Adobe PDF - Charles Louis Davis DVM Foundation
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Adobe PDF - Charles Louis Davis DVM Foundation
6/22/2012 SELECTED GROSS PATHOLOGY OF MICE AND RATS Bruce Williams, DVM, DACVP Dept. of Veterinary Pathology AFIP, Washington DC [email protected] Acknowledgements Mike Eckhaus, NIH Krista La Perle, OSU Paul Stromberg, OSU Dean Percy, Univ. of Guelph 1 6/22/2012 Lung – abscess – Past. Pneumo Lung ‐ carb 2 6/22/2012 Lung‐ acidophilic pneumonia Lung – acidophilic pneumonia 3 6/22/2012 Thymic lymphoma Thymic Lymphoma death by 1y AKR, C58 Retrovirus role 21 4 6/22/2012 26 5 6/22/2012 32 6 6/22/2012 Ileus 37 Colonic hyperplasia 41 7 6/22/2012 Rectal prolapse 43 Liver – white spots 8 6/22/2012 Salmonella‐ typhlitis percy Liver – histiocytic sarcoma C3H, CBA, etc (M>>F) Helicobacters ?? 54 9 6/22/2012 pododermatitis 60 10 6/22/2012 Vesicular pododermatitis‐pox‐ percy Limb loss – pox ‐percy Fight wounds 11 6/22/2012 mites sharpei 72 12 6/22/2012 Skin‐ papillomas Nude mouse ‐ implanted tumor cells ‐ sarcoma 13 6/22/2012 hydronephrosis 14 6/22/2012 15 6/22/2012 King Mouse retroorbital abscess dt trauma – bleeding likely 91 Cystic ovaries 16 6/22/2012 99 Mammary hyperplasia 17 6/22/2012 C3H mouse – mammary carcinoma Rectal prolapse 18 6/22/2012 RATS 112 19 6/22/2012 20 6/22/2012 Fibrinopurulent brochopneumonia – percy 21 6/22/2012 Malocclusion Enteritis ‐ IDIR 22 6/22/2012 Stomach adeno CA Liver – tyzzer’s ‐ percy 23 6/22/2012 Ulcerative dermatitis‐percy 24 6/22/2012 25 6/22/2012 Renal abscesses – C. kutsceri ‐ percy 26 6/22/2012 Bladder stones Cystic calculus Otitis media‐ percy Megaloglobus 27 6/22/2012 Cataracts ‐percy Suppurative endometritis – mycoplasma ‐ percy Fibroadenoma 28 6/22/2012 Interstitial cell tumor – F344‐ percy 29 6/22/2012 Guinea Pigs Coloring Albino guinea pigs are actually not albino at all, but “acromelanic .” Mammary glands Two inguinal conical nipples. 2-4 pups per litter. (Not “piglets”!) Vesicular glands Boars have prominent vesicular glands which have been misinterprete d as uterine horns! 30 6/22/2012 Vaginal closure membrane The membrane is open at estrus, parturition, and day 26-27 of gestation. Pregnancy Imminent delivery signalled by separation of symphysis. Pups are precocious. Streptococcus pneumoniae •Fibrinous pleuopneumonia e •Not common today, but infected colonies can have up to 50% carriers. Bordetella bronchiseptica •In pet guinea pigs, is important. •Mortality most common in young guinea pigs in winter. •Interspecies transmission can occur. • Transmission is primarily airborne. Adenovirus infection • Necrotizing bronchopneumoni a • Focuses on airways •Low morbidity and mortality, so current estimates of incidence may be low. 31 6/22/2012 Rhabdomyomatosis Incidental finding – foci of glycogen laden cardiomyocytes. Metastatic calcification May affect soft tissues or viscera. Cause unknown by dietary factors are suspected. Moist dermatitis Malocclusion Continuous growth like other rodents. Overgrown cheek teeth a worse management problem than incisors. Gastric torsion/bloat 32 6/22/2012 intusussusception Fecal impaction Yes, I know this picture sucks!!! Liver – lipidosis – preg toxemia Seen in older guinea pigs due to muscle atrophy or impaired cecotrophy. Spleen salmonella Idiopathic hepatic Subcapsular necrosis areas of coagulative necrosis. May be due to terminal hypoxia. Have to rule out infectious causes. 33 6/22/2012 Malignant lymphoma • Cavian leukemia • C-type retrovirus??? • Usually lung adults • Usually associated with leukemia Liver – leukemia ‐ percy Vitamin C deficiency • Guinea pigs require Vit C. supplementatio n •Vitamin C is cofactor of lysyl oxidas and proline hydroxlase, which are integral in Ribs ‐ scurvy Bumblefoot • Predisposed by poor sanitation, rough flooring, unclipped nails. •May develop osteomyelitis 34 6/22/2012 Parasitic dermatitis ‐ trixascarus Alopecia • Pregnancy • Weaning (loss of baby fur) • Protein deficiency • Rough cages • Parasites • Infections 35 6/22/2012 Guinea Pig Inclusion Conjunctivitis • “Weepy eye” • Chlamydophila psittaci •Widespread self-limiting disease •Young guineas •Can see genitourinary and respiratory Cystic ovary ‐ percy Bordetella – endometritis ‐ percy 36 6/22/2012 Glomerulosclerosis Kidney ‐ polycystic Multifactorial disease of gp’s >1yr. Cause unknown, but glomeruli are largely spared. Urinary calculi Dystocia‐anasarca • Proximity of urethra to anus in older sows predisposes to E. coli cystitis 37 6/22/2012 sters Chinese Hamster •“Grey Hamster” • 11 chromosome pairs Hip glands • Pigmented sebaceous glands • Mark territory •Secrete during sexual arousal 38 6/22/2012 Bloat enterocolitis– hp infection Tyzzers Hymenolepis 39 6/22/2012 Rectal prolapse Polycystic disease Common problem in hamsters – liver most common site. Also seen in repro organs, pancreas, adrenals. Amyloidosis Atrial thrombosis Atrial thrombosis • Syndrome ranges from asymptomatic to CHF. • May show evidence of organization and hypertrophy of heart muscle. 40 6/22/2012 Arteriolar Nephrosclerosis Very similar to disease seen in rat. Cause unknown. Paraovarian cysts Nothing new here – let’s keep moving… Spontaneous hemorrhagic necrosis 41 6/22/2012 Hamster papovavirus • Polyomavirus vey similar to PVM. •Transmissible lymphoma •Keratinizing hair follicle tumors •Virus can cause lytic infection or transformation • D. aurati or D. criceti •Very common in old hamsters ot those being experimentally manipulated Cutaneous lymphoma 42 6/22/2012 43 6/22/2012 44 6/22/2012 PATHOLOGY OF THE RABBIT Bruce Williams, DVM, DACVP Dept. of Veterinary Pathology AFIP, Washington DC [email protected] Oryctolagus cuniculus Lepus europaeus NEW ZEALAND WHITE LOP 45 6/22/2012 JERSEY WOOLY ANGORA Kits •Kindle into a fur nest •Kits in nest for 3 weeks. •Does nurse once daily •Will kill kits from other does. DUTCH BELTED Watenabe Rabbit (Heritable Hypercholesterolemia) Large Intestinal Anatomy Rabbits have a large outpouching of the ileum (sacculus rotundus) and a very long cecum. 46 6/22/2012 Night Feces Rabbits are cecotrophs, and reingest soft fecal pellets which are high in Vit B, K, and various proteins. Bicornuate Uterus Rabbits have no uterine corpus – each horn is attached to an independent cervix. Urinary mineral Ca+2 levels vary radically with diet and urine is main route of excretion. Peg teeth Second row of maxillary incisors in rabbits – used for cutting food. 47 6/22/2012 Sleepy Bunny Pasteurella multocida Conjunctivitis Pulmonary abscess 48 6/22/2012 49 6/22/2012 Suppurative – pneumonia – staph or pasteurella ‐ percy Staphylococcosis •Sporadic outbreaks. •Septicemic disease is frequently fatal. •Most severe outbreaks occurs in kits Staphylococcal Vegetative Valvular Endocarditis detellosis Histopathology similar to P. multocida Abundant heterophilic inflammation Fibrin and edema 50 6/22/2012 Lung – hemorrhage – rabbit hemorrhagic disease ‐ percy CFA – pneumonia Lung – mets uterine adenoCA Heart – atherosclerosis Atherosclerosis 51 6/22/2012 Adrenal – atherosclerosis Cutaneous xanthomas 52 6/22/2012 Vitamin D toxicosis Calcification of renal cortex thymoma RAPID AUTOLYSIS OF THE GUT 53 6/22/2012 Oral Papillomatosis Rabbit Poxvirus Rabbit Poxvirus Rabbit Poxvirus 54 6/22/2012 Trichobezar or “wool block” Tyzzer’s Disease TULAREMIA Francisella tularensis Wild rabbits Necrosis with bacteria in the spleen, liver and lymph nodes Direct contact and insect vectors 55 6/22/2012 Mucoid Enteropathy Cecum – bloody content – coccidia ‐ percy 56 6/22/2012 Mesenteric lipoma Epistaxis ‐rabbit hemorrhagic disease 57 6/22/2012 58 6/22/2012 Edema and cyanosis of the pinna Shope fibroma ‐ percy Rabbit syphilis 59 6/22/2012 Pasteurella multocida Subcutaneous abscesses Mastitis Staphylococcosis •“Blue breast” •Focal necrotizing mastitis due to alpha-toxin of S. aureus 60 6/22/2012 Otitis externa Acariasis – Chyletiella ‐ percy Cuterebra Ringworm 61 6/22/2012 Exfoliative Dermatitis Fight injury ‐ ear •Adult rabbits •Scaling dermatosis and alopecia with interface dermatitis and necrotizing sebaceous adenitis Marginal ear veins and Ear slough Prominent, easily accessible veins along the margin of pinna Repeated venipuncture with thrombosis and infarcts lead to localized tissue necrosis Perineum – urine scald 62 6/22/2012 Feeder Alopecia Hair loss from rubbing against wire cage Boredom and low roughage diets may contribute Fracture Vertebral Fracture Vertebral fracture Fractured vertebrae ‐ percy •Rabbits are osteopenic animals to start with. •Usually lumbosacral (L7) •May have hemorrhage in the psoas muscles. 63 6/22/2012 Proper Handling ‐ Support the hindlimbs!!! Tetanus TORTICOLLOSIS Cataract – congenital Encephalitazoon ‐ percy 64 6/22/2012 Buphthalmia Listeria monocytogenes •Contaminated food and water •Inapparent shedders •Predilection for gravid uterus •Necrotizing metritis, placentitis, hepatitis, and splenitis Uterine Adenocarcinoma •Most common neoplastic disease •80% in 5-6 yr old Oryctolagus. 