An overview of lymphoma - video transcript

Published November 2023
Total time 27:22 minutes

[0:00]
Screen: the words ‘Setting the scene – an overview of lymphoma, Dr Rob Lown’ appear in white on a purple semi-circle. The Lymphoma Action logo is in the top right of the screen.

Screen: Dr Rob Lown appears full screen, speaking to camera.

[0:05]
Dr Rob Lown: Hello there. My name is Doctor Rob Lown. I'm a consultant haematologist and lymphoma specialist from University Hospital Southampton. And today I'm going to give an overview of lymphoma.

[0:20]
I'm going to talk about blood and the immune system and I'm going to talk about how cancer and specifically lymphoma develops. I'm going to talk about how lymphoma presents and how it's diagnosed. I'm going to give a brief description on how we approach the treatment of lymphoma.

[0:41]
Now, when you're given a diagnosis of lymphoma, obviously it's a big shock. And after your clinic appointment, it's very tempting to go online and have a look at some of the resources available. And actually nowadays there are many good resources available on the Internet and these can be used in conjunction with your discussion with your consultant.

Slide: an internet search screen showing the possible results for searching on the word ‘lymphoma’. Dr Rob Lown appears in the top right corner of the screen.
[1:04]
And just typing lymphoma into Google can bring up several reputable websites, but many of these are based outside of the UK. So I'd always recommend you go to the Lymphoma Action website, which has got many excellent resources to support you during your diagnosis and your treatment for lymphoma.

[1:24]
Now one of the limitations of looking up lymphoma on the Internet is lymphoma is not just one disease.

Slide: a word-cloud of lots of words associated with lymphoma.
[1:38]
There are very many different types of lymphoma and when you look it up on the Internet there are so many words associated related to the many different types of lymphoma: which type of lymphocyte lymphoma comes from and whereabouts in the development of the lymphocyte particular types of lymphoma come from.

[1:54]
And so I want to try and give a bit of context to explain where particular lymphomas arise and how they arise.

Slide: a yellow background with a white box containing the words ‘Let’s make some sense of all this!’ appear in black.
[2:02]
So let's make some sense of all of this.

Slide: white background with the words ‘Blood, and how it becomes cancerous. How blood and the immune system develops’ in black.
[2:06]
And a really good place to start is just talking about normal blood. And firstly I'm going to talk about how blood and the immune system develop.

Slide: white background and illustrations of different blood cells appear as described.
[2:15]
Now blood cells actually all develop in the bone marrow in adults. And within our bone marrow we have specialised blood cells called stem cells. And these stem cells reside in the bone marrow and they're able to develop into all of the cells that make up our blood in the immune system. And these can include white blood cells such as lymphocytes and neutrophils, red blood cells which are the specialised oxygen-carrying cells, and platelets which are specialised cells that allow our blood to clot after injury.

Slide: white background with illustrations of the different types of lymphocytes and cell they develop from.
[2:55]
Now this talk is about lymphoma, so we need to focus on the lymphocytes. And within the bone marrow, our stem cells produce ‘parent’ or ‘precursor lymphocytes’. And these precursor lymphocytes are able to develop into the two main types of lymphocytes. These are B-lymphocytes and T-lymphocytes.

Slide: white background. An illustration of the human body showing where the lymphatic system, organs and nodes are.
[3:20]
Now our lymphocytes reside within the lymphatic system and many people may be familiar with the circulation in the body: our arteries and our veins. But actually we have another type of circulation called the ‘lymphatic circulation’.

[3:37]
And the lymphatic system involves many of these lymphatic channels that drain fluid from the body's tissues and organs. And scattered through these channels are specialised organs called lymph nodes: here highlighted by these green dots.

[3:58]
These lymph nodes are concentrated in the neck, in the armpits, in the chest, deep in the abdomen, and also in the groin, as well as the elbows and inside the knees. And the distribution of these lymph nodes very much reflects where we can find lymphoma in the body.

