis: Stomach: Squamous cell carcinoma, breed unspecified, equine.
General Discussion:
Horses have a squamous epithelium-lined esophageal (cardiac) region to the stomach.
Although primary gastrointestinal neoplasia is rare, gastric squamous cell carcinoma (SCC) is the
most common in the horse.
Arise from the large stratified squamous gastric cardiac component and may extend into the
esophagus
Typical Light Microscopic Findings:
Islands, nests, cords and trabeculae of invasive epithelial cells
Large cells with abundant eosinophilic cytoplasm, large pale nuclei with clumped chromatin and
prominent variably sized nucleoli
Anisocytosis, anisokaryosis, prominent intercellular bridging
Well-differentiated tumors form keratin pearls whereas poorly differentiated tumors may show only
keratinization of individual cells
Desmoplastic reaction with plasma cells and extensive infiltrates by neutrophils in highly
keratinized areas
Tumor cells infiltrate lymphatics and blood vessels.
 64

Differential Diagnosis:
Acantholytic SCC exhibits dyshesion and degeneration of neoplastic cells, resulting in cyst
formation with a single layer of neoplastic cells, producing a pseudoglandular pattern.
Spindle cell SCC can be difficult to distinguish from stromal cells because of the fusiform
appearance.
Comparative Pathology:
Rats have a stratified squamous cardiac component to the stomach; SSC may occur spontaneously
or be induced in toxicologic studies.

D-N09 - Cholangiocarcinoma/papilloma - liver, oropharynx - Military macaw

HD: Liver: Separating, surrounding and effacing, approximately 80% of hepatic architecture is an
unencapsulated, infiltrative neoplasm composed of polygonal cells arranged in irregular, branching
and anastomosing tubules and occasional small acini, supported by a moderate to dense
fibrovascular stroma (desmoplasia). Neoplastic cells have variably distinct cell borders, moderates
amount of eosinophilic, often vacuolated cytoplasm, round to oval nuclei, finely stippled chromatin
and a single, distinct basophilic nucleolus. Mitotic figures average 1/10 HPF. Multifocally, rarely
scattered throughout the neoplasm there are degenerate and necrotic hepatocytes and low numbers
of lymphocytes and plasma cells.
Mucosa, oropharynx (per contributor): Extending from a fibrovascular stalk, there is an exophytic
neoplasm, composed of epithelial cells, which form papillary frond like projections, supported by a
fine fibrovascular stroma. Neoplastic cells progress from a hypertrophied, stratum basale through a
thickened stratum spinosum (acanthosis) and stratum granulosum. Cells of the stratum basale are
often elongate and aligned perpendicular to the stroma. Cells have variably distinct cell borders, a
moderate amount of eosinophilic cytoplasm, round to elongate nuclei with finely stippled chromatin
and 1 distinct nucleolus. Mitotic figures average 1 per 10 HPF. Multifocally, scattered within the
dermis are low numbers of lymphocytes and plasma cells and fewer heterophils.
Morphologic Diagnosis: 1. Liver: Cholangiocarcinoma, Military macaw (Ara militaris), avian.
2. Mucosa, oropharynx (per contributor): Papilloma.
General Discussion:
Cholangiocarcinoma is the most common avian hepatic neoplasm.
Scirrhous (desmoplasia) response is common, and is responsible for the dense white fibrous gross
appearance
Papillomas are most commonly reported in psittacine birds, and an etiologic agent is not often
identified.
Oral cavity and cloacal papillomas are more common than esophagus, crop, proventriculus or
ventriculus papillomas.
Internal papillomatosis and cholangiocarcinoma have been reported to occur concurrently, but they
also occur individually. No definitive correlation is known.
Pathogenesis:
Cholangiocarcinoma:
A specific cause of avian biliary carcinomas has not been determined
Papillomas:
Papillomaviral etiology suspected
Typical Light Microscopic Findings:
Cholangiocarcinoma
Infiltrative cords, tubules or ducts of columnar to cuboidal cells
Mitotic figures are few
May induce scirrhous reaction
Papillomas:
Papillary mass with fibrovascular connective tissue stalk
Heavily keratinized stratified squamous epithelium
 65

May see koilocytes (keratinocytes with clear or gray cytoplasm and small smudged or vesicular
nuclei with marginated chromatin) or basophilic intranuclear inclusion bodies at junction of
keratinized and non keratinized epithelium
Giant cytoplasmic keratohyaline bodies within stratum spinosum
In GI tract, may contain mucous glands
Inflammatory cells in the stroma
Differential Diagnosis:
Cholangiocarcinoma (for gross findings):
Cholangioma is a benign, commonly solitary neoplasm.
Bile duct hyperplasia associated with hepatic lipidosis or portal fibrosis
Chronic hepatotoxin-induced bile duct proliferation (e.g. aflatoxicosis)
Papilloma (for gross findings):
Nodular forms of avian pox - diagnosed by histologic visualization of eosinophilic intracytoplasmic
inclusion bodies (Bollinger bodies)
Comparative Pathology:
Cholangiocarcinoma:
Cholangiocarcinoma occurs in all species, more commonly in dogs and cats.
In man, cats and dogs, cholangiocarcinoma has been associated with infections by the liver fluke
Clonorchis sinensis.
Chemically induced biliary carcinomas (i.e. diethylnitrosamine)
Papillomas:
Bovine cutaneous papillomatosis
Equine cutaneous papillomatosis and sarcoids caused by bovine papillomavirus
Inverted papillomata and oral lesions in dogs
Papillomavirus disease in aged Persian cats as well as Asian lions

D-N10 - Plasmacytoma - rectum - dog

HD: Rectum: Expanding the submucosa and elevating the overlying ulcerated mucosa is a well
circumscribed, unencapsulated, highly cellular, one centimeter diameter neoplasm composed of
sheets and vague packets of round cells separated by a fine fibrous connective tissue. Neoplastic
cells have distinct cell borders and moderate amounts of eosinophilic, granular cytoplasm. Nuclei
are eccentrically located, irregularly round to oval, occasionally indented with finely clumped
chromatin and one prominent nucleolus. There is moderate anisokaryosis, multifocal karyomegaly
and rare multinucleate cells. Mitotic figures average 1 per 10 HPF. Admixed with neoplastic cells
are multiple foci of hemorrhage, fibrin, edema and fibrosis. The overlying mucosa is eroded with
multifocal dilated crypts and a focally extensive area of ulceration that is replaced by hemorrhage,
fibrin and edema that extends into the lamina propria. Submucosal tissue surrounding the neoplasm
contains hemorrhage, edema, fibrin and moderate numbers of plasma cells, fewer lymphocytes and
hemosiderin-laden macrophages and rare neutrophils.
Morphologic Diagnosis: Rectum: Plasmacytoma, mixed breed, canine.
Condition Synonyms: Plasma cell tumor
General Discussion:
Generally benign neoplasm of older dogs resulting from monoclonal proliferation of B cells
Most common in the rectum or ileocecal-colic junction; less common in the esophagus, stomach,
lung, spleen, kidney, vertebral canal, and brain;
Cutaneous plasmacytomas occur most often on pinnae and digits.
Metastasis is rare, but can occur to regional lymph nodes.
Typical Light Microscopic Findings:
Well circumscribed, unencapsulated mass within the submucosa, usually not affecting the overlying
mucosa
Pleomorphic round cells with variable amounts of eosinophilic cytoplasm; more differentiated cells
may have perinuclear clear zone (Golgi complex)
 66

Nuclei are round to oval, eccentrically placed, often indented

Variable chromatin pattern; more differentiated cells at periphery with a "clock-face" pattern
Binucleate, multinucleate and karyomegalic cells are frequent.
Mitotic rate may be high.
Cells are vaguely packeted by fine, fibrovascular stroma.
Rare Russell bodies: Intracytoplasmic eosinophilic globules of immunoglobulin
Amyloid (primary, lambda light chains, AL) is rarely present.
Differential Diagnosis:
For histologic appearance:
Mast cell tumor: Toluidine blue or Giemsa positive
Lymphoma: Sheets of lymphocytes
Plasmacytic inflammation of the digestive tract: Mixed cell population, no mass affect
Melanoma: Staining of melanin granules for S-l00 protein, Melan-A and Fontana-Masson
Plasma cell myeloma (multiple myeloma): Hallmarks are hyperproteinemia, hyperglobulinemia and
monoclonal gammopathy. Two of the following required for diagnosis:
Radiographic evidence of osteolysis
Plasma cells in the bone marrow; >30% of nucleated cells
Monoclonal gammopathy
Bence-Jones proteinuria
Comparative Pathology:
Has been reported in the dog, cat, horse, sheep, African hedgehog, and Syrian hamster (cutaneous
and salivary gland)

