Feline Alimentary Lymphoma: A Comprehensive Guide

Feline alimentary lymphoma is a type of cancer that affects the lymphatic system in a cat's digestive tract. It's a serious condition that requires prompt attention from a veterinarian.

The alimentary lymphoma is most commonly found in older cats, typically over the age of 10. It's also more common in cats with a history of gastrointestinal issues.

Cats with alimentary lymphoma may exhibit a range of symptoms, including weight loss, vomiting, and diarrhea. These symptoms can be non-specific, making it challenging to diagnose the condition.

The prognosis for cats with alimentary lymphoma varies depending on the severity of the condition and the cat's overall health. In some cases, treatment can be effective in managing the symptoms and improving the cat's quality of life.

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The causes and development of feline alimentary lymphoma are complex and not yet fully understood. Several factors have been implicated as possible causes, but their involvement remains inconclusive.

One of the potential causes is a virus called Felis catus gammaherpesvirus 1 (FcaGHV1), which infects at least a quarter of cats. The presence of this virus has been detected in some lymphoma cases, although its role in the disease is still unclear.

Research has shown that the presence of circulating FcaGHV1 DNA is associated with significantly shorter survival compared to FcaGHV1 qPCR negative cases. This suggests that the virus may play a role in the progression of the disease, but more studies are needed to confirm this.

Older cats are typically more susceptible to lymphoma, with the range of affected cats spanning 2-17 years.

Cats of any age can be affected, but the risk increases with age.

GI lymphoma, specifically, is also seen in older cats that test negative for FeLV.

Some studies have investigated the prevalence of feline low-grade alimentary lymphoma, but the exact frequency is not specified in the provided information.

Older cats are more likely to develop lymphoma, making age a significant risk factor.

The aetiopathogenesis of feline LGAL is poorly understood, and several factors have been implicated as possible causes, but their involvement remains inconclusive.

The relationship between the AL histological grade and phenotype is particularly unclear.

FcaGHV1, a panlymphotropic virus that infects at least one quarter of cats, has been implicated as a possible aetiological agent.

The detection of two human gammaherpesviruses in some lymphoma cases suggests a possible role for FcaGHV1 in feline LGAL.

However, one study found no correlation between FcaGHV1 DNA or whole blood virus load and a diagnosis of lymphoma.

The presence of circulating FcaGHV1 DNA was associated with significantly shorter survival compared to FcaGHV1 qPCR negative cases.

Feline low-grade alimentary lymphoma (LGAL) shares more characteristics with human indolent digestive T-cell lymphoproliferative disease (LPD) than previously thought.

The pathogenesis of human indolent digestive T-cell LPD is poorly understood, mainly due to its rarity in humans.

Feline LGAL, being more common, might serve as a suitable animal model to elucidate some of the pathogenic mechanisms underlying human indolent T-cell LPD of the gastrointestinal tract.

Humans, dogs, and cats share a common environment through domestication, which could explain why they are affected by closely-related diseases resulting from variations in gene expression.

This commonality is reflected in the fact that dozens of disease-causing variants have been successfully identified in pets, with most being directly informative for humans.

The development of genomics tools and the facilitating haplotype structure in pets make them valuable mammalian models in medical genetics, including comparative oncology.

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Feline alimentary lymphoma (LGAL) presents with a range of clinical signs, with weight loss being the most common symptom, affecting 80-90% of cats.

Clinical signs can include vomiting, anorexia, diarrhoea, icterus, splenomegaly, polydipsia/polyuria, and lethargy, although these are not pathognomonic and can overlap with other diseases.

The clinical course of LGAL is chronic and progressive, taking weeks or months to develop, with a median time interval of 365 days between the onset of signs and presentation.

Chronic inflammation is a major concern in the development of lymphoma, particularly in cats. Up to 60% of AL cases are associated with concurrent inflammatory bowel disease (IBD).

Chronic intestinal inflammation can increase the risk of developing AL. IBD has been described in up to 60% of AL cases.

