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  • Disciplina: Oncologia
  • Specie: Gatto

Lymphoma is very common in cats, accounting for about 90% of haematopoietic neoplasms and 30% of all feline neoplasms. The estimated incidence is 200 new cases per year in 100,000 cats at risk. Nevertheless, most of the data available in the literature refer to the era prior to vaccination against Feline leukaemia virus (FeLV) and do not reflect the current situation accurately.

Risk factors for the development of lymphoma include infection with FeLV (particularly for the multicentric, mediastinal, extranodal and leukaemic forms), passive exposure to smoke, chronic inflammatory conditions (including chronic inflammatory bowel disease [IBD]) and genetic factors.

 

CLASSIFICATION


The classification of feline lymphomas is based on cell morphology, histological grade, immunophenotype and anatomical site involved. Most lymphomas in cats are intermediate grade (30-40%) or high grade (50-60%). Only in the intestine do low-grade lymphomas prevail; these typically have a T-cell immunophenotype. Most of the renal and mediastinal lymphomas are high grade.

With regards to immunophenotype, B-cell lymphomas are predominant, accounting for up to 70% of the cases. Pure hepatic, leukaemic and mediastinal lymphomas do, however, often have a T-cell immunophenotype. There are also descriptions of T-cell-rich B-cell lymphomas (Hodgkin’s like) and “non T, non B” (NK type) lymphomas in felines.

 

ANATOMICAL FORMS


Various anatomical forms of lymphoma are recognized, as described below.

Mediastinal lymphoma is characterized by mediastinal lymphoadenomegaly, sometimes associated with a pleural effusion. Affected cats are typically young (2-3 years old) and FeLV-positive (90% of cases). They develop cough, dyspnoea, exercise intolerance, regurgitation, dysphagia, anorexia and, occasionally, unilateral or bilateral Horner’s syndrome.

Alimentary tract lymphoma is fairly common in cats. The clinical, histological and immunophenotypic data must be evaluated as a whole in order to reach the diagnosis. Mucosa-associated lymphoid tissue (MALT) lymphoma has a T-cell origin and is typically a small-cell (low-grade) lymphoma. MALT lymphoma develops in the small bowel, giving rise to widespread thickening of the bowel wall (Fig. 1); it may remain confined to the mucosa for a relatively long period, but inexorably progresses reaching first the mesenteric lymph nodes and then the other abdominal viscera (transmural spread). The main differential diagnosis is IBD. A diagnostic algorithm has recently been proposed to differentiate between low-grade lymphoma and IBD. The first evaluation is morphological (histopathology) and is followed by immunohistochemical stains and, only as a last investigation, by clonal studies. A full thickness biopsy, rather than an endoscopically obtained sample, is recommended in order to make the definitive diagnosis.

In the distal part of the small bowel, caecum and colon, B-cell lymphomas are more common; these arise from mucosal lymphoid follicles (Peyer’s patches) and are typically highly malignant. The lesions are transmural and there is often concomitant involvement of the spleen, peripheral lymph nodes and bone marrow.

Large granular cell lymphoma (LGL) accounts for about 10% of alimentary lymphomas and derives from uncontrolled proliferation of cytotoxic T lymphocytes or natural killer (NK) cells. This is a large-cell, transmural lymphoma that initially involves the ileus, jejunum and mesenteric lymph nodes, but rapidly metastasises to other abdominal viscera and the bone marrow. Laboratory examinations show neutrophilic leucocytosis, anaemia, hypoalbuminaemia, hypocalcaemia and increased concentrations of liver transaminases and bilirubin. The finding of more than 13% of large granular lymphocytes in the circulation must be considered pathological.

Multicentric lymphoma is characterized by enlargement of a single lymph node (Fig. 2) or generalised lymphadenomegaly, with or without systemic or extranodal involvement. Histopathological studies are always necessary to make the definitive diagnosis.

Extranodal lymphomas. The nervous tissue lymphomas involve the central nervous system (brain and spinal cord) or peripheral system and may be primary or part of a multicentric lymphoma. Up to 40-50% of cats with renal lymphoma also have concomitant cerebral involvement. Renal lymphoma is frequent and affects adult cats. It may be primary or be part of an abdominal or multicentric lymphoma. The signs are vague, non-specific and secondary to renal failure. Renal lymphoma is often accompanied by cerebral involvement, so there may be signs such as irritability, personality changes, weakness, loss of coordination and proprioceptive deficits. Ocular lymphoma is fairly common and as for the other extranodal lymphomas can be primary or part of a multicentric lymphoma. Common signs are photophobia, blepharospasm, epiphora, hyphaema, hypopyon, ocular or retro-orbital masses, uveitis and retinal detachment. Nasal lymphoma is frequent; the signs are similar to those of an upper respiratory tract infection. For prognostic and therapeutic purposes it is important to distinguish between pure nasal and nasopharyngeal lymphomas. Cerebral or systemic involvement occurs in some cases, so staging is essential. Cutaneous lymphomas are rare in cats and usually affect elderly animals. These are usually non-epitheliotropic tumours that are characterized clinically by a pruriginous erythroderma and plaques that tend to become confluent.

