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Lymphoma

Feline lymphoma is a loose generic term for any feline tumour affecting lymph cells or lymph nodes[1].

Lymphomas are irregular (neoplastic) growth of lymphoid tissue as tumors, which can affect a single organ (e.g. kidney, mesenteric or mediastinal lymph node, spleen or liver). Whereas lymphoma have been classically defined as neoplastic cells found in fluid exudates (such as ascitic fluid), lymphosarcoma usually refers to solid tumours within organs, but such classification is academic and from a clinical perspective. However, since treatment regimens are pragmatically identical, we have adopted the generic term lymphoma to refer to any neoplastic change of lymphocytes that does not involve leukemia. Lymphomas may occur within a lymph node (nodal) or outside lymph node tissue (extra-nodal). The type of white cell involved can be either B, T or NK cell lineage lymphocytes. Regardless of classification, feline lymphoma invariably receive the same veterinary treatment[2].

Hematopoietic tumors are the most frequently occurring tumors in domestic cats, and they account for about 33% of all feline tumors. Lymphosarcoma accounts for up to 90% of the hematopoietic tumors in cats, with an estimated incidence of 200 cases/100,000 cats at risk. No increased prevalence has been reported for any sex or breed of cat. The usual age of cats at diagnosis is between 2 and 6 years.

  • Multicentric lymphoma – generally involves multiple lymph nodes and possibly multiple organs. This form is more closely associated with feline leukemia and the prognosis for this form is not as good, especially if the cat is feline leukemia positive[3].
  • The thymic form – also associated with feline leukemia, and limited to the chest cavity (thymus gland and associated lymph nodes).
  • Mesenteric lymphoma – very common in cats over 10 years of age. The intestinal form affects the small intestine but sometimes the stomach, leading to (gastric lymphoma. This form is least likely to be associated with feline leukemia.
  • Low-grade alimentary lymphoma (LGAL) – aged cats, usually confined to intestinal lumen. Clinically indistinguishable from lymphocytic-plasmacytic irritable bowel disease[4]
  • Cutaneous lymphoma

Contents

  • 1 Causes
  • 2 Clinical signs
  • 3 Diagnosis
  • 4 Treatment
  • 5 References

 

Causes

  • Inflammatory processes – no definitive proof exists as yet to conclude that chronic inflammation leads to formation of feline lymphoma, but inflammation-associate neoplasia is well-established[5]. An association between chronic inflammatory bowel disease and development of feline T-cell lymphoma has been suggested[6]. Concurrent lymphocytic-plasmacytic IBD has been identified in other regions of the alimentary tract in up to 20% of cats with LGAL[7].
  • Environmental – a variety of chemicals such as aromatic benzenes, organophosphates and dioxins (DDT and 2,4,5-T) are implicated in human lymphoma[8], and cannot be excluded as possible causes of feline lymphoma.
  • Nutritional – the proven relationship between nutrition and neoplasia in humans suggests a plausible link between nutrition and lymphoma in cats, although more work is needed in this area[9][10].
  • Bacterial – Spirochetes have been observed in a feline epitheliotropic T- cell gastrointestinal tract lymphoma and a natural killer-like T cell lymphoma. There were Helicobacter spp-like organisms and Spirochetes in a cougar affected with gastroduodenal adenocarcinoma and rectal adenoma[11]. Unlike in human lymphomas associated with Helicobacter pylori or Borrelia burgdorferi, the etiologic significance of spiral-shaped bacteria is not clear in feline lymphoid neoplasms. Records of bacteria belonging to the genus Helicobacter, such as Flexispira suggests a possible synergistic role of bacteria in the etiopathogenesis of feline lymphoma.
  • Genetic – breed predisposition (e.g. Maine coon) and familial susceptibility have been implicated anecdotally but no evidence to prove such hypotheses has surfaced.
  • Viral – FeLV – in some cases, lymphoma in cats follows infection with the feline leukemia virus (FeLV). FeLV has a strong association with development of mediastinal and muticentric lymphoma in cats (60 fold increased risk)[12]. FIV also increases the risk of lymphoma formation in cats, but less so, compared with FeLV (5 fold increased risk). An indirect role is favoured for FIV in the development of extranodal B-cell neoplasms in cats[13]. Possible effects of the FIV infection that can lead to lymphosarcoma include activation of ß lymphocytes with the eventual emergence of malignant cells from the proliferating ß-cell pool, chronic dysregulation of the immune system, or activation of oncogene pathways that facilitate the malignant transformation of normal cells.

