Systemic Pathology

JPC SYSTEMIC PATHOLOGY
NERVOUS SYSTEM
January 2017
N-M23
Signalment (JPC #2414433): 8-year-old spayed female domestic shorthair cat
HISTORY: This cat had a four-day history of hind end paresis, hyperesthesia,
hypersalivation, and depression, followed by several episodes of “rage”-type activity.
HISTOPATHOLOGIC DESCRIPTION: Cerebrum, hippocampus: Multifocally within

the hippocampus there is necrosis characterized by loss of neuropil with
replacement by eosinophilic cellular debris and moderate numbers of gitter cells
admixed with multiple foci of hemorrhage and fibrin. Vessels within affected areas
are lined by hypertrophic (reactive) endothelial cells, and vessel walls are
occasionally discontinuous and frequently obscured by fibrin, macrophages, and
neutrophils (fibrinonecrotizing vasculitis). Vessels are surrounded by low numbers of
neutrophils and gitter cells and there is mild perivascular edema. Within the affected
areas, neurons frequently have shrunken, hypereosinophilic, and angular cytoplasm
with pyknotic or karyolytic nuclei (neuronal necrosis) admixed with moderate
numbers of glial cells (satellitosis) and few neutrophils. The adjacent leptomeninges
are mildly expanded by low numbers of previously described inflammatory cells
admixed with mild hemorrhage and edema.
MORPHOLOGIC DIAGNOSIS: Cerebrum, hippocampus: Necrosis, multifocal to

coalescing, marked, with hemorrhage, fibrin, edema, fibrinonecrotizing vasculitis,
and neuronal necrosis, domestic shorthair, feline.
CONDITION: Feline ischemic encephalopathy
CONDITION SYNONYMS: Idiopathic cerebral ischemic necrosis
GENERAL DISCUSSION:
 Feline ischemic encephalopathy sporadically occurs in mature cats, and is
suspected to result from aberrant migration of Cuterebra larvae in the brain via
nasal cavity invasion, although the cause has not been definitively established
 Primarily affected areas of the brain supplied by the middle cerebral artery
PATHOGENESIS:
 Unknown: Ischemic mechanism suspected, but also direct toxicity suspected
 Theory: Aberrant migration of Cuterebra sp.
 Most commonly seen in summer (July – Sept)
 Presumably, toxic effects of the parasite induce vascular spasms leading to
ischemia
TYPICAL CLINICAL FINDINGS:

 Acute, nonprogressive forebrain signs that may resolve over time: Depression
with mild ataxia, behavioral changes, seizures, blindness
 Severity of clinical signs depends on the degree and location of infarction
TYPICAL GROSS FINDINGS:
 Unilateral (occasionally bilateral but asymmetric) ischemic necrosis- sunken,
depressed cerebral white and grey matter; most common in areas supplied by
the middle cerebral artery; may be multifocal or involve up to 2/3 of one
hemisphere
 May be cavitations with secondary ventricular dilatation
 CNS or leptomeningeal hemorrhage
 In chronic cases there can be cerebral atrophy (most severe adjacent to the
middle cerebral artery of the affected hemisphere)
TYPICAL LIGHT MICROSCOPIC FINDINGS:

 Necrosis of the hippocampus and brain stem
 Ischemic neuronal necrosis
 Early inflammatory response limited due to lack of vascularization of the tissue;
neutrophils (early), macrophages (later) in perivascular cuffs and in neuropil
 +/- vascular occlusive lesions (e.g. thrombosis, vasculitis, infarction)
 +/- parasitic tract, often in the caudate nucleus or thalamus; not associated with
ischemic changes
ADDITIONAL DIAGNOSTIC TESTS:

 Elevated protein level in cerebrospinal fluid
DIFFERENTIAL DIAGNOSIS:
Clinical
 Hypoglycemia – symmetrical signs
 Fibrocartilagenous emboli – usually located in spinal cord
 Rabies
Microscopic
 Feline hippocampal necrosis- similar, but usually bilateral and selective for
hippocampus and piriform lobe; cats present with seizures
 Traumatic cerebral encephalopathy
 Hypoglycemia – symmetrical lesions
Parasites – aberrant migration
 Dirofilaria immitis
 Baylisascaris procyonis
COMPARATIVE PATHOLOGY:
 Horses
 Neonatal maladjustment syndrome (“barker” or “convulsive” foals) – probably
due to a circulatory derangement with subsequent cerebral hypoxia, but the
pathogenesis is not understood
 Ischemic laminar necrosis in the cerebral cortex and multifocal
hemorrhage
 Anesthetic-associated cerebral hypoxia
 Intracarotid injection of drugs in horses
 Dogs - ischemia secondary to atherogenic vascular degeneration (atheroma)
due to hypothyroidism; uncommon
 Idiopathic ischemic encephalopathy has been reported in a non-domesticated
felid (lion) and two raccoons
 Humans - cerebrovascular accidents are often secondary to atherogenic
vascular degeneration; occlusion occurs most frequently at the carotid
bifurcation, the origin of the middle cerebral artery, or at either end of the basilar
artery
Signalment Slide A (JPC #1336140): A military working dog
HISTORY: This dog developed severe convulsions.
HISTOPATHOLOGIC DESCRIPTION: Cerebrum (2 sections): Expanding

and infiltrating the neuropil and extending to the cut margins of the tissue is
a 7mm diameter, unencapsulated, poorly circumscribed, densely cellular
neoplasm composed of round to polygonal cells arranged in vague whorls
which are interspersed by numerous small caliber blood vessels and areas
of mild hemorrhage. Neoplastic cells have indistinct borders, small to
moderate amounts of eosinophilic, vacuolated, fibrillar cytoplasm, and
irregularly round nuclei with finely stippled chromatin and one variably
distinct nucleolus. The mitotic rate is less than 1/10 HPF. Multifocally the
adjacent white matter and neuropil is mildly vacuolated (spongiosis) with
few microglial cells (microgliosis) several foci of hemorrhage, and
perivascular infiltrates of lymphocytes, fewer plasma cells and
macrophages (perivascular cuffing).
MORPHOLOGIC DIAGNOSIS: Brain, cerebrum: Astrocytoma, fibrillary,

breed unspecified, canine.
Signalment Slide B (420072): A cat

HISTORY: None
HISTOPATHOLOGIC DESCRIPTION: Spinal cord (3 sections): Affecting

up to 80% of the sections, effacing both gray and white matter, surrounding
and separating remaining neurons, and compressing the central canal, is
an unencapsulated, poorly demarcated, poorly circumscribed, infiltrative,
densely cellular neoplasm composed of polygonal to spindle to round cells
arranged in short interlacing streams and bundles on a moderate
fibrovascular stroma. Neoplastic cells have indistinct cell borders, a large
amount of pale eosinophilic fibrillar cytoplasm, an oval to elongate nucleus
with finely stippled chromatin and 1-3 variably distinct nucleoli. Anisocytosis
and anisokaryosis are marked; mitoses average 2 per 10 HPF. There are
multifocal multinucleated and binucleate cells. Within the neoplasm there
are low numbers of dilated axon sheaths with swollen eosinophilic axons
(spheroids) admixed with scattered neurons that are swollen with central
chromatolysis (degenerate) or, rarely, shrunken, angular and
hypereosinophilic neurons with pyknotic or karyolytic nuclei (necrotic). The
remaining adjacent neuropil is mildly spongiotic with slightly increased
numbers of glial cells (gliosis).
MORPHOLOGIC DIAGNOSIS: Spinal cord: Astrocytoma, anaplastic,

breed unspecified, feline.
GENERAL DISCUSSION:
 Astrocytoma is the most common primary intracranial tumor of
neuroepithelial origin; comprising approximately 25% of all canine
primary CNS tumors
 Diagnosis is based on the histomorphology of the predominant
neuroepithelial cell type transformed
 Increased incidence in the brachycephalic breeds, particularly
the boxer and Boston terrier; usually dogs 6-11 years of age
PATHOGENESIS:
 Low-grade astrocytic tumors in dogs are reported to have mutations
in the p53 gene, overexpress epithelial growth factor receptor genes
(EGFR), and/or mutations of the MYC oncogene
 Recent study found only 3 p53 mutations of 88 canine brain tumors
 Low-grade astrocytic tumors in humans have mutations in
the p53 gene and overexpress platelet derived growth factor-
 (PDGF-) and as astrocytic tumors increase in severity to high
grade tumors there is additional disruption of tumor-suppressing
gene, Rb and the p16 gene
 Mentation changes, seizures, vestibular disturbances, and vision
loss

 Considerable variation with most being poorly defined
 Slower growing tumors are usually poorly defined, firm and white
to pink
 Rapidly growing tumors are often well delineated, soft and mottled
with hemorrhage and necrosis
 Distortion of the sulci and gyri may occur with tumor expansion
 Most common sites in dogs are the telencephalon and
diencephalon

 Tumor cells may palisade around vessels
 Low grade (well differentiated types): Slow growing, uniform cell
population, low mitotic rate
o Fibrillary: Stellate cells with abundant cytoplasm containing
prominent neuroglial fibrils; most common form
o Protoplasmic: Stellate cells with abundant cytoplasm, few
processes and often microcystic areas
o Gemistocytic: Large cells with abundant eosinophilic
cytoplasm and a marginally located nucleus that resemble
gemistocytic astrocytes
o Pilocytic (spongioblastoma): Interwoven bundles of
elongated bipolar cells; recently described in dogs
 Medium grade (anaplastic):
o Same as glioblastoma multiforme without the necrosis and
vascular proliferation
o Very cellular, pleomorphic population of fusiform to polygonal to
round cells
o High mitotic rate with multinucleated giant cells
o Hemorrhage, cysts and edema
 High grade (glioblastoma, “glioblastoma multiforme”):
o Similar to anaplastic but also characterized by necrosis
and/or glomeruloid vascular proliferation; often
pseudopallisading of tumor cells along foci of necrosis
ULTRASTRUCTURAL FINDINGS:
 Cytoplasmic glycogen granules
 10 nm bundles of intermediate filaments
 GFAP (glial fibrillary acid protein) positive; some high grade tumors
lose GFAP reactivity (Astrocytomas in rats are GFAP negative)
 Vimentin positive
 S-100 positive
 AQP4 and p75NTR in one study discriminated between canine
astrocytomas and oligodendrogliomas
Gross
 Oligodendroglioma: Usually well demarcated
 Neuroblastoma: Well circumscribed, pink-grey neoplasm with areas
of hemorrhage, necrosis and calcification
 Medulloblastoma: Usually in cerebellum of puppies, calves and
adult dogs
 Primitive neuroectodermal tumor (PNET): Soft, grey-pink tumors
 Mixed glioma (oligoastrocytoma)
 Inflammatory lesions
 Metastatic brain tumors: Less common than primary tumors
Microscopic
 Oligodendroglioma: Artifactual perinuclear halos, delicate branching
vasculature
 Primitive neuroectodermal tumors: Closely packed round to
polygonal cells in sheets and bands, often with Homer-Wright or
Flexner-Wintersteiner rosettes
 Also reported in cats, pigs, baboon, mice, fowl and rats
 Malignant astrocytoma was most frequent CNS tumor in a survey of
Sprague-Dawley rats (8 cases from 670 rats); most are GFAP
negative and positive for macrophage markers indicating they may
be of monocytic origin
 Oligoastrocytoma reported in a hooded crane
 High grade astrocytoma (glioblastoma multiforme) reported in an
Atlantic spotted dolphin
Signalment (JPC# 1716400): 7-year-old cat
HISTORY: This cat exhibited depression and anorexia of 2 weeks duration

that progressed to convulsions. Sidestepping and placing responses were
absent on the left side.
HISTOPATHOLOGIC DESCRIPTION: Cerebrum, lateral ventricle:

Multifocally expanding the ventricle, and infiltrating, and compressing
adjacent cortical neuropil is a densely cellular, well-circumscribed,
unencapsulated neoplasm composed of polygonal cells arranged in solidly
cellular areas, true rosettes (both Flexner-Wintersteiner and Homer Wright
variants), and pseudorosettes on a fine fibrovascular stroma. Neoplastic
cells have indistinct cell borders, small to moderate amounts of
eosinophilic, fibrillar to granular cytoplasm, and, rare, poorly discernible,
pale luminal cilia. Nuclei are round to oval and basally oriented with dense
to coarsely stippled chromatin. There is minimal anisocytosis and
anisokaryosis and a mitotic rate of 1 per 10 HPF. Within the neoplasm
there are multifocal areas of eosinophilic cellular and karyorrhectic debris
(necrosis), fibrin and hemorrhage. Within the adjacent neuropil, there is
mild lymphocytic perivascular cuffing of blood vessels which occasionally
have a reactive endothelial lining, increased numbers of glial cells (gliosis),
and, rarely at the interface with the neoplasm, moderate numbers of gitter
cells.
MORPHOLOGIC DIAGNOSIS: Cerebrum: Ependymoma, breed not

specified, feline.
GENERAL DISCUSSION:
 Neuroglial tumors derived from ependymal cells lining the ventricles
and central canal of the spinal cord; can arise from the lateral, third,
and fourth ventricles, mesencephalic aqueduct or central canal
 Reported subtypes: Papillary, clear cell, myoxopapillary, tanycytic,
extraventricular, and subependymomas
 Ependymoma is reported in nonhuman primates, dogs, cats, rats,
cattle, horses, deer, and fish; more prevalent in dogs

