Feline Lymphoma

This month’s newsletter considers lymphoma (a form of cancer) in cats. It covers an array of different forms, and as with many cancers, symptoms can be varied and sometimes vague.

As it is one of the more common cancers, it is worth being aware of its existence and being astute in looking out for any signs of its development in your cat, to try and catch it in its earlier stages.   

Clinical Presentation

Lymphoma is more correctly called lymphosarcoma (LSA), and it is a multifactorial systemic disease with many types. It is a cancer of the blood that affects a specific type of white blood cell – the lymphocytes, and it accounts for about one-third of new cancer diagnoses in cats.

The most common form of LSA in cats is alimentary or gastrointestinal (GI) lymphoma, and it accounts for 50-70% of all feline LSA cases. It is most common in seniors with an average age at diagnosis of 9 to 13 years.

Mediastinal lymphoma affects lymphoid organs (thymus or lymph nodes) in the chest and is more often seen in younger cats with an average age at onset of 5 years. This type of LSA has been associated with feline leukaemia virus (FeLV) infection and is less common now with the decline in FeLV infection in cats.

Renal and nasal lymphoma are additional forms of LSA known as extra nodal, since they do not occur in the lymph nodes (LNs).

Lymphoma in cats can manifest with a wide array of clinical signs that may be vague and non-specific. Common signs include lethargy and reduced interest in normal activities, and reduced appetite, along with additional signs that are more specific, reflecting the location of the cancer.

Vomiting and diarrhoea are common with GI LSA, and there may be a distended abdomen and nausea. Mediastinal LSA in the chest can cause difficulty breathing, including rapid breathing or panting; coughing and regurgitation may also occur. Renal LSA in the kidneys can cause increased drinking and urination, and the kidneys may be palpably enlarged. Nasal LSA is often characterised by chronic nasal discharge, bleeding from the nose and sneezing; noisy breathing and facial asymmetry may also be present. Discharge from the eyes can also occur. LSA affecting the lymph nodes (nodal form) may result in visibly enlarged lymph nodes, particularly under the jaw.

Diagnosis

Diagnosing lymphoma requires finding cancerous cells taken from lymph nodes or other organs and examined microscopically. Your veterinarian may also perform baseline screening bloodwork before testing for lymphoma to assess your cat’s overall health and rule out other causes of your cat’s clinical signs.

In some cases, feline lymphoma can be diagnosed with a fine needle aspirate (FNA) for cytology (microscopic examination of the cells). In this test, a veterinarian will insert a needle into an area of concern (an enlarged lymph node, enlarged kidney, thickened region of intestine or fluid present within the chest) and remove a small number of cells. These cells will then be examined under a microscope, looking for cancer cells that indicate lymphoma. Carrying out an FNA may require a local anaesthetic and/or sedation.

Although it is not always possible to obtain a high-quality diagnostic sample via FNA and up to 25% of aspirates may be non-diagnostic, many veterinarians start with this test because it carries minimal risks, side effects and costs compared to surgical biopsy under general anaesthesia. If an FNA is inconclusive or impractical due to the location of the lesion, your veterinarian may instead perform a surgical biopsy. This involves the removal of a piece of tissue from the lesion.

In cases of suspected gastrointestinal lymphoma, this sample may be obtained surgically (by opening your cat’s abdomen and surgically removing a piece of the thickened intestine) or endoscopically (by threading an endoscope down your cat’s intestine and using a camera and specialised tools to remove a piece of the interior surface of the intestine). This sample will be processed and examined under a microscope regardless of the collection technique to assess for lymphoma.

If lymphoma is diagnosed via biopsy, the pathologist can also determine whether your cat is affected with a high-grade or low-grade lymphoma. This determination is based on how rapidly the cancer cells appear to be dividing (mitotic index) and how malignant the cells appear; high-grade lymphoma is fast-growing and more malignant. Low-grade or indolent lymphoma in cats is more likely to respond to chemotherapy, and chemotherapy often results in longer periods of remission. If your cat is diagnosed with lymphoma, additional testing, such as immunohistochemistry (IHC), may be needed to help further characterise the type of lymphoma and develop a treatment plan. IHC uses specialised antibody stains to identify tumour antigens on cytology or histopathology slides.

Treatment

Treatment is based on the use of chemotherapy, radiation therapy (radiotherapy) or both; however, it is unclear which approach is most effective. LSA is sensitive to both chemotherapy and radiotherapy, and your veterinarian (or veterinary oncologist) will make recommendations on the best course of treatment for your pet. Given that LSA is usually a systemic disease, if tests cannot rule out the presence of cancerous cells elsewhere in the body, then chemotherapy is often pursued instead of radiotherapy.

