Lymphoma in Ferrets

Disease Summary

Alternative Names (Synonyms)

Disease Type

Infectious/Non-Infectious Agent associated with the Disease

• Unknown. (B627.9.w9)
• Infectious agent suggested by clusters of cases in multi-ferret households (J29.14.w3) and by transmission of lymphoma via inoculation of either cells or cell-free inocula from a ferret with lymphoma. (B627.9.w9, J355.72.w1)
• Infection with Helicobacter mustelae (Helicobacter mustelae Gastritis in Ferrets) might be involved in development of gastric lymphoma. (B627.9.w9, J29.14.w3, J45.151.w2)

Infective "Taxa"

• Helicobacter mustelae

Non-infective agents

Physical agents

References

Disease Author

Major References / Reviews

Code and Title List

Other References

Code and Title List

Detailed Clinical and Pathological Characteristics

Clinical Characteristics

• Clinical signs vary, depending on the location of the lesion(s). (B232.15.w15, J29.14.w3)
• Clinical signs can be absent for up to six months interspersed with intervals of clinical illness. (B627.9.w9)
• Young ferrets often present with signs similar to a gastric foreign body. Abdominal masses can be palpated in the abdomen; these are enlarged mesenteric lymph nodes. (B232.15.w15)
• Ferrets as young as one year may be affected by mediastinal lymphoma, which is of T-cell phenotype. They may appear asymptomatic until they are handled and then show signs of dyspnoea. (B627.9.w9)
• Weakness and wasting may develop. (J45.151.w2)
• Juvenile ferrets with the acute lymphoblastic form exhibit the following signs:
  • Anorexia. (B628.11.w11)
  • Weakness. (B628.11.w11)
  • Lethargy. (B628.11.w11)
  • Pyrexia. (B628.11.w11)
  • Collapse. (B628.11.w11)
  • Jaundice (icterus). (B628.11.w11)
  • Dyspnoea. (P120.2006.w1,B339.9.w9, B628.11.w11, B629.13.w13, B632.6.w6)
  • Coughing. (B339.9.w9, B627.9.w9, B629.13.w13, B632.6.w6)
  • Regurgitation. (B627.9.w9, B629.13.w13)
• Dyspnoea in cases of lymphadenopathy. (B232.15.w15)
• Adults with lymphosarcoma have signs that may occur later when the disease has advanced. This is known as the lymphocytic form (B602.9.w9), signs include:
  • Anorexia. (B232.15.w15, B627.9.w9, B628.11.w11, B629.13.w13, B632.6.w6)
  • Weight loss. (B232.15.w15, B339.9.w9, B627.9.w9,B628.11.w11, B629.13.w13, B632.6.w6)
  • Lethargy. (B232.15.w15, B627.9.w9, B628.11.w11, B629.13.w13)
  • Vomiting- If the lymphoma is in the pyloric antrum, this may stop gastric emptying and cause vomiting (B232.15.w15, B627.9.w9)
  • Dyspnoea. (B232.15.w15)
  • Jaundice. (B232.15.w15)
  • Posterior lameness or paralysis. (B232.15.w15, B627.9.w9)
    • Associated with spinal (bone, associated muscle) involvement. (J29.14.w3)
  • Signs of upper respiratory infections. (B232.15.w15)
• In cases of abdominal or intestinal lymphoma:
  • Diarrhoea. (B232.15.w15, B627.9.w9, B629.13.w13)
  • Tenesmus. (B232.15.w15, B627.9.w9, B629.13.w13)
  • Abdominal masses. (B232.15.w15)
• With lymphoma of the gastric pylorus:
  • Vomiting (gastric outflow obstructed). (J29.14.w3)
• Preputial cutaneous lymphoma:
  • Large cutaneous lymphoma nodules found, were reported ulcerated and forming crusts. (B627.9.w9) 
• Orbital lymphoma:
  • Protrusion of one or both eyes (exophthalmos), with exposure keratitis, third eyelid protrusion and lagophthalmos. (B627.9.w9, J29.14.w3) 
• Mycosis fungoides (cutaneous epitheliotropic T-cell lymphoma)
  • Multiple areas of alopecia, excoriation (due to pruritis), plaques and crusts over the whole body including the head, limbs and tail. (J29.14.w3)
• Clinical pathology:
  • Lymphocytosis (may be seen more in younger ferrets) or lymphopaenia (may be seen more in older ferrets). (J4.208.w3)

