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Malignant Lymphoma in Dogs

By Peter H. Holmes, BVMS, PhD, Dr HC, FRCVS, FRSE, OBE, Emeritus Professor and Former Vice-Principal, Faculty of Veterinary Medicine, University of Glasgow ; Nemi C. Jain, MVSc, PhD, Professor Emeritus of Clinical Pathology, Department of Veterinary Pathology, Microbiology, and Immunology, School of Veterinary Medicine. University of California ; David J. Waltisbuhl, BASc, MSc, Senior Scientist DPI&F Actest, Yeerongpilly Veterinary Laboratory ; Michael Bernstein, DVM, DACVIM, Director, Medical Services, Angell Animal Medical Center ; Karen L. Campbell, MS, DVM, DACVIM, DACVD, Professor and Section Head, Specialty Medicine, Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois ; Timothy M. Fan, DVM, PhD, DACVIM, Associate Professor, Department of Veterinary Clinical Medicine, University of Illinois ; Wayne K. Jorgensen, BSc, PhD, Science Leader Applied Biotechnology Livestock, Agri-Science Queensland ; Susan L. Payne, PhD, Associate Professor, Department of Veterinary Pathobiology, Texas A&M University

Malignant lymphoma is a common cancer in dogs. It is a progressive, deadly disease caused by the harmful growth of lymphocytes. Lymphoma most commonly arises from lymphoid tissues in the bone marrow, thymus, lymph nodes, or spleen. Other common sites include the skin, eye, central nervous system, and bone. Although it is common, the causes and origin of the disease are not well understood. Possible causes or contributing factors include viral infection, environmental contamination with herbicides, magnetic field exposure, genetic abnormalities, and dysfunction of the immune system.

The signs, response to treatment, and outcome of canine lymphoma will vary depending on factors, such as tumor and patient characteristics, the part of the body involved, and the extent of the disease. Most types of lymphoma are high-grade and involve T cells or B cells. In dogs, lymphoma has been classically characterized by body locations in which they occur: 1) multicentric, which originates in multiple places; 2) alimentary, which occurs in the digestive system, 3) mediastinal, which occurs within the chest; and 4) extranodal, which may involve the kidneys, central nervous system, or skin.

Multicentric lymphoma is by far the most common form, accounting for about 80%-85% of cases. An early sign of multicentric lymphoma is the rapid and nonpainful enlargement of lymph nodes, which may become 3 to 10 times their normal size. In addition to this, cancerous lymphocytes may move into internal organs including the spleen, liver, bone marrow, and other sites. Late in the course of disease, when there are multiple, large tumors, dogs may show general signs of illness, including lack of energy, weakness, fever, loss of appetite, and dehydration.

Alimentary lymphoma is much less common and accounts for less than 10% of all canine lymphomas. Dogs with this form of the disease may have signs related to stomach upset, such as vomiting and abdominal pain. When the disease affects most of the intestinal tract, dogs may have devastating signs, such as loss of appetite, vomiting, diarrhea, and continued weight loss because they cannot digest food properly.

Mediastinal lymphoma is also uncommon. Dogs with this form of the disease may have an enlarged thymus, lymph nodes, or both. As the disease advances, signs may include trouble breathing as fluid builds up in the chest and puts pressure on the lungs. The tumor may block the vein that routes blood from the upper part of the body into the heart. In addition to signs related to breathing, some dogs with mediastinal lymphoma pass large amounts of urine and drink more than normal. This can be caused by an increase in calcium in the blood, a syndrome seen in 10% to 40% of dogs with lymphoma.

The medical problems associated with extranodal lymphoma vary and depend on which organ is affected. Skin lymphoma may appear as single, raised, slow-healing sores or widespread, scaly regions. Signs of lymphoma at other extranodal sites include difficulty breathing (lungs), kidney failure (kidneys), blindness (eyes), seizures (central nervous system), and bone fractures and pain (bone).

Although most cases of lymphoma are high-grade cancers of B cells and T cells, a low-grade form occurs up to 30% of the time. These tumors develop slowly, and dogs may not show any signs of the disease.

Canine lymphoma is often relatively easy to diagnose by taking a small sample of tissue or cells from the affected organ system. In dogs with multicentric lymphoma, a needle biopsy of enlarged lymph nodes usually provides enough cells to confirm the diagnosis. Specialized tests can then help determine the type of lymphoma, which cell types are affected, and the expected outcome.

Treatment and Outlook

Treatment of high-grade, multicentric canine lymphoma with chemotherapy using a combination of drugs is often successful, with more than 90% of all dogs achieving complete remission (a complete reduction of tumors). Individual treatment plans vary with respect to the drugs used, dosage, and frequency and duration of treatment. With chemotherapy, the expected survival time for dogs with B-cell lymphoma is about 12 months. For dogs with T-cell lymphoma, expected survival times are shorter (6 months). Dogs that do not respond to the usual drugs may improve when other treatment plans are used. These alternate plans may include other drugs or radiation. In recent years, treatment has included both initial and longterm medications. Now, similar or improved responses are seen with shorter term therapies, and chemotherapy is often stopped once remission is reached. Bone marrow transplants may even be an option for some dogs.

Treating other forms of lymphoma is often more difficult. Alimentary lymphoma, if concentrated in one area, can be treated effectively with surgery to remove the tumor, together with combination chemotherapy. However, if lymphoma is spread throughout the intestinal tract, the response to treatment is not as good and survival times are shorter (often less than 3 months). The use of combination chemotherapy with or without radiation can give dogs with mediastinal lymphoma considerable improvement in survival times and quality-of-life scores. Dogs with an abnormally high level of calcium in the blood, a condition often associated with mediastinal lymphoma, are also less likely to live for long. Lymphoma involving other extranodal sites, such as the skin, can be managed with surgery, radiation, and chemotherapy as appropriate; however, the disease often stops responding to treatment. Dogs with low-grade lymphoma tend to do well and with chemotherapy can survive longer than two years.

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