[00:00:02] Introduction: Welcome to All Cats Considered, a podcast from the Feline Veterinary Medical Association.
Here we interview professionals from across the veterinary world and take deep dives into the latest evidence-based research developments, studies and guidelines that improve feline health and well-being.
We are the home for veterinary professionals seeking to enhance the care of cats through high standards of practice, continuing education and evidence-based medicine. In each episode you'll hear interviews with a variety of experts in our field covering a wide range of topics and the latest developments in feline health. We'll share the key points you need to know to improve your patients care.
Let's dive in and listen to this week's experts.
[00:00:44] Gómez‑Mejías: So Sandra graduated from the Autonomous University of Barcelona in 2013 and quickly found her way into small animal and emergency practice. She then specialized in oncology, completing both an internship and an ECVIM approved residency at the University of Liverpool where she also went on to lecture in small Animal Oncology. In 2021 she became a European recognized specialist in veterinary oncology and her research interests include feline cancer, cancer epidemiology and tumor biomarkers. And Sandra is the first author of this month's JFMS Spotlight titled Cutaneous Paraneoplastic Syndromes in a Comparative Clinical Review.
Thank you for finding the time to record this episode, Sandra.
[00:01:29] Guillén: No, thank you for inviting me, Yaiza.
[00:01:31] Gómez‑Mejías: Cutaneous paraneoplastic syndrome seem more common in middle age to older cats. But putting age aside, what kinds of clinical signs or bits of history should make us think this could be paraneoplastic rather than just another skin disease?
[00:01:48] Guillén: Yeah, besides age, there are some clinical red flags that we can identify from clinical history, lesion progression and response to therapy that can also make a suspect of cutaneous paraneoplastic syndrome would say. The first one is the fact that paraneoplastic lesions often have atypical patterns compared to allergic, infectious or mutilated skin disease.
So we typically see an acute onset of quite severe and widespread skin lesions in a cat that was otherwise previously healthy.
These lesions tend to have a rapid progression in a lot of cases and they don't typically regress with appropriate empirical therapy. And sometimes we also see an unusual distribution compared to other dermatopathies. A second red flag would be a poor or paradoxical response to the standard treatment. Sometimes we see that there is minimal or no response to antibiotics or antifungals or corticosteroid treatment. Or sometimes there's a trend in the improvement, but there is then relapse that happens quite quickly.
A third red flag that is quite common is that we see concurrent systemic clinical signs together with the skin disease. A lot of these cats, they suffer from weight loss or lethargy, anorexia, particularly those cats that have abdominal tumors. They may also suffer from vomiting or diarrhea or PU/PD. And those that have intrathoracic tumors like thymomas may suffer from respiratory signs concurrently as well.
I would say the fourth red flag would be clinical pathological findings or abnormalities that are not explained, but by the skin disease only. Sometimes we see that these cats, apart from having skin lesions, they also have abnormalities on hematology like non regenerative anemias or a persistent inflammatory leukogram that we cannot explain with the skin lesions or hypoalbuminemia, elevated liver enzymes, these sort of abnormalities.
To summarize, basically, if we have a cat with atypical skin lesions that are progressing very fast, that are not responding to treatment, or that is concurrently systemically ill or having abnormalities on blood tests, I think we should start investigating that and start suspecting that there could be something else.
[00:04:20] Gómez‑Mejías: Thank you so much for sharing this. Very helpful tips. The article mentions that paraneoplastic alopecia and thymoma associated exfoliative dermatitis are the most commonly reported syndromes.
Clinically, how these two look different and how can we tell them apart from the feel and skin conditions that we see every day?
[00:04:39] Guillén: Yeah, so exfoliative dermatitis is an immediate Cutaneous paraneoplastic syndrome. So typically affected cats, they have these generalized scaling erythema alopecia. And normally these lesions, they progress through hyperkeratosis, erosions and crusting, While paraneoplastic alopecia generally presents more with a symmetrical alopecia where the skin appears quite shiny but not fragile.
They also differ on how the lesions are distributed. So cats with exfoliative dermatitis generally have lesions over the head, neck and trunk, while cats with paraneoplastic alopecia generally have alopecia on the ventral abdomen, also the neck in some cases, but mainly the medial aspect of the thoracic and pelvic limbs and perineal regions.
So generally, to diagnose exfoliative dermatitis, we have to consider as well other possible differential diagnosis, such as dermatophytosis, ectoparasitic or allergic diseases, as well as immunity. Skin diseases such as pemphigus or sebaceous adenitis or drug-related reactions, or even epitheliotropic lymphoma can mimic this sort of lesions. So we need to exclude those differentials as well, why? For paraneoplastic alopecia, the main differentials would be, for example, self-induced alopecia due to pruritus or psychogenic disorders. Also, dermatophytosis, demodicosis or hyperadrenocorticism, among others. So generally, the clinical progression of the lesions, the clinical signs of the cat can help us narrowing that differential list. And then we can obviously, depending on our clinical suspicion, do this is specific testing to exclude the other possible dermatoses.
