AFIP Wednesday Slide Conference - No. 4
23 September 1998

Conference Moderator:
MAJ Dana P. Scott, Diplomate, ACVP
Department of Veterinary Pathology
Armed Forces Institute of Pathology
Washington, DC 20307
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Case I - 351-97 (AFIP 2639852)
Signalment: Juvenile striped skunk (Mephitis mephitis), female, 3 and 1/2 months old.
History: Part of a group of juvenile striped skunks that were hand raised from birth by private individuals. These skunks (N=10) were kept in quarantine for 24 days before this skunk (351-97) died. No clinical signs were observed the day before this animal's death. Blood was drawn for CBC and biochemistry the day prior to death.
Gross Pathology: Gross lesions included diffuse, mild icterus in the subcutis and omental adipose tissue, and petechiae and ecchymoses throughout the subcutis. There was approximately 1 ml of clear yellow fluid in the abdominal cavity. The liver was markedly enlarged and diffusely mottled yellow, with an enlarged and edematous gall bladder. Other gross findings included mild bilateral renal enlargement and marked splenomegaly.
Laboratory Results: Blood work revealed a low WBC count (1595). The differential count was segmented neutrophils (32%), lymphocytes (64%), and eosinophils (4%). Biochemistry results demonstrated a very high AST (470 IU/L), ALT (332 IU/L), total bilirubin (1.2 mg/dl), and LDH (1722 IU/L). There was slightly decreased total protein (4.7 gm/dl) and hypoalbuminemia (2.0 gm/dl).
Contributor's Diagnosis and Comments:
1. Liver: Hepatitis, subacute, diffuse, severe, with intranuclear inclusion bodies and multifocal, minimal random necrosis and hemorrhage, consistent with infectious canine hepatitis (canine adenovirus Type 1).
2. Spleen: Congestion, diffuse, severe with intraphagocytic hemosiderosis and few intraendothelial intranuclear amphophilic to basophilic inclusion bodies, compatible with canine adenovirus Type 1.
Viral isolation, histologic features, and electron microscopy confirm a diagnosis of infectious canine hepatitis (ICH) in this striped skunk. Infectious canine hepatitis (canine adenovirus type I) causes disease worldwide in many canidae, including domestic dogs, foxes, skunks, wolves, and coyote (Cabasso 1981, Appel 1987). Karstad et al. (1975) document infectious canine hepatitis causing acute, fatal hepatitis in striped skunks, and suggest that striped skunks may be a natural wildlife host of infectious canine hepatitis.
Infectious canine hepatitis is spread by direct contact, and the host becomes infected by ingestion of viral particles in urine, feces, or saliva of infected animals. Infected urine is the most important source for transmission, and the virus may be shed in the urine for at least 6 months after infection (Appel 1987). Infected animals may die acutely without clinical signs or may have abdominal pain, vomiting, diarrhea, petechial and ecchymotic hemorrhages, and icterus (Appel 1987).
Skunks and foxes with ICH often die acutely with no clinical signs (Cabasso 1981). Canine adenovirus type I has an affinity for hepatocytes, endothelial cells, and Kupffer cells, accounting for the hemorrhage (due to vascular endothelial damage) and icterus (hepatocyte damage) present grossly in many cases (Jones and Hunt 1997).
Animals that recover from infection or that have been vaccinated with a live attenuated adenovirus vaccine may have a transient immune complex uveitis, iridocyclitis, and corneal edema ("blue eye") (Tizard 1996). Dogs that recover from infection are immune to ICH for life (Appel 1987).
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Case 4-1. Liver. Large portal vein to right contains sloughing cells with basophilic intranuclear inclusions. Similar intranuclear inclusions are in most degenerating hepatocytes as well.
AFIP Diagnosis: Liver: Hepatocellular degeneration and necrosis, diffuse, with mild multifocal acute hepatitis and vasculitis, numerous hepatocellular intranuclear inclusion bodies, and rare endothelial intranuclear inclusion bodies, striped skunk (Mephitis mephitis), mustelid.
