Good evening everybody, and welcome to another Thursday night members webinar. My name is Bruce Stevenson, and I have the honour and privilege of chairing tonight's session. I don't think we have any new people on, so usual housekeeping rules.

If you've got any questions, into the Q&A box and we will hold those over to the end. He is not a stranger to us and I welcome him back. Owen Davies is an RCVS an American specialist in veterinary oncology.

He is a Cambridge graduate who spent 9 years in practise before his residency term at the Royal Veterinary College. Since 2017, Owen has worked for Highcroft Referrals in Bristol. He is interested in all aspects of oncology, but especially hemopoietic malignancies, immune therapy for cancer, and perineoplastic disease.

Owen, welcome back to the webinar, vet, and it's over to you. Thank you, Bruce. Thank you everyone for tuning in tonight.

And a big thank you to Webinar vet for having me back. I always enjoy doing these sessions, and it's a pleasure to be talking about something as interesting as feline lymphoma tonight. Now, it's late in the day, so we're gonna keep it easy, and I'm gonna start, as I often do, by showing you some of my cases.

This is Ryan, who's an elderly domestic short-haired cat. What's wrong with his retina? Have a look at that.

Well, I hope you can see that the retina is kind of detached. It's coming into focus in different planes. And commonly when you see old cats with detached retinas, the blood vessels are very engorged and there's haemorrhages behind the retina that you can see.

And in this one, it's a little bit weird because we see if anything, very thin blood vessels, and the retina looks a little bit opaque. And actually, Ryan had ocular lymphoma characterised by retinal involvement. More commonly types of ocular lymphoma in cats present with uveal involvements like these guys here.

But at the very least we can say that ocular lymphoma tends to present with ocular signs. This is Geza, a lovely little chap, and Giza has a very large mass over the frontal sinuses here. So Giza has nasal lymphoma and that presents with nasal signs.

And this is Shadow, and Shadow had bladder lymphoma, believe it or not, and Shadow presented with dysuria. And we've got Tootsie here who had a more common gastrointestinal lymphoma, and Tootsie presented with an abdominal mass and gastrointestinal signs. And finally, we have neuro, who had laryngeal lymphoma, and neuro presented with upper respiratory tract, obstruction and respiratory signs.

So in that little introduction today guys, we have learned something that's very important, and possibly one of the most important points I can get over to you tonight, that feline lymphoma is a very, very different disease compared with canine and human lymphoma. Whereas dogs tend to get peripheral nodal lymphoma, cats tend to get extra nodal lymphoma. Localised to one part of the body, one organ system.

Whereas dogs tend to present healthy and well, cats tend to present sick. Sometimes people ask me what the typical clinical signs are for cats with lymphoma, and that is incredibly variable. It depends on the area of the body or the organ system that's affected.

So, 0.1 feline lymphoma is a unique disease and we should be very, very careful to avoid extrapolating information from the canine or the human version of the disease. This has ramifications for investigation and prognosis and treatment.

And this evening we're gonna talk about my approach to the feline lymphoma, really, going through the diagnosis, some further tests after diagnosis, and how to approach different presentations. And at this time more than ever, with August 2022, it's very important to have budgetary constraints in mind. This, ladies and gentlemen, is lymphoma.

What you're looking at here is a visible clone of cells. Now they may be small, intermediate, or large lymphocytes. They may or may not have morphologic abnormalities, but the key thing is they're all the same.

You're looking at a visible clone of cells. And the principal differential diagnosis in the UK at least, is a reactive lymph node. Now when we talk about a reactive lymph node, we're talking about a node where it's draining a region of the body that the immune system is active in.

It's busy responding to some challenge. And so quite appropriately, you've got lots of different types of lymphocytes here, at different stages in development or activation, responding to different antigens. And so you see big ones, little ones, intermediate ones, and you see a variation in shapes and morphologies as well.

In a reactive lymph node, despite the variation, you should see a majority of small, well-differentiated lymphocytes like these. And lymphoma describes the situation when one of these lymphocytes, and it can be any of them, undergoes malignant transformation and starts proliferating in an uncontrolled way, such that it could efface the rest of the lymphocytes here, and then you end up with something like this, where the lymphoma has occurred from a large lymphocyte. So the diagnosis can be relatively straightforward here, but we come to a problem.

Sometimes you get presented with a cat or a dog where the lymphoma hasn't quite displaced all the other lymphocytes yet. And the cytological picture for that can be very challenging because you've got the clone of lymphocytes among lots and lots of benign reactive lymphocytes, and it can be a really tough call as to whether this is lymphoma or whether it's a reactive process. So I bet, I make this point because it This isn't particularly uncommon to happen in cats.

In my experience, it's much more common for cats to come back with equivocal cytology than it is in dogs. So we need to consider what tests do we do in this situation. If you've heard me talk about dogs, I tend to mention three tests you could consider whether cytology is equivocal.

That's histopathology on a biopsy. The PA test, PCR for antigen receptor rearrangement, or flow cytometry. Well, in cats, flow cytometry isn't very well evaluated yet.

So there aren't many labs offering flow cytometry commercially, in years to come, I hope this will change, but it's not a viable option at most labs at the moment. We could consider the PA test, which is much more available. It's a really clever DNA test, but the big bind for this in my eyes.

Is that it's very poorly sensitive. In English, if a test is in the order of 60% sensitive, it is going to miss at least 1 in 3 cases. And that's a very big compromise with this test.

It's easy to do. You can request it on the material already at the lab and you don't have to resample the cat. It's widely available and the turnaround isn't too bad.

But if you're going to miss one case in 3, that's gonna get you into trouble pretty soon. So I will use par sometimes but try to avoid it if I can. In cats then The options to confirm whether something's lymphoma or not when the cytology is equivocal, well, principally, you've got to look at histopathology if you can.

Now I'm aware we're talking about lymphoma on the budget today. And sometimes it's just not possible to get histopath, not least due to cost concerns. It may be due to anaesthetic safety or the owner's wishes.

