The Animal Health Diagnostic Center at Cornell University's College of Veterinary Medicine is pleased to offer a specialized hepatopathology service. The goal of this service is to provide high quality interpretation of animal liver biopsy specimens by Dr. Sean McDonough, a board certified veterinary pathologists with high level expertise in liver pathology.

Due to the past very high and challenging demand for Dr. McDonough's expertise the AHDC is implementing a scheduling and specialty fee system to assure best service and commit to a set turn-around time for clients to have results in hand. Clients must register for an online account to schedule their submission for the hepatopathology specialty service. Reports will be completed within at most 5 business days of submission.

The AHDC will charge $265 per animal patient for the service that will include a panel of specialty stains described below, digital copper quantification if warranted for an additional $62, and review of all slides and the report by Dr. McDonough. Note that regular liver biopsy review at basic biopsy submission fees can be obtained through the regular anatomic pathology biopsy services. These cases however will not include specialty stains or exclusive review by Dr. McDonough. Escalation of such cases to the specialty service is only possible by scheduling through the Client Resource Team and re-accession to the specialty service at full charge.

Hepatopathology Explained and Submission Guidance

Biochemical parameters for liver disease have significant limitations in terms of sensitivity and specificity. Liver biopsy is a safe and effective means of investigating liver disease in dogs and cats. The biopsy is usually required to definitively diagnose hepatobiliary disease, helps guide treatment decisions and provides important prognostic information.

The liver, like most organs, has a limited repertoire of responses to injury. This limited morphologic expression of injury means that there is overlap of patterns and histopathologic findings among different diseases and more than one pattern or feature may exist at any given time. Thus, a complete but succinct clinical history, results of laboratory testing and imaging information as well as the gross appearance of the liver are essential for proper interpretation of liver biopsies.

In order for histopathology to accurately diagnose liver disease, the biopsy sample must be representative and provide at least 15 portal triads for evaluation. A disease process that is not uniformly and diffusely distributed throughout the liver may be missed if the sampling is inadequate. Similarly, the severity of a disease process may vary considerably between liver lobes. In addition to sampling focal lesions, best practice includes sampling grossly normal liver. Thus, focal lesions and/or a minimum of 3 separate liver lobes should be sampled. Biopsy specimens of specific lesions should be submitted separately. Save samples for aerobic/anaerobic bacterial culture and copper quantification (dogs). Collect bile for aerobic/anaerobic bacterial culture and cytologic analysis.

Wedge biopsies or laparoscopic cup forcep biopsies are preferred because adequately sized biopsies can be acquired from multiple liver lobes. Laparoscopic techniques are not recommended when disease of the common bile duct or gallbladder is suspected, which may require decompression. Tru-cut hepatic needle biopsies are best collected under ultrasonographic guidance. If performing percutaneous needle biopsy, use a 14-gauge needle for dogs and a 16-gauge needle for small dogs or cats. Blind needle biopsies are hazardous in animals with suspected hepatic hilar or mesenteric lymphadenomegaly, involvement of the common bile duct, gallbladder, intestines or pancreas or if multiple organ abnormalities are suspected. In these situations, exploratory laparotomy is more appropriate.

Before biopsy, bleeding tendencies should be evaluated by careful review of the history, physical examination, blood smear (confirm platelets >100,000/ µl), routine coagulation profile (prothrombin time [PT], activated partial thromboplastin time [APTT]), von Willebrand factor activity in high risk breeds, and a buccal mucosal bleeding time. Routine coagulation assessments have low reliability to detect bleeding risk. The mucosal bleeding time is more relevant when performed immediately before the biopsy procedure. Animals suspected to have bleeding tendencies should be treated with vitamin K1 (0.5–1 mg/kg, SC or IM) at 0, 12, and 24 hr. before tissue sampling. If buccal mucosal bleeding time is greater than 5 minutes, a fresh frozen plasma transfusion is indicated as well as the administration of desmopresin acetate (DDAVP, 0.3 to 1 µg per kilogram diluted in saline), which increases plasma von Willebrand factor 2-fold over baseline within one hour as well as plasma activity of factor VIII. Importantly, DDAVP cannot initiate hemostasis in dogs with qualitative defects or complete von Willebrand factor deficiency.

In addition to H&E stained sections, a panel of histochemical stains greatly enhances interpretation of the liver biopsy. The reticulin stain helps assess hepatic architecture, aids in recognition of proliferative foci and defines areas of parenchymal collapse and/or extinction. Masson’s trichrome for fibrillar collagen demonstrates the amount and distribution of fibrosis, complements the reticulin stain in evaluating liver architecture and accentuates individual necrotic hepatocytes. Although hemochromatosis is rare in dogs and cats, the Perls Prussian blue stain for iron is useful for mapping areas of inflammation, identifying Kupffer cell iron sequestration, and aids in proper identification of various pigments (lipofuscin, hemosiderin, bile). Staining sections for copper (Rhodanine) is essential to determine the need for chelation therapy. Significant copper accumulation is often detected serendipitously when the liver is biopsied for another reason.

Dr. Sean McDonough, DVM, PhD, Diplomate ACVP