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Transcript
CL Davis Foundation - Annual Review: Gross Morbid Anatomy of the Diseases of
Animals - 2003
DISEASES OF LABORATORY RODENTS & LAGOMORPHS
Dean H. Percy, DVM, PhD, DACVP
OVC Pathobiology
University of Guelph
Guelph, Ontario, Canada
N1G 2W1
[email protected]
MOUSE
Examples of Skin Lesions in Mice:
1. Mouse with lesion at base of tail:
Morphologic Dx: Circumferential Ulcerative Dermatitis (Base of Tail)
Etiopathogenesis: Fighting Injury (fighting among mail mice after they reach puberty)
Differential Dx: vs “ring tail” in young mice due to low environmental humidity.
2. BALB/c Mouse with Skin Lesions:
Morphologic Dx: Extensive multifocal ulcerative dermatitis.
Pathogenesis: Typical of fighting injuries among aggressive male mice.
3. Mice with Bilateral Focal Nasal Alopecia:
Etiology: “Barbering” - The mouse with the intact vibrissae is the culprit!
4. C57Bl mouse with skin lesions:
Morphologic Dx: Ulcerative Dermatitis
Possible Etiologies: Severe pruritis and self-inflicted injury due to mite infestation;
idiopathic ulcerative dermatitis that occurs in this strain; staphylococcal dermatitis
(opportunistic infection).
5. Mouse with skin lesion in neck region: Morphologic Dx: Ulcerative Dermatitis
Possible Etiologies: Primary staphylococcal infection, mite infestation.
6. Weanling Mouse: Dx: “Ringtail” (associated with low environmental humidity)
7. Mouse with skin lesions on tail: Etiologic Dx: Mousepox
Typical lesions associated with Ectromelia virus infection.
Differential Dx: Fighting injuries.
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8. Weanling Mouse with lesions on feet:
Morphologic Dx: Gangrenous Pododermatitis with Sloughing of Extremities.
Etiology: Ischemic necrosis of extremities due to cotton batton wrapping around feet
and subsequent sloughing of feet.
9. Mouse with loss of extremities: Dx: Infectious Ectromelia (post Mousepox infection).
10. Athymic mouse with Skin Condition (2 slides).
Morphologic Dx: Diffuse Scaling Dermatitis.
Etiologic Dx: Corynebacterium bovis Infection
Immunocompetent mice are relatively resistant to this infection.
11. Mouse with Skin Condition (2 slides).
Morphologic Dx: Diffuse Scaling Dermatitis with Alopecia.
Etiologic Dx: Acariasis
Differential Dx: vs Barbering
Respiratory Tract
1. Lungs from a DBA mouse, age 6 weeks, ruffled hair coat, dyspnea, euthanized.
Morphologic Diagnosis: Acute Interstitial Pneumonitis
Etiologic Diagnoses: Sendai virus infection, pneumonia virus of mice (PVM)
DBA mice are very susceptible to Sendai virus infection.
2. Histopathology: Typical lesions seen with Sendai & PVM virus Infection.
Sendai: Bronchoalveolitis
PVM: Lesions often more extensive at the alveolar level.
Immunocompromised mice are particularly at risk.
3. Lungs from old mouse:
Morphologic Dx: Chronic diffuse bronchopneumonia
Likely etiology: Mycoplasma pulmonis (rarely seen in this species in well-managed facilities).
4. Chronic suppurative bronchopneumonia associated with Pasteurella pneumotropica
Infection. An opportunistic infection capable of producing suppurative lesions in the
respiratory tract and reproductive tract, especially in immunocompromised mice.
5. Lungs from an athymic mouse with history of dyspnea & wasting.
Morphologic Dx: Diffuse pneumonitis with pulmonary edema & emphysema.
Etiologic Dx: Pneumocystosis (Pneumocystis carinii is the most likely candidate).
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5. Lungs from an old mouse. Doing poorly. Euthanized.
Diagnosis: Pulmonary Neoplasm.
Most likely candidate: Bronchioalveolar Carcinoma
Histopathology; Bronchioalveolar tumors
Old classification as alveolar or bronchiolar (CLARA cell) tumors no longer valid.
Now considered to arise from type 2 alveolar pneumocytes.
Pilling, AM. Expression of surfactant protein mRNA in normal and neoplastic lung of
B6C3 mice as demonstrated by in situ hybridization. Vet. Path 36: 57-63, 1999.
Alimentary Tract
1. Young adult mouse with history of weight loss. Euthanized.
Morphologic Dx: Multifocal Hepatitis
Differential Dx: Mouse hepatitis virus (MHV)**, Helicobacter hepaticus infection, Tyzzer’s,
salmonellosis, Proteus mirabilis infection, other viral infections: reovirus infections in young
mice, LCM virus infection, ectromelia virus infection.
2. Examples of typical hepatic lesions seen on histopathology:
MHV: multifocal hepatitis with syncytial giant cells & basophilic nuclear debris.
