Malignant (abnormal) lymphocytes are the source of canine lymphoma. Canine lymphoma, which is a product of the haematological (blood) system, can affect any anatomic organ where lymphocytes live or move around. When the tumour burden is high, clinical indications like lethargy, weight loss, and constitutional impairment are frequently seen in dogs with lymphoma, which most typically presents as an enlarged, non-painful, widespread lymphadenopathy.
Canine lymphoma is caused by the unchecked and pathological clonal growth of lymphoid cells with either a B-cell or T-cell immunophenotype. The bone marrow, thymus, lymph nodes, and spleen are among the organized primary and secondary lymphoid tissues that are most frequently affected by canine lymphoma. The skin, digestive tract, liver, eye, Brain, and bone are extranodal locations that lymphoma can impact in addition to these lymphoid-rich organs. The most prevalent haematological neoplasm in canines is lymphoma, with a frequency of around 0.1% in susceptible canines.
Malignant lymphoma is common, but the mechanisms that lead to it are still poorly understood. However, cutting-edge genetic research has shown that canine lymphoma may be molecularly identified and divided into distinct groups that correlate with biological aggressiveness. Epstein-Barr virus-like retrovirus infection, phenoxy acetic acid pesticide contamination of the environment, exposure to magnetic fields, chromosomal abnormalities, and immunological dysfunction are a few possible reasons.
What are the Clinical Signs of Canine Lymphoma?
Canine lymphoma is complicated cancer with a range of clinical symptoms, therapeutic responses, and prognoses. A number of tumour and host characteristics, including anatomic involvement, disease severity, morphologic subtype, host constitution, and immunological competency, all have an impact on the canine lymphoma's heterogeneity.
High-grade B- or T-cell variations are the most prevalent clinical forms of lymphoma in dogs, and they often present as widespread, painless peripheral lymphadenopathy in 80%–85% of all identified cases. Some organ systems, such as the gastrointestinal tract, skin, mediastinum, and other extranodal locations, are more frequently affected by lymphoma than others. Systemic constitutional indications, such as extreme lethargy, weakness, fever, anorexia, and dehydration, may become visible in dogs with considerable tumour load.
The most prevalent extranodal type of lymphoma, cutaneous lymphoma, affects the skin. Cutaneous lymphomas might present as single, elevated, ulcerative nodules or widespread, diffuse, scaly lesions. Mucocutaneous connections and peripheral lymph nodes are frequently affected. Other extranodal lymphoma clinical signs may include respiratory distress (lungs), renal failure (kidneys), blindness (eyes), seizures (CNS), vomiting, constipation, abdominal pain, anorexia, diarrhoea, hypoproteinemia, and weight loss due to maldigestion and malabsorption (alimentary/intestinal lymphoma), as well as skeletal pain or pathologic fracture (bone).
Low-grade or indolent lymphoma is a molecular subtype of canine lymphoma, despite the fact that high-grade lymphoma of either B or T cell origin is more frequently identified in dogs. The histopathologic subtypes of indolent lymphoma include marginal zone, follicular, mantle cell, and T-zone lymphomas. Dogs commonly experience protracted asymptomatic periods despite treatment for indolent lymphomas, which advance slowly.
Lesions of Canine Lymphoma
Commonly, peripheral and various internal lymph nodes are 3–10 times normal size (multicentric form) and nonpainful on digital palpation. Affected nodes are initially freely movable, but firm. However, with disease progression, lymph nodes can become fixed and compress surrounding normal structures, leading to discomfort or functional compromise. Histologically, effaced lymph nodes are grey-tan in colouration, and when transected will bulge and have a loss of cortical-medullary demarcation.
Diagnosis of Canine Lymphoma
A comprehensive medical assessment should raise the possibility of multicentric lymphoma in the presence of broad, painless lymphadenopathy. Fine-needle aspirate cytology or lymph node biopsy of the afflicted lymph nodes is one of the relevant diagnostic techniques that should be used to rule out other infectious and inflammatory illnesses.
Lymph nodes and tissue aspirates can be analyzed cytologically to detect a monomorphic population of lymphoid cells that can be big (lymphoblastic), intermediate, or tiny (lymphocytic). Despite the ease of diagnosis, traditional cytology is unable to distinguish between the various types of lymphomas, such as diffuse from follicular, cleaved from non-cleaved, and histologic grade (high versus low). B- and T-cell lymphomas can be distinguished using lineage-specific antibodies, and specialized cytology can also offer some insight into prognosis based on immunophenotype.