D-P01 - Coccidiosis - cecum - chicken

HD: Cecum: Diffusely the mucosa is thickened up to 3 times normal and approximately 90% of
enterocytes are swollen and contain coccidial organisms in various stages of development that
peripheralize nuclei. Coccidial forms include: numerous round 30 um diameter macrogamonts with
a single central nucleus and a peripheral ring of 2 um diameter eosinophilic granules; round to oval
15-20 um diameter microgamonts with multiple nuclei; round to irregularly shaped, 15-20 um
diameter thick-walled oocysts; and low numbers of 40-60 um diameter schizonts with many
basophilic, crescent-shaped merozoites. There is mild multifocal degeneration, necrosis, and loss of
enterocytes. The lamina propria, submucosa, multifocally the tunica muscularis, and to a lesser
extent the serosa, are expanded by lymphocytes, plasma cells, fewer heterophils, macrophages,
scattered hemorrhage, fibrin, and edema with few coccidial organisms in the lamina propria. Few
crypts are mildly to moderately ectatic, lined by attenuated epithelium, and contain variable
amounts of heterophils, oocysts, sloughed enterocytes, or necrotic debris (crypt abscess); or are
lined by epithelial cells up to 5 cell layers thick with few mitotic figures (crypt hyperplasia). There
is a heterophilic granuloma in the submucosa with a central zone of degenerate heterophils and
cellular debris surrounded by macrophages, lymphocytes and an outer layer of reactive fibroblasts
and collagen. The cecal lumen is filled with necrotic debris, fibrin, hemorrhage, inflammatory cells,
sloughed enterocytes, coccidia, and clusters of basophilic cocci and bacilli.
Morphologic Diagnosis: Cecum: Typhlitis, lymphoplasmacytic, subacute, diffuse, marked, with
necrohemorrhagic luminal exudate and numerous intra- and extracellular coccidia, etiology
consistent with Eimeria tenella, chicken (breed unspecified), avian.
Etiologic Diagnosis: Cecal coccidiosis (Eimeriosis)
Cause: Eimeria tenella
Condition Synonyms: Eimeriosis
Lifecycle:
Sporulated oocysts ingested > enzymatic degradation > free sporocytes > free sporozoites invade
mucosa > schizogony (intracellular growth, asexual multiplication, periodic release of merozoites
into lumen) > gamogony (sexual reproduction) intracellular gametocyte development >
differentiation into micro- (males) and macrogametocytes (female) > released microgametes
 67

migrate to macrogametocytes > macrogamete > fertilization > zygote > oocyst > discharge in feces
> sporulation in wet, warm soil > sporocysts > sporulation (sporogony) > sporulated oocysts
Typical Gross Findings:
E. tenella: Ceca filled with caseous cores mixed with blood; thickened cecal wall (edema and
cellular infiltrates); petechiae visible from serosal surface; 22um x 19um oocyst
E. necatrix: Mid-intestine distended with yellow to orange mucus; red and white (clumps of
schizonts) foci; ballooning intestinal walls; dysentery; petechiae
E. acervulina: Duodenum with white irregular linear lesions (zebra stripping) to coalescing white
plaques, associated with gamonts and oocysts, on the duodenal mucosa
E. maxima: Mid-intestine; largest species, with a golden brown oocyst wall; discrete focal
hemorrhagic lesions; soft mucoid salmon-pink colored feces. 31um x 21um oocyst
Differential Diagnosis:
Necrotizing typhlitis:
Histomonas meleagridis: Similar cecal lesion; also causes necrotizing hepatitis
Comparative Pathology:
Animal Coccidia Organ affected
Birds
Geese & ducksE. truncata Kidney
Sandhill/whooping E. reichenowi Disseminated
cranes E psittaculae Intestine
Parrots
1st gen schizont - Jejunum - lacteal endothelium
Cattle E. bovis
2nd gen schizont - Cecal & colonic glands
E. ahsata SI
Sheep E. bakuensis SI
E. ovinoidalis Ileum/LI
E. Christenseni SI
Goats E. arloingi SI
E. ninakohlyak-imovea LI
Equine E. leukarti SI
Swine I. suis SI
Canine I. canis Ileum, colon occasionally
Feline I. felis SI, colon occasionally
Mice E. falciformis Colon
E. stiedae Bile ducts
Rabbit E. intestinalis Ileum & cecum
E. flavescens Ileum & cecum

D-P02 - Hepatic coccidiosis - liver - rabbit

HD: Liver: Multifocally bile ducts are greatly enlarged (up to 4 mm) and compress the surrounding
hepatic parenchyma. Ducts are lined by columnar to cuboidal epithelial cells that form branching
papillary projections supported by a delicate fibrovascular stroma. Epithelial cells frequently have
pyknotic nuclei or karyorrhexis and karyolysis (necrosis). Many epithelial cells contain
macrogametes and microgametes in various stages of gametogony. The macrogametes are round,
20-50 um, with a central nucleus, prominent nucleolus, and brightly eosinophilic 3-4 um peripheral
granules. The microgametes are round, 15-25 um, with peripheral lightly basophilic granules.
Within the lumen there are few oocysts, gametocytes and cellular debris. The unsporulated oocysts
 68

are 20-40 um in diameter with thick refractile walls that are often collapsed and contain lightly
basophilic, granular cytoplasm with a nucleus. Ectatic bile ducts are surrounded by a narrow rim of
fibrous connective tissue with few to many infiltrating lymphocytes, macrophages, plasma cells and
degenerate neutrophils. There is moderate lymphangiectasia with periportal edema surrounding the
ectatic ducts. Diffusely there are low numbers of similar inflammatory cells in portal and periportal
areas and mild bile duct hyperplasia
Morphologic Diagnosis: Liver: Cholangiohepatitis, proliferative and lymphoplasmacytic, chronic,
multifocal, severe, with ductular ectasia, and numerous intraepithelial and intraluminal protozoa,
etiology consistent with Eimeria stiedae, New Zealand White rabbit (Oryctolagus cuniculus),
lagomorph.
Etiologic Diagnosis: Hepatic eimeriosis
Cause: Eimeria stiedae
General Discussion:
Eimeria stiedae, a coccidian in the protozoal phylum Apicomplexa, parasitizes bile duct epithelium
in both domestic and wild rabbits (Oryctolagus, Sylvilagus, and Lepus), and is an important cause
of mortality in commercial rabbitries.
Pathogenesis:
Schizogony in biliary epithelium induces bile duct necrosis and subsequent hyperplasia.
Severe portal fibrosis with nonsuppurative biliary hepatitis is common; there is marked thickening
of the basement membrane with deposition of immunoglobulins.
Severely affected livers have functional abnormalities attributable to the compression of liver
parenchyma and bile duct obstruction.
Lifecycle:
Life cycle for each species of Eimeria (>1000) is host specific and direct.
E. stiedae oocysts are shed in feces and sporulate in 3 days (sporulated oocysts contain 4 sporocysts,
each with 2 sporozoites) > Ingested sporozoites excyst in the intestine and invade epithelial cells >
Sporozoites penetrate the duodenal mucosa, pass via the lymphatics and portal circulation to the
liver, and enter the intrahepatic biliary epithelium > Trophozoites (intracellular) undergo nuclear
division (schizogony) > Merozoites released from asexual stages eventually form sexual stages
(male=microgamete, female=macrogamete) which unite to form oocysts
Oocysts are released into the bile and shed in the feces.
Typical Gross Findings:
Lesions generally limited to the liver
Classic: Multiple, raised, linear bosselated (knob-like), yellowish-white to gray, circumscribed
hepatic lesions (yellow inspissated material on cut section)
Typical Light Microscopic Findings:
In later stages: Proliferation of the biliary epithelium; bile ducts enormously enlarged with long
fronds (papillary folds) of hyperplastic cells
Many cells contain various stages of gametogony, and the lumen contains oocysts, gametocytes, and
desquamated epithelial cells.
Inflammation initially neutrophilic; later an admixture of lymphocytes, plasma cells, eosinophils
and few neutrophils
Late stage lesions become fibrotic and may mineralize.
Comparative Pathology:
Crane: Eimeria gruis, E. reichenowi: These parasites develop in multiple organs or tissues in
infected cranes, thus lacking the specificity of infection sites shown by other Eimeria sp. in spite of
morphologic similarity.
Ophidian snakes: E. bitis in gallbladder and bile duct
Ferret: E. furonis in gallbladder and bile duct
Mink: E. hiepei in biliary ducts
Chicken: E. tenella (cecum), E. necatrix, E. acervulina (small intestine)
Goose: E. truncata (kidney tubules)
 69

Mouse: E. falciformis (small and large intestine)

Guinea pig: E. caviae (large intestine)
Cattle: E. zuernii, E. bovis (small and large intestine)
Horse: E. leuckarti (small intestine)
Sheep: E. ovinoidalis (terminal ileum), E. ahsata, E. ovina
Goat: E. ninakohlyakimovae (cecocolic area), E. christenseni, E. arloingi
In the dog, cat and pig, Isospora sp. are more important pathogens. Eimeria does affect adult pigs
but rarely causes clinical disease.