Incubation

• --

Mortality / Morbidity

• --

• Lymphoma is one of the most common diseases of ferrets in the USA. (P120.2006.w1)
• Prognosis is guarded. (B627.9.w9, B232.15.w15)
• Poor long-term prognosis. (J29.14.w3)
• Young ferrets are more likely to die from lymphosarcoma than are adults. (B232.15.w15, B629.13.w13, B632.6.w6)
  • Adults tend to respond better to treatment, as the disease is chronic and has a slower onset. (B629.13.w13)
• If the ferret has another disease or has been treated with prednisolone, it is less likely to recover. (B232.15.w15, B629.13.w13)
• If the ferret's spleen, mediastinum, skin and peripheral lymph nodes are affected, the ferret is more likely to respond to treatment. If the ferret's liver, intestine, a solitary lymph node, abdominal organs and/or bone marrow are affected the ferret is less likely to respond to treatment. (B232.15.w15)

Pathology

Gross pathology

• Respiratory: Pleural effusion in cases of lymphadenopathy. (B232.15.w15)
• Splenic: Splenomegaly. (B232.15.w15)
• Gastric: in cases of lymphoma apparently associated with Helicobacter mustelae infection (Helicobacter mustelae Gastritis in Ferrets), mass in the lesser curvature of the stomach wall. (J45.151.w2)

Histopathology

• Diffuse small lymphocytic lymphoma (low mitotic index), immunoblastic lymphoma and immunoblastic polymorphous lymphoma were seen in one study; mitotic indicies were low, medium or high. (J42.106.w2)
• In juvenile/young ferrets: high grade, diffuse, noncleaved or immunoblastic. (B629.13.w13)
  • Often immunoblastic; high mitotic index. (B631.30.w30)
• In adult ferrets: cell immunoblastic or mature lymphocytic. (B629.13.w13)
  • Lower mitotic index. (B631.30.w30)
• Immunohistochemical staining (histoptahlogical or cytological sample):
  • In a reactive lymph node, cells with B-cell markers (e.g. CD79a) and cells with T-cell markers (e.g. CD3) will both be present; in lymphoma, all the cells will be of one type. (B631.30.w30)

Human Health Considerations

Disease has been reported in either the wild or in captivity in:

• Lymphoma is commonly seen in Mustela putorius furo - Ferret. (P120.2006.w1)

Further information on Host species has only been incorporated for pecies groups for which a full Wildpro "Health and Management" module has been completed (i.e. for which a comprehensive literature review has been undertaken). Host species with further information available are listed below:

Host Species List

• Mustela putorius furo - Ferret

(List does not contain all other species groups affected by this disease)

Disease has been specifically reported in Free-ranging populations of:

• --

Further information on Host species has only been incorporated for species groups for which a full Wildpro "Health and Management" module has been completed (i.e. for which a comprehensive literature review has been undertaken). Host species with further information available are listed below:

Host Species List

• --

(List does not contain all other species groups affected by this disease)

General Information on Environmental Factors/Events and Seasonality

• --

Regions / Countries where the Infectious Agent or Disease has been recorded

• Lymphoma is one of the most common diseases in ferrets in the USA. (P120.2006.w1)
• In the midwest of the USA, lymphomas were found commonly in two-year-olds, then in three-year-olds and then five-year-olds. In Massachusetts they found lymphoma in ferrets more commonly at five years, then three years and then one year. (B627.9.w9)

Regions / Countries where the Infectious Agent or Disease has been recorded in Free-ranging populations

