Lymphoma in animals
Lymphoma in animals is a type of
cancerdefined by a proliferation of malignant lymphocytes within solid organs such as the lymph nodes, bone marrow, liverand spleen. The disease also may occur in the eye, skin, and gastrointestinal tract. It is also known as lymphosarcoma.
Lymphoma in dogs
Lymphoma is one of the most common malignant
tumors to occur in dogs. The cause is genetic, but there also suspected environmental factors involved,cite book|author=Morrison, Wallace B.|title=Cancer in Dogs and Cats|edition=1st ed.|publisher=Williams and Wilkins|year=1998|id=ISBN 0-683-06105-4] including in one study an increased risk with the use of the herbicide2,4-D. [cite journal |author=Zahm S, Blair A |title=Pesticides and non-Hodgkin's lymphoma |journal=Cancer Res |volume=52 |issue=19 Suppl |pages=5485s-5488s |year=1992 |pmid=1394159] This risk was not confirmed in another study. [cite journal |author=Kaneene J, Miller R |title=Re-analysis of 2,4-D use and the occurrence of canine malignant lymphoma |journal=Vet Hum Toxicol |volume=41 |issue=3 |pages=164–70 |year=1999 |pmid=10349709]
Commonly affected breeds
German Shepherd Dog
Golden Retrieveris especially susceptible to developing lymphoma, with a lifetime risk of 1:8. [cite journal |author=Modiano J, Breen M, Burnett R, Parker H, Inusah S, Thomas R, Avery P, Lindblad-Toh K, Ostrander E, Cutter G, Avery A |title=Distinct B-cell and T-cell lymphoproliferative disease prevalence among dog breeds indicates heritable risk |journal=Cancer Res |volume=65 |issue=13 |pages=5654–61 |year=2005 |pmid=15994938 |doi=10.1158/0008-5472.CAN-04-4613]
The cancer is classified into low and high grade types. Classification is also based on location. The four location types are multicentric, mediastinal, gastrointestinal, and extranodal (involving the kidney,
central nervous system, skin, heart, or eye). Multicentric lymphoma, the most common type (by greater than 80 percent), [cite web | title = Canine Malignant Lymphoma: Introduction | work = The Merck Veterinary Manual | year = 2006 | url = http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/10500.htm | accessdate = 2007-01-28 ] is found in the lymph nodes, with or without involvement in the liver, spleen, or bone marrow. Mediastinal lymphoma occurs in the lymph nodes in the thorax and possibly the thymus. Gastrointestinal lymphoma occurs as either a solitary tumor or diffuse invasion of the stomach or intestines, with or without involvement in the surrounding lymph nodes, liver or spleen.cite journal |author=Lowe A |title=Alimentary lymphosarcoma in a 4-year-old Labrador retriever |journal=Can Vet J |volume=45 |issue=7 |pages=610–2 |year=2004 |pmid=15317395] Classification is further based on involvement of B-lymphocytes or T-lymphocytes. Approximately 70 percent are B-cell lymphoma. [cite web|author=Simon, Daniela|year=2006|title=Malignant lymphoma in the dog: Short and long term chemotherapy|work=Proceedings of the North American Veterinary Conference|url=http://www.ivis.org/proceedings/navc/2006/SAE/292.pdf?LA=1|accessdate=2007-01-28] Cutaneous lymphoma can be classified as epitheliotropic (closely conforming to the epidermis) or non-epitheliotropic. The epitheliotropic form is typically of T-cell origin and is also called mycosis fungoides. The non-epitheliotropic form is typically of B-cell origin.cite journal | last = Hoskins | first = Johnny D. | title = Cutaneous paraneoplastic disease | journal = DVM | pages = 6S–7S | publisher = Advanstar Communications | month = May | year = 2006 ]
igns and symptoms
General signs and symptoms include depression, fever, weight loss, loss of appetite, and vomiting. Lymphoma is the most common cancerous cause of hypercalcemia (high blood
calciumlevels) in dogs.cite journal | last = Lucas | first = Pamela | coauthors = Lacoste, Hugues; de Lorimier, Louis-Phillipe; Fan, Timothy M. | title = Treating paraneoplastic hypercalcemia in dogs and cats | journal = Veterinary Medicine | volume = 102 | issue = 5 | pages = 314–331 | publisher = Advanstar Communications | month = May | year = 2007 ] It can lead to the above signs and symptoms plus increased water drinking, increased urination, and cardiac arrhythmias. Hypercalcemia in these cases is caused by secretion of parathyroid hormone-related protein.