Conference Note: Canine adenovirus type-1 (CAV-1) has worldwide serologic homogeneity and shares many immunologic similarities to human adenoviruses, but is antigenically and genetically distinct from CAV-2, a cause of respiratory disease in the dog. In immunohistochemical studies performed at the AFIP, positive staining of intranuclear inclusion bodies was observed in hepatocytes, Kupffer cells, and endothelial cells utilizing antibodies to human adenovirus.
After gaining entry through the oronasal cavity, the virus localizes in the tonsils and then spreads to other lymphoid organs. In rare instances, severe tonsillitis is associated with edema of the larynx or pharynx that can be fatal. The virus reaches the blood via the thoracic duct and viremia ensues, lasting four to eight days post infection. The virus becomes disseminated to other tissues and body fluids, including saliva, urine, and feces. During this phase, the virus localizes and damages hepatocytes and endothelial cells. The cytotoxic effects of the virus cause the initial cellular injuries in the liver, kidney, and eye. In dogs, the hepatic necrosis which occurs during this stage of infection may be self-limiting and restricted to centrilobular areas. The reticulin framework of the liver remains intact, and hepatic regeneration quickly follows with little evidence of clinical disease. In cases with overt clinical signs, either recovery or death occurs after several days of anorexia, apathy, vomiting, diarrhea, and abdominal pain.
Because the virus is endotheliotrophic, widespread intimal damage exposes the underlying subendothelial collagen initiating diffuse activation of the clotting cascade with resultant consumption of clotting factors and platelets. A hemorrhagic diathesis results, and petechiae, ecchymoses, epistaxis and prolonged hemorrhage from venipuncture sites may be observed clinically. Bleeding into the brain occurs in a small percentage of cases, and some sudden deaths in dogs may be caused by acute midbrain hemorrhage.
In rare instances, a peracute form of the disease occurs, and these severely affected dogs become moribund and die with few, if any, clinical signs during initial viremia. The animal is found dead, and owners often suspect poisoning as the cause. This form of the disease in the dog is reminiscent of the clinical history described for this skunk.
Contributor: Wildlife Conservation Society, Department of Pathology, 185th St. and Southern Blvd., Bronx, NY 10460.
1. Appel M: Canine adenovirus type I (infectious canine hepatitis). In: Virus Infections of Carnivores, pp. 29-44, Elsevier Science Publishers, New York, 1987.
2. Cabasso V: Infectious canine hepatitis. In: Infectious Diseases of Wild Animals, Davis, Karstad, Trainer eds., pp. 191-195, Iowa State University Press, Ames, Iowa, 1981.
3. Jones TC, Hunt RD, King NW: Diseases caused by viruses. In: Veterinary Pathology, 6th ed., pp. 241-245, Williams and Wilkins, Philadelphia, 1997.
4. Karstad LR, Ramsden R, Berry TJ, Binn LN: Hepatitis in skunks caused by the virus of infectious canine hepatitis. J Wild Dis 11:494-496, 1975.
5. Tizard I: Immune complexes and type III hypersensitivity. In: Veterinary Immunology: An Introduction, 5th ed., pp.368-371, WB Saunders Company, Philadelphia, 1996.
6. Greene CE: Infectious canine hepatitis. In: Infectious Diseases of the Dog and Cat, 2nd ed., pp. 22-27, WB Saunders Co., Philadelphia, 1998.
International Veterinary Pathology Slide Bank:
Laser disc frame #'s 17187-89; 16883.
Case II - 8004-98 (AFIP 2640591)

Signalment: Canine, male, neutered, German Shepherd Dog, six-year-old.

History: One week prior to euthanasia, this dog was examined by a referring veterinarian for lethargy. Two days later, anterior uveitis (OD) and posterior paresis were evident.
