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CL Davis Foundation - Gross Morbid Anatomy of the Diseases of Laboratory Animals 2004
DISEASES OF LABORATORY RODENTS & LAGOMORPHS
Dean H. Percy, DVM, PhD, DACVP
MOUSE
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. Weanling Mouse: Dx: “Ringtail” Associated with low environmental humidity, but other predisposing
factors may be involved (eg low environmental temperature, dehydration). Annular ridging of the tail
and the dry appearance to the skin of the tail are typical changes.
3. BALB/c Mouse with Skin Lesions:
Morphologic Dx: Extensive multifocal to coalescing ulcerative dermatitis.
Pathogenesis: Typical of fighting injuries among aggressive male mice.
4. Mouse with skin lesion in neck region: Morphologic Dx: Ulcerative Dermatitis
Possible Etiologies: Primary staphylococcal infection, self-trauma due to mite infestation with
secondary bacterial infection.
5. Adult mouse with subcutaneous mass – differentials: Subcutaneous abscess, neoplasm.
Histopathology: Circumscribed lesion with bacterial colonies, etc = typical of staphylococcal infection
(“botryomycosis”)
6. 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). Underlying
predisposing factors for idiopathic dermatitis in this strain also include nutritional deficiencies, etc.
7. Mouse with Skin Condition
Morphologic Dx: Diffuse Scaling Dermatitis with Patchy Alopecia.
Etiologic Dx: Acariasis
Differential Dx: vs Barbering
8. Athymic Mice with Skin Condition (3 slides). There is a diffuse scaling dermatitis with marked
thickening and ridging of affected skin.
Morphologic Dx: Diffuse Scaling Dermatitis. This condition is rare in immunocompetent mice.
Etiologic Dx: Corynebacterium bovis Infection
Immunocompetent mice rarely show any clinical manifestations of the disease, although they may
harbor the organism on the skin as a subclinical infection.
.
9. Mouse with skin lesions on tail: Etiologic Dx: Mousepox
Typical lesions associated with Ectromelia virus infection.
Differential Dx: Fighting injuries.
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CL Davis Foundation - Gross Morbid Anatomy of the Diseases of Laboratory Animals 2004
10. Laboratory Mouse from an animal facility in Asia.
Several animals have developed these lesions (with mortality) over the past few days.
Morphologic Dx: Acute Multivesicular Volar Pododermatitis
Etiologic Dx: Mousepox (due to ectromelia virus)
11. Mouse with loss of extremities (From outbreak in Europe in the 1980’s):
Morphologic Dx: Ectromelia (= loss of extremities following ectromelia virus infection).
12. Weanling Mouse with lesions on feet:
Morphologic Dx: Gangrenous Pododermatitis with Sloughing of Extremities.
Etiology: Ischemic necrosis of extremities due to cotton batton nest material wrapping around
extremitis and subsequent sloughing of the feet.
13. Mice with Bilateral Focal Nasal Alopecia:
Etiology: “Barbering” - The mouse with the intact vibrissae is the culprit!
Respiratory Tract
1. Lungs from a DBA mouse, age 6 weeks, ruffled hair coat, dyspnea, euthanized.
Morphologic Diagnosis: Acute Interstitial Pneumonitis
Possible Etiologic Diagnoses: Sendai virus infection, pneumonia virus of mice (PVM)
DBA mice, although immunocompetent, frequently develop clinical disease with lesions post exposure
to Sendai virus. Immunodeficient mice (athymic, scid/scid, etc, are very susceptible to Sendai virus
infection with mortality.
2. Histopathology: Typical lesions seen with Sendai & PVM virus Infection.
Sendai: Immunocompetent mice: Bronchoalveolitis
Immunodeficient mice: Striking proliferative bronchiolitis & alveolitis.
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).
Differential Dx: Chronic Bronchopneumia due to P. pneumotropica.
