Histopathologic Features, Immunophenotyping, Clonality, and Eubacterial Fluorescence In Situ Hybridization in Cats With Lymphocytic Cholangitis/Cholangiohepatitis

Abstract

Feline lymphocytic cholangitis is a poorly characterized disease complex with respect to histologic lesions, immunophenotype, and etiopathogenesis. Seventy-eight cases of feline lymphocytic cholangitis (n ¼ 51) and feline hepatic lymphoma (n ¼ 27) were reviewed using standardized histopathology, immunophenotyping (B cell and T cell), polymerase chain reaction for T-cell receptor (TCR) gene rearrangement, and fluorescence in situ hybridization (FISH) for eubacteria. Five histopathologic features in cases of lymphocytic cholangitis assisted in its differentiation from hepatic lymphoma: bile duct targeting (n ¼ 32, 62.7%), ductopenia (n ¼ 9, 17.6%), peribiliary fibrosis (n ¼ 37, 72.5%), portal B-cell aggregates (n ¼ 36, 70.6%), and portal lipogranulomas (n ¼ 38, 74.5%). The majority of lymphocytic cholangitis cases (n ¼ 35, 68.6%) were T cell predominant; 15 (29.4%) had an equal mix of B cells and T cells, and 1 (1.9%) had a B cell-predominant infiltrate; 66.6% of hepatic lymphoma cases were T-cell lymphomas. TCR clonality results were unexpected, with 17.1% of cases of lymphocytic cholangitis having clonal or oligoclonal populations and with T-cell lymphomas having variable TCR clonality (63.6% clonal or oligoclonal, 36.3% polyclonal). The majority of lymphocytic cholangitis (n ¼ 32 of 36, 88.8%) and all hepatic lymphoma cases had no detectable eubacteria using FISH. As demonstrated here, bile duct targeting, ductopenia, peribiliary fibrosis, portal B-cell aggregates, and portal lipogranulomas are lymphocytic cholangitis features that, along with polyclonal TCR (83%), help differentiate it from hepatic lymphoma. No strong evidence was found implicating in situ bacterial colonization as an etiopathogenesis of lymphocytic cholangitis.

Presumed primary and secondary hepatic copper accumulation in cats

“…14 Diagnoses of CCHS were made on the basis of detection of lymphocytic or lymphoplasmacytic periportal and portal infiltrates with or without progressive small duct destruction. 15 Cholecystitis was diagnosed by means of detection of lymphoplasmacytic or neutrophilic inflammation in the lamina propria of gallbladder mucosa. Diagnoses of hepatic lymphosarcoma were determined on the basis of findings of monomorphic neoplastic populations of lymphocytes infiltrating the portal tract, periportal tissue, or hepatic sinusoids.…”

“…Diagnoses of hepatic lymphosarcoma were determined on the basis of findings of monomorphic neoplastic populations of lymphocytes infiltrating the portal tract, periportal tissue, or hepatic sinusoids. 15 Diagnoses of hepatic lipidosis were made on the basis of detection of more than 80% of hepatocytes with cytosolic expansion with lipid vacuoles. 16 The discrimination of fat from glycogen-like vacuoles was determined on the basis of H&E staining features: lipid vacuoles are clear, round, and sharp-bordered and often displace the nucleus to the periphery of the cytoplasm in cells in liver samples with macrovesicular lipidosis, but nuclei may remain in a central location in cells in samples with microvesicular lipidosis.…”

“…Further studies are needed to evaluate the analgesic effects of butorphanol in raptors. (Am J Vet Res 2014;75: [11][12][13][14][15][16][17][18] See the midmonth issues of JAVMA for the expanded table of contents for the AJVR or log on to avmajournals.avma.org for access to all the abstracts.…”

Hepatic progenitor cells in canine and feline medicine: potential for regenerative strategies

“…In light of the similar presence of HPCs in liver disease in cats, one would also expect a highly activated and comparable HPC niche in these animals [14,31]. Recent unpublished data indeed show similar involvement of HSCs, macrophages and laminin in the feline HPC niche (Figure 3) [Unpublished observations section: Valtolina et al].…”

“…Literature on HPCs focuses on mouse, rat, and human. There are few publications on canine HPCs and even fewer on cat or other species and it is clear that the HPC response is often referred to as ‘bile duct proliferation’ when observed in liver histological sections [8,14]. In this terminology there is no suggestion of the presence and activation of stem cells, implying that the presence of HPCs in the liver of dogs and cats is not widely recognized and that there is no consensus on terminology in veterinary pathology.…”