So I'm going to share with you a couple of cases which illustrate ways you may be able to get around the need for histopathology. Let's revisit Ryan, the elderly cat with a detached retina. Now, I can tell you that I am not in the business of FNA and retinas.

How do we get to the diagnosis with Ryan? Well, we found disease that was clinically silent in his abdomen. And that's always worth doing.

So we did a routine survey ultrasound of the abdomen. We saw this large hypoechoic lymph node that doesn't really look like a lymph node, does it? It's been infiltrated to that extent, and we got a good cytological diagnosis from there.

We treated for the lymphoma, and when the retina reattached, I'm glad to say he regained vision, and that kind of proved our hypothesis that the retina had lymphoma infiltration. Here's another cats Norman, who's 11 years. Norman presented with hyperexia, weight loss, and a mobile, painless abdominal mass, masses rather.

And on ultrasound, we saw two key findings. He had a very large hypoechoic lymph node in the mid abdomen, 5 by 7 centimetres, and that's absolutely huge for a cat, isn't it? The second finding was he had diffuse markedly thickened intestines, 9 millimetre wall thickness is roughly, or at least twice the width it should be.

It wasn't just thickened intestines, there was an absence of layering in the intestines too. So we already knew that Norman had a high likelihood of lymphoma before we took cytology from the lymph node, or the cytology came back as reactive. A horrible, frustrating situation where the clinical pathologist said, I think we could have lymphoma here, but I can't quite call it.

So what do we do with Norman? What do you consider? Well, the first option I discussed with Norman's owners was doing a laparotomy and biopsying the node.

And I think this is one situation where I as a specialist can say, I think it's absolutely fine to do a really small laparotomy incision. The point of doing the laparotomy, the sole point of it is to get a histo sample from the node. So you could do a tiny laparotomy as small as possible, poke a bit of the node through.

Hack off a wedge, hemostas it adequately and pop it back and then sew it up, with durable material anticipating the need for chemotherapy in the near future. And in that situation, a smaller laparotomy, the better. There's less healing, so we can get chemo done sooner if we need to.

So That would be my ideal option in Norman's case, but, actually, his owner said, I'm afraid we really haven't got much money to do that at all. I think Norman had about 2000 pounds left on his insurance, and that was it. The surgical procedure may have absorbed half or three quarters of that.

So what do we do? Well, I'll tell you what we did. We treated him We gave him a test dose of steroids and biblastine as treatment for the lymphoma.

We gave him a supportive care. And we monitored him. And I'm happy to say that at 7 days, the gastrointestinal mass was 50% smaller and he was feeling much better.

And that proved the, proved the trial of these drugs. Some of you might wonder why we tried blastine rather than vincristine, and that's simply because he already had gastrointestinal signs and bincristine can make these worse. One of the good things about bnblastine.

Is that it tends to be minimally upsetting to the gastrointestinal tract, and it's a great choice in these GI cases. Incidentally, been blasting has been shown to be, equivalent to beingcristine in its efficacy for treating feline lymphoma too. So with this guy, we gave him a trial of treatment, and I hope it's not quite as reckless as it may initially sound.

That's because you need to bear in mind the reason why our jobs are done by people and not by computers. That is, we have to collate all the information from the different sources. We have access to all the pieces of the jigsaw.

And let's consider for a second what differential diagnoses we'd have in a cat with a huge abdominal mass and markedly thickened intestines with loss of wall layering. Lymphoma's got to be 1 to 9 out of 10, hasn't it? But we shouldn't forget that granulomatous disease, for example, FIP or mycobacterial disease, would be less likely possibilities.

You could also get things like visceral or intestinal mast cell tumours doing things like this as well. And in theory, in cytology of any enlarged lymph node, you could consider it might just be a reactive lymph node, but I might argue that if this lymph node was so big and its architecture so dis distorted, that reactive disease would be very hard to believe. So these are the differentials that we had in this particular case.

And even though the cytology isn't diagnostic of any of these, it can be very helpful in the big picture because you know what? It's just describing lymphocytes. If we had granulomatous disease or another neoplasm, we'd see cells as well as or instead of lymphocytes.

OK. I also think that in a situation of the lymph node being so big, reactive really isn't an appropriate differential diagnosis. So the cytology wasn't diagnostic of anything, but let's not forget it was still very helpful because under the constraints that Norman had presented, there was only one viable diagnosis here.

Now, something that helped me with the confidence in making that decision is that we've taken cytology very thoroughly. We haven't just taken one stab of the lymph node. We had sampled several places in this lymph node.

We had checked the cytology in-house to make sure we had lots of nucleated cells. And we sent you, I think about 6 or 7 slides. So being thorough like that and making sure we had a good sale yield, maximise the confidence we can have in this test.

And for those of you who want to avoid the stress of having to make such a call yourself and getting equivocal cytology, this is probably something that we might have avoided if we'd given the clinical pathologist more information in the first place. OK. The reason why it's good to write lots of history on the submission form is not for the, interest levels of the clinical pathologists, it's because they're part of the clinical team, or so they should be.

They're clinical. And so our history is providing them with the, with the differential diagnoses that are possible. So if we tell them that we've got a lymph node the size of a grapefruit, they should hopefully be thinking that reactive lymph node is not an appropriate differential diagnosis.

If we tell them that things like the only other differential would be mast cell disease or granulomatous disease and they're only seeing lymphocytes, then I think they're much more likely to come back with a diagnosis in all probability this is lymphoma. So my second key point then, if you've got equivocal cytology or non-diagnostic cytology, always consider histopathology first. If you're not able to, if it's tough, look for the diagnosis elsewhere if you can.

It could be clinically silent but easy to sample. And finally, when all else has been exhausted, consider a therapeutic trial, but please, before you do this, make sure you have very carefully considered the quality of your test results. If cytology says it's non-diagnostic, but it's based on just one little stab where most of the specimen was blood, you might want to consider repeating that test.