Histopathology: M. pulmonis infections: Chronic bronchopneumonia with peribronchial cuffing with
lymphocytes & syncytial cell formation in the bronchial epithelium (as shown).
4. Thoracic organs from laboratory Mouse.
Morphologic Dx: Chronic Localized Bronchopneumonia
Etiologic Dx: Pasteurella pneumotropica Infection An opportunistic infection capable of producing
suppurative lesions in the respiratory tract and reproductive tract, especially in immunocompromised
mice.
Differential Dx: Other chronic bacterial infections (mycoplasmosis, streptococcal infection), or
pulmonary neoplasm.
Histopathology: Chronic suppurative bronchopneumonia
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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).
Histopathology: Chronic alveolitis with alveolar flooding and large numbers of typical
trophozoites within the alveolar exudate. Confirmation via methenamine silver stains.
6. Lungs from an old mouse. Doing poorly. Euthanized.
Diagnosis: Pulmonary Neoplasm.
Most likely candidate: Alveolar/Bronchiolar Carcinoma
Histopathology; Alveolar/Bronchiolar tumors
Alimentary Tract
1. (a) Young adult immunocompetent mouse with history of weight loss. Euthanized.
Morphologic Dx: Multifocal Hepatitis
Most likely candidate: Mouse hepatitis virus (MHV)
(b) Scid/scid mouse: Morphologic Dx: Acute Multifocal to Coalescing Hepatitis
Lesions are often extensive in immunocompromised mice.
Histopathology: MHV: multifocal hepatitis with syncytial giant cells & basophilic nuclear debris.
2. Scid/bg Female Mouse:
Morphologic Dx: Multifocal to coalescing Hepatitis
Histopathology: Acute focal coagulation necrosis (Etiologic Dx: Proteus mirabilis Infection)
3. Adult mouse.
Morphologic Dx: Splenomegaly & Multifocal Hepatitis (Consistent with Acute Septicemia)
Histopathology: Acute Typhlitis
Etiologic Dx: Acute Salmonellosis
a) Examples of Hepatitis Associated with Specific Viral infections :
Reovirus infections in young mice, acute LCM virus infection, ectromelia virus infection.
(b) Examples of Hepatitis Associated with Bacterial Infections
Helicobacter hepaticus infection, Tyzzer’s, salmonellosis, Proteus mirabilis infection.
4.
Adult mouse with hepatic lesion.
Morphologic Dx: Chronic Parasitic Hepatitis
Etiology: Cysticercus fasciolaris
Definitive Host: Cat (Taenia taeniaformis)
5. Cryptosporidial cholangitis in athymic mouse (histopathology)
6. Suckling pup.
Morphologic Dx: Acute Enteritis
Histopathology: Typical “balloon cells” in small intestine with MHV, blunting of villi, etc
(vs rotavirus infection).
7. Mouse with rectal prolapse:
Possible etiologies: Chronic colitis associated with Citrobacter, Helicobacter, non lactose-fermenting
strain of E.coli, infections, & pinworm infestations. Helicobacter spp
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Histopathology: Chronic proctitis (H. hepaticus).
8. 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; Proliferative intestinal lesion.
Urogenital System
1. Renal Amyloidosis
2. Morphologic Dx: Obstructive Nephropathy (note the dilated ureters)
3. Male mouse with urethral plug. = secretions released from the accessory sex glands at the
time of death. An incidental finding.
4. Morphologic Dx: Chronic Pyometra
(P.pneumotropica, Klebsiella oxytoca are likely candidates re. bacteria).
5. Adult mice (littermates); 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. Note the uterine walls are
relatively translucent vs pyometra.
6. Adult female mouse with axillary mass:
Morphologic Dx: Mammary adenocarcinoma
Retrovirus-associated. There are several strains of mouse mammary tumor virus (MMTV).
Cardiovascular System
1. 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.
2. Histopathology: Polyarteritis
Hematopoietic System
1.
Adult SCID mouse with thymic mass.