Other examples of acute hepatitis with mononuclear cell infiltration include acute
Helicobacter hepaticus infections, acute LCM virus infection, reovirus infection in suckling
mice, etc.
3. Cryptosporidial cholangitis in athymic mouse (histopathology)
4. Juvenile mice with a history of diarrhea & weight loss (affected & control littermate)
Dx: Chronic Proliferative Colitis (2 slides)
Etiology: Citrobacter rodentium (Transmissible colonic hyperplasia)
Histopathology; Review of proliferative colonic lesions.
5. Mouse with rectal prolapse:
Possible etiologies: Chronic colitis associated with Citrobacter, Helicobacter, E.coli
infections, & pinworm infestations.
Urogenital System
1. Male mouse with urethral plug. = secretions released from the accessory sex glands at the
time of death. An incidental finding.
2. Adult mice; Morphologic Dx: Mucometra
Differential Dx: Chronic metritis (pyometra)
Mucometra is seen occasionally in litters of mice born with obstructions downstream,
resulting in the accumulation of uterine secretions & expansion of the uterine horns.
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3. Adult female mouse with axillary mass:
Morphologic Dx: Mammary adenocarcinoma
Retrovirus-associated in this species
There are several strains of mouse mammary tumor virus (MMTV).
Cardiovascular System
Heart from DBA mouse:
Morphologic Dx: Multifocal epicardial mineralization/calcification
Commonly encountered in certain strains of mice (eg DBA mice).
Usually an incidental finding.
Mineralized foci may occur elsewhere (eg muscles of the tongue & sclera)
Histopathology: Epicardial degeneration with mineralization.
Hematopoietic System
1.
Adult SCID mouse with thymic mass.
Most likely diagnosis: Thymic Lymphoma
2. Adult CD-1 mouse with lymphadenopathy.
Most likely diagnosis: Lymphoma/Lymphosarcoma (probably B cell type)
3. Histopathology: Review of lymphoreticular neoplasms
(lymphoma, follicular center lymphoma, histiocytic sarcoma)
Reference Text:
Maronpot, R.R. et al. Pathology of the Mouse. Cache River Press, Vienna, Illinois, 1999.
Notes:
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RAT
Examples of Skin Lesions in the Laboratory Rat
1. Juvenile Rat with skin lesions (2 slides).
Morphologic Dx: Bilateral Ulcerative Dermatitis
Etiopathogenesis: Primary staphylococcal (Staph aureus) infection with subsequent severe
pruritis & & aggressive scratching. Occasionally “mini outbreaks” of this condition occur,
particularly in young adult rats. The initiating factors are often obscure.
2. Weanling rat with lesions on the tail.
Diagnosis: “Ringtail”
Etiopathogenesis:
Low environmental humidity (eg < 20%) is recognized to be the primary cause.
3. Old Rat with mass at the external ear canal.
Dx: Zymbal’s Gland Adenocarcinoma
Locally invasive but not metastatic.
Histopathology: Example of microscopic findings.
4. Rat with lesions on the ears.
Morphologic Dx: Proliferative & Disfiguring Otitis Externa
Etiologic Dx: Acariasis (Notoedres muris infestation)
5. Rat with encrustations around the eyes.
Dx: Chromodacryorrhea. Porphryin pigment secreted by the Harderian lacrimal glands are
secreted & released in excess & accumulate around the eyes in the Astressed@ laboratory
rat. The underlying cause: Varies from infectious disease (eg SDA), to shipping stress, etc.
The porphyrins will fluoresce under an ultraviolet light source.
Histopathology; Demonstration of porphyrin pigment in Harderian lacrimal gland.
6. Old Sprague-Dawley rat with ocular changes.
Diagnosis: Bilateral Cataracts
In albino animals, retinal degeneration & cataract formation have been associated with
exposure to above recommended environmental light intensity
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References:
1. Fox, J.G. et al. Ulcerative dermatitis in the rat. Lab. Anim. Sci. 27: 671-678, 1977.
2. Harkness, J.E. & Ridgeway, M.D. Chromodacryorrhea in laboratory rats: Etiologic
considerations. Lab Anim Sci 30: 841-844, 1980.
3. Percy, D.H. & Barthold, S.W. Pathology of Laboratory Rodents & Rabbits.
Iowa State University Press, 2001.
Respiratory Tract
1. Wistar rat, age 8 months.
Morphologic Dx: Cranioventral Bronchopneumonia
Possible Etiologies: Chronic mycoplasmal infection (M. pulmonis)**
cilia associated respiratory (CAR) bacillus, Corynebacterium kutscheri infection,
primary viral infections with secondary bacterial infections or viral infection superimposed
on an existing bacterial infection(eg SDA virus, Sendai virus, PVM).
