LYMPHOMA IN PETS
Lymphoma is a malignant tumor of a specific type of blood cell called the lymphocyte. Lymphocytes are cells which are important to the immune system in the body. One of their many functions is to make antibodies which help the body fight off disease. Lymphoma occurs when mutations in the DNA of a lymphocyte cause its normal safety mechanisms to fail and the cell to replicate uncontrollably. These abnormal lymphocytes accumulate, causing enlargement of lymph nodes and disruption of normal organ function.

Location Lymphoma can occur almost anywhere in the body. The most common location in dogs is the lymphatic system which is an extensive network of vessels with nodes throughout the body. This is called multicentric lymphoma. The most common external sites for lymph node enlargement are under the chin (mandibular lymph nodes), in front of the shoulders (prescapular lymph nodes), under the front leg (axillary lymph nodes), under the rear legs (inguinal lymph nodes), and behind the knees (popliteal lymph nodes). Lymph nodes can also be enlarged within the abdominal and thoracic cavities. Other common sites for lymphoma are the gastrointestinal system (this is the most common location in cats), mediastinum (the space in the thorax between the lungs and in front of the heart), and skin. Less common sites for lymphoma are the eye, the brain and abdominal organs such as the liver, spleen and kidney.

Clinical Signs
Lymphoma causes different clinical signs depending on its location. Dogs with multicentric lymphoma affecting only the lymph nodes almost always feel great. The disease is usually discovered by owners who notice the "lumps" which are enlarged lymph nodes or by veterinarians on routine physical examinations. Some dogs with multicentric lymphoma will have vague signs such as decreased appetite, lethargy and weight loss. Gastrointestinal lymphoma can cause problems such as vomiting, diarrhea or weight loss. Mediastinal lymphoma can cause shortness of breath or can be associated with decreased appetite, vomiting and weight loss secondary to high calcium. Dogs with ocular lymphoma can present for red eyes, painful eyes or even blindness.

Diagnosis
Lymphoma is usually diagnosed with a fine needle aspirate. This involves inserting a small gauged needle into a lymph node or abnormal tissue and spreading cells onto a microscope slide. This is a noninvasive relatively fast and inexpensive test which is diagnostic in most cases. Sometimes, however, a definitive answer cannot be determined by a small sample of cells on a slide, in which case a biopsy is needed. A biopsy involves obtaining a larger piece of tissue using either a small biopsy instrument on an awake animal ,or with surgery to remove an entire lymph node or part of an organ.

Clinical Staging
Diagnostic tests can be done to determine the extent of the disease in the body in animals with multicentric lymphoma. Stage 1 is involvement of only 1 lymph node. Stage 2 is involvement of multiple lymph nodes but only on the front or back part of the body. Stage 3 is involvement of lymph nodes all over the body. Stage 4 is involvement of the liver and/or spleen. Stage 5 indicates bone marrow involvement. To stage a dog with lymphoma requires a complete blood count, chemistry profile, abdominal ultrasound, thoracic radiographs and a bone marrow aspirate. These tests will provide the most thorough assessment of your pet's condition but are not essential to decide a course of treatment.

Histological Grading
The tumor grade is determined by the pathologist reading a biopsy. They use characteristics of the cells to try to determine how the tumor will behave. A high grade tumor is potentially faster growing and has a higher chance of metastasis than a low grade tumor. Technically it is impossible to assess tumor grade using a sample obtained by a fine needle aspirate, however some pathologists will comment on the differentiation of the cells which can suggest whether a tumor is high or low grade. Most canine lymphoma is intermediate to high grade.

Cytochemical staining
A cytochemical stain is a test which is done on a tumor sample to determine what specific type of lymphocytes are present. Most canine lymphomas originate from B cells however a small percentage originate from T cells. This information is relevant to the prognosis of the pet, as dogs with T cell lymphoma have a lower chance of responding to chemotherapy and a shorter average survival. Cytochemical staining is not done on every patient and is not required to make a decision about treatment.

Treatment
The treatment of choice for lymphoma is chemotherapy. Surgery to remove the disease is very rarely done for 2 reasons. We assume that lymphoma cells have the potential to be everywhere in the body, and lymphoma is generally very responsive to chemotherapy. Our goal with treatment is to achieve complete remission (meaning there is no evidence of disease on physical examination or diagnostic tests such as blood work, x-rays or ultrasound) and keep the animals feeling good. Often enlarged lymph nodes will shrink within 6-24 hours after giving chemotherapy. There are many different chemotherapy protocols used to treat lymphoma. Below are a few of the options that we offer.

1. Prednisone - Prednisone is a steroid which is toxic to lymphoma cells. Alone prednisone can provide improvement of quality of life and partial or complete remission for up to 3-4 months. The advantages of this option are low cost, minimal visits to the vet and minimal side effects. Prednisone can, however, cause increased drinking, urination, panting and appetite.

2. Prednisone plus oral chemotherapy such as Leukeran or Cytoxan - The addition of oral chemotherapy can increase the chances of remission and possibly the duration of remission with minimal adverse effects. The cost is generally between $25-75 per month for drugs depending on the size of the pet. Reevaluation of a physical examination and blood work are recommended every 1-2 months while on these drugs.

3. COAP Protocol - This is a multidrug chemotherapy protocol which involves a combination of oral medications given at home (Prednisone and Cytoxan) and injectable drugs (Cytosar and Vincristine) given weekly at LVRC for eight weeks. After 8 weeks, animals are put on a "maintenance" protocol which involves different oral medications given at home (Leukeran, Methotrexate, and Prednisone) and monthly Vincristine injections. The maintenance protocol is continued as long as the animal is in remission, after which "rescue" protocols are used. These protocols include both oral and injectable drugs. The estimate cost for the 8 week COAP induction protocol is $1200-1400. The maintenance protocol is about $200 per month. Using the COAP induction protocol, the maintenance protocol and rescue protocols, the average survival is about 10-12 months. Adverse effects are uncommon using the COAP protocol, occurring in 10% of dogs or less.

4. Wisconsin Madison Protocol - This induction protocol involves the use of multiple oral and injectable chemotherapy drugs weekly for 11 weeks, then every other week for 15 more weeks. After a total of 26 weeks, all chemotherapy is stopped until the animal comes out of remission. At that point the protocol is started over. The average survival using these protocols is a little over a year. The estimate for the first 11 weeks is $1700-1900 and for the total 6 months $4000-5000. Adverse effects are again uncommon but can occur in about 25% or less of dogs.

Prognosis
Unfortunately, lymphoma is a disease that we do not cure. Complete remission is achieved in about 80-90% of dogs and about 50% of cats treated with some multidrug chemotherapy protocol. A second remission can be achieved using rescue protocols in about 50% dogs. Dogs that have signs of illness at the time of presentation, high calcium, gastrointestinal involvement, or T-cell lymphoma have a poorer prognosis. Eventually the disease becomes resistant to all drugs and progresses in the face of treatment. At that point animals start to have significant clinical signs associated with their disease, and their quality of life declines to the point that euthanasia is the most humane option for them. Signs that animals are having poor quality of life or are suffering can include not wanting to eat (even treats), lack of ability to sleep comfortably and unwillingness to do their normal activities (such as playing ball, going for walks, greeting owners at the door). In spite of the poor long-term prognosis in dogs with lymphoma, most clients who treat their pets are pleased with their decision, because we do everything we can to insure that the pets are happy and feeling great during their course of therapy.