65 6/22/2012 Endometrial Venous Aneurysms •Associated with persistent urogenital bleeding. •Nonpregnant multiparous does Testicular Neoplasia Interstitial cell tumors are most common Sertoli cell tumors and seminomas have also been reported Kidney – calculus 66 6/22/2012 Kidney – end stage – fibrosis PITUITARY ADENOMA 67 SELECTED GROSS PATHOLOGY OF LABORATORY RODENTS AND RABBITS 2012 Gross Morbid Pathology of the Diseases of Animals July 2012 CSU College of Veterinary of Veterinary Medicine, Ft. Collins, CO Instructor: Bruce H. Williams, DVM, DACVP Dept. of Veterinary Pathology, AFIP (202) 782-2650 Email: [email protected] PURPOSE The purpose of this seemingly interminable block of instruction is to gain knowledge and experience in the gross diagnosis of diseases of the laboratory rodents and lagomorphs. Of course, the study of disease in this species far exceeds what can be presented in a three hour block of time, but I will attempt to cover a number of diseases of interest. In some cases, inclusion or exclusion from this collection was the result of the availability of high-quality photographs. I am a firm believer that one can learn far more from one excellent photograph of a single entity, than from many poor ones. If the only available image is of poor quality, the image won’t leave a lasting impression, and the student learns nothing. I have included a brief morphologic diagnosis for each entity. The formulation of concise, accurate morphologic diagnoses is a major pursuit of every good pathologist, especially those who seek certification in this specialty. The formulation of a good morphologic diagnosis is a learned skill; for those seeking additional experience in this endeavor, I would suggest attendance at the annual C.L. Davis Foundation Descriptive Pathology Course (given often in Europe and South America, as well as in the US). . 1 Slide Organ No. 1 Condition Morphologic Diagnosis Notes INTRODUCTION 2 3 4 5 CARDIOVASCULAR SYSTEM 6 Heart Cardiomyopathy Multifocal myocardial fibrosis and myofiber necrosis and loss More common in males, lower incidence than in rats, similar histo to other species – look for fibrosis. 7 Pericardium Dystrophic calcification Multifocal to coalescing pericardial and epicardial mineralization Common in BALB/c, C3H, DBA. Usually on right ventricle. 8 Heart Atrial thrombosis Left atrial thrombosis Common in aged mice with proteinuria. Amyloidosis is often part of the process. 9 RESPIRATORY SYSTEM 10 Lung Pulmonary abscess Focally extensive unilateral pulmonary abscess This is P. pneumotropica, a bacterial opportunist. Also consider Corynebacterium, Staph and Streptobacillus. 11 Lung CAR Bacillus Diffuse subacute to chronic bronchopneumonia with bronchiectasis Underdiagnosed in mice. B6 predisposed, but should look for pre‐ existing viral infection like Sendai and PVM. 12 Lung Interstitial pneumonia Diffuse granulomatous interstitial pneumonia Lots of causes – Pneumocystis, acidophilic macrophage pneumonia, alveolar proteinosis, and bacterially‐complicated 2 viral diseases. 13 14 Lung Acidophilic macrophage Diffuse granulomatous pneumonia interstitial pneumonia B6, Swiss and 129 mice. Alveolar macrophages are expanded by intracytoplasmic acidophilic crystals – associated with Ym1 and/or Ym2 chitinases. 15 Lung Pulmonary adenoma Pulmonary adenoma Fairly common in mice. A strains with activation of K‐ras have 100% incidence by 18 mo. 16 Lung Multiple pulmonary neoplasms Metastatic vertebral osteosarcoma Multiple pulmonary nodules usually represent metastatic tumors, but multiple pulmonary adenomas may also be seen 17 18 HEMOLYMPHATIC SYSTEM Lymph nodes Malignant lymphoma Malignant lymphoma Most lymphomas in mice arise as of a result of retroviral infection. This one is Moloney murine leukemia retrovirus. 19 20 Thymus Thymic malignant lymphoma Almost 100% incidence in AKRs and C58, and common in SCIDs 21 22 Spleen, liver Splenic and hepatic lymphoma Most lymphomas in mice arise in the spleen and are of B‐cell origin. Even nude mice develop a lot of lymphomas. 23 Spleen, liver Histiocytic sarcoma Splenic and hepatic 3 Associated findings include hyaline droplets in histiocytic sarcoma 24 renal tubules, marked EMH,, and decreased myelopoiesis. Always look in the uterus for this neoplasm. GASTROINTESTINAL SYSTEM 25 26 Teeth 27 28 Salivary gland Lymph node Malocclusion Malocclusion Myoepithelioma Salivary gland myoepithelioma There is usually a hereditary basis, although there is usually no demonstrable abnormalities of the jaws. Rodent teeth grow continually so malocclusion is usually devastating. Most common in BALB/c females. Bone marrow hyperplasia is a common associated condition. R/O mammary adenocarcinoma 29 Esophagus Megaesophagus Megaesophagus Seen in Swiss ICRC – affected animals have a longer segment of the esophagus with smooth muscle as well as myenteric plexus aplasia. 30 Stomach Gastric necrosis Gastric glandular hemorrhage and necrosis Many possible causes – ulcers as well as alcohol and saccharin. 31 Stomach Gastric hypertrophy Diffuse gastric glandular hypertrophy and hyperplasia. May be seen in immunodeficient mice; unknown cause. 32 Stomach Gastric ulcers Multiple gastric ulcers Tough being a lab mouse. 33 Stomach Gastric papillomas Multiple gastric papillomas Arise in the squamous portion of the stomach; may be genotypes and 4 carcinogens 34 Small intestine Diarrhea in young mice Multiple causes in weanlings to include a) enterotropic mouse coronavirus, rotavirus, reovirus, norovirus, and several bacterial infections. 35 Small intestine Enzootic diarrhea of infant mice Diffuse superficial necrotizing enteritis with villar atrophy EDIM is a disease of mouse pups which results in necrosis at the villar tips, villar blunting, and difficulty in digesting milk. 36 Presentation Greasy mouse syndrome Diffuse steatorrhea This is the result of reovirus‐3 infection – also see necrotizing encephalitis, myocarditis, or hepatitis. 37 Small intestine Ileus Diffuse intestinal dilation Paralytic ileus is seen in the 2nd week following gestation in C57s. May be the result of Avertin anesthesia in Swiss mice, or in the old days, IP pentobarb. 38 39 40 Colon Proliferative lesions Intestinal adenomas and polyps Apc knockouts or Mins are animal models for colonic neoplasms in humans 41 Mesentery Fat necrosis Multifocal mesenteric fat necrosis May result from pancreatitis or a choline‐ deficient diet. 42 Colon Transmissible colonic hyperplasia Diffuse colonic mucosal hyperplasia Used to be only Citrobacter rodentium, now need to consider Helicobacter, E.coli, and some transgenics. 5 43 Colon Pinworms Diffuse catarrhal colitis Syphacia obvelata and Aspicularis tetrapteris. Direct life cycle, rarely clinical. 44 Rectum Rectal prolapse Rectal prolapse C. rodentium, atypical lactose‐fermenting E. coli, Helicobacter sp., pinworms. 45 HEPATOBILARY SYSTEM 46 Skin Icterus Icterus R/o hepatic disease, intravascular hemolysis 47 Liver Mouse hepatitis virus Multifocal to coalescing hepatic necrosis This used to be the scourge of nude mouse colonies. Also look in spleen, lymph nodes, bone marrow, and necrosis of pulmonary endothelium. 48 Liver Tyzzer’s disease Multifocal to coalescing hepatic necrosis Starts in the colon and goes up portal vein to liver. Need to rule out all of the other causes of hepatic necrosis since they all look alike! 49 Liver Salmonellosis Multifocal to coalescing necrosuppurative hepatitis In rodents, salmonella affects the liver, spleen and lymph nodes more than the intestinal tract. 50 Liver Cestodiasis Multiple intrahepatic and abdominal cysticerci Taenia taeniaformis – careful of cats getting into your colony or feed. 51 Liver Hepatic cysts Multiple hepatic cysts 52 Liver Histiocytic sarcoma Hepatic histiocytic sarcoma 6 Morphologically looks very much like lymphoma – look for hyaline droplets in the kidney, lesion in the uterus, or increased EMH. 53 Liver Hepatoma Hepatoma May be seen spontaneously in old mice, but also may be induced by Helicobacter and carcinogens. 54 Liver Hepatic carcinoma Hepatic carcinoma May be seen in association with Helicobacter hepaticus. More common in males. 55 INTEGUMENTARY SYSTEM 56 Eyelids Periocular dermatitis Bilateral suppurative blepharoconjunctivitis BALB/c, 129, and J crosses predisposed. R/O C. kutscheri, Staph, Strep, Streptobacillus, Pasteurella pneumotropica, Pseudomonas 57 Facial skin Botryomycosis Multifocal to coalescing pyogranulomatous dermatitis with Splendor‐ Hoeppli material Botryomycosis is a disfiguring skin condition which may result from cutaneous infection by Staph aureus, Staph xylosus, or Pseudomonas aeruginosa. 58 Feet Bacterial pododermatitis Focally extensive chronic suppurative pododermatitis Due to Staphylococcus infection. 59 Skin Ulcerative dermatitis of B6 mice Multifocal necrotizing dermatitis Multifactorial cause including strain predisposition, sensitivity to ectoparasites, secondary bacterial infection, and vasculitis. 