 Neurological signs, consistent with a slow-growing, space occupying
lesion
 Ataxia, circling, head tilt
 Reflexes are not affected until the lesion is well advanced

 Slow-growing, expansile neoplasm, with variable demarcation
replacing and compressing the brain or spinal cord
 Gray and fleshy but may be dark from hemorrhage if they project
into a ventricle
 +/- Cavitations
 May metastasize locally via cerebrospinal fluid
 Often cause secondary hydrocephalus
 Well-circumscribed, densely cellular, expansile neoplasm comprised
of polygonal cells arranged in sheets, pseudorosettes, and rosettes
 Pale eosinophilic fibrillar cytoplasm, with indistinct cellular
borders; basally located nuclei are round to oval with
hyperchromatic chromatin; variable mitotic rate
 Papillary variant: Branching papillary stroma covered by
recognizable ependymal cells; spinal cord ependymomas may be
more papilliferous, cells embedded in mucinous intercellular stroma
 Clear cell variant: Resemble oligodendroglioma with perinuclear
halos
 Tanycytic variant: Elongated cells with fibrillar processes forming
bundles and fascicles
 True rosettes: Appear as tubular cavities lined by cells of epithelial
appearance, bound together by desmosomes, have surface cilia
anchoring phosphotungstic acid hematoxylin (PTAH) - positive
blepharoplast, and are more common in feline ependymoma
o Flexner-Wintersteiner rosettes are a spoke- and wheel-shaped
cell formation with a lumen
o Homer Wright rosettes are a circular or spherical groupings of
tumor cells around a pale, eosinophilic, central area that
contains neurofibrils but lacks a lumen
 Pseudorosettes form around blood vessels and are characterized by
a perivascular nuclear free zone
 Malignancy characterized by increased cellular atypia and mitoses
 Intercellular tight junctions and microvilli that project into a lumen or
interdigitate between cells
 Cells lining cavities or papillae have desmosomes, cilia, and
cytoskeletal ciliary basal bodies (blepharoplasts)
 Clear cell variant: cells filled with dense whorls of intracytoplasmic
intermediate filaments

 Phosphotungstic acid-hematoxylin (PTAH) positive staining of basal
bodies
 Most canine ependymomas stain negative for GFAP, while feline
and equine often stain positive; most likely to be positive in anuclear
areas of pseudorosettes
 In a recent study of feline ependymoma, GFAP and pancytokeratin
staining did not correlate with tumor variant
 Human ependymomas stain strongly with anti-epithelial membrane
antigen antibody (EMA); however information about immunoreactivity
of domestic animal ependymomas to EMA is not available
Grossly:
 Astrocytoma, high-grade – also have hemorrhage and necrosis
 Neuroblastoma – also grow by expansion into spinal cord; contain
neuroblastic (Homer-Wright) rosettes and stain with neuronal-specific
cell markers
 Thoracolumbar spinal cord tumor of young dogs (nephroblastoma)
 Choroid plexus tumor – No rosettes and keratin positive; may cause
obstructive hydrocephalus; commonly arise within fourth ventricle
 Meningioma – may be associated with pia mater of choroid plexus
Microscopically:
 Medulloblastoma – pseudorosette formation
 Spinal ependymomas are very rare in species other than man
NERVOUS SYSTEM
March 2017
N-T02
Signalment (JPC #2137343) Slide A: A 5-year-old cat
HISTORY: None
HISTOPATHOLOGIC DESCRIPTION: Medulla oblongata and cerebellum:

Within the vestibular nuclei and extending into the white matter of the
medulla oblongata, there are bilaterally symmetrical areas of rarefaction
and hemorrhage measuring up to 2 mm in diameter that are centered upon
vessels with fragmented endothelium and surrounded by abundant hyaline
material (fibrinoid and necrotizing vasculitis). Within the affected areas
there is disruption and vacuolation of the neuropil (spongiosis), with
replacement by gliosis, reactive astrocytes, gemistocytes, and cellular
debris (necrosis). Neurons are shrunken, hypereosinophilic, with pyknotic
nuclei (necrotic) or have dispersion of Nissl substance and a peripheral
nucleus (chromatolysis). There are occasional round, swollen,
hypereosinophilic axons (spheroids) within dilated myelin sheaths. Vessels
are reactive, with hypertrophied endothelial cells, and are surrounded by
edema, fibrin, and hemorrhage. Neuronal cell bodies within adjacent, less
affected nuclei are pale and swollen (degeneration).
MORPHOLOGIC DIAGNOSIS: Medulla oblongata with vestibular nuclei:

Polioencephalomalacia, bilaterally symmetric, marked, with fibrinoid and
necrotizing vasculitis, hemorrhage, neuronal necrosis, degeneration and
chromatolysis, and gliosis, breed unspecified, feline.
Signalment (JPC #1199288) Slide B: Holstein calf
HISTORY: Six other calves out of 17 were found dead. The calf was
prostrate with a temperature of 102.2F when first examined. It had been ill
for 10 days with CNS signs and transient diarrhea. After an additional
week, it was euthanatized.
HISTOPATHOLOGIC DESCRIPTION: Cerebrum: Multifocally there is

marked vacuolation (spongiosis) of both the cortical gray matter and
superficial white matter and rarefaction of cortical gray matter in a laminar
pattern at the gray-white matter interface, characterized by neuronal
necrosis and loss of the neuropil with gliosis, moderate numbers of gitter
cells, fewer gemistocytic astrocytes, and abundant edema. There are few
dilated, hypereosinophilic axons (spheroids). Vessels within affected areas
are often lined by hypertrophied endothelial cells, and cuffed by several
many lymphocytes, plasma cells and macrophages which occasionally
extend into the surrounding neuropil. The meninges are expanded by clear
space (edema) and infiltrated by the previously described inflammatory
cells.
MORPHOLOGIC DIAGNOSIS: Cerebrum, cortex: Polioencephalomalacia,

cortical, laminar, focally extensive, with neuronal necrosis, edema,
spongiosis, and mild lymphoplasmacytic and histiocytic
meningoencephalitis, Holstein, bovine.
CAUSE: Thiamine (Vitamin B1) deficiency
ETIOLOGIC DIAGNOSIS: Nutritional polioencephalomalacia
CONDITION: Polioencephalomalacia
SYNONYMS: Chastek paralysis (carnivores)
GENERAL DISCUSSION:
 Progressive encephalopathy associated with thiamine deficiency in
carnivores (fox, cat, mink) and a less well-established association with
thiamine deficiency in young ruminants
 Thiamine is a dietary requirement of carnivores; deficiency may be
caused by:
 Decreased thiamine intake
 Consumption of fish containing thiaminase
 Excessive heating of foods
 Preservation of meat with sulfur dioxide
 Upper gastrointestinal disease causing decreased absorption of
thiamine
 Bracken fern and horsetail (Equisetum arvense) are thiaminase
containing plants, and will produce thiamine deficiency in horses eating
these plants
 Thiamine is produced in ruminants by microbial synthesis; deficiency
may be seen in the very young prior to establishing a functional ruminal
flora or in adults caused by:
 Grain overload and overgrowth of thiaminase-producing bacteria
 Ingestion of thiaminase-containing plants (bracken fern, horsetails)
 Ingestion of sulfur and sulfur compounds
 Associated with cobalt deficiency, molasses, and high urea diets
 Liver and muscle are primary sites of thiamine storage
PATHOGENESIS:
 Phosphorylated thiamine is the coenzyme cocarboxylase, which is
involved in oxidative decarboxylation reactions throughout the body
 Cocarboxylase is a cofactor for: Transketolase, alpha-ketoglutarate
dehydrogenase, pyruvate dehydrogenase and branched-chain alpha-
keto acid dehydrogenase
 Transketolase is utilized in the hexose monophosphate shunt, is active
in the white matter and is important in the metabolism of
oligodendrocytes
 The exact pathogenesis is unknown; however, the following factors are
believed to play a role:
 Free-radical injury to the blood-brain barrier > vacuolation of neuropil
 Degenerative changes in glia > rupture > increased extracellular
space > vascular dilation
 Decreased transketolase activity > decreased glucose utilization >
metabolic burst > production of lactic acid > focal lesions
 Activity of ATP-dependent sodium and water transport mechanisms
in neurons is reduced leading to intraneuronal swelling, elevated
intracranial pressure, and necrosis of neurons
 Ruminants: Increased sulfur intake > sulfate reduced to sulfite > sulfite
cleaves thiamine into pyrimidine and thiazole
 Neurons in mid to deep lamina of parietooccipital lobes are
preferentially affected.

 Transient diarrhea before onset of neural signs
 Abrupt onset of depression, muscle tremors, cortical blindness
 Ventriflexion of neck in carnivores
 Ataxia progressing to recumbency with opisthotonus, teeth grinding,
nystagmus, and extensor rigidity
 Thiamine deficiency is always attended by elevation of blood
pyruvate

 Carnivores: lesions pass through the sequence of vacuolation >
vascular dilation > hemorrhage > necrosis
 Lesions are in areas of vulnerability, primarily periventricular grey
matter and occasionally the middle laminae of the occipital and
temporal cortex; more specifically, the inferior colliculi and the medial,
red, and lateral geniculate nuclei are affected
 Petecchial hemorrhages, bilaterally symmetrical in brain stem nuclei,
most often the caudal colliculi and other paraventricular nuclei;
often grossly visible in colliculi and vestibular nuclei
 May see myocardial degeneration and necrosis that is more
prominent in the right versus the left ventricle
 Ruminants: Swollen cerebrum; flattened gyri; narrow
sulci; prominent cerebral cortical necrosis with unaffected cerebellar
cortex; cerebral cortical atrophy; raretentorial herniation and coning of
the cerebellum in severe cases
 Yellow discoloration of cerebrocortical gray matter; affected
areas autofluoresce under ultraviolet light; possible due to ceroid-
lipofuscin or mitochondrial ATP synthase.
 Hydrocephalus ex vacuo occurs in long term cases

 Carnivores: Caudal colliculi most consistently affected
 Initial change is vacuolation in nuclei of special
susceptibility(lateral geniculate bodies, caudal colliculi, red nuclei)
 Vacuolation of neuropil (status spongiosis), vascular dilation,
endothelial hypertrophy, edema, and hemorrhage (often terminal
event)
 Gliosis and neuronal necrosis
 Recovered animals develop intense astrogliosisin affected areas
 Ruminants: Marked laminar cerebral cortical necrosis
 Degeneration and necrosis of neurons of the middle to deep
cortical laminae
 Infiltration by moderate numbers of macrophages in necrotic areas
 Laminar pattern of cerebral cortical edema and necrosis; astrocyte
swelling
 In advanced cases with prolonged survival, areas of marked atrophy
of cerebral gyri with attenuated or absent gray matter zone

 Response to injectable thiamine
 Rumenal gas elevation for sulfur
 Elevated blood pyruvate; decreased erythrocytic transketolase activity
 Microscopic differentials for laminar necrosis in ruminants:
 Lead poisoning: basophilic stippling of RBCs, intranuclear inclusions
in renal tubular epithelia, hepatocytes and osteoclasts
 Salt toxicity: circumstantial in ruminants but well established in pigs
 Hypoxia
 Sulfur toxicity: high sulfur intake
 Horse: Bracken fern and horsetail (Equisetum arvense) are thiaminase
containing plants
 Other encephalomalacias in equine include:
 Leukoencephalomalacia (moldy corn disease): Fumonisin B1
from Fusarium verticillioides (F. moniliforme) and F.
proliferatumresults in necrosis of white matter of the cerebral
hemispheres
 Nigropallidal encephalomalacia: Yellow star thistle ingestion
causes malacia of pallidus and substantia nigra
 Swine: Salt toxicity or water deprivation: Laminar necrosis with infiltrate
of eosinophils
 Man: Wernicke’s encephalopathy, due to thiamine deficiency results in
symmetric paraventricular malacia of the gray matter
 Sled dogs encephalopathy: thalamic necrosis
 Small breed dogs (pug, Yorkies, maltese, shihtzu, Chihuahua):
Necrotizing meningoencephalitis or granulomatous
meningoencephalitis; unilateral
 Cats: Leukoencephalomyelopathy by feeding a gamma-irradiated dry
diet with elevated peroxide and reduced vitamin A concentrations
 Aquatic animals: Higher susceptibility due to fish-based diet that may
contain thiaminase (especially smelt)
 Ataxia with white matter degeneration is reported in lions, cheetahs,
cats, English Foxhounds, Landrace-cross pigs, rats, and nonhuman
primates where deficiencies in vitamins A, B12 (cobalamin),B3
(nicotinamide),B6 (pyridoxine),
and B1 (thiamine) have been implicated
NERVOUS SYSTEM
April 2017
N-V17
Signalment (JPC #1948535): 8-month-old spayed female lilac-point

Himalayan cat
HISTORY: This cat exhibited ataxia, anterior uveitis, and chorioretinitis.

