- Email: [email protected]
Cholangiohepatitis
PAG E 4
A D VA N C E S
to differentiate from a well-differentiated malignant lymphoma or lymphoproliferative disorder. Progressive lymphocytic cholangitis/cholangiohepatitis has been characterized as a form of chronic lymphocytic cholangitis with the duct-destructive lesion. Suppurative cholangitis/ cholangiohepatitis may precede the development of lymphocytic cholangitis/ cholangiohepatitis.
Objectives
• To refine the histopathologic features
FELINE LYMPHOCYTIC CHOLANGITIS/ CHOLANGIOHEPATITIS Background Cholangitis and cholangiohepatitis are common acquired liver disorders of the cat, second only to the prevalence of hepatic lipidosis. Cholangitis has 4 main subcategories: neutrophilic cholangitis, lymphocytic cholangitis, destructive cholangitis and chronic cholangitis associated with liver fluke infestation. These subclassifications are based on the type of cellular infiltrate, degree of periportal fibrosis, presence of destructive lesions in the bile ductules, and evidence of fluke infestation. Lymphocytic cholangitis, including lymphocytic cholangiohepatitis, nonsuppurative cholangitis, nonsuppurative cholangiohepatitis, and lymphocytic portal hepatitis, is the most common category. Lymphocytic cholangitis is clinically silent during its initial stages and usually is chronically established at the time of liver biopsy and definitive diagnosis. There is no confirmed age or breed predisposition for lymphocytic cholangitis, but there is a common association between inflammatory bowel disease, pancreatic inflammation, and lymphocytic cholangitis. Histologic features of lymphocytic cholangitis vary, reflecting disease chronicity. Well-recognized features include small lymphocytes infiltrating the portal region, a variable degree of portal fibrosis, and biliary ductular or oval cell proliferation. Some cats have lymphocytes that target bile ductules and infiltrate into the biliary epithelium, causing progressive loss of ducts. In others, expansion of an infiltrating mantle of lymphocytes can be hard
of lymphocytic cholangitis, with a focus on the inflammatory infiltrate, apparent targeting of bile ductules, bile ductular proliferation, and portal fibrosis.
• To characterize and compare the infil-
trative lymphocyte populations in cats with advanced lymphocytic cholangitis, cats with modest portal inflammation, cats lacking inflammatory lesions, and cats with lymphoma, using immunophenotyping, and polymerase chain reaction (PCR) detection of T-cell receptor (TCR) gene rearrangement.
• To investigate the potential role of active bacterial infection in lymphocytic cholangitis using fluorescence in situ by hybridization (FISH).
Procedure Seventy-eight cases of feline hepatic disease consisting of lymphocytic cholangitis (51 cats) and feline hepatic lymphoma (27 cats) were reviewed using histopathology, immunophenotyping (B-cell and T-cell), PCR for TCR gene rearrangement, and FISH for eubacteria.
Results Five histopathologic features in cases of lymphocytic cholangitis differentiated it from hepatic lymphoma: bile duct targeting (62.7%), ductopenia (17.6%), peribiliary fibrosis (72.5%), portal B-cell aggregates (70.6%), and portal lipogranulomas (74.5%). The majority of lymphocytic cholangitis cases (68.6%) were T-cell predominant (29.4% had an equal numbers of B-cells and T-cells, and 1.9% had a B-cell-predominant infiltrate), and 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.
A D VA N C E S
The majority of lymphocytic cholangitis (88.8%), and all hepatic lymphoma cases had no detectable eubacteria using FISH.
Author Conclusion Bile duct targeting, ductopenia, peribiliary fibrosis, portal B-cell aggregates, and portal lipogranulomas and lymphocytic cholangitis, along with polyclonal TCR (83%), help differentiate lymphocytic cholangitis from hepatic lymphoma. In situ bacterial colonization was not identified as a cause of lymphocytic cholangitis.
Inclusions Twenty-one figures, 3 tables, 34 references.
Editor Annotation These authors evaluated a large number of cat livers with moderate to marked lymphocytic infiltration using a multicenter study. Lymphocytic plasmacytic inflammatory hepatitis was quite prominent with hepatic lymphosarcoma occurring in approximately one-third of the cases. The study demonstrated difficulty in determining which cases were inflammatory cases and which were lymphoma. This can be a problem in inflammatory bowel disease as well. There are some cases that appear to be a small-cell lymphoma which respond to therapy when diagnosed as intestinal lymphoma. The authors demonstrated some criteria that suggested much of the inflammation in this instance was directed against bile duct structures. They determined that bacterial infection was not a prominent aspect of this lymphocytic plasmacytic inflammatory process. Additional studies will be required to identify the cause. The most important aspect of this type was that wedge biopsies or larger biopsies of liver tissue and not needle biopsies were the most beneficial samples in providing differentiation of lymphosarcoma from inflammatory hepatitis. Immunophenotyping was an important tool in this study. They identified cases of lymphoma that were not monoclonal lymphoma but were oligoclonal lymphoma. This observation is being reported by researchers in other species. Good communication with your pathologist will be important to differentiate these disease processes in liver biopsies. (LDM) Warren A, Center S, McDonough S, et al. Histopathologic features, immunophenotyping, clonality, and eubacterial fluorescence in
itu hybridization in cats with lymphocytic cholangitis/cholangiohepatitis. Vet Pathol 2011;48:627-641.