Make sure you've considered all differential diagnoses, and you might want to chat with colleagues or local specialists and things to make sure that you're not missing anything. And then this isn't for every client. I think we all know that.

Some clients we trust more than others, some were happy to work with us more than others. And you need to make sure you've got the right client and that they're counselled fully, particularly if the therapeutic trial doesn't go the way we want it to, we need to make sure that the client isn't going to be blamedful of us. Instead, there'll be understanding of the way we've handled the less than perfect, but real world situation.

So let's move on. Let's say we've diagnosed in the case of lymphoma, and a common question I get asked is what tests should I do now? Let's start with FELV and FIV tests.

Now it's cheap, quick, easy to do in-house, quite reliable. And these things can be very intimately linked with lymphoma. If a cat is FELV positive, he or she will have a 62 times greater risk of developing lymphoma.

If he or she is FIV positive, it will be a 5.6 times greater risk of developing lymphoma. But we already know they've got lymphoma.

So once they've got lymphoma, what's the effect? Actually, I don't think it's very significant at all. The I think although the older literature tends to say that FELV and FIV status is prognostic in feline lymphoma, there's actually very few, rigorous studies that are backing that up.

And I think what they're meaning is that where, where you have end stage clinic. FELV characterised by blood dysgrasia or bone marrow issues, for example, among others, or FIV characterised by AIDS-like disease, you will have a very weak patient with very few reserves and little ability to withstand the treatment. Happily, there's some modern studies from areas of the world where these infections are much more prevalent, showing that actually, FELB and FIV positivity have very little effect on the prognosis at all.

So I don't think it's critical. If I'm on a shoestring budget, would I do that test? No, I don't think I would.

Now in canine lymphoma, we know the importance of T cell or B-cell immuno phenotype. And taking it a step further, the WHO classification of the lymphoma cytology. These are really, really important in dogs.

But would I request them in cats? No. Not routinely, not at all.

The things that matter in cats. The first thing is that the anatomic site. The area, the extranodal tissue that's affected by the lymphoma, correlates strongly with the behaviour and the type of lymphoma that you're going to find there.

Now, sometimes if it helps the pathologist to do the T cell or B cell immunostaining to work out whether it's lymphoma in the first place, I'll request that test. For example, in an elementary lymphoma, if you've got a mix of T cells and B cells, it's probably less likely to be diagnostic. But if you've got a population that's all T or all B, that's much more likely to confirm the diagnosis of lymphoma.

So that's probably the, the main reason I might suggest doing T cell or B cell to confirm the diagnosis. Once we got the diagnosis, the prognostic significance is weak. There have been studies on the histology of feline lymphoma.

They're not at the levels of power that we'd like to make a definitive categorization. But I think what we do know so far is that the histological types of lymphoma seem to have minimal effect on the prognosis. There's only two types that have been shown to have a markedly different behaviour, and that's not driven so much by the histological type, but by the grade.

OK. And just to be clear here, when we're talking about the histological type, we're talking about whether these are T lymphocytes or B lymphocytes, the size of them, where they're found in the tissue, the way they are arranged, and the way they relate to each other. When we're talking about the grade, we're talking principally about the the mitotic activity.

So you can have different types of his histological types of lymphoma with different grades within them. And so it's the grade rather than the histological type that is most important in the prognosis of feline lymphoma. So my key point here.

Is to dictate the treatment and the prognosis of a case of lymphoma. The most important things to make sure you you're aware of are the grade. And the anatomic site.

Grade is something that should really be dictated by histology as a gold standard. But, a good cytologist can often give you a strong indication of the grade as well. And as we'll go on to talk about the clinical presentation can also tell you whether a low-grade lymphoma is an appropriate differential or not.

Another thing people wonder about is should I stage a case of feline lymphoma? And I have here the staging system for feline lymphoma. Which you'll see is, is actually very similar to the canine version.

It's just been altered a bit to allow for the quite high prevalence of solitary GI masses with or without lymph node involvement in cats. And to get the stage for the feline lymphoma, you could start with a CBC, biochemistry, urinalysis, image the chest and the abdomen. Take fine needle aspirates of liver, spleen, and other enlarged structures, and then take a bone marrow aspirate.

But the prognostic and therapeutic significance is actually weak. OK, very, very little effect on the prognosis or the treatment that you give. I'm not pooh-poohing staging, I think it's important because if the cat has clinical signs, these are often middle-aged to older cats.

You know, it's not improbable that these clinical signs may be related to something else. We want to know what that something else is. Is it going to be made worse with chemotherapy or steroids?

If it's diabetes, it quite possibly would be. Also, we want to know where the cancer is in the cat, so we can monitor the cat well enough. Again, if, if we're going OK on treatments, but then new clinical signs develop, it would be nice to know if that area related to the clinical signs had lymphoma in in the first place.

And very importantly, there are some cats that we can consider to treatment with a local therapy rather than chemo. Local therapy being surgery or radiation therapy. And I think in feline lymphoma, this is more relevant than in canine lymphoma.

So, staging rarely affects prognosis or choice of drugs, but it's useful to detect concurrent disease, to form a baseline for monitoring, or to assess whether surgery or radiation could be used. And in cases where I'm on a shoestring budget, I often have a big discussion with the owner about whether we stage or not. And ultimately, I think we'd all prefer to spend money on the treatment of the cats rather than the staging of the cat.

However, the owner needs to be included in that decision if things like this are skipped. So I'm gonna show you some common presentations of feline lymphoma now and outline how I tackle them. We'll start with the most common, the alimentary lymphomas.

And out of these, the most common is the low grade elementary lymphoma, OK. And this is 50 to 80% of GI lymphomas. And it's usually made up of small cells.