[4:22]
As well as lymph channels and lymph nodes, our body also contains other specialised lymphoid organs including the thymus which is really important for the development of T-lymphocytes, and also the spleen which can be affected by many different types of lymphoma.

Slide: an illustration of a lymph node, showing the various key parts of the node, the blood vessels and how the lymph flows through it.
[4:44]
Now this is a diagram of a lymph node and lymph nodes are highly specialised organs which, amongst other things, are important in the management of infection.

[4:56]
And when we get infection in our body, the infectious particles, such as bacteria or viruses, can be taken into the lymph node through the lymph channels or through the blood vessels, where they can be detected in specialised areas of the lymph node called the follicles.

[5:16]
So the role of the lymph node is to both detect infection and fight it off. But also it has a very important role in remembering infection. So should we get the same infection in months or years down the line, the immune system is better at clearing that infection before indeed it makes us unwell.

Slide: white background with the words ‘Lymphocytes have to learn to fight infection’ in black. Photos and icons of children being taught appear.
[5:38]
So lymphocytes need to learn to fight infection. They don't come out of the bone marrow automatically being able to fight off all infections, they have to be trained, similar to the way we have to educate our children to be the specialist of the future: the lawyers, the doctors, the astronauts, the accountants, our lymphocytes have to be educated through a schooling system which can train them to fight off infection.

Slide: The previous illustration of a lymph node appears in the top left of the screen. Illustrations of development process of the B-lymphocyte including the lymphocytes, follicle, and developed cells, appear as described.
[6:05]
And this happens within the lymph node itself, particularly for B-lymphocytes. So let's take this batch of these immature lymphocytes. These are naive lymphocytes: they're ‘naïve’ because they haven't encountered infection before. And they have to be trained.

[6:26]
And here we have the follicle of the lymph node. This is this area here [indicates area on the screen with pointer-arrow]. And within the follicle is this central area called the germinal centre surrounded by a mantle zone. And that name ‘mantle’ is important when we think of a particular type of lymphoma.

[6:46]
So those immature lymphocytes enter into the lymph node and into the follicle of the lymph node. And in the lymph node they undergo a process of development, of mutation, something called somatic hypermutation if you like the terminology.

[7:06]
When lymphocytes undergo this process they can become much more specialised at fighting infection and lymphocytes which are successful at doing this are able to then leave that lymph node and become specialised lymphocytes.

[7:23]
Those that fail to become specialised, die off. And those successful cells – in particular – can become memory cells which will remember the infection for the future, or they can become antibody- producing cells, or plasma cells that produce protein that circulates in our bloodstream and which can attack infection before it makes people unwell. And this is the normal development process of the B-lymphocyte. And as you'll see later in this talk, particular lymphomas can arise at different stages of this process.

Slide: white background with the words ‘Blood, and how it becomes cancerous. How cells become cancerous’ in black.
[8:01]
So let's talk now in general terms about how cells can become cancerous.

Slide: white background, illustration of normal neutrophils and lymphocytes. Representation of cell growth signals appear as green ‘plus’ signs, and controlled cell death as red ‘minus’ signs.
[8:06]
Importantly, we need to see what happens normally and what normally causes cells to divide and grow. So within our bloodstream, we usually have X number of white blood cells: neutrophils and lymphocytes. But when we get an infection, our body produces a signal that causes cell growth – a cell growth signal – and that's represented by these green pluses on this slide.

[8:36]
This causes the white blood cells to divide and grow so they can better off fight the infection. And what's happening in the body at this time is our white blood cell count in our blood test rises, and the lymph nodes can grow. And that's a normal side effect of infection.

[8:56]
And when the infection is getting better, we go through a recovery phase. And this is where we need a controlled cell-death because we don't need those white blood cells anymore; the body needs to go back to where it was at the beginning. So those redundant cells, those cells that aren't needed, have a negative signal – a cell death signal – and they disappear and we're back to where we were beforehand. And that's what normally happens in response to infection.