D-P03A - Amebiasis - liver, mesentery, kidney - Pilot black snake

HD: 1. Liver: Affecting 50% of normal tissue architecture, there are multifocal to coalescing areas
of degeneration (cytoplasmic swelling and vacuolization) and coagulative necrosis (pyknosis or
karyolysis with loss of cellular detail and maintenance of cellular borders), or lytic necrosis (loss of
cellular and tissue architecture with replacement by karyorrhectic and cellular debris) and few,
heterophils, macrophages, and lymphocytes. Multifocally, there are many 10-20um diameter amebic
trophozoites with a thin cell wall, abundant granular to vacuolated basophilic cytoplasm, and a 5-
7um round to oval nucleus with marginated chromatin and a lightly basophilic karyosome. There
are scattered colonies of 1 x 2um coccobacilli. Blood vessels are congested and contain few
trophozoites and rare bacterial emboli. Vessel walls are multifocally disrupted by heterophils and
karyorrhectic debris (necrotizing vasculitis).
2. Mesentery: The fibroadipose tissue is moderately expanded by clear space and dilated lymphatics
(edema), fibrin, few degenerate heterophils, karyorrhectic debris, and hemorrhage. Multifocally,
there are many colonies of coccobacilli.
3. Kidney with spermatic ductules: Within 50% of the renal tubules, epithelial cells are swollen and
vacuolated (degeneration), or are shrunken and hypereosinophilic with pyknosis (necrosis).
Multifocally, vessel walls are disrupted by heterophils and karyorrhectic debris (necrotizing
vasculitis). Multifocally, the interstitium is mildly expanded by hemorrhage, fibrin, rare heterophils,
and scattered colonies of coccobacilli. There are rare fibrin thrombi within glomeruli.
Morphologic Diagnosis: 1. Liver: Hepatitis, necrotizing, acute, multifocal to coalescing, random,
moderate, with necrotizing vasculitis, and parenchymal and intravascular amebae and coccobacilli,
Pilot Black snake (Elaphe obsoleta), ophidian.
2. Mesentery: Steatitis, necrotizing, acute, diffuse, moderate, with hemorrhage, fibrin, and edema.
3. Kidney: Degeneration and necrosis, tubular, diffuse, with hemorrhage, fibrin thrombi, vasculitis,
and colonies of coccobacilli.
Etiologic Diagnosis: Amebic hepatitis
Cause: Entamoeba invadens
General Discussion:
Obligate protozoan parasites with direct life cycle
Entamoeba invadens
Causes ulcerative colitis and hepatitis with high morbidity and mortality in snakes and lizards
Most turtles and crocodiles are resistant; serve as reservoirs
Entamoeba histolytica
Causes amebic dysentery in humans and nonhuman primates (especially Old World), and rarely
infects other species (dogs, cats, pigs, cattle)
Many infections are asymptomatic.
Zoonotic in human beings, nonhuman primates, dogs, cats, and other animals
Pathogenesis:
Amebae are usually nonpathogenic inhabitants of the large bowel lumen.
Diet, immune status, and parasite species and virulence influence pathogenicity.
Trophozoites may disseminate to brain, liver, and other organs through blood vessels and
lymphatics and produce large, lytic lesions (amebic abscesses).
Typical Gross Findings:
 70

Necrohemorrhagic and ulcerative colitis frequently with a fibrinonecrotic membrane, +/- enteritis,
gastritis
Thickened and friable intestinal wall, covered by a necrotic membrane
Lumen filled with blood, necrotic debris, and mucus
Necrosis and abscesses in brain, liver, lungs, and kidneys
Typical Light Microscopic Findings:
Diffuse necrohemorrhagic colitis; erosion and ulceration; necrosis down to the muscularis mucosa
Flask-shaped ulcers in colon, with a narrow neck through the mucosa and a broad base in the
submucosa
Amebae commonly present in small clusters in mucus on colonic surface, in necrotic exudate, and
in adjacent viable tissue
E. histolytica: Spherical to irregular, surrounded by a clear halo, 10-50 um, nucleus with a central
dense karyosome and chromatin plaques at the periphery, light staining, granular cytoplasm with
remnants of erythrocytes and glycogen (PAS positive)
E. invadens: Similar to E. histolytica, but 10-35um with darker cytoplasm and agranular at one pole
Differential Diagnosis:
Other causes of colitis in primates:
Shigella flexneri, S. sonnei: Necrohemorrhagic colitis; differentiate with culture
Salmonella enteritidis, S. typhimurium: Necrotizing, suppurative enterocolitis and possibly
septicemia; pyogranulomas in other organs
Campylobacter jejuni, C. coli: Lesions usually less severe; affects both small and large intestine;
spiral bacteria evident with silver stains; colonic mucosa sometimes hyperplastic
Yersinia enterocolitica, Y. pseudotuberculosis: Necroulcerative enterocolitis; large colonies of gram-
negative bacteria in necrotic centers nearly always diagnostic
Balantidium coli: Ulcerative colitis; ciliated trophozoites 40-60um in diameter; kidney-shaped
macronucleus
Other causes of gastroenteritis in snakes:
Salmonella sp.
Proteus sp.
Coccidia (Eimeria sp., Isospora sp., Caryospora sp.)
Comparative Pathology:
Dogs and cats: Clinical disease rare, signs and lesions similar to those in primates; dissemination
rare, usually with immunosuppression (i.e. distemper infection); usually infected via cysts in human
feces; dogs and cats rarely pass cysts in feces, so generally not considered a public heath hazard
Gastric amebiasis due to E. histolytica reported in a wallaby
Gastric amebiasis due to E. histolytica also occurs in leaf-eating primates (Colobus monkey, Silver-
leafed monkey) due to higher stomach pH that is conducive to survival of amebae; erosive and
ulcerative gastritis
Amphibians: Several species susceptible to Entamoeba ranarum; signs and lesions similar to those
in E. invadens in snakes
Infections by free-living amebae are relatively rare, but increasingly reported; usually not
pathogenic; may cause fatal disease, especially in immunosuppresed patients:
Naegleria fowleri: Acute fatal necrohemorrhagic meningoencephalitis; usually invades olfactory
mucosa and migrates to brain via olfactory nerves; reported in humans (primary amebic
meningoencephalitis or PAM), cattle, and a South American tapir; most human cases occur in
healthy young individuals
Acanthamoeba sp.: Granulomatous amoebic encephalitis (GAE) and pneumonia, and keratitis; in
humans; usually invades cribriform plate; reported in sheep, cows, dogs, birds
Balamuthia mandrillaris: Granulomatous amoebic encephalitis (GAE) and respiratory infections in
humans, a baboon, orangutan, and sheep; acute and necrotizing meningoencephalitis in gorillas and
other Old World primates; granulomatous nephritis and meningoencephalitis in a dog
Sappinia diploidea: Necrohemorrhagic amebic meningoencephalitis in humans
 71

Hartmanella sp.: Gangrenous pneumonia in a bull; cervical lymphadenitis in sheep

Willaertia sp.: Reported in a dog with gastric ulcers
Entamoeba bovis: Nonsuppurative ileitis and typhlitis; necrotizing and pyogranulomatous
lymphadenitis in pronghorn antelope fawns

D-P03B - Amebiasis - colon - snake

HD: Colon: There is diffuse loss of mucosal architecture with replacement by a coagulum of fibrin,
cellular and karyorrhectic debris, pyknotic nuclei, and hemorrhage admixed with 10-20 um
diameter amebic trophozoites with a nucleus and karyosome. Transmurally but primarily in the
submucosa and serosa, the colon is expanded by clear space and dilated lymphatics (edema), fibrin,
and few heterophils, lymphocytes, macrophages, plasma cells, and amebic trophozoites. Multifocal
blood vessels contain small amounts of fibrin and/or trophozoites. There is atrophy of mesenteric
adipocytes. The lumen contains a small amount of fibrinonecrotic exudate.
Morphologic Diagnosis: Colon: Colitis, necrohemorrhagic, acute, diffuse, severe, with transmural
and intravascular amebae, edema, and mesenteric fat atrophy, snake, ophidian.
Etiologic Diagnosis: Amebic colitis
Cause: Entamoeba invadens