Diagnosis: Thymic Lymphoma
2. Adult CD-1 mouse with lymphadenopathy.
Diagnosis: Lymphoma/Lymphosarcoma (probably B cell type)
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CL Davis Foundation - Gross Morbid Anatomy of the Diseases of Laboratory Animals 2004
3. Morphologic Dx: Hepatic Tumor
Differential Dx: Primary Hepatic tumor (Hepatocellular Carcinoma), Lymphoreticular tumor.
Dx: Histiocytic Sarcoma (confined to liver, but often multiple organs involved.
Reference Text:
Maronpot, R.R. et al. Pathology of the Mouse. Cache River Press, Vienna, Illinois, 1999.
RAT
Examples of Skin Lesions in the Laboratory Rat
1. Juvenile Rat with skin lesions (3 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.Suckling rat pup with lesions on the tail (multiple circumferential contractions).
Diagnosis: “Ringtail”
Etiopathogenesis: Low environmental humidity (eg < 20%) is recognized to be the primary cause,
although other factors,(eg low environmental temperature, degree of hydration) may be also be
involved.
3. Old Rat with mass at the external ear canal.
Dx: Zymbal’s Gland Adenocarcinoma
Locally invasive but not metastatic.
Histopathology: Illustrating both sebaceous gland & squamous cell components.
4. Rat with lesions on the ears.
Morphologic Dx: Proliferative & Disfiguring Otitis Externa
Etiologic Dx: Acariasis (Notoedres muris infestation)
Differential Dx: Chronic Auricular Chondritis
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 “stressed” laboratory rat, whether
an infectious disease, shipping stress, etc. The porphyrins fluoresce under an ultraviolet light source.
6. Old Sprague-Dawley rat with ocular changes.
Diagnosis: Bilateral Cataracts
This is an example of so-called senile cataracts, but they may be chemically induced.
Respiratory Tract
1. Wistar rat, age 8 months.
Morphologic Dx: Cranioventral Bronchopneumonia
Possible Etiologies: Chronic mycoplasmal infection (M. pulmonis)**
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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, 18 months.
Morphologic Dx: Chronic Bronchopneumonia
Note the subpleural aggregates of lymphoid tissue and the discoloration of the affected areas of lung.
Most likely candidate: Chronic mycoplasmosis (CAR bacillus may also be involved).
3. 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
Histopathology: Chronic Mycoplasmal Endometritis, CAR Bacillus.
4. Wistar rats, age 6 weeks (2 cases). Recent arrivals from a commercial supplier. Found dead.
Morphologic Dx: Acute Fibrinopurulent Pleuritis & Bronchopneumonia (#1)
Morphologic Dx: Subacute Fibrinous Pleuritis (#2)
Etiology: Streptococcus pneumoniae
Differential Dx: vs C. kutscheri infection
Note: S. pneumoniae infections are now rare in well managed facilities.
5. Respiratory Infections in Laboratory Rats of Obscure Etiopathogenesis:
Lungs from young adult Wistar Rat.
Morphologic Dx: Acute Multifocal to Diffuse Pneumonitis
Example of pneumonitis due to Rat Respiratory Virus (form outbreak in France)
(a) Idiopathic pneumonitis associated with so-called rat respiratory virus (RRV)
Based on current information, the causative agent is a poorly characterised RNA virus.
Focal alveolitis, with marked perivascular lymphocytic infiltration are typical findings.
(b) Eosinophilic granulomatous pneumonitis in Brown Norway (BN) Rats
Frequently encountered in young adult BN rats.
Marked granulomatous alveolitis with focal to diffuse infiltrates of macrophages & eosinophils.
Lesions are consistent with a parasitic infection, but the controversy re. the etiology continues. .
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.