Slide: white background. Illustration of normal cells undergoing genetic changes to become cancer cells. Representation of cell growth signals appear as green ‘plus’ signs, and controlled cell death as red ‘minus’ signs.
[9:27]
Now cancer cells develop because their DNA undergoes a genetic change or mutation. Now this can happen just by chance, or it can happen because of environmental insults, just smoking, which can increase the risk of genetic damage.

[9:47]
I'm often asked in clinic, why did this happen to me? And sometimes the answer is just bad luck. And why is it bad luck? Well, the reality is our bodies are making cancerous cells all the time. If you looked in detail at all of my cells, you would find many cells that had the potential to become cancerous.

[10:07]
But in the vast majority of cases, these cells don't become cancerous. Because we know cancer cells require a signal to grow and they need to not have a signal to tell them to die, just like we saw has happened in a normal response to infection. And almost always when cancer cells develop, the cell doesn't get enough growth signal, but it does get a death signal because our cells have evolved to die off if they become dangerous.

[10:36]
But also our immune system is highly trained and it can kill off cancerous cells. So these cells either die by themselves because they're not getting the right signals, or the immune system, particularly our T-cells, can go in and kill off the cancerous cell.

Slide: white background with illustration of normal cells becoming cancerous and then developing to become a mass of cells.
[10:54]
So how does cancer develop? Well, it's that bad luck in some cases or because of repeated insults, for example from smoking (although that's not the case in lymphoma) that causes cancer cells not to die off and to start to divide. And with time, a dividing cancer cell can become a mass of cancer cells or a tumour.

[11:14]
And this is because cancer cells are making or getting too much growth signal. They're blocking the dying signal - the death signal. And they're able to evade the immune system for example, by putting flags up on their surface, which stop the T-cells from coming in and killing them off. So cancer cells can develop several ways to survive and sometimes can become very expert in doing that. And this is a challenge for us as cancer doctors to find ways to get around these mechanisms.

Slide: white background and illustrations of different blood cells and how they develop from the bone marrow and stem cells.
[11:49]
So with that in mind, we can look at this diagram and I can explain where certain type of blood cancers arise in this stage of cell development. For example, from stem cells we have acute leukaemia, and a rare leukaemia called chronic myeloid leukaemia. From our white blood cells: lymphoma and chronic lymphocytic leukaemia. And then from our red cells and platelets: two related conditions called polycythemia and essential thrombocythemia. And of course we're going to concentrate on lymphoma.

Slide: white background with the words ‘Lymphoma. What are the different types of lymphoma?’ in black.
[12:22]
So what are the different types of lymphoma?

Slide: white background with graphics showing the top-level classification (different names) of types of lymphoma. A photo of Thomas Hodgkin also appears.
[12:24]
Now, when you look this up, the most common classification we see is between Hodgkin and non-Hodgkin lymphoma.

[12:33]
And now Hodgkin lymphoma was described by a physician from Guy's Hospital in London, Thomas Hodgkin, some 200 years ago, even before microscopes were invented in a way that allowed people to look at this disease under a high power and be able to look at the detail of it. But we know now that Hodgkin lymphoma looks very different from other types of lymphoma down the microscope, and it's more likely to affect younger people than other types of lymphoma.

Slide: white background with graphics showing the classification (different names) of types of non-Hodgkin lymphoma.
[13:02]
And every other lymphoma is grouped under this non-Hodgkin lymphoma group. But of course, there's much more detail to it than that. I often use this to teach my medical students, but also when I have patients who have a new diagnosis of lymphoma in clinic. And I will divide lymphomas into two main groups.

[13:25]
There are the fast-growing lymphomas, also known as high-grade or aggressive lymphomas. And these lymphomas often will make people symptomatic quickly. Lymph nodes can grow in a period of weeks or sometimes even days. And often high-grade fast-growing lymphomas need treatment quickly.

