Lymphoma in animals
Encyclopedia
Lymphoma in animals is a type of cancer
defined by a proliferation of malignant
lymphocyte
s within solid organs such as the lymph node
s, bone marrow
, liver
and spleen
. The disease also may occur in the eye
, skin
, and gastrointestinal tract
. It is also known as lymphosarcoma.
s to occur in dogs. The cause is genetic
, but there also suspected environmental factors involved, including in one study an increased risk with the use of the herbicide
2,4-D
. This risk was not confirmed in another study.
Breeds that are commonly affected include Boxer
, Scottish Terrier
, Basset Hound
, Airedale Terrier
, Chow Chow
, German Shepherd
, Poodle
, St. Bernard
, Bulldog
, Beagle
, Rottweiler
and Golden Retriever
. The Golden Retriever
is especially susceptible to developing lymphoma, with a lifetime risk of 1:8.
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), 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. Classification is further based on involvement of B-lymphocytes
or T-lymphocytes
. Approximately 70 percent are B-cell lymphoma. 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.
(high blood calcium
levels) in dogs. 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.
Gastrointestinal lymphoma causes vomiting, diarrhea, and melena
(digested blood in the stool). Low serum albumin
levels 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
.
Signs for lymphoma in other sites depend on the location. Central nervous system involvement can cause seizure
s or paralysis
. Eye involvement, seen in 20 to 25 percent of cases, can lead to glaucoma
, uveitis
, bleeding within the eye, retinal detachment
, and blindness. Lymphoma in the bone marrow causes anemia
, low platelet
count, and low white blood cell
count.
of affected lymph nodes or organs confirms the diagnosis, although a needle aspiration of an affected lymph node can increase suspicion of the disease. X-ray
s, ultrasound
, blood analysis, and bone marrow biopsy reveal other locations of the cancer. The stage of the disease is important to treatment and prognosis
.
Each stage is divided into those with systemic symptoms (loss of appetite, weight loss, etc.) and those without.
, 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 mitoxantrone
are 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.
Allogeneic and autologous stem cell transplantations (as is commonly done in humans) have recently been shown to be a possible treatment option for dogs. Most of the basic research on transplantation biology was generated in dogs. Current cure rates using stem cell therapy in dogs approximates that achieved in humans, 40-50%.
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.
Isotretinoin
can be used to treat cutaneous lymphoma.
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).
(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. Younger cats tend to have T-cell lymphoma and older cats tend to have B-cell lymphoma. Older cats tend to have gastrointestinal lymphoma without FeLV infection, although tests more sensitive to low level FeLV infections and replication-defective FeLV have found that many of these cats have been previously exposed. 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.
ic, immunoblastic, and large cell
lymphoma. Low grade lymphoma is only found in the small intestine, while large grade can commonly be found in the stomach.
, 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. 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). 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 disease
because the signs are so similar in cats. A biopsy is necessary to do this. One approach to differentiate inflammatory bowel disease from is to test the infiltrating lymphocytes for their monoclonal origin in lymphomas.
is 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 prednisone. Gastrointestinal lymphoma has also commonly been treated with a combination of prednisolone and high dose pulse chlorambucil
with 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.
About 75% of cats treated with chemotherapy for lymphoma do go into remission, unfortunately, most cats who have an initial remission relapse, and the median survival for a cat with lymphoma who is treated with chemotherapy is just 6 months. However, about one-third of cats treated with chemotherapy will survive more than 2 years after diagnosis, and a small number of these cats may be cured of their disease. Untreated, most cats with lymphoma die within 4–6 weeks. Most cats tolerate their chemotherapy well, and fewer than 5% have severe side effects. Cats do not lose their fur from chemotherapy, though loss of whiskers is possible. Other side effects include low white blood cell count, vomiting, loss of appetite, diarrhea, or fatigue, but these can typically be controlled well, and most cats have a good quality of life during treatment. If a cat relapses after attaining remission, the cat can be treated with different chemotherapy drugs to try to obtain a second remission, but the chances of obtaining a second remission are much lower than the chances of obtaining a first remission, and the second remission is often shorter than the first.
s and is the most common cancer in young ferrets. There is some evidence that a retrovirus
may play a role in the development of lymphoma like in cats. 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
. 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. 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 lymphocyte
count. Treatment includes surgery for solitary tumors, splenectomy
(when the spleen is very large), and chemotherapy. The most common protocol uses prednisone, vincristine, and cyclophosphamide. 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 C
and 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.