 

Clinical signs

The most common clinical signs were weight loss, inappetence, vomiting and/ or diarrhea, lethargy, and polyphagia. Vomiting and/or diarrhea were considered chronic in 11 of 15 cats. Abdominal palpation is usually abnormal. The most common ultrasonographic finding are increased intestinal wall thickness with preservation of layering.

Feline lymphoma has several different forms. In all forms, the tumors consist of abnormal proliferations of lymphoid tissue. Because lymphocytes and lymph tissue are found throughout the body, lymphoma can appear almost anywhere and affect a wide number of organs. Lymphoma more commonly appears, though, in three parts of the body. The location is often associated with the cause of the lymphoma and influences the symptoms, treatment, and prognosis.

In all forms, the treatment outcome is more guarded if the cat is positive for Feline leukemia virus (FeLV).

 

Diagnosis

Diagnosis of lymphoma in cats is based on a series of observations and tests. A physical exam may revealing swellings in the lymph nodes or GI tract. X-rays, ultrasounds, or physical examinations may show tumors or swellings in other internal organs.Testing for FeLV and FIV may reveal that a cat is positive for one of these diseases, which increases the likelihood that she could develop feline lymphoma. A chemistry panel and complete blood count (CBC) may reveal particular organ involvement or an anemia, particularly in the multicentric form or in the FeLV positive cat. Fine needle aspirate or biopsies are often diagnostic for feline lymphoma. When a trained pathologist examines a fine needle aspirate or a biopsy, he or she is looking for a uniform population of immature lymphoid cells, which confirms feline lymphoma.

Hematological changes include mild anaemia, monocytosis and/or neutrophilic leucocytosis (Lingard, et al, 2009). Hypoalbuminaemia appears to be a relatively constant sign, depending primarily on the grade of lymphoma, with high-grade cases showing greater extents of hypoalbuminaemia[14].

Other causes of gastrointestinal disease with signs of vomiting, weight loss and/or diarrhoea include irritable bowel disease, gastritis, FIP, bacterial gastroenteritis, parasites, and obstructive causes (e.g. pyloric stenosis, foreign body, Intussusception, intestinal polyps.

Differential diagnoses of non-lymphoma neoplasia associated with lymphoid tissues include Feline Hodgkin’s-like disease, B-cell lymphoma, Follicular lymphoma, and DPLH – distinctive peripheral lymph node hyperplasia


Table. 1. Histological classification of lymphoproliferative diseases in cats[15]


Low grade Chronic lymphocytic leukemia CLL
Small lymphocytic lymphoma SLL
Small lymphocytic intermediate lymphoma SLLI
Small lymphocytic plasmacytoid/plasmacytoma SLLP
Follicular small cleaved-cell lymphoma FSC
Follicular mixed-cell lymphoma FM
Intermediate grade Follicular large-cell lymphoma FL
Small cleaved-cell lymphoma SCC
Mixed-cell lymphoma MC
Large-cell lymphoma LC
Large cleaved-cell lymphoma LCC
High grade Acute lymphocytic leukemia ALL
Immunoblastic lymphoma IB
Immunoblastic small-cell lymphoma IBS
Immunoblastic polymorphous lymphoma IBP
Small noncleaved-cell lymphoma SNC
Lymphoblastic lymphoma LB
Lymphoblastic convoluted-cell lymphoma LBC

 

Treatment

The remission and survival rates of cats with lymphoma vary depending on the cat’s FeLV status, the location of the tumor(s) and how quickly the tumor is diagnosed and treated. In general, about 70% of cats will respond to the chemotherapy treatment. On average, these cats will live an additional 4 to 16 months. However, about 30% – 40% of the cats that respond will go into a more complete remission that can last for 2 years or longer. This potential response is encouraging and is the reason that treatment for lymphoma in cats is so highly recommended. Cats that are not treated have an average survival time of only 4 to 6 weeks once the diagnosis has been made. Cats that are infected with FeLV or FIV have a lower rate of response to therapy as well as a shorter average survival time when treated[16].