The exact chemotherapy drugs and schedule used depends on the form/location and grade of LSA, owners’ wishes, goal of treatment, how aggressively the cancer is behaving, how sick a cat is at the start of treatment and any abnormalities in organ function (particularly kidneys and liver). Chemotherapy is thought to be most effective when we use a combination of drugs; therefore, most protocols use 4 to 6 different drugs in a multi-drug protocol (using cyclophosphamide, vincristine and prednisolone with or without doxorubicin as in COP and CHOP protocols).

Initially, treatments are given more frequently (such as once weekly) and then, depending upon the response and protocol used, are gradually spread out and/or discontinued after 25 weeks, although the COP protocol has also been evaluated in a 10-week course of treatment. Other options for therapy may consist of using a single chemotherapy drug (such as doxorubicin or lomustine) or a combination of two drugs, such as prednisolone and chlorambucil (for low-grade alimentary LSA). A disadvantage of single-agent therapy is that remission rates and expected survival times are much more difficult to predict.

Blood tests are generally performed before each chemotherapy treatment to monitor for side effects (such as a low blood cell counts) and to determine response to treatment, while radiographs and/or ultrasound scans may be repeated less frequently. If a patient comes out of remission or relapses, rescue therapy using a new combination of drugs or doses, or different drugs can be offered. While the chances of obtaining a second remission are lower, there are some cats that do respond well and have additional time with a good quality of life.

If chemotherapy is not an option due to how sick your cat is, or due to financial or travel concerns, corticosteroids (prednisolone) can be used as part of hospice care. Although prednisolone does not treat LSA, it can temporarily reduce clinical signs and buy your cat some time while end-of-life decisions are made.

Side effects

Most cats tolerate chemotherapy very well and experience minimal side effects. Serious side effects are only seen in 5 to 10% of the patients treated. If side effects are serious or intolerable, these can usually be dealt with by either lowering or delaying the dose of the offending drug or by substituting a different drug. Side effects may include nausea, loss of appetite, vomiting, diarrhoea, extreme tiredness or infection. Certain chemotherapy agents can affect organ function over time. Cats tend not to lose their hair, but may lose their whiskers and have a different texture to their fur secondary to chemotherapy.

Prognosis

The prognosis for feline LSA depends on the form/location and grade of the LSA, how sick the cat is at the start of treatment, the cat’s FeLV status and how quickly the disease is diagnosed and treated. A positive response to treatment in the first few weeks is probably the best positive prognostic factor, and patients that respond by going into remission seem to achieve the longest survival. The response rate for either chemotherapy or radiotherapy is reported to be between 66% and 75%. Ideally, outcomes of studies should be reported as 1- or 2-year, or longer, survival rates rather than median survival times, as this is more meaningful to the owner and similar to human studies that use 5-year survival as a measure of ‘cure’.

Cats with low-grade LSAs have a better prognosis, potentially living for two years or longer with treatment, while those with high-grade LSAs may have a prognosis closer to 6-12 months. Response to treatment is a key factor, with cats achieving complete remission often having a median survival time of around 8.3 months, while those with partial or no response may have significantly shorter survival times. Median survival time is the time at which half of the treated cats are still alive.

Most cases of gastrointestinal LSA are low-grade LSA. With treatment, approximately 70% of cats with low-grade LSA will go into remission. While LSA is never truly cured, remission is used as a term to describe the temporary resolution of all signs of LSA. The average remission for low-grade LSA is two to three years, meaning two to three years without any signs of disease.

High-grade gastrointestinal LSA, however, does not respond as well to treatment. Only 25-50% of cats with high-grade LSA achieve remission with treatment. Typically, this period of remission lasts only 2-9 months, and then cats become ill again.

Mediastinal LSA in cats with FeLV infection carries a poor prognosis, with an average survival time of 3 months. In cats unaffected by FeLV, mediastinal LSA often shows at least a partial response to chemotherapy. These cats show an average survival time of 9-12 months, with the initial response to treatment often indicating survival time.

Nasal LSA has a fair to good prognosis as it is often a localised disease that can be treated with radiotherapy, with a reported median survival time (MST) from 12-30 months. Most cases that recur are due to local recurrence rather than due to systemic disease, although kidneys appear to be a frequent site for distant disease development.

Renal LSA, unfortunately, carries a poor prognosis. Average survival with this type of LSA is only 3-6 months, though there are isolated reports of cats surviving far longer. Renal LSA tends to spread to the brain and central nervous system; this occurs in approximately 40% of renal LSA cases and worsens the prognosis for this disease.

For an in-depth description of a case of nasal lymphoma in a cat, please visit the Animal Cancer Trust Charity website for Darcey’s story.

www.animalcancertrustcharity.co.uk/information/owner-stories-and-case-studies

It can be seen from this article that lymphosarcoma is a complicated and varied cancer, with many different forms and a variety of different symptoms and outcomes.

The main purpose of this article is to raise awareness. Despite the fact that the severity and prognosis of the cancer can vary enormously, there are treatments available and life expectancy can be extended, depending on when the diagnosis is made and how the individual reacts to treatment.