 

STAGING


Various investigations are required for the clinical staging of lymphomas in cats:

  • blood tests: complete blood count, blood-chemistry, tests for Feline immunodeficiency virus (FIV)/FeLV
  • urinalysis
  • cytological or histological evaluation of bone marrow
  • histological evaluation of the lymph nodes or organs involved. Cytology of lymph node needle biopsies is often inadequate for making a definitive diagnosis in cats, particularly when the differential diagnosis includes some benign hyperplastic syndromes typical of the feline species
  • immunophenotyping
  • abdominal ultrasonography
  • chest X-rays.

Once the staging investigations have been completed, the clinical stage can be defined according to the World Health Organization criteria:

Stage I

  • single neoplasm (extranodal)
  • involvement of a single anatomical area (nodal), including a primary thoracic neoplasm

Stage II

  • single extranodal neoplasm with involvement of a regional lymph node
  • involvement of two or more nodal areas on the same side of the diaphragm
  • two single neoplasms (extranodal) with or without involvement of regional lymph nodes on the same side of the diaphragm
  • primary gastrointestinal neoplasm (usually in the ileo-caecal area), easily resectable, with or without involvement of mesenteric lymph nodes

Stage III

  • two single extranodal neoplasms on different sides of the diaphragm.
  • involvement of two or more nodal areas cranially and caudally to the diaphragm
  • extensive, non-resectable primary intra-abdominal lesions
  • paraspinal or epidural neoplasms, independently of other sites of neoplasm

Stage IV

  • stage I-III with involvement of the liver and/or spleen

Stage V

  • stage I-IV with initial involvement of the central nervous system and/or bone marrow.

 

TREATMENT


Since feline lymphoma is a systemic disease, the treatment of choice is chemotherapy, administered according to different therapeutic protocols. Remission rates and survival depend largely on the anatomical site and histological grade of the malignancy. For examples, animals with pure nasal lymphoma treated with radiotherapy have a long survival, while those with a high-grade intestinal lymphoma have a very poor prognosis. The survival of cats with low-grade intestinal lymphoma may exceed 2 years.

Radiotherapy is indicated in cats for localised forms of spinal, nasal or mediastinal lymphoma.

Surgery is indicated in the case of intestinal lymphoma with obstruction or perforation of the bowel.

 

 