[13:47]
The slow-growing lymphomas are often known as low-grade or indolent lymphomas. These may not cause symptoms, and they may have been present for many years before diagnosis. And they don't always require treatment straightaway.

[14:05]
And then within both these groups we have B-cell and T-cell types of these lymphomas. And this gives us a really nice framework then in which we can put the main types of lymphoma.

[14:19]
So if we first look at fast growing B-cell lymphomas, we have diffuse large B-cell lymphoma, by far the most common type of this fast-growing B cell lymphoma, but also rarer lymphoma such as Burkitt lymphoma and some mantle cell lymphomas. Fast growing T-cell lymphomas include anaplastic large cell lymphoma and peripheral T-cell lymphoma.

[14:44]
And then we have slow growing B-cell lymphomas including the most common which is follicular lymphoma, marginal zone lymphoma and mantle cell lymphoma. And then finally we have this rare group of slow-growing T-cell lymphomas; most commonly these are the skin or ‘cutaneous’ T-cell lymphomas.

Slide: white background with the words ‘Lymphoma. Where in the cell cycle do different types of lymphoma come from?’ in black.
[15:07]
So where in that cell cycle – cell development – do the different types of lymphoma come from? I said I'd talk through this.

Slide: an illustration of a lymph node, showing the various key parts of the node, the blood vessels and how the lymph flows through it. Additional illustrations of the follicle appear.
[15:14]
So let's go back to our lymph node and we've talked already about the follicle, which is where the action really happens in terms of B-lymphocyte development. And within these follicles, we have this central area – the germinal centre – and then around it the mantle zone.

Slide: repeat of the slide that shows how B-cells develop. Arrows appear at different stages of the development that indicate different types of lymphoma.
[15:32]
And we've talked through how B-cells go into the germinal centre, mutate and can become memory cells or antibody cells. So where in this process do these different types of lymphoma arise from?

[15:48]
Well, firstly, if we look at our immature naive B-lymphocytes, we see some patients with chronic lymphocytic leukaemia, a very similar condition called small lymphocytic lymphoma, they are very similar, and they can arise – not in all cases – but they can arise from these immature B-cells.

[16:08]
From our germinal centre we see the common lymphomas arise. So follicular lymphoma arises within the follicle (hence the name), and diffuse large B-cell lymphoma certain types arise within this germinal centre, and also Burkitt lymphoma and we think Hodgkin lymphoma (though it's a bit less clear with Hodgkin). From the mantle zone of course, we have mantle cell lymphoma arising as these lymphocytes exit the germinal centre through the mantle before leaving the lymph node.

[16:43]
From these antibody cells or plasma cells, we have conditions such as Waldenstrom's or lymphoplasmacytic lymphoma, and also a related blood cancer called myeloma.

[16:54]
And then finally from these memory cells we can see another type of chronic lymphocytic leukaemia or small lymphocytic lymphoma.

[17:04]
And there are many other different types of lymphoma which I haven't included here, but these are the more common ones.

Slide: white background with the words ‘Lymphoma. How do we diagnose and stage lymphoma?’ in black.
[17:12]
So how do we diagnose and stage lymphoma?

Slide: illustration of a person checking their armpit for swollen lymph nodes. The illustration of the body showing the lymphatic system also appears.
[17:15]
Now, many people who come to see the doctor will have a lump and it will be in the areas that are usually quite easy to feel. You remember that picture of the lymph node groups, and we described this concentration of lymph nodes in the neck, in the armpits, as you can see in this picture, and in the groin. These are the areas that we can readily feel because they're just underneath the skin. However, there are other areas where lymph nodes are more common, such as the tummy and in the chest. So we do not-uncommonly see people coming to clinic without any lymph nodes that we can feel, but when they have a scan, we can see a lump in the chest, we can see a lump in the tummy.