In one study, MDR1 gene expression was found to be greater in cats with lymphogranulomatosis alimentaris (LGAL) than in cats with IBD.

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LGAL typically affects ageing cats, with a median age of 13 years.

Male cats are more likely to be affected, making up a significant proportion of cases.

Some studies have found that domestic shorthair and Siamese breeds are over-represented in cases of LGAL, although a specific breed association has not been consistently found.

These demographic factors can help veterinarians identify at-risk cats and tailor their approach to diagnosis and treatment accordingly.

Weight loss is the most common clinical sign of low-grade alimentary lymphoma (LGAL), affecting 80-90% of cats. This is a significant indicator that should not be ignored.

Vomiting is another frequent symptom, occurring in 70-80% of cats with LGAL. This can be a sign of a more serious underlying issue.

Anorexia, or loss of appetite, is also a common clinical sign, affecting 60-70% of cats. This can lead to further complications if left untreated.

Diarrhea is a symptom that affects 50-65% of cats with LGAL. This can be a sign of a gastrointestinal issue.

Icterus, or yellowing of the skin and eyes, is a less common symptom of LGAL, but it can still be a sign of a more serious issue.

Diagnosis of feline alimentary lymphoma can be challenging due to overlapping clinical signs and diagnostic features with other gastrointestinal diseases.

Clinical signs alone are not sufficient to confirm a diagnosis of LGAL, and other conditions such as metabolic diseases, endocrinopathies, and infectious diseases must be ruled out first.

Diagnostic imaging and clinicopathological testing can help identify other potential causes of gastrointestinal disease.

To confirm a diagnosis of LGAL, more advanced diagnostic techniques such as immunohistochemistry and PCR for Antigen Receptor Rearrangement (PARR) may be required.

Gastrointestinal endoscopy can be used to visualize the mucosa and collect biopsy samples, but macroscopic differentiation between inflammatory lesions and LGAL lesions is not possible.

In some cases, exploratory coeliotomy may be preferable to endoscopy, as it allows for full-thickness biopsies to be taken from various sites.

Multiple systematic biopsies of all digestive areas are recommended to increase the chances of obtaining a definitive diagnosis.

Diagnosis of lymphoplasma cell lymphoma (LGAL) in cats can be challenging due to its non-specific clinical signs. The condition can mimic other gastrointestinal diseases, making it essential to rule out metabolic diseases, endocrinopathies, and infectious diseases through clinicopathological testing and diagnostic imaging.

To differentiate LGAL from other gastrointestinal diseases, dietary trials can be used to eliminate food-responsive enteropathy as a possible cause. However, distinguishing LGAL from inflammatory bowel disease (IBD) can be more challenging due to overlapping clinical signs and diagnostic findings.

Gastrointestinal endoscopy is a valuable investigative tool in feline gastroenterology, allowing for direct visualization of the mucosa and collection of intestinal biopsy samples. However, macroscopic differentiation between inflammatory lesions and LGAL lesions is not possible by endoscopic examination.

Exploratory coeliotomy may be a preferable option to endoscopy for diagnosing LGAL, as it allows for full-thickness biopsies to be taken from various sites, including the jejunum and ileum, which are the most frequent locations of LGAL.

To confirm the diagnosis of LGAL, more advanced diagnostic techniques such as immunohistochemistry and PCR for Antigen Receptor Rearrangement (PARR) may be required.

Here are the key diagnostic steps for LGAL:

Hypoalbuminaemia is a common issue in cats with gastrointestinal disease, affecting approximately 70% of those with AL, 49% with LGAL, and 77% with IBD.

Biomarkers such as hypocobalaminaemia are of significant diagnostic and prognostic value. Between 50 and 80% of LGAL cases are associated with hypocobalaminaemia, with levels typically above 290 ng/L.

Immunohistochemistry is a crucial diagnostic tool in veterinary medicine, and it's essential to understand how it works.

Formalin-fixed, paraffin-embedded tissue sections are used for immunohistochemical assessments, which involve labeling specific cells with antibodies.