60 61 Skin Coryneform‐associated hyperkeratosis Diffuse hyperkeratotic dermatitis This is a problem in nude mice. C. bovis is lipophilic and grows well in the keratin crust. 7 62 63 64 Feet, tail Mousepox Focally extensive gangrenous pododermatitis Diffuse necrohemorrhagic enteritis Diffuse fibrinonecrotic enteritis The ectromelia virus, which causes mousepox, is a systemic disease which often results in amputation of extremities and the tail. Also look for splenic fibrosis in survivors. Intracytoplasmic inclusions are prominent. 65 Tail Ringtail Multifocal annular cutaneous necrosis of the tail Ringtail is usually caused by a combination of high temperatures and low humidity, but must rule out strangulation by cotton nesting material. 66 Skin Cagemate trauma Multiple traumatic bite wounds Usually seen when cage adult males caged together. DBA, Swiss, Balb/C’s predisposed. 67 Pelage Barbering Focally extensive traumatic alopecia Barbering is usually done by a dominant female who doesn’t have any hair loss. Loss of whiskers is very humiliating as they are important to mice. Barbering has been implicated in a number of cases of barbering. 68 69 Skin Ectoparasite hypersensitivity Focal dorsal cervical ulcerative dermatitis. Fur mites, including Myobia and Myocoptes are most often implicated. Make sure it is not cagemate trauma. 70 Pelage Pediculosis Diffuse pelagic pediculosis Polyplax serrate is uncommon; used to transmit Mycoplasma coccoides 8 71 Skin and subcutis Anasarca Anasarca Usually the result of renal disease. 72 Skin Rhino mouse mutation Diffuse alopecia and follicular dyskeratosis Spontaneous hairless mutation which also are immunodeficient. 73 Haired skin Cutaneous papillomas Multiple cutaneous papillomas TgAC mice with Ras mutation, also numerous carcinogens like TPA. 74 Haired skin of tail Neural crest tumor Neural crest tumor Seen in the tail skin and pinnae of FVB mice 75 Subcutis Xenotransplantation Transplanted sarcoma line Nude mice are extensively used for tumor transplantation. 76 ENDOCRINE SYSTEM 77 78 Pituitary gland Pituitary adenoma Pituitary adenoma Far lower incidence than in the rat, female B6 are most common. Tumors are prolactin+, arise in the pars distalis and often compresses the brain. 79 Thyroid gland Bilateral thyroid carcinomas Bilateral thyroid carcinomas Ret/PTC1 transgenic mouse, and there are other models. 80 URINARY SYSTEM 81 Kidneys Amyloidosis Bilateral renal amyloidosis Common in older mice and mice with lymphoma. AA amyloid – also seen in intestine and many other organs. Look for atrial thrombosis and ascites. 82 Urinary bladder Mouse urologic syndrome Urinary outflow obstruction MUS is a form of obstructive uropathy due to retention of ejaculated coagulum in the urethra. B6 and ICR mice are 9 predisposed. 83 Kidney Hydronephrosis Unilateral hydronephrosis R/O Uroliths, transitional cell neoplasm, chronic urogenital inflammation. Congenital in the B6. 84 Urinary bladder Urolithiasis Cystic urolithiasis In various strains of mice, oxalate, phosphate, cysteine, and struvite uroliths have been reported. Cystic urolithiasis, suppurative pyelonephritis, and hydronephrosis This case caused by infectious with Proteus mirabilis. Proteinuric mice have increased incidence in that the protein serves as organic matrix as a nidus for stone formation. 85 NERVOUS SYSTEM 86 87 88 Cranium 89 90 Cerebrum Meningocele Hydrocephalus Meningocele/ meningoencephalocele Focally extensive internal hydrocephalus Relatively common in C57Bl – affected mice nurse, but die soon after Diffuse mild hepatic capsule mesothelial hyperplasia 91 Periorbital tissues Retro‐orbital abscess Focally extensive suppurative orbital cellulitis Retro‐orbital bleeds are not only brutal and unnecessary, they may also be dirty. 92 Globe Corneal ulceration Focally extensive corneal ulcer and exophthalmos Most often seen as a result of high levels of environmental ammonia or post‐anesthetic. 93 Globe Cataract Bilateral cataracts Previously done with 10 94 hyperbaric oxygen or radiation; now transgenic models. REPRODUCTIVE SYSTEM 95 Ovary Ovarian cysts Bilateral cystic rete ovarii Very common in aged mice, C3H and MRL predisposed. 96 Ovary Teratoma Ovarian teratoma Rare except in LT/Sv strains. 97 Testis Testicular teratomas Common in strain 129 mice – 10% in 3 weeks, 95% in homozygotes. 98 Uterus Cystic endometrial hyperplasia Diffuse cystic endometrial hyperplasia with ovarian cyst Very common in aged mice and not often associated with bacterial infection. 99 Uterus, vagina Imperforate vagina Imperforate vagina with diffuse hydrometra Congenital problem in BALB/C, B6 and DBA. 100 Uterus Pyometra Multifocal segmental suppurative endometritis Possible causes include M. pulmonis, K. oxytoca, P. multocida. May be complicated by imperforate vagina. 101 Vagina Vaginal prolapse Vaginal prolapse Usually due to dystocia. 102 Mammary gland Mammary hyperplasia Diffuse mammary hyperplasia Most often the result of prolactin‐secreting lesions in the pituitary. Multiparous FVB/N females may develop this without pituitary lesions. 103 104 Mammary gland Mammary adenocarcinoma Mammary adenocarcinoma Note the ulceration. Mammary ACs in the mouse may be due to mouse mammary tumor retrovirus, carcinogens, and various sex 11 hormones. 105 Prepuce, rectum Preputial abscess Rectal prolapse, preputial abscess and paraphimosis S. aureus is a common cause of preputial abscesses in C57BL mice. 106 Seminal vesicles Seminal vesiculitis Unilateral seminal dilation and unilateral vesicular atrophy Aged B6 males may develop dilatation or atrophy or both. Seminal vesiculitis may result in abdominal distention. 107 Bulbourethral glands Cystic bulbourethral glands Bilateral cystic bulbourethral glands Theses glands contribute to the formation of the copulatory plug. May be complicated by bacterial infection as well. 108 Urogenital tract True hermaphrodite True hermaphrodite This is an unusual presentation of the hermaphrodite – testis and epididymis on one site, ovary and uterus on the other. 109 MUSCULOSKELETAL SYSTEM 110 Tibiotarsal joints Infectious arthritis Bilateral suppurative tibiotarsal arthritis 111 Spinal column Vertebral osteosarcoma Focal vertebral osteosarcoma with compression of subjacent spinal cord. 112 DISEASES OF RATS 113 CARDIOVASCULAR SYSTEM 114 Mesenteric arteries 115 Abdominal viscera in situ Polyarteritis nodosa R/O C. kutscheri, S. moniliformis, M. pulmonis Most common in males Multifocal to coalescing necrotizing and proliferative and hypertensive rats. Has been pretty much mesenteric arteritis bred out of most colonies. Multifocal to coalescing necrotizing and proliferative mesenteric arteritis with 12 hemoabdomen. 116 117 118 119 RESPIRATORY SYSTEM Lung Chronic pulmonary mycoplasmosis Multifocal to coalescing suppurative bronchopneumonia with bronchiectasis Far less common today than used to be. Infections are potentiated by concurrent viral disease and high environmental pneumonia. R/O CAR bacillus, C. kutscheri 120 Lung Corynebacterium kutscheri Multifocal to coalescing necrosuppurative pneumonia C. kutscheri is a latent organism that results in abscesses in numerous organs. In the lung, they are distributed throughout all lobes; bronchiectasis is not a feature. 121 Thorax Streptococcus pneumonia Diffuse fibrinous pleuropneumonia When you see this much fibrin in lab animals, at least think Strep for a moment. Similar lesions in man, NHPs and guinea pigs. 122 Lung Interstitial pneumonia Diffuse interstitial pneumonia Not a specific entity, so consider Sendai virus, pneumonia virus of mice, rat coronavirus, and Pneumocystis. 123 Lung Pneumocystis muris Diffuse granulomatous interstitial pneumonia Recently identified as the cause of rat respiratory virus. 124 Thoracic cavity Chylothorax Chylothorax 125 HEMATOLYMPHATIC SYSTEM 13 126 Liver, spleen Large granular leukemia 127 Hepatic and splenic lymphoma Classic disease of F344s, results in blastic lymphocytes in all organs. Blood leukocytes can exceed 350,000! GASTROINTESTINAL SYSTEM 128 Teeth Malocclusion Malocclusion Hypsodont teeth grown continuously. 129 Salivary gland Rat coronavirus (sialodacryoadenitis virus) Focally extensive sialoadenitis and porphyria 130 Lacrimal gland Ocular lesions result from damage to the Harderian gland and porphyria. In glandular tissue, necrosis and edema is centered on ducts. Watch out for pulmonary lesions as it is a coronavirus….. Dacryorrhea 131 Salivary gland Diffuse necrotizing sialoadenitis with edema 132 Small intestine Infectious diarrhea of infant rats Diffuse superficial necrotizing enteritis with villar atrophy Villar atrophy result sin mild curd in the proximal intestine. Look for syncytia in enterocytes. E. faeciumdurans results in a similar gross picture. 133 Stomach Gastric adenocarcinoma Gastric adenocarcinoma Causes include carcinogens (MNNG) and duodenal reflux. 