Canine Lymphoma

• • Also Known As: Canine Lymphoma, Lymphosarcoma

  • Nature: Cancer of malignant lymphocytes. Uncontrolled clonal expansion of lymphoid cells (B-cell or T-cell).

  • Affected Tissues:

    • Primary/Secondary Lymphoid Tissues: Bone marrow, thymus, lymph nodes, spleen.

    • Extranodal Sites: Skin, intestinal tract, liver, eye, CNS, bone. Less common involvement includes heart, tonsils, pancreas.

  • Etiology (Causes): Incompletely characterized, likely multifactorial.

    • Potential Factors: Infectious viruses or bacteria, environmental contamination (phenoxyacetic acid herbicides, other chemicals), strong magnetic fields, chromosomal abnormalities, immune dysfunction.

  • Epidemiology:

    • Most common hematopoietic neoplasm in dogs.

    • Incidence: Approaching 0.1% of susceptible dogs.

    • Age: Usually middle-aged to older dogs.

    • Sex: No significant association.

    • Breeds: Some breeds at increased relative risk (Boxer, Rottweiler, Golden Retriever), but any breed can be affected.

  • Clinical Findings (Manifestations): Heterogeneous cancer with variable signs, responses, and survival.

    • Common Forms (High-Grade B-cell or T-cell):

      • Generalized, nonpainful, peripheral lymphadenopathy (80%-85% of cases). Affected nodes are 3-10x normal size, firm, initially movable, can become fixed.

    • Less Common Forms (Primarily Affecting Other Organs):

      • Alimentary Lymphoma: < 10% of cases. Affects GI tract or mesenteric lymph nodes.

        • Focal lesions: Signs of partial/complete luminal obstruction (vomiting, constipation, abdominal pain).

        • Diffuse involvement: Marked/debilitating GI disturbances (anorexia, vomiting, diarrhea), hypoproteinemia, weight loss (malabsorption/maldigestion).

      • Mediastinal Lymphoma: Small fraction of cases. Enlargement of cranial mediastinal lymph nodes, thymus, or both. Often high-grade malignant T-cell lymphoma from thymus.

        • Signs with advanced disease: Respiratory distress (pleural fluid, lung compression), cranial vena cava syndrome.

        • Associated Paraneoplastic Syndrome: Humoral hypercalcemia of malignancy (10%-40% of dogs). Leads to polyuria with secondary polydipsia. Confirmed by measuring ionized calcium, PTH, PTHrP.

      • Cutaneous Lymphoma: Most common extranodal form. Lesions appear as solitary/raised/ulcerative nodules or generalized/diffuse/scaly lesions. Often involves peripheral lymph nodes and mucocutaneous junctions.

      • Other Extranodal Sites: Clinical signs vary by site.

        • Lungs: Respiratory distress.

        • Kidneys: Renal failure.

        • Eyes: Blindness.

        • CNS: Seizures.

        • Bone: Skeletal pain, pathological fracture.

    • Systemic Constitutional Signs: Can occur with more advanced disease or substantial tumor burden/hypercalcemia.

      • Lethargy (profound).

      • Weight loss (> 10%).

      • Constitutional decline.

      • Weakness.

      • Fever.

      • Anorexia.

      • Dehydration.

      • Can become severe and life-limiting.

    • Low-Grade (Indolent) Lymphoma: Molecular variant.

      • Histopathologic Subtypes: Marginal-zone, follicular, mantle-cell, T-zone lymphomas.

      • Involvement: Most commonly spleen or lymph nodes.

      • Clinical Progression: Slow.

      • Often subclinically affected for prolonged time.

  • Lesions (Macroscopic):

    • Lymph nodes: Enlarged (3-10x), nonpainful, firm. Gray to tan coloration on transection, bulge and lose cortical-medullary demarcation.

    • Liver/Spleen: Hepatosplenomegaly, diffuse enlargement or multiple pale nodules.

    • GI tract/Mesenteric nodes (Alimentary form).

  • Diagnosis:

    • Suspicion based on generalized, nonpainful lymphadenopathy on clinical exam.

    • Methods:

      • Fine-Needle Aspiration (FNA) with Cytologic Evaluation: Highly effective and practical. Assesses proportions of lymphocytes. Key hallmark: Predominantly homogeneous population of monomorphic, medium to large lymphocytes. More challenging for small/intermediate lymphocytes.