A panel of antibodies is used to identify different cell lineages, including T cell lineages (CD3), B cell lineages (CD20), macrophages (myeloid/histiocyte antigen), and more.

The expression of each cluster of differentiation (CD) is visually and independently assessed by pathologists, who examine sections from each sample.

CD3 and CD20 expression profiles are particularly important in diagnosing gastrointestinal tract diseases, such as feline low-grade intestinal T cell lymphoma.

In the case of feline low-grade intestinal T cell lymphoma, a significant elevation of the CD3+ T cell count in the epithelium is observed, with a median count of 97 per 100 cells.

The proportions of CD20+ B cells in the epithelium and the lamina propria are very low, typically around 5% and 20%, respectively.

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Immunohistochemistry can also help identify specific markers, such as CD56, which is typically negative in most cases of feline low-grade intestinal T cell lymphoma.

The median Ki67 proliferation index is around 20% in the epithelium and 30% in the lamina propria, indicating a moderate level of cell proliferation.

Staining for phosphorylated human STAT3 (pSTAT3) is typically negative, while staining for pSTAT5 is positive in all cases, which is a key characteristic of feline low-grade intestinal T cell lymphoma.

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A major challenge of diagnosing feline alimentary lymphoma is distinguishing it from inflammatory bowel disease, as their clinical presentations overlap.

The clinician must carefully consider the aetiology, signalment, clinical signs, and diagnosis of the two conditions to make an accurate diagnosis.

Feline alimentary lymphoma can present with similar symptoms to inflammatory bowel disease, making it difficult to diagnose without proper examination and testing.

Clonality testing is a crucial step in distinguishing between different conditions.

To determine the clonality of a tumor, a multiplex polymerase chain reaction assay can be used, as seen in a study where DNA was extracted from a tumor biopsy and a matched peripheral blood sample.

This assay detects clonal T cell receptor gamma (TCRγ) chain gene rearrangement, which is considered monoclonal when only one peak is detected.

A study using this assay found that a rearrangement was considered polyclonal when no peaks or more than 4 peaks were detected.

The quality of the genomic DNA used in clonality testing is crucial, and it's recommended to use a commercial kit to extract the DNA.

A study used the E.Z.N.A Tissue DNA Kit to extract genomic DNA from feline tissue, and the resulting DNA was assayed to determine its concentration and quality.

The threshold for DNA concentration was set to 30 ng/μL, with desired 260/280 ratios of 1.8–2.0 and 260/230 ratios above or equal two (2.0–2.2).

PCR-based lymphocyte clonality assays are commonly used to detect clonality.

In one study, a 189 base pair fragment of the feline androgen receptor gene was amplified using the primer sets V1F2, V3F3 and V3F4.

The size of the PCR products was accurately determined using capillary electrophoresis, and the presence and size of the products were verified in triplicate to ensure reproducibility.

A study found that identical PCR triplicates verified the reproducibility of the clonality patterns, which were interpreted as described previously.

Distinguishing Low-Grade Alimentary Lymphoma from Inflammatory Bowel Disease can be a challenge for clinicians due to overlapping clinical presentations.

A major hurdle is distinguishing LGAL from IBD, as their symptoms often mimic each other.

LGAL and IBD have different aetiologies, with LGAL being a type of cancer and IBD being an inflammatory condition.

The signalment of the two conditions also differs, with LGAL typically affecting older dogs and IBD affecting dogs of various ages.

Clinical signs such as weight loss, vomiting, and diarrhea can be present in both conditions, making diagnosis difficult.

Diagnosing LGAL requires a definitive diagnosis through biopsy or other diagnostic tests, while IBD diagnosis is often made through a combination of clinical signs, laboratory tests, and response to treatment.

A summary of the two conditions can be found in Table 4, which compares their aetiology, signalment, clinical signs, and diagnosis.

Combination chemotherapy is a treatment option for feline alimentary lymphoma. This involves using two or more medications together to fight the cancer.