134 HEPTOBILIARY SYSTEM 135 Liver 136 Liver Tyzzer’s disease Multifocal necrotizing hepatitis R/O include C. piliforme, S. typhimurium, S. enteritidis and other gram negatives. Multifocal necrotizing hepatitis and myocarditis Look for lesions in the intestine, liver, and heart in terminal cases. Ileal dilatation may be the gross lesion in the intestine. 14 137 Liver Cysticercus taeniaformis Multiple hepatic cysticerci The pathogenesis in the rat is unusual in that hepatic sarcomas may be a long‐term sequel. 138 Liver Hepatic neoplasia Hepatic histiocytic sarcoma Lots of ruleouts: lymphoma, fibrosarcoma, and abscesses due to C. kutscheri, S. pneumonia, K. pneumonia and P. aeruginosa. INTEGUMENTARY SYSTEM 139 140 Haired skin Ulcerative dermatitis Bilateral acute ulcerative and suppurative dermatitis This condition usually starts with trauma, and is complicated by S. aureus. 141 Skin, tail Ringtail Multifocal annular necrotizing caudal dermatitis Similar to mice – genetics, hydration, and nutritional status also hypothesized to play a role 142 Ear pinna Auricular chondritis Bilaterally symmetrical granulomatous auricular chondritis Presumed to be immune‐ mediated as affects strains like SD and Wistar, but also seen in association with metal implants. 143 Zymbal’s gland Zymbal’s gland neoplasm Zymbal’s gland tumor Most are benign, but they do look ugly. The histology will be a mixed squamous sebaceous tumor… 144 Haired skin Squamous cell carcinoma Squamous cell carcinoma A number of carcinogens can be painted on the skin (azo dyes, anthracene), and are rarely spontaneous. 145 Subcutis Hemangiosarcoma Multiple subcutaneous hemangiosarcoma May be induced by chemicals or genetic manipulation. Usually 15 visceral in origin. 146 Subcutis Subcutaneous emphysema 147 148 149 Diffuse subcutaneous emphysema Possible airway trauma. Looks like a hedgehog to me. ENDOCRINE SYSTEM Pituitary gland Pituitary gland adenoma Pituitary gland adenoma Prolactin‐secreting chromophobe tumors of the pars distalis. 150 Thyroid Thyroid adenoma Unilateral thyroid adenoma May be a genetic manipulated model (aren’t they all?!) or induced by simvastatin. 151 Pancreas Islet cell tumor Pancreatic islet cell tumor Can be induced in the rat with pyrollizzidine alkaloids. Look for hypoglycemia 152 Adrenal medulla Pheochromocytoma Adrenal pheochromocytoma Common neoplasm in certain strains of rats; complex pheochromocytomas also contain neurons. 153 URINARY SYSTEM 154 Kidney Chronic progressive nephropathy Diffuse renal glomerulonephritis This is a very well=known condition in inbred strains of rats, and lesions may appear as early as 3 months. When you see a golden color to kidneys, think glomerulonephritis (except in cats, which have a lot of lipid in their tubules) 155 Kidney Corynebacterium kutscheri Multifocal suppurative embolic nephritis During stress or immunosuppression, abscesses will be seen in 16 multiple organs. 156 Urinary bladder Urolithiasis Usually associated with urinary calculi in the rat. Diffuse proliferative cystitis with struvite uroliths Ammonium magnesium phosphate, carbonate and oxalate are common. Don’t confuse with agonal copulatory plugs. 157 158 159 160 Diffuse hemorrhagic cystitis NERVOUS SYSTEM Brain Kilham rat parvovirus Multifocal cerebral and cerebellar hemorrhage and malacia 161 162 Inner ear Eye This virus attacks endothelium, resulting in thrombosis and infarction. It can also result in cerebellar hypoplasia following in utero infection. Otitis media Bilateral suppurative otitis media Possible etiologies ‐ Mycoplasma pulmonis, CAR bacillus,P. pneumo‐ tropica, P.aeruginosa Hyphema and exophthalmos Hyphema Usually traumatic, but may be associated with sialodacryoadenitis and corneal injury. 163 Harderian gland Rat coronavirus Unilateral harderian gland necrosis May result in exophthalmos dacryorrhea, and corneal ulceration. 164 Eyes Cataracts Bilateral lenticular cataracts ICR (inherited cataract rat) is an animal model. 165 REPRODUCTIVE SYSTEM 166 Uterus Pyometra Diffuse suppurative endometritis Mycoplasma pulmonis 167 Mammary gland Mammary Mammary fibroadenoma Extremely common in the rat. Large firm, usually 17 fibroadenoma 168 169 Scrotum non‐ulcerate mass – can be anywhere on the body except maybe on top of the middle of the head…. Kilham rat parvovirus Multifocal scrotal dermal hemorrhage KRV is endotheliotropic. Scrotal and testicular hemorrhage is a classic lesion. 170 Preputial adenocarcinoma Preputial gland adenocarcinoma Preputial gland adenocarcinoma This neoplasm of apocrine glands can also be seen arising from the clitoral gland in the female rat. 171 Prostate gland Prostatitis Diffuse suppurative prostatitis There is an E‐coli induced model of bacterial prostatitis. 172 173 Testis Interstitial cell tumor Testicular interstitial cell tumor Do know what this looks like with the tunics intact, and on opened testis (2nd slide). This is a very common neoplasm in inbred rat strains. 174 Peritoneum Mesothelioma Peritoneal mesothelioma 175 Testis Mesothelioma are common neoplasms in the rat. In the testis, look for the concurrent ICT. Testicular mesothelioma 176 DISEASES OF GUINEA PIGS 177 Skin, pinna Acromelanism Acromelanism 178 Plantar aspect of feet 179 Teats Normal GPs have two paired conical inguinal nipples 180 Vesicular glands Normal Male GPs have extremely large vesicular glands. 181 Penis Normal The end of the penis has to horny “styles” on either 18 side of the urethra. 182 Vulva Vaginal closure membrane Like other hystricomorphs, females have a vaginal closure membrane which is perforated only at estrus and parturition. 183 Presentation Pregnancy Sows can more than double their weight during pregnancy – infants are large and precocious. 184 Lung Bordetella bronchiseptica Multifocal to coalescing suppurative bronchopneumonia B. bronchoseptica is one of the most important GP pathogens. Due to its predilection for ciliated epithelium, it causes classic bronchopneumonia and may be also recovered from the tympanic bulla and uterus. 185 Lung, heart Streptococcus pneumonia Diffuse severe fibrinosuppurative pleuropneumonia and fibrinous pericarditis When you see this amount of fibrin, think Strep. Suppurative lesions in multiple organs and fibrinosuppurative exudates in body cavities are characteristic. High mortality may be seen in outbreaks. 186 Lungs Adenoviral pneumonia Bilaterally symmetrical necrotizing bronchitis and bronchiolitis Bronchopneumonia and patchy consolidation of lobules are the result of plugging of airways with necrotic epithelium. 187 Heart Rhabdomyoma Focally extensive cardiac muscle glycogenosis Grey‐white foci throughout the heart, primary in the right ventricle. The condition is currently thought to be a 19 glycogen metabolism disorder 188 Aorta Aortic mineralization 189 Heart Metastatic calcification 190 Cheek teeth Malocclusion Malocclusion of cheek teeth Normal growth of cheek with lingual entrapment teeth in guinea pigs results in lingual spur formation in the mandible, and buccal spurs in the maxilla. 191 Facial skin “Slobbers” Moist facial dermatitis “Slobbers” is a result of malocclusion in rodents and lagomorphs. 192 Stomach Bloat Diffuse gastric dilatation Gastric dilatation and volvulus are occasionally seen as a sporadic finding; predisposing factors have not been identified. 193 Intestine Intussusception Focal jejunal intussusception 194 Intestine Cryptosporidium wrairi Diffuse catarrhal and hyperplastic enteritis 195 Anus Fecal impaction 196 Liver Salmonellosis Focally extensive aortic mineralization Metastatic calcification is a common finding in older guinea pigs, and maybe worsened by diets with low magnesium, high calcium, and high phosphorus diets. Young guinea pigs less than 6 months manifest disease with ill thrift, weight loss, and diarrheic feces. Seen in geriatrics due to loss of muscle tone or impaired cecotrophy. Multifocal to coalescing necrotizing and granulomatous hepatitis 20 Remember that in lab rodents, Salmonella is more common as foci of 197 Spleen Multifocal to coalescing necrotizing and granulomatous hepatitis 198 Liver Idiopathic hepatic necrosis Multifocal to coalescing An occasional finding in hepatic coagulative necrosis guinea pigs, terminal blood flow changes in the liver are postulated to be the cause. 199 Cervical lymph node Cervical lymphadenitis Focally extensive suppurative cervical lymphadenitis Cervical lymph nodes are a characteristic location for abscesses due to S. zooepidemicus (Lancefield Group C). Inoculation is usually the result of oral abrasions with contamination. Most guinea pigs harbor the organism in the nasopharynx. 200 Cervical lymph nodes Cavian leukemia Cervical node lymphoma Massive numbers of lymphoblasts within circulating blood and infiltrating numerous organs. Both type C retrovirus particles have been seen in the disease, and it has been transmitted by transplanted cells and cell‐free extracts. 