Results
AFIP Wednesday Slide Conference - No. 21
- 26 March 1997
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- Conference Moderator: LTC Catherine L. Wilhelmsen
Diplomate, ACVP
U.S. Army Medical Research Institute of Infectious Disease
Attn: MCMR-UIP
Bldg. 1425
Fort Detrick, MD 21702-5011
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- Return to WSC Case Menu
Case I - 950952 (AFIP 2554551)
- Signalment: Adult male cynomolgus monkey (Macaca fascicularis).
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- History: This monkey was a placebo control in a double-blinded
efficacy protocol to evaluate a new Q-fever vaccine. The monkey
was aerosol exposed to Coxiella burnetii live organisms and died
unexpectedly 10 days post aerosol challenge.
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- Gross Pathology: Marked diffuse pulmonary consolidation,
mild splenic enlargement and diffuse reddening of femoral bone
marrow.
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- Laboratory Results: Sequential chest radiographs on
days zero and five post aerosol exposure were essentially normal,
but radiographic examination performed on the day of death demonstrated
severe generalized increase in alveolar opacity, with air bronchograms,
consistent with severe generalized pneumonia.
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- Contributor's Diagnosis and Comments: Lungs, left
and right apical and diaphragmatic lobes: Pleuropneumonia, interstitial,
fibrinopurulent and histiocytic, subacute, diffuse, marked, with
obliterating fibrinous alveolitis and with bronchiolar and type
II pneumocyte hyperplasia.
- The immediate cause of death was likely a combination of
hypoxia and cardiovascular collapse due to fatal Q-fever pneumonia,
possibly with myocarditis as a contributing factor. Immunohistochemical
staining of the lung microsections demonstrated intracellular
Coxiella burnetii antigen within macrophages and within a few
granulocytes. Some extracellular C. burnetii antigen was also
observed. Other lesions observed, perhaps induced by C. burnetii
infection, were mild, multifocal subacute, lymphohistiocytic
epicarditis and myocarditis, paracortical lymphocytic hyperplasia
of mediastinal lymph nodes, myodegeneration of skeletal muscle
and hyperplasia of hematopoietic precursor cells in the bone
marrow. Incidental lesions in this wild caught monkey were mineralized
schistosome eggs in the liver and intestine, colonic nematode
granulomas consistent with oesophagostamiasis, mesenteric vasculitis,
and lymphoplasmacytic gastritis. The spleen was within normal
limits histologically.
- Human Q fever is a zoonotic disease transmitted to man from
infected animals, usually sheep, cattle and cats. Infection among
animals can be tickborne, but spread to humans is usually airborne,
via inhalation of infectious aerosols. Pulmonary Q fever is rarely
fatal in humans. Fatal human cases are characterized by an interstitial
pneumonia resembling viral pneumonia or ornithosis. A nonhuman
primate Q fever model was established in cynomolgus monkeys at
Fort Detrick in the late 1970's to test experimental Q fever
vaccines.
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- AFIP Diagnosis: Lung: Bronchopneumonia, fibrinosuppurative
and histiocytic, subacute, diffuse, severe, with type II pneumocyte
hyperplasia, and fibrinosuppurative pleuritis, cynomolgus monkey
(Macaca fascicularis), primate.
- Conference Note: Additional findings in some sections
include bronchus- associated eosinophilic infiltrates and pigment
likely secondary to Pneumonyssus sp. lung mites.
Q fever is a zoonosis. Worldwide, the most common animal reservoirs
for Coxiella burnetti are cattle, sheep, and goats. When infected,
these ungulates shed the desiccation-resistant organism in urine,
feces, milk, and especially birth products. Domestic animals
are probably infected by ticks in most cases. C. burnetti naturally
infects over 40 species of ticks found on five continents. There
is a wildlife cycle of infection, including birds, wild rabbits,
desert rats, mice, and bandicoots. Humans are generally infected
incidentally by inhalation of aerosols containing the organisms.
- Coxiella burnetti is a member of the Rickettsiaceae family.