6. Old Rats (2): Morphologic Dx: Subpleural Alveolar Histiocytosis
7. Immunocompromised Adult rat that died during the course of the experiment.
(a) Morphologic Dx: Acute Bronchopneumonia with Multiple Abscessation
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Most likely Etiology: Corynebacterium kutscheri
The focal raised suppurative lesions with hemorrhagic periphery are typical of acute
coynebacterial infections. There are frequently predisposing factors associated with this infection
(eg immunosuppression).
(b) Old rat with multifocal renal cortical abscessation (systemic C. kutscheri infection).
8. 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 organism on the damaged valve & resultant endocarditis.
7. Rat on a protein-deficient diet. Dyspnea & weight loss. Euthanized.
Morphologic Dx: Diffuse 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 (hereditary predisposition)
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, tracheitis.
3. Suckling Rat. Died.
Morphologic Dx: Acute Enteritis
Etiologic Dx: Rotavirus (Infectious diarrhea of infant rats [IDIR])
Histopathology: Vacuolation of enterocytes lining tips of villi with intracytoplasmic inclusions.
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.
5. (a) Laboratory rat, age 10 weeks. Representative animal from an outbreak of this disease.
Morphologic Dx: Acute fibrinous periorchitis
Etiologic Dx: Rat parvovirus (RV) infection
Differential Dx: Polyserositis associated with acute Streptococcus pneumoniae infection.
(b) Juvenile laboratory rat. Focal hepatitis associated with Kilham’s rat virus (RV) infection.
Intranuclear inclusions.
(c) Sections of brain from young rat that died post inoculation with RV.
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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 cortex & medulla.
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. Male Rat with Ventral Midline Mass
Morphologic Dx: Preputial Gland Tumor
Differential Dx: Preputial Gland Adenoma or Adenocarcinoma, Preputial Gland Abscess
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.
Adult Rat.
Morphologic Dx: Chronic Suppurative Endometritis
Associated with chronic M. pulmonis infection. Other bacteria (eg P.pneumotropica,) are possibilities.
4. Old Sprague-Dawley female rats 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.
5. 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. (a) Old laboratory Rat:
Dx: Polyarteritis
Note the marked tortuosity of the mesenteric vessels.
(b) Mesenteric vessels from an aged laboratory rat.
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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 (SHR)
rat]. 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.
Histopathology: Mesothelioma
Hematopoietic System
1. (a) Old Fischer (F344) Rat: Dx: Large Granular Lymphocytic Leukemia (LGL)
The rat strain, age, & the marked splenomegaly are useful clues re. the likely candidate……
(b) Organs from an old F344 rat.
Dx: Large Granular Lymphocytic Leukemia (LGL)
Differential Dx: Lymphoma
This malignancy is common in F344 rats. Note the splenomegaly, the enlarged liver, and the icteric
appearance of the lungs & liver.
2. Histopathology: Impression smear of spleen from F344 rat with LGL.
Note the granules present in the cytoplasm of some of the malignant lymphocytes.
(a) Histiocytic Sarcoma: Histopathology
“Rat Baiting” in England (1823) “Billie” killed a record 100 wild rats in 5 ½ minutes.
Note: 1. In rats, unlike mice, malignancies of the hematopoietic system and mammary glands are not
normally associated with endogenous retrovirus infections.
2. Unlike mice, hamsters, etc. laboratory rats do not develop spontaneous amyloidosis.
References:
1. Fox, J.G. et al. Ulcerative dermatitis in the rat. Lab. Anim. Sci. 27: 671-678, 1977.
3. 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.
SYRIAN HAMSTER
1. Mesenchymal tumors in young Syrian hamster – Role of neonatal hamsters as an in vivo
method of screening for potential oncogenic viruses (rarely used to-day)
2. Sendai rhinopneumonitis in Syrian Hamsters (histopathology)
3. Lymphocytic choriomeningitis (histopathology)
4. Hamster lymphoma with trichoepithelioma
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(Associated with hamster polyoma virus [HaPV] infection)
5. 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)
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.