[18:00]
Sometimes we see lymphoma developing some of the lymphoid organs, particularly the spleen and in the thymus as well.

[18:09]
But of course lymphocytes are also in the blood. Blood is everywhere so we can see lymphoma develop in the brain, in the eyes, in the gut, in the skin, literally anywhere: it’s one of those conditions that can arise anywhere in the body, but most commonly in these areas of the lymphatic system.

Slide: white background with the words ‘B-symptoms’ in black. Additional images appear representing the three common B-symptoms.
[18:31]
Now, lymphoma is commonly associated with what are known as B-symptoms and there are three specific symptoms that are more a feature of aggressive or fast-growing lymphomas perhaps than the slow-growing lymphomas.

[18:43]
And these include weight loss. Night sweats which typically are drenching so the sheets are soaked and people will often have to change their pyjamas, change their sheets or sleep on a towel. And also fevers which are unexplained, i.e. they're not caused by an infection. But because lymphoma can be anywhere in the body, it can affect any of the body's organs. There are many other potential symptoms of lymphoma and again, I'd like to point you towards the Lymphoma Action website for more information on that.

Slide: white background with the words ‘Tests for lymphoma’ in black and an image of a person in a scanner.
[19:16]
Now, some tests are more common in patients with lymphoma. So when you see the doctor and after your clinic appointments, you may have blood tests, you may have scans including an ultrasound, CT scan or a PET scan.

[19:30]
And many people will require a biopsy. And again, there are many different ways of doing biopsies. It can be done with a very fine needle, although that is not always accurate. It can be done with a bigger needle called a ‘core biopsy’. It can be done using surgery, generally under anaesthetic where a whole lymph node or part of a lymph node can be removed, or also we can do it in a bone marrow biopsy.

Slide: white background with the words ‘Staging lymphoma’ in black
[19:58]
Once lymphoma has been diagnosed, then we stage the lymphoma and staging is a way of describing how widespread the lymphoma is. And we use a staging system called the Ann Arbor Staging System and it's split into 4 stages.

Slide: white background with the words ‘Staging lymphoma’ in black. Images of the body showing the stages of lymphoma appear on screen as they are described.
[20:17]
Stage 1 involves just one or one group of lymph nodes.
Stage 2 involves two groups of lymph nodes, but they have to be on the same side of the diaphragm. And you can see the diaphragm here, which basically splits the body into two. So for example, in this picture, there's lymph nodes in the neck and the armpit, but there's nothing below the diaphragm, so this is stage 2. This could also be a patient with lymph nodes in the groin and the tummy but nothing above the diaphragm, and that would also be stage 2.
And together, stage 1 and 2 are sometimes referred to as early stage or localised.
Stage 3 lymphoma involves two or more groups of lymph nodes on both sides of the diaphragm. For example, it could be in the neck and the groin, or it could be in multiple sites on both sides of the diaphragm, but it has to involve lymph nodes on both sides of the diaphragm.
And stage 4 typically involves lymph nodes, though not always, but it also involves the body's organs with two or more areas of involvement of the body's organs, for example, the liver, the lungs, or the bone marrow.
And together, stage 3 and 4 are often referred to as advanced.

Slide: white background with the words ‘Lymphoma. How do we treat lymphoma?’ in black.
[21:43]
So finally, I just want to briefly talk about how we treat lymphoma. And I'm going to use some of the examples I've given earlier in this talk to illustrate how scientists have been able to develop treatments that target each stage of the cell development.

Slide: illustration of a tumour cell with graphics representing how chemotherapy works.
[22:00]
So here's our tumour cell, which we know can divide and become a lump of tumour cells or tumour. And the first type of treatment which many people will be familiar with or would have heard of is chemotherapy.

[22:13]
Now, chemotherapy is able to damage DNA, or damage the mechanisms that allow cells to grow and divide. So if we give chemotherapy to a cell, when it tries to divide, it dies off. And this is the main mechanism for chemotherapy drugs.