[00:06:34] Gómez‑Mejías: So you started talking about a little bit about the differentials you considered in your workup when it cutaneous paraneoplastic syndrome is on your differential list. How do you usually complete this workup?
[00:06:49] Guillén: Yeah, the initial diagnostic test should normally include a complete hematology biochemistry profile. If we don't know if the cardia is FALB or FIV positive, we should probably test for that as well.
And depending on the type of lesions and the progression, we may consider as well, for example, endocrine testing, or investigation for ectoparasites, dermatophyte and microbial overgrowth. To obtain a diagnosis. Ultimately, we need a combination of tests that include skin biopsies and imaging to be able to localize basically the primary tumor and rule out all the preferential diagnosis for those cats.
Once we have located the tumor either inside the thorax or the abdomen, we generally have to confirm what tumor type we're dealing with, either using cytology or histopathology.
This will help us characterize the type of tumor, but also the extent of it. For example, if we have a cat with a pancreatic mass and concurrent nodules in the liver, and we want to assess if those two are related, we are going to conceive a sampling of both the primary mass but also the liver nodules to assess for metastatic disease.
Having said that, if you have, for example, a cat where you document, you know, a mediastinal mass and the cat concurrently has exfoliated dermatitis or, you know, lesions compatible with it, such as scaling, erythema or erosions or crusting all over the body, you can have a very high degree of suspicion just based on the clinical presentation and imaging findings.
[00:08:31] Gómez‑Mejías: Thank you. And how important is getting good quality samples?
[00:08:37] Guillén: Yeah, so generally to obtain a definitive diagnosis is important to, to have a good quality sample because this is going to guide not only treatment but also the prognosis for those cats. So that's going to allow us to know, inform better our caregivers to assess, you know, what's the best treatment option in most cases. You know, we may consider surgery as the first treatment choice. However, if the tumor is too extensive, like it happens in some aggressive pancreatic and biliary cancers, we may instead treat systemically with chemotherapy or consider palliative treatment if we think that the cancer is too advanced or the quality of life of the cat cannot be returned to what it used to be.
[00:09:27] Gómez‑Mejías: I see.
So once we've made the diagnosis, how does that information help us guide owners, especially when it comes to prognosis?
[00:09:37] Guillén: Yeah, so the tumor type is going to give us a lot of information about the prognosis. For example, in cats that have thymoma and associated exfoliative dermatitis, we know that after surgery, these cats can have a good outcome with survivals over two and a half years. And we have reports as well of cats that have hepatocellular carcinoma and paraneoplastic alopecia and that can achieve also long-term outcomes after excision of this liver tumor.
However, then we have other tumor types like biliary and pancreatic carcinomas in cats that are typically, well, sometimes associated with this paraneoplastic alopecia. We see that these cancers, they have an aggressive behavior and are a lot of times, we do have metastasis or cardiac diagnosis. So generally, the prognosis for those cats tends to be quite poor.
Despite this, it's worth highlighting that there is a proportion of cats with pancreatic and biliary cancer that they may have an early disease stage or just localized disease without metastasis. And those cats with appropriate surgery can do better than previously expected with such cancers.
While there are other types of cancers, for example, there are some reports of cats with lymphoma and associated paraneoplastic cutaneous necrosis and paraneoplastic skin fragility syndrome, where we know that potentially chemotherapy could effectively treat the underlying lymphoma and lead to a fair outcome in those cases where we see a good response. So, yeah, it depends which cancer we are treating with and what the treatment options are for that particular cat.
[00:11:25] Gómez‑Mejías: That makes sense. So while we are still investigating or planning treatment, are there things we can do earlier on to give the cats some relief?
[00:11:37] Guillén: Yeah, that's a really good question. We do see that some of these cats with cutaneous paraneoplastic syndromes, they often have secondary bacterial or yeast infections, and this is because they have this impaired skin barrier function.
So while working on this review paper, we also looked at the responses that were seen in these cuts that were treated with medical management alone. Without tumor removal or any anti cancer drugs.
And those scars that were treated, let's say supportively with antifungal or antibiotic treatment generally had some improvement, but it was very short lasted.
So similarly with other, you know, cutaneous paraneoplastic syndromes that we know that are immune mediated, some of these cats may benefit from steroids. But the reports suggest again that some cats may not respond to steroids alone or that these improvement may just be very like mild and short lasted.
So despite this, despite not having a lot of evidence that this type of treatments are going to improve significantly the quality of life of these cats, given that inflammation is somehow limited for some of these cutaneous paraneoplastic syndromes, I think in the palliative setting, I would still recommend symptomatic treatment as it may provide some temporary relief for some obvious cats.
[00:13:10] Gómez‑Mejías: I see, thank you. That's very helpful too. If we are able to completely remove a non-invasive thymic epithelial tumor, how likely is it that the skin signs will actually resolve?
[00:13:22] Guillén: That's a really good question as well, because in the majority of cats undergoing excision of thymomas and exfoliative dermatitis actually resolve. But what we could see in our literature review is that in some of these cats, the resolution is not immediate. It can take one to six months. So we need to give them time after surgery and follow up on them. And on the skin lesions during this postoperative period and up to, you know, those six months, there are some reports of cats that after excision of these thymomas didn't have resolution of the skin lesions.
It's very difficult to tell whether in those reports we just didn't give these cats enough time, or those cats were not followed up for enough long periods to allow for the skin lesions to resolve. Or the other option could be that maybe there was some residual tumor left during the surgery and that's why the skin lesions resolved only partially.
So it's very difficult to tell because that information in some of these studies is not provided, but they seem like plausible explanations in those scenarios.
[00:14:33] Gómez‑Mejías: Thank you. Interesting.
So moving now onto some of the rarer syndromes mentioned in the article, what clinical signs or lab findings should ring alarm bells for something like superficial necrolytic dermatitis?
Yeah.
[00:14:52] Guillén: When looking at superficial necrolytic dermatitis in cats is actually quite a rare syndrome. We could only find four cases in the literature with this sort of paraneoplastic syndrome.
One of these cats had a glucagonoma and another one have a hepatic neuroendocrine carcinoma, and then the two others have hepatic and pancreatic carcinomas. And in all these four cases, the lesions were mainly characterized by the presence of severe erythema, thick crusts, ulcers and erosions.
And some of these cats have also hyperkeratosis and deep fissures of the skin, which were generally quite painful or even associated with self-trauma.
So the most common areas affected in these cats generally were the ventral paws and other areas of friction and trauma, such as the muscle, the periocular region, perianal regions and perigenital regions as well.
What is interesting of this syndrome is that most of these cats, they had concurrent systemic clinical signs and they were unwell. Either they presented with lethargy, anorexia, vomiting or weight loss.
And what is also even more interesting is that polyuria and polydipsia, which is actually one of the main presenting clinical signs in dogs and people because of concurrent diabetes mellitus and insulin resistance, is something that was not reported in any of these cats. So it's, it's quite a striking difference with could see then we have also some other abnormalities, particularly in the biochemistry panel where we can see elevation of liver enzymes, hyperglycemia again because of this insulin resistance. But this again was only reported in two of the four cats and the other two basically had pretty unremarkable biochemistry. So again, it seems like some of these clear the signs or abnormalities are a bit more subtle in cats compared to other species.
And what we also know is that in humans and dogs we can use also the fasting plasma glucagon to be able to diagnose this syndrome, which tends to be elevated in those cases with superficial necrolytic dermatitis. And this together with the presence of hypoaminoacidemia is supportive of the diagnosis.
We don't know how these tests, you know, how helpful those can be in cats, but we know that there is a validated glucagon ELISA test that can be used in cats. So it's something that again for future cases we can consider. But in those reports, none of them actually they made the diagnosis based on this test. Instead the expression of glucagon was made on basically immunochemistry.
[00:17:44] Gómez‑Mejías: Knowing about your interest in biomarkers, the article highlights how complex the mechanisms behind cutaneous paraneoplastic syndromes can be. Is there any ongoing research into these biomarkers or mediators that might help clinicians identify these tumors more reliably in the future?
[00:18:03] Guillén: Yeah, probably because these syndromes are so rare and possibly underdiagnosed in cats. There is currently limited research focused on identifying specific mediators or biomarkers that would help with the diagnosis in these cats. What complicates things even further is the fact that we don't know that much about the pathogenesis of feline cutaneous paraneoplastic syndromes. And this is so complex and remains quite poorly understood.
So because of that, there are no current clinically validated tumor derived markers like cytokines or autoantibodies, aside from the glucagon assay that we just mentioned for diagnosis of superficial necrotic dermatitis.
What I could find is there is one report of a cat with paraneoplastic pemphigus reported in the literature where they could actually find and identify antibodies against epidermal antigens in that cat. So that's something that again, it could help future cats with a similar presentation and suspected paraneoplastic pemphigus.
So yeah, overall I think it would be very interesting to perform like potentially proteomics or metabolomics or cytokine profiling to identify candidate mediator patterns in these affected cats. But I think it's unlikely that these sort of tests could replace imaging or histology at the time of diagnosing them. But it would be really interesting to know a little bit more about the pathogenesis of these syndromes because it's really, really unusual presentation in general.
[00:19:49] Gómez‑Mejías: I'm really looking forward to seeing what happens in the future and what's discovered.
So today this discussion really highlights how important it is for all of us in general practice to look beyond the skin and consider what might be happening systemically in our feline patients. Recognizing these patterns can make a real difference. Thank you so much, Sandra, for sharing your expertise.
[00:20:10] Guillén Thank you, Yaiza , for inviting me. It's been a pleasure to chat to you.
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