Lymphosarcoma (Lymphoma) in Dogs

Lymphoma is a malignant cancer that affects dogs and consists of malignant lymphocytes, which are a type of white blood cell in the body. It can take up residence in any tissues where lymphatics or lymphocytes are present. In a healthy animal, the lymphoid system is an important part of the immune system’s defense against infectious agents, such as viruses and bacteria.

Lymphoid tissue is normally found in many different parts of the body, including the lymph nodes, liver, spleen, gastrointestinal tract, and skin. Lymphoma is the most common hematopoietic cancer for canines, and it accounts for 7-14% of all cancers diagnosed in dogs. Canine lymphoma is similar to non-Hodgkin’s lymphoma (NHL) in humans, and, microscopically, the lymphocytes look similar in both NHL and canine lymphoma. NHL is the 7th most common type of cancer diagnosed in humans.

Canine lymphoma is caused by a population of lymphocytes that are cancerous and are either B or T-cell immunophenotype. It is further classified beyond its immunophenotype based on its location.

Types of Lymphoma in Dogs

• Multicentric. The multicentric form occurs in the lymph nodes. This is the most common presentation of lymphoma seen in dogs. It accounts for 80-85% of documented cases.
• Alimentary. The alimentary form involves the gastrointestinal tract. This is a less common form of lymphoma in dogs, accounting for less than 10% of cases.
• Mediastinal. The mediastinal form occurs in the mediastinum, which is located in front of the heart in an organ called the thymus. Hence, this form of lymphosarcoma is often called mediastinal lymphoma.
• Cutaneous. The cutaneous form occurs in the skin. Skin lesions are usually the only type seen, but enlarged lymph nodes and changes to the mucocutaneous junctions are presented on occasion.
• Leukemia. Acute lymphoblastic leukemia occurs when the disease starts in the bone marrow.
• Indolent. Indolent lymphoma has very distinct behavior when compared to the other forms, since it is slow growing and patients are often asymptomatic.

Lymphoma can occur in dogs of any age, but is most commonly seen in aging dogs. Breeds that are at a higher than average include Rottweilers, Scottish Terriers, Boxers, Golden Retrievers, Basset Hounds, and German Shepherds. Males and females are affected equally. There may be a genetic basis for this disease in Boxers, Cocker Spaniels, and Irish Setters. Further research showed that Boxers tended to develop more aggressive T-cell based lymphoma, while Rottweilers and German Shepherds tended towards B-cell immunophenotypes.

Clinical Signs

Clinical signs in dogs with lymphoma are highly variable depending on the location of the cancer and progressiveness of the disease. Some dogs will have multiple, vague clinical signs, while others will only have enlarged lymph nodes.

Clinical signs include:

• Enlarged lymph nodes
• Lethargy
• Fever
• Inappetence
• Weight loss
• Vomiting
• Diarrhea
• Increased thirst/urination
• Swollen legs
• Ulcerated skin lesions
• Flaky/redness of skin lesions
• Trouble breathing/elevated respiratory rate

Diagnosis of Lymphoma in Dogs

If lymphoma is suspected in a patient, a complete medical history and physical exam is completed by a veterinarian. Based on these findings, further diagnostic tests are needed to recognize lymphosarcoma and exclude other diseases.

Tests may include:

• Blood work. Complete blood count (hemogram or CBC) is performed to evaluate your pet for anemia, low platelet count, or abnormal circulating lymphocytes. Serum biochemistry tests can be performed to evaluate the general health of your dog and determine the effect of lymphosarcoma on other organ systems. High blood calcium concentration (hypercalcemia) occurs in some animals with lymphosarcoma and can cause increased water consumption, increased urination, and kidney dysfunction.
• Urinalysis. Urinalysis can be performed to evaluate kidney function or identify presence of urinary tract infection. Dogs with lymphoma often have increased thirst and urination, which can affect their urine concentrating ability.
• Chest Radiographs. Chest radiographs are recommended for dogs that are having trouble breathing. They are also used in the staging process to look for underlying spread of disease or to identify the primary location of the tumor. Chest X-rays allow evaluation for a mediastinal mass, enlarged lymph nodes in the chest, or involvement of the lungs in the disease process. The mediastinum (a collection of lymphoid tissue located in front of the heart) can be the primary disease site in some dogs with lymphosarcoma. In addition, lymphosarcoma can be associated with fluid accumulation in the chest cavity.
• Fine Needle Aspirate. This procedure is the most common way of diagnosing lymphoma. A small needle sample of tissue is taken from enlarged lymph nodes or organs and sent to a pathologist to look for cancer cells. Fluid that has accumulated in the chest can also be withdrawn for analysis. With the aid of ultrasound examination, needle aspirates can also be obtained from internal abdominal organs (liver, kidney, spleen) or from a mediastinal mass in the chest.
• Biopsy. A biopsy specimen can be collected if the diagnosis cannot be made on the basis of cytologic evaluation of a fine needle aspirate. This can be obtained by one of several different methods, using sedation, local anesthesia, or general anesthesia (for lymph node removal).
  • Biopsy specimens can be collected by endoscopy when gastrointestinal lymphosarcoma is suspected. Endoscopy involves the use of a long flexible scope and light source to examine the inner surface of the stomach and intestines. Several areas in the stomach and intestines are biopsied and submitted for examination by a veterinary pathologist. Biopsies can also be taken during exploratory abdominal surgery depending on the location of concerning tissue. Biopsies taken during endoscopy are very small and may not be conclusive. If these samples are not conclusive, exploratory abdominal surgery can be performed to take larger biopsies from the gastrointestinal tract and to evaluate other abdominal organs like the liver, spleen, and kidneys.
• Abdominal Ultrasound. Abdominal ultrasound examination can be used to identify enlargement of abdominal organs and lymph nodes in the abdomen. This procedure can also be used to guide the needle during biopsy procedures.
• Bone Marrow Aspirate. A bone marrow aspirate is performed to determine if the disease process has affected the bone marrow. The bone marrow is responsible for making red and white blood cells and platelets. Bone marrow aspirates are usually performed using sedation and local anesthesia. The most common sites used to obtain bone marrow are the humerus (just below the shoulder) and the hip (ileum). Response to treatment may be adversely affected if lymphosarcoma is found in the bone marrow.
• PARR. PARR is a test that helps to distinguish the immunophenotype of a dog’s lymphoma. This helps to differentiate between T-cell and B-cells, create a treatment protocol, and judge long-term prognosis and life expectancy.

Treatment of Lymphoma in Dogs

The goal for treatment of canine lymphoma is clinical remission, which means resolution of clinical signs and maintenance. Curing lymphoma is often not possible, so the goal is to remain in remission for as long as possible.

Treatment for lymphoma may include the following:

Chemotherapy

Chemotherapy is the most commonly recommended treatment for dogs with lymphoma. A dog is said to be in remission when clinical evidence of the cancer disappears after treatment. Achievement of remission by chemotherapy does not mean that the animal is cured, and cancer is likely to return if treatment is discontinued. The most common chemotherapy protocol for canine lymphoma is called CHOP.

Commonly used drugs include:

• Prednisone (a cortisone-like drug)
• Vincristine (Oncovin)
• Cyclophosphamide (Cytoxan)
• L-asparaginase (Elspar)

Depending upon the drug, treatment can be given by injection under the skin (subcutaneously), intravenously, or orally. Combinations of these drugs work better than a single drug protocol.

Chemotherapy is very successful in dogs with lymphoma. Initial treatment success rate in dogs that receive aggressive chemotherapy is >90%. Working with an oncology team to create an individualized treatment plan is highly recommended.

