ferret pathology last - ferret health advancement at msunormal pyloric junction ... • normal gut...

Pathology of the Pathology of the Domestic FerretDomestic Ferret

MattiMatti KiupelKiupel

Dental DiseaseDental Disease

Broken teeth Broken teeth -- rarely require treatmentrarely require treatment

Dental DiseaseDental Disease

Periodontal DiseasePeriodontal Disease

Periodontal disease Periodontal disease –– also rarely requires treatmentalso rarely requires treatment

MucocelesMucoceles

•• Occasionally seen on top of head Occasionally seen on top of head or inside mouthor inside mouth

•• Difficult to surgically correctDifficult to surgically correct

•• SquamousSquamous cell carcinoma most commoncell carcinoma most common•• Often advanced at diagnosis, radical surgical Often advanced at diagnosis, radical surgical excision is only documented cureexcision is only documented cure

•• Predilection to invade jaw bonesPredilection to invade jaw bones•• Low Low metastaticmetastatic potential, but massive tissue potential, but massive tissue destructiondestruction

•• FibrosarcomaFibrosarcoma, poor prognosis, poor prognosis

Oral Oral NeoplasiaNeoplasia

MegaesophagusMegaesophagus

•• Uncommon Uncommon diseasedisease

•• Primary Primary middlemiddle--aged aged malesmales

•• No apparent No apparent causecause

•• IntrathoracicIntrathoracicdilationdilation

•• Treat as other Treat as other domestic domestic speciesspecies

MegaesophagusMegaesophagus•• SecondarySecondaryCandidiasisCandidiasis

•• Usually develop Usually develop aspiration aspiration pneumonia or pneumonia or severe esophageal severe esophageal ulceration, ulceration, necessitating necessitating euthanasiaeuthanasia

Aspiration Aspiration PneumoniaPneumonia

Helicobacter mustelaeHelicobacter mustelae•• Ubiquitous disease Ubiquitous disease •• All ferrets infected by 2 wks of ageAll ferrets infected by 2 wks of age•• Contributes to debility in older Contributes to debility in older

ferrets (> 4 years)ferrets (> 4 years)•• 10% will show clinical signs 10% will show clinical signs

during lifetimeduring lifetime•• Gastric damage due to physical Gastric damage due to physical

destruction of gastric mucosa destruction of gastric mucosa coupled with profound coupled with profound lymphoplasmacytic inflammationlymphoplasmacytic inflammation

•• Elevated pH and Elevated pH and gastringastrin levelslevels•• Associated with gastric ulcersAssociated with gastric ulcers•• Gross lesions usually absentGross lesions usually absent•• Pinpoint ulcers in pylorusPinpoint ulcers in pylorus

Helicobacter mustelaeHelicobacter mustelae

Helicobacter mustelaeHelicobacter mustelae

Pyloric junction in 4Pyloric junction in 4--year year old ferret with old ferret with H. mustelae H. mustelae (HE, 10X)(HE, 10X)

Normal pyloric junction Normal pyloric junction in adult ferret (HE, 10X)in adult ferret (HE, 10X)

Helicobacter mustelaeHelicobacter mustelae

•• Chronic atrophic gastritisChronic atrophic gastritiswith resultant with resultant hypochlorhydriahypochlorhydria

•• Bacteria damage to Bacteria damage to mucosa via three mucosa via three mechanisms:mechanisms:

•• Direct cytotoxic effect Direct cytotoxic effect to mucus neck cellsto mucus neck cells

•• Inhibitory effect onInhibitory effect onparietal cell acid productionparietal cell acid production

•• NonNon--autoimmune inflammatory disease autoimmune inflammatory disease (lymphoplasmacytic gastritis)(lymphoplasmacytic gastritis)

Helicobacter mustelaeHelicobacter mustelae

•• Diagnosis:Diagnosis:•• Most readily made Most readily made from pyloric from pyloric biopsiesbiopsies

•• Characteristic Characteristic lympho/plasmacyticlympho/plasmacyticgastritisgastritis

•• ArgyrophilicArgyrophilicextracellularextracellular spiral spiral bacteria associated with mucus superlayer bacteria associated with mucus superlayer or within cryptsor within crypts

Gastric UlcersGastric Ulcers

•• Common in ferrets and other Common in ferrets and other mustelidsmustelids under stressfulunder stressfulconditions or with concurrent diseaseconditions or with concurrent disease

