Lymphoma

Introduction | Causes & Prevention | Symptoms & Signs | Diagnosis & Test | Treatment Options

Lymphoma

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Introduction

Lymphoma is a cancer (neoplasia) that affects lymph nodes and other organs containing lymphoid tissue. In domestic dogs, the term typically is used to refer to malignant multicentric lymphoma, also called lymphosarcoma, which is a progressive, multisystemic disease caused by overgrowth of certain cells in the bone marrow, thymus, lymph nodes, liver, spleen and/or other tissues. Multicentric lymphoma is the most common lymphoma in domestic dogs. However, localized forms of lymphoma can also occur in dogs, including lymphoma of the central nervous system (CNS lymphoma), chest (mediastinal lymphoma), skin (cutaneous lymphoma), mouth and gums (oral cavity lymphoma) and gastrointestinal tract (alimentary lymphoma; affects the stomach, small intestine, large intestine (colon) and/or rectum). Lymphoma can also localize to the eyes, kidneys, liver and bone.

Causes & Prevention

Causes of Canine Lymphoma
The causes of canine lymphoma are not known. However, there appears to be a genetic component to this disease, because certain breeds are disproportionately affected. Most lymphomas probably occur secondary to some random genetic mutation or other abnormal chromosomal recombination event. Many authorities suggest that these genetic changes can be caused or exacerbated by chronic retroviral infection, immune system compromise or electromagnetic radiation. They also may be caused by exposure to environmental carcinogens such as household cleaners, agricultural chemicals, herbicides or second-hand smoke, although these theories have not yet been proven.

Prevention
There is no known way to prevent canine lymphoma.

Special Notes
Canine lymphoma is common and can be a potentially fatal disease in domestic dogs. Fortunately, aggressive chemotherapy in combination with other protocols has proven successful in many cases in achieving remission, especially in cases of multicentric lymphoma, which is by far the most prevalent form of lymphoma in dogs. Unfortunately, lymphoma does tend to be progressive. For some reason, female dogs seem to respond better to treatment than do males, and small dogs seem to respond better than large dogs. Treatment is not recommended for female dogs during periods of pregnancy.

Symptoms & Signs

Introduction
Noticeable signs of lymphoma in dogs are typically nonspecific and highly variable, depending upon which form of lymphoma is involved (multicentric, central nervous system, cutaneous, gastrointestinal).

Symptoms of Canine Lymphoma
The symptoms of lymphoma usually commonly mimic the symptoms of many other diseases or disorders. Most owners of dogs with multicentric or disseminated lymphoma first find pronounced enlargement of the lymph nodes on the underside of their dog's neck, beneath and slightly behind the chin. These are the submandibular lymph nodes (the mandible is the lower jaw bone). Affected dogs normally do not seem painful when their submandibular lymph nodes are palpated and show no other unusual symptoms. Other signs that owners may notice include one or more of the following:

Depression
Lethargy (profound)
Exercise intolerance
Fever
Dehydration
Weight loss
Loss of appetite (inappetance; anorexia)
Vomiting
Diarrhea
Constipation
Dark tarry stool (melena; digested blood showing up in the stool)
Distended abdomen
Abdominal discomfort
Increased thirst and intake of water (polydypsia)
Increased volume of urinate (polyuria)
Cough
Difficulty breathing; shortness of breath (dyspnea)
Difficulty swallowing
Drooling
Skin nodules or masses (single or multiple)
Skin scaling
Bruised or ulcerated skin lesions
Hair loss (alopecia; uncommon)
Itchiness (pruritis; uncommon)
Neurological signs: circling, disorientation, lack of coordination (ataxia), seizures, behavior changes, vision abnormalities
Multicentric lymphoma - usually shows up first as painless but enlarged peripheral lymph nodes. Owners may see or feel these in areas under the jaw, in the armpits, in the groin area or behind the knees. Enlargement of the liver and/or spleen can also occur, causing the abdomen to distend. This is the most common form of lymphoid cancer in dogs.

Gastrointestinal (alimentary) lymphoma - is a malignant form of cancer that can show up anywhere along the gastrointestinal tract (stomach, small intestine, large intestine, rectum). Clinical signs of gastrointestinal lymphoma include vomiting, diarrhea, weight loss, lethargy, depression, diarrhea and melena. Low serum albumin levels and elevated blood calcium levels commonly accompany alimentary lymphoma, although these can only be detected by veterinary evaluation of blood samples. This is the second most frequent form of lymphoma in dogs.