Gross Pathology: Throughout the right kidney, but particularly in the medulla, were small yellow-white foci. The body of T13 was friable, yellow-tan, and dorsally displaced. The T13/ L1 disk was absent. The body of L1 was rough and red.
Laboratory Results: Spinal radiographs revealed collapse of the T13/L1 intervertebral disk space with lysis and periosteal bone proliferation of the T13 and L1 vertebral bodies. A myelogram revealed compression of the spinal cord in this area. Cytology of a fine-needle aspirate of the affected disk revealed fungal hyphae and spores. Aspergillus terreus was isolated.
Contributor's Diagnosis and Comments: Kidney: Tubular-interstitial nephritis, pyogranulomatous, with thromboangiitis, hemorrhage, and numerous fungal elements (septate hyphae and spores).
This case is an example of disseminated Aspergillus terreus infection in a dog. German Shepherd Dogs are probably predisposed to infection with this saprophytic fungus. In the kidney, the medulla is usually affected more than the cortex. Vertebrae are common sites of fungal localization. The pathogenesis obviously involves hematogenous dissemination (mycethemia). In section, Aspergillus terreus spores that branch laterally from septate hyphae are termed aleuriospores.
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Case 4-2. Kidney. There is multifocal liquefactive necrosis of medullary collecting tubules characterized by an infiltrate of neutrophils, histiocytes, and occasional faint 5-10µ yeasts.
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Case 4-2. Kidney. Lumena of necrotic collecting tubules are filled with pale fungal hyphae and surrounded by neutrophils and fewer macrophages.
AFIP Diagnosis: Kidney: Nephritis, necrosuppurative, multifocally extensive, severe, with necrotizing vasculitis and numerous fungal hyphae, German Shepherd Dog, canine, etiology consistent with Aspergillus sp.
Conference Note: Aspergillus sp., common saprophytic molds, are not usually pathogens, but cause opportunistic infections. Aspergillosis is most common and severe in poultry, especially chicks and turkey poults, where infection is due to contaminated bedding and may occur as an epizootic with high mortality.

In people and cats, disseminated aspergillosis occurs most frequently in hosts that are debilitated or immunosuppressed by a variety of underlying conditions such as neoplasia (malignant lymphoma), infectious agents (panleukopenia, FeLV, AIDS), and drug therapy (glucocorticoids, prolonged antibiotic use). Disseminated canine aspergillosis is a rare disease most often caused by Aspergillus terreus. It occurs most commonly in German Shepherd Dogs. Predisposing factors leading to disseminated aspergillosis in dogs may include optimal environmental conditions for growth of the organism, infection with particularly virulent fungal strains, and a genetically based immunodeficiency, such as a defect in mucosal immunity or defects in phagocyte or neutrophil function. Unlike disseminated aspergillosis, nasal aspergillosis in the dog is most commonly caused by A. fumigatus.
The exact portal of entry for A. terreus is unknown, but fungal conidia or aleuriospores may enter the host and establish initial infection through the respiratory or gastrointestinal tract. In man, infection follows inhalation of spores, and organisms proliferate within previously diseased areas of the lung, such as resolved tuberculosis lesions. Alternatively, some infections may be initiated by surgery or intravenous inoculation. Once entry is gained and infection is established, the ability of the organism to invade and disrupt vessels allows hematogenous spread via circulating aleuriospores. In section, aleuriospores are lateral branching spherical vesicles occasionally found along thin-walled fungal hyphae of A. terreus. The GMS method demonstrated numerous aleuriospores in this case. These distinctive structures allow specific histopathologic diagnosis of A. terreus infection.