2. Sprague-Dawley rat, age 24 months. History of weight loss, dyspnea.
Morphologic Dx: Chronic Pulmonary Abscessation (right lung)
Etiology; Mycoplasma pulmonis
Differential Diagnosis: vs Chronic CAR bacillus infection
3. Wistar rat, age 6 weeks. Recent arrival from a commercial supplier. Found dead.
Morphologic Dx: Acute Fibrinopurulent Bronchopneumonia
Etiology: Streptococcus pneumoniae
Differential Dx: vs C. kutscheri infection
Note: S. pneumoniae infections are now rare in well managed facilities.
3. Other poorly characterized respiratory conditions in laboratory rats:
(a) Idiopathic pneumonitis associated with so-called rat respiratory virus (RRV)
Based on current information, the virus is antigenically related to members of the
Hantavirus genus.
(b) Eosinophilic granulomatous pneumonitis
Frequently encountered in young adult Brown Norway (BN) rats.
No evidence of infectious agent based on available information.
1. Albers, TM, & Clifford, C.B. Eosinophilic granulomatous pneumonia: A strain-related lesion of high
prevalence in the Brown Norway rat. Contemporary Topics 39: #4: 61-62, 2000.
2. Elwell, M.R. et al. Have you seen this? Inflammatory lesions in the lungs of rats. Toxic. Pathol. 25:
429-531, 1997.
3. Livingston, RS, et al. Serologic diagnosis of rat respiratory virus (RRV) infection. Contemporary Topics
40: #4: 58, 2001.
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4. Immunocompromised Adult rat that died in the course of the experiment.
Morphologic Dx: Acute Bronchopneumonia with Multiple Abscessation
Most likely Etiology: Corynebacterium kutscheri
The focal suppurative lesions with hemorrhagic periphery are typical of acute coynebacterial
infections. There are frequently predisposing factors associated with this infection
(eg immunosuppression).
4. Old rat with multifocal renal cortical abscessation (systemic C. kutscheri infection).
5. Adult rat with jugular catheterization. Doing poorly, euthanized.
Morphologic Dx: Vegetative Endocarditis (tricuspid valve)
History: Rat had an indwelling jugular catheter & water supply was contaminated with
Pseudomonas aeruginosa. Catheter extended into the rt chamber, impinging on the tricuspid
valve  localization of Pseudomonas on damaged valve & endocarditis.
6. Rat in a protein-deficient study. Dyspnea & weight loss. Euthanized.
Morphologic Dx: Pulmonary Edema & Emphysema
Etiology: Pneumocystis carinii
Etiologic Dx: Pneumocystosis
Most often encountered in animals in an immunocompromised state.
Strains of P. carinii characterized to date appear to be species-specific. Thus, isolates from
rats do not appear to be transmissible to other laboratory animal species.
Alimentary Tract
1. Adult rat. Dx. Malocclusion.
2.
Wistar rat, age 8 weeks. Chromodacryorrhea, intermandibular swelling.
Etiologic Dx: Rat Coronavirus Infection (Sialodacryoadenitis) [SDA]
Morphologic Dx: Acute Sialoadenitis
Histopathology: Acute sialoadenitis & dacryoadenitis & reparative changes.
Corneal drying & resultant megaloglobus associated with residual lesions in lacrimal glands.
3. Suckling Rat. Died.
Morphologic Dx: Acute Enteritis
Etiologic Dx: Rotavirus (Infectious diarrhea of infant rats [IDIR])
Histopathology: Syncytial cells in enterocytes lining tips of villi.
Differential Dx: Acute Enterococcal (streptococcal) Enteritis
4. Juvenile laboratory rat. Died.
Morphologic Dx: Multifocal Hepatitis & Multifocal to Segmental Myocarditis
Etiologic Dx: Tyzzer’s Disease
Etiology: Clostridium piliforme
The “triad” of lesions seen with Tyzzer’s: Liver, terminal small intestine, heart.
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5. Juvenile laboratory rat. Focal hepatitis associated with Kilham’s rat virus (RV)
infection. Intranuclear inclusions.
6. Sections of brain from young rat that died post inoculation with RV.
Dx: Hemorrhagic encephalopathy associated with RV infection.
Urinary System
1. Kidneys from old male rat.
Dx: Chronic Progressive Glomerulonephropathy (“old rat nephropathy”)
Note the pitting of the cortical surface & the discoloration of the corex & medulla.
An important cause of disability and mortality in older rats, especially males.
Histopathology: Examples of thickening of glomerular basement membranes,
proteinaceous casts in tubules, etc associated with PGN.
2. Hydronephrosis. Congenital hydronephrosis occurs occasionally in laboratory rats.
3. Section of Urinary bladder from laboratory rat.
Morphologic Dx: Verminous Cystitis
Etiology: Trichomasoides crassicauda
Reproductive & Endocrine Systems
1.
Old Sprague-Dawley female rat with inguinal mass:
Dx: Fibroadenoma
Differential Dx: vs mammary adenocarcinoma
The distinct lobulated appearance is typical for fibroadenomas in this species.
Rarely, if ever metastasize but can grow to phenomenal size.
Particularly common in some strains – eg female Sprague-Dawley rats.