6. Old hamster with skin lesions.
Morphologic Dx: Diffuse scaling dermatitis with alopecia
Etiologic Dx: Acariasis (Demodex spp) [most likely diagnosis]
Hamsters frequently harbor mites, but usually is a subclinical infection.
Immunocompromised animals (eg old age, concurrent disease, etc) may develop clinical disease.
Histopathology; Demodex infestation
7. Tapeworm Identification in Laboratory Rodents;
Hymenolepis nana (The larger)
Hymenolepis diminuta (The smaller)
8. Adult hamster with history of chronic diarrhea.
Dx: Chronic enterocolitis due to Giardiasis
Infected animals are usually asymptomatic, but old age or concurrent disease may precipitate clinical
disease.
9. 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.
10. Heart from an old hamster.
Dx: Atrial thrombosis
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.
11. Old hamster. Most likely diagnosis?
Dx: Chronic Progressive Glomerulonephropathy.
Differential Dx: vs amyloidosis
12. Old hamster.
Dx: Renal amyloidosis
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.
13. Adult hamster. Incidental changes seen at post mortem.
Dx: “Polycystic Disease”
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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.
14. “Polycystic Liver Disease” in the liver of old Syrian hamster.
Note the striking cystic structures involving the liver. Unusual to see lesions this extensive.
15. 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.
MONGOLIAN GERBIL
1. Normal Harderian Gland & Porphrin Pigment
2. 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.
2. Young gerbils. Profuse diarrhea of acute onset & subsequent death.
(a) Morphologic Dx: Multifocal hepatitis
Etiologic Dx: Tyzzer’s Disease (Clostridium piliforme)
Differential diagnoses: vs salmonellosis.
(b) Morphologic Dx: Acute Transmural Hemorrhagic Ileitis
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.
(c) H&E-stained section of heart – Acute interstitial myocarditis
Mongolian gerbils are exquisitely susceptible to Tyzzer’s disease.
3. Progressive Glomerulonephropathy
4. Multifocal chronic cardiomyopathy with interstitial fibrosis
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5. Lung: “Heart failure cells”
6. Reproductive tract of an old Gerbil. Diagnosis?
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
1. Example of typical pulmonary arterioles in guinea pig (histopathology).
2. Heart. Differential Diagnoses: Rhabdomyomatosis, “metastatic calcification”,
Myocardial degeneration associated with vitamin E deficiency (a long shot!)
Histopathology: Dx: Rhabdomyomatosis
Vacuolation of myofibers typical of the glycogen deposition (considered to be an incidental finding).
Histopathology #2: Multifocal myocardial degeneration with mineralization/calcification.
3. Pancreas (Interlobular fat deposition – normal finding in guinea pigs)
4. Perivascular Lymphoid Nodules in the lung
5. 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.
Debout et al. Increase of guinea pig natural killer cells (Kurloff cells) during leukemogenesis.
Cancer Letters 97: 117-122, 1995.
Skin Conditions in the Guinea Pig
1. Young guinea pig.
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”
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2. Young adult guinea pig.
Dx: Dermatophytosis
Clinical cases are relatively rare in laboratory animal facilities to-day.
Histopathology: Trichophyton mentagrophytes.
Respiratory System
1. (a) Lungs from adult guinea pig with history of recent dyspnea. Euthanized.
Morphologic Dx: Acute Cranioventral 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
bronchopneumonia. Histopathology: Lesions associated with B. bronchiseptica infections.
(b) Chronic suppurative endometritis (associated with B. bronchiseptica infection).
2. 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)
4. Guinea Pig Cytomegalovirus (Intranuclear inclusions in duct of salivary gland)
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
Acute necrotizing bronchiolitis & alveolitis (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.
Lymphopoietic System:
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!!)
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.
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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.
Urinary & Reproductive Systems
1. Old sow with pregnancy toxemia.
Types: (a) Metabolic (b) Circulatory
Histopathology: Metabolic form: Marked fatty infiltration in the liver (hepatic lipidosis)
2. 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.