Multicentric lymphoma presents as painless enlargement of the peripheral lymph nodes. This is seen in areas such as under the jaw, the armpits, the groin, and behind the knees. Enlargement of the liver and spleen causes the abdomen to distend. Mediastinal lymphoma can cause fluid to collect around the lungs, leading to coughing and difficulty breathing. Hypercalcemia is most commonly associated with this type. [cite web | title = Hypercalcemia of Malignancy | work = The Merck Veterinary Manual | year = 2006 | url = http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/40404.htm | accessdate = 2007-01-28 ]
Gastrointestinal lymphoma causes vomiting, diarrhea, and
melena(digested blood in the stool). Low serum albuminlevels and hypercalcemia can also occur.
Lymphoma of the skin is an uncommon occurrence. The epitheliotropic form typically appears as itchy inflammation of the skin progressing to nodules and plaques. The non-epitheliotropic form can have a wide variety of appearances, from a single lump to large areas of bruised,
ulcerated, hairless skin. The epitheliotropic form must be differentiated from similar appearing conditions such as pemphigus vulgaris, bullous pemphigoid, and lupus erythematosus. [cite journal |author=Bhang D, Choi U, Kim M, Choi E, Kang M, Hwang C, Kim D, Youn H, Lee C |title=Epitheliotropic cutaneous lymphoma (mycosis fungoides) in a dog |journal=J Vet Sci |volume=7 |issue=1 |pages=97–9 |year=2006 |pmid=16434861]
Signs for lymphoma in other sites depend on the location. Central nervous system involvement can cause
seizures or paralysis. Eye involvement, seen in 20 to 25 percent of cases,cite web | last = Ogilvie | first = Gregory K. | title = Canine Lymphoma: Protocols For 2004 | work = Proceedings of the 29th World Congress of the World Small Animal Veterinary Association | year = 2004 | url = http://www.vin.com/proceedings/Proceedings.plx?CID=WSAVA2004&PID=8710&Category=1265&O=Generic | accessdate = 2006-08-20 ] can lead to glaucoma, uveitis, bleeding within the eye, retinal detachment, and blindness. Lymphoma in the bone marrow causes anemia, low plateletcount, and low white blood cellcount.
Biopsyof affected lymph nodes or organs confirms the diagnosis, although a needle aspiration of an affected lymph node can increase suspicion of the disease. X-rays, ultrasound, blood analysis, and bone marrow biopsy reveal other locations of the cancer. The stage of the disease is important to treatment and prognosis.
*Stage I - only one lymph node or lymphoid tissue in one organ involved.
*Stage II - lymph nodes in only one area of the body involved.
*Stage III - generalized lymph node involvement.
*Stage IV - any of the above with liver or spleen involvement.
*Stage V - any of the above with blood or bone marrow involvement.Each stage is divided into those with systemic symptoms (loss of appetite, weight loss, etc.) and those without.
Complete cure is rare with lymphoma and treatment tends to be palliative, but long remission times are possible with
chemotherapy. With effective protocols, average first remission times are 6 to 8 months. Second remissions are shorter and harder to accomplish. Average survival is 9 to 12 months. The most common treatment is a combination of cyclophosphamide, vincristine, prednisone, L-asparaginase, and doxorubicin. Other chemotherapy drugs such as chlorambucil, lomustine(CCNU), cytosine arabinoside, and mitoxantroneare sometimes used in the treatment of lymphoma by themselves or in substitution for other drugs. In most cases, appropriate treatment protocols cause few side effects, but white blood cell counts must be monitored.