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
defined by a proliferation of malignant
Malignant
Malignancy is the tendency of a medical condition, especially tumors, to become progressively worse and to potentially result in death. Malignancy in cancers is characterized by anaplasia, invasiveness, and metastasis...
lymphocyte
Lymphocyte
A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
s within solid organs such as the lymph node
Lymph node
A lymph node is a small ball or an oval-shaped organ of the immune system, distributed widely throughout the body including the armpit and stomach/gut and linked by lymphatic vessels. Lymph nodes are garrisons of B, T, and other immune cells. Lymph nodes are found all through the body, and act as...
s, bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
, liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
and spleen
Spleen
The spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...
. The disease also may occur in the eye
Eye
Eyes are organs that detect light and convert it into electro-chemical impulses in neurons. The simplest photoreceptors in conscious vision connect light to movement...
, skin
Skin
-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
, and gastrointestinal tract
Gastrointestinal tract
The human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....
. It is also known as lymphosarcoma.
Lymphoma in dogs
Lymphoma is one of the most common malignant tumorTumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
s to occur in dogs. The cause is genetic
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
, but there also suspected environmental factors involved, including in one study an increased risk with the use of the herbicide
Herbicide
Herbicides, also commonly known as weedkillers, are pesticides used to kill unwanted plants. Selective herbicides kill specific targets while leaving the desired crop relatively unharmed. Some of these act by interfering with the growth of the weed and are often synthetic "imitations" of plant...
2,4-D
2,4-Dichlorophenoxyacetic acid
2,4-Dichlorophenoxyacetic acid is a common systemic pesticide/herbicide used in the control of broadleaf weeds. It is the most widely used herbicide in the world, and the third most commonly used in North America...
. This risk was not confirmed in another study.
Breeds that are commonly affected include Boxer
Boxer (dog)
Developed in Germany, the Boxer is a breed of stocky, medium-sized, short-haired dog. The coat is smooth and fawn or brindled, with or without white markings. Boxers are brachycephalic , and have a square muzzle, mandibular prognathism , very strong jaws and a powerful bite ideal for hanging on to...
, Scottish Terrier
Scottish Terrier
The Scottish Terrier , popularly called the Scottie, is a breed of dog. Initially one of the highland breeds of Terrier that were grouped under the name of Skye Terrier, it is one of five breeds of terrier that originated in Scotland, the other four being the modern Skye, Cairn, Dandie Dinmont, and...
, Basset Hound
Basset Hound
The Basset Hound is a short-legged breed of dog of the hound family. They are scent hounds, bred to hunt rabbits and hare by scent. Their sense of smell for tracking is second only to that of the Bloodhound....
, Airedale Terrier
Airedale Terrier
The Airedale Terrier is a breed of the terrier type that originated in Airedale, a geographic area in Yorkshire, England. It is traditionally called the "King of Terriers" because it is the largest of the terrier breeds...
, Chow Chow
Chow Chow
Chow chow is a breed of dog that was developed in China, where it is referred to as Songshi Quan , which literally means "puffy-lion dog".- Appearance :...
, German Shepherd
German Shepherd Dog
The German Shepherd Dog , also known as an Alsatian or just the German Shepherd, is a breed of large-sized dog that originated in Germany. The German Shepherd is a relatively new breed of dog, with its origin dating to 1899. As part of the Herding Group, the German Shepherd is a working dog...
, Poodle
Poodle
The Poodle is a breed of dog. The poodle breed is found officially in toy, miniature, and standard sizes, with many coat colors. Originally bred as a type of water dog, the poodle is highly intelligent and skillful in many dog sports, including agility, obedience, tracking, and even herding...
, St. Bernard
St. Bernard (dog)
The St. Bernard is a breed of very large working dog from the Italian and Swiss Alps, originally bred for rescue. The breed has become famous through tales of alpine rescues, as well as for its large size.-Appearance:The St. Bernard is a large dog...
, Bulldog
Bulldog
Bulldog is the name for a breed of dog commonly referred to as the English Bulldog. Other Bulldog breeds include the American Bulldog, Olde English Bulldogge and the French Bulldog. The Bulldog is a muscular heavy dog with a wrinkled face and a distinctive pushed-in nose...
, Beagle
Beagle
The Beagle is a breed of small to medium-sized dog. A member of the Hound Group, it is similar in appearance to the Foxhound, but smaller, with shorter legs and longer, softer ears. Beagles are scent hounds, developed primarily for tracking hare, rabbit, and other game...