It is a highly pleomorphic coccobacillus measuring 0.3 X 1.0
µm and having a cell wall similar in composition to those
found in gram-negative bacteria. C. burnetti survives within
the phagolysosome of the host. C. burnetti contains plasmids
that appear to differ among isolates associated with different
clinical syndromes. The discovery of a spore stage explains the
extraordinary ability of C. burnetti to withstand harsh environmental
conditions. The ability to destroy the spore stage is the current
standard by which adequate milk pasteurization is measured.
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- Contributor: Pathology Division, U.S. Army Medical
Research Institute of Infectious Diseases, Fort Detrick, Frederick,
MD 21702-5011.
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- References:
1. Baca OG, Paretsky D: Q fever and Coxiella burnetii: a model
for host-parasite interactions. Microbiol Rev 47:127-149, 1983.
- 2. Gonder JC, Kishimoto A, Kastello MD, Pedersen CE, Larson
EW: Cynomolgus monkey model for experimental Q fever infections.
J Inf Dis 139:191-196, 1979.
- 3. Marrie TJ: Q-fever pneumonia: Med Grand Rounds 3:354-365,
1985.
- 4. Marrie TJ, Stein A, Janigan D, Raoult D: Route of infection
determines the clinical manifestations of acute Q fever. J Inf
Dis 173:484-487, 1996.
- 5. Reimer LG: Q fever. Clin. Microbiol Rev 6:193-198, 1993.
- 6. Urso FP: The pathologic findings in rickettsial pneumonia.
Am J. Clin Pathol 64:335-342, 1975.
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- International Veterinary Pathology Slide Bank: None.
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Case II - 15374-96 (AFIP 2548135)
- Signalment: One approximately 8-week-old, 16 kilogram,
crossbreed pig was submitted for postmortem examination. Lung
and heart were submitted from another pig by the practitioner.
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- History: Sudden death, or recumbency with paddling.
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- Gross Pathology: The carcass appeared gaunt and slightly
dehydrated. Multiple small pustules ranging in size from 1 to
8 millimeters were present on the skin. Multiple gray foci were
present on serosal and cut surfaces of the liver. Moderate splenomegaly
was noted. Lungs were congested and multiple petechia were diffusely
distributed over visceral pleural surfaces. The left carpal joint
contained cloudy yellow fluid.
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- Laboratory Results: Actinobacillus suis was isolated
from lung, liver, kidney, spleen, skin pustules, and joint swabs
of the left carpus.
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- Contributor's Diagnosis and Comments: Liver, hepatitis,
necrotizing, random, with intralesional bacterial emboli - Actinobacillus
suis.
- Multiple random areas of coagulative necrosis are distributed
throughout congested hepatic parenchyma. Colonies of small bacilli
can be seen in centers of necrotic foci. Lesions in other organs
are: moderate diffuse neutrophilic alveolitis; septic emboli
in heart, kidney, spleen and intestines; and focal necrosuppurative
to ulcerative dermatitis. Naturally occurring actinobacillosis
of swine is characterized by multiple septic emboli in many tissues,
as exhibited in this case.
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- AFIP Diagnosis: Liver: Hepatitis, peracute to acute,
necrotizing, random, multifocal, moderate, with bacillary emboli,
mixed-breed, porcine.
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- Conference Note: Actinobacillus suis can infect pigs
of all ages, but infection is most serious in very young animals.
In neonates and suckling pigs, A. suis causes an acute and rapidly
fatal septicemia; death can occur within 15 hours. Cyanosis,
petechial hemorrhage, fever, respiratory distress, neurologic
disturbances, and arthritis may be present. Similar signs have
been reported in piglets infected with A. equuli or A. equuli-like
organisms. In mature animals, A. suis infection can be confused
with erysipelas. These animals may have erythematous skin lesions,
fever, and inappetence. Abortion, metritis, and meningitis have
also been reported in sows.
- A. suis infection occurs via the aerosol route or by gaining
entry through breaks in the skin. The organism spreads rapidly
throughout the body once it has entered the circulatory system.
Relatively little is known about the virulence factors of A.
suis with the exception of the ash operon, which encodes an RTX
toxin. The RTX toxins described for Actinobacillus pleuropneumonia
are cytolysins with the ability to lyse erythrocytes, and kill
lymphocytes, epithelial cells, and macrophages. These toxins
act by forming pores in the cell membranes. At sublytic concentrations,
the RTX toxins affect oxidative metabolism of phagocytic cells.