      • Tissue Biopsy with Histologic Evaluation: Gold standard for morphological subtyping and histologic grade.

      • Immunophenotyping: Categorizes B-cell (CD79a) or T-cell (CD3) types.

      • Molecular Diagnostic Techniques: Helpful.

        • Flow Cytometry: Based on physical characteristics and surface markers (CD markers).

        • PARR Assay: Determines clonality, sensitive for confirming neoplastic origin.

  • Staging: Performed to assess extent of disease after diagnosis.

    • Requires diagnostic imaging, bone marrow assessment.

    • WHO Clinical Staging System:

      • Stage I: Single node/tissue in single organ (excluding bone marrow).

      • Stage II: Many lymph nodes in regional area (with/without tonsils).

      • Stage III: Generalized lymph node involvement.

      • Stage IV: Stage I, II, or III with liver or spleen involvement.

      • Stage V: Stage I, II, III, or IV with manifestation in blood and involvement of bone marrow or other organ systems.

      • Substages: 'a' (absence of systemic signs), 'b' (presence of systemic signs - fever, >10% weight loss, hypercalcemia).

  • Treatment: Systemic with chemotherapy is common. Primary goal is palliative.

    • Response to Treatment: Generally responsive to conventional systemic chemotherapy (initial response rate ≥ 90%). Leads to improved quality of life and overall survival time. Eventual relapse is expected in most dogs (except some indolent forms).

    • Chemotherapy Protocols:

      • High-Grade Lymphoma (Most Common):

        • Combination: Most common protocols are CHOP-based (Cyclophosphamide, Hydroxydaunorubicin/doxorubicin, Vincristine, Prednisone). L-asparaginase optional (for ill/relapsed dogs).

        • Median Survival Times (Multidrug): ~12 months (B-cell), ~6-8 months (T-cell).

        • Other Agents (Naive/Relapsing): Lomustine, mitoxantrone, rabacfosadine.

      • Single-Agent:

        • Generally less durable remission than combination protocols.

        • Doxorubicin monotherapy: Can achieve complete remission, median survival 6-8 months (lower response than CHOP). Extravasation can be catastrophic. Cumulative cardiotoxicity results in lifetime dose limit.

        • Prednisone monotherapy: Improves quality of life, induces remission (typically 1-2 months). Multidrug resistance can develop.

      • Novel Agent: Verdinexor (SINE inhibitor) - conditionally approved 2021. Response/duration appear lower than multidrug protocols. May be additional option.

      • Low-Grade (Indolent) Lymphoma: Low-intensity oral protocols (chlorambucil and prednisone) often provide prolonged survival (> 2 years).

    • Other Treatment Modalities:

      • Surgery: Effective for focal alimentary lymphoma (with combination chemotherapy). Splenectomy effective for localized/low-grade splenic involvement (potentially without chemotherapy).

      • Radiotherapy: Inclusion of half-body RT with chemotherapy might improve longterm control. Focal ionizing RT combined with chemo for mediastinal lymphoma (especially with pleural effusion/dyspnea).

      • Autologous Bone Marrow Transplant: Aggressive treatment involving intense chemoradiation and reinfusion of bone marrow cells. Available at select institutions.

    • Outcomes by Anatomical Form:

      • High-Grade Multicentric: Favorable outcomes expected.

      • Other Forms: Often more difficult and less rewarding management.

        • Alimentary (diffuse): Poor clinical responses and short survival times (< 3 months).

        • Mediastinal: Favorable survival times and good quality of life with chemo +/- focal RT.

        • Cutaneous: Control for limited time (< 3-6 months).

        • Indolent: Prolonged survival (> 2 years).

    • Prognosis Without Treatment: Dogs die or are euthanized within 4-6 weeks.

  • Key Points (Summary):

    • Most common hematopoietic tumor.

    • Diagnosis often by physical exam + cytologic evaluation of FNA of enlarged lymph nodes.

    • Most dogs respond positively to systemic chemotherapy, with improved quality of life and overall survival.

    • Heterogeneous disease; thorough diagnostic testing/categorization influences treatment/prognosis.

  • For More Information:

    • Veterinary Cancer Society

    • Canine Lymphoma Education Awareness and Research

    • Pet health content regarding malignant lymphoma in dogs.