, Rottweiler
Rottweiler
The Rottweiler is a medium to large size breed of domestic dog that originated in Rottweil, Germany. The dogs were known as "Rottweil butchers' dogs" because they were used to herd livestock and pull carts laden with butchered meat and other products to market...
and Golden Retriever
Golden Retriever
The Golden Retriever is a medium-sized breed of dog. They were historically developed as gundogs to retrieve shot waterfowl such as ducks and upland game birds during hunting and shooting parties. As such, they were bred to have a soft mouth to retrieve game undamaged and have an instinctive love...
. The Golden Retriever
Golden Retriever
The Golden Retriever is a medium-sized breed of dog. They were historically developed as gundogs to retrieve shot waterfowl such as ducks and upland game birds during hunting and shooting parties. As such, they were bred to have a soft mouth to retrieve game undamaged and have an instinctive love...
is especially susceptible to developing lymphoma, with a lifetime risk of 1:8.
Classification
The cancer is classified into low and high gradeGrading (tumors)
In pathology, grading is a measure of the cell appearance in tumors and other neoplasms. Some pathology grading systems apply only to malignant neoplasms ; others apply also to benign neoplasms. The neoplastic grading is a measure of cell anaplasia in the sampled tumors arising from the...
types. Classification is also based on location. The four location types are multicentric, mediastinal
Mediastinum
The mediastinum is a non-delineated group of structures in the thorax, surrounded by loose connective tissue. It is the central compartment of the thoracic cavity...
, gastrointestinal, and extranodal (involving the kidney, central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
, skin, heart, or eye). Multicentric lymphoma, the most common type (by greater than 80 percent), 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
Thymus
The thymus is a specialized organ of the immune system. The thymus produces and "educates" T-lymphocytes , which are critical cells of the adaptive immune system....
. 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. Classification is further based on involvement of B-lymphocytes
B cell
B cells are lymphocytes that play a large role in the humoral immune response . The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells and eventually develop into memory B cells after activation by antigen interaction...
or T-lymphocytes
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
. Approximately 70 percent are B-cell lymphoma. 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
Mycosis fungoides
-External links:* * *...
. The non-epitheliotropic form is typically of B-cell origin.
Signs and symptoms
General signs and symptoms include depression, fever, weight loss, loss of appetite, loss of hair or fur and vomiting. Lymphoma is the most common cancerous cause of hypercalcemiaHypercalcaemia
Hypercalcaemia is an elevated calcium level in the blood. . It can be an asymptomatic laboratory finding, but because an elevated calcium level is often indicative of other diseases, a workup should be undertaken if it persists...
(high blood calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
levels) in dogs. 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
Parathyroid hormone-related protein
Parathyroid hormone-related protein is a protein member of the parathyroid hormone family. It is occasionally secreted by cancer cells . However, it also has normal functions.- Function :PTHrP acts as an endocrine, autocrine, paracrine, and intracrine hormone...
.
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.
Gastrointestinal lymphoma causes vomiting, diarrhea, and melena
Melena
In medicine, melena or melaena refers to the black, "tarry" feces that are associated with gastrointestinal hemorrhage. The black color is caused by oxidation of the iron in hemoglobin during its passage through the ileum and colon.-Melena vs...
(digested blood in the stool). Low serum albumin
Serum albumin
Serum albumin, often referred to simply as albumin is a protein that in humans is encoded by the ALB gene.Serum albumin is the most abundant plasma protein in mammals. Albumin is essential for maintaining the osmotic pressure needed for proper distribution of body fluids between intravascular...
levels 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
Pemphigus
Pemphigus is a rare group of blistering autoimmune diseases that affect the skin and mucous membranes.In pemphigus, autoantibodies form against desmoglein. Desmoglein forms the "glue" that attaches adjacent epidermal cells via attachment points called desmosomes...
, bullous pemphigoid
Bullous pemphigoid
Bullous pemphigoid, also referred to as BP, is an acute or chronic autoimmune skin disease, involving the formation of blisters, more appropriately known as bullae, at the space between the skin layers epidermis and dermis.-Signs and symptoms:...
, and lupus erythematosus
Lupus erythematosus
Lupus erythematosus is a category for a collection of diseases with similar underlying problems with immunity . Symptoms of these diseases can affect many different body systems, including joints, skin, kidneys, blood cells, heart, and lungs...
.
