Results
AFIP Wednesday Slide Conference - No. 28
14 May 1997
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- Conference Moderator: Dr. Hellen M. Acland
Diplomate, ACVP
School of Veterinary Medicine
University of Pennsylvania
New Bolton Center
382 W. Street Road
Kennet Square, PA 19348
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Case I - 96-2604 (AFIP 2550468)
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- Signalment: 1-year-old, Simmental, heifer, bovine
(Bos taurus).
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- History: The heifer was presented to the Kansas State
Veterinary Teaching Hospital because of failure to respond to
treatment for an apparent pneumonia. Physical examination revealed
bilateral corneal edema, mucopurulent nasal discharge, enlarged
peripheral lymph nodes and respiratory distress.
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- Gross Pathology: At gross necropsy, there were multiple
2-5 mm oral ulcers and bilateral corneal opacities. External
lymph nodes were enlarged but on cut surface the cortex and medulla
were still evident. Yellowish, turbid fluid that clotted on exposure
to air, was present in both the thorax and abdominal cavities.
The lungs were congested but not obviously pneumonic. Segmental
areas of intestine were reddened with tarry ingesta in the colon.
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- Laboratory Results: See contributor's comments.
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- Contributor's Diagnosis and Comments: Colon (some
recipients have ileum), colitis, lymphocytic with lymphocytic,
necrotizing arteritis/periarteritis and transmural edema, severe,
diffuse.
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- Condition: malignant catarrhal fever (MCF).
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- Histologic lesions included widespread vasculitis, particularly
involving small & medium size arteries. Lesions were especially
prominent in lymph nodes, intestines, kidneys and central nervous
system. Lesions were particularly prominent in vessels of the
vascular plexus around the pituitary.
- Cattle on this farm had fence-line contact with sheep. A
serum sample from this heifer was positive for malignant catarrhal
fever using a competitive inhibition ELISA performed at Washington
State University.
- Bovine virus diarrhea was included in the differential diagnosis.
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- AFIP Diagnosis: Colon: Vasculitis, lymphohistiocytic,
necrotizing, multifocal, moderate, with diffuse, mild to moderate,
subacute, erosive colitis, Simmental, bovine.
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- Conference Note: The conference participants agreed
with the contributor's diagnosis of colitis caused by the malignant
catarrhal fever (MCF) virus.
- MCF virus is a gammaherpesvirus which causes a fatal systemic
disease of cattle and many other ruminants. Lymphoid organs and
the respiratory and gastrointestinal tracts are primarily affected.
It is of worldwide distribution and generally sporadic in occurrence;
however, severe herd outbreaks have occurred. Susceptible species
include: cattle, bison, deer, banteng, gaur, kudu, other ruminants,
and rabbits. Syrian hamsters and guinea-pigs may also be susceptible.
- There are two forms of the disease which are clinically and
morphologically very similar. 1. The wildebeest-associated form
occurs primarily in Africa but can occur worldwide in exotic
animal collections. Wildebeest are inapparent carriers of the
alcelaphine herpesvirus 1 (AHV-1). The main source of infection
is healthy wildebeest calves under 4 months of age which shed
cell-free virus in ocular and nasal secretions. 2. The sheep-associated
form is a worldwide problem in domestic cattle and farmed deer.
Sheep-associated MCF is prevalent in some parts of the United
States. Sheep have been incriminated as inapparent carriers of
the disease. The identity of the causative agent has not been
definitely proven; however, there is increasing evidence that
sheep-associated MCF is caused by a herpesvirus related to AHV-1.
- The pathogenesis of MCF is clearly unique but poorly understood.
It is thought that cell-free virus is shed by aerosol from the
carrier, which infects the upper respiratory tract and/or tonsils
of susceptible animals. MCF virus infects a specific sub-population
of T-lymphocytes known as large granular lymphocytes which have
both natural killer cell function and are suppressors of T-lymphocyte
proliferation. It is hypothesized that the MCF virus causes dysfunction
of these large granular lymphocytes resulting in a diffuse, benign,
polyclonal T-lymphocyte hyperplasia (suppressor dysfunction)
and a fatal tissue destruction (killer cell dysfunction).
