Welcome, everybody, and thank you for joining me for this hour of lecture about tumours of the respiratory tract. Very sorry that I, I can't be doing this particular lecture in person, but I do hope that it's informative. And again, you can see my email here at the bottom of the slide.
Please feel free to reach out with any questions that you have after the lecture, and I will do my absolute best to answer them for you. So, quick outline about what we're gonna talk about. We're gonna sort of cover three different types of respiratory tumours today.
We're gonna start by talking about nasal tumours, and then we'll move to tumours of the mediastinum, and then finish off with primary lung tumours. So, without further ado, let's start by talking about nasal tumours. So in general, we think about nasal tumours as being relatively uncommon, but we do see a fair bit of them and just like most other kinds of cancer, they do seem to be more common in older animals.
We see more of them in dogs than cats, and as far as sort of what might make them occur does seem that in certain circumstances, living in an urban environment, things like a passive. Cigarette smoke that might be possible carcinogens that could contribute to the incidence. We do see more of this disease in Dolichocephalic breeds and in brachycephalic breeds, and I guess there's two competing theories about that.
So one would be that In a dolichocephalic breed, more of the particulates like smoke, etc. Actually get trapped in the nasal cavity rather than going down into the lungs. But the second possibility is, in a long-nosed dog breed, there's just more nose cells, and then statistically, there's just a higher likelihood of one of those cells turning into a tumour by bad luck.
So it could be a combination of both too. What kinds of tumours do we see in the nose? So in dogs, about 2/3 of the, of the tumours that we see are carcinomas, and the most common histotype would be an adenocarcinoma, so something arising from the glands in the nose.
We can also sometimes see squamous cell carcinoma in the nose as well. Sarcomas make up roughly the other 1/3, and it's a mixture of different kinds of sarcomas. We can see osteos, we can see chondros, we can occasionally see fibrosarcoma of the nose as well.
In cats, lymphoma really dominates lymphoma is probably 75% of the nasal tumours that we see, and then carcinomas make up the rest. So nasal sarcomas in cats are fairly uncommon actually. In general, with the exception of of nasal lymphoma in cats and rarely in dogs when it's seen, we really think of, of nasal tumours as being primarily a local disease problem.
So metastasis can occur. It's actually fairly uncommon at the time of diagnosis, about 10% of dogs may have spread to the local lymph nodes, but rarely to the lung. However, at the time of death on knee cropsy, more than that, maybe 40% of dogs may have evidence of pulmonary metastasis, but interestingly, it's very, very rare for that to be the cause of death.
It's usually, even with very aggressive treatment, local disease progression, that's actually the thing that causes the problems first. How's the dog likely to present if they end up being diagnosed with a nasal tumour? So, the most common presenting complaint is gonna be epitaxis, and often it'll start off being unilateral and they may progress to bilateral, sort of as time goes on.
And again, it's important for us to certainly think about the fact that there are other differential diagnoses for epitaxis other than nasal tumours. And here's our little dammit list that can just help us to think about some of the other things that we can see. So we can see inflammatory or immune-mediated diseases, things like systemic coagulopathy or hypertension are certainly on the list as well.
We can see foreign bodies, we can see 2/3 abscesses, we could certainly see trauma that could also cause epistaxis. So see, there's, these are some of the other things that we'd want to keep on our differential list. As we're sort of going through our list of diagnostics.
Some of the other clinical signs that we could see an animal present for other than epistaxis, could be sneezing or reverse sneezing, upper respiratory stridor. Facial deformity or swelling, exophthalmia, and rarely, we can actually see an animal present for CNS signs. So, seizures, altered mentation, etc.
If in fact, the, the tumour has penetrated the cribiform plate. One of the things that we know is fairly common is for us to see some amount of improvement of these clinical signs. With symptomatic therapy, so things like anti-inflammatory drugs and antibiotics, so initially it's possible to, to be misled and to think that what we might be dealing with is a primary infectious process if we see a response to antibiotics.
But quite often actually, what's occurring here is what we're effectively doing is, is addressing a secondary infection that's present. Over top of a tumour, and that certainly can improve our clinical signs transiently, but we don't want to be sort of misled into thinking that that automatically indicates a primary infectious process. So, on physical examination, there are certainly some things that we want to pay special attention to when we have a, a nasal tumour on our differential list.
And Some of these are we want to carefully evaluate airflow through the nostrils, and this can be done in a number of different ways with a glass slide. It can be done simply by occluding the nostrils one side at a time. Some people will put up a couple of strands of cotton wool and actually see if they're displaced through the nose.
Sometimes you can see crusting, serocellular crusting at the nays. It's great to look for facial symmetry. Both on the exterior of, of the muzzle and the sinuses, but also on the hard palate.
A good oral dental exam is a nice thing to do, even if it's, you know, fairly cursory when they're awake, to make sure that they don't have anything that might be consistent with a tooth root abscess. It's good to try and retropulse both eyes and make sure that they re retropulse equally. Again, because we can see these tumours actually infiltrate the retroorbital space.