Signs for lymphoma in other sites depend on the location. Central nervous system involvement can cause seizure
Seizure
An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...
s or paralysis
Paralysis
Paralysis is loss of muscle function for one or more muscles. Paralysis can be accompanied by a loss of feeling in the affected area if there is sensory damage as well as motor. A study conducted by the Christopher & Dana Reeve Foundation, suggests that about 1 in 50 people have been diagnosed...
. Eye involvement, seen in 20 to 25 percent of cases, can lead to glaucoma
Glaucoma
Glaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye...
, uveitis
Uveitis
Uveitis specifically refers to inflammation of the middle layer of the eye, termed the "uvea" but in common usage may refer to any inflammatory process involving the interior of the eye....
, bleeding within the eye, retinal detachment
Retinal detachment
Retinal detachment is a disorder of the eye in which the retina peels away from its underlying layer of support tissue. Initial detachment may be localized, but without rapid treatment the entire retina may detach, leading to vision loss and blindness. It is a medical emergency.The retina is a...
, and blindness. Lymphoma in the bone marrow causes anemia
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
, low platelet
Platelet
Platelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days...
count, and low white blood cell
White blood cell
White blood cells, or leukocytes , are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a...
count.
Diagnosis
BiopsyBiopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
of affected lymph nodes or organs confirms the diagnosis, although a needle aspiration of an affected lymph node can increase suspicion of the disease. X-ray
X-ray
X-radiation is a form of electromagnetic radiation. X-rays have a wavelength in the range of 0.01 to 10 nanometers, corresponding to frequencies in the range 30 petahertz to 30 exahertz and energies in the range 120 eV to 120 keV. They are shorter in wavelength than UV rays and longer than gamma...
s, ultrasound
Ultrasound
Ultrasound is cyclic sound pressure with a frequency greater than the upper limit of human hearing. Ultrasound is thus not separated from "normal" sound based on differences in physical properties, only the fact that humans cannot hear it. Although this limit varies from person to person, it is...
, blood analysis, and bone marrow biopsy reveal other locations of the cancer. The stage of the disease is important to treatment and prognosis
Prognosis
Prognosis is a medical term to describe the likely outcome of an illness.When applied to large statistical populations, prognostic estimates can be very accurate: for example the statement "45% of patients with severe septic shock will die within 28 days" can be made with some confidence, because...
.
- Stage I - only one lymph node or lymphoid tissueLymphatic systemThe lymphoid system is the part of the immune system comprising a network of conduits called lymphatic vessels that carry a clear fluid called lymph unidirectionally toward the heart. Lymphoid tissue is found in many organs, particularly the lymph nodes, and in the lymphoid follicles associated...
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.
Treatment
Complete cure is rare with lymphoma and treatment tends to be palliativePalliative care
Palliative care is a specialized area of healthcare that focuses on relieving and preventing the suffering of patients...
, but long remission times are possible with chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
. 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
Cyclophosphamide
Cyclophosphamide , also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group....
, vincristine
Vincristine
Vincristine , formally known as leurocristine, sometimes abbreviated "VCR", is a vinca alkaloid from the Catharanthus roseus , formerly Vinca rosea and hence its name. It is a mitotic inhibitor, and is used in cancer chemotherapy.-Mechanism:Tubulin is a structural protein that polymerizes to...
, prednisone
Prednisone
Prednisone is a synthetic corticosteroid drug that is particularly effective as an immunosuppressant drug. It is used to treat certain inflammatory diseases and some types of cancer, but has significant adverse effects...
, L-asparaginase
Asparaginase
Asparaginase is an enzyme that catalyzes the hydrolysis of asparagine to aspartic acid. Asparaginases are naturally occurring enzymes expressed and produced by microorganisms. Different types of asparaginases can be used for different industrial and pharmaceutical purposes. The most common use of...
, and doxorubicin
Doxorubicin
Doxorubicin INN is a drug used in cancer chemotherapy. It is an anthracycline antibiotic, closely related to the natural product daunomycin, and like all anthracyclines, it works by intercalating DNA....
. Other chemotherapy drugs such as chlorambucil
Chlorambucil
Chlorambucil is a chemotherapy drug that has been mainly used in the treatment of chronic lymphocytic leukemia...
, lomustine
Lomustine
Lomustine is an alkylating nitrosourea compound used in chemotherapy. It is in the same family as streptozotocin. This is a highly lipid soluble drug, and thus crosses the blood brain barrier. This property makes it ideal for treating brain tumors, and is its primary use...
