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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. 1 CL Davis Foundation - Annual Review: Gross Morbid Anatomy of the Diseases of Animals - 2003 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). 2 CL Davis Foundation - Annual Review: Gross Morbid Anatomy of the Diseases of Animals - 2003 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. 3 CL Davis Foundation - Annual Review: Gross Morbid Anatomy of the Diseases of Animals - 2003 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: 4 CL Davis Foundation - Annual Review: Gross Morbid Anatomy of the Diseases of Animals - 2003 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 5 CL Davis Foundation - Annual Review: Gross Morbid Anatomy of the Diseases of Animals - 2003 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. 6 CL Davis Foundation - Annual Review: Gross Morbid Anatomy of the Diseases of Animals - 2003 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. 7 CL Davis Foundation - Annual Review: Gross Morbid Anatomy of the Diseases of Animals - 2003 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. 8 CL Davis Foundation - Annual Review: Gross Morbid Anatomy of the Diseases of Animals - 2003 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. 9 CL Davis Foundation - Annual Review: Gross Morbid Anatomy of the Diseases of Animals - 2003 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) 10 CL Davis Foundation - Annual Review: Gross Morbid Anatomy of the Diseases of Animals - 2003 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 11 CL Davis Foundation - Annual Review: Gross Morbid Anatomy of the Diseases of Animals - 2003 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? 12 CL Davis Foundation - Annual Review: Gross Morbid Anatomy of the Diseases of Animals - 2003 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 13 CL Davis Foundation - Annual Review: Gross Morbid Anatomy of the Diseases of Animals - 2003 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” 14 CL Davis Foundation - Annual Review: Gross Morbid Anatomy of the Diseases of Animals - 2003 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 15 CL Davis Foundation - Annual Review: Gross Morbid Anatomy of the Diseases of Animals - 2003 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. 16 CL Davis Foundation - Annual Review: Gross Morbid Anatomy of the Diseases of Animals - 2003 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. 17 CL Davis Foundation - Annual Review: Gross Morbid Anatomy of the Diseases of Animals - 2003 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) 18 CL Davis Foundation - Annual Review: Gross Morbid Anatomy of the Diseases of Animals - 2003 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 19 CL Davis Foundation - Annual Review: Gross Morbid Anatomy of the Diseases of Animals - 2003 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) 20 CL Davis Foundation - Annual Review: Gross Morbid Anatomy of the Diseases of Animals - 2003 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] 21