Overview

Canine lymphoma is a malignant proliferation of lymphocytes affecting lymphoid tissue throughout the body. The multicentric form (generalized peripheral lymphadenopathy) accounts for 80-85% of cases in dogs. Other forms include mediastinal (thymic), alimentary, cutaneous, and extranodal (renal, CNS, ocular). Lymphoma is classified by World Health Organization (WHO) stage (I-V) based on extent of disease and substages (a = asymptomatic, b = symptomatic). Fine needle aspiration of an enlarged lymph node is the first diagnostic step — cytology is highly diagnostic for lymphoma. Histopathology and immunophenotyping (CD3 for T-cell, CD79a/Pax5 for B-cell) on biopsy samples refine diagnosis, guide prognosis, and direct treatment. The most common multi-agent chemotherapy protocol is CHOP (cyclophosphamide, doxorubicin/hydroxydaunorubicin, oncovin/vincristine, prednisone). Median survival with CHOP for multicentric lymphoma is 12-14 months; ~25% of dogs survive >2 years.

WHO Staging (Multicentric Lymphoma)

Stage Extent of Disease
Stage I Single lymph node involvement
Stage II Regional lymph node involvement (multiple nodes, single region)
Stage III Generalized lymph node involvement (all peripheral nodes)
Stage IV Stage III + thymic and/or splenic involvement
Stage V Bone marrow and/or blood involvement (+ any of the above)

Substage a: No clinical signs · Substage b: Systemic signs present (weight loss, lethargy, fever, anorexia)

Common Clinical Signs

Painless, firm peripheral lymphadenopathy (submandibular, prescapular, popliteal, prefemoral) Lethargy / exercise intolerance Weight loss (despite normal appetite) Anorexia Mediastinal form: dyspnea, cough, non-pruritic cough with retching Alimentary form: vomiting, diarrhea, melena Cutaneous form: solitary or generalized nodular skin lesions Renal lymphoma: polyuria/polydipsia Neurologic form: paresis, seizures

Diagnostic Approach

Diagnostic Test Expected Findings
Fine Needle Aspiration (FNA) Cytology Lymphoid cells at high cellularity with large lymphocytes, mitotic figures, and "lymphoglandular bodies". Cytology of enlarged peripheral lymph nodes is diagnostic in ~95% of multicentric lymphoma cases. Minimally invasive — always start here.
Biopsy with Immunophenotyping Tissue architecture preserved for WHO classification. IHC: CD3+ = T-cell lymphoma (worse prognosis in most forms). CD79a/Pax5+ = B-cell lymphoma. B-cell lymphoma typically has better response to CHOP and longer survival.
CBC May be normal in early stages. Anemia (non-regenerative or regenerative), thrombocytopenia, lymphocytosis with atypical lymphocytes in circulating blood (Stage V). Leukemia may be present.
Serum Chemistry Hypercalcemia of malignancy (especially T-cell mediastinal lymphoma) — elevated ionized calcium. May see elevated LDH (proliferation marker). Hypoalbuminemia in some cases with GI involvement.
Abdominal Ultrasound Hypoechoic hepatomegaly and splenomegaly. Loss of corticomedullary distinction in nodes. Mesenteric lymphadenopathy. Helps stage (III vs IV) and identify alimentary/substage involvement.
Thoracic Radiographs Mediastinal lymphadenopathy (mediastinal form), pulmonary metastases. 3-view thoracic series recommended for staging.
Bone Marrow Aspiration Required if hematologic abnormalities present, to confirm or rule out Stage V. Lymphoid blasts in marrow = Stage V. Also helps differentiate Stage V lymphoma from acute lymphoid leukemia (ALL).

Differential Diagnoses

  • Reactive lymphadenopathy — Infection (pyoderma, dental disease, systemic fungal), immune-mediated disease (IMHA, SRMA), vaccination reaction. Lymph nodes are firm but often softer in reactive hyperplasia. Cytology: mixed lymphoid population, no lymphoma criteria.
  • Metastatic neoplasia — Other primary cancers metastasizing to lymph nodes. Melanoma, carcinoma. Cytology shows epithelial cells with malignant criteria — distinct from lymphoid origin of lymphoma.
  • Hemangiosarcoma (splenic masses) — Splenomegaly without lymphadenopathy. Hemorrhagic abdominal effusion common. Cytology of fluid or masses differentiates.
  • Leishmaniasis — Geographic differential (Mediterranean). Lymphadenopathy + splenomegaly. Cytology shows Leishmania amastigotes inside macrophages. Check travel history.
  • Ehrlichiosis / Anaplasmosis — Tick-borne. Lymphadenopathy, thrombocytopenia. Serology or PCR differentiates. Usually acute onset with fever history.

Treatment & Prognosis by Immunophenotype

The standard of care for multicentric lymphoma is the CHOP protocol (25-week multi-agent chemotherapy): vincristine, cyclophosphamide, and doxorubicin (hydroxydaunorubicin) on a rotating weekly/bi-weekly schedule with continuous prednisone. B-cell lymphoma patients: median survival 12-16 months, ~30% reach 2-year survival. T-cell lymphoma patients: median survival 6-8 months, lower remission rates. Single-agent COP protocol is a lower-cost alternative with slightly shorter survival. Steroid-only protocols offer palliative benefit but survival is much shorter (median 2-3 months). Rescue protocols (lomustine, doxorubicin if not used initially, L-asparaginase) are used when primary remission fails.