Definition

Malignant transformation of lymphocytes

Pathophysiology

Viral (FeLV) or chemical (tobacco smoke) oncogenesis

Systems Affected

• Gastrointestinal
• Hemic/Lymphatic/Immune
• Nervous-most common spinal cord tumor in cats
• Ophthalmic
• Renal (high rate of relapse in central nervous system)
• Respiratory-nasal, thoracic cavities

Genetics

N/A

Incidence/Prevalence

• About 90% of hematopoietic tumors and 33% of all tumors in cats.
• Prevalence-41.6–200 per 100,000 cats.

Geographic Distribution

Regional differences may relate to differences in FeLV prevalence.

Signs

Causes

FeLV

Risk Factors

• FeLV exposure.
• Exposure to environmental tobacco smoke (relative risk 2.4, increases linearly with duration and quantity of exposure).
• FIV infection.

Differential Diagnosis

• Mediastinal form-congestive heart failure; cardiomyopathy; chylothorax; pyothorax; hemothorax; pneumothorax; diaphragmatic hernia; allergic lung disease; thymoma; ectopic thyroid carcinoma; pleural carcinomatosis; acetaminophen toxicity.
• Alimentary form-foreign body ingestion; intestinal ulceration; intestinal fungal infection; inflammatory bowel disease; intussusception; lymphangiectasia; other gastrointestinal tumor.
• Renal form-pyelonephritis; amyloidosis; glomerulonephritis; chronic renal failure; polycystic kidneys; feline infectious peritonitis.
• Multicentric form-systemic mycotic infection; immune-mediated disease; toxoplasmosis; lymphoid hyperplasia; hypersensitivity reaction; plague (specifically if prominent cervical lymphadenopathy as with Hodgkin-like form).

CBC/Biochemistry/Urinalysis

• May see anemia (negative prognostic factor), leukocytosis, and lymphoblastosis.
• May find high creatinine, high serum urea nitrogen, high hepatic enzyme activity, hypercalcemia (rare), and monoclonal gammopathy.

Other Laboratory Tests

FeLV testing: usually negative in older cats and in cats with (LGLL), usually positive in younger cats and those with mediastinal (85%) or CNS lymphoma, renal (45% positive), multicentric (20%), intestinal (15%).

Imaging

• Thoracic radiography-may see mediastinal mass, pleural effusion, abnormal pulmonary parenchymal patterns (rare), perihilar or retrosternal lymphadenomegaly.
• Abdominal ultrasonography-may see diffuse echotexture changes in the liver, spleen, and kidneys, focal or diffuse thickening of the intestines and the gastric wall, abdominal lymphadenopathy, intestinal/gastric mass.
  • Hypoechoic subcapsular thickening is associated with renal lymphoma.
  • Despite thickening of intestines, layering may be preserved.
• Computed tomography-space-occupying mass effect in affected area, especially used for nasal lymphoma.

Diagnostic Procedures

• Aspiration or biopsy of a mass or lymph node.
• Aspirate often sufficient to diagnose LCL, biopsy often required for SCL.
• Can be challenging to distinguish SCL from IBD.
• PARR testing can be done to determine if lymphocyte population is monoclonal (consistent with lymphoma) or not; sensitivity for detecting T-cell and B-cell LSA is 78% and 50%, respectively.
• Staging: CBC/Chemistry profile/Urinalysis/FeLV/FIV testing, thoracic radiographs, abdominal ultrasound, regional lymph node aspirates for localized lesions, ± bone marrow aspirate depending on CBC findings serum cobalamin level in SCL.

Pathologic Findings

• Gross-usually white to gray in color with areas of hemorrhage and necrosis.
• Cytologic-monomorphic population of lymphoid cells, sometimes with prominent, multiple nucleoli and coarse nuclear chromatin.
• Histopathologic-vary; several morphologic classification schemes in use.
  • Nasal lymphoma is most often immunoblastic B-cell origin.
  • Hodgkin's-like lymphoma is characterized by Reed-Sternberg cells and few neoplastic cells in a background of a reactive T-cell population with histiocytes and granulocytes.
  • LGL lymphoma most commonly affects the intestine and mesenteric lymph nodes.
  • B-cell most common in stomach (100%) and large intestine (88%), T-cell most common in small intestine (52%, most common location in gut).
  • In GI lymphoma, LCL more common than SCL when both cytologic and histopathologic samples are evaluated.

Appropriate Health Care

Outpatient whenever possible, supportive care if needed.

Nursing Care

Fluid therapy, antiemetics, appetite stimulants, thoracocentesis, etc. when indicated.