The clinical course deteriorated to the point where the cat was euthanized.
Grossly, there were bilateral corneal protrusions with central (2-3 mm)
erosions, a faintly mottled liver with gray-white foci and nodules on the left
kidney.
HISTOPATHOLOGIC DESCRIPTION: Cerebrum and diencephalon:

Multifocally expanding Virchow-Robin space up to 2-5 times normal and
infiltrating the perivascular and periventricular neuroparenchyma, as well as
the choroid plexus, are numerous lymphocytes, plasma cells, fewer Mott
cells, epithelioid macrophages, and few neutrophils. Vessel walls (primarily
venous) are often obscured or disrupted by previously described
inflammatory cells (phlebitis) or are lined by hypertrophied (reactive)
endothelial cells. There is periventricular rarefaction and loss of the
neuroparenchyma (necrosis) with replacement with variable amounts of
eosinophilic proteinaceous fluid. Multifocally, the ependymal lining of the
lateral ventricle and third ventricle is disrupted by the previously described
cellular infiltrate with areas of loss. The third ventricle is filled with
eosinophilic proteinaceous fluid and few of the previously described
inflammatory cells. Within the adjacent neuroparenchyma there is a mild to
moderate gliosis composed of scattered reactive and gemistocytic
astrocytes, gitter cells, and microglia, with vacuolation of the
neuroparenchyma (spongiosis). Occasionally, myelin sheaths are dilated
and rarely contain swollen hypereosinophilic axons (spheroids).
MORPHOLOGIC DIAGNOSIS: Cerebrum and diencephalon:

Meningoencephalitis perivascular and periventricular, granulomatous and
lymphoplasmacytic, diffuse, marked, with necrosis, phlebitis, ventriculitis,
and choroiditis, Himalayan cat, feline.
ETIOLOGIC DIAGNOSIS: Coronaviral encephalitis
CAUSE: Feline infectious peritonitis virus (Feline coronavirus – FCoV)
CONDITION: Feline Infectious Peritonitis (FIP)
GENERAL DISCUSSION:
 FIP is a group 1 coronavirus that has two subtypes, 1a and 1b
 The best documented example of generation of coronavirus species
through homologous recombination is present in group 1a
coronavirus, which is the generation of FCoV [also called feline
infectious peritonitis virus (FIPV) in some publications] type II strains
by double recombination between FCoV (FIPV) type I strains and
canine coronavirus (CCoV)
 Feline Infectious Peritonitis (FIP): fatal, systemic disease associated
with feline coronavirus (FCoV) infection; infects domestic and wild felids
 FIP causes a fibrinous to granulomatous serositis, protein-rich effusions
in body cavities, and granulomatous inflammatory lesions in several
organs
 Family Coronaviridae, genus Coronavirus; enveloped, single-stranded
RNA virus
 Predisposing factors: young (< 3 years old) cats; immunosuppression;
multi-cat households
 Prevalence of FCoV infection: high (up to 90%), but only 5% develop
FIP; mortality in cats with FIP is up to 100%
 FIP is a common cause of neurologic disorders in cats; 13% of cats with
FIP develop neurologic signs
 Prominent in catteries that breed Devon Rex, British shorthair, Birman,
Burmese and Abysinnian
PATHOGENESIS:
 Transmission is via oronasal via feces; rarely saliva, mutual grooming,
close contact, sharing food bowl, grooming tools; transplacental is
uncommon
 There are two proposed mechanisms for the development of vasculitis
based on multiphasic nature of disease
 Type III immune mediated disease (chronic necrotizing vasculitis)
 Activation of viral infected macrophages, resulting in release of
cytokines and alterations in endothelial junctional complexes and
vascular leakage (acute phlebitis)
 Target cells are monocytes and macrophages; FCoV-infected
circulating monocytes are thought to be responsible for viral
dissemination
 Both serotypes can use ‘‘dendritic cell (DC)–specific intercellular
adhesion molecule (ICAM) grabbing nonintegrin’’ (DC-SIGN, CD209), a
C-type lectin, which recognizes high-mannose oligosaccharides as
ligands, to infect monocyte-derived dendritic cells
 Co-localization and binding inhibition studies confirmed that DC-SIGN
and not APN is involved in the entry process of serotype I FCoV in
monocytes, whereas for serotype II FCoV, both APN and DC-SIGN play
a role in the infection of monocytes
 Specifically, for serotype II, binding is mediated by APN, but DC-SIGN
is important for either internalization or a subsequent step
 Cats infected with nonmutated FCoV > virus replicates in enterocytes >
asymptomatic infection or diarrhea > shed virus intermittently or
continuously
 Key event in FCoV becoming virulent is spontaneous viral genetic
mutation during replication in the infected host
 At present, 3 key features have been identified as essential
prerequisites for the development of FIP lesions:
 1. Systemic infection with virulent FCoV (ie, FIPV)
 2. Effective and sustainable FIPV replication in monocytes, and
 3. Activation of FIPV-infected monocytes:
 The monocytes strongly express cytokines, such as tumor
necrosis factor (TNF)–a and IL-1b, and adhesion molecules, such
as CD18, that allow their interaction with activated endothelial
cells and express enzymes, such as matrix metalloproteinase-9,
which dissolve the vascular basement membrane at sites of
monocyte emigration
 The endothelial cells appear systemically activated, and the
restrictive distribution of vascular lesions (ie, affecting veins and
only in selected organs) is likely a consequence of selective
responsiveness of the endothelium
 Cats with FIP show increased vascular endothelial growth factor
(VEGF) transcription in (virus-infected) monocytes and increased
serum VEGF levels
 Furthermore, peritoneal exudate cells of cats with FIP exhibit high
TNF-a mRNA levels and were previously shown to release IL-1b
and IL-6, and even alveolar macrophages collected by
bronchoalveolar lavage from FIP cats show significant
upregulation of TNF-a, GM-CSF, granulocyte (G)–CSF, IL-6, and
other B-cell differentiation factors, all suggesting strong
generalized monocyte/macrophage activation in response to FIPV
 Two recognized biotypes:
 Feline enteric coronavirus (FECV) > minimal disease
 Feline infectious peritonitis virus (FIPV) > severe systemic immune-
inflammatory disorder
 2 clinical forms of FIPV
 “Effusive” (Wet) – intracavity effusions and abdominal
distension
 “Dry” parenchymatous form – “neurological” or “brain and eye”
form
 Clinical signs and pathologic findings are due to vasculitis and
phlebitis and organ failure resulting from damage to blood vessels that
supply them
 Host cell mediated immune response determines severity of FIP
lesions
 Strong cell-mediated immunity (CMI) > viral replication terminated
 Partial CMI > non-effusive (dry) form
 No CMI > effusive (wet) form
 Antibody-dependent enhancement is enhanced form of FIP may occur
in cats with preexisting antibodies

 Neurologic signs
 Ataxia, nystagmus, seizures, incoordination, intention tremors,
hyperesthesia, behavioral changes, cranial nerve deficits
 If FIP lesions affect peripheral nerves or spinal column then
lameness; progressive ataxia; tetraparesis, hemiparesis, or
paraparesis
 Other clinical findings
 Nonspecific: chronic fever, weight loss, anorexia, lethargy; stress
leukogram
 Ascites, thoracic and/or pericardial effusion
 Dyspnea, tachypnea, muffled heart sounds
 Abdominal masses on palpation (omental/visceral adhesions;
mesenteric lymphadenopathy)
 Chronic diarrhea, vomiting, obstipation, thickened intestines on
palpation
 Eyes: anterior uveitis; retinal changes – occasional granulomatous
inflammation, cuffing of retinal vasculature, +/- hemorrhage,
detachment
 In-utero infections: stillborn or clinically affected kittens
 Clin path:
 Lymphopenia
 Mild to moderate regenerative anemia
 Hyperproteinemia due to hypergammaglobulinemia
 Other laboratory parameters, such as liver enzymes, bilirubin,
urea, and creatinine, might be helpful, but high values merely
reflect organ damage, which is most likely a consequence of
FIP lesions
 FIP effusions typically have a very high protein content (>35
g/l) but a low cellularity (<5000 nucleated cells/ml), with a
dominance of macrophages and neutrophils; when sufficient
cells are present, the demonstration of viral antigen in
macrophages confirms the diagnosis with a very high PPV
 Acute phase protein, a1 acid glycoprotein (AGP):
 Serum levels are highly elevated in cats with FIP (>3 mg/ml)
but are also high in other inflammatory conditions or neoplastic
diseases, such as lymphoma
 Furthermore, AGP levels may also rise in asymptomatic
FCoV carriers, especially from households with endemic
infection
 However, when interpreted alongside pretests (ie,
epidemiological factors, clinical information, and FCoV
serology), moderate AGP increases are useful discrimination
parameters when the probability of FIP is high, whereas with
low FIP probability, only very high AGP levels support the
diagnosis of FIP

 CNS lesions: meninges thickened and opaque; mild to moderate
hydrocephalus with accumulation of a protein-rich exudate
 Other gross findings
 FIP lesions are common in peritoneum, kidney, and uvea
 Fibrinous pleuritis, peritonitis, and/or pericarditis with thoracic,
abdominal, and/or pericardial effusion
 Multifocal granulomatous lesions in various organs, including eyes,
CNS, and intestine - lesions commonly found only in ileocecocolic
junction, but may be present in other areas (e.g. colon or small
intestine)
 Mesenteric lymphadenopathy
 Eyes are not routinely examined, but will have lesions
 Anterior uveitis – may be subtle depending on time of
diagnosis
 Keratic precipitates - (important clinical hallmark)
 Retinal changes – occasional granulomatous inflammation,
cuffing of retinal vasculature, +/- hemorrhage, detachment

 Granulomatous to necrotizing phlebitis and periphlebitis
 Neurologic lesions:
 Noneffusive form usually causes leptomeningitis, chorioependymitis,
focal encephalomyelitis, and ophthalmitis
 Effusive form usually causes a pyogranulomatous vasculitis in the
vessels of the leptomeninges and the periventricular white matter
(around the fourth ventricle)
 Additional lesions:
 Cell/protein-rich exudates or effusions
 Interstitial pneumonia, interstitial nephritis, splenic and lymph node
histiocytosis, lymphoid hyperplasia/depletion, enteritis,
panophthalmitis, anterior uveitis, keratic precipitates (large globular
accumulations of macrophages and neutrophils adherent to the
corneal endothelium)
 FIP virus present in macrophages in lesions
 Pleomorphic, spherical enveloped virions; 60-120nm in diameter
(average 100 nm)
 Virions appear in dilations of endoplasmic reticulum and matrix of large
vacuoles
 Characteristic petal-shaped surface projections (peplomers) responsible
for crown-like ("corona") appearance of virus

 Histopathology (if pathognomonic lesions present); detection of
intracellular FCoV antigen (immunofluorescence or
immunohistochemistry); RT-PCR
 There are no pathognomonic laboratory changes
 CSF in many cats with neurologic signs associated with FIP have
normal CSF taps; positive anti-coronavirus IgG titer; elevated protein
(50-350 mg/dL); pleocytosis
 Effusion is modified transudate or exudate; clear to yellow, viscous
fluid, fibrin; low cellularity (<1000 nucleated cells/ml); increased
protein content (>35g/L), LDH (>300IU/L), alpha-amylase (pancreatic
involvement)
 Most consistent finding is increase in total serum protein
concentration due to increase in globulins (monoclonal or polyclonal
hypergammaglobulinemia), but only reflects chronic antigenic
stimulation
 Intracellular FCoV Ag by immunoflourescence or
immunohistochemistry (CCV2-2 is more sensitive than FIPV3-70)
 Causes of meningitis and encephalitis in cats:
 Feline leukemia (Type C Retrovirus, Retroviridae)
 Feline immunodeficiency virus (Lentivirus, Retroviridae)
 Rabies (Lyssa virus, Rhabdoviridae)
 Pseudorabies (Porcine herpesvirus-1, alphaherpesvirus)
 Toxoplasma gondii, Cryptococcus neoformans
 Identification of Bartonella henselae in two cats with
pyogranulomatous myocarditis and diaphragmatic myositis
 Leukoencephalomyelopathy in cats similar to spontaneous outbreaks
by feeding a gamma-irradiated dry diet with elevated peroxide and
reduced vitamin A concentrations
 Cheetahs are highly susceptible to developing FIP; possibly due to
genetic deficiency in cellular immunity
 Few reports of lions in captivity
Emerging coronaviral diseases in animals include:

 Epizootic catarrhal enteritis and feline infectious peritonitis (FIP)–like systemic
disease in ferrets
 A fatal systemic disease in dogs
 Mink epizootic catarrhal gastroenteritis.
Coronaviruses in other species:

 Avian: Infectious Bronchitis (chickens); Coronaviral enteritis of turkeys
(Bluecomb disease)
 Bovine: Bovine coronavirus
 Canine: Canine coronavirus
 Ferrets: ferret systemic coronavirus
 Mice: Mouse Hepatitis Virus
 Rats: Sialodacryoadenitis virus
 Porcine: Transmissible gastroenteritis virus; Hemagglutinating
encephalomyelitis virus; Porcine respiratory coronavirus; Porcine
epidemic diarrhea (corona-like virus)

SPECIAL SENSES
May 2018
S-V03
Signalment (JPC #1725431): Six-month-old female cat
HISTORY: Tissue from a six-month-old female cat that developed an eye

infection that was treated with topical medication for several weeks.
During this time, the cat became lethargic and ataxic. After a period of
anorexia lasting three weeks, the cat was euthanized.
HISTOPATHOLOGIC DESCRIPTION: Eye and eyelid: All parts of the uvea,

the choroid, ciliary body, and iris, are moderately expanded by
multifocal, often perivascular infiltrates of neutrophils, macrophages,
and fewer lymphocytes and plasma cells, admixed with abundant fibrin
and edema. Multifocally throughout the uvea and adjacent sclera, blood
vessels are lined by reactive endothelium with occasional expansion of
the tunica media and adventitia by edema and infiltration by a similar
population of inflammatory cells (vasculitis). The retina is detached from
the underlying hypertrophic retinal pigment epithelium (RPE), and
folded, with eosinophilic proteinaceous material and few neutrophils
(exudate) and sloughed RPE cells in the space between the retina and
RPE. There is multifocal loss of photoreceptor cells and cells in the inner
nuclear and ganglion layers with exposure of prominent Muller’s fibers,
vacuolation (axonal degeneration or spongiosis) and atrophy or
degeneration of remaining ganglion cells. Multifocally, the optic nerve is
vacuolated, and contains microglia with ingested myelin (gitter cells).
Within the anterior chamber there is abundant eosinophilic proteinaceous
material with fibrin and moderate numbers of neutrophils and
macrophages (hypopyon). This material and inflammatory population
bilaterally fills and obscures the iridocorneal drainage angles and also fills
lymphatics. Both the bulbar and palpebral conjunctivae are moderately
expanded by fibrin, edema, and lymphoplasmacytic nodular and
perivascular infiltrates.
MORPHOLOGIC DIAGNOSIS: Eye: Uveitis and scleritis, pyogranulomatous

and lymphoplasmacytic, marked, with pyogranulomatous vasculitis,
retinal detachment, hypopyon, and optic nerve degeneration, breed
unspecified, feline.
ETIOLOGIC DIAGNOSIS: Feline coronaviral uveitis
CAUSE: Mutated feline enteric coronavirus (feline infectious peritonitis

virus)
GENERAL DISCUSSION:
 Family Coronaviridae, genus Coronavirus - enveloped, single

stranded, positive sense RNA viruses
 Feline infectious peritonitis (FIP) is a worldwide, invariably fatal,
sporadic, low prevalence viral disease of domestic and wild felids
caused by feline coronavirus (FCoV)
 Purebred domestic cats and certain species of large cats
(e.g. cheetahs, lions) may be genetically predisposed to developing
FIP
 FECV infects and replicates only in enterocytes, causing diarrhea or
asymptomatic infection; FIPV infects and replicates primarily in
macrophages, resulting in macrophage activation and systemic
infection
 Most cats that die of FIP have ocular involvement; this is
detected by coagulation of the aqueous with acidic fixatives
(indicating increased aqueous protein)
PATHOGENESIS:
 Fecal-oral transmission and possibly inhalation of FCoV > replication

in enterocytes / lymphoid system > mutation (FIPV), virus able to
replicate in macrophages > secondary macrophage associated
viremia > dissemination to multiple organs and vessels > host
immune response
 Mutation is presumed to occur at 3c gene of feline enteric
coronavirus
 The progression of disease depends on the cat’s immune response:
o Strong cell-mediated immune response: Results in
activation of macrophages, FIP virus replication is
terminated, and cleared
o Weak or ineffective cell-mediated response: Delayed (Type
IV) hypersensitivity response; noneffusive (dry form)
syndrome ensues, with a less florid macrophage response in
tissue and reduced virus production; this form has a more
prolonged clinical course (1-6 months)
o No/ineffective cell-mediated immunity: Antibody is
produced, but there is a failure to generate a cell-mediated
response and cats develop effusive disease (wet
form); vasculitis results from both Type III
hypersensitivity response [primary immune complex
deposition] and activation of macrophages; this syndrome
has a rapid clinical course, progressing to death in 1-12 weeks
 Granulomatous inflammation and granulomatous phlebitis (due to
enhanced adhesion of virally infected monocytes/macrophages to
endothelial cells)
 Antibody-mediated lysis of infected macrophages in or around
vessels (predominantly veins) may enhance the inflammatory
reaction
 Release of substance from infected cells causes apoptosis of
bystander lymphocytes
 Noneffusive (dry form): Typically granulomatous inflammation,

localized in the lymph nodes, kidneys, uvea, meninges, ependyma,
and choroid plexus of the brain and spinal cord with vague signs of
dullness, weight loss and anorexia and CNS signs (ataxia,
nystagmus, seizures) in 12.5% of cases
 Ophthalmic signs are far more common in the noneffusive form and
include anterior uveitis, chorioretinitis, miosis, nystagmus, aqueous
flare, hypopyon, hyphema, blepharospasm, and epiphora
o Clinicopathological features:
 Neutrophilia with left shift
 Lymphopenia
 Nonregenerative anemia ([HCT] <30%; anemia of chronic
disease)
 Cerebral spinal fluid elevated protein levels (56-348
mg/dL with normal <25 mg/dL) and pleocytosis (100-
10,000 nucleated cells/mL)
 Effusive (wet form): Weight loss, dyspnea, tachypnea, mild

pyrexia, icterus, scrotal enlargement, palpable abdominal
distention and masses (from adhesions)
o Clinicopathological Features:
 Plasma proteins typically elevated because
of hypergammaglobulinemia (may be polyclonal or
monoclonal) due to chronic inflammation and antibody
production
 Effusion is a high protein exudate or modified
transudate with a high protein
concentration (>3.5g/dL)
 Albumin:globulin ratio less than 0.8 and typically 0.45
or less (albumin level remains normal or falls slightly
and globulin levels increase, possibly through
stimulation of B cells by IL-6)
 Elevated Alpha1-acid glycoprotein (AGP) >1500 ug/mL
 Neutrophillia with left shift
 Noneffusive form – Granulomatous lesions in various organs (on

surface and throughout)
o Eye: Keratic precipitates in anterior chamber, uveitis,
panophtalmitis, and fibrin within anterior chamber,
hypopyon, hyphema, corneal edema
o Colon: Thickened with a gross appearance similar to
alimentary lymphosarcoma
o Abdominal and thoracic lymph nodes: Lymphadenopathy
o Kidneys: Enlarged with vasculocentric pyogranulomas
o Brain: Hydrocephalus with gelatinous foci resembling
cryptococcosis possible in cats with neurologic involvement
 Effusive form – Pleural effusion (40%) and effusive peritonitis
(60-70%) with up to 1L of viscous clear to yellow fluid
o The surfaces of abdominal and/or thoracic contents covered
with small (1-2 mm) white plaques of fibrin with a granular
appearance; large amounts of fibrin can result in adhesions on
visceral and peritoneal surfaces
o Orchitis and periorchitis (reported, but uncommon) - scrotal
swelling and enlarged testicles
TYPICAL LIGHT MICROSCOPIC FINDINGS
 Phlebitis (vessels typically surrounded by a zone of necrosis and a

mixed inflammatory cell infiltrate); most common in retrobulbar
area, in the optic nerve sheath, and retina
 Presence of large globular accumulations of macrophages and
neutrophils adherent to corneal endothelium (keratic
precipitates) is an important clinical hallmark
 Pyogranulomas, large or small, consolidated or numerous, focal
tissue necrosis
 Leukocytes infiltration is heaviest in ciliary body and limbic sclera
and usually is an even mix of leukocytes, but can be purely
histiocytic
 The most common ocular manifestation is granulomatous anterior

uveitis with variable chorioretinitis, retinal separation, peripheral
anterior synechia, preiridal fibrovascular membrane, lens luxation,
and iridocorneal angle closure
 Increased GFAP expression in the retina in FIP cases and
proliferation of Müller cells in cases of retinal detachment
 In cases of severe inflammation, B-cells and plasma cells
predominate over T-cells and macrophages; macrophages
expressing FCoV antigens are believe to be derived from blood
through calprotectin immunolabeling
 Coronaviruses are 80-160 nm in diameter and have a distinctive

fringe of petal-shaped peplomers or spikes that resemble a crown
or corona; peplomers are approximately 20 nm long and 7 nm wide
at the tip
 Virions may form paracrystalline arrays
 Gold standard for diagnosis is IHC demonstrating viral antigen

within uveal WBCs
 Clinical signs and typical gross and histologic findings are critical
diagnostically
 There is a lack of specificity of serologic tests for the FIP virus due
to cross reaction with other antigenically related coronaviruses
 Rivalta’s test of abdominal effusion
 Many cats have coronaviral antibodies from prior FECV infection,
which are indistinguishable from FIPV antibodies; however, a
negative or very high (1:1600) FIP (coronaviral) titer can exclude or
support an FIP diagnosis
 Detection of intracellular FCoV antigen by immunoflourescence or
immunohistochemistry (CCV2-2 more sensitive than FIPV3-70)
 Virus detection tests include:
o RT-PCR (reverse transcriptase polymerase chain reaction) –
can perform on abdominal or thoracic effusions
o Direct FA – monoclonal antibodies against FIP N protein
o Immunohistochemistry
o Electron microscopy
 Anterior uveitis in the cat: Neoplasia (malignant lymphoma),

trauma, infectious (feline leukemia virus, feline immunodeficiency
virus, toxoplasmosis, protothecosis, cryptococcosis, bacterial
septicemia)
 Ocular FIP has been reported in non-domestic felids (African lion)
Other Coronaviruses:
 Avian:
o Chickens: Avian infectious bronchitis virus -
tracheobronchitis, nephritis
o Turkeys: Bluecomb virus - enteritis
 Bovine: Bovine coronavirus - gastroenteritis (winter dysentery);
bovine respiratory coronavirus
 Canine: Canine coronavirus - enteritis
 Guinea pigs: Coronavirus-like infection - enteritis, wasting
syndrome
 Mice: Mouse hepatitis virus - hepatitis, enteritis, encephalomyelitis
 Mink: Mink enteric coronavirus
 Ferret:
o Ferret enteric coronavirus – enteritis, pyogranulomatous
panopthalmitis reported.
o Ferret systemic coronavirus infection - similar to dry form of
FIP but no effusion, icterus, or increased bilirubin
 Rabbits:
o Rabbit coronavirus - enteritis
o Rabbit pleuritis virus - pleural effusion disease and
cardiomyopathy
 Rats: Sialodacryoadenitis virus
 Swine:
o Transmissible gastroenteritis virus (TGEV)
o Porcine epidemic diarrhea virus - gastroenteritis
o Hemagglutinating encephalomyelitis virus - vomiting, wasting,
encephalomyelitis
o Porcine respiratory coronavirus - mutation from TGEV