- The characteristic histologic lesions of MCF are proliferation
and infiltration of large, granular, lymphoblastoid cells, particularly
around blood vessels and in T-cell dependent areas of lymph nodes
and the spleen. There is an irregular segmental angiitis in many
tissues, predominantly of medium-sized arteries, which affects
all components of the walls of arteries and veins.
Contributor: Kansas State Department of Diagnostic Medicine/Pathology,
1800 Denison Ave, Manhattan, KS 66506.
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- References:
1.Jubb KVF, Kennedy PC, Palmer N (eds): Pathology of Domestic
Animals, 4th ed., Vol 2, pp. 163-173, 1993.
- 2. Coetzer JAW, Thomson GR, Tustin RC (eds): Infectious Diseases
of Livestock with special reference to Southern Africa. Volume
II, Oxford University Press, pp. 946-957, 1994.
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- International Veterinary Pathology Slide Bank:
Laser disc frame #4997-9, 9357, 18604, 19541, 20189, 21981-5.
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Case II - no label (AFIP 2554466)
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- Signalment: A newborn Suffolk x Dorset sheep.
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- History: Ten of a group of 23 first parity ewes aborted
fetuses (last trimester of gestation) during a 5 day period.
A larger group of mature ewes housed on an adjacent pasture had
already completed the lambing season without significant reproductive
losses. A new ram had been introduced to the flock at the start
of the breeding season and had serviced both groups of ewes.
Treatment with oxytetracycline appeared to halt the abortion
storm.
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- Gross Pathology: No gross abnormalities were noted
in any of the 6 mildly autolytic fetuses or placentas examined.
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- Laboratory Results: Campylobacter jejuni was recovered
from one or more of: lung, stomach contents, and placenta from
5/6 of the fetuses necropsied. C. jejnuniidentification was based
on the following criteria: growth under microaerophilic conditions,
Gram stain morphology, nalixidic acid sensitivity, cephalothin
resistance, positive reaction for sodium hippurate and catalase.
Paired sera from the ram and 6 of the aborting ewes were tested
for Toxoplasma, Chlamydia and Coxiella titers. A single seroconversion
for Toxoplasma was identified.
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- Contributor's Diagnosis and Comments: Placentitis,
neutrophilic, with intracellular bacteria.
Etiology: Campylobacter jejuni.
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- Very large numbers of bacteria are visible in this inflamed,
edematous chorioallantois. These short, weakly gram-negative
rods are visible within endothelial cells, capillary lumina and
in the chorionic stromal tissue. Bacteria can occasionally be
identified within trophoblasts. Hemorrhage and intravascular
fibrin thrombi are present in some areas but a vasculitis is
absent in most of the sections examined. The bacteria retain
Warthin-Starry stain but are Machiavello-negative. Other than
a mild suppurative bronchopneumonia, no other microscopic abnormalities
were noted in this fetus.
- C. jejuni normally inhabits the intestinal tract of sheep
and numerous other species, including humans. This organism is
capable of inducing gastrointestinal disease in dogs and humans
(ie. zoonotic) and causes vibrionic hepatitis in chickens. It
is a common cause of ovine abortion, with the proportion of affected
ewes varying with the immune status of the flock. In this outbreak,
only first parity sheep aborted, a pattern also often seen with
ovine chlamydial abortion. The introduction of a new ram may
have been incidental, as the same ram serviced the remainder
of the flock, which experienced no abortions. The first parity
ewes were noted to have decreased body condition in comparison
to the rest of the flock and this may have contributed to the
severity of the abortion storm.
- This case is unusual since such large numbers of organisms
are visible in the H&E sections - a features previously reported
in experimental but not field cases of C. jejuni abortion1. Other
important causes of ovine abortion include Toxoplasma gondii,
Chlamydia sp., other Campylobacter species, Flexispira rappini,
Salmonella sp. and Coxiella burnetii. 2,3
AFIP Diagnosis: Placenta: Placentitis, necrotizing, acute,
diffuse, severe, with intratrophoblastic, intravascular, and
extracellular bacilli, Suffolk-Dorset mixed-breed, ovine.
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- Conference Note: Campylobacter jejuni and C. fetus
are among the most commonly diagnosed causes of ovine abortion.
These abortions occur in the last half of gestation. Grossly,
placentitis is rarely apparent. Fetuses are often slightly to
moderately autolytic. Fetal lesions often include a fibrinous
peritonitis and hepatomegaly with multifocal target-shaped areas
of hepatic necrosis. Suppurative placentitis and pneumonia of
varying severity are usually present. These fetal lesions are
typical but not pathognomonic of Campylobacter sp. infections.