Slide: illustration of a tumour cell with graphics representing how antibodies and other drugs work.
[22:34]
Another group of drugs we use are antibodies. Now we've talked about antibodies already: our body, our plasma cells produce normal antibodies to fight off infection. And scientists have been able to re-engineer antibodies not to target infection, but to target proteins or markers on the surface of cancer cells. And when they bind to these markers, they're able to either kill off the cell directly or encourage other cells of the immune system to come in and kill off the cell.

[23:08]
We also talked about cancer cells requiring this growth signal in order to grow and divide and develop. And scientists have also developed drugs that can target this growth signal, block this growth signal. And one class of drugs includes ibrutinib, which is used for chronic lymphocytic leukaemia, mantle cell lymphoma. And drugs of its class are used in other types of lymphoma as well and can be very effective, stopping these cells from growing.

[23:37]
Of course, cancer cells can be very good at turning off that death signal: they can block that death signal so they don't die off. And we now have drugs that can unblock that death signal. For example, venetoclax, again used in chronic lymphocytic leukaemia, is extraordinarily effective at getting this rare leukaemia under control.

[23:59]
And finally, we have immune therapies – or cell therapies -  and these are drugs that can improve the way the immune system works in order to get a better response against that cancer. One example of this is CAR-T cells. These are genetically engineered T-lymphocytes that can target and directly kill off cancer cells. And these can be very effective therapies in some people in whom other treatments have not worked.

Slide: illustration of a tumour cell with graphics representing how radiotherapy works.
[24:31]
So the other type of treatment that is commonly used for lymphoma is radiotherapy. Radiotherapy essentially is very powerful X-rays that are able to directly damage and kill cells. Radiotherapy is very good for patients whose lymphoma is just in one area, or for lymphoma that may be causing particularly bad symptoms.

[24:56]
Now of course we don't use all these treatments at once and in some patients the lymphoma will come back after the initial treatment. And having such a diverse range of treatments allows us to offer patients several lines of treatment even if the lymphoma relapses several times.

Slide: white background with the words ‘Treatment’ in black, and a bullet list of key points appear on screen.
[25:17]
The other thing about lymphoma in fact, is that it doesn't always need treatment straightaway. And some people for example, those with low-grade lymphoma, those without symptoms, those with normal blood counts, those with no evidence of damage or imminent damage to the body's organs, and those without particularly large lymph nodes, may not need treatment at all for some time. And in fact this period of time can be quite long.

[25:46]
And in some patients, although it's unusual, the lymphoma doesn't necessarily grow at all and can even regress. And so these patients are often offered what's called active monitoring or we used to call it ‘watch and wait’ where you're seen by your lymphoma doctor in clinic. You may have some blood tests done. And after a period of years, you may not even need to be seen in clinic regularly, but you can get in touch with the team should you have worrying symptoms. And we know that active monitoring does not increase the risk of coming to harm from your lymphoma in the longer term, neither does it reduce the effectiveness of treatment that you may eventually be offered.

Slide: white background with the words ‘Summary’ in black, a photograph of some cells on the right side of the screen, and a bullet list of key points appear on screen.
[26:32]
So to summarize, blood and immune cells are made in the bone marrow. Lymphoma develops from specialised immune cells called lymphocytes. Lymphocytes learn to fight infection within the lymphatic system, and different lymphomas arise at different stages of lymphocyte development. Lymphoma treatment has developed from research into how normal lymphocytes function.

Screen: Dr Rob Lown appears full screen, speaking to camera.
[27:02]
So I hope you found this talk helpful. Thank you very much.

Total time 27:22 minutes

Disclaimer

This transcription has been automatically generated. However, Lymphoma Action has taken all reasonable steps to check its accuracy. The content is not intended to be medical advice. If you are looking for specific medical advice for your own personal circumstances always consult your medical team.