Liver Biopsy Bootcamp

Tiffany M. Graham, M.D.

(Surgical Pathology/GI Fellow)

A Quick 

Overview...

Be sure to review the basics of liver histology (see my Liver & Gallbladder page) prior to delving any deeper into this topic. I cover a lot of the basic liver anatomy, physiology, and normal histology findings in those posts and will assume you have mastered these prior to reviewing this topic.

Before I begin, I must let you know that this tutorial is based in part on the Liver Biopsy Crash Course courtesy of Western University on MedEd Portal... I highly recommend this resource and excellent tutorial they created. You can view their full tutorial by Clicking HERE to open in a new tab then download the program and open via any web browser with the most updated version of Flash.

 

Unfortunately, I could only get it to work on Internet Explorer and had some glitches viewing a few of their slides. In an effort to master the art of signing out a liver biopsy, I am making this similar tutorial, but in a slightly altered format. I  just wanted to be upfront and let you know that a lot of this information can be found on their free, open-source program. While there is a good amount of overlap between the material covered, it is not presented in the same fashion and may include (or exclude) additional details. I made an effort to cite any image from their tutorial, but if I missed any, please let me know. 

There are quite a few terms that are thrown around a lot whenever you review any liver pathology textbook. I have put a few of these "high yield buzz words" below for my visually-inclined folks. Please take some time to familiarize yourself with these as they can be very subtle and are absolutely vital to making a proper diagnosis when evaluating any liver biopsy.

Near-Normal Appearance​

Portal Cellular Infiltrates

(Lymphoid aggregates = Hep C)

(Bile) Ductular Reaction

Lobular Injury-

"Interface Hepatitis"

Steatosis- Fatty Liver

Fibrosis

Forms nodules = Cirrhosis

Masses or Cystic Lesions

  1. How many portal tracts are present in the biopsy?

    • Typically, a minimum of 4-6 portal tracts​ are required to be considered "adequate"

    • For transplant livers, we ideally want to see a minimum of 10 portal tracts

  2. Is the architecture of portal tracts in relation to central veins normal or abnormal?

  3. Evaluate each of the structures in every single portal tract: (portal vein, hepatic artery, bile duct)

    • Does the vein represent  approximately 75% of the portal tract? (this is a normal finding)

    • Is every artery paired with a bile duct that is approximately the same size?

      • Are bile ducts missing or damaged in any of the portal tracts?  (see inflammation section below)?​​​

      • Is there a bile ductular reaction (increased # of small (proliferating) bile ducts at the periphery of the portal tract)?

  4. Is there any inflammation within the portal tract? (if YES, answer the questions below)

    • How many of the portal tracts are affected? (Rare, Few, Most, All)

    • Does the inflammation affect the entire portal tract, or only specific structures? Are any of these structures atypical/destroyed by the inflammation?

      • Portal vein (endothelialitis)​

      • Hepatic artery (arteritis)

      • Bile ducts (ductopenia, epithelial atypia, ductular reaction) 

    • Do the inflammatory cells completely expand the portal tract?

    • Does any inflammation "flow out" of the portal tract and into the adjacent hepatocytes? 

      • NOTE: This is also referred to as "piecemeal necrosis" or "interface hepatitis"​

    • Which inflammatory cell type(s) are present?​

      • ​Lymphocytes​
      • Plasma cells

      • Neutrophils

      • Eosinophils

      • Histiocytes/macrophages

    • Are there any granulomas identified?

      • Do they appear to affect a particular structure?​

  5. Assess the liver lobules (hepatocytes)

    • Is there any necroinflammatory activity?​ How severe?

      • Piecemeal necrosis? (Interface hepatitis)​

      • Coagulative necrosis? (around the central veins/ ischemic type)

      • Apoptosis? (Hepatitis C)

    • Is there cholestasis?

    • Is there steatosis? (aka fatty, bubbly, vacuolated) 

      • Microvesicular? (small vacuoles in cytoplasm, nucleus is in center) 

      • vs. Macrovesicular? (large cytoplasmic vacuole that pushes the nucleus to the side- looks like a signet ring)

      • What percentage of the biopsy is affected?

        • Typically this is assessing MACROvesicular ​

      • Is there steatohepatitis? (steatosis plus any combination of the following...)