D-P03C - Amebiasis - colon - Golden Lion tamarin

HD: Colon: Multifocally, affecting 50% of normal tissue architecture, there is necrosis and loss of
the mucosa with replacement by abundant eosinophilic cellular and karyorrhectic debris admixed
with numerous 1 x 2um bacilli. Adjacent to and admixed with necrotic debris there are small to
moderate numbers of lymphocytes, plasma cells, macrophages, and neutrophils that extend into the
tunica muscularis. Within necrotic areas, there are few 10-25 um diameter amebic trophozoites with
clumped to globular basophilic cytoplasm, and an eccentric, 3-4um diameter nucleus with a
karyosome. Intestinal crypts contain numerous filamentous bacteria and necrotic debris.
PAS: Amoebae have PAS positive cytoplasmic granules.
Morphologic Diagnosis: Colon: Colitis, necrotizing, subacute, multifocal, moderate, with PAS-
positive amebae and few bacterial colonies, Golden Lion tamarin (Leontopithecus rosalia),
nonhuman primate.
Etiologic Diagnosis: Amebic colitis
Cause: Entamoeba histolytica

D-P04 - Hepatocystis kochi infection - liver - African green monkey

HD: Liver: Randomly, disrupting and replacing 15% of the hepatic parenchyma there are scattered,
variably sized granulomas characterized by a central area of eosinophilic cellular debris admixed
with abundant degenerate eosinophils and neutrophils, bounded by a layer of deeply eosinophilic
hyalinized material, many epithelioid macrophages, eosinophils, fewer neutrophils, plasma cells,
lymphocytes, and occasional multinucleate giant cells. Adjacent hepatocytes are shrunken and
hypereosinophilic with hyperchromatic nuclei (degeneration). Multifocally and randomly within the
parenchyma there are lobulated protozoal cysts (merocysts) ranging from 300-1800 um in diameter.
Cysts have a thin eosinophilic hyaline capsule, and contain myriad 2-3 um merozoites. Larger, more
mature merocysts have a large central cavity of fibrillar eosinophilic material (colloid). There are
multifocal portal and perivascular lymphocytes, plasma cells and eosinophils. Diffusely hepatocytes
have foamy to clear cytoplasm (vacuolar change, glycogen type).
Morphologic Diagnosis: Liver: Granulomas, eosinophilic, random, with mild multifocal
lymphoplasmacytic portal hepatitis, and protozoal merocysts with myriad merozoites, etiology
consistent with Hepatocystis kochi, African Green monkey (Cercopithecus aethiops), nonhuman
primate.
Etiologic Diagnosis: Hepatic hepatocystosis
Cause: Hepatocystis kochi
General Discussion:
 72

Most common malarial parasite of African primates

Family Plasmodiidae; also includes the genera Plasmodium, Haemoproteus, and Leucocytozoon
Its primary effect is interference in research data
Typically the infection is asymptomatic
Differential Diagnosis:
Plasmodium sp. – do not form mature merocysts with a central area of colloid
Tuberculosis - granulomas without merocysts
Comparative Pathology:
Species infected by different Hepatocystis sp.:
Multiple nonhuman primates of Africa
Fruit bats
Oriental squirrels
Deer mice
Hippopotami

D-P05 - Histomoniasis - liver, cecum - chicken

HD: Liver: Involving approximately 50% of normal tissue architecture are random, multifocal to
coalescing areas of necrosis, with loss of hepatocytes and replacement with eosinophilic cellular
and karyorrhectic debris, numerous macrophages and lymphocytes, scattered foreign body-type
multinucleate giant cells with up to 7 nuclei, and heterophils. Diffusely there are many 15-20 um
diameter, round, lightly eosinophilic to amphophilic protozoal trophozoites, occasionally with
centrally located 3-5 um diameter basophilic nuclei. Trophozoites within the cytoplasm of
macrophages and multinucleate giant cells are often surrounded by a clear zone.
Cecum: Diffusely expanding the lamina propria, separating cecal glands and extending into the
submucosa and tunica muscularis, there are large numbers of lymphocytes and plasma cells, with
fewer macrophages and heterophils. Within the lamina propria and rarely the submucosa, there are
numerous 10-20 um diameter protozoal trophozoites. Multifocally the crypt glands are hyperplastic
characterized by piling 2-3 layers deep with increased numbers of mitotic figures. The cecal lumen
is filled with a dense core of eosinophilic cellular and karyorrhectic debris, erythrocytes, similar
inflammatory cells, fibrin, and numerous rods (cecal core). Focally within the cecal lumen, there is
a 100 um ascarid characterized by a 1 um cuticle, coelomyarian-polymyarian musculature,
pseudocoelom, lateral alae, lateral chords and an intestine lined with many uninucleate columnar
cells.
Morphologic Diagnosis: 1. Liver: Hepatitis, necrotizing and granulomatous, multifocal to
coalescing, moderate, with many protozoal trophozoites, etiology consistent with Histomonas
meleagridis, chicken, avian.
2. Cecum: Typhlitis, lymphoplasmacytic, histiocytic, and heterophilic, diffuse, moderate, with
fibrinonecrotic core, and many protozoal trophozoites.
Etiologic Diagnosis: Hepatic histomoniasis
Cause: Histomonas meleagridis
Condition Synonyms: Blackhead; Infectious enterohepatitis
General Discussion:
Histomoniasis is a disease of gallinaceous birds (e.g. turkey, chicken, peafowl, guinea fowl,
pheasant, and quail) and is caused by Histomonas meleagridis, a flagellated amoeboid protozoan.
Primary lesions are in the liver and ceca.
Ubiquitous in chickens; high morbidity, usually low mortality
Turkey poults 3-12 weeks old are most susceptible, with high mortality if untreated.
Two forms of the organism: With flagella (in cecal lumen) and without flagella (tissue forms)
Flagellated form - 3-16um diameter with a single flagellum; may contain cytoplasmic food
vacuoles, granules, and bacteria
Aflagellate - basal granule near the nucleus
Invasive - at periphery of lesion (8-17um), amoeboid, form pseudopods
 73

Vegetative - in vacuoles near center of lesions (12-21um), more numerous

Resistant - in older parts of lesion (4-11um), smaller, eosinophilic
Certain bacteria (e.g. Escherichia coli, Clostridium perfringens) play a role in the development and
severity of lesions.
Lifecycle:
In the bird cecum, eggs of Heterakis gallinarum (intermediate host), a cecal nematode, become
infected with trophozoites (mechanism unknown) > infective eggs passed in feces > earthworms
(paratenic or transport hosts) ingest infective nematode eggs > birds ingest infective nematode eggs
or earthworms > in bird cecum, trophozoites released from nematode egg > penetrate cecal wall >
lose flagella (appear amoeboid) > vascular invasion > dissemination to the liver
Typical Light Microscopic Findings:
Cecum: Fibrinonecrotic to hemorrhagic cecal core; pale, slightly blue, ovoid histomonads in
lacunae in the lamina propria and muscularis mucosa; granulomatous inflammation in more chronic
lesions
Liver: Histomonads as individual or clusters within macrophages; heterophils, macrophages, and
lymphocytes
Kidney and spleen: Necrosis, granulomatous inflammation, few multinucleated giant cells

D-P06 - Cryptosporidia sp. infection - stomach - boa constrictor

HD: Stomach, glandular portion: Diffusely the gastric mucosa is expanded up to ten times normal
thickness by a proliferation of mucus neck cells that often separate, compress and replace granular
cells of gastric glands. Lining apical and luminal glandular epithelium and free within the lumen are
myriad 2-6 um diameter, round, pale amphophilic to basophilic protozoa with variably distinct 1-2
um basophilic nuclei. Multifocally the lamina propria contains small numbers of lymphocytes,
plasma cells and fewer heterophils. Diffusely, gastric glands are separated by clear space and
multifocally lymphatics are ectatic and contain an eosinophilic, amorphous substance (edema).
Occasionally gastric glands are distended by sloughed epithelial cells, cellular debris and few
basophilic, 1 X 6 um bacilli.
Morphologic Diagnosis: Stomach: Gastritis, proliferative, chronic, diffuse, moderate, with myriad
free and apically attached protozoa, etiology consistent with Cryptosporidium sp., Boa constrictor
(Boa constrictor), ophidian.
Etiologic Diagnosis: Gastric cryptosporidiosis
Cause: Cryptosporidia sp.
Respiratory disease is most significant in birds while enteric disease predominates in mammals.
However, most infections are asymptomatic.
The parasite is engulfed by the epithelial cell membrane forming a parasitophorous vacuole where
the organism resides in an intracellular but extracytoplasmic environment.
Typical Light Microscopic Findings:
Hyperplasia of mucus neck cells of the gastric glands
Replacement of the granular cells by mucus cells
Edema of lamina propria and muscular tunics
+/- inflammation and necrosis
In mammals: Villus atrophy with blunting and fusion and hypertrophy of crypt epithelium
Numerous organisms attached to brush border of epithelial cells
Comparative Pathology:
Ruminants: C. parvum (intestine), C. andersoni (abomasum)
Other mammals: C. parvum; C. muris generally asymptomatic
Birds: C. baileyi, C. meleagridis; C. baileyi most common in chickens and turkeys, causing
intestinal (cloaca and bursa of Fabricius) and respiratory infections
Reptiles: C. serpentis
Fish: C. nasorum
Cryptosporidium sp. are zoonotic but oocysts from birds do not generally infect humans.
 74

Severe fatal infections occur in Arabian foals with CID; humans and monkeys infected with HIV
and SIV, respectively; and humans with drug-induced immunosuppression. C. parvum was
responsible for the largest waterborne outbreak of diarrhea in U.S. history.