The distribution of gross lesions in this dog is similar to the findings reported in a retrospective study of ten dogs with disseminated aspergillosis. Lesions in these dogs frequently developed in the kidneys, spleen, long bones, and the epiphyses of vertebra and sternebra. Terminal capillary loops and slow blood flow characterize these anatomical locations. The renal medulla has numerous arteriolae rectae which terminate in capillary loops, and may explain the predominate medullary distribution of lesions in this dog. The organism's ability to invade and disrupt vessels leads to activation of the coagulation cascade, thrombosis, and infarction. Vascular stasis and thrombosis are important in the development of osteomyelitis.

Conference participants discussed Fusarium sp. as another cause of fungal nephritis. Fusarium is an environmental saprophyte which may be found as a part of the normal microflora of the canine skin. The organism has been reported as an infrequent cause of mycotic disease in dogs, including cases of ascending unilateral pyelonephritis in a Newfoundland and disseminated disease in a German Shepherd. The organism in the Newfoundland occurred as dense mycelial mats of branching septate fungal hyphae with occasional terminal globose heads; aleuriospores were not described. Immunohistochemistry confirmed the identity of the organism.

Contributor: Animal Disease Diagnostic Laboratory, ADDL-1175, Purdue University, West Lafayette, IN 47907.
1. Kabay MJ, Robinson WF, Huxtable CRR, McAleer R: The pathology of disseminated Aspergillus terreus infection in dogs. Vet Pathol 22:540-547, 1985.
2. Day MJ, Holt PE: Unilateral fungal pyelonephritis in a dog. Vet Pathol 31:250-252, 1994.
3. Jones TC, Hunt RD, King NW: Diseases caused by fungi. In: Veterinary Pathology, 6th ed., pp. 506-507, Williams and Wilkins, 1997.
4. Day MJ: Canine disseminated aspergillosis. In: Infectious Diseases of the Dog and Cat, 2nd ed., pp. 409-412, WB Saunders Co., Philadelphia, 1998.
5. Cotran RS, Kumar V, Robbins SL: Infectious diseases. In: Robbins Pathologic Basis of Disease, 5th ed., pp. 355-356, WB Saunders Co., 1994.
Case III - Fac. Med. Vet. da USP 2 (AFIP 2641266)
Signalment: Adult, male, howler monkey, Alouatta fusca, Cebidae, New World non-human primate.
History: This free-ranging howler monkey was kept in captivity for six months due to an ongoing reintroduction program. During this period, the animal was identified with a microchip and submitted to multiple serological assays, including rabies, leptospirosis, malaria and Lyme disease, and periodical clinical examination. After this period, the monkey was released in a remaining tropical rain forest close to São Paulo City. Ten days after reintroduction to the wild, it was found in an agonal state due to a dog attack.
Gross Pathology: Grossly, the howler monkey presented with extensive multifocal hemorrhages associated with dog bites. Within the oral cavity, there were multiple, two to five millimeter diameter, soft, white, isolated to coalescing masses which affected the mucosa of the lower lip and the craniomedial aspect of the tongue. Other major findings were pulmonary edema, typhlitis due to Enterobius sp., and multifocal ulcerative colitis.
Laboratory Results:
1. Heart blood cultures: Negative.
2. Liver cultures: Negative.
3. Serological essays for rabies, malaria, Lyme disease, leptospirosis: Negative.
4. Immunohistochemistry assays for papillomavirus (polyclonal antibody-DAKO ä, dilution 1:8000): Positive.
5. Immunohistochemistry assays for human papillomavirus types 6, 11, 18 (monoclonal antibody NOVOCASTRAä, dilution 1:40): Negative.
6. In situ hybridization for detection of DNA of human papillomavirus types 6, 11, 16, 18, 30, 31, 33, 35, 45, 51 and 52 (DAKOä): Negative.
Contributor's Diagnosis and Comments: Mucosa, lower lip: Acanthosis, moderate, associated with marked koilocytosis, fusion of rete ridges, and minimal hyperparakeratosis (Focal Epithelial Hyperplasia, FEH - Heck's Disease) due to papillomavirus, howler monkey (Alouatta fusca), Cebidae, New World non-human primate.
Focal Epithelial Hyperplasia (FEH), also known as Heck's disease, is an uncommon condition, occurring only in the oral cavity, and related to papillomavirus infection. It has been described in humans (South, Central, and North American Indians and Eskimos), chimpanzees (Pan troglodytes), pygmy chimpanzees (Pan paniscus) and the domestic rabbit. FEH has never been reported in New World Primates.

Grossly, FEH is defined as well-circumscribed or coalescing, slightly elevated, soft masses or papules, 0.1 to 0.5 cm in diameter, affecting mainly the lower lip and buccal mucosa. Lesions are usually white to pink. Microscopically, FEH is mainly characterized by mild to severe focal acanthosis associated with elongation and fusion of the rete ridges and keratinocyte vacuolization (koilocytosis).

In humans, in situ DNA hybridization exams revealed that human papillomavirus types 13 and 32 are markedly specific for FEH. In non-human primates, molecular biology assays were performed in the pygmy chimpanzee, revealing the presence of an agent related to HPV-13, tentatively named pygmy chimpanzee papillomavirus.

In the present case, the gross and microscopic features are in accordance with those described in the literature for FEH. The nature of the viral antigen was determined using a rabbit polyclonal antibody to bovine papillomavirus. Subsequent immunohistochemistry assays for HPV and in situ HPV DNA hybridization exams were negative, suggesting the possibility that the agent is not related to the known papillomaviruses. Further studies are planned to clarify this possibility.
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Case 4-3. Lip. There is proliferation and ballooning degeneration of the acanthocytes. Within the clear cytoplasm are numerous minute, granular inclusions. (The surface is to the right).
AFIP Diagnosis: Oral mucosa, epithelium: Hyperplasia, diffuse, severe, with numerous koilocytes, vacuolar degeneration, and few intranuclear inclusions, howler monkey (Alouatta fusca), nonhuman primate.
Conference Note: Papillomaviruses are a large, heterogenous group of small, double-stranded DNA viruses noted for their ability to induce epithelial proliferation. Papillomaviruses are usually species and target cell specific.
The term multifocal papilloma virus epithelial hyperplasia (MPVEH) has been suggested as a more appropriate name for FEH because it describes the nature and pathology of the disease. Microscopically, the lesions are characterized by acanthosis of the mucosal epithelium, anastomosing rete ridges which often point radially toward the center of the lesion, parakeratotic hyperkeratosis, and vacuolar degeneration of keratinocytes. Within the hyperplastic basal layers of the epithelium, a few keratinocytes may be swollen with abundant clear cytoplasm and contain an irregularly enlarged nucleus with central amphophilic to basophilic granularity. The nuclear changes are highly diagnostic for MPVEH in humans. In this howler monkey, rare basal epithelial cells demonstrate similar histologic changes. The term "mitosoid" has previously been applied to the nuclear changes in human lesions; however, the term is confusing, may lead to erroneous interpretations, and should be avoided.
Explanations for the epidemiological distribution of human disease noted by the contributor are varied, and several socioeconomic and genetically based hypotheses have been proposed. Papillomaviruses may demonstrate a viral site specificity for infection, and this mechanism is proposed for MPVEH and HPV32. The site of viral specificity is dependent on the numbers and distribution of cell membrane receptors. Affected families or ethnic groups may have higher numbers of these cell receptors and thus a greater likelihood of infection. It has also been observed that MPVEH often affects individuals in lower income groups, suggesting that malnutrition, chronic immunodeficiency, and poor hygiene may correlate with risk of infection and disease transmission.
Several DNA and RNA viruses are known to be oncogenic in humans and animals. Human papillomaviruses are involved in the genesis of a variety of epithelial tumors in man, including benign squamous papillomas as well as squamous cell carcinoma of the cervix and anogenital region. The oncogenic properties of papillomaviruses are related to products of two early papillomaviral genes, E6 and E7.