So often people refer to it, particularly psychologically, as small cell lymphoma. It can present with weight loss, hyperexia, vomiting, diarrhoea, usually be going on for several months. These are older cats and it's often the legacy of chronic GI inflammation.

Lots of these guys have had triaditis or IBD or pancreatitis for a number of years. And that diagnosis is probably correct. There's a big school of thought now that says the low-grade lymphomas can evolve from this chronic inflammation.

On physical examination. This should be a cat that you think could easily have IBD, OK? So the clinical signs will overlap with that of an IBD.

You will get thickened intestines, but they shouldn't be markedly thickened. It could even be normal. You could get enlarged lymph nodes, but the architecture should be pretty much normal and the lymph nodes shouldn't be massive, OK?

And so I tend to discuss this with people, or recommend that people think of this as a high grade IBD rather than a low grade lymphoma. It is, it benefits from being treated in the way that you treat a lot of IBDs with diet, so making sure that vitamin B12 is OK and stuff like that. And as they'll come on to, they can be treated with prednisolone and cloambicil if needed as well.

To get to a diagnosis, you normally need gastrointestinal biopsies. If you look at the distribution of cases here, most of them tend to occur in the middle of the small intestine. And take note, this is further than the end most endoscopes can reach.

To make sure you've got the diagnosis correct, you often need more than just an epithelial biopsy. So full thickness biopsies are usually the way to go. And as I said, they can be treated with loambiil and Preds, over 80% respond to treatment, and they'll stay in remission for 1.5 for over 2 years.

Often survive up to about 3 years. When they come out of remission again you can use cyclophosphamide, glinastine, blastine, a COT protocol, or even abdominal radiation. So they can have a long course.

They're treated in a way which is much more like the treatment of IVD than the treatment of the high grade lymphomas, as we'll see. And I think where a lot of people fall down is they think, oh, it's lymphoma now, we need to go with crambisil and Pred and nothing else matters. We can really improve the quality of life for these guys and the response to treatment by thinking about all the other things we think about in management of an IBD case.

So my take home message with this, please think of it as a high grade IBD. Now, we tend to lump the intermediate and the high grade gastrointestinal lymphomas together. Although histologically they might be a bit different, clinically, they behave in the same way.

Now, these guys will present in a very different way. They'll present with abdominal masses, hugely distorted lymph nodes, can't possibly be reactive. They'll have, either huge intestinal masses or marked thickening of the guts with loss of layering.

So clinically, you should be able to distinguish this from the low-grade lymphomas. You can also get involvement of other organs as I'll go on to talk about in a minute. The distribution of these is also very different, you know, it tends to affect the stomach, whereas the low grade ones don't, tends to leave the proximal, and mids small intestine alone.

And then things like ileum, or colon can be affected, less commonly afterwards. So this is an aggressive disease, make no mistake. And this is the one where you talk about cop or chop chemotherapy in the vast majority of cases.

Sometimes people ask whether surgery can be considered if you've got a focal lesion, and I think that's a fair comment. However, that's rarely going to cure the disease. The disease can be insidious and very often involves lots of other sites in the abdomen.

So I would choose to consider surgery if you've got a focal mass that's causing obstruction. It's perforated or causing a lot of haemorrhage. In other words, it's got something you need to deal with right now and you can't wait for chemotherapy to work or not to work.

So if I was doing surgery, I would nearly always follow up with chemo afterwards. And chemo tends to have a lower response rate than for the low grade disease, 50 to 60% respond. And the average survival is usually between 3 and 10 months depending on the study.

But some of these cats, approximately 1/3, will live longer than a year, and in my experience, some of these guys can live for several years. So a good outcome is not impossible. OK.

Sadly though, it is the minority of cases. And finally, we have a third and rarer type of gastrointestinal lymphoma, but it's actually not that rare. It's, you know, 7 to 10% of cases.

Whereas the low-grade cases tend to be T cells and the high-grade cases tend to be B cells. The large granular lymphoma cases tend to be cytotoxic T cells or NK cells, natural killer cells, and the disease is characterised by these magenta granules within the, within the lymphocytes there. This is an incredibly aggressive disease.

In presentation, it's often clinically indistinguishable from the intermediate or high grade, lymphomas. The distribution of cases is slightly different. It's very rare to affect the stomach, tends to be more small intestinal.

It's possibly more likely to present with a cat who's extremely sick at presentation with a patomegaly, splenomegaly, renomegaly, you get jaundice, you can get fusions as well. But in, on the most part, it does overlap with the high grade cases. And regrettably, The response to chemotherapy is uniformly poor.

You don't get a third of cases living longer than a year with this particular disease. There's not really a chance of a long-term outcome. Some studies have shown average survival in the order of weeks.

Some more recent studies talk about the best survivals being up to several months. But really, you'd be doing very well if you treat these cases and you'll get into the 3 or 4 month mark. So it's only about 30% respond to the treatment here.

And again, we haven't figured out the best way to treat these, so it's a copholomaine-based treatment of the things that are most used. So those 3 diseases, then those 3 very different diseases are the gastrointestinal lymphomas, and I'm gonna show you a case study here. This is a cat called Tootsie, who became a good friend of mine.

Tootsie presented with gastrointestinal signs and weight loss. Had a mobile, painless abdominal mass masses, large kidneys. And had quite a moderate azotemia here with high creatinine and high phosphate.

On ultrasound we saw this. So if you're not used to looking at ultrasound, we've got a transverse section of markedly thickened intestines there, and you can't see any layering. OK.

We also saw, and I apologise, I haven't got the pictures, moderate, large bright kidneys. And right at the edge of the kidneys, you saw a lifting of the renal capsule with hypoechoic material. So, we sampled the mass at the ileocholic junction and we got haemorrhage, necrosis, inflammation.

We sampled the lymph node and we got reactive, possible predominance of medium sized lymphocytes, that horrible equivocal cytology situation. So what do you want to do next? Just to summarise, we've got a large mass at the ileose colic junction, large lymph node.