Suggested readings


  1. Bertone ER, Snyder LA, MooreAS: Environmental tobacco smoke and risk of malignant lymphoma in pet cats.Am J Epidemiol, 156: 268, 2002.
  2. Caciolo PL, Nesbitt GH, Patnaik AK et al: Cutaneous lymphosarcoma in the cat: a report of nine cases. J Am Anim Hosp Assoc, 20: 491-496, 1984.
  3. Carreras JK, Goldschmidt M, Lamb M et al: Feline epitheliotropic intestinal malignant lymphoma: 10 cases (1997-2000).J Vet Intern Med, 17: 326, 2003.
  4. CoutoGC: What is new on feline lymphoma?J Feline Med Surg, 3: 171, 2001.
  5. Darbes J, Majzoub M, Breuer W et al: Large granular lymphocyte leukemia/lymphoma in six cats.Vet Pathol, 35: 370, 1998.
  6. Day MJ, Henderson SM, Belshaw Z et al: An immunohistochemical investigation of 18 cases of feline nasal lymphoma. J Comp Pathol, 130: 152, 2004.
  7. EttingerSN: Principles of treatment for feline lymphoma.Clin Tech Small Anim Pract, 18: 98, 2003.
  8. Evans SE, Bonczynski JJ, Broussard JD et al: Comparison of endoscopic and full-thickness biopsy specimens for diagnosis of inflammatory bowel disease and alimentary tract lymphoma in cats.J Am Vet Med Assoc. 229: 1447, 2006.
  9. FanTM: Lymphoma updates.Vet Clin North Am Small Anim Pract, 33: 455, 2003.
  10. Gabor LJ, Malik R, CanfieldPJ: Clinical and anatomical features of lymphosarcoma in 118 cats.Aust Vet J, 76: 725, 1998.
  11. Gabor LJ, Canfield PJ, MalikR: Immunophenotypic and histological characterisation of 109 cases of feline lymphosarcoma.Aust Vet J, 77: 436, 1999.
  12. Haney SM, Beaver L, Turrel J et al: Survival analysis of 97 cats with nasal lymphoma: a multi-institutional retrospective study (1986-2006).J Vet Intern Med. 23: 287, 2009.
  13. Kiupel M, Smedley RC, Pfent C et al: Diagnostic algorithm to differentiate lymphoma from inflammation in feline small intestinal biopsy samples. Vet Pathol, 48: 212, 2011.
  14. Krick EL, Little L, Patel R, et al: Description of clinical and pathological findings, treatment and outcome of feline large granular lymphocyte lymphoma (1996-2004). Vet Comp Oncol. 6: 102, 2008.
  15. Lane SB, Kornegay JN, Duncan JR et al: Feline spinal lymphosarcoma: a retrospective evaluation of 23 cats.J Vet Intern Med, 8: 99, 1994.
  16. Little L, Patel R, Goldschmidt M: Nasal and nasopharyngeal lymphoma in cats: 50 cases (1989-2005).Vet Pathol. 44: 885, 2007.
  17. Louwerens M, London CA, Pedersen NC, Lyons LA: Feline lymphoma in the post-feline leukemia virus era. J Vet Intern Med, 19: 329, 2005.
  18. Mahony OM, Moore AS, Cotter SM et al: Alimentary lymphoma in cats: 28 cases (1988-1993).J Am Vet Med Assoc, 207: 1593, 1995.
  19. MooneySC, Hayes AA, Matus RE et al: Renal lymphoma in cats: 28 cases (1977-1984).J Am Vet Med Assoc. 191: 1473, 1987.
  20. Moore AS, OgilvieGK: Lymphoma. In Ogilvie GK, Moore AS (a cura di), Feline Oncology. Veterinary Learning Systems, Trenton, 2001.
  21. Richter KP: Feline gastrointestinal lymphoma.Vet Clin North Am Small Anim Pract, 33: 1083, 2003.
  22. Sfiligoi G, Théon AP, Kent MS: Response of nineteen cats with nasal lymphoma to radiation therapy and chemotherapy.Vet Radiol Ultrasound. 48: 388, 2007.
  23. Spodnick GJ, Berg J, Moore FM, CotterSM: Spinal lymphoma in cats: 21 cases (1976-1989).J Am Vet Med Assoc, 200: 373, 1992.
  24. Vail DM, Moore AS, Ogilvie GK, VolkLM: Feline lymphoma (145 cases): proliferation indices, cluster of differentiation 3 immunoreactivity, and their association with prognosis in 90 cats.J Vet Intern Med, 12: 349, 1998.
  25. Vail DM: Hematopoietic tumors. B. Feline lymphoma and leukemias. In:Withrow SJ, Vail DM(a cura di), Withrow & MacEwen’s Small Animal Clinical Oncology. Saunders, Filadelfia, IV edizione, 2007.
  26. Valli VE, Jacobs RM, Norris A et al: The histologic classification of 602 cases of feline lymphoproliferative disease using the National Cancer Institute working formulation.J Vet Diagn Invest, 12: 295, 2000.
  27. Valli VE, Jacobs RM, Parodi AL et al: Histological Classification of Hematopoietic Tumors of Domestic Animals. World Health Organization International Histological Classification of Tumors of Domestic Animals, seconda series, volume VIII. Washington DC: Armed Forces Institute of Pathology, American Registry of Pathology, 2002.
  28. Walton RM, HendrickMJ: Feline Hodgkin's-like lymphoma: 20 cases (1992-1999).Vet Pathol, 38: 504, 2001.
  29. Williams LE, Pruitt WA, Thrall DE: Chemotherapy followed by abdominal cavity irradiation for feline lymphoblastic lymphoma. Vet Rad Ultrasound, 51: 681, 2010.
  30. WilsonHM: Feline alimentary lymphoma: demystifying the enigma. Topics Comp An Med. 23: 177, 2008.
  31. Zwingenberger AL, Marks SL, Baker TW, Moore PF: Ultrasonographic evaluation of the muscolaris propria in cats with diffuse small intestinal lymphoma or inflammatory bowel disease.J Vet Intern Med. 24: 289, 2010.