        •  inflammation (often PMNs)

        • ballooned/large hepatocytes

        • Mallory bodies/Mallory hyaline (intermediate filaments within cytoplasm​ of injured hepatocytes & chemotactic for PMNs)

        • +/- fibrosis

        • The differential diagnosis = alcoholic steatohepatitis (ASH), non-alcoholic steatohepatitis (NASH)- obesity, diabetes, drugs

          • ASH vs. NASH cannot be DDx on histology alone! ​

  6. Are special stains required? What do they show? (if performed)

    • Masson's Trichrome:

      • Assess the degree of fibrosis and overall architecture​ 

      • BLUE/GREEN = Collagen

      • Normally, portal tracts have a small amount of collagen and central veins have a thin, fibrous rim

      • ASH/NASH: Zone 3 peri-cellular/sinusoidal fibrosis ("Spidery fibrosis")

    • Iron:

      • Increased in hemochromatosis, chronic blood transfusion, iron overloaded state, and others

      • Useful to DDx iron/hemosiderin (POS) from lipofuscin or bile pigment which stain similarly on routine H&E, but neg on iron

    • PAS-D:

      • The diastase (D) will digest glycogen in hepatocytes to help highlight any Alpha 1 antitrypsin globules

      • Also stains ceroid-laden Kupffer cells which may suggest recent lobular injury when numerous

    • Orcein

      • Helps visualize elastic fibers

        • Elastic fibers within fibrous septa indicate chronicity (rather than collapse)​

      • Stains Copper binding protein (Wilson's dz)

        • Copper binding protein within zone 1 hepatocytes may suggest cholestasis​

      • Stains Hepatitis B surface antigen

    • Reticulin

      • Assess the architecture and thickness of hepatocyte plates/"cords" 

        • Normally, each "plate" is only 1 hepatocyte/cell layer thick between the black staining reticulin fibers

        • Diffuse "twin-cell" plates = Regenerative hyperplasia

      • Helps to assess the thickness of each hepatocyte "cord"

      • Nodular distortion is often more obvious with a reticulin stain

      • This stain is especially helpful in patients with portal hypertension but a non-cirrhotic liver on histology or trichrome stains

NOTE: At many institutions, Trichrome (Masson's), PAS-D and Iron stains are routinely performed on all "medical liver biopsies" or when there is hepatitis (especially when this is a first time liver biopsy on a patient). We typically perform additional stains on a case-by-case basis for transplant liver biopsies that aim to assess for transplant rejection depending on the histologic findings, how long it has been since their transplant, and previous biopsy results. Often, we do not perform these routine stains on liver biopsies performed to evaluate for possible metastatic disease, but instead workup any tumor to determine whether it is metastatic vs. primary hepatobiliary tumor. This is by no means "set in stone" and each case should be assessed individually to ensure that the proper diagnosis is reached.

Major patterns of pathology in medical liver:

                         (Click to learn more about each pattern) 

1. Hepatitic pattern

2. Biliary pattern

3. Steatotic pattern

4. Vascular pattern

How to sign out a medical liver explant

How to assess and sign out Hepatitis C

Example format for

Sign Out:

Liver, native, [core/wedge] biopsy:

   - Portal findings:

   - Lobular findings:

   - Fibrosis.

   - See comment.

Autoimmune Hepatitis

  • Portal based chronic inflammation, usually plasma cells

  • Often prominent necroinflammatory (interface) activity with lobular injury as seen by:

    • Acidophil bodies (apoptotic/dead hepatocytes- dense pink cytoplasm without nucleus)

These posts contain high yield information collected from various educational resources including textbooks, journal articles, educational websites and more. They are intended for educational use only. I strongly believe the spreading of knowledge and depth of learned information should be encouraged in today's society rather than coveted. However, membership is required to view these posts  and should be used solely for educational purposes only. It is FREE to sign up. I strongly try to credit any and all sources of information by providing links directly to the source, in a caption, and/or via a list of references. If you feel that I have not credited a source properly or want a complete list of references, please feel free to reach out and I can address your concerns. Thank you kindly.

  • Facebook - Black Circle
  • Twitter - Black Circle
  • Pinterest - Black Circle

DISCLAIMER: THIS WEBSITE DOES NOT PROVIDE MEDICAL ADVICE

These posts contain high yield information collected from various educational resources including textbooks, journal articles, educational websites and more. They are intended for educational use only and should NOT be taken as medical advice. I strongly believe the spreading of knowledge and depth of learned information should be encouraged in today's society rather than coveted. Membership is required to view these posts  and should be used solely for educational purposes only.