2. Tissues from Old Fischer 344 rats:
Dx: Interstitial Cell Testicular Tumors
Very common in old male F344 rats. Note the lobulated raised tumors that are dull yellow in
appearance with foci of hemorrhage, typical gross changes seen with these interstitial
(Leydig) cell tumors. Have been associated with elevated serum calcium levels.
3. Laboratory rat, age 10 weeks. Representative animal from an outbreak of this
disease.
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CL Davis Foundation - Annual Review: Gross Morbid Anatomy of the Diseases of
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Morphologic Dx: Acute fibrinous periorchitis
Etiologic Dx: Rat parvovirus (RV) infection
4. Specimen from an old rat.
Dx: Pituitary gland adenoma
Common in some strains of rats when they reach the geriatric category.
Cardiovascular System & Peritoneal Cavity
1. Mesenteric vessels from an aged laboratory rat.
Dx: Polyarteritis
Pathogenesis: Antigen-antibody complexes often present in the damaged and dilated
sections of the mesenteric vessels. Elevated blood pressures (eg common in the
spontaneously hypertensive rat (SHR) strain).
Other sites: Pancreatic & spermatic vessels.
2. Adult Fischer 344 (F344) carcass. History of reduced food intake & ascites.
Dx. Mesothelioma (malignant)
This neoplasm is most frequently seen in the F344 strain.
Hematopoietic System
1. Organs from an old F344 rat.
Dx: Large Granular Lymphocytic Leukemia (LGL)
Differential Dx: Lymphoma
This malignancy is relatively common in F344 rats. Unlike mice, malignancies of the
hematopoietic system in rats are not retrovirus-associated.
Note the splenomegaly, the enlarged liver, and the icteric appearance of the lungs & liver.
2. Histopathology:
(a) Impression smear of spleen from F344 rat with LGL.
Note the granules present in the cytoplasm of some of the malignant lymphocytes.
(b) Histiocytic Sarcoma: Examples.
Note: 1. In rats, unlike mice, malignancies of the hematopoietic system and mammary glands
are not normally associated with endogenous retrovirus infections.
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2. Unlike mice, hamsters, etc. laboratory rats do not develop spontaneous amyloidosis.
3. Male rats, unlike male mice, do not normally fight when they reach puberty.
SYRIAN HAMSTER
Examples of Diseases of the Skin in the Hamster
1. Old hamster with skin lesions.
Morphologic Dx: Diffuse scaling dermatitis with alopecia
Etiologic Dx: Acariasis (Demodex spp) [most likely diagnosis]
Apparently hamsters frequently harbor mites, but usually is a subclinical infection.
Events that could compromise normal immune function (eg old age, concurrent disease, etc)
may result in clinical disease.
Histopathology; Demodex infestation
2. Adult hamster with lesions on the feet.
Morphologic Dx: Chronic ulcerative pododermatitis
Etiology: Occurs occasionally in Syrian & Chinese hamsters on poor quality wood shavings.
Invasion of the subcutaneous tissue with wood slivers  chronic pododermatitis.
3. Young adult hamster with skin lesions.
Dx: Cutaneous lymphoma
Differential Dx: vs cutaneous tumors associated with hamster papovavirus infection
References:
1. Saunders, GK & Scott, DW. Cutaneous lymphoma resembling mycosis fungoides in the
Syrian hamster. Lab Anim Sci 38: 616-617, 1988.
2. Barthold, SW et al. Further evidence for papovavirus as the probable etiology of
transmissible lymphoma of Syrian hamsters. Lab Anim Sci 37: 283-288, 1987.
Alimentary System
1. Young hamster with history of profuse diarrhea. Euthanized in extremis.
Dx: Transmissible ileal hyperplasia/ proliferative ileitis
Etiology: Lawsonia intracellularis
Differential Diagnoses: Antibiotic-associated enterocolitis (eg post clindamycin therapy)
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Rx with such a narrow-spectrum antibiotic frequently results in a fatal overgrowth with
Clostridium difficile. Enteritis has also been associated with other bacterial infections in this
species (eg. Campylobacter, hemolytic E. coli).
Histopathology: Changes associated with Lawsonia intracellularis, and Campylobacter spp.
3. Adult hamster with history of chronic diarrhea.
Dx: Chronic enteritis due to Giardiasis
Infected animals are usually asymptomatic, but old age or concurrent disease may
precipitate clinical disease.
2. Adult hamster. Incidental changes seen at post mortem.
Dx: “Polycystic Disease”
Associated with the formation of “blind” tubules during early development. As these animals
age, clear fluid accumulates in these structures resulting in cystic areas at sites such as liver,
pancreas, and epididymis.
Histopathology: Cystic structures are lined by cuboidal to flattened epithelium.
3. “Polycystic Liver Disease” in the liver of old Syrian hamster.
Note the striking cystic structures involving the liver. Unusual to see lesions this extensive.
Urinary System
1. Old hamster. Most likely diagnosis?
Dx: Renal amyloidosis.
Amyloidosis is most commonly seen in old female hamsters. The administration of female
sex hormones experimentally will accelerate the deposition of amyloid P in both males and
females. Other organs (liver, adrenals, etc) may be involved. Confirmation of the presence
of amyloid would require the appropriate special stains (eg thioflavin T, Congo red)
Histopathology: Renal amyloidosis.
2. Old hamster. Most likely diagnosis?
Dx: Chronic Progressive Glomerulonephropathy.
Differential Dx: vs amyloidosis
Histopathology: Renal lesions are similar to those seen in other small rodents (thickening
of glomerular basement membranes, dilation of tubules with casts in tubules, etc)
Reference: Coe, JE & Ross, JJ. Amyloidosis and female protein in the Syrian hamster.
Concurrent regulation by female sex hormones. J exptl Med 171: 1257- 1266, 1990.
Cardiovascular & Lymphopoietc Systems
1. Heart from an old hamster.
Dx: Atrial thrombosis
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A common cause of death in aged hamsters, mice, etc. The mural thrombus is usually
present in the left auricle or left atrium. Often accompanied by a consumptive coagulopathy.
2
Young adult hamster. Diagnosis?
Dx: Lymphoma
Note the marked enlargement of the lymph nodes and the diffuse infiltration with
discoloration and enlargement of the liver.
“Epizootics” of lymphoma occasionally occur in hamster colonies. Associated with a hamster
papovavirus (HaPV) infection.
Histopathology: Lymphomas associated with HaPV infection usually have cutaneous
tumors of the skin as well.
MONGOLIAN GERBIL
Example of Disease of the Skin
Young adult Gerbil. Diagnosis?
Dx: “Nasal dermatitis” / Chronic Ulcerative Nasal Dermatitis
Etiopathogenesis: Associated with the normal release of porphyrins from the Harderian
lacrimal glands, collection around the external nares, and chemical dermatitis, often with a
concurrent localized secondary staphylococcal infection. Animals normally spread the
porphyrins over the pellage as part of the grooming process. Failure to groom properly may
result in accumulation of porphyrins at this site and eventually, nasal dermatitis.
Histopathology: Harderian gland & porphyrins
Alimentary Tract
Young gerbil. Profuse diarrhea of acute onset & subsequent death. Morphologic dx?
Morphologic Dx: Multifocal hepatitis
Etiologic Dx: Tyzzer’s Disease (Clostridium piliforme)
Differential diagnoses: vs salmonellosis
Mongolian gerbils are exquisitely susceptible to Tyzzer’s disease.
Histopathology: (a) Warthin-Starry stained section of liver to illustrate the typical “bundles” of
bacilli associated with the hepatic lesions.
(b) H&E–stained section of ileum to illustrate a typical transmural lesion.
Neoplasms
Reproductive tract of an old Gerbil. Diagnosis?
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Dx: Ovarian tumor
Most likely type as seen in this species: Granulosa cell ovarian tumor
Examples of other neoplasms identified in this species: Adenocarcinomas of the ventral marking
gland, adrenocortical tumors, & tumors of the skin.
GUINEA PIG
Skin Conditions in the Guinea Pig
1. Young guinea pig.
Most likely etiologic diagnosis: Pediculosis.
Infestations with biting lice (Gliricola porcelli) are relatively common in conventional facilities.
Other parasitic infections of the skin: eg mite infestation
Causes of alopecia in this species include “barbering”, idiopathic hair loss associated with
pregnancy & lactation in sows, dermatophyte infections, & “metabolic disorders”
2. Young adult guinea pig.
Dx: Dermatophytosis
Clinical cases are relatively rare in laboratory animal facilities to-day.
Histopathology: Trichophyton mentagrophytes.
Respiratory System
1. Example of perivascular lymphoid nodules (histopathology)
2. Example of typical pulmonary arterioles in guinea pig (histopathology).
3. Lungs from adult guinea pig with history of recent dyspnea. Euthanized.
Morphologic Dx:Acute Cranioventral (or anteroventral) Bronchopneumonia
Most likely etiology: Bordetella bronchiseptica
Other possible etiologies: Streptococcus pneumoniae, adenovirus infection.
Manifestations of pneumonia due to Bordetella vary from an acute to a chronic suppurative
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bronchopneumonia.
Histopathology: Examples of lesions associated with B. bronchiseptica infections.
4. Lungs from young guinea pig that was recently shipped to a research facility.
Morphologic Dx: Acute fibrinous pleuropneumonia.
Most likely etiology: Streptococcus pneumoniae (vs Bordetella infection)
Histopathology: Note the acute fibrinous pneumonia with pleuritis
In general, S. pneumoniae infections produce a more necrotizing pneumonic process
(vs Bordetella)
5. Lungs from a young guinea pig. History of dyspnea of sudden onset & death.
Morphologic Dx: Acute cranioventral bronchopneumonia
Possible etiologies: Viral: acute adenoviral bronchoavleolitis, parainfluenza 3
Bacterial: Acute Bordetella or Streptococcal infection
Histopathology: Etiologic Dx: Adenoviral bronchoalveolitis
There is an acute necrotizing bronchiolitis & alveolitis. Disease with mortality is normally
confined to young guinea pigs. Adult animals normally do not develop clinical disease following
experimental inoculation with guinea pig adenovirus.