Contributor: University of Nebraska, Lincoln Veterinary
Diagnostic Center, Lincoln, NE 68583-0907.
References:
1.Christianson C: Clinical significance of Actinobacillus suis.
American Assoc. of Swine Practitioners, Proceedings, 1990.
- 2. Cutlip RC, et al: Septic embolic Actinobacillosis of swine:
A case report and laboratory reproduction of the disease. Am
J Vet Res 33(8):1621-1626, 1972.
- 3. Jang SS, et al: Actinobacillus suis-like organisms in
horses. Am J Vet Res 48(7):1036-1038, 1987.
- 4. Jones JET, et al: Endocarditis in the pig caused by Actinobacillus
equuli: A field and experimental case. Br Vet J 127:25-29, 1971.
- 5. Liver E, Larsen HJ: Infection with Actinobacillus suis
in pigs. Acta Vet Scand 19:313-315, 1978.
- 6. MacDonald DW, et al: Actinobacillus suis infections in
Alberta swine, 1973- 1975: Pathology and Microbiology. Can Vet
J 17(10):251-254, 1976.
- 7. Randall CJ, et al: Actinobacillus suis infections in pigs.
J Comp Path 84:113- 119, 1974.
- 8. Miniats OP, Spinato MT: Actinobacillus suis septicemia
in an SPF swine herd - a case report. IPVS, pg. 158, 1988.
- 9. Pedersen KB: Actinobacillus infektioner hos svin. Nord
Vet-Med 29:137-140, 1977.
- 10. Sanford SE, et al: Actinobacillus suis outbreaks in pigs
in Ontario: Pathology and bacteriology of a creeping epidemic.
IPVS, pg. 183, 1990.
- 11. Windsor RS: Actinobacillus equuli infection in a litter
of pigs and a review of previous reports on similar infections.
Vet Rec 92:178-180, 1973.
- 12. Gyles CL, Thoen CO (eds): Pathogenesis of Bacterial Infections
in Animals. second edition, Iowa State University Press, pp.
191-194, 1993.
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- International Veterinary Pathology Slide Bank: None.
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Case III - N96-177 (AFIP 2544359)
- Signalment: 8-year-old Belgian Malinois dog.
- History: This dog presented in June 1995 with clinical
signs of orchitis. Castration was performed. On histopathologic
examination, granulomas that contain fungal organisms consistent
with Coccidioides immitis were found. Serology was also positive
for coccidioidomycosis. The dog was treated with ketoconazole
for 6 months. At the end of the treatment period, a positive
titer for coccidioidomycosis was still present. The dog developed
osteolytic and productive lesions of the second and third lumbar
vertebrae. Biopsies confirmed osteomyelitis caused by Coccidioides
immitis. Euthanasia was performed.
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- Gross Pathology: None.
- Laboratory Results: None.
- Contributor's Diagnosis and Comments:
- 1. Vertebra, (L4), periosteum, endosteum and marrow: Osteomyelitis,
chronic, granulomatous, multifocal to coalescing, severe with
fungal spherules/sporangia, proliferative, periostitis and endosteitis,
Belgian Malinois, canine.
2. Lumbar skeletal muscle, myocytes and interstitium: Myositis,
granulomatous, multifocal to coalescing, moderate, with fungal
spherules/sporangia and focally extensive, myofiber regeneration.
3. Spinal cord, lumbar segment (L4), dura: Perineuritis, chronic
multifocal to coalescing, mild.
4. Spinal cord, lumbar segment (L4), dura: Metaplasia, osseous,
focal, mild.
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- Coccidioides immitis is a geophilic, dimorphic fungus. The
free-living mycelial phase in the soil produces arthroconidia
which are the source of infection for mammals. Animals are infected
following inhalation of arthroconidia, although direct inoculation
through the skin has caused infection. Once inside the mammalian
host, the arthroconidia are transformed to the parasitic spherular
phase. The large spherules (20 to 100 m in diameter) grow, mature
and divide internally to produce endospores. When released, the
endospores spread the infection locally or to distant sites via
lymphatics or blood. Disseminated canine coccidioidomycosis carries
a guarded prognosis. Most dogs respond well initially but relapse
when treatment is discontinued, as in this case.