• --

General Information on Investigation / Diagnosis

• History, clinical signs, imaging (radiography, ultrasonography, clinical pathology and cytology/histopathology. (J29.14.w3)
• Diagnosis can be difficult as clinical signs vary considerable. (P120.2006.w1, B232.15.w15)
• Physical examination. (B627.9.w9)
  • Abnormalities present will vary depending on the organ system(s) involved. (J213.7.w5)
  • e.g. firm, well-defined peripheral lymph nodes, hepatomegaly, splenomegaly. (J213.7.w5)
• Radiography:
  • Anterior mediastinal masses may be visible. (B631.30.w30, J29.14.w3, J213.7.w5)
  • Pleural effusion may be present. (B631.30.w30, J29.14.w3, J213.7.w5)
  • Splenomegaly and hepatomegaly may be visible. (J213.7.w5)
  • Renal enlargement may be visible. (J213.7.w5)
• Ultrasonography:
  • Ultrasonography can detect masses in the abdomen and abnormal architecture of infiltrated visceral organs (spleen, liver, kidneys, thymus). (B632.6.w6, B631.30.w30, J29.14.w3, J213.7.w5)
  • Ultrasound is useful for assisting with taking a fine needle aspirate biopsy. (B339.9.w9, B627.9.w9, B631.30.w30, B632.6.w6)
• Biopsy & cytological/histopathological examination:
  • Detection of abnormal lymphocytes in a cytological or histological sample provides definitive diagnosis. (J29.14.w3)
  • Peripheral lymph node biopsy or nodectomy with histopathological evaluation, particularly the popliteal lymph node. (P120.2006.w1, B627.9.w9, B629.13.w13)
  • Needle biopsy from a peripheral lymph node can be difficult, as they lie in fat pads. An excisional biopsy may be necessary and the popliteal lymph node is easier to locate. This is found on the caudal hind leg between the hip and the stifle. (B232.15.w15)
  • Cytological or histological examination can be carried out on blood, tissue aspirates or biopsies. (B232.15.w15, B628.11.w11, B629.13.w13)
  • Thicker biopsies are recommended from enlarged lymph nodes to prevent false negatives from fine needle aspirates. (B339.9.w9, B632.6.w6)
    • Neoplastic cells must be differentiated from reactive or inflammatory changes. (J29.14.w3)
    • Monomorphic atypical lymphocytes effacing normal tissue architecture indicates lymphoma. (J29.14.w3)
  • Bone marrow biopsy aspiration can be carried out on ferrets that show signs of leukaemia, anaemia or atypical lymphocytes. (B629.13.w13)
    • With lymphocytic leukaemia, a uniform population of neoplastic cells is present. (J29.14.w3)
  • Immuohistochemistry is useful on cytological samples. (J213.7.w5)
• Heamatology & biochemistry
  • Biochemistry may be affected, depending on the organ which is affected. (B232.15.w15, B629.13.w13)
    • e.g. elevated liver enzymes if there is hepatic involvement. (J29.14.w3)
  • Haematology may show mild anaemia with increased or decreased white blood cell count. (B627.9.w9, B629.13.w13)
    • Lymphocytosis is common, but older animals are often lymphopaenic.
    • More than 3500/mm³ or relative count more than 60% of lymphocytes may suggest lymphosarcoma and other tests should be carried out to confirm this. (B232.15.w15, B339.9.w9 B629.13.w13)
  • Note: Care should be taken not to diagnose lymphoproliferative disease on the basis of peripheral lymphocytosis alone. Peripheral lymphocytosis may occur for many other reasons. (B232.15.w15)
  • Repeat haematology three or four weeks later, if lymphocytosis is still present a biopsy should to be carried out on the bone marrow or lymph node. (B232.15.w15)

Staging:

Lymphoma may be staged as in dogs; this assists in prognosis: (B631.30.w30, J213.7.w5)

• Stage 1: single site only.
• Stage 2: two or more sites, on the same side of the diaphragm.
• Stage 3: multiple lymphatic sites (spleen, lymph nodes) on both sides of the diaphragm.
• Stage 4: multiple sites on both sides of the diaphragm, with non-lymphatic tissue or bone marrow involved.

• Environmental Assessment
• History & Documentation
• Physical Examination of Mammals
• Clinical Pathology of Ferrets
• Imaging in Ferret Diagnosis and Treatment
• Necropsy of Mammals
• Treatment and Care
• Chapter 2 - B36 Field Manual of Wildlife Diseases - Specimen Collection and Preservation
• Chapter 3 - B36 Field Manual of Wildlife Diseases - Specimen shipment
• Appendix A - B36 Field Manual of Wildlife Diseases - Sample specimen history form

Similar Diseases (Differential Diagnosis)

• Extramedullary haemopoiesis, especially if there is splenomegaly present. (B232.15.w15)
• Note: A rapidly growing thymic mass can cause dyspnoea and be misdiagnosed as cardiomyopathy or pneumonia. (B602.9.w9, B627.9.w9, B628.11.w11)