Mediastinal lymphoma - where the cancer is localized to tissues in the chest cavity - can cause fluid to build up around the lungs. This can lead to coughing and labored breathing (dyspnea), mimicking the signs of congestive heart failure.

Lymphoma of the skin (cutaneous lymphoma) - is uncommon in dogs. When it does occur, it usually shows up with hair loss (alopecia) and visible bumps on the skin. It can also be itchy (pruritic) and vary widely in appearance, ranging from a single lump to large areas of bruised, ulcerated and/or hairless skin.

Lymphoma of the central nervous system (CNS) - is very uncommon in dogs. When lymphoma is localized in the CNS, dogs typically present with neurological signs such as circling, seizures, behavior changes and incoordination.

Dogs at Increased Risk
Lymphoma is most common in middle-aged to older dogs, although dogs of any age can be affected. There is no recognized gender predisposition for this disease. However, some breeds reportedly have an increased risk of developing lymphoma, including the Golden Retriever, Basset Hound, German Shepherd, Boxer, Scottish Terrier, Airedale Terrier, Bulldog, Poodle and Saint Bernard. A strong familial association has been established in some lines of Bull Mastiffs, Rottweilers and Otter Hounds. Pomeranians and Dachshunds reportedly have a decreased risk of developing lymphoma. The reasons for these breed differences in risk of lymphoma development are not well understood.

There may be an association between canine lymphoma and exposure to certain environmental herbicides, household or agricultural chemicals, smoke and/or electromagnetic radiation, although the reason for the connection remains unclear. Dogs living in industrial areas where paints, solvents or other chemicals are common tend to have a higher incidence.

Diagnosis & Tests

Introduction
Lymphoma typically causes very general clinical signs in domestic dogs, which can mimic symptoms of viral or bacterial infection and a number of other diseases. However, canine lymphoma is not particularly difficult to diagnose, as long as the dog's owner is able to proceed with and complete the diagnostic process.

How Lymphoma is Diagnosed in Dogs
The initial data base for a dog presenting with nonspecific symptoms of illness first involves a thorough physical examination and a complete history. Routine blood work and a urinalysis are also typically part of an initial work-up. The complete blood count may disclose anemia and elevated immature white blood cells, which are suggestive of lymphoma. The serum chemistry panel may show elevated blood calcium levels, abnormal liver enzyme levels and kidney abnormalities. The most reliable way to diagnose lymphoma in dogs is to take samples from enlarged lymph nodes and/or other affected organs. Usually, the attending veterinarian will recommend a fine needle aspirate (FNA) of one or more enlarged peripheral lymph nodes. This simple procedure involves inserting a small needle into the suspicious lymph nodes and withdrawing fluid and cells through an attached syringe. The sample is then expressed onto a glass slide and examined under a microscope to identify any cellular abnormalities. This process, called cytology, can in many cases be definitively diagnostic of lymphoma.

If FNA and cytology are inconclusive, and often even if they point strongly to lymphoma, biopsies of one or more enlarged lymph nodes normally will be taken. A biopsy involves surgically removing pieces of tissue, rather than only sampling cells, from the questionable organs or areas. Biopsies typically require heavy sedation, and sometimes general anesthesia. Biopsy samples are then submitted to a pathology laboratory, where they are processed and evaluated for abnormalities by a technique called histopathology. Biopsy and histopathologic tissue evaluation are the gold standard for diagnosing canine lymphoma. Suspicious lymph nodes can also be entirely removed surgically, for more thorough histopathologic examination.

Bone marrow aspiration or biopsy can be helpful in assessing whether lymphoma has spread widely throughout the dog's body. Chest and abdominal radiographs (X-rays), together with ultrasound examinations, are especially helpful in identifying abnormally enlarged lymph nodes, affected organs (especially liver and/or spleen) and isolated masses. A cerebrospinal fluid (CSF) tap can be useful if the dog is showing neurological signs. A genetic screening test for canine lymphoma has recently become commercially available and apparently is based on genetic markers that are identifiable from a blood sample. Other advanced diagnostic tests for lymphoma include immunocytochemistry, immunohistochemistry, flow cytometry and PCR (polymerase chain reaction) amplification of chromosome sequences.

Special Notes
Even though lymphoma usually causes nonspecific symptoms, it is fairly easy for veterinarians to diagnose if there are no significant financial or other constraints on the part of the dog's owner.