The E7 viral protein binds to the cellular tumor suppressor gene retinoblastoma protein (Rb). This affects the ability of the Rb gene product (pRb) to bind and sequester cellular transcription factors involved in the initiation of DNA synthesis. With these transcription factors liberated from pRb, the molecular controls on the cell cycle are released, DNA synthesis is triggered, and the normally quiescent cells quickly reenter the cell cycle resulting in indiscriminate proliferation.
The E6 protein binds to and inactivates p21, the product of the cellular tumor suppressor gene p53. Normally, when cellular DNA is damaged, as occurs in viral infections or due to mutagenic chemicals, p53 accumulates in the nucleus and acts by inducing the transcription of p21. When functional, p21 protein is a potent inhibitor of the cyclin-dependent kinase system (it inhibits the formation of cyclin/CDK complexes) and blocks the phosphorylation pRb. The pRb protein remains in the active, unphosphorylated state, thus preventing the cell from entering the S phase of the cell cycle. This pause in the cell cycle allows for repair of damaged cellular DNA. With inactivation of p21 protein, cells with damaged DNA are allowed to reenter the cell cycle and proliferate without proper repair, thus leading to potential oncogenesis.
Both the p53 gene and Rb gene act in the nucleus and work by inhibiting the cell cycle. Unlike the Rb gene, however, p53 does not continually police the normal cell, but is activated during periods of damage to cellular DNA. Should the DNA repair mechanisms fail, the p53 gene stops the cell from dividing and activates the cell-suicide genes in the process known as apoptosis. Apparently, papillomaviruses may act to prevent this fail safe mechanism of p53, and uncontrolled, sometimes malignant proliferation of virally infected cells occurs.
Contributor: University of São Paulo, Faculty of Veterinary Medicine and Zootechny, Department of Pathology, Av. Prof. Orlando Marques de Paiva 87, Cidade Universitária, São Paulo SP 05508-900, Brazil.

1. Anderson DC, McClure HM: Focal epithelial hyperplasia, chimpanzees. In: Monographs on Pathology of Laboratory Animals: Nonhuman Primates, Jones, Mohr, Hunt eds., pp. 233-237, Springer-Verlag, New York, 1993.
2. Viraben R, et al.: Focal Epithelial Hyperplasia (Heck disease) associated with AIDS. Dermatology 193:261-262, 1996.
3. Van Ranst M, et al.: A papillomavirus related to HPV type 13 in oral focal epithelial hyperplasia in the pygmy chimpanzee. J Oral Pathol Med 20:325-321, 1991.
4. Roman CB, Sedano HO: Multifocal papilloma virus epithelial hyperplasia. J Oral Surg Oral Med Oral Path 77:631-635, 1994.
5. Kumar V, Cotran RS, Robbins SL: Neoplasia. In: Basic Pathology, 6th ed., pp.153-167, WB Saunders Co., Philadelphia, 1997.
Case IV - 568-94 (AFIP 2639850)
Signalment: Nine-year-old, adult, female leopard cat (Felis bengalensis).
2 histology images (previously improperly labeled 4-1)
History: This animal had no history of current medical problems. The keeper reported she had eaten her dinner normally the night before. The following morning, she exhibited respiratory distress. With handling, the dyspnea progressed to respiratory arrest, and the cat died shortly after intubation.

Gross Pathology: The lungs were firm and mottled, and the right anteroventral lobe was plum colored. The trachea contained moderate amounts of blood-tinged foam. There were no other gross lesions. A lung swab was submitted for bacterial culture. Tissues were frozen at minus 70o C.
Laboratory Results: Viral isolation of the lung tissue was positive for feline herpesvirus. Aerobic bacterial cultures of the lung had no growth. Immunoperoxidase staining for toxoplasmosis was negative.