SPECIAL SENSES
April 2018
S-N07
Signalment (JPC# 4066796): 12-year-old intact domestic shorthair cat.
HISTORY: This cat had corneal perforation of unknown duration,

suspected cataracts and suspected anterior lens luxation of the right eye
(OD), and the eye was enucleated. Grossly, the right globe was 1.9 cm in
nasolateral diameter, and had a white-tan, raised mass at 3-6 o'clock. On
cut section, the mass was firm to slightly gritty and obscured the ciliary
body and a portion of the iris. The lens was opaque and slightly irregular.
The retina was detached, and the peripheral iris was irregular
segmentally.
HISTOPATHOLOGIC DESCRIPTION: Eye, globe: Within the anterior
chamber, extending from the lens epithelium, adherent to the
fragmented lens capsule, infiltrating the choroid, and incorporating the
detached atrophic retina is a well-demarcated, infiltrative, moderately
cellular, unencapsulated, multilobulated neoplasm composed of
neoplastic chondrocytes evenly dispersed within a light blue partially
mineralized chondroid matrix. In the center of the neoplastic lobules,
chondrocytes are within lacunae, have a moderate amount of clear to
highly vesiculated cytoplasm, and a round pink nucleus with a prominent
nucleolus. At the periphery of neoplastic lobules, neoplastic cells are
more spindled to stellate with a moderate amount of vesicular
amphophilic cytoplasm, an ovoid to elongate nucleus with finely stippled
chromatin, and 0-1 variably distinct nucleoli. Mitotic figures are
predominantly within the peripheral spindle cell population and average 3
per 10 40x HPF (2.37mm2). The cartilaginous matrix contains foci of
mineralization. The neoplasm adheres to a break in the lens capsule and
extends partially circumferentially around the lens. Lens fibers
multifocally undergo marked subcapsular spindle cell metaplasia, mild
subcapsular cartilaginous metaplasia, and mineralization. There is a
multifocal thin prelenticular fibrous membrane that is up to 250um thick
and extends around the lens and extends to the ciliary body (cyclitic
membrane). The neoplasm distorts the ciliary body and is unilaterally
confluent with the iris which is elevated and adhered to the corneal
endothelium (anterior synechia) by a membrane of loosely arranged
collagen (pre-iridal fibrovascular membrane) and moderate numbers of
lymphocytes, plasma cells, and pigment laden macrophages. The
neoplasm extends under (external to) the ciliary body and into the
choroid and along a detached segment of retina; there is abundant clear
space separating layers of the choroid (edema). The retina displays
marked atrophy of all layers, most prominently of the inner retinal layers
with cystic degeneration of the outer retinal layers. There is a small
amount of subretinal proteinaceous exudate and hypertrophy of the
retinal pigmented epithelium. The anterior aspect of the iris distant to
the neoplasm is covered by a thin fibrovascular membrane (pre-iridal
fibrovascular membrane) that extends across and occludes the
iridocorneal angle, and onto the corneal endothelium. This fibrovascular
membrane contains moderate numbers of lymphocytes and fewer
macrophages and plasma cells that infiltrate the edematous anterior
aspect of the iris. There is a central break in Descemet’s membrane with
associated corneal thickening due to stromal infiltration with numerous
lymphocytes, plasma cells, fewer macrophages, and melanin-laden
macrophages, and ingrowth of small caliber blood vessels
(neovascularization). There is diffuse vacuolation and hypertrophy of the
corneal endothelium and mild hyperplasia of the corneal epithelium.
MORPHOLOGIC DIAGNOSIS:
1. Eye, globe: Chondrosarcoma (post-traumatic ocular sarcoma).

2. Eye, lens: Lenticular rupture with subcapsular fibrous and
chondroid metaplasia.
3. Eye, cornea: Keratitis, lymphoplasmacytic and histiocytic, focally
extensive, chronic, moderate, with Descemet’s membrane rupture.
ETIOLOGIC DIAGNOSIS/CONDITION: Feline post-traumatic ocular sarcoma

(FPTOS); primary ocular sarcoma
GENERAL DISCUSSION:
 Feline posttraumatic ocular sarcoma (FPTOS), first recognized as a

condition in 1990, is the second most common primary ocular
neoplasm in cats according to one primary source, and the third
most common according to another
 FPTOS can be highly locally invasive, extension along the optic
nerve or peripheral nerve to the brain is common, local orbital
recurrence following enucleation is common, and distant metastasis
may occur
PATHOGENESIS:
 Ocular trauma (especially penetrating injury) or severe ocular

disease is the presumed initiating event, followed by a period of
dormancy that typically lasts multiple years (average 5-7 years)
 The neoplasm is believed to arise from a malignant
transformation of lens epithelial cellsbecause:
o Lens capsule rupture is noted in almost all cases, whereas it
is rarely present in other non-FPTOS large ocular tumors
o Neoplasms are initially centered on the lens
o Some neoplasms are immunopositive for lens structural
protein crystalline αA, less often are immunopositive
for smooth muscle actin (SMA, which lens epithelium can
express in diseased states such as cataracts),
and occasionally express cytokeratin (this may reflect the
origin of the lens epithelium from surface ectoderm, although
cytokeratin expression is usually lost during embryogenesis)
o Neoplastic cells multifocally deposit lens capsule/basement
membrane-type material

 FPTOS typically occurs in cats with a prior history of severe ocular
disease
 Tumors typically demonstrate a long latency period (range 2 months
to >10 years), with an average of 5-7 years
 Most neoplasms are recognized late in the disease process when the
globe is almost filled by the neoplasm, the lens may be collapsed,
and the neoplasm may extend into the sclera and/or optic nerve
 Initially, the tumor tends to surround the lens (especially in the

area of lens capsule rupture or wrinkled lens capsule), then lines
the inside of the eye (especially the choroid); the inclination to
“line the globe” is a repeatable feature that is useful in
distinguishing primary ocular sarcoma (FPTOS) from rare
metastatic sarcomas, and eventually the highly
infiltrativeneoplasm effaces the uvea +/- extension into the sclera
and/or optic nerve
 Cellular morphology: features vary from fibrosarcoma to
osteosarcoma to giant cell tumor (even within the same eye);
typically, neoplastic cells are spindle with severe pleomorphism, a
high mitotic index, and multinucleate cells may be present
 Matrix: Individual neoplastic cells or segments of individual
neoplastic cells may be separated by basement membrane-type
material, and a small percentage of neoplasms have osteoid and/or
chondroid material deposition
 Lens: The lens is often ruptured, and in advanced cases there may
only be remnant lens capsule fragments
 Infiltration: extension beyond the sclera is a poor prognostic
indicator, optic nerve involvement is a poor prognostic indicator,
intracranial extension along the optic nerve and rare metastasis
have been described (present in up to 60% of cases according to one
source)
ADDITIONAL DIAGNOSTICS:
 Immunohistochemistry/histochemistry:
o Vimentin (almost 100%)
o +/- Lens structural protein crystalline αA(33%)
o +/- Smooth muscle actin (SMA, ~20%)
o +/- Broad spectrum cytokeratin (~15%)
o Matrix material: PAS positive, type IV collagen
immunoreactive
 There are three morphological variants of FPTOS, all of which tend

to line the inner aspect of the globe:
o Spindle cell variant: lens epithelium derived, 70% of FPTOS
o Round cell variant: cells are pleomorphic and express both
T- and B-lymphocyte markers and may represent post-
traumatic/chronic inflammatory lymphoma, 24% of FPTOS;
this tumor is more likely to be effacing than the spindle cell
variant and is less likely to line the inner aspect of the globe;
it may extend beyond the sclera but is less likely to infiltrate
the optic or peripheral nerves; there is often extensive
necrosis with peritheliomatous growth pattern; cells are not
immunoreactive for vimentin, SMA, or cytokeratin
o Osteosarcoma/chondrosarcoma variant: 6% of FPTOS; similar
features to the spindle cell variant with the addition
of chondroid, cartilaginous, and/or osteoid material
 Feline intra-ocular neoplasms:
o Feline diffuse iris melanoma (S-N02) is the most common
ocular neoplasm in cats and the eventual outcome is virtually
always glaucoma
o Tumors of ocular neuroectoderm: iridociliary epithelial tumor
(adenoma or carcinoma) (S-N03), medulloepithelioma,
retinoblastoma (rare in veterinary medicine)
o Intraocular chondrosarcoma, not related to trauma, has been
documented very rarely in cats; the tissue origin is unclear,
possibly multipotent mesenchymal stem cells of the
trabecular meshwork, cancer stem cells, or vascular
pericytes; neoplastic cells are compressive rather than
infiltrative, and there appears to be favorable survival rates
following enucleation
 Posttraumatic ocular sarcoma is almost exclusively a condition of

cats, with two reports described in rabbits (both rabbits were
negative for cuniculi and bacterial infection via histochemical
staining and PCR)
 FPTOS has similarities with feline vaccine associated sarcomas:
traumatic initiating event, long period of dormancy, and similar
histologic characteristics
 Primary ocular neoplasms are most frequently reported in dogs and
cats, and are inexplicably rare in other domestic species; most
primary intra-ocular neoplasms have negligible metastatic
potential
 Metastatic ocular neoplasms are not uncommon; with the
exception of malignant lymphoma, carcinomas are reported
more frequently than sarcomas

SPECIAL SENSES
May 2018
S-N06
Signalment (JPC # 2241434): Cocker spaniel
HISTORY: Tissue from a cocker spaniel with a long-standing history of

otitis externa
HISTOPATHOLOGIC DESCRIPTION: Slide S-N06a: Glabrous skin, ear

canal: Expanding the dermis, and elevating the overlying, hyperplastic
epidermis, is an unencapsulated, well-circumscribed, moderately-
cellular, polypoid neoplasm composed of cuboidal cells lining variably
ectatic to cystic tubules, occasionally piling up to form multiple layers
and papillary projections, supported by a moderate fibrovascular stroma.
Neoplastic cells have indistinct cell borders, moderate amounts of
eosinophilic granular cytoplasm, and round to oval nuclei with finely-
stippled chromatin and one distinct nucleolus. Mitoses average 1 per 10
HPF. Diffusely, lumina of tubules are filled with pale homogeneous
eosinophilic to gray-brown material (cerumen), few sloughed epithelial
cells, macrophages, degenerate neutrophils and necrotic debris.
Multifocally, there are few scattered lymphocytes, plasma cells, and
macrophages that often contain intracytoplasmic brown material
(cerumen). Diffusely, the epidermis is hyperplastic with acanthosis,
occasional rete ridges and mild orthokeratotic hyperkeratosis. There is
multifocal epidermal erosion and ulceration.
MORPHOLOGIC DIAGNOSIS: Glabrous skin, ear canal: Ceruminous gland

adenoma, cocker spaniel, canine.
Signalment (JPC #1416286): Cat
HISTORY: Both ear canals contained variably sized nodules projecting

from the pinna and occluding the canal. The nodules were white to dark
blue and firm.
HISTOPATHOLOGIC DESCRIPTION: Slide S-N06b: Haired skin, ear canal:

Expanding the dermis, focally distorting the auricular cartilage, and
elevating the hyperplastic, ulcerated epidermis, is an unencapsulated,
poorly-circumscribed, infiltrative, densely-cellular neoplasm composed of
polygonal cells arranged in nests, tubules and acini with multifocal
luminal papillary ingrowths supported by a moderate fibrovascular
stroma. Neoplastic cells have variably distinct cell borders, moderate
amounts of finely granular, eosinophilic, often vacuolated cytoplasm, and
irregularly round to oval, occasionally vesiculate, nuclei with finely
stippled chromatin and 1-2 magenta nucleoli. There is moderate
anisokaryosis and anisocytosis. Mitoses average 2 per HPF. Focally within
the subcutis, a vessel contains a nest of neoplastic cells surrounded by
fibrin. The stroma contains multifocal aggregates of many lymphocytes,
fewer plasma cells, neutrophils, and macrophages that are often laden
with brown). material (cerumen Adjacent ceruminous glands are ectatic,
lined by attenuated cuboidal cells and are variably filled with abundant
brown to eosinophilic secretory product (cerumen), necrotic debris,
sloughed epithelial cells, macrophages, degenerate neutrophils and
occasionally acicular cholesterol clefts. Multifocally, sebaceous glands
are mildly hyperplastic. Diffusely, the epidermis overlying the neoplasm
is hyperplastic, with acanthosis and rete ridge formation. There is
multifocal mild orthokeratotic hyperkeratosis and epidermal ulceration
and erosion.
MORPHOLOGIC DIAGNOSIS: Haired skin, ear canal: Ceruminous gland

carcinoma, breed unspecified, feline.
GENERAL DISCUSSION:
 Ceruminous glands are modified apocrine sweat glands within the

external auditory meatus; glands are surrounded by myoepithelial
cells
 The majority are malignant in cats while the majority are benign
in dogs
 Ceruminous gland adenocarcinomas are the most common
malignant neoplasm in the external acoustic meatus of both dogs
and cats
 Usually occur in the older animal
 Mixed or complex ceruminous gland tumors are morphologically
similar to apocrine gland tumors
PATHOGENESIS:
 Represents a continuum from benign to malignant

 May develop secondarily to recurrent bouts of otitis externa;
inspissation of cerumen may play a role in development
 Adenocarcinomas are locally invasive, expansile and may
metastasize to the regional lymph nodes, lungs and systemic viscera
 Head-shaking, scratching at the ear, hemorrhage from the ear canal

 +/- peripheral vestibular signs (head tilt, nystagmus), deafness,
Horner's syndrome
 Smooth nodular or pedunculated, often exophytic, mass in the ear

canal
 Difficult or impossible to distinguish from cystic dilation and
epithelial hyperplasia (hyperplastic polypoid otitis externa),
especially in cocker spaniels
 Smooth or ulcerated, soft or firm, and brown on cut section
 Adenomas: Usually <1 cm diameter, exophytic, only ulcerated if
secondarily infected
 Carcinomas: Larger, more likely to be ulcerated; may invade the
surrounding parotid salivery gland, soft tissues, or bone; may
form a mass at the base of the ear