•• May be associated with May be associated with Helicobacter Helicobacter mustelaemustelae

•• Clinical signsClinical signs•• Often Often nonspecificnonspecific

•• InappetenceInappetence•• LethargyLethargy•• Tarry StoolsTarry Stools

Tarry stool (contrast with fresh blood)Tarry stool (contrast with fresh blood)

Gastric UlcersGastric Ulcers

Gastritis and Gastric UlcersGastritis and Gastric Ulcers

Inflammatory Bowel DiseaseInflammatory Bowel Disease

• Seen in many species• Not really a true disease,but an endpoint of a number of processes

• Marked mesenteric lymphadenopathy

• Clinical pathology:• Decreased Albumin• Elevated lymphocyte count

• Elevated hepatic enzymes

• Elevated lipase?

Inflammatory Bowel DiseaseInflammatory Bowel Disease

• No obvious clinical signs, may affect all ages• Two distinct types:

• Lymphocytic enteritis• Eosinophilic enteritis

• Prolonged disease course• Likely multiple causes

• Known causes:- ECE- Helicobacter

• Unknown causes• Dietary components?• Normal gut flora?

Inflammatory Bowel DiseaseInflammatory Bowel Disease

• Derangement of normal gut immune response

• Progressively increasing inflammatory response results in damage to gut lining

• Loss of villi, absorptive surface, and digestive enzymes

• Malabsorption/maldigestion

Inflammatory Bowel DiseaseInflammatory Bowel Disease

•• VillarVillar atrophy and bluntingatrophy and blunting•• Increased number of intraepithelial lymphocytesIncreased number of intraepithelial lymphocytes

•• Most severe form Most severe form •• Unknown Unknown aetiologyaetiology•• Wasting disease, young ferrets (< 14 months)Wasting disease, young ferrets (< 14 months)

EosinophilicEosinophilic EnteritisEnteritis

•• IvermectinIvermectin effective, parasitic?effective, parasitic?•• Sometimes peripheral Sometimes peripheral eosinophiliaeosinophilia, lesions in other organs, lesions in other organs•• Only Only micoscopicmicoscopic lesions: lesions: SplendoreSplendore HoeppliHoeppli material! material!

EosinophilicEosinophilic EnteritisEnteritis

Proliferative ColitisProliferative Colitis

““Cobblestone” appearance of colonCobblestone” appearance of colon

•• Sporadic disease of youngSporadic disease of youngmale ferrets male ferrets

•• Clinical signs:Clinical signs:•• Frequent, painfulFrequent, painfuldefecationdefecation

•• Frank blood or mucousFrank blood or mucousin stoolin stool

•• AnorexiaAnorexia•• Weight lossWeight loss•• Abdomen painful on Abdomen painful on palpationpalpation

•• Exacerbated by stressExacerbated by stress•• May progress to anemia,May progress to anemia,deathdeath

Proliferative ColitisProliferative ColitisLawsoniaLawsonia intracellulareintracellulare•• Affects colon only in ferretsAffects colon only in ferrets•• Grossly thickened colonGrossly thickened colon

GI ParasitesGI Parasites

GiardiaGiardia lamblialamblia in a ferretin a ferret

•• Uncommon:Uncommon:•• CoccidiaCoccidia•• GiardiaGiardia

•• Pathogen? Pathogen?

•• Nematodes Nematodes -- rarerare•• Yeasts Yeasts -- commensalcommensal

•• EimeriaEimeria furonisfuronis, E. , E. ictaluriictaluri•• Generally asymptomatic, usually minimal gross lesionsGenerally asymptomatic, usually minimal gross lesions•• May see biliary infections in kits, may be lifeMay see biliary infections in kits, may be life--threatening threatening •• May have bloody diarrhea, oral ulcers in severe casesMay have bloody diarrhea, oral ulcers in severe cases

CoccidiosisCoccidiosisSchizontsSchizonts and gametocytes and gametocytes of E. of E. furonisfuronis

Villar blunting and lossVillar blunting and loss

CoccidiosisCoccidiosis

ECEECE•• “Epizootic catarrhal enteritis”“Epizootic catarrhal enteritis”•• High morbidity, low mortalityHigh morbidity, low mortality•• Asymptomatic carriers, oftenAsymptomatic carriers, oftenpet store kitspet store kits