Contributor's Diagnosis and Comments: 1. Bronchi and bronchioles: Bronchitis and bronchiolitis, subacute, necrotizing, multifocally extensive, moderate to severe, with extension into alveolar tissue, and intraepithelial intranuclear inclusion bodies (feline herpesvirus Type I). 2. Alveolar edema and emphysema, multifocally extensive, moderate to severe. 3. Peribronchiolar glands: Hyperplasia, moderate.
Feline viral rhinotracheitis (FVR) is an infection of all Felidae and is caused by feline herpesvirus type I (FHV-1), a member of the Alphaherpesvirinae subfamily of Herpesviridae.1,3,6 The first documented isolation of the FVR virus in an exotic felid was reported at the St. Louis Zoo in 1977 where it caused the deaths of three out of five clouded leopards (Felis nebulosa) in a single outbreak.
In domestic cats, infection with FHV-1 accounts for 40 to 50% of all upper respiratory diseases.1 The virus has a predilection for the epithelium of nasal passages, pharynx, soft palate, conjunctivae, tonsils, and, to a lesser extent, trachea.4 Clinical signs correspond to these sites of viral replication and consist of paroxysmal sneezing, coughing, salivation, fever, and serous to mucopurulent nasal and conjunctival discharges.4 Although morbidity is quite high, most cats recover within two weeks with supportive care. Many of these cats become asymptomatic carriers and may shed virus at later times of stress.
This leopard cat had an unusual presentation. No lesions were found in the nasal passages, oral cavity, tonsils, or conjunctivae. Histologic lesions were limited to the lower respiratory tract and centered on the bronchi and bronchioles with extension into the adjacent alveolar tissue. As viral inclusions were not identified in the initial sections, other causes of feline respiratory disease were considered including feline calicivirus, feline reovirus, the feline-adapted strain of Chlamydia psittaci (feline pneumonitis agent), Mycoplasma felis, Bordetella bronchiseptica and Pasteurella multocida. However, bacterial cultures and Giemsa stains for Chlamydia were negative. Immunoperoxidase staining for toxoplasmosis was also negative. Additional recuts of lung tissue revealed smudgy to clearly distinct intranuclear inclusion bodies in sloughed bronchiolar epithelial cells. Tissue was submitted for viral isolation and was positive for feline herpesvirus.
As was the case in the St. Louis outbreak, there was no identifiable source of exposure of the cats to the virus. No management changes (i.e., shipment, handling, change of enclosures) had occurred for an extended period of time before the disease onset. The most likely explanation in these cases is that there was a recrudescence of a latent infection. Although in domestic cats subsequent infections are usually less severe than the initial infection, this may not be true of exotic felids. Many zoos now vaccinate on a six month basis due to the high mortality rate.
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Case 4-4. Lung. There is proliferation of type II pneumocytes. Alveoli are filled with macrophages, fewer lymphocytes and edema and occasionally contain syncytia. Alveolar septae are thickened by fibrin, histiocytes and large pneumocytes.
AFIP Diagnosis: Lung: Pneumonia, bronchointerstitial, necrotizing, acute to subacute, diffuse, with alveolar edema, few syncytial cells, and numerous amphophilic and eosinophilic intranuclear inclusions, leopard cat (Felis bengalensis), feline.
Conference Note: Herpesviruses infect a wide variety of animals from insects through vertebrates, and with the possible exception of sheep, a herpesvirus is the cause of at least one major disease in each of the domestic species. Herpesviruses are classically divided into three subfamilies: a-herpesvirinae, b-herpesvirinae, and g-herpesvirinae. Generally, the a-herpesvirinae are rapidly growing, cytolytic viruses that have the ability to establish latent infections in nerve ganglia (especially the trigeminal), and may have a broad host range. Examples are numerous but include infectious bovine rhinotracheitis, coital exanthema of equids, duck plague, and pseudorabies. The cytomegaloviruses, or b-herpesvirinae, have a restricted host range, slow viral replication which does not cause cell lysis until several days after infection, and may remain latent in secretory glands, lymphoreticular tissue, kidneys, and other tissues. A few examples include equine cytomegalovirus infection (EHV-2) and inclusion body rhinitis of swine (porcine herpesvirus-2). The final group, the g-herpesvirinae, are known for their predilection to infect and remain latent within lymphoid cells, though they may cause cytocidal infections in epithelial and fibroblastic cells. Classic examples include Epstein-Barr virus in man and malignant catarrhal fever of bovids (Alcelaphine herpesvirus 1).