We've got large kidneys with this weird hypoechoic material under the capsule. If you think back to how to 20 minutes ago. In this case, we did the the gold standard.

We took Tootsie to surgery. Resected the mass and took a biopsy of the mesenteric lymph node and the perinephric tissue. And on histopath, we've got B cell high grade lymphoma at all sites.

Now, we're talking about lymphoma on the budget today. And to be honest, I, I always try to manage these cases in a parsimonious way anyway. I think we missed the trick with this case.

Because renal cytology is often reasonably more, reasonably clear cut. There should be very, very few lymphocytes in the kidneys. So we got the diagnosis with Tootsie taking biopsies.

I think if we'd aspirated, carefully aspirated the hypoechoic material underneath the capsules of the kidneys in this cat, we would probably have got a large population of large lymphocytes like we have here. And that should have been diagnostic. So we might have been able to avoid surgery in this particular case, but as it was, I think it was good to have removed that intestinal mass, which could have caused its own trouble like obstruction.

And this poses another question here. We've got lymphoma in the kidneys, and we've got lymphoma in the gastrointestinal tract. And if you look at the studies of some of the descriptions in textbooks, it talks about renal lymphoma.

And it talks about high grade gastrointestinal lymphoma as well. OK, so which one is this? Well, my point here is, does it really matter?

Because if you look at the survival times here and the reported treatments, they're very, very similar. And the bigger issue is that now we've got access to better ultrasound and CT and we're imaging these guys more, we're finding that the places where lymphoma chooses to live in a cat's abdomen are much more varied than we first thought. So, abdominal lymphoma, I think, is a better term.

And I would like to see this term used more in recognition of the fact that it's rarely just the guts. It could be the guts and the pancreas or guts, pancreas, lymph nodes, kidneys, or rarely just the kidneys. It could be kidneys, pancreas, it could be kidneys, retroperitoneal space, etc.

So the more you look for it in different places, the more you're gonna find it there. And because the behaviour of the disease and the reported treatments are the same, I think abdominal lymphoma is the is the term I prefer to use. Now we've got a video of renal lymphoma here.

And this isn't Totsy, but just to show you what I was meaning about the hypoechoic rim, if you look here, the top of the kidneys, you can see a kind of black patch. Between that and the white perinephric fat. And that's quite a characteristic sign of renal lymphoma.

So more about renal lymphoma then cats can have lymphoma in the kidneys and they may or may not be azotemic. Usually bilateral, but it doesn't have to be. And it's as few as 25% of cases that are confined to the kidneys.

OK. Underlines my point about abdominal lymphoma. You're often gonna find it in other organs in the abdomen if you look for it there.

Many of you may know about the long-standing description of CNS lymphoma commonly occurring with renal lymphoma. And that's based on one widely quoted study from the 1970s. I don't dispute that.

I think it is quite common for CNS lymphoma to co-occur with renal lymphoma. But I don't think there's anything special about renal lymphoma here. I think it's the whole abdominal lymphoma thing.

This was a cat, who had abdominal lymphoma, and the owner hadn't noticed this ocular sign you see here. The cat was visual and the cranial nerve assessment was actually pretty normal. Once we started treatment for the abdominal lymphoma and after, you know, week one and got into remission, the eye returned to normal.

And whereas we were, I think PLR and menace negative in the picture on the left, those reflexes have been restored in the picture on the right. So when we're talking about abdominal lymphoma. I don't think it's necessary to split it up into different organ systems.

Disease very commonly occurs in multiple sites and frequently extends to extra abdominal sites too, not least the central nervous system. I think at least that the strict, segregation of different anatomic forms of lymphoma in the feline abdomen is a bit too academic and arbitrary. Let's talk about a different type of lymphoma now.

This is Geza, our friend from the start. Geza has a big mass over the frontal sinuses. And you can see it started to eat through the bone up here.

And this is nasal lymphoma. Nasal lymphoma is a less aggressive disease in most cases. Than abdominal lymphomas.

And that's him looking bright and happy. Very beautiful. After just one dose of treatment, in this case, asparaginase.

Nasal lymphoma commonly doesn't present with a mass over the frontal sinuses, that's only about 1/5 of cases. It mostly presents like chronic rhinitis. Mostly with nasal discharge or sneezing, for example.

And diagnosis can be done most commonly by biopsy. CT or MRI is very useful if, if the client can afford it to plan the biopsy and determine whether the crib reform plate is intact. And that's very useful to know, especially if they're going for radiation therapy, you really want the crib reform plate to be intact.

CT or MRI can also be useful for showing you where the bone has been denuded, and you might be able to get a diagnosis with a needle, just with a fine needle aspirate if you know the right place to stick it, by seeing that the bone has been eroded there. So, as for a lot of head, head and neck tumours, CT really, really is helpful if you can. But if you can't, you could just be old school and take a blind biopsy.

Now, nasal lymphoma may be a focal disease and it often is. So that's a useful thing to know. 20% co-occur with disease in the abdomen.

And that's useful to know as well. If we've got a focal disease, particularly at an extremity of the body, we can consider radiation. And that can be a good treatment for this disease.

So as I say, radiation therapy, in cases like this. Can give an average survival time of 1.5 to 3 years with no chemo.

Please remember though that 20% of these cases involve disease at the sites, and it would be pretty silly to spend all the money on radiation of the nose and leave the abdomen alone if there's disease there. So before radiation, you need to stage these guys thoroughly to make sure that you can't find disease elsewhere. We're talking about lymphoma on a budget this evening and frankly, it's cheaper in a lot of cases.

To go with chemotherapy, because you don't necessarily have to stage them. The chemo will get in the body and work systemically, find the disease wherever it is. Well, that's the idea.

And the survival time for cats treated with chemotherapy is very similar to those treated with radiation. There's no survival benefit shown for chemotherapy and radiation therapy together, but from a common sense point of view, if you've treated with radiation first, you could always reserve the chemotherapy to use when the disease relapses. So in Giza's case, we gave one COP protocol and that kept the disease under control for almost 2 years.