•• Older animals more severely Older animals more severely affectedaffected

•• Prolonged shedding of virusProlonged shedding of virus

Ferret Enteric Ferret Enteric CoronavirusCoronavirus

•• CoronavirusCoronavirusparticles asparticles asviewed in viewed in cells and cells and feces by TEMfeces by TEM

ECEECE

•• Viral infection of Viral infection of villarvillar tipstips•• Necrosis of cellsNecrosis of cells•• Loss of surface area and Loss of surface area and brush border enzymesbrush border enzymes

•• Passive Passive secretorysecretory diarrheadiarrhea•• MalabsorptionMalabsorption•• Mucus Mucus hypersecretionhypersecretion

Normal ferret jejunumNormal ferret jejunum

ECE with ECE with villarvillar atrophy, fusion atrophy, fusion and blunting and and blunting and lymphocyticlymphocyticenteritisenteritis

Ferret Enteric Ferret Enteric CoronavirusCoronavirus

•• Diagnosis:Diagnosis:-- Clinical signs and historyClinical signs and history-- HistologyHistology-- IHCIHC-- Clinical pathologyClinical pathologynot not specificspecific

Ferret Enteric Ferret Enteric CoronavirusCoronavirus

M 2 7 9 12 + M 2 7 9 12 + -- -- M 2 7 9 12 + M 2 7 9 12 + --FECV was detected consistently in FECV was detected consistently feces of affected ferrets from in saliva of affected ferrets from day 0 to day 26 day 0 to day 26

Ferret Enteric Ferret Enteric CoronavirusCoronavirus

Ferret Systemic Ferret Systemic CoronavirusCoronavirus

Ferret Systemic Ferret Systemic CoronavirusCoronavirus

Ferret Systemic Ferret Systemic CoronavirusCoronavirus

Ferret Systemic Ferret Systemic CoronavirusCoronavirus

Ferret Systemic Ferret Systemic CoronavirusCoronavirus

Ferret Systemic Ferret Systemic CoronavirusCoronavirus

•• PCR for corona virusPCR for corona virusyielded 650bp fragmentyielded 650bp fragment

•• Sequencing showed Sequencing showed amplified viral genome amplified viral genome was distinct from FeCoV and was distinct from FeCoV and most closely related to FECVmost closely related to FECV

•• Does this represent a new manifestation of FECV?Does this represent a new manifestation of FECV?–– Too early to tellToo early to tell–– Only small portion of genome sequencedOnly small portion of genome sequenced

•• Future directionsFuture directions–– Further characterize the virusFurther characterize the virus

•• Relatedness to FECVRelatedness to FECV•• Identify potential mutations that causesIdentify potential mutations that causes

disseminated diseasedisseminated disease

Ferret Systemic Ferret Systemic CoronavirusCoronavirus

M 1 2 3 4 5M 1 2 3 4 5

Ferret RotavirusFerret Rotavirus

Ferret RotavirusFerret Rotavirus•• RotavirusRotavirusparticles asparticles asviewed in viewed in cells and cells and feces by TEMfeces by TEM

Gastrointestinal Foreign BodiesGastrointestinal Foreign Bodies

NO house is completely ferretNO house is completely ferret--proofed!proofed!

•• Very common in ferretsVery common in ferrets•• High index of suspicions in ferrets less than 1 year of ageHigh index of suspicions in ferrets less than 1 year of age•• May be seen in bored, May be seen in bored, caged ferrets.caged ferrets.

•• Latex, rubber, cloth Latex, rubber, cloth most popularmost popular

•• Hairballs Hairballs -- Less common thanLess common thantraditional foreign bodiestraditional foreign bodiesFerret Ferret trichobezoarstrichobezoars!!

Oral TraumaOral Trauma

Other types Other types of injuries of injuries may occur may occur from from exploring exploring the the environment environment with one’s with one’s mouth.mouth.