High-dose pulse chlorambucil and prednisolone were used in a study to treat cats with LGITL. Chlorambucil was given orally once a day at a dose of 15 mg/m², every 3 weeks for 4 consecutive days. Prednisolone was given orally once a day at a dose of 3 mg/kg, with the dose tapered to 1 mg/kg once clinical remission was achieved.

The regimen was continued indefinitely if no adverse events were observed. This means that the treatment was ongoing, with regular monitoring to ensure the cat's safety and effectiveness of the treatment.

The median overall survival time in this study was 329 days. This means that half of the cats lived for at least 329 days after starting treatment.

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The prognosis for feline alimentary lymphoma, or LGAL, is generally good with a high remission rate when treatment is carried out over several months or years.

Most cats with LGAL can achieve remission with proper treatment, but relapse, comorbidities, or euthanasia remain common causes of death.

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The initial response to chemotherapy is the most significant prognostic indicator for LGAL, with a strong correlation between successful treatment and remission.

However, other factors such as age, weight, sex, and the presence of extra-intestinal lesions do not appear to affect treatment outcomes.

Lethargy, vomiting, and anorexia at initial diagnosis are considered negative prognosis factors, indicating a poorer chance of successful treatment.

It's unclear whether LGAL can progress to more aggressive forms of lymphoma in the long term, but ongoing research is working to answer this question.

Feline alimentary lymphoma has characteristics in common with human digestive T-cell lymphoma, specifically indolent digestive T-cell lymphoproliferative disease (LPD). This similarity suggests that domestic cats could be a valuable model for comparative biomedical research, particularly in the field of oncology.

The domestic cat's genetic makeup and environment make them a suitable candidate for studying human diseases, including cancer. In fact, research has shown that humans, dogs, and cats share common signatures of coevolution, including epigenetic markers.

Feline low-grade alimentary lymphoma (LGAL) is a common condition in cats, with most patients still alive with a persistent disease after several years of follow-up. This makes it an attractive model for studying human indolent digestive lymphoma, where little is known about the mechanisms involved in its pathogenesis.

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Feline low-grade alimentary lymphoma (LGAL) has characteristics in common with indolent digestive T-cell lymphoproliferative diseases in humans, according to the latest WHO classification.

The clinical, histological, and phenotypic features of feline LGAL and human indolent digestive T-cell LPDs are compared in Table 7 and Fig. 5, highlighting their similarities.

Feline LGAL is more common than human indolent digestive T-cell LPD, making it a suitable animal model for studying the disease.

Humans and cats share a common environment through domestication, leading to common signatures of coevolution, including epigenetic markers.

This shared environment might explain why humans and cats are affected by closely-related diseases resulting from variations in gene expression.

Domestic cats are considered a valuable model for comparative biomedical research, offering opportunities for comparative and translational advances in both human and veterinary oncology.

Feline LGAL is clinically indolent, with most patients still alive with a persistent disease after several years of follow-up.

However, three cases have been reported where patients died from aggressive T-cell lymphoma several years after being diagnosed.

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The study was approved by the investigational review board at Alfort National Veterinary School in France, with a reference number of 2017-05-09.

Between July 2016 and July 2018, gastrointestinal tract biopsies were collected from all cats referred to Alfort National Veterinary School's small animal clinic for suspected LGITL.

Tissue sections were reviewed by board-certified veterinary and human pathologists, who were blinded to the subject's clinical history.

The pathologists classified the biopsies according to the 2016 revision of the WHO classification of human lymphoma, the WHO classification of canine lymphoma, and the sixth edition of Jubb, Kennedy, and Palmer's "Pathology of Domestic Animals."

22 cats with a final histological diagnosis of LGITL were included in the study.

Feline alimentary lymphoma is a serious condition that requires prompt attention.

The prognosis for cats diagnosed with alimentary lymphoma is generally poor, with a median survival time of 3-4 months without treatment.

However, with chemotherapy, cats can live for up to 12 months or more, depending on the stage and type of lymphoma.

It's essential for cat owners to work closely with their veterinarian to monitor their cat's condition and adjust treatment plans as needed.

Early detection and treatment can significantly improve a cat's quality of life and prolong its lifespan.