Note the large basophilic intranuclear inclusions in affected airways.
Histopathology #2: Example of alveolitis associated with parainfluenza-3 infection. PI-3 virus
seldom causes clinical disease, but can cause transient lesions in the respiratory tract.
References:
Blomquist, G.A. et al. Transmission pattern of parainfluenza virus 3 in guinea pig
breeding herds. Contemporary Topics 41: #4: 53-57, 2002.
Kunstyr, I. et al. Adenovirus pneumonia in guinea pigs. An experimental reproduction of
the disease. Laboratory Animals 18: 55-60, 1984.
Alimentary System
1. Young adult guinea pig: Dx: Malocclusion
The incisors & cheek teeth continue to grow throughout life in guinea pigs.
Defective apposition will result in failure to wear & overgrowth of incisors &/or cheek teeth.
2. Young adult guinea pig.
Morphologic Dx: Acute Enterotyphlitis
Differential Dx: “Antibiotic toxicity” with subsequent overgrowth of Clostridium difficile,
coronaviral enteritis, cryptosporidiosis, coccidiosis.
Histopathology; Etiologic Dx: Coccidiosis (Eimeria caviae)
Histopathology: Examples of crytopsporidiosis, organisms adherent to enterocytes of small
intestine; & coronavirus infection.
3. Tissues from old guinea pig.
Diagnosis: “Metastatic calcification/mineralization”
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Note the chalky deposits on the serosal surface of the stomach, etc, typical of this condition.
Sparschu, GL & Christie, RJ. Metastatic calcification in a guinea pig colony. A pathological
survey. Lab Anim Care (Sci) 18: 520-526, 1968.
Hematopoietic/Lymphopoietic System
1. Impression smear from spleen of adult sow.
Diagnosis: Kurloff Cells
Note the eosinophilic finely granular mass in the cytoplasm of Kurloff cells.
Now considered to be the guinea pig counterpart of natural killer (NK) cells in other species.
Guinea pigs have a relatively low incidence of spontaneous neoplasms. Tempting to
speculate that these “NK cells” may be particularly efficient at recognizing & eliminating any
malignant cells as they arise in this species.
Debout et al. Increase of guinea pig natural killer cells (Kurloff cells) during
leukemogenesis. Cancer Letters 97: 117-122, 1995.
2. Heart. Diagnosis?
Differential Diagnoses: Rhabdomyomatosis, “metastatic calcification”,
Myocardial degeneration associated with vitamin E deficiency (a long shot!)
Histopathology: Dx: Rhabdomyomatosis
Note the vacuolation of myofibers typical of the glycogen deposition (the glycogen is washed
in specimens fixed with formalin). Normally considered to be an incidental finding.
Histopathology #2: Multifocal myocardial degeneration with mineralization/calcification.
3. Adult guinea pig.
Morphologic Dx: Chronic Suppurative Lymphadenitis (bilateral)
Etiologic Dx: Chronic streptococcosis
Etiology: Streptococcus zooepidemicus
Differential Dx re. etiology: vs Streptobacillus moniliformis (a long shot!!)
Based on experimental inoculation studies, there are several possible portals of entry for S.
zooepidemicus: breaks in the oral mucosa, via nasal cavity, conjunctival sac, etc.
Murphy, JC et al. Cervical lymphadenitis in guinea pigs. Infection via intact ocular and
nasal mucosa by Streptococcus zooepidemicus. Lab Anim Sci 41: 251-254, 1991.
4. Young adult guinea pig.
Diagnosis? Lymphoma
Note the marked enlargement of abdominal lymph nodes, etc.
Often associated with a guinea pig retrovirus infection.
Urinary & Reproductive Systems
1. Kidney from a guinea pig, age 6 years.
Morphologic Diagnosis: Multifocal renal cortical pitting & discoloration
Diagnosis: Segmental Nephrosclerosis
This is a relatively common finding at necropsy in older guinea pigs.
There are a number of hypotheses, but the etiopathogenesis of this disease has not been
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adequately studied and resolved.
Histopathology: Note the relative sparing of glomeruli, the chronic tubular degeneration &
regeneration, and the relative absence of inflammatory cell infiltrates.
2. Old sow: Diagnosis?
Diagnosis: Cystic rete ovarii
Pathogenesis: Remnants of these embryonic structures persist and later in life, as fluid
accumulates in these blind ducts, they enlarge and appear as large fluid-filled cysts.
3. Organs from an old sow: Diagnosis?
Diagnoses: Cystic rete ovarii
Uterine Mass: Probably leiomyoma (confirmed on microscopic examination)
Histopathology: Cystic rete ovarii: Structures lined by ciliated cuboidal epithelial cells.