An oncologist’s protocol may include:

• Drugs used
• Dosages
• Route of administration
• Frequency of administration
• Length of treatment

Side Effects of Chemotherapy

The most common adverse effects of cancer chemotherapy are gastrointestinal symptoms (loss of appetite, vomiting, diarrhea) or a decreased white blood cell count, which may increase the risk of secondary infection. Dogs generally do not experience the hair loss that affects humans undergoing chemotherapy. In fact, dogs usually tolerate chemotherapy much better than humans. The risk of a serious adverse effect that would require hospitalization is small (perhaps 5 to 10%). If adverse effects do occur, your veterinarian may change the protocol to prevent them during future treatments.

Eighty to 90% of dogs treated for lymphosarcoma by chemotherapy achieve remission, and average survival time is one year with B-cell lymphoma and 6 months with T-cell. Ten to 15% of dogs treated for lymphosarcoma survive 2 years or more.

Radiation

In serious cases, an oncologist may recommend either whole body radiation or half body radiation. This is commonly used in conjunction with chemotherapy and can extend disease-free intervals. An oncologist will also create a radiation protocol similar to chemotherapy protocol. This includes how many treatments are recommended, how far they are spaced out, what sedation/anesthetic protocol would be used for treatment, and a list of facilities where chemotherapy is being administered (if unavailable).

Radiation therapy requires referral to a specialty institution with specialized equipment and training. It may be recommended if an animal has lymphosarcoma localized to a single site. It is essential, in this situation, to conduct a thorough search for other areas of involvement. Chemotherapy should be used in conjunction with radiation therapy if other areas of involvement are suspected.

Adverse effects vary depending upon the region of the body treated and the number of treatments given. Animals must be anesthetized for each treatment to prevent movement during radiation exposure. Treatment of one-half of the body has been used in dogs that have come out of remission. If a good response is obtained, the other half of the body is treated 3 to 4 weeks later. Adverse effects from this type of radiation therapy are similar to those observed after chemotherapy and include gastrointestinal symptoms and low white blood cell counts.
Radiation can also be used if lymphosarcoma is present in a specific location of the body that shows signs of discomfort or other clinical signs. This type of treatment is called palliative radiation therapy, and involves use of a few large doses of radiation to the affected area. Adverse effects are minimal with this type of radiation therapy.

Relapse

It often is possible to treat pets successfully a second time using different drugs or radiation therapy when relapse occurs. Different treatment approaches are necessary because the malignant lymphocytes have become resistant to the previous drug regimen. It is more difficult to treat animals experiencing a second or third relapse, and remission times generally are shorter.

Palliative Care

Lymphoma can also be managed without chemotherapy and/or radiation through at-home corticosteroid treatment. This can be successful for short-term treatment when further advanced treatments are declined or failing. Treatment success rates are much lower with this treatment, but they can be far more expensive. Long-term prognosis is usually <3 months with just corticosteroid treatment.

Follow-Up Care for Dogs with Lymphoma

Promptly seek veterinary care if your dog develops vague signs of illness (loss of appetite, lethargy, unexplained weight loss) or abnormal swellings under the skin of the neck, shoulders, armpits, or thighs.

Dogs that are under the care of an oncologist for treatment of lymphoma may have transient gastrointestinal upset or decreased appetite. Working with your veterinarian to create the best medication plan to manage these clinical signs is essential. This often involves managing their nausea and using appetite stimulants to counteract reduced appetite.

White blood cell count may decrease after chemotherapy and increase the risk of secondary bacterial infection. Signs to watch for include lethargy and loss of appetite. A rectal thermometer can be used to monitor temperature at home. A temperature of greater than 102.5°F in an animal that is lethargic is cause for concern. Seek veterinary care promptly if you think your pet has an infection. Hospitalization to provide fluid therapy and intravenous administration of antibiotics may be necessary. Your veterinarian will monitor your dog’s white blood cell count during chemotherapy and may adjust drug dosage or schedule.