Lymphomas

Definition

Malignant neoplasm that arises in lymphoid cells.

Lymphoma may arise anywhere in the organs or tissue where there are lymphocytes. This can include: lymph nodes, thymus, spleen, liver, gastrointestinal tract, nervous system, skin, and occasionally bronchiole associated lymphoid tissue of the lungs.

Clinical Signs

Clinical signs can vary depending on location and extent of the disease. May see any of the following:

Node enlargement (e.g., neck, axilla, groin, popliteal, mediastinum)
Facial/neck swelling due to partial blockage of the cranial (superior) vena cava (seen with tumor presence)
Porphyrin staining (e.g., eye(s), nose)
Weight loss
Lethargy
Anemia
Poor appetite
Dyspnea (difficulty breathing)
Tachypnea (rapid breathing)
Skin lesions / cutaneous masses
Pruritus (itching)
Hindlimb weakness/paresis (may be intermittent)
Hepatomegaly (liver enlarged)
Splenomegaly (spleen enlarged)

*Note: for additional information on recognizing various signs of pain or discomfort refer to: Signs of Pain In Rats.

Etiology

The term lymphoma actually refers to a group of neoplasms that may arise from B-cell, T-cell, or NK (histiocytes, non B, non T, also called Natural Killer cells) lymphocytes. Research in laboratory SD rats indicates that primary neoplasms of the lymph nodes tend to be uncommon. There is also some indication that when lymphoma is present it tends to be of T-cell origin.

The cause of lymphoma or lymphosarcoma is unknown. Some theories suggest a viral origin or attributed to immune deficiencies. The disease tends to affect aging or elderly rats.

The lymphatic system has several functions such as the transporting of lymph (an alkaline colorless fluid), lymphocyte (white blood cells) and antibody production, and the breakdown of fats and fat-soluble substances from the intestine. The lymphatic system includes nodes, lymph ducts, lymph vasculature (or tubules) that transport lymph, spleen, thymus, liver, and other tissue where lymphocytes may be found.

The formation of lymph is regulated by exchange of fluid between capillaries and tissue. The lymphatic system as a whole helps to drain any excess fluid and protein from organs and tissue. The lymph nodes (containing lymphocytes, a part of the body’s defense mechanism) act to remove bacteria and foreign substances from the lymph while it circulates through the body. It then reintroduces this fluid, once it’s filtered, back into the blood stream.

When infection, inflammation, or neoplasia is present, swelling and enlargement of the lymph nodes can be seen as a result. Many times, especially with the presence of lymphoma, enlargement of the organs like the spleen and liver can be detected by palpation or on X-ray.

Lymphomas may be classified by morphology, cytology, histology, and immunophenotyping depending on the classification system used (see reference at the end of this article). In other words, lymphomas may be classified based on:

How the cells appear under a microscope.
Types of genetic mutation carried.
If the cells are clustered together to form a nodule, or are they diffuse, having spread to other nodes, spread through the lymph system, or spread to organs.
What type of cell did they arise from (B-cell, T-cell, NK-cell).
Where it is they occur in the body.

Anatomical classification can be organized by locations, and clinical signs may correlate. This system is often used by veterinarians treating dogs, cats, and ferrets, and may be practical for smaller mammals like rats as well. Anatomical categories are as follows:

Mediastinal– tumor may involve the thorax, displacing the trachea, and placing pressure on the lungs leading to pleural effusion and respiratory distress.
Alimentary– may involve mesenteric nodes and gut. Tumor growth may cause abdominal enlargement or pressure on intestines. It may be difficult for the rat to pass feces.
Multicentric– lymphoma that has spread throughout other lymph nodes of the body an organs. Enlargement of the liver (hepatomegaly), and spleen (splenomegaly) can often be seen on X-ray, or palpated.
Cutaneous– lymphoma to the skin seen as lesions. Can appear as red, crusted areas with hair loss (e.g., mycosis fungoides). May be confused with allergic dermatitis.
Extranodal– outside of the lymph nodes, it may appear as a single mass.
Central nervous system– lymphoma present in this area causing pressure can result in weakness or paralysis of the hind limbs.
Bone marrow– lymphoma to bone marrow can be present with any of these categories. A complete blood count often reflects anemia.

