Multi-Centric / Central Nervous System Lymphoma

What is Multi-centric Lymphoma?

Multicentric lymphoma mostly affects the external lymph nodes. They may or may not involve other organs. But in a vast majority of cases, it has been observed that lymphoma eventually invades the organs and the healthy tissues are replaced by the diseased ones. Death occurs mostly due to organ failure as the organ becomes dysfunctional under the impact of the disease.

What are the symptoms of Multicentric Lymphoma?

Multicentric lymphoma is the most common type of lymphoma found in dogs. It is characterized by painless swelling of the lymph nodes. Hepatosplenomegaly (enlargement of spleen and liver) and bone marrow involvement are common. Most of the dogs do not show any distinctive signs of illness. But symptoms like anorexia, weight loss, ascites (abnormal accumulation of fluid in the abdomen), dyspnea (difficulty in breathing), polydipsia (abnormal thirst), polyuria (excessive passage of urine), fever, anemia, hemorrhage, sepsis (inflammation of the whole body) might be palpable.

How is Multicentric Lymphoma Diagnosed and Staged? 

For most dogs suspected of having lymphoma, a thorough physical examination should entail a complete blood count with a differential cell count, a platelet count, serum biochemistry profile, and urinalysis. Finally, obtaining tissue or cytologic specimens for a definitive diagnosis is essential. In multicentric lymphoma there should be a thorough physical and rectal (relating to the rectum) examination including palpation of all assessable lymph nodes. The mucous membranes should be examined closely for pallor (extreme or unnatural paleness), icterus (jaundice), petechiae (pinpoint flat round red spots under the skin surface caused by intradermal hemorrhage), and ulceration, because these indications could be of anemia or thrombocytopenia (low blood platelet count) secondary to myelophthisis or immune-mediated disease or may be evidence of a major organ failure. Abdominal palpation is also essential for it may reveal organomegaly, intestinal wall thickening, or mesenteric lymphadenopathy (swelling of the mesenteric nodes).

In animals with anemia or evidence of bleeding, a reticulocyte (young red blood cells) count and coagulation studies may be indicated. If some dogs have high total protein evidence or evidence of an increased globulin fraction (globulin is one of the two types of serum proteins, the other being albumin) on a biochemistry profile, serum proteins should be examined by serum electrophoresis. Morphologic examination of the tissue and cells that comprise the tumor is essential for the diagnosis of lymphoma. In most cases, a diagnosis of lymphoma can be made through fine needle aspirates of affected lymph nodes or other tissues.

Diagnostic ultrasonography and ultrasound-guided fine-needle aspiration or needle biopsy may be helpful in the evaluation of the involvement of liver, spleen, or abdominal lymph nodes.

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What is the treatment for Multicentric Lymphoma? 

The treatment approach is determined by the stage of the disease. In the absence of treatment, most of the dogs with lymphoma succumb to the disease in 4-6 weeks. Systemic chemotherapy continues to be the treatment of choice for most patients. The standard chemotherapy protocol combines cyclophosphamide, doxorubicin, vincristine, and prednisone. Currently, the most effective chemotherapeutic agents for lymphoma are doxorubicin, L-asparaginase, polyethylene, glycol, (PEG)-L- asparaginase, vincristine, cyclophosphamide, and prednisone. Other singe-agent drugs that are considered secondary include vinblastine, actinomycin-D, mitoxantrone, chlorambucil, methotrexate, DTIC, 9-aminocamptothecin, ifosfamide, cytosine, arabinoside, gemcitabine, lomustine, and dolastatin-10. Of these, cytosine, arabinoside, ifosfamide, dolastin-10 and gemcitabine appear to be the least effective. With the sole exception of doxirubicin, induction with single agent chemotherapy does not result in durable remission durations compared with standard combination protocols.

With the increase in the availability of generic drugs, protocols are becoming readily available to a broad section of veterinary clients. In the instances where lymphoma recurs, reinduction is attempted by reintroducing the re-induction protocol that was successful initially. In most of the cases, the response and length of reinduction are half of those seen in the initial therapy. Some animals certainly enjoy long-term re-inductions, especially if the patient had a good response in the first therapy and was off it when the recurrence occurred.