Allogenic stem cell transplantation (as is commonly done in humans) has recently shown to be a possible treatment option for dogs. [cite journal |author=Lupu M, Sullivan E, Westfall T, Little M, Weigler B, Moore P, Stroup P, Zellmer E, Kuhr C, Storb R |title=Use of multigeneration-family molecular dog leukocyte antigen typing to select a hematopoietic cell transplant donor for a dog with T-cell lymphoma |journal=J Am Vet Med Assoc |volume=228 |issue=5 |pages=728–32 |year=2006 |pmid=16506937 |doi=10.2460/javma.228.5.728] Most of the basic research on transplantation biology was generated in dogs.
When cost is a factor, prednisone used alone can improve the symptoms dramatically, but it does not significantly affect the survival rate. The average survival times of dogs treated with prednisone and untreated dogs are both one to two months. Using prednisone alone can cause the cancer to become resistant to other chemotherapy agents, so it should only be used if more aggressive treatment is not an option.
Isotretinoincan be used to treat cutaneous lymphoma.
Untreated dogs have an average survival time of sixty days. [cite journal |author=Siedlecki C, Kass P, Jakubiak M, Dank G, Lyons J, Kent M |title=Evaluation of an actinomycin-D-containing combination chemotherapy protocol with extended maintenance therapy for canine lymphoma |journal=Can Vet J |volume=47 |issue=1 |pages=52–9 |year=2006 |pmid=16536229] Lymphoma with a histologic high grade generally respond better to treatment but have shorter survival times than dogs with low grade lymphoma. Dogs with B-lymphocyte tumors have a longer survival time than T-lymphocyte tumors. Mediastinal lymphoma has a poorer prognosis than other types, especially those with hypercalcemia. Clinical stage and substage have some prognostic value, with poorer prognosis associated with Stage V disease, and with substage b (clinical illness at time of presentation).
Lymphoma in cats
Lymphoma is the most common malignancy diagnosed in cats.cite web | title = Feline Leukemia Virus and Related Diseases: Introduction | work = The Merck Veterinary Manual | year = 2006 | url = http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/57000.htm | accessdate = 2007-01-28 ] Lymphoma in young cats occurs most frequently following infection with
feline leukemia virus(FeLV) or to a lesser degree feline immunodeficiency virus(FIV). These cats tend to have involvement of lymph nodes, spine, or mediastinum. Cats with FeLV are 62 times more likely to develop lymphoma, and cats with both FeLV and FIV are 77 times more likely.cite book|author=Ettinger, Stephen J.;Feldman, Edward C.|title=Textbook of Veterinary Internal Medicine|edition=4th ed.|publisher=W.B. Saunders Company|year=1995|id=ISBN 0-7216-6795-3] Younger cats tend to have T-cell lymphoma and older cats tend to have B-cell lymphoma. [cite journal |author=Seo K, Choi U, Bae B, Park M, Hwang C, Kim D, Youn H |title=Mediastinal lymphoma in a young Turkish Angora cat |journal=J Vet Sci |volume=7 |issue=2 |pages=199–201 |year=2006 |pmid=16645348] Cats living with smokers are more than twice as likely to develop lymphoma.cite web | last = O'Rourke | first = Kate | title = Lymphoma risk in cats more than doubles if owners are smokers | work = JAVMA News | date = November 1, 2002 | url = http://www.avma.org/onlnews/javma/nov02/021101l.asp | accessdate = 2006-08-20 ] Older cats tend to have gastrointestinal lymphoma without FeLV infection, [cite web | title = Gastrointestinal Neoplasia | work = The Merck Veterinary Manual | year = 2006 | url = http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/23307.htm | accessdate = 2007-01-28 ] although tests more sensitive to low level FeLV infections and replication-defective FeLV have found that many of these cats have been previously exposed. [cite web|author=Richter, Keith P.|year=2006|title=Feline gastrointestinal lymphoma|work=Proceedings of the North American Veterinary Conference|url=http://www.ivis.org/proceedings/navc/2006/SAE/285.pdf?LA=1|accessdate=2007-01-28] The same forms of lymphoma that are found in dogs also occur in cats, but gastrointestinal is the most common type. Lymphoma of the kidney is the most common kidney tumor in cats, and lymphoma is also the most common heart tumor.