The Ann Arbor staging system (other than cutaneous lymphomas) is often useful in humans and some animals to determine appropriate course of treatment depending on the stage.

Low-grade: diffuse small and large cell, single node or extra nodal site or limited to single organ.
Intermediate grade: more than one lymph node involvement, with extra nodal or regional node involvement.
High-grade: involving immunoblastic cells, general node and organ involvement.
Miscellaneous: a composite of lymphomas, unclassifiable. Mycosis fungoides included in this.

Because the prognosis for rats with lymphoma is grave, and because chemotherapy may not always be suitable, treatment should be based on comfort and quality of life.

Figures

Case Histories of Lymphoma

Fig 1: Epitheliotropic Lymphoma (also known as Mycosis Fungoides) in 24-month-old rat (Prin)
Fig 2: Systemic Lymphoma in 12-month-old hairless rat (Marceau)
Fig 3: Management of Lymphoma in a Domestic Rat (Rattus norvegicus)
Fig 4: Immunoblastic lymphoma with metastasis in 18-month-old male rat (Apollo)

Diagnostics

Obtain history to include: genetic background if known, any / or recent or ongoing illness.

Fine needle aspirate and analysis of an enlarged lymph node.

Biopsy of a tumor or enlarged lymph node.

Complete Blood Count (CBC), and Serum Chemistry.
Blood tests may show abnormal findings that can include leukocytosis (elevated number of white cells in blood), anemia, thrombocytopenia (low platelets that can result in abnormal bleeding), elevated BUN (blood urea nitrogen) and creatinine, and elevated hepatic enzymes.

Radiologic exam (*note: dorsal displacement of the trachea may be seen with mediastinal masses)

Ultrasonography

Treatment

Depending on location, size of tumor and extent of disease process, surgery or chemotherapy may be an option. However, in many cases with rats, by the time the disease becomes evident the spread of lymphoma is fairly diffuse. The goal of any treatments listed below should be to provided quality and comfort to the rat’s life.

Broad-spectrum antimicrobials for secondary infections.
Corticosteroids (e.g., prednisone) to reduce inflammation brought on by tumor presence (noted to have antitumor activity in the presence of lymphoma).

Chemotherapy options:

Immunochemotherapy with interferon alpha-2a. Used to aid the body in reducing tumor cell proliferation (growth and reproduction), while helping to strengthen the body’s immune response. (not as yet available in the Rat Medication Guide)
Chemotherapy protocol using L-asparaginase and lomustine in combination with prednisone, and a premed such as diphenhydramine. For further information on this treatment regimen protocol refer to Fig. 3: Management of Lymphoma in a Domestic Rat (Rattus norvegicus)

In the event surgery for tumor removal is an option the following post-op analgesia may be given:

For severe pain or first 24 hours post-op: Buprenex (buprenorphine), or Torbugesic (butorphanol).
For mild to moderate pain: Banamine (flunixin meglumine), Metacam (meloxicam), or carprofen. Do not use if a corticosteroid has already been prescribed.
*Note: for pain not controlled by the use of an NSAID (e.g., Banamine, meloxicam, or carprofen), alone, consider alternating or co-administering with a narcotic (e.g. buprenorphine or butorphanol) or narcotic-like (e.g., tramadol) medication.

For information pertaining to medications refer to the Rat Medication Guide.

Euthanasia should be a consideration if quality of life impaired.

Nursing Care

If surgery is not an option:

Give medications as prescribed by veterinarian.
Provide a safe environment.
If mobility is impaired, provide for one level cage with soft bedding/litter.
Keep the food and water within easy reach.
Provide additional food and fluid supplements if appetite is poor (see suggestions listed under: If surgery is an option).