 Hallmark: intraluminal deeply-eosinophilic to brown/orange
colloid-like material (cerumen); +/- small brown intracytoplasmic
globules in neoplastic epithelium
 Adenomas: Proliferation of well-differentiated acini and
ductsusually surrounded by a single layer of myoepithelial cells;
ducts are often cystic, lined by papillary projections, and contain a
deeply eosinophilic or orange secretory product; atypia and
mitoses are infrequent; seldom exceed 1 cm
 Carcinomas: Not markedly different from adenomas but have less
secretion, more cellular anaplasia, may show invasion into an
abundant peripheral fibrous stroma or entry into blood vessels or
lymphatics
 Mixed tumors: Infrequent; myoepithelial proliferation, bone or
cartilage formation
 Gross appearance is indistinguishable from hyperplastic polypoid

otitis externa; may resemble feline inflammatory polyps
 Carcinomas may be confused with salivary carcinoma when they
invade the parotid salivary gland, or bone, and when very
anaplastic
 Other neoplasms of the external ear: Squamous cell carcinoma
(most important skin tumor affecting the ear), carcinoma of
undetermined origin, histiocytoma (dog), basal cell tumor,
chondroma, chondrosarcoma and rhabdomyomas (cat)
 A case report of a complex ceruminous gland adenocarcinoma in a

brown-footed ferret and a Scottish wildcat hybrid (Felis silvestris)
 Horses: Sarcoids and dentigerous cysts may occur at the base of the
ear
 Laboratory rats: Under certain conditions (especially after long-
term administration of some carcinogens), Zymbal's glands(under
the mucosa of the ear or in the subcutis ventral to the ear) can
become the origin of sebaceous adenomas or carcinomas
PC SYSTEMIC PATHOLOGY
SPECIAL SENSES SYSTEM
May 2018
S-N05 (NP)
Signalment (JPC # 844012): Cat
HISTORY: Tissue from a cat with exophthalmus because of progressive

retrobulbar swelling beginning in the zygomatic arch.
HISTOPATHOLOGIC DESCRIPTION: Lacrimal gland, conjunctiva and

retrobulbar skeletal muscle: Expanding the lacrimal gland, infiltrating
the conjunctival sub epithelial connective tissue and extending to the cut
border is an unencapsulated, densely cellular, multilobular neoplasm that
is subdivided by narrow bands of dense fibrous connective tissue.
Neoplastic polygonal cells are arranged in cords, tubulopapillary
projections and acinar structures, on a prominent basement membrane,
and that frequently palisade along a moderate fibrovascular stroma.
Neoplastic cells have variably distinct cell borders, a moderate amount of
finely vacuolated to eosinophilic, granular cytoplasm and one irregularly
round to oval, often basally located nucleus, with finely stippled
chromatin and 1-2 nucleoli. There is mild anisokaryosis and anisocytosis.
The mitotic count is 1-2 per 10 HPF. Multifocally, the surrounding
fibroadipose tissue and ocular muscle are expanded by edema,
hemorrhage and few lymphocytes and plasma cells.
MORPHOLOGIC DIAGNOSIS:Lacrimal gland, conjunctiva and retrobulbar
skeletal muscle: Lacrimal gland adenocarcinoma, breed unspecified,
feline.
SYNONYMS: Adenocarcinoma of the gland of the third eyelid; neoplasm

of nictitans
GENERAL DISCUSSION:
 Orbital tumors may be primary to the orbit, occur as a result of

local extension from an adjacent structure (such as the salivary
gland) or develop subsequent to hematogenous dissemination
 Primary tumors predominate in dogs; secondary tumors are more
common in cats
o Lacrimal gland adenocarcinoma is the most common primary
orbital epithelial neoplasmin dogs (although
infrequent); locally invasive,often recurs after excision but
metastases are not reported
 Lacrimal glands:
 Compound tubuloalveolar or tubuloacinar; serous to mucous

proportion varies with species
 Cats have serous glands; dogs have mixed glands
 Located in the dorsolateral quadrant of the orbit posterior to the
sclera and adjacent to the third eyelid
TYPICAL CLINICAL/GROSS FINDINGS:
 Pink lobulated mass in the dorsolateral quadrant of the orbit

 Unilateral proptosis
 Deviation of the globe
 Transient epiphora
 Secondary keratoconjunctivitis, corneal ulceration, retinal
detachment
 May be derived from acinar or tubular portions of gland

 Normal Iobulated appearance of gland is lost; acinar structure is
disorganized
 Cords and tubules of neoplastic cells on a fibrous stroma
 Lacrimal gland adenoma (acinar or tubular): Smooth expansile
proliferation of well-differentiated acini of vacuolated columnar
epithelial cells
 Zygomatic salivary gland neoplasm: May infiltrate the orbit
(zygomatic gland is infraorbital and a mixed salivary gland with a
prominent mucinous component); histologically and biologically
similar to lacrimal gland adenocarcinoma (lacrimal gland is
supraorbital and a purely serous gland in cats); distinguishing
lacrimal gland tumor from rare zygomatic tumor is based primarily
on location; the zygomatic gland is ventromedial
 Inflammation and prolapse of the gland of the third eyelid ‘cherry
eye’: non neoplastic condition where the gland of the third eyelid
extrudes from the conjunctiva forming a mass like appearance
 Conjunctival neoplasms:
o Meibomian gland neoplasm: most common ocular neoplasm in
dogs, histological appearance consistent with sebaceous
adenomas; Meibomian gland epitheilomas are composed of
densely packed sheets of basal reverse cells forming well
defined lobules
o Conjunctival squamous cell carcinoma: common aggressive
conjunctival epithelium neoplasm in domestic animals, most
common in cattle and horses;
o Granular cell tumor: Affects eyelids of canine, most often at
the medial canthus, comprised of abundant PAS positive
granules
o Apocrine cystadenomas (hidrocystomas): benign lesion
affecting the eyelids of domestic animals, multiple variably
sized cysts lined by cuboidal epithelium; most often seen in
Persian cats
o Conjunctival melanocytic neoplasm: Second most common
canine eyelid tumors arises from the conjunctiva and limbus
o Conjunctival vascular neoplasms: arise in the conjunctiva
lamina in dogs, cats and horses; most likely a continuum from
hemangioma to hemangiosarcoma; locally invasive and can
metastasize
o Conjunctival mast cell tumor: Sheets of well differentiated
granules mast cells; most common tumor of feline eyelids
o Conjunctival papilloma: exophytic neoplasm often arising
from the bulbar conjunctiva; typically viral induced
o Conjunctival lymphoma: Ocular manifestations occur in dogs
and cats often associated with systemic lymphoma
 Mouse: rodents have a complex lacrimal gland system including
both intra and extraorbital lacrimal glands, in addition to the
Harderian gland; Harderian gland neoplasms are lobulated, white to
tan, and often fill the retro-orbital space; Harderian gland
adenocarcinomas are highly invasive with infiltration to the
adjacent bone overall less differentiation an can metastasize to the
lung; lacrimal gland papillary cystadenomas or solid adenomas are
composed of well differentiated epithelial cells;
 Dogs: Equal prevalence of orbital sarcomas and carcinomas;
approximately equal frequency of primary orbital tumors and those
occurring as a result of local extension from the nose, mouth or
other structures

SPECIAL SENSES
May 2018
S-N03 (NP)
Signalment (JPC Accession # 1421244): Cat; age, gender and breed

unspecified.
HISTORY: This cat had an abnormal pupillary opening, and the eye was
surgically removed.
HISTOPATHOLOGIC DESCRIPTION: Eye: Diffusely expanding and effacing

all parts of the anterior uvea including the iris and infiltrating the ciliary
body, filtration angle, scleral plexus, and limbus is an unencapsulated
neoplasm composed of sheets of round cells separated by a fine
fibrovascular stroma. The neoplastic cells have distinct borders, a scant
amount of eosinophilic cytoplasm, an irregularly round nucleus with
clumped chromatin and one variably distinct nucleolus. The mitotic rate
averages 1 per HPF. There is mild anisokaryosis and anisocytosis.
Neoplastic cells also infiltrate the ora ciliaris retinae, and unilaterally
into the choroid, and are present in low numbers within the anterior,
posterior, and vitreous chambers. Throughout the iris, limbus, and spaces
of Fontana, lymphatics are mildly to moderately dilated (edema).
MORPHOLOGIC DIAGNOSIS: Eye, uvea: Lymphoma, breed unspecified,

feline.
GENERAL DISCUSSION:
 Intraocular lymphoma is the most common metastatic neoplasm

in both cats and dogsand is usually bilateral and presents as part of
systemic disease; ocular involvement is especially prevalent in cats
and typically occurs late in the course of the disease
 Lymphoma of the anterior uveal tract (iris, ciliary body, choroid) is
most common presentation, but may also involve the retrobulbar
tissue, conjunctiva, and eyelid
 Signs range from nodular iris infiltration to uveitis with hypopyon
and hyphema
 Involvement of the choroid, or the trabecular meshwork and
iridocorneal angle may result in retinal detachment and secondary
glaucoma respectively
 Involvement of the cornea is associated with advanced systemic
disease and suggests poor prognosis
 Cats infected with FeLV or FIV have a higher incidence of lymphoma
 Primary intraocular lymphoma is uncommon and is typically
unilateral; ocular lymphoma is second most common variant of
feline post-traumatic ocular sarcomas
 Anterior uveitis is most common presentation with thickening of

uvea and lighter color to iris
 Exophthalmos if metastasis is in orbit and uveitis when ocular
tissues are invaded
 Other clinical signs include—keratitis, vascularization, corneal
edema, corneal hemorrhage, miosis, hypopyon, aqueous flare,
secondary glaucoma, lens luxation, retinal hemorrhage, panuveitis,
or a dense white circumcorneal band
 Iridial color change and pallor from infiltrating neoplastic cells

 Dyscoria (abnormal pupillary shape or form)
 Uveal tract distorted by white to tan nodules
 Often bilateral and most commonly involves the anterior uvea (iris
and ciliary body)
 Iris and ciliary body are most frequently infiltrated by neoplastic

lymphocytes with scant cytoplasm
 Less frequently neoplastic cells extend into the choroid
 Occasionally there is a mixed population of neoplastic cells which
may exhibit an epithelioid appearance
 Cytology: Aqueous humor aspirate with dogs presenting with

anterior uveitis
 PARR
 Anterior uveitits
 Malignant angioendotheliomatosis: Malignant intravascular
lymphoma that arises from neoplastic lymphocytes of the vascular
bed
 Melanoma is the most frequent primary intraocular tumor in the
cat, and melanocytic tumors are the most common intraocular
tumors in all species
 Iridociliary adenoma, adenocarcinoma, ocular sarcoma
 Dogs: Diffuse infiltration of the anterior uvea is typical; distinct

masses are uncommon
 Cattle: Retrobulbar lymphoma is common, is part of generalized
lymphoma, and is the most frequent cause of exophthalmos; adult
lymphosarcoma typically associated with BLV, disease is rare in
BLV-free animals
 Horses: Systemic lymphoma is the most common neoplastic disease
observed in the equine eye; infiltration of conjunctiva and eyelids
(including third eyelid) are most common ocular manifestations
 Koala: Lymphoma associated with koala retrovirus (KoRV)
 Chickens: Marek’s disease (Gallid herpesvirus-2) causes iridial
lymphoma

