Felis ISSN 2398-2950

Lymphoproliferative disease

Contributor(s): Laura Garrett, Irene Rochlitz, Danielle Aberdein , John Munday

Introduction

  • Includes:
    • Lymphoma.
    • Acute lymphoblastic leukemia (ALL).
    • Chronic lymphocytic leukemia (CLL).
    • Feline autoimmune lymphoproliferative syndrome (FALPS).
    • Myeloma-related disorder (MRD).
    • Feline immunodeficiency virus-associated lymphadenopathy (FIVAL).
    • Distinct peripheral lymph node hyperplasia of young cats (DPLNH).
    • Generalized lymphadenopathy resembling lymphona (GLRL).
    • Plexiform vascularization of lymph nodes (PVLN).
  • Cause: unknown for most. Feline leukemia virus (FeLV) contributes to some types of lymphoma and ALL. Feline immunodeficiency virus (FIV) is associated with a mildly increased risk of lymphoma in some studies. FIVAL is the result of the acute plase of FIV infection.
  • Signs: non-specific signs such as weight loss with or without vomiting and diarrhea most common for lymphona and MRD, although variable depending on the organ most severely affected. Leukemias can present with signs referable to cytopenia due to neoplastic cell infiltration of bone marrow, eg anemia, thrombocytopenia, granulocytopenia. Enlargement of multiple lymph nodes rarely seen in feline lymphoma, but this is the principle clinical sign for cats with FALPs, FIVAL, DPLNH, and GLRL. Cats with DPLNH can also have fever, lethargy, anorexia, and hepatosplenomegaly.
  • Diagnosis: hematology, cytology of any discrete masses, biopsy followed by histology and immunohistochemistry of affected organs, PCR for antigen receptor rearrangements (PARR) testing.
  • Treatment: cytotoxic drugs for lymphoma, ALL, CLL and MRD. No treatment has been shown to be beneficial in FALPS, no treatment required for FIVAL, DPLNH, GLRL, and PVLN.
  • Prognosis: fair to guarded if lymphoma or MRD, poor if ALL or FALPs; good to fair if CLL, good for FIVAL, DPLNH, GLRL, and PVLN.

Pathogenesis

Etiology

  • Lymphoma. Some forms are predisposed by feline leukemia virus (FeLV) Feline leukemia virus disease with multicentric and mediastina Mediastinal lymphoma forms most often associated with infection. The alimentary form of lymphoma Alimentary tract: neoplasia is most common and this has not been shown to be caused by FeLV. Some studies have reported mildly increased rates of lymphoma in cats infected by feline immunodeficiency virus.
  • ALL. Many affected cats are infected by feline leukemia virus.
  • CLL. Possible association with FeLV, although few cases of this have been reported.
  • FALPS. Genetic disorder in lymphocyte apoptosis.
  • FIVAL. Transient lymphoproliferation after infection by feline immunodeficiency virus.
  • DPLNH, GLRL. Possible association with FeLV.
  • PVLN. Unknown, possibly ischemic damage to the node.

Pathophysiology

Lymphoma

  • These are proliferations of neoplastic lymphoid cells. Any of the different subtypes of lymphoid cells can become neoplastic but neoplasms of T-lymphocytes are thought to be more common in cats. The most common location for lymphoma in cats is the gastrointestinal tract, although renal and hepatic forms are also common. Any organ can be affected by this neoplasm so that cats with lymphoma can present with a variety of clinical signs of disease.
  • Paraneoplastic effects, eg hypercalcemia (rare) Hypercalcemia: overview.

Leukemia

  • Infiltration of bone marrow by neoplastic lymphocytes can result in myelophthisic anemia, neutropenia, or thrombocytopenia. Increased blood viscosity can result in multiple thrombi.

Feline autoimmune lymphoproliferative syndrome

  • Cats present early in life with marked non-neoplastic lymphoproliferation.
  • The marked proliferation of lymphocytes expands lymphoid tissues throughout the body.