Treatment Options

Introduction
Chemotherapy is the go-to treatment for canine lymphoma. In most cases, the cancerous lymphatic cells are distributed throughout the dog's body, as are the chemotherapeutic drugs used to destroy them. The objective therapeutic goal is to achieve complete remission of the cancer. Subjectively, the goal of treatment is to restore the patient's pain-free quality of life for as long as possible. Chemotherapy protocols are complicated and rapidly evolving. A veterinary oncologist (cancer specialist) is the best person to discuss and advise owners about treatment options for canine lymphoma.

Staging
A veterinarian normally will "stage" lymphoma to help the dog's owner decide on a treatment protocol. The stages of lymphoma in dogs basically are as follows:

Stage I - only one lymph node (or lymphoid tissue in one organ) is involved.
Stage II – multiple lymph nodes or a chain of lymph nodes in a localized area are involved.
Stage III – Widespread, generalized lymph node involvement; most or all peripheral lymph nodes are affected.
Stage IV - any or none of the above, plus liver and/or spleen involvement.
Stage V - any or none of the above, with bone marrow involvement, blood involvement or involvement of any non-lymphoid organ.
Each stage can further be classified into substage A (the dog has no observable symptoms of illness), or substage B (the dog is showing signs of illness, such as loss of appetite, lethargy, weight loss, or the like).

Treatment Options for Lymphoma in Dogs
Chemotherapy is defined as the treatment of illness or disease using chemical agents. Some chemotherapeutic medications can be given orally, while others must be given intravenously (IV) on an inpatient basis. Moreover, chemotherapeutic protocols may involve administration of only one drug or a combination of drugs. Multi-agent chemotherapy typically results in better remission rates and a more rewarding overall outcome than does single agent therapy. Chemotherapy targets rapidly-dividing cells.

Treatment protocols are rapidly changing, and chemotherapeutic drugs can have severe and potentially fatal side effects. Current protocols for treating canine multicentric lymphoma can involve use of a number of different drugs, including cyclophosphamide, vincristine, prednisone, L-asparaginase and doxorubicin, among other. Other chemotherapy drugs, such as chlorambucil, lomustine, cytosine arabinoside and mitoxantrone, are sometimes used in the treatment of lymphoma as well, either singly or in addition to other drugs. It is extremely important to closely monitor white blood cell counts and remission status throughout the course of chemotherapy.

While used much less commonly than chemotherapy, radiation therapy is being explored to treat lymphoma in combination with drug treatment. Early research suggests that certain chemotherapeutic protocols, used in combination with radiation, improve remission rates and extend the disease-free interval in dogs with multicentric malignant lymphoma.

Dogs with lymphoma isolated to a single or several lymph nodes, and those with focal gastrointestinal lymphoma, may be able to be treated successfully by surgical removal of the lymph node or mass followed by chemotherapy and/or radiation. Chemotherapy with or without radiation treatment has improved survival times in dogs suffering from mediastinal lymphoma. Cutaneous lymphoma can be treated with single or multi-agent chemotherapy, although the disease tends to become refractory to treatment and the results are much less rewarding.

Stem cell transplantation is commonly used to treat people with lymphoma and is another possible treatment option for dogs. In fact, much of the basic research on stem cell transplantation was generated from dogs. When cost is a restricting factor, steroid drugs such as prednisone can be prescribed to help alleviate the symptoms of lymphoma, although this will not significantly affect the survival rate. Prednisone may also cause the cancer to become resistant to other chemotherapeutic agents and typically is only used if more aggressive treatment is not an option.

Prognosis
Some cancers do not respond particularly well to chemotherapy. Fortunately, canine lymphoma – especially the common multicentric form – usually does. Radiation treatment is available for some types of cancer as well and is being used increasingly in conjunction with chemotherapy, with the hope of improving remission rates. During any chemotherapy treatments, the patient will need frequent blood tests and monitoring to be sure that the treatment is not adversely affecting his or her organs or overall health. Of course, in pets and in people, there can be a number of unpleasant side effects from chemotherapy and/or radiation treatment, including severe gastrointestinal upset, allergic reactions and hair loss, among others.

Current treatment protocols can help to extend a dog's life after a diagnosis of lymphoma. Dogs with lower stage lymphoma have a better prognosis than those with higher stage disease. Unfortunately, lymphoma is almost always progressive and, ultimately, fatal. Treatment of lymphoma rarely cures the disease. Instead, it hopefully will make the patient feel a bit better, and live a bit longer, with a significantly improved quality of life if remission is achieved.

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