Electrical Electrical cord injurycord injury

MycobacteriosisMycobacteriosis

•• Chronic wasting disease in ferretsChronic wasting disease in ferrets•• Minimal zoonotic potential, usually M. Minimal zoonotic potential, usually M. aviumavium

MycobacteriosisMycobacteriosis

•• Especially GIEspecially GI--tract and mesenteric lymph nodestract and mesenteric lymph nodes•• Histology: Large foamy macrophages with acid fast bacteriaHistology: Large foamy macrophages with acid fast bacteria

Mycobacterium genavenseMycobacterium genavense

Mycobacterium genavenseMycobacterium genavense

Clostridium Clostridium perfringensperfringens

• Cl. perfrigens type A most common (normal flora?!)• Mainly in black-footed ferret kits, coagulative necrosis

GI NeoplasiaGI Neoplasia•• Lymphoma is most commonLymphoma is most common•• Association with chronic inflammation of gut?Association with chronic inflammation of gut?•• Most lead to GI signsMost lead to GI signs•• Radiography, Radiography, ultrasound are ultrasound are useful in diagnosisuseful in diagnosis

•• NonNon--lymphomas lymphomas carry at better carry at better prognosisprognosis

•• Surgical excisionSurgical excision

GI T cell lymphoma

Intestinal LymphomaIntestinal Lymphoma

GI B cell lymphoma

Intestinal BIntestinal B--cell Lymphomacell Lymphoma

Intestinal BIntestinal B--cell Lymphomacell Lymphoma

Immunoblastic cellsCentroblastic cells

CD79aCD79a

Intestinal BIntestinal B--cell Lymphomacell Lymphoma

TransmuralTransmural TT--cell Lymphomacell Lymphoma

TransmuralTransmural TT--cell Lymphomacell Lymphoma

TransmuralTransmural TT--cell Lymphomacell Lymphoma

CD3CD3

Mucosal TMucosal T--cell Lymphomacell Lymphoma

Mucosal TMucosal T--cell Lymphomacell Lymphoma

CD3CD3

Mucosal TMucosal T--cell Lymphomacell Lymphoma

Mucosal TMucosal T--cell Lymphomacell Lymphoma

Mucosal TMucosal T--cell Lymphomacell Lymphoma

Feline TCRG VFeline TCRG V--NN--J alignment CDR3 region J alignment CDR3 region Moore et al., Vet Moore et al., Vet ImmunolImmunol ImmunopatholImmunopathol 106: 167106: 167--178, 2005178, 2005

CDR3CDR3

3’ V segment3’ V segment J segmentJ segmentN regionN region

5’ primer5’ primer 3’ primer3’ primerPCRPCR

Other ConditionsOther Conditions•• Salmonella sp.:Salmonella sp.:

•• Should be considered aShould be considered apossibility for diarrhea possibility for diarrhea whenever raw meat or whenever raw meat or poultry is fedpoultry is fed

•• Usually a group outbreakUsually a group outbreak•• May be cultured from fecesMay be cultured from feces•• At necropsy At necropsy -- culture bileculture bile

•• Rectal Rectal ProlapseProlapse::•• From strainingFrom straining•• Treat the primary cause:Treat the primary cause:

•• Dietary changeDietary change•• Viral infectionViral infection•• GI parasitesGI parasites

Hepatic Hepatic LipidosisLipidosis

•• Common physiologic findingCommon physiologic finding•• Inanition and mobilization Inanition and mobilization of peripheral fat storesof peripheral fat stores

•• 20% are 20% are multifocalmultifocal rather rather than diffusethan diffuse

•• May be mistaken for May be mistaken for metastaticmetastatictumors!tumors!

•• Often results in Often results in elevated ALT, elevated ALT, SAP readingsSAP readings

•• Ferrets do not Ferrets do not get “fatty liver get “fatty liver syndrome.”syndrome.”

Hepatic Hepatic LipidosisLipidosis

•• High percentage of High percentage of malignancy in this organmalignancy in this organ

•• Lymphoma most Lymphoma most common common

•• Primary neoplasms Primary neoplasms exhibit slow growthexhibit slow growth

Hepatic carcinomaHepatic carcinoma

•• Slow growing neoplasmSlow growing neoplasmthat eventually replacesthat eventually replacesfunctioning liver, resultingfunctioning liver, resultingin liver failurein liver failure

•• Some tumors may cause Some tumors may cause fatal hemorrhagefatal hemorrhage

Hepatic Hepatic NeoplasmsNeoplasms

BiliaryBiliary TumorsTumors•• Carcinomas Carcinomas –– uncommonuncommon•• CystadenomasCystadenomas –– benignbenigntumors, but may replace tumors, but may replace entire lobes over timeentire lobes over time

•• Surgical excision of all cysticSurgical excision of all cysticlesions is recommendedlesions is recommended

Hepatic Hepatic NeoplasmsNeoplasms

Hepatic Hepatic NeoplasmsNeoplasms

CytokeratinCytokeratin

CD31CD31