D-P07 - Spironucleus muris infection - small intestine - mouse

HD: Small intestine: Mucosal glands are multifocally mildly ectatic and contain numerous
eosinophilic, piriform to spindled, flagellated protozoal organisms that are approximately 2 x 7um
and contain two indistinct, basophilic nuclei. Smaller numbers of similar organisms are present in
the lumen and lining villar epithelium.
Morphologic Diagnosis: Small intestine, crypts and lumen: Extracellular piriform flagellated
protozoa, numerous, etiology consistent with Spironucleus muris, mouse, murine.
Etiologic Diagnosis: Intestinal spironucleosis
Cause: Spironucleus muris
General Discussion:
An elongate, 7-9 x 2-3um, flagellated, binucleate protozoan found in the small intestine or cecum of
mice, rats, hamsters and various wild rodents worldwide.
Member of the Hexamitidae family (with Giardia, Pentatrichomonas, and Trichomonas)
Found in up to 80% of healthy, adult mice
May cause disease in juveniles or adults who are stressed, immunosuppressed or immunodeficient
Infected mice may be unsuitable for immunologic experiments since they may respond poorly to
antigens; cultured macrophages from infected mice are sometimes incapable of normal RNA
synthesis.
Typical Light Microscopic Findings:
Often no associated inflammation
In acute infections, the lamina propria and submucosa may be edematous and contain neutrophils.
Pale eosinophilic trophozoites are present in the intervillous spaces.
In chronic infections, ectatic crypts contain lymphocytes, plasma cells, cellular debris, and
numerous parasites.
Rarely, the organisms may invade the mucosa and lamina propria.
Differential Diagnosis:
Gastrointestinal protozoa in mice:
Giardia muris, Hexamitidae family: Usually in the lumen; has a rolling motion (as opposed to spiral
motion) on direct smears
Eimeria sp. (E. falciformis, E. musculi, E. schueffneri, E. krijgsmanni, E. keilini, E. hindlei):
Oocysts in mucosa; more common in wild mice; inapparant infection in adults and marked colitis in
juveniles
Cryptosporidium sp. (C. parvum, C. muris): Attach to the brush border of gastric (C. muris) or small
intestinal (C. parvum) epithelium; C. muris usually nonpathogenic; C. parvum associated with
cholangiohepatitis with focal hepatic necrosis in nude and SCID mice
Comparative Pathology:
Spironucleus meleagridis: Infectious Catarrhal Enteritis of Poults; watery to catarrhal inflammation
and atony of the upper intestine
Spironucleus columbae: Catarrhal enteritis in pigeons
Spironucleus elegans: Enteritis in fish

D-P08 - Draschia megastoma infection - stomach - horse

HD: Stomach: Expanding the submucosa and elevating the overlying mucosa, there is an oval
3x1.25cm multilobular fibrous inflammatory nodule, containing multiple irregularly shaped
cavitated lobules. Central cavities contain multiple sections of adult nematodes and few mixed
bacilli. Nematodes have a smooth cuticle with two symmetrical lateral alae,
coelomyarian/polymyarian musculature, prominent lateral cords containing excretory canals, an
intestine lined by many uninucleate cells, a muscular esophagus with a triradiate lumen and
 75

eosinophilic material in the pseudocoelom. Females have a large uterus containing many larvated
eggs with a thin shell. There are occasional free larvae. Nematodes are surrounded by thick walls of
eosinophilic cellular debris and dense collagen with centrally radiating capillaries (granulation
tissue), infiltrated by many plasma cells, lymphocytes, macrophages, and eosinophils. There are few
scattered perivascular lymphocytes and plasma cells within the less affected adjacent submucosa.
Morphologic Diagnosis: Stomach, submucosa: Gastritis, granulomatous and eosinophilic, nodular,
with many adult nematodes, etiology consistent with Draschia megastoma, breed not specified,
equine.
Etiologic Diagnosis: Gastric draschiaiasis
Etiologic Synonyms: formerly Habronema megastoma
Cause: Draschia megastoma
General Discussion:
D. megastoma, Habronema muscae and Habronema majus
Stomach nematodes of equids
Draschia can infect the intestine; H. muscae rarely affects cecum
Larvae of all 3 species can infect the skin (“summer sore”) and conjunctiva
Flies act as intermediate hosts.
Pathogenesis:
Habronema sp. live free in the gastric lumen and on the gastric mucosa; Draschia sp. burrows into
the submucosa forming granulomatous nodules.
Aberrant deposition of larvae on skin and eye may cause hypersensitivity reaction with
granulomatous and eosinophilic dermatitis and conjunctivitis.
Lifecycle:
Seasonal occurrence corresponds with that of the fly intermediate host.
Adult worms in stomach > larvated eggs > hatch (L1) in the intestine > passed in feces and ingested
by the larvae of the intermediate host fly (H. muscae and D. megastoma use the housefly, Musca
domestica and other Musca sp; H. majus uses the stable fly, Stomoxys calcitrans) > develops into
infective L3 in the fly larvae > fly develops to adult > L3 migrate from hemocele into the proboscis
> deposited around the horse’s mouth > swallowed and mature in the stomach
Typical Gross Findings:
Stomach:
H. muscae and H. majus penetrate gastric glands or lie in the lumen; large numbers of worms may
cause inflammation and chronic erosive gastritis.
Draschia sp. penetrate deeply into the glandular mucosa in the cardia near the margo plicatus and
produce 2.5-10 cm diameter tumor-like nodules containing worms, caseous material, and pus.
Hemorrhage or gastric perforation can occur.
Eyes: Larvae at the medial canthus in the conjunctival sac
Wart-like red or yellow lesion which may caseate or calcify
Raised yellow gritty plaques (“clinically pathognomonic”) on the conjunctiva; raised, red
granulomas 1-5cm from the medial canthus
Skin: Synonyms: Cutaneous habronemiasis, summer sores, swamp cancer
Differential Diagnosis:
Cutaneous lesions: Pythiosis, botryomycosis, onchocerciasis, exuberant granulation tissue, equine
sarcoid, squamous cell carcinoma, nodular collagenolytic granuloma
Common secondary infection of many cutaneous lesions, particularly penile squamous cell
carcinoma
Comparative Pathology:
Stomach worms in domestic animals
Dog: Physaloptera sp., Gnathostoma sp.
Cat: Physaloptera sp., Gnathostoma sp., Cylicospirura felineus, Ollulanus tricuspis
Horse: Trichostrongylus axei, Gastrophilus sp.
Swine: Hyostrongylus rubidus, Ascarops sp., Physocephalus sp., Simondsia sp., Gnathostoma sp.,
 76

Ollulanus tricuspis
Cattle, sheep, goats: Haemonchus sp., Mecistocirrus sp., Ostertagia sp.