The etiopathogenesis of this disease has not been adequately studied and resolved.
Histopathology: Relative sparing of glomeruli, the chronic tubular degeneration & regeneration, and
the relative absence of inflammatory cell infiltrates.
3. Old sow:
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. James Lind, ship’s surgeon in the 18th century & the feeding of limes to sailors to prevent scurvy
2. Young guinea pig. History of lameness & doing poorly.
Diagnosis: Scurvy
Periarticular hemorrhages are typical findings.
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CL Davis Foundation - Gross Morbid Anatomy of the Diseases of Laboratory Animals 2004
3. Young adult guinea pig.
Diagnosis: Scurvy
Histopathology: Examples skeletal lesions associated with scurvy.
(proliferation of poorly-differentiated fibrous tissue, microfractures, hemorrhage, etc)
4. Tissues from old guinea pig.
Diagnosis: “Metastatic calcification/mineralization”
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.
Neoplasms
1. Bronchial adenoma
2. Trichoepithelioma
3. Young adult guinea pig.
Diagnosis: Lymphoma
Note the marked enlargement of abdominal lymph nodes, etc.
Often associated with a guinea pig retrovirus infection.
DOMESTIC & WILD RABBITS
Examples of Lesions of the Skin in the rabbit
1. Young adult rabbit:
Morphologic Dx: Diffuse scaling dermatitis & moderate alopecia
Etiologic Dx: Acariasis [Demonstration of mites (Chyletiella spp) required].
Differential Dx: vs “barbering”, dermatophyte infection
2. Hock from adult New Zealand White buck.
Morphologic Dx: Chronic Ulcerative & Necrotizing Plantar Podermatitis
Staphylococci are frequently isolated from these lesions.
3. Young rabbit kits.
Dx: Multifocal suppurative dermatitis = pyoderma (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.
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CL Davis Foundation - Gross Morbid Anatomy of the Diseases of Laboratory Animals 2004
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: Psoroptes cuniculi
6. Young doe: Breeding Age:
Dx: Fighting Injuries (aggressive buck)
7. Cottontail rabbit with proliferative lesion on foot.
Most likely Dx: Shope’s fibroma
Poxvirus related antigenically to myxomatosis virus.
Histopathology: Intracytoplasmic eosinophilic inclusions in the fibroblasts in the underlying dermis.
8. 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.
9. 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.
Miscellaneous Viral:
1. Cottontail Rabbit: Lymphoma (Herpes sylvilagus)
2. Herpes simplex encephalitis
Respiratory System
1. Chronic “Snuffles”
2. Turbinates: Normal & Atrophic Rhinitis Secondary to Chronic Pasteurellosis
Note the marked excavation of turbinates in the affected animal.
3. Lungs from adult New Zealand White doe.
Morphologic Dx: Chronic cranioventral bronchopneumonia
Etiologic Dx: Pasteurellosis (P. multocida)
Differential Dx: vs Bordetella bronchiseptica infection
4. Lungs from adult New Zealand White doe.
Morphologic Dx: Acute fibrinohemorrhagic bronchopneumonia
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CL Davis Foundation - Gross Morbid Anatomy of the Diseases of Laboratory Animals 2004
Etiologic Dx: Pasteurellosis
5. Lungs from adult New Zealand White buck.
Morphologic Dx: Acute suppurative bronchopneumonia.
Histopathology. Examples of fibrinous & suppurative bronchopneumia.
Suppurative & Necrotizing Lesions Associated with P. multocida or Staph aureus Infection
1. Morphologic Dx: Chronic bilateral suppurative otitis media (P. multocida)
2.