Activity

Normal

Diet

No change, can add n-3 fatty acids to diet (fish oil origin).

Client Education

• Emphasize that side effects are treatable and should be addressed promptly.
• Inform client that the goal is to induce remission and achieve a good quality of life for as long as possible.

Surgical Considerations

• To relieve intestinal obstructions or perforations and remove solitary masses.
• To obtain specimens for histopathologic examination.

Radiation Therapy

Possible option for localized lesions, such as nasal cavity or mediastinum.

Drug(s) Of Choice

• Chemotherapy-there are many variations of similar combination protocols, all with similar efficacy.
• High-grade lymphoma can respond to CHOP-based protocols (cyclophosphamide, doxorubicin, vincristine, prednisone/prednisolone) such as the University of Wisconsin–Madison protocol (alternating drugs in repeated sequence) or COP-based protocols (cyclophosphamide, vincristine, prednisone/prednisolone).
• Vinblastine has similar efficacy but less GI toxicity compared to vincristine.
• SCL can respond to oral chlorambucil (either low dose daily/every other day or high dose pulsed) and prednisone/prednisolone.
• Consult a veterinary oncologist for doses, schedules, and to help assess best option(s) for treatment.

Contraindications

Avoid doxorubicin in cats with preexisting renal failure as high-cumulative dosages have been demonstrated to potentially be nephrotoxic.

Precautions

• Myelosuppression secondary to chemotherapy-more in FeLV-positive cats.
• Seek advice before initiating treatment if you are unfamiliar with cytotoxic drugs. Some drugs such as vincristine and doxorubicin are vesicants and can cause tissue sloughing if leaked outside the vein.

Possible Interactions

None

Patient Monitoring

• Physical examination and CBC-before each chemotherapy treatment and 1 week after each new drug is administered, or if there are concerns about low cell counts.
• Diagnostic imaging-as necessary depending on location to assess response to therapy.

Prevention/Avoidance

Avoid exposure to or breeding FeLV-positive cats.

Possible Complications

• Leukopenia/neutropenia.
• Sepsis.
• Anorexia, vomiting, weight loss; may need imaging tests to distinguish between chemotherapy side effects and lymphoma progression.

Expected Course and Prognosis

• Depends on initial response to chemotherapy, anatomic type, FeLV status, and tumor burden.
• Median survival according to treatment (overall 50–70% response rate):
  • Prednisone alone-1.5–2 months.
  • COP/CHOP-based chemotherapy-6–9 months.
  • Doxorubicin-based and lomustine rescue therapy reported for refractory LSA.
• Median survival according to FeLV status:
  • Negative = 7 months (17.5 months if low tumor burden).
  • Positive = 3.5 months (4 months if low tumor burden).
• Median survival according to anatomic location:
  • Renal-FeLV-negative, 11.5 months; FeLV-positive, 6.5 months.
  • Nasal = 1.5–2.5 years with radiation and chemotherapy.
• Chemotherapy may not improve survival over radiation alone.
• Higher radiation doses (>32 Gy) result in longer survival.
• Mediastinal-about 10% of patients live >2 years.
• Alimentary-8 months.
• Peripheral multicentric-23.5 months.
• If localized (median remission time)-114 weeks.
• Median survival according to histology (tumor grade or subtype):
  • SCL of gastrointestinal tract with or without additional visceral involvement: 95% overall response to chlorambucil and prednisone for median survival of approximately 2 years (longer in complete vs. partial remission).
  • LGLL∼30% response for median survival 57 days.
  • Cats with Hodgkin-like lymphoma can do well for extended periods of time, even without treatment (months to years).
• Weight loss during first month of treatment of LCL associated with shorter survival.
• Clinical response after 1 cycle of COP chemotherapy associated with longer survival.

Associated Conditions

• Hypoglycemia (rare)
• Monoclonal gammopathy (rare)
• Hypercalcemia (10–15%)

Age-Related Factors

Young cats with lymphoma are generally FeLV-positive.

Zoonotic Potential

None

Pregnancy/Fertility/Breeding

Do not use chemotherapy in pregnant animals.

Synonyms

• Lymphosarcoma
• Malignant lymphoma

Abbreviations

• CNS = central nervous system
• FeLV = feline leukemia virus
• GI = gastrointestinal
• IHC = immunohistochemistry
• LCL = large cell lymphoma
• LGLL = large granular lymphocyte lymphoma
• LSA = lymphoma
• PARR = PCR (polymerase chain reaction) for antigen receptor rearrangement
• SCL = small cell lymphoma

Client Education Handout Available Online