- There is no known risk of direct transmission of C. immitis
from companion animals to humans. Caution should be used in handling
animals with draining cutaneous wounds and dressings from these
animals.
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- AFIP Diagnosis:
- 1. Vertebra, fourth lumbar (per contributor): Osteomyelitis,
granulomatous, diffuse, severe, with multiple granulomas, osteonecrosis,
new bone formation, and fungal spherules, Belgian Malinois, canine,
etiology consistent with Coccidioides immitis.
2. Skeletal muscle: Myositis, granulomatous, focally extensive,
moderate, with granulomas, myofiber atrophy, fibrosis, and regeneration.
3. Bone marrow: Hyperplasia, myeloid, diffuse, moderate.
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- Conference Note: Coccidioides immitis is a soil organism
restricted to the lower Sonoran life zone, which is characterized
by sandy, alkaline soil, high environmental temperature, low
rainfall, and low elevation. Geographically, this area includes
parts of the southwestern United States, Mexico, Central America
and South America. Coccidioidomycosis has been described in man,
all species of domestic animals and in a variety of wild animals.
- In the soil, C. immitis occurs as a saprophytic mycelial
phase which gives rise to readily aerosolized arthroconidia.
In host tissue arthroconidia transform into spherules that gradually
enlarge up to 20-100 µm in diameter. Rarely, spherules
may reach up to 200 µm in diameter. The nuclei within the
spherule divide to form numerous uninucleate endospores, 2-3
µm in diameter (endosporulation). When released from the
spherule, each endospore will form a new mature spherule at 37°C,
or a mycelium at room temperature. In the body, the endospore
may mature at the site of release or spread to other tissue via
lymphatics or the blood. Endospores are not considered infectious
to other animals (arthroconidia from the mycelial phase are highly
infectious), although a recent case of coccidioidomycosis was
diagnosed in a veterinarian exposed to disseminated coccidioidomycosis
while examining a horse at necropsy.
- The major route of infection is by inhalation of arthroconidia.
Following inhalation, the spores enter the bronchioles and alveoli,
then extend into the peribronchiolar tissue, moving toward the
lung surface and causing subpleural lesions. There is an initial
influx of neutrophils, followed by monocytes, lymphocytes, and
plasma cells. With massive exposure or depressed cellular immunity,
pulmonary infection may become extensive, and the organisms can
spread to the mediastinal and tracheobronchial lymph nodes, eventually
becoming widely disseminated. Boxers and Doberman Pinchers reportedly
have a greater incidence of disseminated disease than other dogs.
In disseminated coccidioidomycosis, the organs usually affected,
in decreasing order of frequency, are bones and joints, visceral
organs (primarily the spleen, liver, and kidneys), heart and
pericardium, testicles, eye and retina, and central nervous system.
The skin alone is rarely involved; draining fistulas are usually
associated with underlying osteomyelitis. Primary localized skin
lesions associated with penetrating wounds are reported but are
rare.
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- Contributor: Department of Defense Military Working
Dog Center, Lackland Air Force Base, TX.
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- References:
1. Ziemer EL, Pappagianis D, Madigan JE, Mansmann RA, Koffman
KD: Coccidioidomycosis in horses: 15 cases (1975-1984). J Am
Vet Assoc. 201(6), pp. 910- 16, 1992.
- 2. Fowler ME, Pappagianis D, Ingram I: Coccidioidomycosis
in llamas in the United States: 19 cases (1981-1989). J Am Vet
Assoc. 201(10):1609-1614, 1992.
- 3. Greene RT, Troy GC: Coccidioidomycosis in 48 cats: a retrospective
study (1984-1993). J Vet Int Med 9(2):86-91, 1995.
- 4. Stoltz JH, Johnson BJ, Walker RL, Pappigianis D: Coccidioides
immitisabortion in an Arabian mare. Vet Pathol 31(2):258-59,
1994.
5. Khohn GJ, Linne SR, Smith CM, Hoeprich PD: Acquisition of
coccidioidomycosis at necropsy by inhalation of coccidioidal
endospores. Diagn Microbiol Infec Dis 15(6):527-30, 1994.
- 6. Jubb KVF, Kennedy PC and Palmer N (eds): Pathology of
Domestic Animals; Academic Press, 4th ed., Vol. 2, pp. 518, 668-670,
1993.
