Canine Lymphoma


Lymphoma Characteristics
1. Disease of lymphocytes and commonly originates in lymph nodes, but can arise in any tissue
2. Most common hematopoietic tumor affecting dogs and cats
3. Has no known cause, though in cats has been linked to feline leukemia and feline immunodeficiency virus
4. Canine lymphoma is seen primarily in middle age to older dogs
5. While there is not a proven breed disposition, it is frequently seen in Golden Retrievers, Labrador Retrievers, Boxers, Beagles and Flat Coat Retrievers
6. Lymphoma in companion animals is comparative to Non-Hodgkins Lymphoma in people
Presentation and Diagnosis
1. Majority of canine lymphoma cases are presented with generalized lymphadenopathy (enlarged lymph nodes) that owners noticed and alerted their veterinarian to
2. Diagnosis is made by taking a sample of lymph node, most commonly by fine needle aspirate but can be done via lymph node biopsy, and sending to a pathologist
3. Either cytology or histopathology is frequently diagnostic and with more specialized testing can give results on whether cancer is B-Cell or T-Cell origin
Staging the Patient
1. Once diagnosis of lymphoma has been made, it is recommended to stage patient to determine extent of cancer within the body
2. Staging is done through a series of tests, including
1. Chest radiographs to look for increase in size of lymph nodes located around mediastinum and for pulmonary involvement
2. Abdominal ultrasound to look for changes in abdominal organs, especially liver and spleen, and to check for abdominal lymph node involvement
3. Complete blood count, chemistry profile and urinalysis to alert of alterations in body function prior to any treatment
4. Bone marrow aspirate to look for proliferation of cancer cells in the marrow.
5. Staging system commonly used is based on the World Health Organization TNM classification of tumors in domestic animals, Geneva 1980:
WORLD HEALTH ORGANIZATION CLINICAL STAGING FOR DOMESTIC ANIMALS WITH LYMPHOMA 
STAGE
	CRITERIA
	I
	Single lymph node
	II
	Multiple lymph nodes in a regional area
	III
	Generalized lymphadenopathy
	IV
	Liver and/or spleen involvement (with or without stage III)
	V
	Bone marrow or blood involvement and/or any non-lymphoid organ (with or without stages I-IV)
	Substage a
	Without clinical signs of disease
	Substage b
	With clinical signs of disease
	Predicting Remission
1. Factors
1. Once staging has been completed, treatment protocols can be initiated using that information to loosely predict remission factors
2. Remission factors include:
1. Stage of cancer
2. Type of lymphoma (B-Cell or T-Cell)
3. Substage (whether patient was ill at time of presentation)
1. Rates and Times
1. Combination chemotherapy protocol will offer highest remission rates, although it is important to note – treatment is aimed at quality of life for an extended period of time after diagnosis versus a cure
2. Remission rates vary, based on protocol chosen
3. Patient remission times are from the time patient is considered in strongest remission (either partial remission or complete remission), which is usually within the first few treatments, to relapse
4. Less than 3% of canine patients are cured of their cancer
B-Cell or T-Cell Lymphoma?
1. Further testing on sample can be done to assess whether lymphoma is B-Cell or T-Cell, both of which are 
2. found in lymphatic system
1. B-Cells are also known as Bursa Cells and they produce antibodies
2. T-Cells are also known as Thymus Cells and they are responsible for signaling additional chemical defenses of the body to ward off an infectious attack
3. PARR testing (PCR for antigen receptor) can be done on lymph node samples (aspirate or biopsy samples) and sent to specialized laboratories to find the cell of origin
4. T-Cell lymphoma is found in 1/3 of the cases and carries a poorer prognosis
Chemotherapy
1. Recommended treatment for this systemic disease
2. Following are examples of protocols being used in veterinary medicine for canine lymphoma 
1. CHOP based protocol (many different variations, but a commonly used protocol is the University of Wisconsin, Madison protocol for canine lymphoma) – 5 agents: Prednisone, L-Asparaginase (Elspar), Vincristine (Oncovin), Cyclophosphamide (Cytoxan), Doxorubicin (Adriamycin)