SPECIAL SENSES
May 2018
S-N02 (NP)
Signalmnent (AFIP 2149189): German shepherd dog
HISTORY: This German shepherd military working dog was euthanized

following diagnosis of multicentric lymphoma. At necropsy, the cornea of
the left eye was opaque.
HISTOPATHOLOGIC DESCRIPTION: Slide 2A: Eye: Arising from the iris,

expanding and effacing the remaining iris and ciliary body, infiltrating
and partially blocking the filtration angle, and infiltrating the cornea and
sclera is a large, multinodular, poorly demarcated neoplasm that fills and
expands the anterior compartment. Neoplastic cells are arranged in short
streams and bundles on a fine fibrovascular stroma and are characterized
by: variably distinct cell borders, a moderate amount of eosinophilic
cytoplasm that contains abundant dark brown granular pigment (melanin)
that often obscures the nucleus, round to oval nuclei with finely stippled
chromatin and often a single, prominent nucleolus. The mitotic rate is 0-
1 per 10 HPF 40x fields. Multifocally there are variably sized areas of
coagulative necrosis admixed with free melanin granules. Scattered
throughout and surrounding the neoplasm are numerous
melanomacrophages, occasional lymphocytes and plasma cells, and rare
single cell necrosis. Multifocally dissecting the neoplasm and adhered to
the posterior capsule of the lens is a broad band of collagen admixed with
fibrin, melanocytes and melanophages (cyclitic membrane). Diffusely the
retina is absent and the remaining underlying retinal pigment epithelium
is hypertrophied (“tombstoning”).
MORPHOLOGIC DIAGNOSIS: Eye, uvea: Melanocytoma, German shepherd

dog, canine.
Signalment (AFIP 2348405): Tissue from a cat
HISTORY: There is a white to pale yellow-colored nodule involving the

ciliary body and iris.
HISTOPATHOLOGIC DESCRIPTION: Slide 2B: Eye: Diffusely expanding

the iris and ciliary body up to 2.5 mm, infiltrating the adjacent sclera,
and blocking the filtration angle is an unencapsulated, poorly
demarcated, polygonal to spindle cell neoplasm. Neoplastic cells are
arranged in nests and packets and, rarely, form short streams that
encompass multiple small caliber dilated vessels and are separated by a
scant fibrovascular matrix. Neoplastic cells have variably distinct cell
borders and a moderate amount of finely granular eosinophilic
cytoplasm. Occasionally the cytoplasm contains a brown granular
pigment (melanin). Nuclei are round to oval with finely stippled
chromatin and a single prominent nucleolus. Mitoses average 1-2/HPF.
Scattered throughout the neoplasm are melanomacrophages and
multifocal single cell necrosis. Multifocally within the posterior chamber
there is a moderate amount of fibrin.
Slide 2C: Warthin-Starry 3.2: Many of the neoplastic cells contain

variable amounts of intracytoplasmic, silver-positive (agyrophilic),
granular material (melanin).
MORPHOLOGIC DIAGNOSIS: Eye, iris: Melanoma, diffuse, breed not

specified, feline.
ETIOLOGIC DIAGNOSIS: Ocular melanoma
GENERAL DISCUSSION:
 Anterior uveal melanocytoma is by far the most common

intraocular tumor in dogs
 Primary melanomas of the eye and adnexa are common in the dog
and cat, less common in the horse
 Biological behavior of ocular melanomas depends heavily upon
species and location
PATHOGENESIS:
 Melanomas arise in the skin of the lid margin, conjunctiva, anterior

uvea, limbus and choroid
 In dogs, intraocular tumors typically arise from melanocytes in the
root of or adjacent to the ciliary body (anterior uveal
melanocytoma)
 Feline diffuse melanomas start as patchy iris hyperpigmentation
that very slowly progresses to diffuse iris hyperpigmentation and
thickening over several years; the eventual outcome is virtually
always glaucoma
Dogs:
 Anterior uvea (most common intraocular tumor in dogs):These

are usually benign; a mitotic index greater or equal to 3per 10
HPF indicates malignancy
 Lid margin (second most common): Typically benign
 Conjunctiva (infrequent): Histologically and behaviorally malignant
 Limbus, epibulbar: Histologically and behaviorally benign;
composed of large plump melanocytes
 Choroid (rare): Benign; can cause retinal detachment resulting in
infiltration of overlying retina and adjacent optic nerve
Cats:
 Feline diffuse iris melanomas (FDIM, most common site in

cats): Usually present with a diffuse iris thickening and
hyperpigmentation;Metastasis occurs but is hard to predict and
has been linked to large tumor size and intrascleral spread;
metastatic foci grow very slowly and rarely cause clinical signs;
FDIM often leads to glaucoma
 Conjunctiva (rare): Histologically and behaviorally malignant
 Limbus: Histologically and behaviorally benign
Horses:
 Most horses with intraocular melanocytic neoplasms have cutaneous

melanoma
 The iris is most often affected
 Pigmented expansile nodules that can spread transclerally and

circumferentially within the globe
 Glaucoma from occlusion of the ciliary cleft occurs in about half of
affected dogs
 Uveitis and hyphema are frequently associated conditions
 Feline iridial melanomas present with diffuse iridal thickening,
hyperpigmentation (although they can sometimes be poorly
pigmented), and glaucoma
 Uveitis from tumor necrosis and hyphemafrom tumor induced

neovascularization are often seen
Dogs:
 Anterior uvea: These neoplasms usually arise from the melanocytes

of the iris root or adjacent ciliary body and are composed of lightly
pigmented spindle cells and usually fewer heavily pigmented plump
melanocytes identical to those of limbal melanomas
 Lid margin: Resemble benign cutaneous melanomas
 Conjunctiva: Well pigmented, bland melanocytes with little
anisokaryosis or mitotic activity with invasive clusters of angular
epithelioid cells with marked anisocytosis and numerous mitotic
figures
 Limbus, epibulbar: Large plump melanocytes with a central nucleus
and abundant cytoplasmic pigment; few or no mitoses
 Choroid: Well-pigmented, cytologically bland, often with retinal
detachment
Cats:
 Diffuse iridal melanomas infiltrate the stroma of the iris, the ciliary
cleft, overlying sclera, peripheral cornea, and ciliary body
 Pleomorphic cells varying from spindle to multinucleated
epithelioid cells; light pigmentation with foamy eosinophilic
cytoplasm and distinct cell borders
 Bleachingwith permanganate or oxalic acid often aids in

cytomorphologic interpretation of heavily pigmented neoplasms
 Warthin-Starry 3.2, Fontana-Masson method, immunohistochemical
staining
 Electron microscopy may be used to verify melanocytic origin
 Pigmented uveal nodules (uveal cysts). These fluid-filled cysts may

be congenital or arise secondary to trauma or inflammation and are
benign incidental findings, non-progressive and non-neoplastic
 Canine diffuse uveal melanosis: Distinct clinical entity with diffuse
growth pattern within uvea; may be indistinguishable form uveal
melanoma; common in Cairn terriers
 Common locations for melanomas in different species:

 Conjunctiva: Canine, feline, porcine
 Eyelid: Rat
 Anterior uvea, iris: Canine, equine (young, grey horses), bovine,
feline, rodent (F344 rat)
 Choroid: Canine

SPECIAL SENSES
April 2018
S-M14 (NP)
Signalment (JPC #1690931): A ten-year-old Siamese cat
HISTORY: This cat had a black spot on one eye for approximately one
year. The spot was surgically removed. A similar spot had been removed
three years previously.
HISTOPATHOLOGIC DESCRIPTION: Cornea: Over 90% of the stroma is

composed of hyalinized, golden brown to eosinophilic, acellular material
that retains tissue architecture (stromal coagulative necrosis). In the
affected area there is diffuse loss of epithelium and endothelium and
multifocal loss of Descemet’s membrane. There are multifocal
depressions along the surface that occasionally extend into the deep
stroma. In the remaining area of the cornea, there is a focal loss of
epithelium (ulcer) and clear space separating stromal fibers (edema).
MORPHOLOGIC DIAGNOSIS: Cornea: Necrosis, coagulative, focally

extensive, with pigmentation and loss of epithelium (sequestrum), and
ulceration, Siamese, feline.
CAUSE: Unknown
CONDITION: Corneal sequestrum
SYNONYMS: Corneal black spot, corneal mummification, corneal nigrum,

superficial stromal sequestration, focal corneal degeneration
GENERAL DISCUSSION:
 Central or paracentral focal degeneration of the cornea stroma with

an accumulation of a brown pigment surrounded by variable
amounts of inflammation
 Flat, initially non-ulcerated, brown to black necrotic spot in the
central cornea, usually unilateral, characterized by lack of
epithelial attachment
 Corneal sequestrum presumed to be an uncommon sequel to
corneal ulceration
 Cats of all ages effected, except the neonate; usually young adults
 Persian(often bilateral), Himalayan and Siamese cats
overrepresented
PATHOGENESIS:
 Unknown
 Possible contributing factors
 Corneal trauma(especially in flat-faced breeds such as Persians)
 Chronic ulcerative keratitis
 Brachycephalic conformation with lagophthalmos
 Exposure keratopathy
 Chronic corneal irritation
 Topical corticosteroids
 Feline Herpes virus (FHV-1) infection in non-predisposed breeds
 Primary corneal dystrophy
 Altered corneal stromal metabolism
 Qualitative tear film deficiencies
 Sequestrum will eventually slough with replacement by granulation
tissue; takes weeks to months; usually surgery is elected prior to
this stage of disease
 Nature of pigment is unknown, thought to be derived
from porphyrins in tear film
 Separate studies support and refute the presence of iron or melanin
 Blepharospasm, lacrimation, protrusion of the third eyelid

 May be asymptomatic
 Discrete central, flat superficial orange-brown discoloration of

the central cornea
 Usually unilateral, occasionally bilateral
 Adjacent cornea may be ulcerated, edematous, and vascularized
 Bland corneal epithelial desiccation – easily mistaken for artifact

 Noninflammatory necrosis of stromal keratocytes, often with
hyalinization
 Necrosis of stromal keratinocytes with pallor, hyalinization, and
vague orange-brown discolorationof affected stroma without
inflammation; mineralization is rare
 Overlying epithelium may be ulcerated or intact, with growth over
the surface of dead stroma (if intact usually evidence of previous
ulceration)
 Older lesions may have a deep margin of mononuclear leukocytes
with occasional macrophages and giant cells
ULTRASTRUCTURE
 Amorphous, electron-dense substance along the intact basal
epithelial basement membranes
 Corneal ulceration
 Loosely packed collagen fibrils with necrotic keratocytes between
collagen layers
 Foreign bodies
 Melanocytoma or melanoma
 Corneal pigmentation
 Mineral deposits
 Dog: Canine persistent (recurrent) ulcer syndrome

o Boxers predisposed
o Corneal injury > abnormal/degenerate superficial corneal
stroma > regenerating corneal epithelial hemidesmosomes
unable to anchor properly to abnormal stroma > regenerating
corneal epithelium slides off easily > non-healing or
recurrent shallow central corneal erosion/ulcer
o Corneal epithelial basal lamina is often not apparent
microscopically; multiple clefts separate hyperplastic
epithelium from underlying stroma; pyknotic and lytic
keratocyte nuclei (apoptosis) and pallor within superficial
stroma; usually less severe than the stromal devitalization
associated with feline corneal sequestrum
 Horse: Less frequent and less well characterized than dogs or cats;
often associated with superimposed fungal infection.
SPECIAL SENSES SYSTEM
April 2018
S-M13
Signalment (AFIP #1744913): Breed and gender not specified, 17-year-

old cat
HISTORY: This cat had bilateral retinal hemorrhage and systemic

hypertension.
HISTOPATHOLOGIC DESCRIPTION: Eye: The retina is diffusely thinned

with loss of the photoreceptor layer; pseudocyst formation (up to
1X0.5mm) in the photoreceptor layer; 75% reduction of the inner nuclear
layer; loss of ganglion cells; vacuolation of the nerve fiber layer or
plexiform layer (spongiosis or axonal degeneration). Focally, the retinal
architecture is completely obscured by hemorrhage and fibrin admixed
with low numbers of fibroblasts and scattered macrophages containing
phagocytized erythrocytes and golden-brown granular pigment
(hemosiderin). Multifocally, the tunica media of vessels in the retina and
choroid is moderately thickened and variably expanded by brightly
eosinophilic, hyalinized homogenous material (hyalinization).
Occasionally smaller retinal and choroidal vessels are surrounded by
increased clear space (edema), and there is choroidal sclerosis and loss of
the retinal pigment epithelium. There is multifocal hypertrophy of the
retina pigment epithelium (retinal detachment). The heavily pigmented
epithelium of the posterior iris forms several knob-like projections that
frequently have a clear center (pigmented iridal cysts).
MORPHOLOGIC DIAGNOSIS: Eye, retina: Degeneration, diffuse, marked

with detachment, choroidal and retinal vascular hyalinization, focal
hemorrhage, and photoreceptor layer pseudocysts, breed unspecified,
feline.
CONDITION: Hypertensive retinopathy
GENERAL DISCUSSION:
 Hypertensive retinopathy, secondary to systemic hypertension, is an

increasingly frequent cause of retinal and choroidal lesions and
blindness in cats over 10 years of age; 80-100% of cats with
systemic hypertension have concurrent retinopathy
 Most cases are associated with chronic renal failure; less common
causes include hyperthyroidism, cardiac abnormalities, diabetes
mellitus, chronic anemia, high-salt diets, pheochromocytoma,
hyperadrenocorticism, acromegaly, primary hyperaldosteronism,
and polycythemia
 Dogs and cats are most frequently affected
 The eye is frequently the first organ to clinically manifest systemic
hypertension
 Hypertension in cats is commonly defined as systolic pressure
greater than 160 -170 mmHg; cats with hypertensive retinopathy
often have systolic blood pressures at or above 200 mmHg
PATHOGENESIS:
 Diseased nephrons > decreased GFR > increased renin (produced by