- 7. Ettinger SJ and Feldman EC (eds): Textbook of Veterinary
Internal Medicine,4th Edition, Vol, 1, pp. 444-448, 1995.
International Veterinary Pathology Slide Bank:
Laser disc frame #21879, 21884, 21885, 21886.
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Case IV - 95:1407 (AFIP 2558104
Signalment: Mature, male, grey squirrel (Sciurus carolinensis)
- History: No history was provided.
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- Gross Pathology: The skin of the right axilla had
three raised, sparsely haired, reddened, firm nodules which were
approximately 5mm in diameter.
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- Laboratory Results: None available.
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- Contributor's Diagnosis and Comments: Haired skin:
Dermatitis, subacute, multifocal, nodular, moderate with fibroplasia,
acanthosis, ballooning degeneration, mild orthokeratotic hyperkeratosis,
and eosinophilic intracytoplasmic inclusion bodies, grey squirrel
(Sciurus carolinensis).
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- Etiology: Leporipoxvirus (squirrel pox virus).
- Squirrel pox virus in a member of the Leporipoxvirus genus
of the family Poxviridae. The myxoma and Shope fibroma viruses
of rabbits also belong to the genus Leporipoxvirus.
- The virus has been successfully transmitted into grey squirrels
by experimental inoculation and experimental transmission by
mosquitoes. Infection of adult squirrels results in cutaneous
lesions, whereas juveniles develop multi- organ proliferative
or neoplastic epithelial and fibropapillomatous poxvirus lesions.
- The cutaneous papules of squirrel poxvirus infection may
be numerous and involve all areas of the skin. Histologically,
the skin papules are composed of two components, a dermal and
an epidermal component. The dermal component is characterized
by fibroplasia with a moderate infiltrate of lymphocytes, plasma
cells, histiocytes, and a few neutrophils. The overlying epidermis
is acanthotic, has ballooning degeneration of the stratum spinosum
and contain eosinophilic, intracytoplasmic inclusion bodies.
Orthokeratotic hyperkeratosis may or may not be present. Ulceration
of the epidermis can occur with crust formation and secondary
bacterial or fungal infection.
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- AFIP Diagnosis:
- 1. Haired skin: Atypical mesenchymal proliferation, nodular,
with epidermal hyperplasia, ballooning degeneration, spongiosis,
and eosinophilic intracytoplasmic inclusion bodies, grey squirrel
(Sciurus carolinensis), rodent.
2. Haired skin, subcutaneous adipose tissue: Steatitis, granulomatous,
multifocal, moderate.
3. Haired skin, deep skeletal muscle: Myositis, chronic, multifocal,
mild, with myofiber atrophy and regeneration.
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- Conference Note: Participants agreed with the contributor's
diagnosis. The relationship of the steatitis and myositis to
the poxviral lesion is uncertain.
- In the grey squirrel, multiple fibromas have been reported
to occur in the skin, heart, lung, kidney, liver, mesentery,
testes, and lymph nodes. The pathogenesis of the disseminated
squirrel fibroma is not completely understood, but it is believed
that the virus spreads hematogenously.
- Poxviruses are known to cause tumors or tumor-like lesions
in man and a variety of other animals. Examples include Yaba
disease in African monkeys, molluscum contagiosum in humans,
horses, macropods and chimpanzees, lumpy skin disease in cattle,
genital papillomatosis in swine, sheep pox, contagious ovine
ecthyma, myxomatosis in European rabbits (Oryctalagus spp.),
and fibromas in cottontail rabbits (Sylvilagus spp.)
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- Contributor: University of Connecticut, Department
of Pathobiology, 61 North Eagleville Road, U-89, Storrs, CT 06269-3089.
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- References:
1. O'Connor DJ, Diters RW, Nielsen SW. Poxvirus and multiple
tumors in an eastern grey squirrel. JAVMA 177:792-795, 1980.
- 2. Hirth RS, Wyand DDS, Osborne AD, Burke, CN. Epidermal
changes caused by squirrel poxvirus. JAVMA 155:1120-1125, 1969.
International Veterinary Pathology Slide Bank:
Laser disc frame #21035, 21036, 21037.
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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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