Identical lesions can be produced by Flexispira rappini. Differentiation
of the two bacteria can be made by culture or fluorescent antibody
techniques.
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- Contributor: Veterinary Laboratory Service, Ontario
Ministry of Agriculture and Rural Affairs, Bldg #43, McGilvray
St, Guelph, Ontario, Canada, N1H, 6R8.
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- References:
1. Hedstrom, OR, Sonn RJ, Lassen ED, Hultgren BD, Crisman
RO, Smith BB, Synder SP: Pathology of Campylobacter jejuni Abortion
in Sheep. Vet Pathol 24:419- 426, 1987.
- 2. Jubb, KVF, Kennedy PC, Palmer N (eds): Pathology of Domestic
Animals, Vol. 3, Academic Press, pp. 402-404, 1993.
- 3. Kirkbride CA: Diagnosis in 1,784 ovine abortions and stillbirths.
J Vet. Diag Invest 5:398-402, 1993.
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- International Veterinary Pathology Slide Bank:
Laser disc frame #9350, 9485.
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Case III - 95P1032 (AFIP 2551665)
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- Signalment: 1-day-old, female, Arabian horse, equine.
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- History: The foal was weak at birth. Upon presentation
to the teaching hospital, it had abnormal lung sounds.
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- Gross Pathology: Both lungs were diffusely stiff and
contained a moderate number of 0.5-1 mm white foci. The cranioventral
1/3 of the right lung was atelectatic. Multiple, randomly distributed
1.5-2 mm white foci were present on the liver and there was diffuse
adrenocortical hemorrhage.
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- Laboratory Results: An arterial blood sample had PO2
of 28, PCO2 of 61.7 and pH of 7.245. Fluorescent antibody test
for EHV-1 were negative but the virus was isolated. Two different
type of E. coli were isolated from lung and liver.
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- Contributor's Diagnosis and Comments:
- 1. Lung: bronchiolitis, necrotizing, multifocal, acute, moderate
with eosinophilic, intranuclear inclusions and bronchopneumonia,
serofibrinous, multifocal, acute, severe, due to aspiration.
2. Liver: hepatitis, necrotizing, multifocal, acute, moderate.
3. Adrenal gland: adrenalitis, necrohemorrhagic, diffuse, acute,
severe with eosinophilic intranuclear inclusions.
- Etiology: Equine herpesvirus 1.
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- The case is typical of neonatal death due to in utero infection
with equine herpesvirus (EHV). Readily identifiable inclusion
bodies were difficult to find in most of the liver sections.
They were more easily found in lung and adrenal. Isolation of
different types of E. coli is attributed to the general weakened
condition of the foal and aspiration pneumonia.
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- AFIP Diagnosis:
- 1. Lung: Pneumonia, bronchointerstitial, necrotizing, acute
to subacute, diffuse, moderate, with syncytial cells and eosinophilic
intranuclear inclusion bodies, Arabian horse, equine.
2. Liver: Hepatitis, necrotizing, portal and random, acute, multifocal,
moderate, with eosinophilic intranuclear inclusion bodies.
3. Adrenal: Adrenalitis, necrotizing, peracute to acute, multifocal,
moderate, with eosinophilic intranuclear inclusion bodies.
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- Conference Note: In utero infections with equine herpesvirus
1 usually result in near term abortions, although, as in this
case, foals may be born alive at or near term but die within
the first few days of life due to severe interstitial pneumonia
and secondary bacterial infections.
.
The horse is the natural host for 5 recognized herpesviruses:
EHV-1 Equine viral abortion and neurologic disease
EHV-2 Currently recognized as a gamma herpesvirus
EHV-3 Equine coital exanthema
EHV-4 Rhinopneumonitis virus
EHV-5 Currently recognized as a gamma herpesvirus
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- EHV-1,3 and 4 are all alpha herpesviruses. Some confusion
existed concerning EHV-1 and EHV-4 which were originally thought
to be a single virus capable of causing both respiratory disease
and abortion storms. Subsequently, the viruses were separated
into subtype 1 (abortion) and subtype-2 (respiratory disease).