Table 2. The University of Pennsylvania feline weekly sequential lymphoma protocol (2009)


Treatment week Drug, dosage and route
1 L-asparaginase (Leunase) 400 IU/kg SQ weekly
2 Chlorambucil (Leukeran/Vincristine) 0.5 mg/m2, IV
3 Cyclophosphamide 50mg PO (25mg PO day 1 and 25mg PO on day 3)
4 Vincristine 0.5mg/m2, IV
5 Methotrexate 2.5 mg PO
6-9 Repeat week 2-5

 

References

  1. ↑ Mooney SC, Patnaik AK, Hayes AA, MacEwen EG (1987) Generalized lymphadenopathy resembling lymphoma in cats: six cases (1972–1976). J Am Vet Med Assoc 190:897-900
  2. ↑ August, J.R. (2006). Consultations in feline internal medicine. Elsevier Saunders, Missouri
  3. ↑ Steele KE, Saunders GK, Coleman GD (1997) T-cell-rich B-cell lymphoma in a cat. Vet Pathol 34:47-49
  4. ↑ Lingard AE, Briscoe K, Beatty JA, et al (2009) Low-grade alimentary lymphoma: clinicopathological findings and response to treatment in 17 cases. J Feline Med Surg 11: 692-700
  5. ↑ Schafer, M & Werner, S (2008) Cancer as an overhealing wound: an old hypothesis revisited. Nat Rev Mol Cell Biol 9:628
  6. ↑ Valli, VE ((2007) Enteropathy-type T-cell lymphoma. In Valli, VE (Ed): Veterinary comparative haematopathology. Blackwell Publishing, Oxford. pp:318
  7. ↑ Lingard, AE et al (2009) Low-grade alimentary lymphoma: clinicopathological findings and response to treatment in 17 cases. JFMS 11(8):692-700
  8. ↑ Lymphomainfo.net
  9. ↑ Grace PB, Taylor JI, Low Y, Luben RN, Mulligan AA, Botting NP, et al (2004) Phytoestrogen concentrations in serum and spot urine as biomarkers for dietary phytoestrogen intake and their relation to breast cancer risk in European prospective investigation of cancer and nutrition — Norfolk. Cancer Epidemiol Biomarkers and Prev 13:698-708
  10. ↑ Setchell KD, Briwb NM, Lydeking-Olsen E (2002) The clinical importance of the metabolite equol: a clue to the effectiveness of soy and its isoflavones. J Nutr 132:3577-3584
  11. ↑ Ezura, K et al (2007) Immunoblastic lymphoma of germinal center origin in a cat. Can Vet J 48(2):211–213
  12. ↑ Shelton, GH et al (1990) Feline immunodeficiency virus and feline leukaemia virus infections and their relationships to lymphoid malignancies in cats: a retrospective study (1968-1988). J Acquir Immune Defic Syndr 3623
  13. ↑ Beatty, JA et al (1998) Feline immunodeficiency virus (FIV)-associated lymphoma: apotential role for immune dysfunction in tumorigenesis. Vet Immunol Immunopathol 65:309
  14. ↑ Gabor, LJ, Malik, R & Canfield, PJ (1998) Clinical and anatomical features of lymphosarcoma in 118 cats. Aust Vet J 76:725
  15. ↑ Barrs, VR & Beatty, JA (2010) In August, JR (Ed): COnsultations in feline internal medicine. Vol 6. Elsevier Saunders, Philadelphia. pp: 187
  16. ↑ Day MJ, Kyaw-Tanner M, Silkstone MA, Lucke VM, Robinson WF (1999) T-cell-rich B-cell lymphoma in the cat. J Comp Pathol 120:155-167

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