Dogs with Multicentric Lymphoma

Clinical Staging, Oxidative Markers, and Interleukin Expression at the Time of Diagnosis

Resumo

Background: Lymphoma is one of the most prevalent malignant neoplasms in dogs and may occur in various anatomical locations. The multicentric form is the most common, accounting for approximately 75% of canine lymphoma cases. Given the high incidence and clinical significance of this disease, this study aimed to evaluate clinical staging, oxidative profile, and interleukin expression in dogs diagnosed with multicentric lymphoma at the time of diagnosis.

Materials, Methods & Results: Dogs with cytological diagnoses of multicentric lymphoma, without prior treatment or concurrent diseases, were included. Eleven dogs were evaluated through standardized oncological examination, including lymph node measurement, imaging exams for clinical staging, hematological analysis, oxidative stress biomarkers, and gene expression of IL-6, IL-10, and VEGF in polymorphonuclear (PMN) and peripheral blood mononuclear cells (PBMC). Results were obtained at diagnosis, before treatment initiation. Statistical analysis included absolute and relative frequencies for qualitative variables and means and standard deviations for quantitative variables. Most animals were classified in advanced stages, with 72.7% in stage IV and 27.3% in stage V, and all presented generalized lymphadenomegaly. Substage b was observed in 54.5% of patients, with clinical signs including hyporexia, fever, respiratory distress, and hemorrhagic manifestations. Hematological alterations were detected in 90.9% of cases, including anemia and thrombocytopenia, with thrombocytopenia significantly associated with clinical signs (P < 0.05), suggesting prognostic relevance. Leukogram findings were variable and nonspecific, including leukocytosis, leukopenia, neutrophilia, and lymphocyte alterations. IL-6 expression was low in both PBMC and PMN, whereas IL-10 was more frequently expressed in PMN. VEGF showed high expression, particularly in PMN (100%) and PBMC (77.8%), suggesting an important role in tumor angiogenesis and progression. Oxidative stress analysis demonstrated alterations in TBARS, reactive oxygen species (ROS), catalase, glutathione S-transferase (GST), and myeloperoxidase, indicating disruption of redox homeostasis at diagnosis. It was concluded that multicentric lymphoma is a systemic disease that disrupts body homeostasis and directly impacts prognosis. Advanced staging (IV-V), hematological alterations, including thrombocytopenia, and high VEGF expression at diagnosis were associated with a poorer prognosis.

Discussion: The findings reinforce that multicentric lymphoma is a systemic disease frequently diagnosed at advanced stages, contributing to severe clinical presentation and unfavorable prognosis. The high frequency of stages IV and V reflects both aggressive biological behavior and the difficulty of early detection in clinical practice. Hematological alterations, particularly thrombocytopenia, were associated with clinical manifestations and may serve as accessible prognostic indicators. The low IL-6 expression may be related to the predominance of B-cell lymphomas, while elevated VEGF expression supports its role in angiogenesis, tumor maintenance, and disease progression, potentially being associated with worse clinical outcomes. Oxidative stress markers highlight an imbalance between pro-oxidant and antioxidant mechanisms, contributing to tumor development and systemic impairment. Despite limitations such as small sample size and absence of immunophenotyping, the integration of clinical, hematological, oxidative, and molecular findings provides a broader understanding of the pathophysiology of canine multicentric lymphoma and may contribute to improving prognostic evaluation and therapeutic approaches.

Keywords: neoplasia, cancer, biomarkers, oxidative status.