Rarely, other molecular methods like flow cytometry and PCR for antigen receptor rearrangements (PARR) can offer supplementary data to support a conclusive diagnosis when a diagnosis remains unclear.
Treatment of Canine Lymphoma
Systemic chemotherapy is frequently necessary for the treatment of canine lymphoma, with most dogs getting this type of therapy experiencing objective responses, along with corresponding improvements in quality of life and lengthened survival durations. Despite the extraordinarily high (90% or higher) initial response rates to systemic chemotherapies, the vast majority of dogs eventually relapse with an illness that progressively grows resistant to further treatments. Since only a small percentage of dogs receive a cure from conventional medicines, palliative care is the main focus of contemporary treatments.
Vincristine, doxorubicin, cyclophosphamide, l-asparaginase, and prednisone are the most frequently utilized chemotherapeutic drugs in combination treatments. The dosage, frequency, and length of each treatment protocol vary; and so are the benefits and drawbacks of each treatment plan.
For dogs with B-cell lymphoma, the anticipated survival time with combination chemotherapy is 12 months, however, for dogs with T-cell lymphoma, the anticipated survival periods are frequently in the range of 6 months.
The successful care of various anatomic forms of lymphoma is frequently more challenging and less gratifying, e.g., alimentary lymphoma has poor clinical responses and short survival periods (i.e., 3 months), despite the favourable outcomes anticipated in treating high-grade multicentric lymphoma.
Dogs with low-grade, indolent lymphomas typically have acceptable clinical prognoses. Longer survival times (>2 years) are frequently achieved with the implementation of low-intensity oral chemotherapy protocols (chlorambucil and prednisone), and in some dogs with localized and low-grade disease (e.g., splenic involvement), a splenectomy can be a successful and long-lasting treatment option without the need for adjuvant chemotherapy administration.
References
Fan, T. M. (2003). Lymphoma updates. Veterinary Clinics: Small Animal Practice, 33(3), 455-471.
Benjamin S E, Sorenmo K U, Krick E L, Salah P, Walsh K A et al (2021) Response-based modification of CHOP chemotherapy for canine B-cell lymphoma. Vet Comp Oncol PubMed.
Hughes K L, Ehrhart E J, Rout E D, Harris L J, Fernandez M (2021) Diffuse Small B-Cell Lymphoma: A High-Grade Malignancy. Vet Pathol PubMed.
Cawley J R, Wright Z M, Meleo K, Post G S, Clifford C A (2020) Concurrent use of rabacfosadine and L-asparaginase for relapsed or refractory multicentric lymphoma in dogs. J Vet Intern Med 34(2), 882-889 PubMed.
Harris L J, Rout E D, Labadie J D, Avery P R, Fernandez M et al (2020) Clinical features of canine nodal T-cell lymphomas classified as CD8+ or CD4-CD8- by flow cytometry. Vet Comp Oncol 18(3), 416-427 PubMed.
Boyé P, Floch F, Serres F, Geeraert K, Clerson P (2019) Evaluation of serum thymidine kinase 1 activity as a biomarker for treatment effectiveness and prediction of relapse in dogs with non-Hodgkin lymphoma. J Vet Intern Med 33(4), 1728-1739 PubMed.
Chalfon C, Martini V, Comazzi S, Aresu L, Stefanello D et al (2019) Minimal residual disease in lymph nodes after achievement of complete remission predicts time to relapse in dogs with large B-cell lymphoma. Vet Comp Oncol 17(2), 139-146 PubMed.
Al-Nadaf S, Rebhun R B, Curran K M, Venable R O, Skorupski K A (2018) Retrospective analysis of doxorubicin and prednisone as first-line therapy for canine B-cell lymphoma. BMC Vet Res 14(1), 356 PubMed.
Batschinski K, Dervisis N, Kitchell B, Newman R, Erfourth T (2018) Combination of Bleomycin and Cytosine Arabinoside Chemotherapy for Relapsed Canine Lymphoma. J Am Anim Hosp Assoc 54(3), 150-155 PubMed.
Vail D M, Pinkerton M, Young K M (2020) Hematopoietic tumours. In: Withrow & MacEwen’s Small Animal Clinical Oncology. 6th edn. Saunders pp 688-711.
Kansas State University modified UW-Madison lymphoma protocol for dogs Lymphoma: chemotherapy protocols.