201 Liver 202 Stifles Hypovitaminosis C (scurvy) Bilateral periarticular hemorrhage 203 Costochondral junction Streptococcus equi Diffuse costochondral osteodystrophy Hepatic lymphoma 21 necrosis in the liver and spleen than enteritis. It looks like a typical gram‐ negative sepsis. Vitamin C is a cofactor for lysyl and proline hydroxylases, a requirement of the proper cross‐linking of Type I and IV collagen. Deficiency results in mineralized abnormal cartilage that cannot be remodeled and converted to bone. Deficient type IV collagen results in increased capillary fragility. Other lesions include odontoblastic defects, decreased cholesterol metabolism, decreased resistance to bacterial infections, and aberrations in amino acids. 204 Hind feet Ulcerative pododermatitis Bilateral chronic suppurative pododermatitis “Bumblefoot”, is a common problem in guinea pigs associated with wire cages, poor sanitation, and obesity. The infection is often due to coagulase‐positive S. aureus and severe cases may be associated with systemic amyloidosis. 205 Face Sarcoptic mange Focally extensive ulcerative and eosinophilic dermatitis Trixacarus caviae, the sarcoptid mite of the guinea pig causes intense pruritus and crusting excoriations over the body. Hematologic signs may be seen, and severe pruritus may result in seizures. 206 Hair Pediculosis Diffuse pelagic pediculosis Gliricola porcelli and G. ovalis are large common lice that are often seen in guinea pigs. 207 Face Dermatophytosis Focally extensive proliferative and hyperkeratotic dermatitis Usually due to T. mentagrophytes, dermatophytosis is common in guinea pig colonies (although most 22 animals are asymptomatic. 208 Abdomen Telogen effluvium 209 Haired skin Trichofolliculoma Diffuse alopecia Telogen effluvium can occur in a number of conditions, especially pregnancy, weaning, or other stressful conditions. Trichofolliculoma is the most common skin neoplasm of gps, is invariable benign, and differentiates toward all three segments of the hair follicle. 210 Perineum Urine scald Focally extensive perineal exfoliative dermatitis Urine scald in any pet rodents or lagomorphs suggests poor husbandry/sanitation. 211 Eye Guinea pig inclusion conjunctivitis Focally extensive suppurative conjunctivitis Usually seen in gps from 4‐8 weeks, GPIC (due to C. psittaci )is usually a self‐ limiting disease. Other syndromes, such as pneumonia or abortions have been reported. 212 Eye “Pea eye” Unilateral prolapse of the third eyelid The third eyelid is prolapsed as a result of swelling of the lachrymal gland and/or local fatty tissue. Lethal white Multiple defects 25% of the offspring of roan or Dalmatian guinea pigs are homozygous for the roan allele, resulting in a constellation of birth defects including white coloration, microopthalmia, deafness, malocclusion, 213 Presentation 23 malabsorption, and a poor immune system. 214 Inner ear Otitis media Torticollis Otitis media is common ‐ S pneumoniae, Bordetella, S. zooepidemicus, Pseudomonas. Always crack bulla at necropsy. 215 Ovaries Cystic rete ovarii Bilateral ovarian cysts Cystic rete ovarii are associated with decreased reproductive performance in sows aged 1.5 years or older. 216 Uterus Bordetella bronchiseptica Diffuse chronic and suppurative endometritis B. bronchiseptica is occasionally isolated from the uterine tract, and during outbreak, pregnant sows may abort or deliver stillborn. 217 Uterus Mucometra Mucometra Mucometra, hydrometra, and cystic endometrial hyperplasia have all been reported in association with cystic rete ovarii. 218 219 Kidney Segmental nephrosclerosis Multifocal to coalescing fibrosing interstitial nephritis GPs have a characteristic pattern of segmental fibrosis which parallels chronic progressive renal disease in other species. Note the very large size of the adrenal gland in the GP. In segmental nephrosclerosis, the glomeruli are largely spared. 220 Kidney Polycystic kidney Multiple renal cortical cysts 24 It happens in guinea pigs just like in other species. 221 Urinary bladder Urolithiasis 222 Fetus, presentation Anasarca 223 Multiple cystic calculi Cystic calculi are seen in older sows, and chronic bacterial UTIs are considered a major predisposing cause. Dystocia is a common problem in gps due to the large size at births. DISEASES OF HAMSTERS 224 Presentation Syrian or Golden Hamster 225 Presentation Chinese or gray hamster 226 Cheek pouches Normal 227 Hip glands Normal 228 Presentation Diarrhea 229 Ileum Lawsonia intracellulare Most Golden Hamsters today originated from the same litter captured in Syria in 1930, resulting in a low number of MHC genes due to extensive inbreeding. Cheek pouches are highly distensible and an anatomically privileged site. Sebaceous glands used for scent marking. “Wet tail” is a commonly abused term for a variety of bacterial causes of enteritis in this species. Diffuse proliferative ileitis 25 The classic cause of “wet‐ tail” in this species, L. intracellulare results is epizootics in younger animals, primarily weanlings, with resistance occurring about 10‐12 weeks. Environmental changes can result in disease in older animals. In outbreaks, morbidity of 60% and mortality of 90% is expected. 230 Small intestine Helicobacter pylori Diffuse proliferative ileitis A range of Helicobacter species have been identified in hamsters, and they can also be infected with H. pylori. Gastritis and intestinal metaplasia have been identified in hamsters infected with H. aurati. 231 Cecum Giardia muris Chronic lymphoplasmacytic typhlocolitis Giardiasis in hamsters are usually asymptomatic, but some animals develop marked distention, both acute and gaseous and chronic with marked mural thickening. 232 Intestine Clostridium difficile Focally extensive transmural Clostridial infections in necrotizing enteritis this species are associated with antibiotic administration. Administration of –mycins and –cillins will precipitate overgrowth with C. difficile, toxin production, and death. 233 Liver Clostridium piliforme Multifocal to coalescing necrotizing hepatitis Epizootics of Tyzzer’ disease, primarily in weanlings, may occur following environmental changes. Clostridial spores persist for up to 2 years in the environment. 234 Small intestine Rodentolepis nana Segmental catarrhal enteritis R. nana infections are common but asymptomatic, and the life cycle is a direct one. Focally extensive rectal prolapsed and exenteration This sequel to the multiple forms of “wet‐tail” in this 235 236 Rectum Rectal prolapse 26 species is not uncommon. Pick one. 237 Liver, accessory sex glands Polycystic disease Multiple hepatic, intestinal, and peritesticular cysts Considered to be on congenital origin, liver cysts (generally of biliary origin) are often accompanied by cysts in the gonads, accessory sex glands, and pancreas. 236 Liver Amyloidosis Diffuse hepatic amyloidosis 237 Kidney 238 Kidney Amyloidosis is a common cause of renal insufficiency and mortality in older hamsters, but may be seen as early as 5 mos. Affected livers have a prominent lobular pattern, and in the kidney, deposition being in the glomerulus. Diffuse renal amyloidosis Don’t confuse single renal cysts (incidental) with PKD. 239 240 Left atrium Atrial thrombosis Focally extensive atrial thrombosis Atrial thrombosis is often associated with amyloidosis, although cardiac insufficiency may also play a role. Changes also occur in coag and fibrinolytic parameters in affected animals. May be seen in up to 33% in some colonies. 241 Presentation Anasarca Anasarca Usually secondary to chronic renal disease and proteinuria. 242 Kidneys Nephrosclerosis Diffuse bilateral chronic progressive nephropathy. Very similar to that seen in rats, it is a common cause of disease in mortality in older 27 hamsters, and may confound chronic renal research protocols in this species. 243 Ovary Paraovarian cysts This finding is occasionally seen in hamsters. 244 Uterus Pyometra Diffuse hemorrhagic and necrotizing endometritis This one was P multocida. 245 Brain Spontaneous hemorrhagic necrosis of the CNS Focally extensive liquefactive cerebral necrosis This condition has been seen in third trimester fetuses and newborn hamsters and is reproduced by feeding dams a vitamin E‐deficient diet. Most affected pups are cannibalized. 246 Liver, mesenteric lymph nodes Hamster papovavirus‐ associated lymphoma Hepatic lymphoma Hamster papovavirus is the agent of transmissible lymphoma, which primarily causes epizootics within naïve colonies. Enzootic infections of colonies require slaughter to rid the colony of the virus. 247 Haired skin Hamster papovavirus‐ associated trichoepithelioma Cutaneous trichoepitheliomas Caused by the same virus as transmissible lymphoma, this form is more commonly seen in infected adults, and tumors do contain infectious virus (although it is likely not necessary for transmission.) These tumors are only seen in association with virus. 248 Haired skin Demodicosis Diffuse hyperkeratotic and proliferative dermatitis D. auratus and D. criceti occur naturally in the Syrian hamsters. Infection 28 is common, and lesions are rarely seen except in older animals. 249 Haired skin Demodicosis Diffuse hyperkeratotic and proliferative dermatitis 250 Presentation Mongolian gerbil Mongolian gerbils are the most common type of gerbil used in research today. Additional types include jirds, sand rats, and antelope rats. Gerbils are diurnal and won’t bite you like hamsters. 251 Presentation Gerbils All sorts of pretty colors. The agouti pattern is the standard color. 252 Presentation Fat sand rat Psamommys obesus, the fat sand rat is gaining in popularity due to a predilection to develop diabetes mellitus on normal rodent chows, and its extremely efficient kidney function. 253 Ventral abdomen Ventral marking gland The ventral marking gland of male gerbils is a modified sebaceous gland, and a site for cutaneous neoplasia. 29 D. auratus and D. criceti occur naturally in the Syrian hamsters. Infection is common, and lesions are rarely seen except in older animals. 254 Adrenal glands 255 Presentation Gerbil pups 256 Nasal planum “Sorenose” 257 258 Tail Presentation Gerbils have extremely large adrenal glands (up to 4x that of other species.) Pups are not precocious, and eyes do not open until around 3 weeks – at which time they may be weaned. Distressed mothers will cannibalize young.. Focally extensive ulcerative nasal dermatitis Sorenose is a common problem in gerbils. When not groomed, porphyrin pigments from the nasolacrimal duct accumulate and irritate the nasal skin. This area is commonly infected by S. aureus as a sequel. “Tail slip” Gerbils should not be picked up by the tail. Tail slip is a degloving injury which is used to escape predators. Epilepsy Epileptiform seizures are common among Mongolian gerbils under stress. Up to 40% are afflicted with the condition, and lines with high incidence are sought after for research purposes. No histologic lesions have been reported. 30 259 Middle ear Aural cholesteatoma 260 Presentation 261 Liver Clostridium piliforme Multifocal to coalescing necrotizing hepatitis Mongolian gerbils are very susceptible to the disease, and are often used as a sentinel to detect the presence of C. piliforme in the research facility. 262 Liver Salmonella enteritidis Multifocal to coalescing pyogranulomatous hepatitis Fatal salmonellosis may be seen as epizootic in weanlings with evidence of paratyphoid nodules, enteritis, and septicemia. 263 Haired skin Ventral marking gland carcinoma Ventral marking gland carcinoma These neoplasms are consistent with squamous cell carcinomas. 264 Ovary Granulosa cell tumor Ovarian granulose cell tumor This is one of the most common neoplasms in gerbils 265 Eye Up to 50% of gerbils over 2 years of age have aural cholesteatomas. These are masses of keratinizing epithelium which arise from the external surface of the eardrum and external auditory canal. Compression can result in destruction of the temporal bone and inner ear structures. Head tilt is a common presenting sign of aural cholesteatoma. Cataracts 266 267 Aural cholesterol granuloma Yeah, they get them. DISEASES OF RABBITS Presentation Normal Oryctolagus cuniculi 31 Oryctolagus cuniculi is the progenitor type for today’s lab rabbit. 268 Lepus europaeus The Common hare of Europe was introduced into North America in the nineteenth century. 269 New Zealand White Originally bred for meat and fur quality, albinistic NZWs are the most commonly used rabbits in laboratories today 270 Lop‐eared rabbit Lops, known for their floppy ears, are among the oldest breeds of domesticated rabbits. 271 Dwarf rabbit Not to be confused with wild pygmy rabbits, dwarf rabbits are much smaller than European rabbits, but may interbreed with them. 272 Dutch rabbit 273 Angora rabbit Another older domesticated breed which is sheared or plucked for its fur. 274 Watenabe rabbit An inbred strain which, due to a single‐gene mutation, exhibits hypercholesterolemia, elevated plasma LDLs, and severe atherosclerosis. 275 Rabbit kits Kits are kindled into a fur nest, where they live for 3 weeks. Does nurse once daily, and will kill kits from other does. 32 276 Normal GI tract GI tract with cecum, appendix, and sacculus rotundus The sacculus rotundus (a.k.a. the “cecal tonsil) is a dilated antrum to the cecum which has abundant lymphoid tissue. The cecum contains about 40% of the total volume of the GI tract. There is also a long appendix off of the tail of the cecum. 277 Cecotrophs 278 Urinary bladder Ammonium magnesium phosphate, calcium carbonate monohydrate, and anhydrous calcium carbonate Urine crystals are found in large amounts in rabbit urine and should not be interpreted as a pathologic change. Approximately 45‐60% of calcium is excreted in the urine. 279 Uterus Bicornuate uterus The left and right uterus are separate for their entire length, uniting to form the vagina. 280 Incisor teeth “Peg teeth” Rabbits possess a pair of secondary incisors, located behind the primary set, known as “peg teeth”. All lagomorphs are equipped with peg teeth. Cecotrophs are mucus‐ covered feces passed at night and are rich in B vitamins and proteins. Cecotrophy is controlled by the adrenal glands, and may be altered during periods of excessive stress. 33 281 282 RESPIRATORY SYSTEM Presentation Pasteurella multocida Bilateral mucupurulent “Snuffles” is the most common rhinitis with mild head presentation of pasteurellosis, tilt with up to 70% of animals affected in some colonies. Direct contact is required for animal‐to‐animal transmission. 283 Torticollis Torticollis is seen when the inflammatory process extends to the inner ear. In affected colonies, otitis media ranges up to 33%, while torticollis rarely hit 5%. Other nervous diseases may also result in torticollis. 284 “Sleepy bunny” P. multocida endotoxin can result in central nervous system depression in septicemic rabbits. 285 Nares Bilateral serous rhinitis Chronic rhinitis is the most common clinical manifestation of this disease. 286 Conjunctiva Focal suppurative conjunctivitis This is another common form of the disease, and culture often yields the organism. Animals with nasolacrimal duct infection may only show epiphora. 287 Lung Multifocal to coalescing fibrinous pleuritis Pneumonia is usually chronic and asymptomatic. Lesions are often sharply demarcated, and necrotizing fibrinosuppurative bronchopneumonia is the most consistent lesion. .Look for concomitant pericarditis. 288 Lung Multifocal to coalescing fibrinosuppurative Walled‐off abscesses may appear in any organ. The pus is usually viscid and difficult to 34 bronchopenumonia drain. The most common site for abscesses is the subcutnaous tissues, especially around the head, neck, and shoulders. 289 Abdominal cavity Focally extensive peritoneal abscess with fibrous peritonitis 290 Cerebrum Unilateral cerebral abscess Look for concomitant rhinitis and ophthalmitis. 291 Tympanic bulla Unilateral suppurative otitis‐media interna The tympanic bullae is not only a common site of infection, but a common site for asymptomatic animals to harbor the bacteria. Many affected animals show no clinical signs, so tympanic bullae should be routinely opened. 292 Uterus Focally extensive unilateral suppurative metritis Spread of P. multocida is usually venereal in these cases. Disease may be worse during the perinatal period. Affected bucks may have suppurative orchitis. 293 294 Nasal cavity and turbinates Diffuse turbinate osteonecrosis and atrophy It is imperative to remove the nasal bones during rabbit necropsies to examine this area. Increased numbers of osteoblasts and osteoclasts may be seen. 295 Lung Diffuse suppurative pleuropneumonia Type C S. aureus has occasionally been associated with “snuffles”. 296 Liver Multifocal embolic suppurative hepatitis The acute septicemic firm is most commonly seen in suckling kits during the first weeks of life and is associated Staphylococcus aureus 35 with high mortality 297 Kidney, heart Suppurative embolic nephritis and myocarditis Rarely, S. aureus may become septicemic in adult rabbits. 298 Heart Multifocal to coalescing vegetative valvular endocarditis This lesion may follow septicemia in an adult animal. 299 Kidney Focally extensive acute Renal infarcts are common renal infarct sequela to vegetative valuvluar endocarditis 300` Lung Bordetella bronchiseptica Diffuse fibrinosupprutive bronchopneumonia Often combined with Pastuerella in the rabbit and can be isolated from normal rabbits. 301 Lung Viral hemorrhagic disease Diffuse severe pulmonary edema with ecchymosis The lung in animals with VHD, although not the primary target, is often severely affected. Thrombosis of many pulmonary vessels is the result of DIC. 302 Lung Herpesvirus sylvilagus Pulmonary lymphoma DDx includes pulmonary granulomas due to Freund’s complete adjuvant. 303 Lung Metastatic uterine adenocarcinoma The most common neoplasm in lab rabbits, the lung is a common site of metastases. Metastatic foci often have a more prominent stroma. 