1. Protocol is typically given weekly with exception of 1 week off after Doxorubicin treatment
2. Remission times are expected to be 10-12 months
1. Doxorubicin – alone this drug is given every 2-3 weeks for a total of 5 treatments
1. Remission times are expected to be 6 months
1. Lomustine (CCNU) – alone this drug is given every 3 weeks for a total of 6 treatments
1. Remission times are expected to be 3 months
1. Prednisone alone – this steroid is used for its anti-tumor activity
1. If used alone,life expectancy is generally 4-6 weeks
Side Effects of Chemotherapy
1. With most commonly used chemotherapy treatments, there is a 25% chance of side effects, including:
1. Lethargy
2. Vomiting
3. Diarrhea
4. Inappetence
1. Side effects are typically self limiting and do not require hospitalization
2. Less than 5% of patients will need medical attention for their side effects
3.  Less than 1% die from complications due to chemotherapy side effects.
Relapse
1. When canine lymphoma patients relapse, cancer will typically present with similar signs, if not the same way it originally presented
2. Depending on timing of relapse, protocols may be repeated or different protocols may be used
3. Many protocols are available for chemotherapy drugs that can be utilized with the goal of achieving additional remission
Life limiting factors
1. Difficulty breathing
2. Difficulty swallowing due to enlarged lymph nodes in the neck and head
3. General lethargy and flu-like symptoms associated with an increase in lymphoblasts in the circulating lymphatic system
4. Rarely do these patients succumb to the disease without assistance of humane euthanasia
References 


Vail, D.M., Thamm, D.H. (2005). Hematopoietic Tumors, in Ettinger, S.J., Feldman, E.C. (Eds.): Textbook of Veterinary Internal Medicine (6th Ed., pp 732-741). St. Louis, MO: Saunders
Chun, R., Garrett, L.D., Vail, D.M. (2007). Cancer Chemotherapy, in Withrow, Vail (Eds.): Small Animal Clinical Oncology (4th Ed., pp. 163-188). St. Louis, MO: Saunders 
Vail, D.M., Young, K.M. (2007). Hematopoietic Tumors, Canine Lymphoma and Lymphoid Leukemia, in Withrow, Vail (Eds.): Small Animal Clinical Oncology (4th Ed.). St. Louis, MO: Saunders
Husbands, B.D. University of Minnesota Veterinary Medical Center, Internal Medicine/Oncology veterinarian
Canine Lymphoma
January 20, 2010 (published)
Michelle Miller, BS, CVT
Lymphoma Characteristics
1. Disease of lymphocytes and commonly originates in lymph nodes, but can arise in any tissue
2. Most common hematopoietic tumor affecting dogs and cats
3. Has no known cause, though in cats has been linked to feline leukemia and feline immunodeficiency virus
4. Canine lymphoma is seen primarily in middle age to older dogs
5. While there is not a proven breed disposition, it is frequently seen in Golden Retrievers, Labrador Retrievers, Boxers, Beagles and Flat Coat Retrievers
6. Lymphoma in companion animals is comparative to Non-Hodgkins Lymphoma in people
Presentation and Diagnosis
1. Majority of canine lymphoma cases are presented with generalized lymphadenopathy (enlarged lymph nodes) that owners noticed and alerted their veterinarian to
2. Diagnosis is made by taking a sample of lymph node, most commonly by fine needle aspirate but can be done via lymph node biopsy, and sending to a pathologist
3. Either cytology or histopathology is frequently diagnostic and with more specialized testing can give results on whether cancer is B-Cell or T-Cell origin
Staging the Patient
1. Once diagnosis of lymphoma has been made, it is recommended to stage patient to determine extent of cancer within the body
2. Staging is done through a series of tests, including
1. Chest radiographs to look for increase in size of lymph nodes located around mediastinum and for pulmonary involvement
2. Abdominal ultrasound to look for changes in abdominal organs, especially liver and spleen, and to check for abdominal lymph node involvement
3. Complete blood count, chemistry profile and urinalysis to alert of alterations in body function prior to any treatment