Nutritional & Metabolic
1. Old sow with pregnancy toxemia.
Types: (a) Metabolic (b) Circulatory
The pathogenesis of pregnancy toxemia will be reviewed.
Histopathology: Metabolic form: Marked fatty infiltration in the liver (hepatic lipidosis)
2. Young guinea pig. History of lameness & doing poorly.
Diagnosis: Scurvy
Periarticular hemorrhages are typical findings.
3. Young adult guinea pig.
Diagnosis: Scurvy
Histopathology: Examples skeletal lesions associated with scurvy.
(proliferation of poorly-differentiated fibrous tissue, microfractures, hemorrhage, etc)
DOMESTIC RABBIT
Examples of Lesions of the Skin in the rabbit
1. Young adult rabbit:
Morphologic Dx: Diffuse scaling dermatitis & moderate alopecia
Etiologic Dx: Acariasis [Demostration of mites (Chyletiella spp) required].
Differential Dx: vs “barbering”, dermatophyte infection
2. Hock from adult New Zealand White buck.
Morphologic Dx: Chronic necrotizing plantar podermatitis
Staphylococci are frequently isolated from these lesions.
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3. Young rabbit kits.
Dx: Multifocal suppurative dermatitis (staphylococcal infection)
Occasionally seen in suckling rabbits in commercial rabbitries.
May become systemic, producing suppurative lesions in liver, lung, etc.
4. Old rabbit with a history of progressive non-pruritic scaling dermatosis
Dx: “Exfoliative Dermatosis”
A recently-recognized syndrome. Refractory to treatment.
White, SD et al. Sebaceous adenitis in four domestic rabbits. Vet Derm. 11: 53-60, 2000.
5. Ear from adult rabbit.
Morphologic Dx: Chronic exudative otitis externa
Etiologic Dx: Acariasis
Etiology: Psorpotes cuniculi
Thanks to the anti-parasitic treatments now available (eg ivermectin), should be a rare
disease.
6. Cottontail rabbit with proliferative lesion on foot.
Most likely Dx: Shope’s fibroma
Causative agent is a poxvirus related antigenically to myxomatosis virus.
Histopathology: Note the intracytoplasmic eosinophilic inclusions in the fibroblasts in the
underlying dermis.
7. Domestic rabbit from California with proliferative lesions around they eyes.
Etiologic Dx: Myxomatosis
Histopathology; Eosinophilic intracytoplasmic inclusions are present in hair follicles.
Myxoid material is present in the perifollicular areas.
8. External genitalia of young adult doe.
Dx: Ulcerative Vulvitis
Etiologic Dx: Treponematosis
Histopathology: Spirochetes in exudate (Warthin-Starry stain)
Respiratory System
1. Lungs from adult New Zealand White doe.
Morphologic Dx: Chronic cranioventral bronchopneumonia
Etiologic Dx: Pasteurellosis (P. multocida)
Differential Dx: vs Bordetella bronchiseptica infection
2. Lungs from adult New Zealand White doe.
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Morphologic Dx: Acute fibrinohemorrhagic bronchopneumonia
Etiologic Dx: Pasteurellosis
3. Lungs from adult New Zealand White buck.
Morphologic Dx: Acute suppurative bronchopneumonia.
Histopathology. Examples of fibrinous & suppurative bronchopneumia.
4. Lungs from a wild rabbit. The carcass was submitted from a practitioner in Australia
Morphologic Dx: Multifocal pulmonary hemorrhage & edema
Etiology: Rabbit calicivirus
Etiologic Dx: Rabbit hemorrhagic disease or Viral hemorrhagic disease
These are typical findings in the lungs at necropsy.
Histopathology: Thrombosis of multiple pulmonary vessels, etc.
5. Turbinates from domestic rabbit with history of chronic catarrhal rhinitis.
Dx: Atrophic rhinitis vs control turbinates
Etiology: P. multocida
6. Ventral view of skull of rabbit.
Morphologic Dx: Chronic suppurative otitis media (bilateral)
Etiology: P. multocida
Other suppurative Lesions
1. Brain from adult rabbit.
Dx: Brain abscess
Likely etiologies: P. multocida, Staphylococcus aureus
2. Organs from adult rabbit.
Morphologic Dx: Multifocal suppurative nephritis & myocarditis
Etiology: Staph aureus
Outbreaks of staph infection occasionally seen in adults, but more common in suckling kits.
3. Suckling kit. Several in the litter have died.
Dx: Multifocal suppurative hepatitis
Etiology: Staph aureus
Alimentary Tract
1. Malocclusion. (note the accessory incisors “peg teeth” behind upper incisors)
2. Trichobeozoar.
3. “Enteritis Complex” (summary of possible etiologic agents)
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1. Rotavirus, 2. Clostridium spiroforme & C.perfringens 3. C. piliforme
4. Escherichia coli 5. Lawsonia intracelluaris 6. Coccidiosis (Eimeria spp).
4. Weanling rabbit.
Dx: Acute enteritis
Most likely etiology: Pathogenic strain of attaching-effacing E. coli.