(CCNU), cytosine arabinoside
Cytarabine
Cytarabine, or cytosine arabinoside, is a chemotherapy agent used mainly in the treatment of cancers of white blood cells such as acute myeloid leukemia and non-Hodgkin lymphoma. It is also known as Ara-C...
, and mitoxantrone
Mitoxantrone
Mitoxantrone is an anthracenedione antineoplastic agent.-Uses:It is used in the treatment of certain types of cancer, mostly metastatic breast cancer, acute myeloid leukemia, and non-Hodgkin's lymphoma...
are 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.
Allogeneic and autologous stem cell transplantations (as is commonly done in humans) have recently been shown to be a possible treatment option for dogs. Most of the basic research on transplantation biology was generated in dogs. Current cure rates using stem cell therapy in dogs approximates that achieved in humans, 40-50%.
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.
Isotretinoin
Isotretinoin
Isotretinoin, INN, is a medication used mostly for cystic acne. It was first developed for brain, pancreatic and other cancers. It is used to treat harlequin-type ichthyosis, a usually lethal skin disease, and lamellar ichthyosis. Its effects are systemic and nonselective...
can be used to treat cutaneous lymphoma.
Prognosis
Untreated dogs have an average survival time of sixty days. Lymphoma with a histologicHistology
Histology is the study of the microscopic anatomy of cells and tissues of plants and animals. It is performed by examining cells and tissues commonly by sectioning and staining; followed by examination under a light microscope or electron microscope...
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. Lymphoma in young cats occurs most frequently following infection with feline leukemia virusFeline leukemia virus
Feline leukemia virus is a retrovirus that infects cats. FeLV can be transmitted between infected cats when the transfer of saliva or nasal secretions is involved. If not defeated by the animal’s immune system, the virus can be lethal...
(FeLV) or to a lesser degree feline immunodeficiency virus
Feline immunodeficiency virus
Feline immunodeficiency virus is a lentivirus that affects domesticated housecats worldwide and is the causative agent of feline AIDS. From 2.5% up to 4.4% of cats worldwide are infected with FIV...
(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. Younger cats tend to have T-cell lymphoma and older cats tend to have B-cell lymphoma. Older cats tend to have gastrointestinal lymphoma without FeLV infection, although tests more sensitive to low level FeLV infections and replication-defective FeLV have found that many of these cats have been previously exposed. 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.
Classification
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 lymphoblastLymphoblast
Lymphoblasts are immature cells which typically differentiate to form mature lymphocytes. Normally lymphoblasts are found in the bone marrow, but in acute lymphoblastic leukemia , lymphoblasts proliferate uncontrollably and are found in large numbers in the peripheral blood.The size is between 10...
ic, immunoblastic, and large cell
Large cell
Large cell is a term used in oncology. It does not refer to a particular type of cell; rather it refers to cells that are larger than would be normally expected for that type...
lymphoma. Low grade lymphoma is only found in the small intestine, while large grade can commonly be found in the stomach.
Symptoms
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 intestineSmall intestine
The small intestine is the part of the gastrointestinal tract following the stomach and followed by the large intestine, and is where much of the digestion and absorption of food takes place. In invertebrates such as worms, the terms "gastrointestinal tract" and "large intestine" are often used to...
, the stomach
Stomach
The stomach is a muscular, hollow, dilated part of the alimentary canal which functions as an important organ of the digestive tract in some animals, including vertebrates, echinoderms, insects , and molluscs. It is involved in the second phase of digestion, following mastication .The stomach is...
, the junction of the ileum
Ileum
The ileum is the final section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms posterior intestine or distal intestine may be used instead of ileum.The ileum follows the duodenum...
, cecum
Cecum
The cecum or caecum is a pouch, connecting the ileum with the ascending colon of the large intestine. It is separated from the ileum by the ileocecal valve or Bauhin's valve, and is considered to be the beginning of the large intestine. It is also separated from the colon by the cecocolic...
, and colon
Colon (anatomy)
The colon is the last part of the digestive system in most vertebrates; it extracts water and salt from solid wastes before they are eliminated from the body, and is the site in which flora-aided fermentation of unabsorbed material occurs. Unlike the small intestine, the colon does not play a...
. 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. 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
Pericardial effusion
Pericardial effusion is an abnormal accumulation of fluid in the pericardial cavity. Because of the limited amount of space in the pericardial cavity, fluid accumulation will lead to an increased intrapericardial pressure and this can negatively affect heart function...