Gastrointestinal lymphoma is classified into low grade, intermediate grade, and high grade. Low grade types include lymphocytic and
small cell lymphoma. High grade types include lymphoblastic, immunoblastic, and large celllymphoma. Low grade lymphoma is only found in the small intestine, while large grade can commonly be found in the stomach.cite journal | last = Matz | first = Michael E. | title = Chronic Vomiting in a Cat | journal = Clinician's Brief | volume = 5 | issue = 1 | pages = 29–31 | publisher = North American Veterinary Conference | month = January | year = 2007 ]
Cats that develop lymphoma are much more likely to develop more severe symptoms than dogs. Whereas dogs often appear healthy initially except for swollen lymph nodes, cats will often be physically ill. The symptoms correspond closely to the location of the lymphoma. The most common sites for alimentary (gastrointestinal) lymphoma are, in decreasing frequency, the
small intestine, the stomach, the junction of the ileum, cecum, and colon. Cats with the alimentary form of lymphoma often present with weight loss, rough hair coat, loss of appetite, vomiting and diarrhea, although vomiting and diarrhea are commonly absent as symptoms. [cite web | last = Gaschen | first = Frédéric | title = Small Intestinal Diarrhea: Causes and Treatment | work = Proceedings of the 31st World Congress of the World Small Animal Veterinary Association | year = 2006 | url = http://www.ivis.org/proceedings/wsava/2006/lecture12/GaschenF2.pdf?LA=1 | accessdate = 2007-01-28 ] The tumor can also cause life-threatening blockage of the intestine. Cats with the mediastinal form often have respiratory distress and fluid in the lung cavity. If lymphoma develops in the kidney, the cat may have increased water consumption and increased urination. Lymphoma of the kidney presents as bilateral kidney enlargement and failure. If the lymphoma is located in the nose, the cat may have discharge from the nose and facial swelling. Lymphoma of the heart causes congestive heart failure, pericardial effusion, and cardiac arrhythmias. Ocular lymphoma in cats often presents as anterior uveitis(inflammation of the inside of the eye). [cite journal | last = van der Woerdt | first = Alexandra | title = Iris Nodule in a Cat | journal = Clinician's Brief | volume = 5 | issue = 6 | pages = 7–8 | publisher = North American Veterinary Conference | month = June | year = 2007 ] Cats who are also infected with FeLV often present with pale mucous membranes due to anemia. Anemia is a common problem in all cats with lymphoma, but hypercalcemia is rare. Diagnosis is similar to dogs, except cats should be tested for FeLV and FIV. It is important to differentiate the alimentary form of lymphoma from inflammatory bowel diseasebecause the signs are so similar in cats. A biopsy is necessary to do this. [cite journal |author=Evans S, Bonczynski J, Broussard J, Han E, Baer K |title=Comparison of endoscopic and full-thickness biopsy specimens for diagnosis of inflammatory bowel disease and alimentary tract lymphoma in cats |journal=J Am Vet Med Assoc |volume=229 |issue=9 |pages=1447–50 |year=2006 |pmid=17078807 |doi=10.2460/javma.229.9.1447]
Treatment and prognosis
Chemotherapyis the mainstay of treatment for lymphoma in cats. Most of the drugs used in dogs are used in cats, but the most common protocol uses cyclophosphamide, vincristine, and prednisolone. Gastrointestinal lymphoma has also commonly been treated with a combination of prednisolone and high dose pulse chlorambucilwith success. The white blood cell count must be monitored. Remission and survival times are comparable to dogs. Lower stage lymphoma has a better prognosis. Multicentric lymphoma has a better response to treatment than the gastrointestinal form, but infection with FeLV worsens the prognosis.
Lymphoma in ferrets
Lymphoma is common in
ferrets and is the most common cancer in young ferrets. There is some evidence that a retrovirusmay play a role in the development of lymphoma like in cats. [cite web | last = Hernández-Divers | first = Sonia M. | title = Ferret Diseases | work = Proceedings of the 30th World Congress of the World Small Animal Veterinary Association | year = 2005 | url = http://www.vin.com/proceedings/Proceedings.plx?CID=WSAVA2005&PID=10894&O=Generic | accessdate = 2007-01-28 ] The most commonly affected tissues are the lymph nodes, spleen, liver, intestine, mediastinum, bone marrow, lung, and kidney.
In young ferrets, the disease progresses rapidly. The most common symptom is difficulty breathing caused by enlargement of the
thymus. [cite web|author=Mayer, Joerg|year=2006|title=Update on ferret lymphoma|work=Proceedings of the North American Veterinary Conference|url=http://www.ivis.org/proceedings/navc/2006/SAE/631.pdf?LA=1|accessdate=2007-01-28] Other symptoms include loss of appetite, weight loss, weakness, depression, and coughing. It can also masquerade as a chronic disease such as an upper respiratory infection or gastrointestinal disease. In older ferrets, lymphoma is usually chronic and can exhibit no symptoms for years. [cite web | title = Ferret Neoplasia | work = The Merck Veterinary Manual | year = 2006 | url = http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/170304.htm | accessdate = 2007-01-01 ] Symptoms seen are the same as in young ferrets, plus splenomegaly, abdominal masses, and peripheral lymph node enlargement.
Diagnosis is through biopsy and x-rays. There may also be an increased
lymphocytecount. Treatment includes surgery for solitary tumors, splenectomy(when the spleen is very large), and chemotherapy. The most common protocol uses prednisone, vincristine, and cyclophosphamide.cite book|author=Hillyer, Elizabeth V.;Quesenberry, Katherin E.|title=Ferrets, Rabbits, and Rodents: Clinical Medicine and Surgery|edition=1st ed.|publisher=W.B. Saunders Company|year=1997|id=ISBN 0-7216-4023-0] Doxorubicin is used in some cases. Chemotherapy in relatively healthy ferrets is tolerated very well, but possible side effects include loss of appetite, depression, weakness, vomiting, and loss of whiskers. The white blood cell count must be monitored. Prednisone used alone can work very well for weeks to months, but it may cause resistance to other chemotherapy agents. Alternative treatments include vitamin Cand Pau d'Arco (a bark extract).
The prognosis for lymphoma in ferrets depends on the their health and the location of the cancer. Lymphoma in the mediastinum, spleen, skin, and peripheral lymph nodes has the best prognosis, while lymphoma in the intestine, liver, abdominal lymph nodes, and bone marrow has the worst.
* [http://www.petcancercenter.org/Cancer_Types_lymphoma.html "Comprehensive guide to cancer in dogs" from Pet Cancer Center]
* [http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/10500.htm "Lymphoma in pets" from Merck Veterinar Manual]
* [http://www.vetmed.wsu.edu/clientED/lsa.asp "Canine lymphosarcoma" from Washington State University Veterinary School of Medicine]
* [http://www.veterinarypartner.com/Content.plx?P=A&A=575 "Lymphoma in dogs" from Pet Health Library]
* [http://www.vetspecialists.co.uk/06_Animal_Welfare/Oncology_Facts/Canine_Lymphoma.html"Lymphoma in the dog" from Davies Veterinary Specialists]
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