Brain abscess (P. multocida or Staph aureus)
3. Pyometra (P. multocida or Staph aureus)
4. Acute Necrotizing Transmural Metritis (Associated with particulary virulent strains of P. multocida).
5. Suckling kit. Several in the litter have died.
Dx: Multifocal suppurative hepatitis & splenomegaly (Staph aureus)
6. Organs from adult rabbit.
Morphologic Dx: Multifocal suppurative nephritis & myocarditis
Etiology: Staph aureus. Outbreaks of staph infection occasionally seen suckling kits and/or adults.
Alimentary Tract
1. Malocclusion. (note the accessory incisors “peg teeth” behind upper incisors)
2. Trichobeozoar.
3. Normal lagomorph digestive tract illustrating sacculus rotundus & appendix
“Enteritis Complex” (summary of possible etiologic agents)
1. Rotavirus, 2. Clostridium spiroforme 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. Young adult rabbits with history of profuse diarrhea with mortality.
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CL Davis Foundation - Gross Morbid Anatomy of the Diseases of Laboratory Animals 2004
Morphologic Dx: #1: Multifocal hepatitis
#2: Transmural fibrinous typhlitis, multifocal hepatitis
Etiologic Dx: Tyzzer’s Disease
8. 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.
9. Rabbit, age 10 weeks. Profuse diarrhea of sudden onset. Died.
Etiologic Dx: Intestinal coccidiosis
10. 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
Infectious agents associated with hepatic lesions in rabbits:
Include: C. piliforme, Staphylococci, Listeria monocytogenes, rabbit calicivirus,
Eimeria stiedae, and in wild rabbits, Yersinia pestis.
11. 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.
Urinary System and CNS
1. Kidneys from adult does. Most likely etiologic diagnosis?
Etiologic Dx: Chronic Encephalitozoonosis
(a) Subacute
(b) Chronic
Histopathology: 1. Chronic interstitial nephrits, Gram positive ovoid organisms associated
with the lesions.
2. Multifocal granulomatous encephalitis (E. cuniculi)
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)
2. Rabbit with CNS signs:
Dx: Leukomalacia associated with Baylisascaris procyonis Infection.
Reproductive System
1. External genitalia of young adult doe.
Dx: Ulcerative Vulvitis
Etiologic Dx: Treponematosis
Histopathology: Spirochetes in exudate (Warthin-Starry stain)
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CL Davis Foundation - Gross Morbid Anatomy of the Diseases of Laboratory Animals 2004
2. Pregnant doe. Died immediately prior to parturition (kindling).
Dx: Acute Listeriosis
Histopathology; Gram positive bacilli associated with liver & placental lesions.
3. “Pregnancy toxemia-fatty liver syndrome”
Occasionally encountered in obese does in advanced pregnancy.
Poorly understood syndrome.
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 adenocarcinoma with metastases
7. 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.
8. Kidneys from young adult New Zealand White rabbit.
Most likely diagnosis: Lymphoma
Not virus-associated in domestic rabbits (vs Herpesvirus sylvilagus - lymphoma in cottontails).
9. Final Case: Vertebral Fracture
General Comments: Some of you attending these CL Davis Gross Sessions may not have seen a
great deal of laboratory animal material. Remember that the disease processes are similar, whether
dealing with conventional domestic animals, wildlife, or whatever. A review of the commonly
encountered infectious diseases, neoplasms, etc. in these species should give you a good basis on
which to build.
Recommend that for this session you concentrate on the images rather than attempting to
follow the notes. The notes include have a fair number of comments re. differential diagnoses, etc.
to assist with your review at a later date.
Acknowledgements: Contributions from colleagues are gratefully acknowledged.
Drs Steve Barthold, Robert Jacoby, Trenton Schoeb, Pat Turner, James Fox, James Murphy, Ricardo
Feinstein,Ron Di Giacomo, Craig Bihun & many others provided invaluable material and advice for this
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CL Davis Foundation - Gross Morbid Anatomy of the Diseases of Laboratory Animals 2004
presentation.
Dean H. Percy
OVC Pathobiology
University of Guelph
Guelph, Ontario, Canada
N1G 2W1
[email protected]
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