JGA cells) > converts angiotensinogen (in liver) > angiotensin I >
increased angiotensin II via ACE (from macula densa of DCT) >
arteriolar vasoconstriction increasing peripheral resistance,
increased sodium reabsorption, and release of aldosterone from the
adrenal cortex, and increased ADH release > distal nephron sodium
retention > volume excess and systemic hypertension
 Ocular lesions are the result of sustained & exaggerated
autoregulatory vasoconstriction > tunica media hypertrophy >
diminished contractile function > fibrous changes > leakage of
plasma into arteriolar wall > hyalinization and leiomyocyte necrosis
> degeneration > rupture of endothelial & muscle cells > leakage of
blood & serum into surrounding retinal tissue > effusive lesions
(edema, hemorrhage, retinal detachment)
 Lesions are bilateral but not necessarily symmetric

 Acute blindness is the most common reason for presentation
 Hyphema and secondary glaucoma
 Retinal vascular tortuosity
 Retinal detachment
 Intravitreal and intra- and subretinal hemorrhages
 Sustained high blood pressure
 In cats with renal dysfunction, the presence or magnitude of
hypertension is unrelated to azotemia; persistent lack of urine
concentrating ability may be the only indication of chronic renal
disease
 Chronic hypertension causes left ventricular hypertrophy, which is
often misdiagnosed as hypertrophic cardiomyopathy
 Intravitreal and intra- and subretinal hemorrhages

 Hyphema
 Retinal edema
 Retinal detachment
 Lesions are primarily in the retinal and choroidal vessels;

characteristic lesions in the small retinal muscular arteries and
larger arterioles
 Mural edema that may progress to a fibrinoid necrosis of the tunica
media or medial hypertrophy with adventitial fibrosis of choroid
and retinal vessels
 Early lesions, likely to be seen only under experimental conditions,
are the result of exaggerated autoregulatory vasoconstriction in
response to systemic hypertension
 Changes secondary to vessel damage:
o Localized retinal necrosis
o Exudative retinal detachment and retinal pigment epithelium
(RPE) hypertrophy (tombstoning)
o Photoreceptor atrophy and loss
o Retinal hemorrhage, edema, and hemosiderin deposition
 Ischemic necrosis of RPE > allows for leakage of
hypertensive edema fluid from the choroid into the
subretinal space

 Various clinical diagnostic tests: Ophthalmoscopy, systolic arterial
blood pressure, clinical pathology, echocardiography, ocular
ultrasound
Retinal disease in cats:
 Taurine deficiency retinopathy (feline central retinal

degeneration): Bilateral photoreceptor degeneration; initially
affects cone outer segments but also eventually affects rods
 Inherited retinopathies: Autosomal dominant early-onset rod and
cone dysplasia with blindness by a few months of age and
autosomal recessive late-onset retinal degeneration with blindness
by 5-10 years of age; high incidence in Abyssinians
 Secondary retinal degeneration and detachment due to trauma,
glaucoma, or infection
 Dogs: At least 60% of dogs with chronic renal failure have systemic
hypertension; ocular lesions associated with systemic hypertension
are similar to the cat; retinal hemorrhage is the most common
hypertension-associated ocular lesion (40%)
 Rats: Spontaneously Hypertensive Rats (SHR) are used as human
models
 Non-human primates:
o Diabetic macaques are used as human models for diabetic
retinopathy/microvascular disease;
o Hypertension due to catecholamines from
pheochromocytomas resulting in myocardial fibrosis as well as
hyalinization and medial thickening of coronary arteries
recently reported in New World primates (cotton-top tamarin,
golden lion tamarin, black howler monkey and black-handed
spider monkey); swollen axons (“cotton-wool spots”) are a
hallmark of hypertensive retinopathies in primates and may
be seen early in the course of disease
References:
SPECIAL SENSES
April 2018
S-M10
Signalment (AFIP Accession #2382810): A cat
HISTORY: Tissue from a cat with a history of dysphagia. Large, fleshy

masses were present in the ear and underneath the tongue.
HISTOPATHOLOGIC DESCRIPTION: Oropharyngeal mucosa (per

contributor):
Expanding the submucosal connective tissue and elevating the overlying

mucosa is a polypoid mass that is composed of mature collagen
interspersed with numerous small to medium caliber blood vessels.
Multifocally, there are small aggregates of inflammatory cells throughout
the lesion composed of variable proportions of neutrophils, lymphocytes
and plasma cells, with fewer macrophages. Multifocally, the collagen
bundles are separated by clear spaces and lymphatics are moderately
dilated (edema) and there is multifocal hemorrhage. The mucosal
epithelium is predominantly stratified squamous and forms multiple folds
resembling papillary projections, with few areas of ciliated epithelium.
There is multifocal erosion and ulceration of the epithelium which is
partially covered with eosinophilic debris and fibrin admixed with cellular
and karyorrhectic debris (necrosis) as well as viable and degenerate
neutrophils (serocellular crust).
MORPHOLOGIC DIAGNOSIS: Oropharyngeal mucosa (per contributor):
Polyp, with chronic-active inflammation, erosion and ulceration, breed
unspecified, feline.
GENERAL DISCUSSION:
 Most commonly occurs in cats and dogs, less commonly in horses

 In cats, non-neoplastic inflammatory masses arising within the
middle ear or auditory tube
 Most common non-neoplastic mass in cats, primarily seen in young
cats 1-3 years of age
 In cats, most arise from the middle ear or auditory canal and
undergo expansile growth within the nasopharynx or the external
ear canal
 Recurrence is common
 Cats may have nasopharyngeal polyps originating from the middle
ear, OR inflammatory polyps originating from the nasal turbinates
(also termed feline mesenchymal nasal hamartoma) which is a
separate condition
PATHOGENESIS:
 Proposed causes: chronic upper respiratory tract infection, otitis

media, ascending middle ear infections via auditory tubes,
congenital defects
 There is controversy as to whether polyps are secondary to
inflammation or if the presence of polyps predisposes the patient to
inflammation by impairing auditory tubule drainage
 Nasopharyngeal polyps originate from ciliated epithelium of the
tympanic cavity/middle ear mucoperiosteumor less commonly
from the external ear canal
 Nasal polyps arise from the ethmoturbinates
o Recent argument for designation of inflammatory polyps of
the nasal turbinates in cats (specifically IPNT) as feline
mesenchymal nasal hamartoma, due to presence of woven
bone as part of the proliferating stroma and erythrocyte filled
spaces
 A familial predisposition has been seen in Abyssinian and Himalayan
kittens
 Extension of mass into the pharynx: Dyspnea, dysphagia, stridor,

voice change and gagging
 Involvement with nasal cavity: Sneezing, nasal discharge, and
protrusion through the nares, and epistaxis has been reported
 Involvement with middle ear = ataxia, Horner’s syndrome, and or
facial nerve paralysis
 Moist, glistening and spherical, oval to elongated (often

pedunculated) masses
 Within the ear canal, polyps are usually smooth-surfaced red
masses
 Frequently protrude out of the pharyngeal orifice of the eustachian
tube and can displace the soft palate
 Feline nasopharyngeal polyps consist of loose fibrovascular core

covered with ciliary respiratory or squamous epithelium
o Surface epithelium may undergo squamous metaplasia or be
ulcerated
 The detection of ciliated epithelium aids in the histological
confirmation of nasopharyngeal polyps but presence of
pseudoglands within the core extending to the surface confirms
middle ear origin
 Often accompanied by edema and mixed inflammatory cell
infiltrates (lymphocytes, plasma cells, macrophages, neutrophils)
 Goblet cells may be present
 May have a chronically inflamed edematous core resembling
myxomatous tissue
 Secondary bacterial rhinitis and sinusitis are common
 Older lesions may be more fibrous; may have lymphoid follicles
 Nasal polyps originating from the turbinates in cats may have
woven bone / bony metaplasia(but not nasopharyngeal polyps)
For gross findings:
 Fungal granuloma (cats - Cryptococcus neoformans, dogs-

Rhinosporidium seeberi)
 Neoplasia (pedunculated fibroma, papilloma, adenocarcinoma)
 Hemorrhagic nasal polyps (progressive ethmoid hematoma) are
relatively common in horses and arise from the ethmoid turbinate
region of the nasal cavity
 Nasal polyps arise from middle ear or auditory tube in other
domestic species and are uncommon but also reported in sheep,
horses and dogs

Systemic Pathology

Încărcat de

Informații document

Descriere originală:

Drepturi de autor

Formate disponibile

Partajați acest document

Partajați sau inserați document

Opțiuni de partajare

Vi se pare util acest document?

Este necorespunzător acest conținut?

Drepturi de autor:

Formate disponibile

Systemic Pathology

Încărcat de

Drepturi de autor:

Formate disponibile

JPC SYSTEMIC PATHOLOGY

Signalment (JPC #2414433): 8-year-old spayed female domestic shorthair cat

HISTOPATHOLOGIC DESCRIPTION: Cerebrum, hippocampus: Multifocally within

MORPHOLOGIC DIAGNOSIS: Cerebrum, hippocampus: Necrosis, multifocal to

CONDITION: Feline ischemic encephalopathy

CONDITION SYNONYMS: Idiopathic cerebral ischemic necrosis

TYPICAL CLINICAL FINDINGS:

TYPICAL LIGHT MICROSCOPIC FINDINGS:

ADDITIONAL DIAGNOSTIC TESTS:

Signalment Slide A (JPC #1336140): A military working dog

HISTORY: This dog developed severe convulsions.

HISTOPATHOLOGIC DESCRIPTION: Cerebrum (2 sections): Expanding

MORPHOLOGIC DIAGNOSIS: Brain, cerebrum: Astrocytoma, fibrillary,

Signalment Slide B (420072): A cat

HISTOPATHOLOGIC DESCRIPTION: Spinal cord (3 sections): Affecting

MORPHOLOGIC DIAGNOSIS: Spinal cord: Astrocytoma, anaplastic,

TYPICAL GROSS FINDINGS:

TYPICAL LIGHT MICROSCOPIC FINDINGS:

HISTORY: This cat exhibited depression and anorexia of 2 weeks duration

HISTOPATHOLOGIC DESCRIPTION: Cerebrum, lateral ventricle:

MORPHOLOGIC DIAGNOSIS: Cerebrum: Ependymoma, breed not

TYPICAL CLINICAL FINDINGS:

TYPICAL GROSS FINDINGS:

ADDITIONAL DIAGNOSTIC TESTS:

Signalment (JPC #2137343) Slide A: A 5-year-old cat

HISTOPATHOLOGIC DESCRIPTION: Medulla oblongata and cerebellum:

MORPHOLOGIC DIAGNOSIS: Medulla oblongata with vestibular nuclei:

Signalment (JPC #1199288) Slide B: Holstein calf

HISTOPATHOLOGIC DESCRIPTION: Cerebrum: Multifocally there is

MORPHOLOGIC DIAGNOSIS: Cerebrum, cortex: Polioencephalomalacia,

CAUSE: Thiamine (Vitamin B1) deficiency

ETIOLOGIC DIAGNOSIS: Nutritional polioencephalomalacia

SYNONYMS: Chastek paralysis (carnivores)

TYPICAL CLINICAL FINDINGS:

TYPICAL GROSS FINDINGS:

TYPICAL LIGHT MICROSCOPIC FINDINGS:

ADDITIONAL DIAGNOSTIC TESTS:

Signalment (JPC #1948535): 8-month-old spayed female lilac-point

HISTORY: This cat exhibited ataxia, anterior uveitis, and chorioretinitis.

HISTOPATHOLOGIC DESCRIPTION: Cerebrum and diencephalon:

MORPHOLOGIC DIAGNOSIS: Cerebrum and diencephalon:

ETIOLOGIC DIAGNOSIS: Coronaviral encephalitis

CAUSE: Feline infectious peritonitis virus (Feline coronavirus – FCoV)

CONDITION: Feline Infectious Peritonitis (FIP)

TYPICAL CLINICAL FINDINGS:

TYPICAL GROSS FINDINGS:

TYPICAL LIGHT MICROSCOPIC FINDINGS:

ADDITIONAL DIAGNOSTIC TESTS:

Emerging coronaviral diseases in animals include:

Coronaviruses in other species:

JPC SYSTEMIC PATHOLOGY

Signalment (JPC #1725431): Six-month-old female cat

HISTORY: Tissue from a six-month-old female cat that developed an eye

HISTOPATHOLOGIC DESCRIPTION: Eye and eyelid: All parts of the uvea,

MORPHOLOGIC DIAGNOSIS: Eye: Uveitis and scleritis, pyogranulomatous

ETIOLOGIC DIAGNOSIS: Feline coronaviral uveitis

CAUSE: Mutated feline enteric coronavirus (feline infectious peritonitis

 Family Coronaviridae, genus Coronavirus - enveloped, single

 Fecal-oral transmission and possibly inhalation of FCoV > replication

TYPICAL CLINICAL FINDINGS:

 Noneffusive (dry form): Typically granulomatous inflammation,

 Effusive (wet form): Weight loss, dyspnea, tachypnea, mild

TYPICAL GROSS FINDINGS: