Peering into the brain

On the hunt to discover how the patient died, the pathologist turns to the brain...
17 June 2016

Interview with 

Dr Hugo Ford, Dr James Rudd, Dr Helen Simpson, Dr Prina Ruparelia and Dr Alison Cluroe, Addenbrookes Hospital


On the hunt to discover how the patient died, pathologist Alison Cluroe turns to Neuronsthe brain, with Chris Smith...

Alison - So I'm now going to look at the prostate gland, which is sort of the rubbery gland that sits just at the base of the bladder.

Chris - So the prostate, I can see that. That's about the size of a walnut and sitting around the tube, I presume that's the urethra? The tube comes out of the bladder so the urine can get out.

Alison - That's quite correct. The urethra tube passes straight through the middle of the prostate gland and that's where you have a problem if you've got an enlarged prostate and it gets swollen up, it actually nips off that urethra and so people have trouble passing urine.

Chris - We mentioned we'd seen evidence of past infection in the kidney. That would have come from the bladder so is the bladder normal to your eye though.

Alison - It is. I mean there's a tiny big of hemorrhage down here near the entrance to the prostate gland, but I actually think that's related to the fact that there was a catheter in place.

Now what I've done is I've separated off all the organ but I think, at this point, we might just let the technician take over for a moment and dissect back the scalp tissues so we can actually get the brain for a good examination as well...

Alison - So we've now taken the top of the skull bone off and you can see underneath the brain, which sort of looks like a bag of worms.

Chris - So the brain has come out in it's entirety in one go. You can see at the bottom where it would be connected down to the spinal cord and then up to the bit that would actually sit inside your head.

Alison - I am looking at the underside of the brain. We've got what we call the cerebellum, this is the little bit of the brain that deals with balance. You can see a cord of white tissue hanging over the top of that, that's the spinal cord and then the brain stem just above it.

Chris - The cerebellum's about the size of my fist, give or take, underneath the brain. Then the brainstem - that's what connects the spinal cord up into the main part of what I would like the call the brain proper.

Alison - Yes, that's right. And here you can see these two little structures here. These are the optic nerves. The...

Chris - There's a sort of poking out from the middle of the brain?

Alison - Yes. And we'll just separate those from where they run through the skull and into the backs of the eyes.

Chris - It's interesting because it's grey round the outside and white in the middle, so there is quite literally grey matter in your head?

Alison - Exactly. Grey matter is where the little grey cells and they are the neurons that fire off the impulses that allow us to do all the things we do, and the white matter sitting underneath that is the axon.  And that axon, the reason it looks white is it's surrounded by a substance called myelin which protects it and allows the impulses to pass straight down the axon rather than them shooting off in different directions. So that's why you're seeing this two different contrasting areas of colour when we're slicing the brain here.

So, underneath the grey and the white matter, we have these spaces...

Chris - Right in the heart of the brain there are big holes, but they are quite normal?

Alison - Yes, absolutely. These are called ventricles and these contain cerebrospinal fluid, and cerebrospinal fluid it cushions the brain. It surrounds the brain and it's within the brain so the brain is sort of floating within a bath and that acts as a sort of a bit of protection for any sudden movements. It slows the movements down.

Chris - Like a shock absorber. Nothing abnormal coming up so far in here?

Alison - No. This brain actually looks very, very normal.

Chris - So we put the brain to one side.

Alison - The other organ that we haven't yet from the abdomen is the spleen. Now what I would say about the spleen is it's very soft and I think that the reason for that is that there is evidence of infection. Sometimes you can find at autopsy that there is a softening or a sort of liquefaction, a liquefying of the tissue of the spleen and I think that we have got a clue here to one of the reasons why this gentleman has died.

Chris - Which organ shall be look at next?

Alison - So I'm just going to open the gall bladder and drain away the bile...

Chris - The liver makes bile, doesn't it?

Alison - The liver makes bile. That's the bile, yes. Nothing to worry about in the gall bladder but something of considerable concern in this gentleman's liver. What we can see here are white bumps all over it (2-3 cms in areas), and these are tumour deposits that have extensively spread to involve the liver.

Chris - It's literally covered. If we look at how much of the liver is what should be normal healthy liver tissue and how much is the cancer, I'd say that maybe half of this person's liver is now taken up by these big blobs of tumour.

Alison - Yes, I would say you're right. About 50% has been replaced by tumour. We can see the background liver. This is the brown tissue between the white nodules, and the background liver is also abnormal, in fact. It's got a very congested pattern that we would call a nutmeg pattern, and nutmeg liver is seen when someone has a condition of congenital heart failure. Where the right side of the heart is failing, causes this back pressure on the veins, and that back pressure causes congestion within the organs that need to drain into the right side of the heart. So what you're seeing here when you see this nutmeg appearance is you're seeing normal bits of brown liver and then much darker areas of very congested liver and congested blood vessels.

Chris - These tumours then. The fact that the liver is full of them and they range in size, there are some small ones and some big ones. Does that they didn't come originally from the liver, they've probably come into the liver from somewhere else in the body?

Alison - I think it's more likely that these are what we'd call metastasis. That means they've spread from somewhere else. The liver is not the primary site of the tumour. I mean, obviously now, we've certainly got a malignant process in this gentleman which is likely to have contributed to his death.

Chris - Also with us is Dr Hugo Ford who's a consultant oncologist, or cancer specialist at Addenbrooke's Hospital. When someone actually get's a cancer, why have they got cancer? What has happened to their cells to make them behave in this abnormal way?

Hugo - Well, most commonly, there's some form of damage to the DNA in the cells. And this can come from an external source or it can come from the normal process of cell division and a mutation, which is an error in a replication when your cells are dividing.

Chris - Like a genetic spelling mistake?

Hugo - Like a genetic spelling mistake, and these tend to accumulate.  And all of our cells DNA has, on the end of it, something called a telomere and every time you copy that DNA, a little bit of the telomere get's cut off. They only have a certain number of cell divisions before your reach the end of the telomere and that triggers the cell to die.

In cancer cells, they manage to immortalise themselves by lengthening those telomeres. So the telomere, effectively, doesn't shorten and, therefore, there is not trigger that tells your body that this is a cell that's reached the end of it's life and it needs to die.

Chris - So it carries on growing?

Hugo - So they are immortal and that is one of the key characteristics of many cancer cells.

Chris - Is the liver a common site for cancers to spread to?

Hugo - Yes, it's one of the most common sites for cancer to spread to, in fact.

Chris - Why?

Hugo - The general way by which cancer cells spread is through the bloodstream and that's certainly one of the most common ways, and they do tend to lodge in places where there are filters for the bloodstream. So we commonly see the liver, which is a major site of filtration for the blood. The lungs also, there's a high volume of blood flows through the lungs, and often the bones as well.

Chris - And is it just physically the spread to somewhere else in the body and the growth in another place in the body that makes cancer bad, or can it do other things to you biochemically, and so on?

Hugo - Cancers can cause problems by invading into various tissues that cause damage. But they can make hormones which can cause endocrine problems, for example, or they can produce antibodies which causes inflammation or damage to particular parts of the body. So there are a number of ways in which cancers can damage the body other than the direct invasion.

Chris - If you pick up a cancer that's already spread, what can one do then to work out what the prognosis is for that person?

Hugo - Well the important thing is to find out exactly what one's dealing with. So a biopsy is usually very helpful, and that's taking a sample of tissue from the cancer, looking at it under the microscope, and trying to identify what it's characteristics are. Now that may help you as to where it's come from, but it may also help guide you to the prognosis of the cancer, and the tumour, and how you might wish to treat it.


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