If surgery is an option:

Provide hospital cage during recovery, or if there are concerns that cage mates may groom sutures or wound site.
Provide clean bedding, such as felt, soft t-shirt type material, or ink-free paper towels daily. Avoid litter-type bedding post-op, until healed, to prevent the chance of wound contamination or infection.
Provide additional warmth to maintain body temperature within normal limits. It is essential that the rat does not become overheated or dehydrated. The rat should also be able to move away from the heat source if it becomes uncomfortable. If the rat is unconscious or immobile extreme care must be taken to keep the heat low and stable.
- You can use an isothermic product that is heated in the microwave such as SnuggleSafe®. Make sure to follow the product directions carefully and wrap in a towel before placing in the cage. SnuggleSafe® will provide heat for 12 hours before needing to be reheated. Other similar types of products may vary in re-heat time. Check directions for individual product.
- If using a heating pad (good for long term use) use only the low heat setting, put a thick towel in between the pad and the cage bottom, and place beneath a corner of the cage.
- If none of these options are available you can use a plastic bottle filled with hot water, and wrapped in a towel, in the corner of the cage.
Medicate for post-op pain as needed.
Body wrap may be required if thread sutures are used.
In the event there is dried or excess drainage, the incisional site may be cleaned with a moistened Q-tip (cotton swab), using warm water or normal saline.
For 24 to 48 hours post-op, feed iron-rich foods to prevent anemia (cooked liver, scrambled or hard-boiled eggs).
Provide additional high calorie foods or food supplements such as Nutri-Cal Paste, canned Ensure, soy or soy formula, during recuperation. Include multi-vitamin supplement (can be found in pet store) if food intake is poor. The health supplement co-enzyme Q10 may also be of benefit (refer to the Rat Medication Guide for dosing).
Encourage fluid intake while recuperating, such as water, Jell-O water, or electrolyte replacement drinks such as Pedialyte or Gatorade (which can be found in local grocery stores).
- Please note that Pedialyte is only good refrigerated for 24 hours after opened, but can be frozen as ice cubes and thawed as needed.
- *Note: a juicy type of fruit also provides an additional fluid source in the diet.
Contact veterinarian if any of the following are observed: swelling, redness, or pain at the incision site, or if there are signs of increased weight loss, lethargy, or changes in habits.

Outcome

In the event surgery is performed: Incision site remains free from infection, and post-op pain relieved.
Breathing, heart rate, body temperature in normal limits.
Rat remains well hydrated as seen by moist mucous membranes and good skin turgor.
Comfort level maintained that allows the rat to eat and drink on its own.
Maintains adequate elimination of bladder and bowel.
Able to stand, walk, or scurry without discomfort.
Comfort the owner if euthanasia is required.

Prevention

Seek veterinary care promptly if you detect lumps below your rat’s skin in the neck, armpits, back legs, or groin, or if your rat has signs of illness such as loss of appetite, lethargy, weight loss, or if you see unresolved skin lesions that seem to worsen with home treatment.

References

Hematopathology: Lymphoma Classification. (2007, June 11). Retrieved November 18, 2008, from http://pleiad.umdnj.edu/hemepath/classification/classification.html.
Mohr, U., Dungworth, D., & Capen, C. (1992). Pathobiology of the Aging Rat, Volumes 1. Washington D.C.: Intl Life Sciences Inst.
Otová, B., Sladká, M., Damoiseaux, J., Panczak, A., Mandys, V., & Marinov, I. (2002). Relevant animal model of human lymphoblastic leukaemia/lymphoma–spontaneous T-cell lymphomas in an inbred Sprague-Dawley rat strain (SD/Cub). Folia Biol (Praha), 48(6), 213-26. Retrieved November 18, 2008, from http://fb.cuni.cz/Data/files/Folia%20Biologica/Volume%2048%20(2002)%20No.%206/2002-48-213-218.pdf and http://fb.cuni.cz/Data/files/Folia%20Biologica/Volume%2048%20(2002)%20No.%206/2002-48-219-226.pdf.
Paralec, G., Remarque, E., Barnett, Y., & Solana, R. (1998). T cells and aging. Frontiers in Bioscience, 3, d59-99. Retrieved November 18, 2008, from http://www.bioscience.org/1998/v3/d/pawelec/pawelec.pdf.