, and cardiac arrhythmias. Ocular lymphoma in cats often presents as anterior uveitis
Uveitis
Uveitis specifically refers to inflammation of the middle layer of the eye, termed the "uvea" but in common usage may refer to any inflammatory process involving the interior of the eye....
(inflammation of the inside of the eye). 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 disease
Inflammatory bowel disease
In medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...
because the signs are so similar in cats. A biopsy is necessary to do this. One approach to differentiate inflammatory bowel disease from is to test the infiltrating lymphocytes for their monoclonal origin in lymphomas.
Treatment and prognosis
ChemotherapyChemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
is 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 prednisone. Gastrointestinal lymphoma has also commonly been treated with a combination of prednisolone and high dose pulse chlorambucil
Chlorambucil
Chlorambucil is a chemotherapy drug that has been mainly used in the treatment of chronic lymphocytic leukemia...
with 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.
About 75% of cats treated with chemotherapy for lymphoma do go into remission, unfortunately, most cats who have an initial remission relapse, and the median survival for a cat with lymphoma who is treated with chemotherapy is just 6 months. However, about one-third of cats treated with chemotherapy will survive more than 2 years after diagnosis, and a small number of these cats may be cured of their disease. Untreated, most cats with lymphoma die within 4–6 weeks. Most cats tolerate their chemotherapy well, and fewer than 5% have severe side effects. Cats do not lose their fur from chemotherapy, though loss of whiskers is possible. Other side effects include low white blood cell count, vomiting, loss of appetite, diarrhea, or fatigue, but these can typically be controlled well, and most cats have a good quality of life during treatment. If a cat relapses after attaining remission, the cat can be treated with different chemotherapy drugs to try to obtain a second remission, but the chances of obtaining a second remission are much lower than the chances of obtaining a first remission, and the second remission is often shorter than the first.
Lymphoma in ferrets
Lymphoma is common in ferretFerret
The ferret is a domesticated mammal of the type Mustela putorius furo. Ferrets are sexually dimorphic predators with males being substantially larger than females. They typically have brown, black, white, or mixed fur...
s and is the most common cancer in young ferrets. There is some evidence that a retrovirus
Retrovirus
A retrovirus is an RNA virus that is duplicated in a host cell using the reverse transcriptase enzyme to produce DNA from its RNA genome. The DNA is then incorporated into the host's genome by an integrase enzyme. The virus thereafter replicates as part of the host cell's DNA...
may play a role in the development of lymphoma like in cats. 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
Thymus
The thymus is a specialized organ of the immune system. The thymus produces and "educates" T-lymphocytes , which are critical cells of the adaptive immune system....
. 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. Symptoms seen are the same as in young ferrets, plus splenomegaly
Splenomegaly
Splenomegaly is an enlargement of the spleen. The spleen usually lies in the left upper quadrant of the human abdomen. It is one of the four cardinal signs of hypersplenism, some reduction in the number of circulating blood cells affecting granulocytes, erythrocytes or platelets in any...
, abdominal masses, and peripheral lymph node enlargement.
Diagnosis is through biopsy and x-rays. There may also be an increased lymphocyte
Lymphocyte
A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
count. Treatment includes surgery for solitary tumors, splenectomy
Splenectomy
A splenectomy is a surgical procedure that partially or completely removes the spleen.-Indications:The spleen, similar in structure to a large lymph node, acts as a blood filter. Current knowledge of its purpose includes the removal of old red blood cells and platelets, and the detection and fight...
(when the spleen is very large), and chemotherapy. The most common protocol uses prednisone, vincristine, and cyclophosphamide. 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 C
Vitamin C
Vitamin C or L-ascorbic acid or L-ascorbate is an essential nutrient for humans and certain other animal species. In living organisms ascorbate acts as an antioxidant by protecting the body against oxidative stress...
and Pau d'Arco
Tabebuia serratifolia
Yellow Lapacho is a tree native to forests throughout Central and South America. This plant grows in the Cerrado vegetation of Brazil, reaching up to French Guiana, Bolivia, Paraguay and Northern Argentina...
(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.
See also
- for a major cause of lymphoma in cats, see Feline leukemia
- LymphocyteLymphocyteA lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
- LymphadenopathyLymphadenopathyLymphadenopathy is a term meaning "disease of the lymph nodes." It is, however, almost synonymously used with "swollen/enlarged lymph nodes". It could be due to infection, auto-immune disease, or malignancy....