Most common hemopoietic neoplasm, 8-10% of all canine malignant neoplasms.
Forms: multicentric, thymic, alimentary, cutaneous, CNS, hepatic, renal and others.
Signs : depend on form, eg malaise, polydipsia, polyuria, respiratory distress, vomiting, diarrhea, constipation. Multicentric usually presents feeling well and owners notice 'lumps under jaw'.
Diagnosis : fine needle aspirate and cytology. Biopsy rarely needed.
Treatment : cytotoxic drugs.
Prognosis : poor if no treatment.
Presenting signs
Marked lymphadenopathy (multicentric lymphoma).
Dyspnea/cough (thymic lymphoma).
Vomiting/diarrhea (alimentary lymphoma).
Polydipsia/polyuria secondary to hypercalcemia (multicentric thymic lymphoma, may be any form).
Hepatosplenomegaly (multicentric lymphoma).
Acute presentation
Respiratory distress due to pleural effusion (thymic lymphoma).
Malignant proliferation of lymphoid cells arising in any area containing lymphoid tissue focal or diffuse masses in intestine, skin, thymus or lymph nodes may progress to extranodal sites, eg liver, spleen, bone marrow.
Can be due to malignant proliferation of B or T cell lines.
75% are B cell origin.
T cell tumors have a worse prognosis and poorer survival than B cell tumors.
All T cell tumors should be treated as highly malignant and carry a poor prognosis.
Paraneoplastic effects, eg hypercalcemia , immune-mediated thrombocytopenia and anemia.
Development of 'masses' (usually enlarged lymph nodes).
Lethargy.
Polyuria/polydypsia.
Respiratory distress.
Vomiting.
Diarrhea.
Client history
Often asymptomatic apart from lymphadenopathy.
Multicentric
Depression.
Gross lymphadenopathy.
Thymic
Poor exercise tolerance.
Respiratory distress.
Clinical signs
Gross enlargement of one or more lymph node +/- hepatosplenomegaly (multicentric).
Pleural effusion (thymic).
Palpable abdominal mass (alimentary) or generalized thickened intestinal loops.
Diagnostic investigation
Histopathology
Lymph node : fine-needle aspirate is cheap, quick, simple.
Monomorphic population of large neoplastic lymphoblasts with prominent and multiple nuclei .
Immunological identification of cell markers allow differentiation of B and T cells.
Lymph node biopsy needed with small cell lymphomas. Excisional biopsy recommended because wedge/Tru-cut biopsies may be extremely misleading.
Of any mass identified or intestine in intestinal disease.
Demonstration of malignant lymphoid cells by the cytological or histological examination of affected tissues.
Hematology
Essential if multicentric form to indicate any bone marrow involvement.
May see circulating lymphoblasts . Provides values for assessing possible cytopenic effects of therapeutic drugs.
Biochemistry
Multicentric form : indicators of renal and hepatic involvement .
Lymphoma may result in hypercalcemia and serum calcium (or preferably ionized calcium ) should be measured. Hypercalcemia is a poor prognostic indicator.
Radiography
Large anterior mediastinal mass (thymic), pleural effusion (thymic), or intestinal mass (alimentary) or cardiac changes .
Enlargement of intrathoracic or intra-abdominal lymph nodes , liver, spleen.
Pulmonary involvement appears as a diffuse interstitial pattern.
Contrast radiography
Barium meal may be necessary to show intestinal involvement .
Cytopathology
Bone marrow aspirate indicated if hematological abnormalities identified or to prognosticate. >50% marrow involvement carries a worse prognosis yet may not show CBC changes.
2-D Ultrasonosgraphy
May show enlarged mediastinal or abdominal lymph nodes .
Diffuse hepatic or splenic infiltration will show as mixed echogenicity.
Ultrasound is sensitive for thickening of intestines and identification of focal masses, enlarged mesenteric lymph nodes.
Confirmation of diagnosis Discriminatory diagnostic features
Radiography.
Definitive diagnostic features
Cytology or histopathology.
Gross autopsy findings
Multicentric form : gross lymphadenopathy involving one or more nodes +/- hepato-splenomegaly.
Thymic form : anterior mediastinal mass +/- pleural effusion.
Alimentary form : discrete mass or diffuse intestinal thickening with local lymph node enlargement.
See chemotherapy protocols for alternative regimes.
Different regimes documented - cyclophosphamide , vincristine , prednisolone , asparaginase, doxorubicin often employed.
Induction protocol for 8 weeks:
Cyclophosphamide (50 mg/m2 PO every 48 hours) - best given early morning.
Vincristine (0.5 mg/m2 IV every 7 days). Use catheter to avoid perivascular irritation and sloughing.
Prednisolone (40 mg/m2 PO daily for 7 days then 20 mg/m2 PO every 48 hours).
Best remission rates (85-90%) and survival times (median=12 months; 25% alive at 2 years) are attained with rotating, multidrug therapy which includes doxorubicin.
Surgery
Excise discrete alimentary mass, if obstruction is present, followed by chemotherapy. Response rates and survival times for alimentary are extremely poor.
Corticosteroids : use alone useful short-term regression if chemotherapy not possible. If hoping to initiate chemotherapeutic protocol at later date, significantly lower response rates and survival times if corticosteroids used previously. Median survival on prednisone alone (2 mg/kg SID) is 11 weeks.
Monitoring
Hematology: to monitor cytopenic effects of drugs.
Cyclophosphamide may cause sterile hemorrhagic cystitis.
1. If disease in full remission: continue induction protocol treatment but on alternate week basis for further 4 months. Then one week in 3. Then 1 week in 4.
2. At 6 months may be prudent to change from cyclophosphamide to either melphalan or chlorambucil (5-10 mg/m2 PO every 48 hours) due to potential risk of sterile hemorrhagic cystitis.
Rescue protocol
Majority of cases relapse due to drug resistance development by tumor - rescue treatment includes:
Return to original induction therapy.
Modification of existing treatment - change from vincristine to vinblastine (2 mg/m2 IV every 7 days) - additional drugs, eg L-asparaginase (10,000 iu/m2 SQ every 1-4 weeks).
Change treatment entirely - probably most effective option is doxorubicin (30 mg/m2 IV every 3 weeks).
If it has not been previously administered, do not exceed 180-240 mg/m2 cumulative, life dose or cardiac damage and failure will ensue. Must be given in a perfectly placed IV catheter or severe tissue necrosis will result. Give slowly (0.5 ml/min) to monitor for allergic reactions
Monitoring
Blood cell counts.
Neutrophil count before any chemotherapy must be >2500 cells/ml.
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Other sources of information
Kansas State University modified UW-Madison lymphoma protocol for dogs.
Vetstream contributor(s)
Dr Laura Garrett DVM DipACVIM , School of Veterinary Medicine, Kansas State University, Manhattan, KS 66506-5606, USA.
focal or diffuse masses in intestine, skin, thymus or lymph nodes 
Excisional biopsy recommended because wedge/Tru-cut biopsies may be extremely misleading.
If hoping to initiate chemotherapeutic protocol at later date, significantly lower response rates and survival times if corticosteroids used previously. Median survival on prednisone alone (2 mg/kg SID) is 11 weeks.