(1)
Department of Pathology, Sinai Hospital of Baltimore Pathology, Baltimore, MD, USA
Keywords
HepatitisCholestasisBiliaryPortalSteatosisSteatohepatitisHepatocellularLiver biopsies are usually needle core biopsies. The most common reasons for a biopsy include monitoring disease progression in hepatitis, evaluating a transplanted patient for rejection or graft-versus-host disease (GVHD), investigating elevated liver function tests (LFTs) , or diagnosing a radiographic mass. At many institutions, all non-neoplastic liver biopsy specimens are stained with trichrome (to evaluate fibrosis) and an iron stain (to reveal abnormal stores of iron in the tissue).
Anatomy
Blood comes into the liver via the portal vein (from the gut) and the hepatic artery (from the aorta). These vessels ramify into the small veins and arteries within the portal tracts. Blood gets from the terminal portal vessels to the outgoing central veins via the sinusoids—the long channels lined by hepatocytes. Once in the central vein, blood exits the liver via the hepatic veins, which drain into the inferior vena cava (resulting in a mingling of blood from the liver and lower extremities).
Bile is created by the hepatocytes and is secreted into the bile canaliculi, which eventually coalesce into ductules and ducts in the portal tracts. The bile then exits the liver via the common hepatic duct, which joins the cystic duct (from the gallbladder) to form the common bile duct.
Normal Histology
The liver is composed of three main components—the hepatocytes, the biliary system, and the blood vessels. Hepatocytes are large pink polygonal cells with dense round nuclei. Nucleoli, nuclear size variation, and occasional binucleate cells are okay. The hepatocytes are organized into plates that are one hepatocyte thick and lined by reticulin. Between these plates are the sinusoids for blood. Running perpendicular to the sinusoids, and essentially invisible to light microscopy, are the bile canaliculi: tiny intercellular channels between the hepatocytes.
Bile from the canaliculi makes its way to the bile ducts. The bile ducts are tubular structures with a low cuboidal epithelium (Figure 9.1). They are found in the portal tracts, which also contain branches of the hepatic artery and portal vein. These three components are also called the portal triad. Blood in both vessels is flowing into the liver; bile is flowing out. The portal tract also contains a small amount of connective tissue, which makes it stand out on a trichrome stain. The hepatocytes immediately surrounding the portal tract are called the limiting plate. The portal tract is usually the hotspot for inflammatory processes in the liver and so is important to identify on biopsy.
Figure 9.1.
Portal tract and central vein. The upper panel shows a typical portal tract surrounded by the limiting plate of hepatocytes (1) and containing a branch of the hepatic artery (2), bile ductule (3), and portal vein (4). The lower panel shows a central vein from the same liver. Both panels show extensive macrovesicular steatosis.
The third vessel in the liver unit is the central vein or terminal venule. This is a thin-walled vessel surrounded by hepatocytes and nothing else (see Figure 9.1). It contains blood on its way out of the liver.
The lobule is an architectural unit with the central vein as its center and portal tracts at the periphery. Centrilobular refers to a process surrounding the central vein, as opposed to being centered on the portal triad. The lobule is the most easily visualized anatomic unit (Figure 9.2).
Figure 9.2.
Liver organization. The acinus is a triangular, physiologic unit, while the lobule is a hexagonal anatomically based unit.
The acinus is a functional triangular unit with the portal tracts at the base (as the source of blood flow) and the central vein at the apex. In this model, the hepatocytes closest to the source of blood and oxygen are in zone 1, the base, and the most peripheral hepatocytes are in zone 3, the apex at the central vein. Ischemia and toxic insults affect the zones differently. The acinus is more of a physiologic unit and is used when describing liver findings that vary by zone.
Non-neoplastic or Inflammatory Disease Categories
It is helpful to think of the different liver compartments separately, because histologic findings can often be grouped according to the involved compartment:
Diseases of hepatocytes: viral hepatitis, autoimmune hepatitis, nonalcoholic and alcoholic fatty liver disease, drug toxicity, and metabolic/storage diseases
Diseases of the biliary system: autoimmune biliary diseases (primary sclerosing cholangitis and primary biliary cirrhosis), obstruction, atresia, transplant rejection, GVHD, and drug-induced injury
Diseases of the vasculature: transplant rejection, GVHD, and systemic vasculitides
The portal tract represents a convergence of all three compartments. Therefore, inflammation of the portal tract can be found in all of these diseases.
Pathologic Findings
The liver has only so many ways to respond to an insult or injury. An acute injury in the liver looks similar to that in any other organ: widespread edema, acute and chronic inflammation, and/or necrosis. Subacute or chronic injury generally has mainly mononuclear inflammatory cells as well as individual hepatocyte necrosis or degeneration. The final result of chronic injury from many causes is cirrhosis or end-stage liver disease. Therefore, many diseases in the liver have histologic overlap, and, in the case of cirrhosis, often you cannot tell what the original disease process was. The most important skill in interpreting the liver biopsy is recognizing injury to the different compartments. To attach a diagnosis to this collection of findings (wait for it), clinical correlation is required. Since that is an absolute given in liver pathology, don’t feel the need to include that phrase in your diagnosis. Instead, learn to look for clues in the chart and create a differential diagnosis that accounts for both clinical and histologic findings, with the help of a focused liver textbook. The most common patterns of injury are the following:
Hepatocellular Compartment
Portal inflammation: Inflammatory cells within the portal tract. In viral hepatitis and autoimmune disorders, the infiltrate is predominantly mononuclear. Eosinophils suggest a drug reaction, while plasma cells are often seen in autoimmune hepatitis.
Interface activity (periportal hepatitis, piecemeal necrosis): Inflammation, usually lymphocytic, occurring in the limiting plate and damaging the hepatocytes along that boundary. This looks like portal inflammation spilling out into the hepatocytes (Figure 9.3). Note that the word activity when describing something in the liver does not necessarily mean neutrophils.
Figure 9.3.
Portal inflammation. This is an example of chronic viral hepatitis. Lymphocytes in the portal tract spill out into the limiting plate of surrounding hepatocytes (arrow).
Lobular inflammation: Inflammation, often accompanied by hepatocyte necrosis, farther out from the portal tracts. Spotty necrosis is characterized by little clusters of lymphocytes and/or macrophages destroying individual hepatocytes in the lobules. Do not count lymphocytes in the sinuses, as they are physiologic.
Vacuolar degeneration (balloon cell change, or ballooning degeneration): One way in which hepatocytes become injured and die. The cell swells and the cytoplasm becomes feathery and pale to clear.
Acidophilic bodies: Another way in which hepatocytes die. These cells are similar to dyskeratotic cells in the skin; they are bright pink and shriveled up, with pyknotic nuclei.
Fibrosis: A general term indicating too much collagen. Fibrosis usually begins as an increase in collagen around the portal tract (portal fibrosis) and eventually spreads to connect adjacent portal tracts or central veins by thin webs of collagen (bridging fibrosis). The end stage of the process is cirrhosis, which is the division of the liver into individual nodules of regenerative hepatocytes separated by thick bands of fibrosis (Figure 9.4).
