Lymphoma

Lymphomas are a form of cancer of the cells that make up the immune system, the cells whose normal job is to fight against infection. These cells are found in many places in the body and hence lymphomas can arise almost anywhere. Probably the most common site are the lymph nodes. These are the sort of glands that become swollen in the neck when you have a sore throat, which is a normal response to infection. But in parallel with that, probably swollen glands in the neck is one of the most common presenting features of a lymphoma. But because lymphoid tissue can be found all over the body, lymphomas can cause all sorts of problems and can sometimes be extremely difficult to diagnose. The other important thing about lymphomas is that the cells from which they arise, their normal job is to tour around the body looking for organisms, and so when you have a malignancy of these cells they also tend to tour around the body. So you don't have primary tumours and secondaries in the way you do with many types of cancer. These are what we call liquid cancers and in most patients the disease is widespread at presentation, and this doesn't have the same bad connotation that it would have if, say, you had spread of lung cancer or breast cancer.
 

All the lymphomas arise from the normal lymphoid cells, and the distinction between Hodgkin's and non-Hodgkin's lymphoma was initially an historical one, and it was recognised that Hodgkin's disease was a distinct entity that when you looked down the microscope, you could see some very large cells called Hodgkin's cells or Reed-Sternberg cells. So any lymphoma that had those cells, or almost any lymphoma that had those cells, was called Hodgkin's disease, and by default everything else got called non-Hodgkin's lymphoma. It's not quite just a microscopic distinction, and Hodgkin's disease does behave a little differently. It tends to spread from one node group to the next node group, whereas non-Hodgkin's lymphoma tends to be more likely to jump around. But it's not a major distinction, they are very closely related diseases. 

As for the non-Hodgkin's lymphomas, there is a wide variety of types, and there's probably over twenty different types, and they form a spectrum between very slow-growing tumours that are barely cancerous at all, all the way through to very rapidly-growing tumours that can cause problems very quickly. In general the slow growing ones when you look down the microscope, they are full of small cells not rapidly dividing, and they get called low grade lymphomas, whereas those that are growing very quickly, and when you look down the microscope they tend to be much bigger cells and many of them are dividing, they are called high grade lymphomas. But in the middle there is a fair amount of confusion and grey area, and it's also true that slow-growing, low grade lymphomas over time can pick up further mutations, start growing more quickly, and become high grade lymphomas, and that process is called transformation.
 

You talked about the differences between Hodgkin's and non-Hodgkin's not being great, but they have very different outcomes, don't they, of treatment?

Yes, they do have different outcomes in so far as the vast majority of people with Hodgkin's disease can expect to be cured. Cure rates in excess of 85%, possibly in excess of 90% if you look at all comers, whereas the success rate with non-Hodgkin's lymphoma is not so high and it does depend on what type of non-Hodgkin's lymphoma you have. Paradoxically the most rapidly-growing, aggressive tumours are the easier ones to cure, whereas the slow-growing, indolent tumours, they are much more protected from the effects of chemotherapy and radiotherapy, and although they are easier to treat and keep under control, they are actually much more difficult to totally eliminate.

The aim of the treatment does depend on the exact type of lymphoma that is present, and also the age and general health of the patient. For the vast majority of patients with Hodgkin's disease, the aim of treatment is cure. And that also applies to most people who have rapidly-growing, high grade non-Hodgkin's lymphomas. Perhaps in a very elderly, infirm person, one would take a more conservative approach where you are just trying to keep the disease under control rather than striving for cure, but for most people, one will strive for cure. The reality for most people with low grade lymphomas is that this is a chronic, relapsing condition, and most people are not going to get cured, even though they may live for many, many years with this disease, fit and well. And so in those patients you are trying to extend life, and not just life, but good quality life, and so that has impact on decisions about what treatment one has at what time.
 

The majority of people who have treatment for their lymphoma, whatever the type of lymphoma is, will go into remission, meaning that all signs of the disease go away, and when repeat scans are done, there are no enlarged nodes present. That of course doesn't mean that there is no microscopic disease left, and if there is microscopic disease left behind over time this will come back and is a so-called relapse. The chances of relapse very much depend on what type of lymphoma it was, and also what specific type of treatment was given, but if you look at, say, Hodgkin's disease, people who have chemotherapy for Hodgkin's disease, advanced Hodgkin's disease, once they are in remission, in about 75% of people the disease will never come back, they are effectively cured. And the down side of that is that about 20 / 25% of people at some stage will relapse. In the histologically aggressive, or high grade non-Hodgkin's lymphomas the chances of relapse are again about 25%, whereas in the low grade lymphomas, because its very hard to cure them and totally eliminate them, the malignant cells, relapse is very frequent, although the time frame of that is incredibly variable, anything between months and 20 / 30 years.
 

Lymphoma is an area in which there is a great deal of research activity ongoing. And there are many new drugs under development. There's a whole family of new drugs that have arisen because of an explosion in knowledge about the molecular events that cause lymphoma, and also the biochemical events going wrong in individual cells, so that we now have much more so-called targeted therapy, rather than blunderbuss therapy, and this is giving rise to a generation of new drugs, in fact there are so many potentially exciting new drugs available that it is probably going to be another ten years before we really know which of those are best and what their impact is going to be. 

There are also developments going on, not with drugs, but in manipulation of the immune system, and lymphomas do appear to be one of those types of cancer that may be amenable to therapy by immune mechanisms, and this of course is an extremely exciting area of therapy because there's the hope of achieving cure without all the side effects that go with chemotherapy and radiotherapy. At the moment this treatment is still in its infancy but I think there's lots of reasons to be optimistic that this will have an impact in the future.