Myeloma-related disorders

  • These are a diverse group of neoplasms that consist of lymphocytes that secrete immunoglobulin.
  • Can involve the bone marrow, although a much lower proportion of feline MRDs involve the bone marrow than in people. Feline MRDs often involve the liver and spleen. These also include solitary plasma cell tumors Plasmacytoma
  • Cats often have hyperglobulinemia which may result in blood hyperviscosity which can lead to clinical signs of neurological signs disease and thrombosis.
  • Extensive bone marrow involvement can lead to anemia.
  • Rarely cats present with lameness due to bone lesions.
  • Cats can have solitary extramedullary nodules. This disease manifestation has the best prognosis.

Feline immunodeficiency virus-associated lymphadenopathy

  • Some cats in the acute phase (in the first few weeks after infection) of feline immunodeficiency virus (FIV) infection develop a generalized lymphadenopathy.
  • This can result in mild to moderate enlargement of peripheral lymph nodes. Visceral lymph nodes can also become enlarged, although they are less often affected than peripheral nodes.
  • Enlargement may persist for weeks or months before nodes return to normal size.

Distinctive peripheral lymph node hyperplasia of young cats

  • The disease appears to be very rare and only a small number of cases have been described.
  • Affected cats less than 2 years old. Presenting signs include fever, lethargy, anorexia, hepatosplenomegaly Abdominal organomegaly, and lymphadenopathy. Most often all peripheral lymph nodes are markedly enlarged (up to 3x normal size).  
  • Cats are frequently anemic.
  • Lymphadenopathy resolves over weeks to months regardless of treatment.

Generalized lymphadenopathy resembling lymphoma

  • Cats are typically between 1 and 4 years-old and Maine Coon Maine Coon cats appear to be over-represented.
  • Many cats with this disorder also present with upper respiratory or urinary tract disease.
  • Cats have a mild to moderate enlargement of multiple peripheral lymph nodes without involvement of visceral nodes or other organs.
  • Unlike FIVAL and DPLNH, histology of the enlarged lymph nodes reveals features suggestive of lymphoma.
  • Lymphadenopathy is transient and complete resolution is expected after several months.  

Plexiform vascularization of lymph nodes

  • This disorder is characterized by marked enlargement of a single cervical, retropharyngeal, or inguinal lymph node.
  • Cats do not have symptoms of systemic disease.
  • Histology reveals the lymphocytes in the node have been replaced by proliferation of the capillaries.
  • The lymphadenopathy does not resolve, but surgical excision of the node is curative and remaining nodes remain normal.  

Timecourse

  • Acute over weeks; chronic over months.

Treatment

Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Cannon C M et al (2015) Clinical Signs, Treatment, and Outcome in Cats with Myeloma-Related Disorder Receiving Systemic Therapy. J Am Anim Hosp Assoc 51, 239-248 PubMed.
  • Aberdein D et al (2015) A Novel and Likely Inherited Lymphoproliferative Disease in British Shorthair Kittens. Vet Pathol 52, 1176-1182 PubMed.
  • Campbell M W et al (2012) Chronic lymphocytic leukaemia in the cat: 18 cases (2000-2010). Vet Comp Oncol 11, 256-264 PubMed.
  • Hartmann K (2012) Clinical aspects of feline retroviruses: a review. Viruses 4, 2684-2710 PubMed.
  • Welsh E M et al (1999) Plexiform vascularisation of a retropharyngeal lymph node in a cat. J Small Anim Pract 40, 291-293 PubMed.
  • Callanan J J et al (1992) Clinical and pathological findings in feline immunodeficiency virus experimental infection. Vet Immunol Immunopathol 35, 3-13 PubMed.
  • Mooney S C et al (1987) Generalized lymphadenopathy resembling lymphoma in cats: six cases (1972-1976). J Am Vet Med Assoc 190, 897-900 PubMed.
  • Moore F M et al (1986) Distinctive peripheral lymph node hyperplasia of young cats.Vet Pathol 23, 386-391 PubMed.


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