304 CARDIOVASCULAR SYSTEM 305 Heart, aorta Atherosclerosis Atrial and aortic atherosclerotic plaques 306 Aorta Aortic atherosclerotic plaques 307 Eye, iris Mutiple iridal 36 The Watanabe is the animal model for familial hypercholesterolemia. Hypercholesterolemia may be induced in the NZW with dietary manipulation but research is more commonly performed in LDL‐receptor xanthomas 308 Kidney Renal xanthomas 309 Adrenal glands, cortex Adrenal atherosclerosis 310 Skin Cutaneous xanthomas 311 312 Aorta 313 Kidney Hypervitaminosis D Diffuse aortic mineralization Diffuse renal cortical mineratlization deficient Watenabe rabbits. Homozygotes have plasma cholesterol 8‐14x normal and virtually no LDL receptors on hepatocytes and fibroblasts. Improperly formulated rations with too much Vitamin D may result in medial degeneration and mineralization of major vessels, as well as basement membranes of glomerular vessels and renal tubules. HEMOLYMPHATIC SYSTEM 314 315 Kidney Malignant lymphoma Renal lymphoma Lymphoma is the most common malignancy of lab rabbits, and kidney is the most common site. H. sylvilagus is a common cause in cottontail rabbits and a retrovirus has been postulated in lab rabbits. Changes are often confined to the renal cortex. 316 Thymus Thymoma Thymoma Thymomas are uncommon neoplasms. HHM and exfoliative dermatitis have been reported as paraneoplastic syndromes. Thymic hyperplasia has also been seen in rabbits and should be considered in the differential diagnosis. 317 318 GASTROINTESTINAL SYSTEM GI tract Rapid autolysis Autopsy should be performed as quickly after death as possible. Gas production and rapid decomposition of GI organs is seen in rabbits. Take 37 care incising the abdomen in animals dead longer than 1 hour as the cecum is often expanded and pressing upwards. 319 Teeth Malocclusion Overgrown mandibular Genetic (autosomal recessive) incisors in many rabbit breeds. The mandible is abnormally long in relation to the maxilla, which results in failure of the incisors to wear normally 320 321 Tongue Oral papilloma Focal sublingual papilloma 322 Mandibular gingiva Rabbit pox Multifocal proliferative Characteristic pox lesions may and necrotizing or may not be seen. Infection is stomatitis initially respiratory, with pox lesions seen in multiple organs Multifocal proliferative following viremia. Replication and necrotizing occurs in the lymphoid organs glossitis and skin. Necrosis may be seen in the liver, lung, and spleen. Multifocal to coalescing necrotizing and proliferative pneumonia 323 Tongue 324 Lungs 325 Stomach Trichobezoar Gastric trichobezoar 38 The rabbit is the natural host for rabbit oral papillomavirus. These regressing lesions are most often seen in rabbits between 2 and 18 months and the ventral tongue is the most common spot. Viral inclusions may be seen in the stratum spongiosum “Wool block” – often associated with excessive grooming; low fiber, stress, and a sedentary may be contributing factors. Hepatic lipidosis is commonly associated with the condition. 326 Small intestine Colibacillosis Diffuse necrotizing enteritis with marked villar atrophy Attaching and effacing E. coli is a major cause of diarrhea in rabbitries and occasionally in labs. Disease is most common and severe in sucklings and weanlings which have little E.coli in their normal flora. Infected animals have profuse watery intestinal contents, villar atrophy, a heterophilic infiltrate, and numerous bacteria adherent to the mucosa. Bacteria can also be attached in the cecum and colon. Initial colonization is in the ileum. Concomitant infections with rotavirus or Coccidiosis may be a predisposing factor. Clostridium piliforme Severe dehydration and diarrhea Tyzzer’s disease is a sporadic disease characteristically associated with stressors. Subclinical infection is common, and the disease is most severe in weanlings. Lesions are seen most consistently in the liver, with the GI tract and the heart occasionally affected. Intracytoplasmic, arygyophilic bacilli are most easily demonstrated in cells at the edge of necrotic lesions. 327 Presentation 328 Liver, cecum 329 Heart 330 Liver Multifocal hepatic necrosis; multifocal necrotizing typhlitis Francisella tularensis Multifocal hepatic necrosis 39 Primarily a disease of wild rabbits. Tularemia has been reported in over 100 species of wildlife. Usually diagnosed at necropsy, necrosis is also seen in the spleen, lymph nodes, bone marrow, and rarely, intestinal lesions are seen. 333 Ileum 332 Spleen 333 Jejunum Yersinia pseudotuberculosis Multifocal to coalescing splenitis Mucoid enteropathy 334 Colon 335 Cecum Multifocal to coalescine ileal, mesenteric lymph node and cecal tonsillar necrosis Eimeria intestinalis This is a good DDX for tularemia – acute cases have a necrotizing enteritis, more chronic lesions have caseous lesions in local lymphoid tissue. Generally due to eating contaminated food. Diffuse severe catarrhal colitis The precise pathogenesis of mucoid enteropathy is yet unclear, with cecal dysbiosis as the most accepted cause. Production of lower cecal acetate levels results in production of a substance by cecal bacteria which causes goblet cell hyperplasia in the colon, and also cecum, ileum, and jejunum. The incidence of mucoid enteropathy is increased in animals on low‐ fiber diets. Diffuse necrotizing colitis with serosal hemorrhage C. spiroforme, perfringens, and difficile have all been implicated in enteritis. Any disruption of gut flora predisposes to colonization and toxin production. C. spiroforme and C. perfringens produce type E iota toxin, resulting in necrotizing typhlitis. C. difficile colonization often follows use of penicillin in rabbits. Identification of toxins is important in investigation, as bacterial overgrowth may obscure bacteria at necropsy. Diffuse necrotizing and Coccidiosis is a common heterophilic enteritis problem in rabbitries and labs, and typhlitis especially following changes in management. A number of species have been identified in 40 rabbits, with E. intestinalis and flavescens considered the most pathogenic (with up to 50% mortality in young rabbits). Coccidia are most common seen in the distal half of the intestine and cecum and may be easily identified on fecal flotations. 336 337 Mesentery 338 Liver 339 Cecum 340 Mesentery 341 Cysticercus pisiformis Multiple mesenteric cysticerci Rabbits are the intermediate host for Taenia pisiformis, whose definitive host is the dog. Cysticerci are generally round, translucent, and the scolex is visible as a white dot. Focally extensive necrotizing hepatitis; hepatic lipidosis Migration tracts of Taenia pisiformisi show up nicely against a fat‐filled liver. Passalurus ambiguous Multiple cecal pinworms P. ambiguus is a common parasite of domestic rabbits, and are usually of little significance. Occasionally, diarrhea, impaired weight gains and even death have been seen in severely parasitized animals. Mesenteric lipoma Mesenteric lipoma Occasionally seen in overweight animals. HEPATOBILIARY AND PANCREATIC SYSTEM 342 Presentation Lepine calicivirus (Viral hemorrhagic disease) Epistaxis 343 Liver Diffuse massive hepatic necrosis 344 Lung Diffuse pulmonary edema, with thrombosis and hemorrhage 41 This disease, first recognized in 1984, is now of worldwide concern. This species‐specific calicivirus usually results in explosive outbreaks with mortality highest in adult animals. Massive hepatic necrosis, as well as necrosis in the small intestine and lymph nodes is characteristic; other lesions associated with DIC may be present, with thrombosis in multiple organs. 345 346 Liver 347 Liver Eimeria steidae Pregnancy toxemia 348 This common disease of weanling rabbits decreases in incidence and with age, and adults develop immunity. Most infections are subclinical, but severely parasitize animals may have diarrhea, cachexia, and ascites. Impression smears of bile ducts or gallbladder readily yield diagnosis. Infection with E. stiedae may trigger bacterial enteritis. Diffuse severe hepatic lipidosis Obesity and fasting are predisposing causes for marked hepatic lipidosis in late gestation or the early postpartum period. Multiparous does are at risk, and the condition is rarely seen in obese non‐pregnant rabbits under stress. Metabolic acidosis and ketosis are commonly seen. Adrenocortical lipidosis may also be seen. INTEGUMENTARY SYSTEM 349 Skin 350 Myxomatosis Periocular swelling Nasal and facial swelling, congestion, hemorrhage, and ulceration Pinnal myxedema 351 352 Diffuse proliferative and lymphoplasmacytic cholangitis Haired skin Shope fibroma This leporipox‐induced disease is endemic in the rabbits in Australia, US, and Europe. Following explosive outbreaks, mortality decreases significantly due to selection fo r genetically resistant animals. Histologically, there is proliferation of large mesenchymal cells ( “myxoma cells”) with prominent intracytoplasmic in overlying hyperplastic epithelium. Other proliferative lesions of the lung and vessels, and necrosis in the spleen and lymph nodes have been described. Cutaneous (Shope) Shope fibroma is a viral‐induced 42 353 fibroma 354 Presentation Treponema