Currently, EHV-1 is used to refer to equine abortion virus and
EHV-4 to rhinopneumonitis virus, although not all data supports
this distinction. Both viruses are reported to cause respiratory
disease, but EHV-4 is the common cause. Also, both viruses can
cause abortion, but EHV-1 is the important cause of single or
multiple abortions in mares. An important distinction is that
in fetuses aborted due to EHV-1, the lung is the main organ affected.
EHV-1 is the only one causing neurologic disease (an encephalitis
characterized by a vasculitis) and can result in neonatal deaths,
probably associated with late term fetal infections.
- EHV types 1 and 4 spread rapidly by direct contact, aerosol
transmission, or by ingestion of contaminated food or water.
The virus initially attaches and replicates in the nasal, pharyngeal
and/or tonsillar epithelium. A viremia develops but the virus
can only be isolated from the buffy coat fraction of a blood
sample and is believed to be transported to other tissues via
infected macrophages. There is strong evidence that lymphocytes
and other leukocytes cross the placenta and it is proposed that
infected maternal cells carry virus to the fetus. Recent studies
indicate infection of maternal endothelial cells and subsequent
infection of placental and fetal endothelial cells; this may
be an important part of the pathogenesis of equine viral abortion.
- It is reported that 95% of the abortions due to EHV-1 occur
in the last 3 months of gestation and naturally acquired infection
has not been observed to produce abortion before 5 months of
pregnancy. Death of the fetus does not occur until the onset
of the usually prompt and uncomplicated abortion. The dam shows
no premonitory signs and the fetus is expelled in a fresh state.
- Fetuses aborted due to EHV-1 may show characteristic and
diagnostic lesions which vary in prominence. The most consistent
gross lesion is severe edema of the lungs. Tan to white foci
of necrosis, 2-4 mm in diameter, and petechial hemorrhages may
be visible on the surface of the lungs. Interlobular edema and
fibrin casts within bronchi are other common lung lesions. Subcapsular,
gray to white foci (up to 5 mm) of necrosis are seen in the liver
in about 50% of cases. Other gross changes include edema of the
subcutis and fascia, accumulation of amber fluid in the body
cavities, slight icterus, petechial or ecchymotic hemorrhages
anywhere in the body and occasional hemorrhagic necrosis of renal
cortices.
- The histologic changes due to EHV-1 in lung, liver and adrenal
gland are essentially as seen here. Necrosis of germinal centers
occurs in spleen and in other lymphoid tissues, including thymus
and inclusions may be found in primitive reticular cells in these
areas. The placenta is normal.
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- Contributor: Iowa State University, Department of
Veterinary Pathology, Ames, IA 50011.
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- References:
1. Jubb KVF, Kennedy PC, Palmer N (eds): Pathology of Domestic
Animals, 4th ed., Vol. 3, Academic Press, pp. 436-439, 1993.
2. Giles RC, et al: Causes of abortion, stillbirth, and perinatal
death in horses: 3,527 cases (1986-1991). JAVMA 203(8):1170-5,
1993.
- 3. Hong CB, et al: Equine abortion and stillbirth in central
Kentucky during 1988 and 1989 foaling seasons. J Vet Diagn Invest
5(4):560-6, 1993.
- 4. Ostlund EN: The equine herpesviruses. Vet Clin North Am
Equine Pract 9(2):283-94, 1993.
- 5. Rimstad E, et al: The identification of equid herpesvirus
1 in paraffin- embedded tissues from aborted fetuses by polymerase
chain reaction and immunohistochemistry. J Vet Diagn Invest 5(2):174-83,
1993.
- 6. Edington N; et al: The role of endothelial cell infection
in the endometrium, placenta and foetus of equid herpesvirus
1 (EHV-1) abortions. J Comp Pathol 104(4): 379-87, 1991.
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- International Veterinary Pathology Slide Bank:
Laser disc frame #7673, 18401.
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Case IV - A30819 (AFIP 2550630)
Signalment: 10-year-old, female pony presented for slaughter.
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- History: No previous history available. No antemortem
findings.
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- Gross Pathology: Intraluminal growths in airways of
lung reported by submitting inspection veterinarian.
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- Laboratory Results: None.
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- Contributor's Diagnosis and Comments: Equine pulmonary
granular cell tumor (multicentric, lung).