Specific Medical Treatment

• Antibiotics will only give short periods of remission. (B232.15.w15)
• Corticosteroid therapy may give long periods of remission. (B232.15.w15, B629.13.w13)
• Chemotherapy (P120.2006.w1, B627.9.w9, B629.13.w13), radiotherapy, surgery or a combination of these. 
• Note: Prognosis is guarded. (B627.9.w9, B232.15.w15) 
  • Clients should be informed a complete recovery is rarely achieved. (P120.2006.w1)
  • If the disease is diagnosed early and the treatment is more aggressive, then the recovery is more successful. (B232.15.w15)
  • If the disease is affecting the stomach, intestines, liver, bone marrow or single lymph nodes, there is likely to be a poor response to chemotherapy. (B627.9.w9, J29.14.w3) 

Chemotherapy

• This is usually used in treatment of lymphoma in ferrets; various protocols have been developed; success has been variable. (J29.14.w3)
• A full blood count, biochemistry, radiographs and bone marrow aspirate should be carried out prior to chemotherapy. This allows assessment of the ferret for prognosis and response to the therapy. A complete blood count should be carried out no more than twenty four hours prior to each treatment. (B232.15.w15, B629.13.w13, J29.14.w3)
  • If 50% or more of the bone marrow cells are malignant, then the ferret is unlikely to tolerate chemotherapy. (B232.15.w15, B629.13.w13)
  • Monitor the blood profile and general condition throughout the treatment. If the white cell count falls below 1500/mm³ or the PCV is below 30%, chemotherapy should be stopped. Treatment can be restarted once the blood profile returns to normal. (B629.13.w13) If the ferret is debilitated the treatment should stop, until improved. (B232.15.w15)
  • Note: The cytotoxic drugs used in chemotherapy have side effects such as lethargy, posterior paresis, vomiting, anorexia, hair loss, dyspnoea and collapse. These side effects can be seen up to two weeks from the start of treatment. (B232.15.w15, B629.13.w13)
  • Note: Safety protocols should be followed during the use of antineoplastic drugs. (B629.13.w13)
  • Chemotherapy should be given in combination with any surgical removal of a solid mass. (B629.13.w13)
  • Administration of intravenous agents should be carried out with the ferret sedated and using a preplaced intravenous catheter or vascular access port. (J29.14.w3)

Various protocols have been described for chemotherapy:

• Vincristine, Asparaginase, Cyclophosphamide, Doxorubicin (P120.2006.w1) and prednisolone. These can be given in combinations for 14 weeks. A cannula can be placed in the jugular vein, for routine administration of medication. (B232.15.w15, B629.13.w13)
• Vincristine 0.75 mg/m² intravenously once weekly for up to four weeks. For females weighing 400-500 grams give 0.05 mg and for a 1 kg female ferret give 0.07 mg. For males weighing 1.5 kg give 0.1 mg. Note: Give this medication slowly intravenously under general anaesthesia; perivascular administration causes tissue necrosis. (P120.2006.w1) An indwelling catheter can be used for this purpose. Flushing the catheter before use is recommended. Care should be taken not to use heparin to flush when using doxorubicin, as this will cause doxorubicin to precipitate out. (B232.15.w15, B629.13.w13)
• Cyclophosphamide 50mg/m² orally once weekly for four weeks. (B232.15.w15)
• Doxorubicin 1 mg/kg intravenously every twenty one days for five treatments. This treatment can be given alone or with orthovoltage radiation. (B627.9.w9, B232.15.w15)
• Asparaginase at 400 i.u./kg intraperitoneally once in the first week. (B232.15.w15)
• Protocol one
  • Day one prednisone 1mg/kg orally every twelve hours (To be continued throughout treatment)
  • Day one, eight, fifteen and twenty two, vicristine 0.12 mg/kg intravenously.
  • Day three, twenty four and forty six, cyclophosphamide 10 mg/kg orally or subcutaneously.
  • Day forty six gradually decrease dose to nothing over four weeks.
  • Note: When protocol one is given, weekly blood counts should be run.
• Protocol two:
  • Week one vincristine 0.07 mg/kg intravenously.
  • Week one asparaginase 400 IU/kg intraperitoneally.
  • Week one prednisone 1 mg/kg rally every twenty four hours, through out the therapy.
  • Week two cyclophosphamide 10 mg/kg subcutaneously.
  • Week three doxorubicin 1 mg/kg intravenously.
  • Four to six weeks, same as weeks one to three, but discontinue asparginase.
  • Week eight vincristine 0.07 mg/kg intravenously.
  • Week ten cyclophosphamide 10 mg/kg subcutaneously.
  • Week fourteen methotrexate 0.5 mg/kg intravenously.
  • Continue this protocol in sequence biweekly after the last week.
• Protocol three (this can be used for recurrence of disease:)
  • Doxorubicin 1 mg/kg intravenously every twenty one days for up to five treatments. 
  • Prednisone 1 mg/kg every twenty four hours or divided every twelve hours.