4. Bone marrow aspirate to look for proliferation of cancer cells in the marrow.
5. Staging system commonly used is based on the World Health Organization TNM classification of tumors in domestic animals, Geneva 1980:
WORLD HEALTH ORGANIZATION CLINICAL STAGING FOR DOMESTIC ANIMALS WITH LYMPHOMA 
STAGE
	CRITERIA
	I
	Single lymph node
	II
	Multiple lymph nodes in a regional area
	III
	Generalized lymphadenopathy
	IV
	Liver and/or spleen involvement (with or without stage III)
	V
	Bone marrow or blood involvement and/or any non-lymphoid organ (with or without stages I-IV)
	Substage a
	Without clinical signs of disease
	Substage b
	With clinical signs of disease
	Predicting Remission
1. Factors
1. Once staging has been completed, treatment protocols can be initiated using that information to loosely predict remission factors
2. Remission factors include:
1. Stage of cancer
2. Type of lymphoma (B-Cell or T-Cell)
3. Substage (whether patient was ill at time of presentation)
1. Rates and Times
1. Combination chemotherapy protocol will offer highest remission rates, although it is important to note – treatment is aimed at quality of life for an extended period of time after diagnosis versus a cure
2. Remission rates vary, based on protocol chosen
3. Patient remission times are from the time patient is considered in strongest remission (either partial remission or complete remission), which is usually within the first few treatments, to relapse
4. Less than 3% of canine patients are cured of their cancer
B-Cell or T-Cell Lymphoma?
1. Further testing on sample can be done to assess whether lymphoma is B-Cell or T-Cell, both of which are 
2. found in lymphatic system
1. B-Cells are also known as Bursa Cells and they produce antibodies
2. T-Cells are also known as Thymus Cells and they are responsible for signaling additional chemical defenses of the body to ward off an infectious attack
3. PARR testing (PCR for antigen receptor) can be done on lymph node samples (aspirate or biopsy samples) and sent to specialized laboratories to find the cell of origin
4. T-Cell lymphoma is found in 1/3 of the cases and carries a poorer prognosis
Chemotherapy
1. Recommended treatment for this systemic disease
2. Following are examples of protocols being used in veterinary medicine for canine lymphoma 
1. CHOP based protocol (many different variations, but a commonly used protocol is the University of Wisconsin, Madison protocol for canine lymphoma) – 5 agents: Prednisone, L-Asparaginase (Elspar), Vincristine (Oncovin), Cyclophosphamide (Cytoxan), Doxorubicin (Adriamycin)
1. Protocol is typically given weekly with exception of 1 week off after Doxorubicin treatment
2. Remission times are expected to be 10-12 months
1. Doxorubicin – alone this drug is given every 2-3 weeks for a total of 5 treatments
1. Remission times are expected to be 6 months
1. Lomustine (CCNU) – alone this drug is given every 3 weeks for a total of 6 treatments
1. Remission times are expected to be 3 months
1. Prednisone alone – this steroid is used for its anti-tumor activity
1. If used alone,life expectancy is generally 4-6 weeks
Side Effects of Chemotherapy
1. With most commonly used chemotherapy treatments, there is a 25% chance of side effects, including:
1. Lethargy
2. Vomiting
3. Diarrhea
4. Inappetence
1. Side effects are typically self limiting and do not require hospitalization
2. Less than 5% of patients will need medical attention for their side effects
3.  Less than 1% die from complications due to chemotherapy side effects.
Relapse
1. When canine lymphoma patients relapse, cancer will typically present with similar signs, if not the same way it originally presented
2. Depending on timing of relapse, protocols may be repeated or different protocols may be used
3. Many protocols are available for chemotherapy drugs that can be utilized with the goal of achieving additional remission
Life limiting factors
1. Difficulty breathing
2. Difficulty swallowing due to enlarged lymph nodes in the neck and head
3. General lethargy and flu-like symptoms associated with an increase in lymphoblasts in the circulating lymphatic system
4. Rarely do these patients succumb to the disease without assistance of humane euthanasia
References 


Vail, D.M., Thamm, D.H. (2005). Hematopoietic Tumors, in Ettinger, S.J., Feldman, E.C. (Eds.): Textbook of Veterinary Internal Medicine (6th Ed., pp 732-741). St. Louis, MO: Saunders
Chun, R., Garrett, L.D., Vail, D.M. (2007). Cancer Chemotherapy, in Withrow, Vail (Eds.): Small Animal Clinical Oncology (4th Ed., pp. 163-188). St. Louis, MO: Saunders 
Vail, D.M., Young, K.M. (2007). Hematopoietic Tumors, Canine Lymphoma and Lymphoid Leukemia, in Withrow, Vail (Eds.): Small Animal Clinical Oncology (4th Ed.). St. Louis, MO: Saunders
Husbands, B.D. University of Minnesota Veterinary Medical Center, Internal Medicine/Oncology veterinarian