My final thing to say on the nasal lymphoma is just a little bit of a warning. But most of the time it's a less aggressive or slower moving disease, shall I say, than the abdominal lymphomas. But please be aware that sometimes on rare occasions, you can get this horrible large granular lymphoma in the nasal cavity as well, and that is an aggressive disease.

I'll mention briefly peripheral nodal lymphomas in cats, characterised by peripheral nodal enlargement, a bit like a lot of dogs present. Don't mistake this for the more common types of lymphoma at extranodal sites because around 25% of these guys will have a degree of peripheral lymph node involvement. I guess you have to make a judgement call when you first see a cat as to where the bulk of the disease is.

If the bulk of the disease is in the abdomen with one or two peripheral lymph nodes moderately enlarged, we call that abdominal disease. If you can't really find much disease elsewhere other than peripheral lymph nodes, which are really pretty big, we call it primary nodal. This is another very aggressive disease, I'm afraid, and has been associated with FELV in the past, but it doesn't have to be.

Where I have seen this in more cases, not would be young cats. Can often have involvement of multiple organs and bone marrow as well, and they often present very, very ill. Now, if you see a case like this, remember that you've got some very important infectious disease differential diagnosis.

For example, mycobacterial disease in the UK. And in certain parts of the world where it's warm and wet, then you've got fungal disease to consider too. And in even more restricted geographic localities.

We still have bubonic plague. Your sinosis. And that can also present by enlargement of lymph nodes associated with the head and neck as well.

So make sure you're OK with the travel history of the cats before you go try to biopsy one of these nodes with an appropriate PPE. So for the peripheral nodal lymphoma in cats, we tend to talk about the chop, cop, or lomasine-based chemotherapy protocols. Annoyingly, there's an important differential here of a low grade lymphoma.

Which is the Hodgkin-like lymphoma. These presents with enlargement of peripheral lymph nodes, often without other clinical signs, OK? So it could be a perfectly happy cat with incidentally recognised very, very large lymph nodes.

Usually head and neck that can sometimes involve other parts of the body too, and you need histopathology for diagnosis. So this lymphoma is quite interesting. The lymphoma cells are few and far between.

They're these multinucleated giant cells that you see here. And the B-cell immuno phenotype, but they kick out a lot of cytokines to recruit in lots of benign T cells, and so it's a T cell rich B cell lymphoma. I'm telling you this because if you just stick a needle in these lymph nodes, you'll get a load of small lymphocytes, and it'll probably come back as reactive or even normal lymph node.

You may miss the cancer cells, which are few and far between. So you really need a biopsy to be able to diagnose this. It's worth knowing about because it can have a pretty good outcome.

I would stage these cases thoroughly because where the disease isn't anywhere else, you could consider surgery or radiation. That doesn't tend to cure the disease, but it can kick it down the road for at least a year or so. Ultimately, they tend to progress and in my experience, that's characterised by abdominal lymph node involvement.

So I tend to offer them a chemotherapy with Crabicillin Pred, just like for other low-grade diseases after surgery. If diseases turn up elsewhere, I'd kind of say that's the best way to go in the first place. So my next key point then is that surgery or radiation therapy are more likely to have a role in the treatment of feline lymphoma than canine.

And if you're considering one of these cases like a Hodgkin's-like lymphoma case or a nasal lymphoma case, make sure you stage these cases thoroughly beforehand. And finally, let's talk about the treatment of lymphomas. I'm doing this as a group, really, because it shouldn't be always rarely a disease-specific thing.

If you've got a low-grade gastrointestinal on a Hodgkin-like lymphoma, I'd recommend use of clorabiil and Pred. The doses of these things are well described, the BSAVA formulary being the place to start. Sometimes you get histologies from other parts of the body which present like a high grade lymphoma.

But the histopathology says it's low grade. Nasal lymphoma is what I'm thinking about principally here. Now, I'm sure the histology is right, but I would let the clinical behaviour of the disease be the decider.

And I've seen a few nasal lymphomas come back as low grade on histology, but they behave as intermediate or high-grade cases, and so I would treat them as such with the cop or chop type protocol or radiation. I don't think chlorambuil and Pred would have a, a role there. And with the intermediate or high-grade lymphomas, well, I'm afraid the jury is out on the best treatment to use, and that's the key difference between dogs and cats.

Many people would use COC protocol. Many would also use the COP protocol. And if you're unfamiliar with these, with cop we're talking about cyclophosphamide, vincristine and prednisolone.

And the COC protocol is pretty much the same thing, just as much cyclophosphamide, just as much fincristine, just as much prednisolone, but with the addition of doxorubicin. So note the H for doxorubicin and the O for vincristine because oncologists can't spell. So you've got people using both, and there's a kind of belief that Chop may be better.

It kind of feels right in your mind because the course goes on a lot longer. It involves more drugs, it's much more intense. A lot of people know that it works better in dogs and it works better in people, so why shouldn't it be the better treatment for cats?

And I can get that, get that train of thought. Well, let's look at this summary of the big publications on feline lymphoma to date, OK? These green ones are the cases treated with COC protocols.

Complete responses in a 70%, sometimes as low as 50%, but 70% isn't unusual. Survival time not reached at the top. Or 272 days or 388 days or 484 days.

And let's look at the studies where they use CHOP. Average survival time, you know, 47%, 38%, so sorry, response rate I'm talking about. 67% is kind of the best.

And average survival as well, 97 days, 210 days, 211 days. So if you look at the consensus of the publications, there's very little support for use of the CHOC protocol. And when you consider doxorubicin being used on its own, then we talk about only 26% of cats responding and having an average survival of 84 days here.

So certainly in a big group of cats, there doesn't seem to be a benefit of the COC protocol on its own. What seems to be highly prognostic is whether the cat responds to the treatment that you're giving. CR here is complete response, PR is partial response, and NR is no response, OK?

