AFIP Wednesday Slide Conference - No. 28

14 May 1997
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)

Signalment: 1-year-old, Simmental, heifer, bovine (Bos taurus).
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.
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.
Laboratory Results: See contributor's comments.
Contributor's Diagnosis and Comments: Colon (some recipients have ileum), colitis, lymphocytic with lymphocytic, necrotizing arteritis/periarteritis and transmural edema, severe, diffuse.
Condition: malignant catarrhal fever (MCF).
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.
AFIP Diagnosis: Colon: Vasculitis, lymphohistiocytic, necrotizing, multifocal, moderate, with diffuse, mild to moderate, subacute, erosive colitis, Simmental, bovine.
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.
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.
International Veterinary Pathology Slide Bank:
Laser disc frame #4997-9, 9357, 18604, 19541, 20189, 21981-5.

Case II - no label (AFIP 2554466)

Signalment: A newborn Suffolk x Dorset sheep.
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.
Gross Pathology: No gross abnormalities were noted in any of the 6 mildly autolytic fetuses or placentas examined.
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.
Contributor's Diagnosis and Comments: Placentitis, neutrophilic, with intracellular bacteria.

Etiology: Campylobacter jejuni.
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.
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.
Contributor: Veterinary Laboratory Service, Ontario Ministry of Agriculture and Rural Affairs, Bldg #43, McGilvray St, Guelph, Ontario, Canada, N1H, 6R8.
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.
International Veterinary Pathology Slide Bank:
Laser disc frame #9350, 9485.

Case III - 95P1032 (AFIP 2551665)

Signalment: 1-day-old, female, Arabian horse, equine.
History: The foal was weak at birth. Upon presentation to the teaching hospital, it had abnormal lung sounds.
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.
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.
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.
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.
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.
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
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.
Contributor: Iowa State University, Department of Veterinary Pathology, Ames, IA 50011.
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.
International Veterinary Pathology Slide Bank:
Laser disc frame #7673, 18401.

Case IV - A30819 (AFIP 2550630)

Signalment: 10-year-old, female pony presented for slaughter.
History: No previous history available. No antemortem findings.
Gross Pathology: Intraluminal growths in airways of lung reported by submitting inspection veterinarian.
Laboratory Results: None.
Contributor's Diagnosis and Comments: Equine pulmonary granular cell tumor (multicentric, lung).
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.
AFIP Diagnosis: Lung: Granular cell tumor, pony, breed unspecified, equine.
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.
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.
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.
International Veterinary Pathology Slide Bank:
Laser disc frame #19155-6.
Lance Batey
Captain, VC, USA
Registry of Veterinary Pathology*
Department of Veterinary Pathology
Armed Forces Institute of Pathology
(202)782-2615; DSN: 662-2615
* 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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