D-P09 - Prosthenorchis elegans infection - ileum - Moustached tamarin

HD: Ileum, two sections: Transmurally disrupting the intestinal wall and elevating the overlying
ulcerated mucosa is a 5mm nodule that contains a central cavity with a 1 X 1.75 mm cross section
of an adult acanthocephalid parasite. The parasite has a thin outer cuticle and a thick hypodermis
(up to 150 um) composed of a felted layer and cross fibers containing lacunae channels, outer
circular and inner longitudinal muscle layers, and a pseudocoelom containing lemnisci with
compressor muscles. The parasite is surrounded by a thin layer of degenerate neutrophils and
eosinophils, which are further surrounded by a zone of epithelioid macrophages, neutrophils,
eosinophils, lymphocytes and plasma cells that are enmeshed in thick concentric bands of mature
fibrous connective tissue (pyogranuloma). Fibrous connective tissue is multifocally mildly
separated by increased clear space (edema) and inflammatory cells, which occasionally form
aggregates. Focally the mucosa is ulcerated with replacement by karyorrhectic and cellular debris
and degenerate neutrophils. Within the ulcerated area is a partial section of an adult acanthocephalid
parasite.
Morphologic Diagnosis: Ileum: Enteritis, pyogranulomatous and eosinophilic, nodular, transmural,
with focal ulceration, and adult acanthocephalid parasites, Moustached tamarin (Saguinus mystax),
nonhuman primate.
Etiologic Diagnosis: Intestinal prosthenorchiasis
Cause: Prosthenorchis elegans
General Discussion:
P. elegans is a member of the Phylum Acanthocephala, also known as thorny- or spiny-headed
worms, and is an important parasite of native and wild-caught New World monkeys from Central
and South America (Squirrel monkeys, marmosets, Pygmy marmosets, tamarins, Titi monkeys,
Spider monkeys, and Cebus monkeys).
Intermediate host: Several species of cockroaches and certain beetles
Typical Light Microscopic Findings:
Ileum, cecum and colon with numerous deep ulcers containing adult parasites with a hook-laden
proboscis embedded deep in the intestinal wall
Ulcers extend into submucosa and tunica muscularis and are surrounded by necrotic debris and
fibroblastic tissue containing focal and diffuse aggregates of neutrophils, eosinophils, macrophages,
lymphocytes, plasma cells and occasionally colonies of bacteria.
Morphology of acanthocephalids:
Cylindrical pseudocoelomates; separate sexes
Retractable proboscis armed with rows of hooks (spines)
Hypodermis thicker than muscle layers; consists of two layers (felted layer and cross fibers
containing lacunar channels)
Two layers of somatic muscles: outer circular and inner longitudinal
Absent digestive tract (nutrients absorbed through thin cuticle)
Lemnisci with compressor muscles (may function in proboscis extrusion)
Prosthenorchis elegans:
Females up to 50 mm long, males 18-25 mm long; trunk transversely wrinkled, not
pseudosegmented; narrow neck with 6 spiral rows of 5-7 curved hooks.
Anterior end has a distinctive collar with 18-20 festoons (not in P. spirula).
Eggs: Brown, double-shelled, 42X65 um; central embryo with a central mass containing numerous
nuclei
Differential Diagnosis:
Intramural nodules in New World monkeys:
Prosthenorchis spirula: Lacks a collar
Molineus torulosus: Characteristic strongyle intestine
 77

Intramural nodules in Old World monkeys:

Oesophagostomum (nematode): Adults are extremely small and totally embedded in the parasitic
nodule. Eggs easily distinguishable from Prosthenorchis sp. in that they are not double shelled.
Comparative Pathology:
In captivity, bush babies, lemurs, pig-tailed macaques, gibbons, and chimpanzees may become
infected if housed in close proximity with infected animals.
Smaller acanthocephalans:
Polymorphus sp. and Filicolis sp.: Waterfowl and fishes; intermediate host=crustacean; lesions
similar to Prosthenorchis in NHP
Other acanthocephalans that parasitize mammals:
Moniliformis moniliformis: Wild rodents and great apes; cockroach intermediate host; very long (up
to 32 cm); pseudosegmented (easy to misdiagnose as a cestode); no distinctive scalloped collar in
the neck region
Macracanthorhynchus hirudinaceus (thorny-headed worm of swine): Wild and domestic swine;
dung beetle intermediate host; affects small intestine
Macracanthorhynchus catalinum and M. ingens: Foxes, wolves, badgers, skunk, raccoons, mink,
moles, occasionally the dog
Oncicola canis: Dog, coyote, domestic cat, lynx, bobcat; arthropod intermediate host; armadillo
paratenic host; affects small intestine
Oncicola campanulutus: Domestic cats

D-P10 - Spirocerca lupi infection - esophagus - dog

HD: Esophagus: Focally expanding and disrupting the tunica muscularis and elevating the mucosa
and submucosa is a 14 x 8 mm nodule composed of cross and tangential sections of an adult
nematode surrounded by an inflammatory infiltrate composed of abundant plasma cells, fewer
lymphocytes, neutrophils, hemosiderin-laden macrophages and eosinophils admixed with reactive
fibroblasts, separated by variably sized bands of collagen and many small caliber blood vessels. The
nematode is 1 mm in diameter and has a 8 um thick, smooth, pigmented cuticle, coelomyarian-
polymyarian musculature, prominent lateral cords, a pseudocoelom containing small amounts of
eosinophilic granular material, a large digestive tract lined by uninucleate columnar epithelium with
long, prominent microvilli (brush border), and reproductive organs. Multifocally there are moderate
numbers of similar inflammatory cells within the submucosa, muscular tunics and serosa.
Morphologic Diagnosis: Esophagus: Esophagitis, lymphoplasmacytic and eosinophilic, chronic,
nodular, marked, with adult nematode, etiology consistent with Spirocerca lupi, breed unspecified,
canine.
Etiologic Diagnosis: Esophageal spirocercosis
Cause: Spirocerca lupi
General Discussion:
Spirurid nematode of canids (dog, fox, wolf, coyote, jackal) and some wild felids (lynx, snow
leopard) and other carnivores
Two species: S. lupi (tropics and the US) and S. artica (northern Russia)
Lesions usually in the esophagus, stomach, and aorta; however, other locations possibly involved
(urinary bladder, kidneys, subcutaneous tissue, spinal vertebrae) because of aberrant larval
migration
S. lupi is associated with esophageal osteosarcoma and fibrosarcoma. The mechanism of neoplastic
transformation is unknown. Many factors may play a role (parasitic metabolic products, viruses,
and/or chemical substances). Sarcomas may be extensive and may metastasize to the lungs and
elsewhere. There is a report of a pulmonary fibrosarcoma associated with an ectopic worm.
Comparative Pathology:
Parasites associated with neoplasia (Mnemonic SOCCS)
Spirocerca lupi: Esophageal sarcomas in dogs
Opisthorchid flukes: Cholangiocarcinoma in man, cats
 78

Cysticercus fasciolaris (Taenia taeniaeformis): Hepatic sarcoma in rats

Clonorchis sinensis: Cholangiocarcinoma in man, cats
Schistosoma haematobium: Urinary bladder transitional cell carcinoma in man

D-P11 - Heterakis isolonche infection - cecum - Golden pheasant

HD: Cecum: Focally within the submucosa and elevating the mucosa, is a mass composed of
multiple, discrete, up to 2mm, circular nodules. The nodules are composed of spindle cells arranged
in whorls and interlacing bundles with varying numbers of macrophages, multinucleated giant cells,
lymphocytes, and plasma cells. Within several nodules are multiple, up to 750um, cross sections of
an adult nematode with a thin smooth cuticle, cuticular alae, polymyarian/coelomyarian
musculature, lateral cords, a pseudocoelom, an intestinal tract lined by cuboidal to columnar
uninucleate cells with a brush border, an ovary and a uterus containing developing ova. There is a
single cross section of a nematode larva. Within some nodules there are granulomas with a central
core of eosinophilic and karyorrhectic debris, surrounded by a thin rim of epithelioid macrophages,
multinucleated giant cells, and fewer fibroblasts, lymphocytes and plasma cells. Diffusely in the
lamina propria there are moderate numbers of lymphocytes, plasma cells, and occasional
heterophils. Vessels are congested and there are occasional hemosiderin-laden macrophages and
free red blood cells. Multifocally numerous small coccobacilli adhere to the luminal epithelium.
Morphologic Diagnosis: Cecum: Typhlitis, granulomatous, multifocal, moderate, with atypical
nodular mesenchymal proliferation, and adult and larval nematodes, etiology consistent with
Heterakis isolonche, Golden pheasant (Chrysolophus pictus), avian.
Etiologic Diagnosis: Cecal heterakiasis
Cause: Heterakis isolonche
General Discussion:
Most heterakids are non-pathogenic, with the exception of Heterakis isolonche.
H. isolonche reported in ducks, grouse, pheasants, prairie chickens and quail; most common in the
pheasant
Typical Light Microscopic Findings:
Lymphoplasmacytic to granulomatous typhlitis
Nodules of proliferating fibrous tissue induced by larvae
The nature of this reaction is controversial; it has been considered granulomatous, fibroplastic or
neoplastic. Although the nodules are highly cellular and show a striking sarcomatous appearance,
no malignant transformation has been reported.
Nodules of spindle cells arranged in whorls and interlacing bundles have been described as
“sarcomatous” or “pseudoneoplastic”.
This nodular proliferation is not seen in quail and grouse.
Granulomas form in response to dead parasites.
Parasite morphology
Thin smooth cuticle, cuticular alae, lateral cords, a pseudocoelom
Polymyarian/coelomyarian musculature
Intestinal tract: Cuboidal to columnar uninucleate cells with a brush border
Ovary and a uterus contains developing eggs
Comparative Pathology:
Heterakis gallinarum: No significant pathology, but carries Histomonas meleagridis, the etiologic
agent of blackhead in gallinaceous birds
Rodents: Heterakis spumosa