And these survival curves are easy to interpret. You have 100% of cats alive up here, 0% alive down here, and it follows that the cats who do better have a curve that is nearer 100% or longer. And those that do worse have a curve that is nearer gets down to zero sooner.

So the complete responders have a significantly better survival and partial responders who have a significantly better survival than the non-responders. So a key point, response to treatment. Is by far the most important prognostic indicator in intermediate to high grade feline lymphoma, and that applies to all anatomical sites, and there's very few ifs or buts.

There's no benefit shown a COC protocol over COP protocol in a group of cats. So it's good news, really. It's a good budget option.

For treating feline lymphoma is the six-week COP protocol. In Christine and cyclophostide are some of the cheapest, widely used, well available, and often quite, you know, well understood by vets, cytotoxic drugs that we have. So this 6-week protocol would involve 6 weekly injections of inpristine and oral cyclophosamide on 2 occasions, given if we can on a different day to the vincristine injection.

Alongside this we give a tapering course of prednisolone. And if the disease is in complete remission, no disease can be found anywhere rather. At the end of the treatment, you could give lorabil and Pred to maintain it.

In other words, you try to downstage the disease with Irving Christine, the cyclophosphamide and then treat it like a low grade disease afterwards. So, there's still very few treatment protocols that have been shown to, to be better than this. The way I interpret this, thinking that complete response is what we want and the cats who do best are those who completely respond to treatment.

Would be you start with something, it could be the cock protocol, it could be the CO protocol, it could be something else. It doesn't really matter. You just got to see whether the cat responds to it.

And that gives us flexibility to consider expense, convenience, ease of administration, number of vet visits, risk of adverse effects in making the decision rather than having a best treatment to use. So I'd say start the treatment, doesn't matter what it is. Assess response after only a few weeks.

If you've got a complete response, keep going and finish the protocol. Partial response, change your protocol. Adding other drugs, let's give that cat every chance of getting a complete response.

So the way I often do things is plan only a few weeks in advance. I'll give half of the COP protocol, and I restage. And then if we got a complete response, we'll finish.

Restage at the end, everything's under control. Maintenance therapy. If re-staging shows that you've only got a partial response, then I go off piste.

I add in doxorubicin usually I kind of make it a CO protocol. Only 26% of cats respond to doxorubicin, but what if this cat is one of those 26% for this particular cat, it may be a life-saving drug. So I add in Doo at that point or if that's difficult, say costs are involved, low mass team would be another good choice as well.

And so forth. If it reststaging at week 9, I find only a partial response, I'll talk about adding in another drug at that point as well. Now if costs don't stretch to a or funds don't stretch to a COP protocol.

A cheaper alternative would be week 1 vincristine, week 2 oralommatine. And then repeating, I mean, I apologise, there's actually an error here. It would be after low mustine, you'd want at least, 2 or 3 weeks without any treatment.

So this is more like week 5 in Christine and then week 6 Lomusteine again. Alongside a tapering course of prednisolone. You'd restage after a couple of these cycles if you're in complete remission, continue, do a couple more.

Well you could consider taking a risk and down, staging the treatment just slowmine only and giving that for a couple of cycles. If you've got the partial response only, well then try adding in doxorubicin. Or you could very pragmatically, brutally pragmatically counsel the owner that the further we go without getting response to drugs, the less likely we get, well, less likely we are to have response to other drugs that we add in.

So we could consider PTS and that's a decision I would support as well. And finally, we could do a similar thing of, you know, alternative being Christine and Lemastines, but without the Christine. Lomustine is, after all, an oral drug, and it doesn't have the expense of being given intravenously like in pristine.

So iblo Mateen, tapering Gared, re-stage, and then considering continuing if in complete response or changing impartial response. And finally, the most palliative approach would be just prednisolone on its own. People sometimes ask me the dose to use and, well, the nature of palliative treatment is controlling clinical signs.

So I would say start with 2 megs per gig orally every day, you could increase or decrease as needed to control clinical signs and maintain welfare. I'm not going to talk much about rescue therapies for cats because we're talking about lymphoma on a budget now. And also, in quite a grim way, rescue therapies rarely have a durable response in cats.

We're aware of some dogs who can do brilliantly with a second lymphoma treatment protocol. That's not really a thing with cats. I would look at rescue therapies in the same way.

I'd look at diversifying the treatment that they're on if they're only partial responders, thinking of the drugs that they haven't had, and talking about adding those in. And very brief digression here. People often ask me about side effects of these drugs.

Please be aware that they're different in cats to dogs. All drugs can cause gastrointestinal upsets and myelosuppression to lesser or greater degrees. Now vincristine actually is very light on the bone marrow and it can be useful like that.

But it can cause gastrointestinal upsets, usually not too bad. And it can cause peripheral neuropathies as well. And we might see that might plant a great walking or other kind of issues with locomotion.

In a similar vein, it can affect the myoteric plexus of the gut and cause ileus. So if you're given a cap in Christine and he or she is straining to poo, you could swap to blastine next time, and that usually resolves the ileus and it maintains the pressure on the lymphoma. We know that cyclophosphamide can cause sterile hemorrhagic cystitis in dogs, but that's not an issue in cats.

It doesn't tend to cause many GI signs. Myelosuppression is the principal side effect of this drug, and that means you can dose escalate if you need to. We know that doxorubicin can cause cardiotoxicity in dogs, and that's not a thing in cats.

Instead, nephrotoxicity. And bear in mind as well if you can call it an adverse effect that the majority of cats don't respond. Lomusine as well can be hepatotoxic in dogs, so that can be a lethal effect.

It can also cause severe and delayed myelage suppression. So the myelosuppression thing is the same in cats as it can be in dogs. They can get very myelosuppressed for a very long time in some cases, but the hepatotoxicity isn't.