  (B629.13.w13)

• A novel lymphoma protocol has been developed by Tufts Cummings School of Veterinary Medicine. This includes prednisolone, L-asparaginase, cyclophosphamide, cytarabine, methotrexate, chlorambucil and procarbazine. This extends over twenty six weeks and blood counts are recommended seven times during this treatment protocol. (P120.2006.w1)

Glucocorticoids

• In patients that are unable to receive antineoplastic treatment, glucocorticoids can be used. 0.5 mg/kg orally every twelve hours and increased to control clinical signs. 
  • Ferrets respond well initially to glucocorticoids. (B632.6.w6)
  • Note: Glucocorticoids should not be used in asymptomatic ferrets, as resistance can occur. (B232.15.w15)
  • Prednisolone 2 mg/kg daily for three months. This has been reported to improve the ferret's appetite and attitude, and reduce tremors. Clinical signs can reappear four to six weeks after the end of treatment. (B232.15.w15) 
    • Alternatively prednisone 1 mg/kg orally once daily. (B629.13.w13)
    • Prednisone should not be started before a biopsy is taken, as remission can be rapid. (P120.2006.w1)
    • If clinical signs reappear then it will be refractory to treatment of other agents. (P120.2006.w1, B232.15.w15, B629.13.w13)

• Radiotherapy is sometimes used, e.g. in combination with oral prednisolone and injectable chemotherapy in the  successful treatment of a spinal lesion. (J29.14.w3)

Other treatments

• Vitamin C can be used as an antioxidant and to stimulate the immune system (B629.13.w13) at 50-100 mg/kg twice daily. (B232.15.w15)
• Pau d'Arco, a natural antibiotic tree bark extract, to support the immune system. Give three to five drops orally every twelve hours. (B629.13.w13) there are no formal controlled studies regarding the safety and efficacy of this treatment. (J29.14.w3)
• Other natural remedies such as pycnogenol and essiac have been used; there are no formal controlled studies regarding the safety and efficacy of these treatments. (J29.14.w3)

Note: 

• Chemotherapy may cause immunosuppression. Therefore ferrets undergoing this treatment may be susceptible to infections or organ failure. (B627.9.w9)
• Remission is indicated by a normal blood count and resolution of organomegaly. (B629.13.w13)
• Lymphosarcoma may recur any time from three months to several years. Because of this, reassessment should be carried out every one to three months. (B232.15.w15) 

• Clinical Pathology of Ferrets
• Oral Medication and Syringe Feeding of Ferrets
• Venipuncture / Blood sampling / Intravenous Catheterization in Ferrets
•  

General Nursing and Surgical Techniques

• Supportive treatment includes adequate nutrition and hydration during specific medical treatment; syringe-feeding may be needed. (J29.14.w3)
• A good quality diet is required which is high in meat protein and fat. Supplement with Nutri-plus gel (Virbac). (B232.15.w15) This is especially important during chemotherapy. (B232.15.w15)
• The client needs to be informed how important good nutritional support, compliance of medication and close monitoring of the ferret is during treatment and recovery. (B629.13.w13) 
• Affected organs can be removed, but this disease is likely to be systemic. (B232.15.w15)

• Treatment and Care - Supportive Care and Nursing
• Food and Feeding for Mammals - Convalescent diets / Nutritional support
• Oral Medication and Syringe Feeding of Ferrets

Preventative Measures

--

• Preventative Medicine for Mammals

Environmental and Population Control Measures

Ferrets

• --

• Environmental and Population Management - General