Results
AFIP Wednesday Slide Conference - No. 20
March 12 1997
- Conference Moderator: LTC William H. Baker
Diplomate, ACVP
Walter Reed Army Institute of Research
Division of Pathology
Washington, D.C. 20307-5100
-
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Case I - A95-401 (AFIP 2549261)
- Signalment: 1-year-old, male, rhesus monkey (Macaca
mulatta).
- History: This monkey was inoculated intravenously
with a pathogenic, cloned variant of SIVmac239 four months prior
to sacrifice. There was a recent history of dehydration, anorexia,
cutaneous erythema, and weight loss.
- Gross Pathology: There was weight loss (1.7 Kg, normal=2.0-2.4
Kg) and abdominal adipose tissue was sparse. The right middle
lung lobe was atelectatic, pale pink to purple, and somewhat
firm on palpation. The mesenteric and ileocecal lymph nodes were
enlarged (approximately 2-3 times normal), white, and soft on
palpation.
- Laboratory Results: Microbiology: A few coagulase-negative
staphylococci, small numbers of alpha streptococci, and few Pseudomonas
mirabilis were cultured from lung. No significant organisms were
cultured from the colon or heart blood.
- Contributor's Diagnosis and Comments:
1. Trachea: tracheitis, lymphoplasmacytic, chronic-active,
diffuse, moderate with squamous metaplasia and apical protozoa.
2. Lung: bronchiolitis, lymphoplasmacytic, chronic-active, diffuse,
with squamous metaplasia and apical protozoa.
3. Lung: pneumonia, bronchointerstitial, subacute, multifocal,
moderate.
- Etiologies:
Trachea: Cryptosporidium sp.
Lung: Cryptosporidium sp. and cytomegalovirus (CMV).
- In the section of trachea there are multiple 2 micron diameter
basophilic spherical protozoa adhered to the mucosal surface.
There is attenuation of the epithelium, loss of goblet cells
and cilia. Glands in the lamina propria have squamous metaplasia
with protozoa of similar morphology adhered to the epithelium
of some cells, and inflammatory cellular debris in lumina. In
the lamina propria there are diffuse to aggregated lymphoplasmacytic
cellular infiltrates, admixed with few eosinophils, between and
around the glands. Capillaries are congested.
- Affecting approximately 40% of lung parenchyma are multifocal
areas of inflammation which are primarily associated with the
pulmonary vessels, smaller airways, and the interstitium. In
bronchi, the epithelial cells have numerous 2 micron diameter
basophilic spherical protozoa adhered to the apical surface with
few intra- epithelial leukocytes present. This is accompanied
by loss of goblet cells and cilia. The submucosal glands have
squamous metaplasia with protozoa adhered to the epithelium.
The proprial stroma has diffuse infiltrates of lymphocytes and
plasma cells which extend between and around the submucosal glands.
Alveoli immediately surrounding bronchi are collapsed. Multifocally
and circumferentially arranged around bronchioles and blood vessels
are varying admixtures of lymphocytes, plasma cells, macrophages,
eosinophils and neutrophils; there is mild perivascular edema.
The lumina of some bronchioles and alveoli have accumulations
of neutrophils, macrophages, and debris partially occluding lumina;
this is accompanied by type II pneumocyte hyperplasia and rare
cytomegalic cells with intranuclear inclusions. The inflamed
interstitium is expanded due to infiltrates of mixed mononuclear
cells and granulocytes.
The genus Cryptosporidium (phylum, Apicomplexa; family, Cryptosporiidae)
includes ubiquitous protozoan parasites that infect fish, reptiles,
birds, and mammals, and that grow and reproduce within epithelial
cells (i.e., intracellular, extra cytoplasmic). Cryptosporidiosis
is not a common finding in SIV-infected macaques, but when present
is usually found in the small intestine resulting in a chronic
diarrhea syndrome producing malnutrition. The pathogen is sometimes
found in the gall bladder, biliary ducts, and pancreatic ducts
resulting in proliferative lesions in each. Respiratory cryptosporidiosis
is apparently rare in macaques, particularly when it is the only
system infected. Immunohistochemistry (IHC) performed on sections
of lung identified the organism attached chiefly to the tracheal
and bronchial epithelium, but a few organisms were identified
both within macrophages and free in the lumina of bronchioles
and alveoli. Multiple sections of intestine, pancreas, gall bladder,
and liver were negative.
- When respiratory disease is found in macaques with AIDS,
it is common to find more than one etiologic agent. Other respiratory
pathogens found in these animals include SIV (giant cell pneumonia),
Pneumocystis carinii, CMV, Mycobacterium avium, and to a lesser
extent Toxoplasma gondii and various bacteria and fungi. The
tracheitis and bronchitis in this animal were compatible with
cryptosporidiosis, and C. parvum is the most likely etiology.
However, significant numbers of organisms were not detected by
IHC in the bronchioles or alveoli suggesting a possible separate
etiology for pneumonia. In some sections, CMV inclusions may
be observed, and moderate numbers of CMV positive cells were
detected by in situ hybridization; low numbers of SIV positive
cells were detected. The bacteria recovered from the lung were
considered to be contaminants.
- Perivascular inflammatory lymphohistiocytic infiltrates and
pulmonary lymphoid hyperplasia can be manifestations of SIV-induced
pulmonary lesions. Pulmonary CMV may present as an interstitial
pneumonia. The pneumonic lesions in this animal may represent
mild CMV infection, CMV/SIV co-infection, or a manifestation
of all three etiologies.
- The means by which primary respiratory cryptosporidiosis
developed is not known. The organism may have become dislodged
from the upper airway. Other significant microscopic findings
in this animal included cytomegaloviral orchitis, cytomegaloviral
meningitis, mild enteritis, and a non-specific degenerative myelopathy.
- AFIP Diagnosis: 1. Trachea; bronchi: Tracheobronchitis,
lymphoplasmacytic and eosinophilic, diffuse, moderate, with luminal
epithelial hyperplasia, loss of cilia and goblet cells, multifocal
squamous metaplasia, tracheobronchial adenitis, and numerous
protozoa, rhesus monkey (Macaca mulatta), primate - etiology
consistent with Cryptosporidium sp.
2. Lung: Pneumonia, bronchointerstitial, subacute, diffuse, moderate,
with type II pneumocyte hyperplasia and rare cytomegalic/karyomegalic
cells with eosinophilic intranuclear inclusion bodies.
- Conference Note: The conference participants agreed
with the contributor's diagnoses. Rare intranuclear inclusion-bearing
cytomegalic cells were found within epithelial cells and vascular
smooth muscle cells in some sections. This case illustrates the
importance in looking for multiple etiologic agents in animals
suspected of having immunosuppressive disease.
- Contributor: New England Regional Primate Research
Center, P.O. Box 9102, Southborough, MA 01772-9102.
-
- References:
1. Baskin GB, Murphey-Corb M, Martin LN, et al: Lentivirus-induced
pulmonary lesions in rhesus monkeys (Macaca mulatta) infected
with simian immunodeficiency virus. Vet Pathol 28:506-513, 1991.
- 2. Blanchard JL, Baskin GB, Murphey-Corb M, et al: Disseminated
Cryptosporidiosis in simian immunodeficiency virus/delta-infected
rhesus monkeys. Vet Pathol 24:454-456, 1987.
- 3. Current WL, Reese NC, Ernst JV, et al: Human Cryptosporidiosis
in immunocompetent and immunodeficient persons. N Engl J Med.
308:1252-1257, 1983.
- 4. Fayer R and Ungar LP: Cryptosporidium spp. and Cryptosporidiosis.
Microbiol Rev. 50:458-483, 1986.
- 5. Hoerr FJ, Ranck FM, Hasting TF: Respiratory cryptosporidiosis
in turkeys. JAVMA 173:1591-1593, 1978.
- 6. Kestler H, Kodmana T, Ringler D, et al: Induction of AIDS
in rhesus monkeys by molecularly cloned simian immunodeficiency
virus. Science. 248:1109-1112, 1990.
- 7. Kovatch RM and White JD: Cryptosporidiosis in two juvenile
rhesus monkeys. Vet Pathol. 9:426-440, 1972.
- 8. Naidu, YM, Kestler HW, Li Y, et al: Characterization of
infectious molecular clones of simian immunodeficiency virus
(SIVmac) and human immunodeficiency virus type 2: Persistent
infection of rhesus monkeys with molecularly cloned SIVmac. J
Virol. 62:4691-4696, 1988.
- 9. Simon MA, Chalifoux LV and Ringler DJ: Pathologic features
of SIV-induced disease and the association of macrophage infection
with disease evolution. AIDS Res Hum Retroviruses 8:327-337,
1992.
- 10. Sun, T: Current topics in protozoal disease (Review):
Am J Clin Pathol. 102:16-29, 1994.
-
- International Veterinary Pathology Slide Bank:
Laser disc frame #Cryptosporidium: 21239, 23314, 23316, 12573.
Cytomegalovirus: 13124.
-
Case II - NADC 96-1 (AFIP 2548580)
- Signalment: 6-week-old female pig.
- History: This pig was part of a group of pigs that
were inoculated intra-nasally with Bordetella bronchiseptica,
strain 4609. This pig developed pneumonia 5 days post- inoculation
(PI) and was necropsied.
-
- Gross Pathology: Marked acute multifocal suppurative
bronchopneumonia.
-
- Laboratory Results: B. bronchiseptica was isolated
from lung tissue. Numerous bacteria and bacterial antigen by
immunocytochemistry were present in the cilia of epithelial cells
lining the nasal conchae, trachea, and bronchi. Bacteria and
antigen were also present in small portions of cilia within the
alveoli of some pigs. These detached portions of cilia presumably
came from bronchi or trachea and entered alveoli during inspiration.
Bacterial antigen was also present in the cytoplasm of macrophages
and neutrophils within alveolar lumens.
- Sections of lung contain marked multifocal infiltrates of
neutrophils, cell debris, seroproteinaceous fluid and red blood
cells. Such exudates were present within dilated bronchi, bronchioles,
and the adjacent alveolar lumens. The epithelium lining of some
bronchi and bronchioles is multifocally denuded.
-
- Contributor's Diagnosis and Comments: Marked acute
to subacute bronchopneumonia with hemorrhages and rod-shaped
bacteria associated with cilia. Etiology: Bordetella bronchiseptica
- B. bronchiseptica colonizes ciliated cells of the respiratory
tract. This results in a suppurative rhinitis and possibly pneumonia
that eventually changes into a lymphoplasmacytic rhinitis and
chronic pneumonia. In chronic lung lesions, there can be prominent
peribronchial and peribronchiolar fibrosis. B. bronchiseptica
is associated with conchal atrophy (atrophic rhinitis) and can
induce moderate to severe conchal atrophy experimentally. Several
studies have shown that if pigs are cleared of the B. bronchiseptica
infection, the conchae can return to near normal size. Therefore,
conchal atrophy caused by B. bronchiseptica has been termed reversible
or nonprogressive. Toxigenic strains of Pasteurella multocida
can also induce conchal atrophy; however, the conchae do not
typically regrow after clearance of these organisms. Therefore,
P. multocida induced conchal atrophy is termed irreversible or
progressive. Combined infections of B. bronchiseptica and P.
multocida produce severe forms of conchal atrophy that are irreversible.
Both toxigenic and non-toxigenic strains of P. multocida can
cause pneumonia and pleuritis.
- B. bronchiseptica produces a variety of virulence factors
and toxins. These include attachment factors such as fimbriae,
filamentous hemagglutinin, and pertactin. Toxins include: dermonecrotic
toxin, adenylate cyclase, and tracheal cytotoxin. B. bronchiseptica
does not produce pertussis toxin. Of the above toxins, very little
is known about their influence on respiratory disease and conchal
atrophy. Many assume that the dermonecrotic toxin induces conchal
atrophy; however, this has not been clearly demonstrated. Thus,
little can be said about the virulence of B. bronchiseptica isolates
from pigs until more is known about the virulence factors and
toxins. P. multocidacolonizes tonsil to a greater degree than
turbinate, trachea, and lung. The toxin of P. multocida can be
produced by either A or D strains. Experimentally, the toxin
increases the number of osteoclasts in long bones of rats, induces
osteoclast formation in vitro, decreases the proliferation rate
of chondrocytes in the growth plate of long bones, and causes
hepatic and testicular necrosis.
-
- AFIP Diagnosis: Lung: Pneumonia, necrohemorrhagic,
fibrinous, diffuse, severe, with vasculitis, fibrin thrombi and
cilia-associated bacilli, breed unspecified, porcine.
-
- Conference Note: The conference participants agreed
with the contributor's diagnosis and well written comments. Atrophic
rhinitis continues to be an important cause of economic loss
to the swine industry.
- Contributor: USDA/ARS/National Animal Disease Center,
P.O. Box 70, 2300 Dayton Road, Ames, IA, 50010-0070.
- References:
1. Ackermann MR, Rimler RB and Thurston JR: Experimental model
of atrophic rhinitis in gnotobiotic pigs. Infection and Immunity,
59:3626-3629, 1991.
- 2. Goged NT: Pasteurella multocida toxin: The characterization
of the toxin and its significance in the diagnosis and prevention.
AMPIS (Acta Pathology, Microbiology, and Immunology Scandinavian).
February: 1-55, 1992.
- 3. Gagné S and Martineau-Diozé B: Nasal epithelial
changes induced in piglets by acetic acid and by Bordetella bronchiseptica.
J Comp Pathol 109:71-81, 1993.
- 4. Magyar T, Chanter N, Lax AJ, Rutter JM, Hall GA: The pathogenesis
of turbinate atrophy in pigs caused by Bordetella bronchiseptica.
Vet Microbiol 48:693- 701, 1988.
- 5. Register KB, Ackermann MR, and Dyer D: Nonradioactive
colony lift- hybridization assay for detection of Bordetella
bronchiseptica infection in swine. J Clin Microbiol 33:2675-2678,
1995.
-
- International Veterinary Pathology Slide Bank:
Laser disc frame #7514, 12716, 13993, 12939, 2242.
-
Case III - Dog-2 Sanofi (AFIP 2557308)
-
- Signalment: 11-month-old male Beagle.
- History: Dog was found dead on study day 32. No significant
abnormalities were observed up to study day 31. On study day
32, ptyalism, dyspnea and weakness were observed prior to death.
- Gross Pathology: Oral mucosa was pale. Subcutaneous
tissue in the neck was disrupted by a hematoma and fascia was
edematous and pale green. In the thoracic cavity, hemothorax
was accompanied by pale green areas in parietal pleura and adhesions
between the lung and parietal pleura.
- Laboratory Results: None.
- Contributor's Diagnosis and Comments: Pleuritis, granulomatous,
chronic, marked.
- Etiologic agent unknown; no bacteria observed with Gram stain
and no fungal elements with PAS stains.
- Additional significant lesions observed included the following:
granulomatous pleuritis of the diaphragm with Gram+ cocci; subacute
periarterial inflammation of the carotid artery with Gram+ cocci;
and marked granulomatous serositis of the esophagus with Gram+
cocci.
- This lesion is considered traumatic in origin, probably caused
by esophageal injury before initiation of the study, as the dogs
were not gavaged. Initial inflammation in the cervical region
then extended into the thorax. The cause of the hematoma and
hemothorax were not identified.
-
- AFIP Diagnosis: Lung: Pleuritis, chronic-active, proliferative,
diffuse, severe, with diffuse atelectasis and fibrino-cellular
thrombi, Beagle, canine.
- Conference Note: Conference participants discussed
the difference between chronic active pleuritis and mesothelioma.
The regular, even distribution of this lesion and the presence
of inflammation argue against a diagnosis of mesothelioma. Reactive
mesothelium is often pleomorphic and must be differentiated from
neoplastic mesothelium.
- Pleuritis can be caused by numous different bacteria and
is often secondary to pneumonia. Other pathways by which infectious
agents may reach the pleura include hematogenous or lymphatic
spread, direct extension from the esophagus or abdominal viscus,
and traumatic penetration through the thoracic wall.
-
- In the dog, the most common causes of pleuritis are Actinomyces,
Nocardia, and Bacteroides spp. Mixed bacterial infections are
common and a variety of organisms may be present, including Corynebacterium
spp., Pasteurella spp., E. coli, Fusobacterium necrophorum, Pseudomonas
spp., and streptococci.
- Contributor: Sanofi Research Division, 9 Great Valley
Parkway, Collegeville, PA, 19426.
- References:
Jubb KVF, Kennedy PC, Palmer N (eds): Pathology of Domestic Animals,
4th ed., Vol. 2, Academic Press, pp. 697-698; 443-444, 1993.
- International Veterinary Pathology Slide Bank:
Laser disc frame #Pleuritis: 2460, 2461, 8770, 9223, 9529, 23916.
Mesothelioma: 0648, 2867, 5665, 20938.
-
Case IV - 95-4682N (AFIP 2550440)
- Signalment: 5-year-old, female, mixed breed dog.
-
- History: Sudden onset of weakness and depression.
Physical exam revealed pale mucous membranes and tachycardia.
The dog had been diagnosed with Addison's disease two weeks previously
and was on prednisone therapy. Soon after admission, the dog
went into cardiac arrest and died.
-
- Gross Pathology: Necropsy revealed massive hepatic
necrosis and hemorrhage, generalized icterus and petechiae in
lung, mouth, esophagus, stomach, intestine and urinary bladder.
Hemorrhage was present in the stomach and intestine. The adrenal
glands were small.
-
- Laboratory Results: Packed cell volume on day of presentation
was 14.
-
- Contributor's Diagnosis and Comments: Hepatic necrosis,
centrilobular to coalescing, severe, with intranuclear inclusion
bodies, consistent with adenovirus infection.
- Infectious canine hepatitis is a rare disease and typically
occurs in young dogs where it causes mild to severe clinical
disease. It is unusual for the disease to occur in the older
dog and cause sudden death. This dog died of hemorrhage probably
caused by disseminated intravascular coagulation (DIC). The dog
had renewed it's annual DHL vaccine 4 months previous.
- AFIP Diagnosis: Liver: Hepatitis, necrotizing, acute,
multifocal to coalescing, severe, with hemorrhage and rare basophilic
intranuclear inclusion bodies, mixed-breed, canine, etiology
consistent with canine adenovirus type 1.
-
- Conference Note: Infectious canine hepatitis is caused
by canine adenovirus type 1 (CAV1). CAV1 is unusual among the
adenoviruses, in that it is capable of causing severe generalized
disease affecting including liver, lung, eye, brain, and kidney.
CAV1 is distinct from canine adenovirus type 2, which usually
causes a mild respiratory infection in the dog. Coyotes, wolves
and raccoons are also susceptible to CAV1. CAV1 has special tropism
for endothelium, mesothelium, and hepatic parenchyma. Virions
are assembled in the nucleus and are released during cell lysis.
Oral or conjunctival exposure is presumed to be the natural route
of infection. Viral replication occurs initially in the tonsils;
the resulting tonsillitis can be severe with extensive edema
of the throat and larynx. Fever accompanies the tonsillitis and
precedes the viremic phase, which is of short duration and accompanied
by severe leukopenia. The order of infection of Kupffer cells,
sinusoidal endothelium and hepatocytes is unclear, but all are
affected. As stromal collapse does not occur, there is rapid
hepatic regeneration with no significant residual lesions in
survivors. Hemorrhage of serosa, gingiva, lungs and the brain
are due to viral infection of capillary and venule endothelium.
Disseminated intravascular coagulation is a frequent complication
that begins in the early viremic phase. Thrombocytopenia results
from severe vascular endothelial damage with adhesion of platelets
in sinusoids. Although the production of clotting factors may
be somewhat reduced, the effect of accelerated consumption is
greater. Ocular lesions may develop between 7 and 21 days of
infection. There is inflammatory edema of the iris, ciliary body,
and corneal propria with viral antigen in all but the cornea;
cellular infiltrates of the iris and filtration angle are principally
plasma cells. This lesion represents a local type III hypersensitivity
reaction to virus-antibody complex deposition in the small blood
vessels of the ciliary body and iris, and the resulting interference
with normal fluid exchange. During ICH recovery, the virus is
eliminated from most organs, but tends to persist in the kidney,
with virus being shed in urine for up to 9 months post-infection.
-
- Contributor: Department of Biomedical Sciences &
Pathobiology, College of Veterinary Medicine, VA Tech, Blacksburg,
VA 24061-0442.
-
- References:
1. Kelly RW: The liver and Biliary System. In: Pathology of Domestic
Animals, eds. Jubb KVF, Kennedy PC and Palmer N. 4th ed, vol
2, pp. 364-366, 1993.
- 2. Fenner, et al.: Veterinary Virology, Academic Press, pp.
330-335, 1993.
-
- International Veterinary Pathology Slide Bank:
Laser disc frame #15725.
-
- 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
-
- * 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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