The liver under the microscope

Right. Well, this sample came from a patient who had a secondary tumour deposit in her liver. The primary tumour was located in the colon. And resecting secondary deposits in the liver is now recognised to be an effective treatment for some people who have metastatic cancer from the colon.

Right. So when we receive the specimen, it’s a large specimen that comes down to our department in a bucket with formalin fixative.

We examine the specimen grossly, identify areas of interest, and then sample small pieces, which are then processed through various stages into paraffin wax blocks. And from those paraffin wax blocks, thin sections about five micrometres thick are cut and stained using various methods depending on what feature we would like to demonstrate.

OK. So the image you can see here is projected from my microscope. And it corresponds roughly to a single normal liver lobule. So the entire field here is roughly in real life about one millimetre across. The majority of what you can see here– these pink cells– are hepatocytes, which form the bulk of the normal liver. But there are one or two other important landmarks to point out. At the bottom right, we have a portal tract.

This begins in the centre of the liver in the area known as the hilum, and then forms smaller and smaller branches throughout the rest of the substance of the liver. And here we have a small portal tract which carries three main structures. The first are branches of the bile duct– shown here and here– lined by a single layer of epithelial cells, biliary epithelial cells. And these carry bile, formed in hepatocytes, to the hilum of the liver, then into the common bile duct, which drains into the duodenum. The second structure to point out– here and here– is a small branch of the hepatic artery, which carries oxygenated blood to the liver.

And the third structure, which is bigger than the artery but has a thinner wall, is a branch of the portal vein. The red material in the lumen here represents red blood cells. And the portal vein carries blood drained from the gut and other organs that are drained by the portal venous system.

The other landmark to point out– as part of the normal liver microanatomy, or lobule– is the small branch here of the hepatic vein. And essentially, the blood from the hepatic artery and the portal vein flows in between liver cells in tiny channels known as sinusoids– which you can barely see here. There’s occasional slit-like spaces here, which are the sinusoids, before moving into the hepatic vein. And then this drains into larger and larger branches of the hepatic vein, eventually into the vena cava and then into the right side of the heart.

Now I did say that this woman was not known to have any preexisting liver disease. And in fact, most of the hepatocytes you can see here are normal. However, some of the hepatocytes have got holes in them, like this one here or this one here or down here. These holes actually in life were occupied by lipid droplets which dissolved during our processing procedure. And this is known as fatty change. Fatty change is extremely common in Western communities. The two main causes being excess alcohol consumption, but increasingly the commonest cause now are complications related to the metabolic syndrome characterised by obesity, type 2 diabetes, hyperlipidemia, and various other features. And this woman was known to be overweight.

And this is almost certainly the cause of the fatty change we’re seeing here.

Yes, certainly. So this sample came from a man who was known to have longstanding liver disease. He suffered from a condition called primary sclerosing cholangitis, which is a reasonably common cause of chronic liver disease in the United Kingdom. It’s frequently associated with another condition known as ulcerative colitis, which is an inflammatory condition affecting the colon. In the case of this man, attempts to manage the condition using medical treatment eventually proved to be unsuccessful. And he developed end-stage liver disease for which the only currently effective treatment is liver transplantation.

So this differs from the previous case in two ways. The first thing I should point out is that the method we have used to stain this particular section is different to the conventional hematoxylin and eosin stain. In this case, the section has been stained with a method known as hematoxylin Van Gieson. And using this method, we are able to highlight collagen fibres which stain red. Now in the normal liver, these red collagen fibres are confined to portal tracts, which as I explained in the previous case, contain branches of the bile duct, the hepatic artery, and portal vein. And they’re also present in the walls of the hepatic veins, which drain blood.

But in this particular liver, you can see that there’s a lot more red collagen than there should be. And in fact, what’s happened is that this red collagen has replaced normal hepatocytes. And what we’re left with are small nodules– these green areas of surviving hepatocytes– many of which are completely surrounded by bands of fibrous tissue.