D-P12 - Pinworm infection - colon - chimpanzee

HD: Colon: Diffusely, there is a decrease in number of colonic crypts. Infiltrating and expanding
the lamina propria, extending into the submucosa and multifocally cuffing vessels are many
lymphocytes, plasma cells, and eosinophils. Several submucosal arteries are lined by hypertrophied
endothelial cells, with occasionally transmigrating eosinophils within the tunica media. Within the
 79

colonic lumen, there are few cross sections of a 150-200 um diameter nematode with a thin cuticle,
lateral alae, platymyarian-meromyarian musculature, and a muscular esophagus with a triradiate
lumen.
Small intestine: Multifocally many eosinophils, lymphocytes and plasma cells expand the lamina
propria and submucosa. Within the lumen there are cross-sections of nematodes as described above.
Morphologic Diagnosis: Colon; small intestine: Colitis and enteritis, lymphoplasmacytic and
eosinophilic, diffuse, moderate, with few intraluminal nematodes, etiology consistent with
Enterobius sp., chimpanzee (Pan troglodytes), nonhuman primate.
Etiologic Diagnosis: Intestinal enterobiasis
Cause: Enterobius sp.
Condition Synonyms: Oxyuriasis
Differential Diagnosis:
Prosthenorchis elegans: Causes pyogranulomatous enteritis with acanthocephalid parasites
Oesophagostomum sp.: Causes iIntramural nodules in the cecum, colon and adjacent mesentery of
wild-caught monkeys
Comparative Pathology:
Enterobius anthropopitheci: Nonhuman primates, chimpanzees, prosimian primates
Enterobius vermicularis: Old World monkeys, great apes. Associated with appendicitis, intestinal
abscesses, infections of the female reproductive tract, peritonitis, and nephritis in captive
chimpanzees; probably transmitted by man; public health concern. Most common worm infection in
western man.
Oxyuris equi: Most common pinworm in domestic animals. Distal intestine, with rectal pruritus in
horses
Skrjabinema ovis: Sheep & goats
Passalurus ambiguus: Ceca of rabbit. Heavy infectious cause impaired weight grains, poor breeding
performace, and death
Syphacia obvelata, Aspicularis tetraptera: Ceca and colon of rats
Syphacia obvelata, Aspicularis tretraptera: Common in laboratory mouse. Heavy infectious
associated with rectal prolapse, intussusception, fecal impaction and diarrhea. In S. obvelata-
infected mice there is increased myelopoiesis and erythropoiesis with displayed altered sensitivity
to IL-17
Pinworms do NOT infect the dog and cat.

D-P13 - Ostertagiasis - abomasum - ox

HD: Abomasum: Multifocally the mucosa is thickened up to twice normal by elongate and
occasionally tortuous glands lined by tightly packed mucous cells that frequently pile up on one
another and replace parietal cells. In the lamina propria, separating and surrounding the glands,
there are few eosinophils, lymphocytes, plasma cells and macrophages, and cells with round to oval
nuclei and abundant eosinophilic cytoplasmic globules (globule leukocytes). Focally in the deep
mucosa there is a 60 um diameter adult nematode with a 10 um-thick cuticle, multiple longitudinal
cuticular ridges, platymyarian/meromyarian musculature, a pseudocoelom, digestive tract, and
gonads that contain eosinophilic globular material. Multifocally, glands are dilated up to 200 um,
are lined by attenuated epithelium, and are filled with eosinophils, macrophages, and cellular debris.
Multifocally there are a few lymphoid nodules in the deep lamina propria, submucosal vessels are
cuffed by few lymphocytes, plasma cells and eosinophils, and there is mild congestion.
Morphologic Diagnosis: Abomasum: Abomasitis, proliferative and eosinophilic, chronic,
multifocal, moderate, with mucous neck cell hyperplasia, parietal cell loss, and trichostrongylid
nematodes, etiology consistent with Ostertagia ostertagi, breed unspecified, bovine.
Etiologic Diagnosis: Abomasal ostertagiasis
Cause: Ostertagia sp.
Family Trichostrongylidae
O. ostertagi: Cattle; less common in sheep and goats; rare in horses
 80

O. circumcincta: Primarily sheep and goats

O. trifuncata: Sheep, goats and cattle
O. leptospicularis: Deer; rare in cattle
Ruminant abomasal nematodes: Hemonchus sp., Ostertagia sp. and Trichostrongylus sp. (HOT). All
trichostrongyles with similar morphology
Hemonchus contortus (sheep and goats) and H. placei (cattle): “Barber pole worm”; 2cm long, red
and white females, red males; adults and L-4 attach to mucosa and suck blood; anemia;
hypoproteinemia/edema; edematous and hemorrhagic abomasal rugae; reddish brown/bloody
abomasal contents
Trichostrongylus axei: Cattle, sheep, goats and horses; similar lesions to Ostertagia sp. (mucous
metaplasia/hyperplasia, decreased parietal cells, erosions, eosinophilic and lymphoplasmacytic
inflammation), smooth cuticle (lack ridges), intraepithelial tunnels, usually occur with other GI
parasites, may also infect small intestine
Differential Diagnosis:
For gross lesions:
Multi-nodular lymphoma: Multiple nodules variable in size
Abomasal coccidiosis: Eimeria sp.
For gross and histologic lesions:
Trichostrongylus axei: Cattle, sheep, goats and horses; similar lesions to Ostertagia sp. (mucous
metaplasia/hyperplasia, decreased parietal cells, erosions, eosinophilic and lymphoplasmacytic
inflammation), smooth cuticle (lack ridges), intraepithelial tunnels, usually occur with other GI
parasites, may also infect small intestine.

Comparative Pathology:
Other causes of mucous neck cell hyperplasia and parietal cell loss
Chronic hypertrophic gastritis: Idiopathic; occurs in dogs (giant hypertrophic pyloric gastropathy of
older small dogs; giant hypertrophic gastropathy of Basenjis and humans (Menetrier disease);
possibly immune mediated
Ollulanus tricuspis in cats and swine
Trichostrongylus axei in cattle, goats and horses
Ostertagia circumcincta in sheep
Hyostrongylus rubidus in swine; causes thin sow syndrome
Nochtia nochti in nonhuman primates

D-P14 - Nochtiasis - stomach - Rhesus monkey

HD: Stomach: Focally there is a polypoid thickening of the mucosa up to 5x normal by hyperplastic
mucous neck cells which alter normal architecture, replace parietal cells, and form long arborizing
pits supported by a well vascularized fibrous stroma. Focally crypts are herniated into the
submucosa and ectatic. Multifocally the lamina propria and submucosa contain many lymphocytes
and plasma cells, fewer neutrophils and eosinophils, and submucosal blood vessels that are mildly
congested. Multifocally gastric pits are dilated and contain abundant eosinophilic cellular debris,
degenerate inflammatory cells, and aggregates of oval, 30 X 50um, thin-shelled, morulated eggs,
and scattered 150-500um cross sections of adult nematodes. Adult nematodes have evenly spaced,
external, longitudinal cuticular ridges, platymyarian/meromyarian musculature, and an intestine
with indistinct morphology. Focally in a longitudinal section there are immature ova within the
ovary.
Morphologic Diagnosis: Stomach: Hyperplasia, mucosal, focally extensive, moderate, with mucus
cell metaplasia, multifocal mild lymphoplasmacytic and eosinophilic gastritis, and adult nematodes
and eggs, etiology consistent with Nochtia nochti, Rhesus monkey (Macaca mulatta), non-human
primate.
Etiologic Diagnosis: Gastric nochtiasis
Cause: Nochtia nochti
 81

Typical Light Microscopic Findings:

Gastric lesions:
Marked hyperplasia of mucus neck cells that are tall-columnar and palisade along papillary
projections
Mucous metaplasia of fundic or pyloric glands
Paucity of parietal cells
N. nochti:
Free parasites are not found in the gastric lumen.
Sixteen distinct, evenly spaced, longitudinal cuticular ridges flared near lateral cords
Pseudocoelom
Platymyarian - meromyarian musculature
Intestine is large and composed of few multinucleate cells.
Reproductive tract (ovary or testis)
Eggs are thin-shelled, ellipsoidal, morulated (i.e., embryonated), and are 60-80 x 35-42 um.
Differential Diagnosis:
Trichostrongylids:
Molineus sp.: Submucosal granulomatous inflammation and serosal nodules in the pyloric region
and small intestine of New World monkeys; small, slender, pale, red worms found on the mucosa.
Spirurids:
Physaloptera tumefaciens: More common in macaques than N. nochti; large nematodes resembling
ascarids attached by the head to the mucosa with protrusion of the body into the gastric lumen;
gastritis and gastric hyperplasia; cockroach intermediate host

Comparative Pathology:
Trichostrongyloid gastritis in other species:
Trichostrongylus axei in cattle, goats and horses
Ostertagia ostertagi in cattle
Ostertagia circumcincta in sheep
Haemonchus sp. in ruminants
Hyostrongylus rubidus in swine
Ollulanus tricuspis in cats, other felids and swine
Hypertrophic gastritis:
Horses – Habronema sp. (focal), Trichostrongylus axei (diffuse)
Dogs – Chronic giant hypertrophic gastropathy (Basenji, Beagle, Boxer, Bull terrier), unknown
etiology

D-P15 - Tetrameriasis - proventriculus - pigeon

HD: Proventriculus: Multifocally, compound tubular glands are markedly dilated, lined by
attenuated epithelium, and contain many cross sections of adult female nematodes that are
approximately 1.5 mm in diameter which compress adjacent glands and elevate the overlying
mucosa. Nematodes have a 3 um cuticle and a pseudocoelom containing abundant homogenous
brightly eosinophilic material (proteinaceous fluid); indistinct musculature; a digestive tract lined
by many uninucleate cuboidal cells with a brush border containing abundant brown pigment; uteri
containing numerous 25 x 50um, oval, thick shelled, embryonated eggs, occasionally with polar
filaments; and variably sized ovaries with ova. Multifocally within the lamina propria of the
primary ducts are several small aggregates of lymphocytes and rare heterophils.
Heart; esophagus; ventriculus; great vessel; and lung: Essentially normal tissue.
Morphologic Diagnosis: Proventriculus, tubular glands and lumen: Duct ectasia, multifocal,
moderate, with intraductal and luminal adult nematodes, etiology consistent with Tetrameres sp.,
breed unspecified, pigeon (Columba livia), avian.
Etiologic Diagnosis: Proventricular tetrameriasis
Cause: Tetrameres sp. (T. americana or T. fissispina)
 82

Differential Diagnosis:
For nematodes in proventriculus:
Tetrameres sp.: Fat, spherical, blood-red worms in the wall of the proventriculus and that distend
glands
Microtetrameres sp.: Lobate, wide, coiled, blood red worms in the wall of the proventriculus (M.
helix: Russian and North American crows and pigeons)
Cyrnea sp.: Spirurids, but lack the marked sexual dimorphism of the Tetramitidae; nonpathogenic;
do not suck blood; do not attach to mucosa or live in glands
C. pileata: Bobwhite quail.
C. colini: Various North American gallinaceous birds.
Dispharynx spiralis (D. nasuta, Acuraria spiralis): Lives on the mucosa of the proventriculus,
esophagus, and rarely intestines of various species of pigeons, chickens, turkeys, and guinea fowl
worldwide; can cause severe ulceration with chronic diffuse fibrosis; most severe in young birds
and the main cause of grouse disease in USA
Echinuria uncinata: In esophagus, proventriculus, gizzard, and small intestine of the duck, goose,
swan; penetrate deep into the mucosa forming large nodules with caseous centers, which can
obstruct the passage of food
Eustrongylides papillosus (E. ignotus): Fish eating birds, ducks and geese; eggs with thick pitted
shells; adults up to 30mm long; may cause nodules in the proventricular glands

Comparative Pathology:
Tetrameres americana: Poultry, quail, turkey, grouse pigeons, ducks and geese; mainly USA and
South Africa
T. fissispina: Ducks, geese, pigeons, rarely chickens, turkeys, and other birds; worldwide
distribution
T. cramii: North American ducks
T. pattersoni: Only in bobwhite quail

D-P16 - Trichostrongylosis - small intestine - Cebus monkey

HD: Small intestine: Focally there is a single 4 mm diameter granuloma, which expands the
submucosa, obliterates the tunica muscularis, and markedly elevates the serosa. The granuloma is
composed centrally of multiple cross and tangential sections of adult nematodes and eggs
surrounded by eosinophilic cellular debris, numerous nondegenerate and degenerate neutrophils,
eosinophils, and epithelioid macrophages. This is further surrounded by numerous lymphocytes and
plasma cells bordered by a 25-30 um thick fibrous capsule. The nematodes are up to 120 um
diameter, have a 5 um thick eosinophilic cuticle with evenly spaced, longitudinal cuticular ridges, a
pseudocoelom, platymyarian/meromyarian musculature, and an intestine lined by few multinucleate
cells with a low brush border. Eggs are 30-50 um in diameter and are thin shelled and non-larvated.
Previously described inflammatory cells infiltrate the overlying serosa and superficial submucosa
and mildly expand the lamina propria. Diffusely there is mild follicular hyperplasia of the gut-
associated lymphoid tissue.
Morphologic Diagnosis: Small intestine: Granuloma, eosinophilic, focal, with adult
trichostrongylids and eggs, etiology consistent with Molineus torulosus, Cebus monkey (Cebus sp.),
nonhuman primate.
EDX: Enteric trichostrongylosis
Cause: Molineus torulosus
GD:
Class Secernentea, order Strongylida, suborder Trichostrongylida
Molineus sp. are small slender pale red worms of the upper digestive tract, pylorus, and
occasionally pancreas and mesentery of nonhuman primates; worms are not found in the terminal
jejunum or ileum.
Molineus torulosus is the only pathogenic species.
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Unknown life cycle

Pathogenesis:
Infective L3 penetrates epithelium and burrows into the submucosa > larvae mature and deposit
eggs > formation of submucosal granulomas > eggs are expelled through channels from granuloma
into the intestinal lumen
Invasion of the host’s vascular system > fibrin thrombi or direct penetration or dissemination via
portal vein > pancreatic ducts > chronic pancreatitis

Typical Clinical Findings:

Usually inapparent disease

Typical Gross Findings:

Duodenum and proximal jejunum
2-6 mm gray-green/black-brown serosal nodules, marbled on cut surface
Nodules communicate with the lumen by 1 mm brownish-red ulcers.
Nodules contain a mass of sexually mature, hair-like worms that measure 1 cm in length.
Mesenteric lymph nodes enlarged and reddish
Pancreas may contain numerous small, gray-yellow nodules.

Typical Light Microscopic Findings:

Submucosal eosinophilic granulomas surrounded by a rim of fibrous connective tissue
Parasitic granulomas associated with large mesenteric blood vessels and vessels at the periphery of
the granuloma; worms and eggs possibly intravascular within fibrin thrombi
Neutrophilic and lymphocytic periductular pancreatitis with intraductular nematodes and eggs;
chronic – pancreatic fibrosis.
Subacute mesenteric and pancreatic lymphadenitis may be present.
Molineus torulosus has the following characteristics: Conspicuous external longitudinal ridges
projecting from the cuticle; platymyarian-meromyarian musculature; intestine composed of few
multinucleate cells with shorter thinner microvillar layer and fewer nuclei than strongylids; large
paired excretory gland cells; copulatory bursa in males

Differential Diagnosis:
Oesophagostomum sp.: Cause serosal nodules predominantly in the colon of Old World monkeys;
very rare in New World species; histologically only larvae present in nodules
Nochtia nochti: Trichostrongyle; produces papillomatous mucosal nodules in the stomach of Old
World monkeys; cuticular ridges external to the lateral cords fused and divergent from one another,
a unique feature of Nochtia
Prosthenorchis: Acanthocephalan; produces serosal nodules in the large intestine, occasionally the
terminal ileum or ileocecal region of New World monkeys; attached to the mucosal surface;
lemnisci and a thick hypodermis are unique microscopic features
Intramural granulomas caused by schistosomes may appear as intestinal nodules, but can be easily
differentiated histologically.
Pancreatic lesions must be differentiated from similar lesions caused by other worms such as
Trichospirura leptostoma, a spirurid.