And we definitely want to palpate the regional lymph nodes as well. As far as diagnostics goes, one of the first things that I really like to do, especially if there's any evidence of lymphadenopathy, is actually to try and obtain a fine needle aspirate of that regional lymph node. So about 10% of dogs, at least with nasal tumours may have evidence of disease in the regional lymph node.
And if they do, obviously, just a simple cytology of that regional lymph node is an incredibly easy and cheap way to achieve a diagnosis. Chest X-rays are a great, a sort of insurance policy to do. Again, the likelihood of finding disease in the thorax at diagnosis is actually very, very low, but especially if we do have an owner who's gonna do a lot of fairly complicated staging and treatment of this disease, it's, it's a great, as I said, insurance policy to make sure that there isn't any other disease process.
Going on in the, in the thorax that might potentially change the owner's approach. Standard pre-anesthetic blood work, making sure the dog is safe to anaesthetize, is a great thing to do, obviously. It's rare that we'll find anything that's indicative or pathonomonic of neoplasia there, however, coagulation studies are actually very useful, in two ways.
One of them is, obviously, To rule out a systemic coagulopathy as one of the potential reasons for epistaxis, and the other is it's nice to be able to do because, if we are gonna get a biopsy from up the nose, it's nice to sort of feel comfortable that, yep, in fact, that dog isn't gonna have life-threatening haemorrhage as a result. And then because severe hypertension can be another thing that's on our differential list, we'll often try and get a blood pressure measurement as well. Some kind of imaging is likely going to be necessary to really get a better sense about what's going on.
And one of the places that will often start is just with plain old flat radiographs, and they can still be actually incredibly useful. And I think we're all familiar with the, the quote unquote skull series that is often performed when we're actually looking at skull radiographs and maybe there's 6 different films that get taken. But really, if a nasal tumour is high on our differential list, it's this, it's this open mouth VD view that's really likely to give us the most information.
And one of the things that we really make sure that the students understand is that positioning, is really, really critical in order to be able to adequately interpret this kind of film. So again, you want to hopefully have a a radiographic X-ray head that tilts, and again, then you want to make sure that you retract the jaw back as far as possible, so you can get a clear shot on that maxilla. And again, making sure that they're straight is actually really, really important because when we're looking at plan all X-rays, really, we're looking at symmetry.
What we're trying to determine is whether things look the same on one side as on the other side. And again, just here's some, some examples here of radiographs from a dog, a normal dog, and then a dog with a nasal tumour. So again, some of the things that we could see on our flat films are things like loss of turbinate architecture, lysis, or deviation of some of the cortical bone, especially at the septum.
Llysis of the soft palate, and you certainly may see increased soft tissue opacity either within the nasal cavity itself or within the frontal sinus as well, either unilaterally or bilaterally. So these are all some of the things that we'd be looking for that certainly wouldn't give us a, a slam dunk diagnosis of nasal cancer, but certainly would increase our index of suspicion. Three-dimensional imaging, like what we can get from a CT scan is generally much more useful in really working out these things for a couple of different reasons.
So certainly one, it really helps guide our tissue sampling in a way that allows us to better maximise the likelihood of getting an answer from a biopsy procedure that we do. It gives us prognostic information. So we do know that with sort of conventional radiation therapy, which is the treatment of choice, significant bony lysis, especially of the cribiform plate, is a negative prognostic factor.
And that could certainly change how some owners choose to treat the disease. And these images that are obtained can actually be used to plan radiation therapy as well. So, MRs can give you beautiful, beautiful soft tissue information.
It can tell you with great, great, specificity, whether there's parentchimal brain involvement from a nasal tumour, but those images can't be readily used for radiation therapy planning. And that's why a CT is generally much better. Fun fact, if you have an owner who, after you have sort of an initial discussion, really seems like they're very interested in pursuing potentially radiation therapy, if in fact, their, their pet is diagnosed with a nasal tumour, it's often helpful to actually refer for a CT scan at the site where the radiation therapy is going to be performed.
And the reason for that is it's very challenging for a radiation oncologist to be able to utilise CT images that are obtained elsewhere. And what that would mean is if an animal goes somewhere to referral hospital for a CT, then go somewhere else for radiation therapy, that CT is usually gonna have to be repeated. And you know, obviously that can invoke some ire among owners.
Why should I have to pay for two scans, blah, blah, blah blah. So again, if you think you have an owner who might be going down the road towards thinking about radiation therapy, sending them directly to the practise with the radiation oncologist for their, for their workup is probably a great sort of cost saving measure to consider. Another thing that we'll commonly do in these patients is rhinoscopy, and that really allows us to potentially visualise abnormal tissue as, as you see sort of at the bottom of this slide, and potentially sample it as well.
And this can be done with rigid scopes, similar to the kind of scope that you would use to scope a joint, for example, and you can also use a flexible scope. And the advantage of a flexible scope is it does allow you to retroflex the scope behind the soft palate. And visualise sort of the caudal area of the nasal cavity in greater detail.
The downside about these, about using rhinoscopy is that the pieces of tissue that we're able to obtain for histopathology are very, very small. Generally with endoscopy. And as a result, sometimes they are subject to unfortunate sampling error.