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- Microscopically, there is marked multifocal peribronchial
replacement of normal architecture by discrete, nodular, unencapsulated
foci which elevate bronchial mucosa and replace or displace associated
mucous glands and cartilage. The foci are characterized by a
monotonous population of round to polygonal cells with primarily
eccentric, round, vesicular nuclei and occasionally, single,
small basophilic nucleoli. There is abundant, distinct, eosinophilic,
finely granular cytoplasm. The cells are randomly dispersed within
a fine, fibrobvascular stroma. There is approximately one mitotic
figure per high power field. Granules within the cells are multifocally
periodic acid-Schiff's positive.
- The tumor is not common in the equine, but does appear to
be a specific entity in the equine in its pulmonary location.
The tumors are usually multicentric and oriented to airways often
compressing the overlying respiratory mucosa and occluding bronchiolar
and bronchial lumina. The gross and histologic appearance of
this case exemplifies this behavior. The primary clinical problem
seen with the tumors is bronchial and bronchiolar obstruction
with respiratory distress.
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- AFIP Diagnosis: Lung: Granular cell tumor, pony, breed
unspecified, equine.
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- Conference Note: The conference participants agreed
with the contributor's diagnosis of pulmonary granular cell tumor.
By immunohistochemistry performed at the AFIP, the neoplastic
cells stained positively for S-100 protein, glial fibrillary
acidic protein (GFAP) and neuron-specific enolase (NSE); these
findings are in agreement with previous reports.
- All granular cell tumors reported in horses have been in
the lungs. Tumors can be single or multiple involving one or
more lobes, usually causing partial or complete occlusion of
the bronchi.
- Equine granular cell tumors are remarkably similar to human
granular cell tumor of the lung. The human tumors occur in the
lower trachea and bronchi, are usually multiple, and often cause
airway obstruction.
- The equine pulmonary granular cell tumor is believed to be
of Schwann cell origin. The cytoplasmic granules of the neoplastic
cells are reported to stain with luxol fast blue and periodic
acid-Schiff counterstain for myelin and myelin-breakdown products.
These findings coupled with positive staining with S-100, GFAP,
and NSE support Schwann cell origin.
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- Contributor: United States Department of Agriculture,
Food Safety Inspection Service, Science-Pathology, Eastern Laboratory,
Russell Research Center, P.O. Box 6085, College Station Road,
Athens, GA 30604.
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- References:
1. Guillou L, Gloor E, Anani PA, Kaelin R: Bronchial granular
cell tumor: report of a case with preoperative cytologic diagnosis
on bronchial brushings and immunohistochemical studies. Acta
Cytologica 35:375-380, 1990.
- 2. Kelley LC, Hill JE, Hafner S, Wortham KJ: Spontaneous
equine pulmonary granular cell tumors: morphologic, histochemical,
and immunohistochemical characterization. Vet Pathol 32:101-106,
1995.
- 3.Mazur MT, Shultz JJ, Meyers JL: Granular cell tumor. Arch
Pathol Lab Med 114:692-696, 1990.
- 4. Meittinen M, Lehtonen E, Lehtola H, Ekblom P, Lehto VP,
Virtanen I: Histogenesis of granular cell tumor - an immunohistochemical
and ultrastructural study. J Pathol 142:221-229, 1984.
- 5. Parker GA, Botha W, Van Dellen A, Casey HW: Cerebral granular
cell tumor (myoblastoma) in a dog: case report and literature
review. Cornell Vet 68(4):507-520, 1978.
- 6. Sanford SE, Hooverj DM, Miller RB: Primary cardiac granular
cell tumor in a dog. Vet Pathol 21:489-494, 1984.
- 7. Turk MAM, Breeze RG. Histochemical and ultrastructural
features of an equine pulmonary granular cell tumor (myoblastoma).
J Comp Path 91:471-481, 1981.
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- International Veterinary Pathology Slide Bank:
Laser disc frame #19155-6.
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- Lance Batey
Captain, VC, USA
Registry of Veterinary Pathology*
Department of Veterinary Pathology
Armed Forces Institute of Pathology
(202)782-2615; DSN: 662-2615
Internet: Batey@email.afip.osd.mil
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- * The American Veterinary Medical Association and the American
College of Veterinary Pathologists are co-sponsors of the Registry
of Veterinary Pathology. The C.L. Davis Foundation also provides
substantial support for the Registry.
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