JPC SYSTEMIC PATHOLOGY

DIGESTIVE SYSTEM

September 2024

D-M07

 

SIGNALMENT (JPC #2372961): Cat

 

HISTORY: Found dead without any clinical signs with the exception of weight loss.

 

HISTOPATHOLOGIC DESCRIPTION: Liver: Diffusely and markedly expanding and bridging between portal areas is a dense inflammatory infiltrate composed of high numbers of lymphocytes, fewer plasma cells, and rare neutrophils and macrophages. This inflammatory infiltrate separates and surrounds bile ducts and occasionally breaches the limiting plate and into adjacent sinusoids, where it separates and surrounds individual hepatocytes that are shrunken with bright eosinophilic cytoplasm and a pyknotic nucleus (piecemeal necrosis). There are varying degrees of fibrosis within portal areas; these occasionally form a thick band separating portal areas from the limiting plate. Adjacent hepatocytes are often pale, swollen, and have vacuolated cytoplasm (degenerate). Bile duct epithelium is often pale with vacuolated cytoplasm and/or shrunken (degeneration), and within areas of inflammation there is often distortion of bile ductule shape. Diffusely, there are increased numbers of small bile ducts (biliary ductular reaction). There are often moderate amounts of granular to globular, yellow-brown, cytoplasmic pigment within centrilobular hepatocytes (lipofuscin or hemosiderin) and Kupffer cells (hemosiderin or bile). The margin of the liver is undulant, rounded, and lobular. The capsule is diffusely and markedly expanded by moderate amounts of clear space (edema) and few previously described inflammatory cells. Portal lymphatics are occasionally dilated.

 

MORPHOLOGIC DIAGNOSIS: Liver: Hepatitis, portal and bridging, lymphocytic, chronic, diffuse, severe, with biliary hyperplasia and portal fibrosis, breed unspecified, feline.

 

CONDITION: Lymphocytic portal hepatitis

 

SYNONYMS: Lymphocytic cholangitis / cholangiohepatitis; nonsuppurative cholangitis / cholangiohepatitis; feline cholangiohepatitis syndrome

 

GENERAL DISCUSSION:

• Relatively common disorder of cats
• Characterized by lymphocytic infiltration in the portal area, variable degree of bile duct and oval cell proliferation, peribiliary and portal-to-bridging fibrosis
• Slowly progressive disease; typically diagnosed in cats older than 4 years of age
• Mild lymphocytic portal hepatitis is common in older cats (>10 years) and may be an aging change or a subclinical form of this slowly progressive disease

 

PATHOGENESIS:

 

TYPICAL CLINICAL FINDINGS:

• Chronic weight loss, depression, lethargy, anorexia, vomiting
• Icterus may be seen due to cholestasis
• CBC/Chemistry findings consistent with cholestasis: Hyperbilirubinemia, hypercholesterolemia, increased ALP and GGT
• UA, coagulation, fecal exam findings consistent with cholestasis: Bilirubinuria, prolonged PT/PTT, steatorrhea

 

TYPICAL GROSS FINDINGS:

• Hepatomegaly, with exaggerated lobular pattern
• Chronic cases: Portal fibrosis

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Portal tracts expanded by lymphocytes (T cells may predominate, or mix of T and B cells) 

• Plasma cells may be admixed in chronic lesions
• Inflammation may obscure bile ducts

• Bile duct and oval cell proliferation variable
• Degenerative changes in biliary epithelium, ductopenia from destructive cholangitis, and portal lipogranulomas
• Portal to bridging fibrosis 
• Intrahepatic bile stasis
• Minimal extension into the periportal hepatic parenchyma

 

ADDITIONAL DIAGNOSTIC TESTS:

 

DIFFERENTIAL DIAGNOSES:

• Lymphoma (main differential): 

• Liver is common site of metastasis, especially if spleen is involved
• Most apparent in portal tracts 
• To differentiate lymphoma from lymphocytic cholangiohepatitis: ductopenia, degeneration of bile duct epithelium, and portal lipogranulomas are NOT expected with lymphoma; PARR also helpful to establish clonality in lymphoma

• Neutrophilic (acute) cholangitis (suppurative cholangitis):

• Relatively common in cats (less so in dogs); most common in middle aged and older cats
• Likely secondary to ascending infection from gastrointestinal tract
• Characterized by neutrophils surrounding or within walls or lumina of bile ducts; biliary epithelial degeneration; may progress to cholangiohepatitis with periportal hepatocyte necrosis
• Commonly associated with pancreatitis and inflammatory bowel disease (triaditis)
• Major duodenal papilla anatomy and associated immune activation and/or inflammation may play a role in these disease processes in cats (Schreeg et. al., Vet Pathol 2024) 

      

COMPARATIVE PATHOLOGY:

• Dogs: Destructive cholangitis has been associated with some chemicals including trimethoprim sulfa but may also have other causes (idiosyncratic drug reaction and distemper virus also implicated); histologic lesions are similar to cholangiohepatitis with ductopenia and inflammation in the portal areas including neutrophils, eosinophils and pigment laden macrophages 
• Cats: Experimental infection with Bartonella henselae is reported to cause mild lymphocytic cholangitis/pericholangitis and lymphocytic hepatitis
• Cattle: Lymphocytic portal hepatitis associated with Ovine Gammaherpesvirus-2 (sheep-associated malignant catarrhal fever)

 

REFERENCES:

1. Cullen JM, Stalker MJ. Liver and biliary system. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. Philadelphia, PA: Elsevier; 2016:307-308, 318. 
2. Headley SA, Oliveira TES, Li J, et. al. Immunohistochemical Detection of Intralesional Antigens of Ovine Gammaherpesvirus-2 in Cattle with Sheep-associated Malignant Catarrhal Fever. J Comp Pathol. 2020;174:86-89.
3. Rothuizen J, Bunch SE, Charles JA, et. al. Morphological classification of billiary disorders of the canine and feline liver. In: WSAVA Liver Standardization Group, eds. WSAVA Standards for Clinical and Histological Diagnosis of Canine and Feline Liver Diseases. Philadelphia, PA: Saunders; 2006:68-69.
4. Schreeg ME, Cullen JM, Robertson J, Gookin JL. Histologic characterization of the major duodenal papilla and association with concurrent biliary, pancreatic, and intestinal pathology in cats. Vet Pathol. 2024;61(2):207-220.
5. Stockham SL, Scott MA. Fundamentals of Veterinary Clinical Pathology. 2nd ed. Hoboken, NJ: Wiley; 2013:678-679.
6. Van Wettere AJ, Brown DL. Hepatobiliary System and Exocrine. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:535. 

 

 

 

Click the slide to view.

---