If reinduction fails or the dog does not respond, the use of so-called rescue agents or rescue protocols can be attempted. These are drugs that are not found in the standard chemotherapy protocol. They are kept in reserve for later use. The most common rescue protocol include single agent or combination use of actinomycin D, mitoxantrone, doxorubicin (if it was not part of the initial protocol), a doxorubicin/dacarbazine combination, lomustine, L-asparaginase, and the combination mechlorethamine, vincristine, procarbazine and prednisone. Approximately, 40-50% of dogs respond, but their median survival rate is 1.5 to 2.5 months.

It has been observed that in some cases, the cancer patients become resistant to certain drugs. They are subjected to long-term continuous infusions, increasing the frequency of treatments, or enhancing the drugs’ circulation time. But no improvement in survival rate has been found.

Among other alternative treatments, autologous vaccines combined with chemotherapy have been shown to have positive effects in dogs. A tumor vaccine extract using killed lymphoma cells combined with Freund’s adjuvant (freund’s adjuvant is an antigen solution emulsified in mineral oil, used as an immunopotentiator [booster of the immune system]) was injected in dogs after remission induction with combination chemotherapy.

Dogs with multicentric lymphoma mostly undergo chemotherapy. However, surgery can be carried out in a couple of cases where the disease is in its initial phase. In such instances, careful staging is important to rule out multicentric involvement. Sometimes splenectomy is recommended only if the disease is receding in other sites and if the splenic enlargement is caused by lymphoma that is not responsive to chemotherapy. It can also be considered as a treatment for hemolytic anemia (anemia due to destruction rather than underproduction of red blood cells) and persistent thrombocytopenia.

Radiation therapy given to patients either after the completion of chemotherapy or during ongoing sessions have been found to be safe and therefore calls for further investigation.

What is the prognosis of Mulitcentric Lymphoma? 

Conventional chemotherapy results in total remission in approximately 60-90% of cases with a median survival time of 6-12 months. In approximately 20-25% of cases, dogs live 2 years or longer after initiation of this treatment. In cases, where the disease recurs and the second round of chemo has to be initiated, the median survival rate is approximately 336 days. Dogs treated with rescue protocols have a survival rate of 1.5-2.5 months. Studies indicated that dogs that underwent splenectomy showed a median survival rate of 14 months.

What is Central Nervous System (CNS) Lymphoma?

It occurs due to the metastasis of multi-centric lymphoma.

What are the Symptoms of Central Nervous System Lymphoma?

They result from metastasis of multicentric lymphoma. Symptoms may vary from paralysis, seizures to paresis (condition typified by partial loss of movement).

What is the Treatment for Central Nervous System Lymphoma?

If tumors are localized local radiation therapy should be consideredChemotherapy is also sometimes combined with CNS irradiation.

What is the Prognosis of Central Nervous System Lymphoma in dogs? 

Overall the response rates are low and of short duration.

Other Types of Lymphoma in dogs:

Alimentary Lymphoma
Mediastinal Lymphoma
Extra Nodal Lymphoma
Cutaneous Lymphoma

Basic Lymphoma information with staging
Ask the Dr. with Dr. Michael Kent on Lymphoma

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Other Articles of Interest:

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Tumors in Domestic Animals- Donald J. Meuten, DVM, PhD, is a professor of pathology in the Department of Microbiology, Pathology, and Parasitology at the College of Veterinary Medicine, North Carolina State University, Raleigh

Withrow and MacEwen’s Small Animal Clinical Oncology– Stephen J. Withrow, DVM, DACVIM (Oncology), Director; Animal Cancer Center Stuart Chair In Oncology, University Distinguished Professor, Colorado State University Fort Collins, Colorado;

David M. Vail, DVM, DACVIM (Oncology) Professor of Oncology, Director of Clinical Research, School of Veterinary Medicine University of Wisconsin-Madison Madison, Wisconsin