panluis‐ cuniculi Focally extensive hyperkeratotic and lymphoplasmacytic vulvitis 355 Vulva 356 Nasal planum Focally extensive hyperkeratotic and lymphoplasmacytic nasal dermatitis 357 Periorbital skin Focally extensive hyperkeratotic and lymphoplasmacytic perocular dermatitis Staphylococcus aureus Multiple cutaneous abscesses 358 359 Haired skin neoplasm composed of large fibroblasts which contain intracytoplasmic eosinophilic viral inclusions. The masses, unlike the changes seen in myxomatosis, are discrete, freely movable, and do not have the mucinous stroma associated with myxomatosis. Also, inclusions in myxoma are limited to epithelial cells. Rabbit syphilis is a common venereally transmitted bacterial disease of rabbits. Histologic changes are confined to the epithelium and superficial dermis with epidermal hyperplasia, necrosis, erosions, and ulcerations with infiltration by predominantly plasma cells and lymphocytes. The diagnosis can be made by darkfield examination of skin scrapings, or the use of silver stains on tissue section Staphylococcal abscesses in adults may be seen in skin, mammary gland, genital tract and respiratory systm, while in kits, they tend to be confined to the skin as multiple suppurative raised lesions a few millimeters in diameter. Neonatal staphylococcal infections may have a high mortality rate. 360 Mammary gland Focally extensive necrotizing mastitis The area of infarction seen in this slide is characteristic of the alpha toxin seen in some strains of coagulase‐positive, type C S. aureus. 361 Haired skin, plantar aspect of Bilateral ulcerative pododermatitis ‐ Overweight males housed on unsanitary wire‐floor cages are 43 metatarsus “sore hocks” predisposed to “sore hocks”. Staphylococcus aureus is the most common isolate from these lesions. 362 Ear pinna Psoroptes cuniculi Diffuse proliferative and hyperkeratotic otitis externa Up to 10,000 mites in one ear. Foul‐smelling crusts. Often see secondary bacterial infection due to self‐trauma 363 Ear, haired skin Sarcoptes scabiei Diffuse proliferative and hyperkeratotic otitis externa Sarcoptic mange has been reported in almost every wildlife species. 364 Haired skin Chylietella parasitovorax Diffuse hyperkeratotic dermatitis Chylietid fur mites result scaliness and hyperkeratosis, but little prurutis. Infections usually occur on the neck and back, but may involve the ventral abdomen. 365 Haired skin Cuterebra Focally extensive cutaneous myiasis Not uncommon in wild rabbits. 366 Haired skin Trichophyton mentagrophytes Multifocal to coalescing proliferative and hyperkeratotic dermatitis Clinical ringworm is uncommon; lesions are seen primarily on the head and ears, with spread to the feet. Lesions are grossly and histologically consistent with that seen in other species. T. mentagrophytes is most commonly isolated, but M. canis is occasionally seen. 367 Haired skin Exfoliative dermatitis Diffuse ulcerative and hyperkeratotic dermatitis and sebaceous adenitis This idiopathic disease primarily occurs in pet rabbits, this condition results in a nonpruritic scaling and alopecia in older animals. Histologically, in addition to hyperkeratosis, there is an interface dermatitis, folliculitis and fibrosis with destruction of sebaceous glands. 368 Ear pinna Traumatic injury Group‐housed adults may engage in fighting, and bucks may become 44 Injection‐related injury 369 370 aggressive against both genders. The external genitalia and pinna are common sites for external traumas Haired skin The ear vein is a common site for administration of intravenous medications and other substances. Extravasation of caustic agents may result in sloughing of the pinna distal to the site of injection. Trichoblastoma Cutaneous trichoblastoma Trichoblastomas are the most common cutaneous neoplasm of the rabbit. The Shope cottontail papillomavirus results in cornified papillomas, generally on the head and face of cottontail rabbits. When inoculated on Oryctolagus, these papillomas have a predilrction for malignant transformation. 371 Haired skin Rabbit papillomavirus Multiple cutaneous papillomas 372 Perineum “Hutch burn” Diffuse ulcerative Hutch burn is usually the result of and heterophilic poor husbandry conditions, with perineal dermatitis maceration and excoriation of skin soiled with urine and feces. “Feeder alopecia” Focally extensive facial alopecia 373 Haired skin, face 374 375 MUSCULOSKELETAL SYSTEM Presentation Vertebral fracture Posterior paresis “Dog‐sitting” posture with urinary incontinence and soiling 376 377 Results from rubbing against wire cage; may be exacerbated by boredom. Radiograph Fracture/luxation 45 Vertebral fracture is seen as a result of improper handling coupling with the rabbit’s fragile skeleton in comparison to muscle mass. Sudden jerking of the hindlimbs may result in fracture or dislocation, most commonly at L7. Hemorrhage of the underlying psoas muscle may be seen at of L7 378 Lumbar vertebrae Fracture of L7 with psoas muscle hemorrhage 379 Presentation Proper handling technique 380 Adductor muscles, pelvis “Splayleg” 381 Presentation Tetanus 382 Splayleg is a descriptive term covering a number of distinct syndromes. This condition may be due to inherited syringomelia, hypoplasia pelvis, femoral luxation and distal foreleg curvature. Diffuse extensor rigidity This is an uncommon finding in laboratory rabbits. NERVOUS SYSTEM 383 Brain 384 Eye, lens 385 necropsy. Eye Encephalitozoon cuniculi Torticollis Lenticular cataract Congenital glaucoma Unilateral buphthalmia 46 E. cuniculi is a common parasite of domestic rabbits. This microsporidian parasite results in granulomatous inflammation in the brain, lungs, kidney, liver, and eye, and is demonstrable via Gram stains. Intrauterine infections of dwarf rabbits often results in lens infection and phacoclastic uveitis. The organism has been largely eliminated in quality laboratory suppliers. R/O Baylisascaris This disease of the NZW usually appears within the first 6 months of life. A primary form of glaucoma, there is underdevelopment of outflow channels with impaired anterior chamber drainage Due to the distensibility of the sclera in affected animals at this age, there is little evident discomfort. 386 REPRODUCTIVE SYSTEM 387 Uterus Cystic endometrial hyperplasia Diffuse cystic endometrial hyperplasia 388 Uterus Listeria monocytogenes Diffuse uterine L. monocytogenes is a gram‐ serosal ecchymosis positive bacillus with a predilection for the gravid uterus in does in advance pregnancy. Infectio nis usually characterized by abortion and sudden death, with emboic showers to the liver, spleen, and lymph nodes. Kits born to infected does have a high mortality, and the doe may become persistently infected, serving as shedders. 389 Liver 390 Uterus 391 Lung 392 Uterus Endometrial venous aneurysm Multiple endometrial venous aneurysms This hereditary condition may develop in multiparous, non‐ pregnant animals, and result in hematuria. At necropsy, clotted blood is present in the uterine lumen, and endometrial varicees are seen histologically. 393 Testes Interstitial cell tumor Unilateral testicular interstitial tumor (normal on right) Occasionally seen in bucks and the most common testicular tumor in the rabbit. 394 Multifocal to coalescing suppurative embolic hepatitis Uterine adenocarcinoma Uterine adenocarcinoma Metastatic uterine carcinoma URINARY SYSTEM 47 Uterine AC is the most common neoplasm of Oryctolagus, with an 80% incidence if does are allowed to reach 5‐6 years of age. Estrogen may play a role in development. Tumors readily explants or metastasize to lung and liver. 395 Kidney E. cuniculi Multifocal to coalescing chronic granulomatous nephritis Renal E. cuniculi infection results in characteristic pitting of the cortex, due to parenchymal loss and fibrosis. Additionally lesions seen microscopically include lymphoplasmacytic inflammation and necrosis of infected tubular epithelium. Gram‐staining the kidney may reveal the gram‐ positive, birefringent spores. 396 Kidney, pelvis and ureter Urolithiasis Multiple renal and ureteral uroliths Uroliths are not uncommon in rabbits due to the high levels of minerals in the urine – calcium carbonate and triple magnesium phosphate. Uroliths are usually poorly formed and soft. 397 Kidney Chronic interstitial nephritis Diffuse chronic lymphoplasmacytic interstitial nephritis Chronic interstitial nephritis is a common finding in older animals. Animals with severe disease may develop metastatic calcification of various tissues. 398 Kidney Renal nephroblastoma Renal nephroblastoma Can be experimentally induced with transplacental ethylnitrosoruea. Good animal model. 399 ENDOCRINE SYSTEM 400 Pituitary gland Pituitary adenoma Pitiuitary adenoma 401 Mammary gland Mammary gland hyperplasia Diffuse mammary gland hyperplasia 402 WE’RE DONE!!! 48 Prolactin‐secreting pituitary gland tumors in NZWs have been associate with mammary dysplasia. Rabbit mammary glands are particularly sensitive to prolactin.