Feline rhinotracheitis virus (FRV) is a typical a-herpesvirus that measures between 120-200nm (average 150nm), contains double-stranded DNA, replicates in the cell nucleus, and becomes enveloped by budding through invaginations of the nuclear membrane. Infection with FVR is naturally acquired through oral, nasal or conjunctival routes by either direct contact or from aerosolized oronasal secretions of virus-shedding infected cats. After an incubation of 24-48 hours, the onset of typical clinical signs of an upper respiratory tract infection occurs, accompanied by profuse salivation and corneal ulcers. While oral ulceration may also be present in FVR, this lesion is more typical of feline calicivirus infections.
Viral replication occurs primarily in the epithelium of nasal cavity, nasopharynx, turbinates, and in the tonsils. Shedding of viral particles may begin as early as 24 hours post infection and may last as long as one to three weeks, though most active viral replication and cell necrosis occur between two to seven days post infection. During this period, the herpesviral intranuclear inclusions are most often present in infected epithelial cells and occasionally within endothelial cells. Because viral replication is normally restricted to areas of lower body temperature, such as the upper respiratory passages, viremia is rare, and resolution of disease normally takes between two to three weeks.
Uncommonly, generalized disease may follow initial upper respiratory tract infection in debilitated or immunocompromised animals and in neonatal kittens. In these cases viremia may be present. Mortality due to FVR is rare in domestic cats, but when fulminating cases of viral infection occur, there is often widespread necrotizing bronchitis, bronchiolitis, and interstitial pneumonia with edema. Viral infection may predispose to fatal secondary bacterial bronchopneumonia.
Contributor: Wildlife Conservation Society, Department of Pathology, 185th St. and Southern Blvd., Bronx, NY 10460
1. Baldwin CA: Feline Viral Rhinotracheitis. In: Veterinary Diagnostic Virology, Castro, Heuschele eds., pp. 189-191, Mosby Year Book, St. Louis, 1992.
2. Boever WK, McDonald S, Solorzand RF: Feline viral rhinotracheitis in a colony of clouded leopards. Veterinary Medicine/Small Animal Clinician Exotic Species. December 1977:1859-1866.
3. Fowler ME: Carnivores. In: Zoo and Wild Animal Medicine, 2nd ed. , pp.834-836, 1986.
4. Jubb KVF, Kennedy PC, Palmer N: The respiratory system. In: Pathology of Domestic Animals, 4th ed., vol. 2, pp. 558-559, Academic Press, 1993.
5. Pedersen NC: Feline herpesvirus type I (feline rhinotracheitis virus). In: Virus Infections of Carnivores, Appel ed., Vol. 1, pp. 227-237, Elsevier Science Publishers, 1987.
6. Wallach JD, Boever WJ: Diseases of Exotic Animals. In: Medical and Surgical Management, pp. 368-369, WB Saunders Company, Philadelphia, 1983.
7. Gaskell R, Dawson S: Feline respiratory disease. In: Infectious Diseases of the Dog and Cat, 2nd ed., pp. 97-106, WB Saunders Co., Philadelphia, 1998.
8. Fenner FJ, et al.: Herpesviridae. In: Veterinary Virology, 2nd ed., pp. 337-368, Academic Press Inc., San Diego, 1993
International Veterinary Pathology Slide Bank:
Laser disc frame #'s 4877 and 15417.
Ed Stevens, DVM
Captain, United States Army
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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