Instead, as this would be predictable, it can be nephrotoxic. And finally, you've got, the mastine can penetrate into the CNS which can be useful for the cases with neurological signs, as can be syarabine at the bottom here. Cytarabine should really be given us a 24 hour CRI to be effective though.

And the last thing I'll say is that Eliparaggenase, which is a really good drug. Again, has a reduced response rate compared to dogs in some reports. So that was a brief digression to talk about the adverse effects of drugs.

Sorry, it was a bit of a whistle stop to her. The key points though. Is that both response rates and adverse effects of chemotherapy drugs are very different in cats to dogs.

And finally, I'll show you a face that you would have seen at the beginning. This guy had laryngeal lymphoma. He's also a very challenging character.

If you measure the difficulty of a cat in terms of the number of nurses that they have to have around him, well, this guy was a three nurse cat, OK? And he often needed, IV sedation for intramuscular sedation for IV chemotherapy. So a few things with dealing with the challenges that cats can present.

I would, I'm a big fan of using gabapentin where possible, and that made a lot of treatment possible with our friend Muro there because fortunately his owner could tablet him. They give it this paper, if you haven't seen it, involves giving 100 milligrammes of gabapentin before each visit to the vets, and that can facilitate a lot of procedures that would otherwise need IM sedation. I think it's really good.

We use this a lot in our clinic. Neuro though, was still difficult and would still not allow IVs. And after discussion with his owner, we elected to treat him with a mustine which the owner could give all relief and asparaginase which we could give subcutaneously.

And we repeated this every 21 days. So it wasn't really having. An intravenous chemotherapy protocol.

We were just seeing him every few weeks. Alongside this we gave prednisolone on a tapering course. We found that controlled the disease quite well and we transitioned him to a maintenance protocol here and he lived for 12 months overall.

There's another oral protocol I've got some colleagues who've used, which involves, just oral medication, so intravenous. This could keep costs down as well. I haven't got much experience of this particular one myself.

And here's a publication of lousine, methotrexate and cytarabine being given as a rescue treatment for feline lymphoma. Now, this only got a medium, disease control of 2 months, but it was used in the rescue setting. We've learned that rescue therapy for cats is very, very difficult.

So there might be cats who are difficult and very resistant to IV treatment. If they can be tableted, this might be something that can be considered. So the point I'm making is that creative or non-tested protocols can be considered to suit the characteristics of a cat, as well as the funding goals of the client.

But the clients will need to understand that these treatments are not fully validated and they could well be inferior to better established treatments. Nevertheless, they're much better than no treatment at all. And I'll end with this.

Again, sometimes people ask me about these, ports, vascular access ports. They're really good. If you haven't seen them before, they involve the surgical placement of this bulb under the skin, secured to, bony prominence, like in front of the hip, for example, and it's attached to this catheter, which is permanently inserted in a big vein, like the femoral vein.

So it can turn an IV axis into a subcutaneous needle stick. So it's good. I think these are really good for cats with bad brains.

I think I wouldn't consider them for the nervous cats and the difficult or aggressive cats, however, because they still involve restraint, they still involve in the needle stick, and I don't think that makes much difference to the cat. So if you needed IV sedation, IM sedation rather, to give chemo to a cat IV, you'd probably need it with these as well. In summary then, I hope I've impressed on you that most cats have extranodal lymphoma and they are sick at presentation.

Where there is a strong clinical suspicion of lymphoma, don't dismiss the diagnosis if cytology is not supportive. Consider histopath, looking at other anatomic sites, and if all else fails, a therapeutic trial to confirm the diagnosis. Anatomic site and grade are the most important pieces of information to get a prognosis and a treatment.

Hodgkin-like disease and low-grade gastrointestinal lymphoma are the low-grade diseases which enjoy extended survival, often with minimal treatment. Intermediate and high-grade lymphoma in cats are lumped together. They have response rates of 50 to 80%, but very variable survival times.

The survival depends on the anatomic site and whether a complete response is achieved. If you're treating a cat that only has a partial response where the lymph nodes or the site of lymphoma shrinks down a bit but doesn't go away. Add or change drugs to maximise the chance of the complete response.

When you're thinking about drugs and cats, bear in mind that the side effects are very different. Particular care with the kidneys needs to be taken. And for some localised diseases like nasal or Hodgkin disease, you can think about radiation therapy as the sole treatment without chemo, but be careful to stage thoroughly first.

After the intermediate high-grade lymphomas that are unmistakably aggressive diseases, there is a significant proportion in the order of 1/3 who will live longer than a year. So that's it. I would like to say a big thank you to my colleagues and they tolerate working with me every day.

Particular thanks to these guys from all over Europe who've supplied some of the images you've seen. As I frequently do a massive acknowledgement to the NHS to whom I'm extremely grateful. Thank you to Webinar vet for asking me to speak again, and thank you ever so much to you guys for tuning in to listen.

I'm really sorry I've run over a bit, but if you've got any questions and the webinar vet team are happy, I'll do my best to answer them now, or you could drop me an email on my email address below. Thank you, everyone. Thank you, Owen.

That was absolutely incredible, as always. You make, these intricate topics seem ever so simple and great, great insight into, to treating on a budget. It, it's been fascinating listening to you.

So thank you so much for your time tonight. Pleasure. We have run over, folks.

I saw nobody left, so nobody minded. But what we will do is if you have any questions, please either drop Owen a an email on his email address there or send it off to Dawn at the webinar vet, and she can get it on to Owen. And, get those answers to you.

Remember, we record all these sessions. So if like me, you're wanting to go back and watch this another 2 or 3 times, it will be on the website in the next couple of days. And you can watch it and pause it and rewind, which is always absolutely fantastic.

Owen, once again, thank you for your time tonight. Really, really appreciate it. Thank you all.

Folks, thank you for attending and to Dawn, my controller in the background, as always, thank you for making everything run seamlessly. From myself, Bruce Stevenson, it's good night.