PAG E 5
A D VA N C E S
to differentiate from a well-differentiated malignant lymphoma or lymphoproliferative disorder. Progressive lymphocytic cholangitis/cholangiohepatitis has been characterized as a form of chronic lymphocytic cholangitis with the duct-destructive lesion. Suppurative cholangitis/ cholangiohepatitis may precede the development of lymphocytic cholangitis/ cholangiohepatitis.
Objectives
• To refine the histopathologic features
FELINE LYMPHOCYTIC CHOLANGITIS/ CHOLANGIOHEPATITIS Background Cholangitis and cholangiohepatitis are common acquired liver disorders of the cat, second only to the prevalence of hepatic lipidosis. Cholangitis has 4 main subcategories: neutrophilic cholangitis, lymphocytic cholangitis, destructive cholangitis and chronic cholangitis associated with liver fluke infestation. These subclassifications are based on the type of cellular infiltrate, degree of periportal fibrosis, presence of destructive lesions in the bile ductules, and evidence of fluke infestation. Lymphocytic cholangitis, including lymphocytic cholangiohepatitis, nonsuppurative cholangitis, nonsuppurative cholangiohepatitis, and lymphocytic portal hepatitis, is the most common category. Lymphocytic cholangitis is clinically silent during its initial stages and usually is chronically established at the time of liver biopsy and definitive diagnosis. There is no confirmed age or breed predisposition for lymphocytic cholangitis, but there is a common association between inflammatory bowel disease, pancreatic inflammation, and lymphocytic cholangitis. Histologic features of lymphocytic cholangitis vary, reflecting disease chronicity. Well-recognized features include small lymphocytes infiltrating the portal region, a variable degree of portal fibrosis, and biliary ductular or oval cell proliferation. Some cats have lymphocytes that target bile ductules and infiltrate into the biliary epithelium, causing progressive loss of ducts. In others, expansion of an infiltrating mantle of lymphocytes can be hard
of lymphocytic cholangitis, with a focus on the inflammatory infiltrate, apparent targeting of bile ductules, bile ductular proliferation, and portal fibrosis.
• To characterize and compare the infil-
trative lymphocyte populations in cats with advanced lymphocytic cholangitis, cats with modest portal inflammation, cats lacking inflammatory lesions, and cats with lymphoma, using immunophenotyping, and polymerase chain reaction (PCR) detection of T-cell receptor (TCR) gene rearrangement.
• To investigate the potential role of active bacterial infection in lymphocytic cholangitis using fluorescence in situ by hybridization (FISH).
Procedure Seventy-eight cases of feline hepatic disease consisting of lymphocytic cholangitis (51 cats) and feline hepatic lymphoma (27 cats) were reviewed using histopathology, immunophenotyping (B-cell and T-cell), PCR for TCR gene rearrangement, and FISH for eubacteria.
Results Five histopathologic features in cases of lymphocytic cholangitis differentiated it from hepatic lymphoma: bile duct targeting (62.7%), ductopenia (17.6%), peribiliary fibrosis (72.5%), portal B-cell aggregates (70.6%), and portal lipogranulomas (74.5%). The majority of lymphocytic cholangitis cases (68.6%) were T-cell predominant (29.4% had an equal numbers of B-cells and T-cells, and 1.9% had a B-cell-predominant infiltrate), and 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.
A D VA N C E S
The majority of lymphocytic cholangitis (88.8%), and all hepatic lymphoma cases had no detectable eubacteria using FISH.
Author Conclusion Bile duct targeting, ductopenia, peribiliary fibrosis, portal B-cell aggregates, and portal lipogranulomas and lymphocytic cholangitis, along with polyclonal TCR (83%), help differentiate lymphocytic cholangitis from hepatic lymphoma. In situ bacterial colonization was not identified as a cause of lymphocytic cholangitis.
Inclusions Twenty-one figures, 3 tables, 34 references.
Editor Annotation These authors evaluated a large number of cat livers with moderate to marked lymphocytic infiltration using a multicenter study. Lymphocytic plasmacytic inflammatory hepatitis was quite prominent with hepatic lymphosarcoma occurring in approximately one-third of the cases. The study demonstrated difficulty in determining which cases were inflammatory cases and which were lymphoma. This can be a problem in inflammatory bowel disease as well. There are some cases that appear to be a small-cell lymphoma which respond to therapy when diagnosed as intestinal lymphoma. The authors demonstrated some criteria that suggested much of the inflammation in this instance was directed against bile duct structures. They determined that bacterial infection was not a prominent aspect of this lymphocytic plasmacytic inflammatory process. Additional studies will be required to identify the cause. The most important aspect of this type was that wedge biopsies or larger biopsies of liver tissue and not needle biopsies were the most beneficial samples in providing differentiation of lymphosarcoma from inflammatory hepatitis. Immunophenotyping was an important tool in this study. They identified cases of lymphoma that were not monoclonal lymphoma but were oligoclonal lymphoma. This observation is being reported by researchers in other species. Good communication with your pathologist will be important to differentiate these disease processes in liver biopsies. (LDM) Warren A, Center S, McDonough S, et al. Histopathologic features, immunophenotyping, clonality, and eubacterial fluorescence in
itu hybridization in cats with lymphocytic cholangitis/cholangiohepatitis. Vet Pathol 2011;48:627-641.
PAG E 5