So, hey, this is just a really big mass, and we're taking some very, very tiny pieces. Sometimes they end up being very superficial, sometimes we do just simply miss the tumour, using these very, very small samples. So there are some other ways that we can potentially achieve a diagnosis.
And one of them is a very simple technique that's called a nasal flush. Sometimes it's also called nasal hydropulsion. And again, one of the real advantages of this technique is it does not require any specialised equipment.
So really, what, what, what you see here is all we need. We need a rubber ear bulb syringe, we need some sterile saline, and we need a bowl to collect everything. So under general anaesthesia, basically the way this procedure works is you fill up the entire syringe all the way to the brim with saline.
Then shove it up the nose and really create a very, very tight seal around the nostril, and then with a really significant amount of pressure, actually flush that saline up the nose. It's going to go off and drain out the mouth. You can see there's actually a collection, basin down here, and sometimes we'll actually see some of the material end up in the back of the throat.
So you really want to make sure that you have a very, very well inflated, endotracheal tube cuff, and that you actually check the back of the throat before you extubate the dog, because sometimes your best little pieces of tissue may actually be back there. So this is a fairly traumatic technique, which is great. It can be very diagnostic.
It's actually quite common to flush out, in some cases quite large pieces of, of tumour tissue using this technique. And in certain circumstances, it can be therapeutic as well. So here's an example where we actually flushed out a here in the states, we call them grass-ons, but you know, a piece of a piece of, vegetable material that the dog actually hoed up into its nose.
Even in dogs who have primary tumours up the nose, we often find that this flush procedure does have some palliative, abilities as well. So we do see at least a transient reduction in sneezing and bleeding and things like that often after a nasal flush. And then a third technique that can be used as a pinch biopsy.
And actually, this is a great technique. So you can use sort of a variety of different kinds of metal biopsy forceps. These particular ones are actually ma uterine biopsy forceps, but they come in a bunch of different sizes.
They're all metal, so they can be steam sterilised very easily. And then the other material is just typical stuff that you would do for any biopsy. So some biopsy cassettes, some needles to tease the sample off, and some formalin.
So one of the things when we're doing a pinch biopsy to make very careful assurance of is that we are not extending our biopsy instrument too far into the nose, in which case, it's conceivable that we could actually be sampling grey matter. So how do we do that? So if you actually measure from the tip of the nose to the medial canthus of the eye, there is no way that if you insert the scope that far on any size dog or cat, That you're going to penetrate the cribiform plate.
So often what we'll do is put a little piece of tape or something like that right at the site, where that measurement comes out, and then grip that very forcefully while we're inserting our biopsy, instrument to make certain that we do not exceed that distance when we're sampling. So it's very, very, very common, especially after this kind of biopsy for some epistaxis to occur. It's rarely life-threatening, but one of the little helpful hints that I've learned over the years is it's always really nice to a forewarn owners about this.
There is going to be some more excessive epistaxis after the procedure. And I will usually offer to hang on to the pet overnight, assuming that there's, you know, somebody who's there overnight. And again, it's not necessarily because there's a huge risk of life threatening haemorrhage, but because it's gonna make a big mess in the owner's car, it's gonna make a big mess potentially in the owner's home when the dog gets home.
If the dog is gonna have some sneezing and bleeding. That's more than what the owner's been experiencing so far. It's just nicer for them to do that in the hospital where it's easy for us to clean it up.
So, nice thing to offer, certainly not mandatory in any stretch of the imagination. So as far as treatment of nasal tumours go, you know, really, we can, we can divide them into sort of three groups. There's kind of definitive therapy, there's sort of middle of the road therapy, and then there's, you know, truly palliative intent therapy.
And with truly palliative therapy, so things like again, intermittent antibiotics, intermittent nasal flushes, non-steroidals, we're looking at a median survival time of about 3 months or so. And non-steroidals, interestingly, do tend to improve clinical signs in, in quite a lot of, of dogs with nasal tumours, but they don't tend to extend life. So they're a wonderful thing to use again, when we're, when we're doing sort of pursuing palliative therapy for nasal tumours, I usually will reach for a non-steroidal over a corticosteroid, unless We're dealing with what's probably lymphoma, just because we do seem to have better palliation with the non-steroidals, and there's a theoretical possibility, especially if we're dealing with a carcinoma, that there could be some amount of of an anti-tumor effect, although it's obviously not profound.
One of the questions that gets asked a lot by owners is, well, gee, can't you just do surgery to, to take out the mass and really that's been looked at in, in several studies and unfortunately, in the majority of studies, surgery is really not superior to symptomatic therapy. And again, I think the reason for that is when it's used by itself, there's just really no way that you can go in there and get out the whole mass unless it's very, very focal and even in that circumstance, you're really not gonna get any kind of of surgical margin of normal tissue. So surgery really is not a useful therapy by itself for this disease, unfortunately.
So what about medical therapy? So again, radiation therapy is a challenging thing to do in a lot of places. It requires travel, it requires anaesthesia.
It sometimes requires time in the hospital for practical reasons. So chemotherapy has been looked at. There are actually two studies that come out of Australia that have looked at chemotherapy for this disease, and the first of these actually dated to a time when there was no radiation therapy anywhere in Australia.
And then there's a second one that's more recent. Both of them were looking at a combination of, paroxicam. You could probably substitute a different NSAID if you'd like with alternating carboplatin and doxorubicin.
So, every 3 weeks they come in and they get one or the other. The official protocol calls for 6 total treatments, so 3 of each. And in, in these two studies, it looks like again, the majority of dogs actually do respond clinically, so again, less sneezing, less bleeding.
When serial imaging has been performed, they actually have seen objective tumour regressions, and in the more recent study, which is larger, probably 20 or 25 dogs, median survival time was about 8 months, so almost 3 times as long as with just palliative therapy. So, again, if radiation therapy is off the table for an owner, it certainly does appear that chemotherapy is something that could be a reasonable consideration. However, the, the gold standard still does remain radiation therapy, and as I mentioned previously, the radiation therapy does require a CT scan, and the, the sort of old gold standard form of radiation therapy that's been used for decades, generally requires somewhere between 2 and 4 weeks of daily treatment, Monday through Friday, .
Each one does require a very brief general anaesthesia. In general, tolerability is quite good. Almost all dogs will have resolution of their clinical signs.
And if you look at all the dogs that are treated with radiation therapy, median survival time is generally in the 12 to 18 month range. So those dogs that do have penetration of the cribiform plate, and those dogs that are diagnosed with what's read out as an anaplastic carcinoma on histopathology. Tend to fall on the short side of the average mark, but beyond that, sort of tumour histotype doesn't matter.
So adenocarcinoma versus squamous cell carcinoma versus chondrosarcoma, all of them tend to have relatively equivalent, outcomes with radiation therapy. Some studies have suggested potentially a little bit of an improved outcome, maybe in the sarcomas compared to the carcinomas, but in most studies, it hasn't reached statistical significance. Cats with nasal lymphoma are a little bit different in that actually, the treatment can be quite efficacious.
If we can convince ourselves that the disease is solitary at the time of presentation, radiation therapy results in virtually 100% clinical response rate, and long term, so greater than 2-year control of the disease is actually quite common. After radiation therapy. So this is a, a really an exceptionally good treatment for nasal lymphoma.
Here's one study that actually looked at, at various treatments for nasal lymphoma in cats, and actually looked at chemotherapy by itself, radiation therapy by itself, or a combination of radiation therapy and chemotherapy. And actually, in this group of patients, you can See, it's the cats that got radiation therapy by itself that actually had the best outcome. So I think one of the take homes here is, I don't really think there's any obvious advantage to combining radiation therapy and chemotherapy in these cases.
I tend to just do radiation and kind of save my chemotherapy for later if we're dealing with relapse down the line. But the other thing to take away from this too is that actually, if you look at the animals that got only chemotherapy, There were not a lot of them, but they didn't do that badly. So we're looking at median survival times, probably in the neighbourhood of about a year with chemotherapy.
So perhaps it's not an ideal treatment. But again, if radiation therapy is off the table, it does appear that conventional chemotherapy, much like we would use for high grade lymphoma in other locations in cats, might be a very reasonable sort of second tier alternative. There's another form of radiation therapy that we can offer that's less expensive, less intensive, may not require a CT scan, and this is what's called palliative radiation therapy.
So this is generally the kind of thing that's, that's done, maybe weekly, maybe just 3 treatments at almost weekly intervals, so 0 days, 07, and 21. Etc. So, quite a few different sort of protocols reported, but these are again less frequent, they're all outpatients, they don't necessarily require advanced imaging, and as a result, they're considerably less expensive.
And again, 70-80% of dogs may have significant improvement in their clinical signs. And depending on the study that's, that's looked at, we're looking at again, median survival times in that sort of 5 to 10 month range. I think if you quoted 8 months, just like what we get from chemotherapy, that's probably reasonable.
So again, either chemotherapy or this, this simple palliative radiation therapy might be very, very reasonable, quote unquote, middle of the road treatment options for an owner to consider if quote-unquote curative intent radiation therapy is sort of more that they're more than they're capable of doing. So other palliative measures that we sort of mentioned before, again, intermittent nasal flush, anti-inflammatory drugs like non-steroidals, and again, potentially intermittent pulse dosing of antibiotics to address any secondary infection that's present, might be a sort of palliative measures that could be considered for an owner who wants to be very conservative. More recently, both here in the states and to a degree in Europe, there's now sort of a newer form of radiation therapy that's available called stereotactic radiation therapy.
And really what this involves is a small number of very, very high doses of, of radiation that are delivered in an incredibly focused and targeted way which really allows very precise targeting of the tumour tissue. And avoidance of the normal tissues that again, are, are really so sensitive to radiation and that are in the field in, in animals with nasal tumours, things like the skin of the muzzle, the eyes, the nasal mucosa, the brain, things like that. So this is just a fancy, what's called a, like a dose colour wash of a dog head with a nasal tumour in it that you can see with a sort of a conventional form of radiation therapy where you just sort of shine down the radiation in two beams, maybe with a little sculpting of the beam.
You can see an awful lot of radiation. Is being, is being dosed to the skin itself, and to some degree, the eyes as well. With either intensity modulated or, or stereotactic radiation therapy, you can use a whole lot more beams, and as a result, really substantially reduce the dose of radiation that's delivered to the skin as well as, again, to the eyes, to the brain, to the nasal and, oh sorry, to the oral mucosa and things like that.
So really with this kind of very, very focused radiation, we're able to get a very high dose of radiation into the dog in a very small number of doses, and from an owner satisfaction perspective, you know, that's really nice because instead of the dog having to be, get 15 daily treatments, but either back and forth or spending time in the hospital, you can get the whole thing done in 3 treatments or sometimes 5 treatments. And in the early studies that have been done using stereotactic radiation therapy for nasal tumours, it does look like the vast majority of dogs improve clinically, about 70% of them will have meaningful tumour shrinkage, and you're looking at median survival times that are kind of in the same range as what's been reported with. Conventionally fractionated radiation therapy, so 12 to 18 month kind of survival times.
One of the things that we've observed here at CSU in, in the first few 100 patients that we've treated is a not in significant risk of late complications like bone destruction. And secondary chronic infection. So we're starting to try and modulate our treatment protocols to try and minimise the likelihood of that, those kinds of side effects occurring.
So again, these dogs aren't dying from tumour necessarily, but they are developing these sort of chronic nasal discharges, having osteomyelitis and bony sequetra up their nose and things like that, that certainly can be problematic. So it's a work in progress, but this is certainly a really nice alternative to conventional radiation therapy that in early studies really appears to be roughly equivalently effective. So, moving on, we're gonna go on to tumours of the Minal space.
So, how's a dog or a cat with a mediasinal mass likely to show up in your practise? So, the most common thing that we're gonna see would be signs related to the respiratory tract. So exercise intolerance, tachypnea, dyspnea, etc.
In dogs, we can see, a syndrome called pre-caval syndrome. This is kind of a, a strange example here. So you can see facial swelling, you can see dependent cervical edoema, you can sometimes see swelling of the four limbs, and this is actually, as a result of restriction of lymphatic flow due to a space occupying mass in, the cranial media stinum.
So, I have never seen or heard of this occurring in a cat, but I don't, I suppose it's not impossible. The other species, of course, where this, this can occur is, is cows. So we do Talk about pre-cable syndrome in cows as well.
Some animals may actually present for polyuria, polydipsia, secondary to hypercalcemia. We know that about 40% of dogs with primary mediastinal lymphoma may be hypercalcemic, but, hypercalcemia has also been reported in some cases of thymoma. So, one important thing is just because a dog is hypercalcemic and has a mediastinal mass doesn't mean we can automatically assume that that is lymphoma.
Again, thymoma is still a possibility. And another thing that's talked about all the time. Is this non-compressible thorax in a cat.
And for the longest time, I was kind of a sceptic about this. So the, for especially during my residency, I said, really? Non-compressible thorax, what does that even mean?
So, you know, during my residency, I compressed the thorax of every single cat that came into the clinic, so hundreds of cats. And when I felt a cat with a, a cranial mediasinal mass, it honestly did have a non-compressible thorax. So this is really a thing.
It's not just something that we teach the students. Occasionally, we can see signs like regurgitation. Or systemic weakness.
And again, this could be a sign of secondary myasthenia gravis, either focal or, or, disseminated, which again is a known perineoplastic syndrome associated with thymoma. So some of the differential diagnoses we would have on our list for a mediastinal mass, the most common too would be lymphoma or thymoma. However, we can see ectopic thyroid tumours in this location, so we can see ectopic thyroid tissue anywhere from the base of the heart to the base of the tongue.
So this is a consideration, and we certainly can see heart-based chemodectomas as well. Rarely, we can see other kinds of things that can occur. We can see metastatic.
Neuroendocrine tumours, metastatic mast cell tumours, other kinds of things that can occur in the space, but you know, these are, these are the most common ones that we see. So generally, after we, we sort of obtain a, a thoracic radiograph, which is what we would do in, in most animals that come in with respiratory distress, etc. We're gonna need to sample these, this lesion and really in order to know what's going on.
And it's really an important distinction to make, because, for example, the most common too, lymphoma and thymoma are treated completely differently, right? So, with thymoma, it's generally a local surgical disease, and lymphoma is generally treated with chemotherapy. So, being able to make the distinction is very, very important.
And generally, what we'll start with is some kind of ultrasound guided sampling of the mass, either a fine needle aspirate or a needle core biopsy. And with a fine needle aspirate, sometimes these can be a little bit tricky because both lymphoma and thymoma are likely to have a cytologic picture that's mostly lymphocytes. So a lot of times, a clinical pathologist may have a little trouble being definitive about the diagnosis based on cytology.
If there are a lot of mast cells in the sample, that is something we see more commonly with thymoma than with lymphoma. And if the mass appears to have a a lot of cysts within it on ultrasound, that's also something that would be more common to see with thymoma than with lymphoma. So one of the things that we can do if we are faced with one of these problematic samples where it's hard to make that distinction is flow cytometry, which can actually be a very useful test for making that distinction between lymphoma and thymoma.
And I'll show you that in just a second. And again, if we're thinking that this is something where local treatment, either surgery or radiation therapy may be in the cards, then a CT scan is gonna be very useful to help us plan our, our local therapy approach. Just a little bit more of a digression about flow cytometry.
So this is a paper that was published a while ago actually from Doctor Avery here at CSU that looked at flow cytometry for the diagnosis of, of thymoma in dogs, and actually, normal thymuses contain lymphocytes, that's their job. They're like an incubator for T cells. But the interesting thing about the, the lymphocytes within thymuses, within, whether they're normal or malignant thymuses, they have a phenotype that's unique.
So they have the markers CD4 and CD8 on their surface. So they have dual markers that identify, in this case, helper T cells and cytotoxic T cells. So you can see, if you have an odd carcinoma, it's gonna be negative for both.
If you have a lymphoma, most of the lymphomas are gonna be CD4 positive and CD8 negative. So this dual positivity is associated with thymoma, and flow cytometry is actually a very good test for being able to assess that. There's some evidence that PCR for antigen receptor rearrangement, which is a different molecular test that's used commonly for lymphoma, can also make this distinction in many cases.
And the advantage of that test is actually it can be done on air dried slides that have already been submitted to the lab and potentially already even been stained. Flow cytometry, alternatively does require live cells. So you'd have to either collect them at the same time that you collect your cytology or get the dog back and, and recollect the samples for flow cytometry if it's needed.
So, what are the treatments for these mediasinal tumours? So if we diagnose a mediasinal lymphoma, generally chemotherapy is the treatment of choice, the kind of chemotherapy that we generally would recommend would be similar to what we would use for other high grade multicentric lymphomas in dogs or cats. So this would generally be sort of a multi-agent injectable chemotherapy protocol, like a chop-based type protocol.
In general, both cat. And dogs with primary mediastinal lymphoma will often fall on the short side of the published survival times. If you look at sort of all the lymphoma data and in dogs, it's because most of these are going to be T cell in origin, and we know that the majority of T cell lymphomas don't do as well as B cell lymphomas.
In cats, a lot of cats with primary mediastinal lymphoma are going to be feline leukaemia positive, and that's a known negative prognostic factor. In thymoma situations, the treatment of choice is surgery. So again, CT scans are very nice first to make sure that we don't have really extensive involvement of the great vessels or things like that in the thorax that might make resection difficult.
But in those cases where surgery is possible, the outcome is actually quite good. So median survival times are in the neighbourhood of about 2 years with surgery. Versus a couple of months in those cases that are treated palliatively, so there's recent data that suggests that radiation therapy can actually provide good palliation in some of these cases, either again high dose stereotactic or palliative radiation therapy can be very good at at controlling clinical signs if they're present.
So again, if a dog has or cat has. Pleural effusion or pre-caval syndrome or things like that, we can often shrink up these masses enough to address those clinical signs. Similarly, actually, very conservative chemotherapy, like, like COP-based chemotherapy, which is a conservative lymphoma-based chemotherapy, can sometimes be useful as a palliative measure in in dogs with thymoma as well.
And in both of these cases, whether it's palliative radiation therapy or whether it's palliative chemotherapy, what we're probably doing here is actually not killing the tumour cells, which is the epithelial component of the tumour, but killing the resident lymphocytes, or at least a subset of them, enough that we're depleting or, or shrinking that mass enough to provide some relief. So is it a cure? No?
Is it necessarily a super long term? Palliative measure, not necessarily, but, but can it be helpful in addressing some of these very serious clinical signs that some of these dogs can present for? Absolutely, it absolutely can.
So that's definitely a reasonable thing to consider, either palliative radiation therapy or very conservative chemotherapy if if surgery is again declined or not possible based on how the imaging looks. So how about chemodectoma? So really, the jury is still out on what the optimal therapy is for these dogs.
There's some very early work that's now almost 20 years old. Again, that comes from Colorado State that actually suggested that dogs who got a pericardectomy, even if they started out without pericardial effusion, actually had a markedly better outcome than those dogs that are not treated with pericardectomy. And again, this is a potentially a nice thing to offer, especially now that more and more places are able to do this thoracoscopically, so minimally invasive, short recovery time.
And again, it certainly may avoid a very significant problem if a dog goes on to develop pericardial effusion or if in fact that's a presenting complaint. There are two studies that have actually looked at very small case numbers using Taserinib or palladia. For the treatment of chemodectommas, and the large majority of dogs that were treated with peladia had at least stable disease for 2.5 months or more.
So there weren't a lot of dogs that experienced objective tumour shrinkage, but quite a few were where their tumours stopped growing for a period of time. And again, this resulted in in median survival times in excess of a year with with tarinib. So this would be something that's definitely a reasonable consideration.
And then again, much like the thymoma during radiation therapy, either conventionally fractionated or stereotactic, can be very effective for these tumours as well. And we're looking at median survival times again in that sort of 1 to 2 year range. .
So quite often what what we'll think about doing is planning on a sort of a succession of treatments. So often we'll talk about starting with radiation therapy, keep toserinib in our back pocket, so if the disease progresses either locally or metastatically, we still have that treatment down the line. If we have an owner who lives close by and who we feel is very, very.
Attuned to their dog, we often won't do a prophylactic pericardectomy in the absence of pericardial effusion. If we have an owner who lives very, very far away and we're worried that they're not gonna be able to get to a veterinarian, in expediently, and we might actually lose a patient from acute pericardial effusion, we certainly do talk to those owners about, about preemptive pericardectomy to avoid the consequences of that pericardial effusion. So again, lots of choices, not one clear winner.
We often prepare owners for some mixture of the three over time. And last but not least, we'll, we'll talk very briefly about primary lung tumours. So In general, if you're looking at just sort of pulmonary lesions in general, we actually see more metastatic disease in the lungs than we do see primary lung tumours in dogs.
In humans, it's a bit of a different story, and the vast majority of the difference is associated with smoking-related disease. Almost all the lung tumours that are observed in dogs and cats are malignant, so benign pulmonary tumours are very, very rare. As far as idiopathological factors go, it does look again like some studies have suggested that there may be an increased incidence in urban environment or in smoking households, which again may have to do with inhaled particulates and things like that.
Dogs that inhale plutonium have a high incidence of lung cancer, but thankfully, that's not a very common occurrence in our clinical practise. So how's an animal with a primary lung tumour likely to show up at our practise? So again, cough, hemoptysis, potentially exercise intolerance, shortness of breath, these kinds of non-specific signs, may very well be seen.
A subset of dogs actually could present for lameness. And actually, this, there's a subset of lung tumours that can actually metastasize to bone. But in dogs, especially dogs with large primary lung tumours, we do also worry about hypertrophic osteopathy, which again is this, sort of symmetrical laying down of, of new periosteal bone.
Generally, it occurs in all the limbs simultaneously and starts at the very distal limbs and works its way up. About 25% of these can be detected incidentally. So you're radiographing the thorax for something else, and you happen to find a primary lung tumour.
And cats, one of the things that, that we always teach about in school is this lung digit syndrome, which is also called metastasis. So if we see a cat with a funny looking digit, we sample it, and it ends up being carcinoma. We always want to look in the, in the chest for a primary lung tumour.
So in cats, not so much in dogs or people, primary lung tumours like to metastasize to the periphery and for whatever reason, most commonly to the digits. I've seen in other places, I've seen them go to the eyeballs, I've seen them go to the tail, to the brain. But for whatever reason, the digits seem to be predisposed, so we always like to keep lung digit syndrome or acrometastasis in mind.
So, chest X-rays are obviously gonna be sort of one of the top things that we use as a diagnostic tool here. And again, the classic appearance of a, of a primary lung tumour is gonna be a usually large and solitary lung mass, often occurring, but not exclusively in a quato dorsal lung field. And again, some animals can certainly present that already have pleural effusion the very first time they're diagnosed, and we certainly want to take a careful look at the lymph nodes as well, although the lymph nodes have to be gigantic if we're talking about the hylar nodes in order for them to be visible on, on plain old flat X-rays.
So, here's an example. Here's a kitty cat that just has a large, solitary lung mass. In this case, it's not in the corto dorsal lung field, but in the car ventral lung field.
And here's a dog. This is a very old radiograph, but again, here's a dog with a, you know, a fairly nondescript, really not all that exciting radiograph on this lateral view. Let's take a look at the, the ventro dorsal projection, and you can see a really, really huge lung tumour that's primarily silhouetted over the heart.
So again, really sort of just lends credence to the thing that again we teach everybody in school about, hey, it's really, really important. To get those orthogonal views and ideally 3, when you're looking for lung pathology, cause sometimes you can really get fooled with only a single view. So, obviously, primary lung tumour is the only possibility of, of things that we can find on these X-rays.
So, primary lung carcinomas would be high on our list, but we can also sometimes see primary lung sarcomas and hisytic tumours, although it's called histiocytic sarcoma, it's technically not a sarcoma, but You know that term is used a lot, so that's something we can definitely see in the lungs. We certainly can see metastatic disease and occasionally we can see a dog with a solitary, somewhat large lesion that ends up being metastatic disease, although multifocal smaller masses would be more consistent with metastatic disease. We can see granulomatous disease of varying kinds.
We can see fungal disease. So here in the United States, there are certain parts of the country where we see a lot of fungal disease, where that's definitely a possibility. Then there are a couple of sort of oddball diseases that can sometimes occur as well.
One of them is called pulmonary infiltrates with eosinophils. That's often multifocal, somewhat patchy, soft tissue opacities, and then there's a disease that you'll find in the literature referred to as pulmonary lymphomatoid granulomatosis. More recent data suggests that this is actually a low-grade form of lymphoma, but again, usually multifocal, plus or minus with lymphadenopathy.
If, again, we have a disease that looks solitary, looks like it, there's a high likelihood that it's going to be a, a primary lung tumour, CT scan is very, very useful in these patients as well. And, obviously, the main reason for that is it really allows us to be much more sensitive with looking in the entire thorax for evidence of disease. So, are there very, very small pulmonary metastases elsewhere that are so small that we can't see them on flat films?
And very importantly, Is there evidence of hyal lymphadenopathy that can sometimes be relatively subtle? So here's just an example of a dog that certainly does have contrast enhancing hylo or tracheobronchial lymph node with the presence of a large primary lung tumour as well. So this lymph node is going to be small enough that you probably would not see it on a plain old X-ray, but again, it's certainly quite obvious here on the CT scan.
And again, we'll, we'll get into it in a second, but this is actually a very important prognostic factor. So having this information will change what some owners might choose to do. What about sampling these lesions?
So, often, again, for a lot of these lesions, we can do an ultrasound-guided fine needle aspirate. That's generally quite a well-tolerated technique. And if we're dealing with a carcinoma, it's certainly quite common that we're gonna be able to establish a diagnosis using that technique.
However, if we have a solitary lesion in a caudal lung lobe without evidence of lymphadenopathy, and you don't live in a fungal endemic area or an area where there are other diseases that can cause, you know, solitary pulmonary masses, it's certainly not wrong to skip that procedure and go right to surgery, you know, with, with appropriate owner education. So I did kind of give it away. Surgery is the treatment of choice for this disease.
So generally, again, it's great for the surgeon to be able to look at all of the lungs at the time of surgery to make sure that there isn't metastasis, that's sort of below the level of detection. And whenever possible, we do recommend that those those tracheobronchial lymph nodes be sampled, if at all possible. So, Again, we spent a lot of time sort of talking to owners about, these kinds of pulmonary surgeries, thoracic surgeries.
And again, if we have an owner who has any personal experience with something like this from their themselves, a family member, a friend, you know, we really have to spend a lot of time talking to them about how different the recovery period is in our dogs and cats than it is in people. So people are in bed for a month. After a thoracotomy, and you know, our dogs and cats are up and walking the day after surgery.
So big, big difference in terms of tolerability there. That's a really important decision factor for some owners. But what about thoracoscopic approaches for this disease?
So for smaller tumours, this is something that definitely can be approached thoracoscopically, and that certainly does decrease the recovery time even more than what we see with, with, just a tho thoracotomy, which is incredibly well tolerated. The big downside is it's incredibly hard to sample those tracheal bronchial lymph nodes, which is again an important staging tool in this disease. So some pros and some cons about a thoragoscopic approach.
So quite a difference in outcome depending on some factors that are fairly easy for us to assess. So one of the simplest is, is the dog showing clinical signs or not, or again, is this dog in that 25% where it was detected incidentally. So the dogs in which it was detected incidentally tend to do about twice as well as those that are clinical at the time of diagnosis.
Nodal status is a huge, huge prognostic factor. So again, in one study, it's a difference of 1 month versus 15 months for dogs with node positive versus node negative disease. So again, this goes back to why am I such a big fan of CT scan before surgery for these dogs, cause there's an awful lot of owners who are gonna rethink doing surgery for a dog who already has metastasis in the lymph nodes because their post-surgical outcome is so poor.
So for a lot of owners, this could actually change what they choose to do. And then histologic grade is actually another very, very important prognostic factor. Unfortunately, we don't have this information until after the fact, so you can't use that as a way to educate the owner about whether they should go to surgery or not.
But again, obviously, dogs with low grade tumours do about 10 times better than dogs with high grade tumours. So what about chemotherapy? We really don't have as much information as we would like about chemotherapy for this disease.
So in dogs with either unresectable, metastatic disease, or in situations where an owner has declined surgery, we certainly have occasionally seen objective tumour shrinkage with some chemotherapy drugs. The two that are, are talked about most commonly are vinaelbine. And carboplatin, both of these are quite well tolerated in dogs, at least here in the States, they're quite inexpensive.
So, if we're wanting something from a palliative perspective, these are certainly reasonable things to consider. We really don't have the best evidence yet or really any evidence yet. About if they are useful when they're used postoperatively, in those patients with high-risk disease, so high grade or node positive disease.
So this is something I feel very comfortable talking to owners about as a consideration, but unfortunately, I really can't quote any statistics or percentages about exactly how well it works. If I'm treating something that's measurable in the thorax, I would generally think about starting with around about 6 weeks of treatment. And then simply taking another chest X-ray and asking if things are better, worse, or the same.
If they're the same or better, keep going. If they're worse, quit or try something different. But again, in that post-operative setting, we do a fair bit of it, but we, again, just can't really tell owners much about exactly how well it works.
And with that, again, I thank you very, very much for your attention. Please remember, I'm more than happy to answer any questions that you might have via email. My email is on that first slide again, dam at colostate.edu.
And again, I look forward to speaking with you, hopefully, live in, my next webinar, which is coming up in March of 2022. Thanks again. Cheers.