Histopathology: Attaching-effacing bacteria on enterocytes of small or large intestine.
5. Weanling rabbits with history of profuse diarrhea.
Most likely etiologic diagnoses: Acute coccidiosis, clostridial infection.
6. Cecum from rabbit with a history of diarrhea of acute onset. Died.
Morphologic Dx: Acute hemorrhagic typhlitis
Likely etiology: Clostridium spiroforme
Histopathology: Cecal smear & H&E section.
7. Rabbit age 10 weeks with history of diarrhea of several days’ duration. Euthanized.
Morphologic Dx: Proliferative/histiocytic enteritis
Etiology: Lawsonia intracellularis
Histopathology; Histiocytic cell infiltrates & intracellular organisms in apices of enterocytes.
8. Rabbit, age 10 weeks. Profuse diarrhea of sudden onset. Died.
Etiologic Dx: Intestinal coccidiosis
9. Sacculated colon from adult rabbit.
Dx: Mucoid enteropathy
May occur as a sequel to a bout of diarrhea. Disruption of the normal Intestinal microflora
has been implicated as an important predisposing factor to the development of ME.
Liver Lesions
Infectious agents associated with hepatic lesions in rabbits:
Include: C. piliforme, Staphylococci, Listeria monocytogenes, rabbit calicivirus,
Eimeria stiedae, and in wild rabbits, Yersinia pestis.
1. Young adult rabbits with history of profuse diarrhea with mortality.
Morphologic Dx: #1: Multifocal hepatitis
#2: Transmural fibrinous typhlitis, multifocal hepatitis
Etiologic Dx: Tyzzer’s Disease
2. Rabbit, age 10 weeks. History of chronic diarrhea & weight loss.
Morphologic Dx: Multifocal to coalescing chronic biliary hepatitis
Etiologic Dx: Hepatic coccidiosis
Etiology; Eimeria stiedae
Histopathology: Chronic proliferative cholangitis
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3. Pregnant doe. Died immediately prior to parturition (kindling).
Dx: Acute Listeriosis
Histopathology; Gram positive bacilli associated with liver & placental lesions.
4. Histopathology: Massive hepatic necrosis (Rabbit Calicivirus = RHD)
Urinary System
1. Kidneys from adult doe. Most likely etiologic diagnosis?
Etiologic Dx: Encephalitozoonosis
Histopathology: 1. Chronic interstitial nephrits, Gram positive ovoid organisms associated
with the lesions.
2. Multifocal granulomatous encephalitis (E. cuniculi)
2. Kidneys from young adult New Zealand White rabbit.
Most likely diagnosis: Lymphoma
Not virus-associated in domestic rabbits.
Lymphoid tumors have been associated with Herpesvirus sylvilagus infections in cottontails.
Eye
1. Buphthalmia (congenital glaucoma)
2. Cataract in dwarf rabbit.
Associated with congenital encephalitozoon infection in some strains of dwarf rabbits.
Dwarf rabbits appear to be particularly susceptible to encephalitozoon infections
(manifestations may include CNS signs, cataracts & uveitis, extensive renal lesions, etc)
Reproductive System
1. Uterus from adult doe.
Dx: Pyometra
Possible etiologies: P.multocida, staphylococci
2. Reproductive tract from doe that died at parturition.
Morphologic Dx: Acute necrotizing transmural metritis
Etiology: P.multocida (occurs occasionally in does around parturition time)
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3. Pituitary adenoma – mammary dysplasia/hyperplasia syndrome.
Associated with prolactin-producing pituitary tumors with resultant mammary gland dysplasia.
Lipman, NS et al. Prolactin-secreting pituitary adenomas with mammary dysplasia in New
Zealand White does. Lab Anim Sci 44: 111-114, 1984.
4. Endometrial venous aneurysms in NZW & Californian rabbits.
(a) Intra-uterine hematomas from fatal case.
(b) Gross appearance of endometrial aneurysms
(c) Histopathology
Bray, MV et al. Endometrial venous aneurysms in three New Zealand White rabbits.
Lab Anim Sci 42: 360-362, 1992.
5. Old Dutch belted doe. History of anorexia & ascites.
Diagnosis: Uterine adenocarcinoma with multiple peritoneal implants
6. Uterus from old doe.
Dx: Uterine adenocarcinoma
Note the multiple site involvement – common with these neoplasms.
Histopathology: Uterine adenoca & metastases
7. “Pregnancy toxemia-fatty liver syndrome”
Occasionally encountered in obese does in advanced pregnancy.
Poorly understood syndrome.
Acknowledgements: Contributions from colleagues are gratefully acknowledged.
Drs Steve Barthold, Robert Jacoby, James Fox, James Murphy, Ricardo Feinstein, Brian
Binnington, Craig Bihun & many others provided invaluable material for this presentation.
[email protected]
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