Disease overview and who is affected
Merck defines canine lymphoma as uncontrolled clonal expansion of lymphoid cells of B-cell or T-cell type. The disease usually involves bone marrow, thymus, lymph nodes and spleen, and it can also arise in skin, gut, liver, eye, central nervous system and bone [1]. Incidence estimates differ by source: about 20 per 100,000 dogs in one review [3], and an estimated annual incidence of 25 per 100,000 in a Blood Advances review [4].
Merck reports that middle-aged to older dogs are typically affected, with no significant sex association. Boxers, Rottweilers and Golden Retrievers are named as examples of breeds at increased relative risk, though any breed can develop the disease [1]. The Blood Advances authors list a longer set of predisposed breeds and report that genome-wide association studies in golden retrievers identified candidate genes [4]. Merck describes the cause as incompletely characterized and likely multifactorial [1].
The 2025 Animals review reports that B-cell tumors account for 60% to 80% of canine lymphomas and T-cell tumors for 10% to 38% [2]. Diffuse large B-cell lymphoma (DLBCL) is the most common subtype, at about 40% of all canine lymphomas, according to the Blood Advances review [4].
Clinical presentation
Affected peripheral and internal nodes are often 3 to 10 times normal size, firm, and freely movable early in the disease, per Merck [1]. Merck reports that dogs with a heavy tumor burden or paraneoplastic hypercalcemia can show severe lethargy, weakness, fever, anorexia and dehydration [1].
Less common anatomic forms present differently. Merck reports alimentary lymphoma in fewer than 10% of cases, with vomiting, diarrhea, weight loss and protein loss when the gut is diffusely involved. It describes mediastinal lymphoma arising from the thymus as predominantly high-grade T-cell, and as causing respiratory distress from pleural fluid or compression in advanced disease [1]. Humoral hypercalcemia of malignancy occurs in 10% to 40% of dogs with lymphoma, according to Merck, and can drive polyuria and polydipsia [1]. The Animals review describes hypercalcemia as almost exclusively associated with T-cell lymphoma [2]. It reports anemia prevalence of 30% to 77% and links anemia to a worse prognosis [2].
Diagnosis
Merck states that generalized, nonpainful lymphadenopathy "should raise suspicion for multicentric lymphoma" [1]. Merck describes fine-needle aspiration with cytology as a highly effective and practical method for identifying monomorphic populations of lymphoid cells [1]. The Animals review describes it as a rapid, sensitive and minimally invasive way to diagnose high-grade disease [2]. The typical cytologic finding is a fairly uniform population of medium to large lymphocytes [1].
There are known pitfalls. Merck notes that lymphomas made up of small or intermediate cells are harder to diagnose on cytology and may need biopsy or molecular testing [1]. The Animals review reports that cytology may be inadequate for low-grade disease or atypical lymphoid proliferations [2]. The Blood Advances authors note that accurate classification requires assessment of tumor architecture. In practice, they say, node biopsy is kept for equivocal cases [4].
Tests used to confirm and characterize the tumor, as described in the sources:
- Histology with immunohistochemistry, using CD79a for B cells and CD3 for T cells [1].
- Flow cytometry, which Merck says can give a definitive diagnosis from cell size, complexity and surface markers [1].
- PARR (PCR for antigen receptor rearrangement), which tests whether lymphocytes are clonal [1][2].
- A complete blood count with platelets and a biochemistry profile that includes total or ionized calcium [2].
Staging and classification
Merck and the Blood Advances review describe the WHO clinical staging system as the routine scheme [1][4]. Merck's wording is given below.
| Stage | WHO criteria as quoted by Merck [1] |
|---|
| I | "Involvement limited to a single node or lymphoid tissue in a single organ (excluding bone marrow)" |
| II | "Involvement of many lymph nodes in a regional area (with or without involvement of the tonsils)" |
| III | "Generalized lymph node involvement" |
| IV | "Stage I, II, or III with liver or spleen involvement" |
| V | "Stage I, II, III, or IV with manifestation in the blood and involvement of bone marrow or other organ systems" |
Substage a means no systemic signs, and substage b means systemic signs are present. Merck lists fever, more than 10% weight loss, or hypercalcemia as examples [1].
For routine cases, the Animals review reports that imaging is mainly limited to thoracic radiographs, because stage III and stage IV carry no prognostic distinction. Cranial mediastinal lymphadenopathy does carry prognostic weight [2]. The Blood Advances authors add a caveat. Dogs with T-zone lymphoma, an indolent (slow-growing) subtype, often have circulating lymphocytosis, which places them in stage V, but they still survive a long time. For that reason, stage "should be taken in the context of WHO disease classification" [4].
According to Merck, indolent subtypes include marginal-zone, follicular, mantle-cell and T-zone lymphomas, and these progress slowly [1].
Treatment
Merck describes the primary goal of treatment as palliative. It notes that "only a small fraction of dogs achieve a cure with conventional treatment options" [1]. For high-grade disease, the most common combination is CHOP: cyclophosphamide, doxorubicin, vincristine and prednisone. Merck describes L-asparaginase as optional and often reserved for clinically ill dogs or relapse [1]. The Animals review describes an intensive induction phase aimed at complete remission, followed by a less-intensive maintenance phase. It also reports that long-term maintenance chemotherapy remains questionable [2].
Other approaches described in the sources:
- Doxorubicin alone can achieve complete remission with median survival of 6 to 8 months, at lower response rates than CHOP, according to Merck. Merck also warns that extravasation can be catastrophic and that cumulative cardiotoxicity sets a lifetime dose limit [1].
- Prednisone alone can improve quality of life and induce remission, typically for 1 to 2 months, but Merck notes multidrug resistance can develop [1].
- For indolent lymphoma, Merck reports that chlorambucil and prednisone often give survival beyond 2 years [1]. The Blood Advances authors describe active surveillance as a common initial approach [4].
- For T-cell disease, the Blood Advances authors report some evidence favoring more alkylator-heavy protocols. They note that randomized trials have not been done [4].
- Rabacfosadine is the first fully FDA-approved lymphoma treatment for dogs, per the Blood Advances review [4]. In a study of 59 dogs, rabacfosadine alternated with doxorubicin produced a 93% overall response, with pulmonary fibrosis in six dogs [2].
- Merck reports that verdinexor received conditional FDA approval, with lower response rates and durations than multidrug chemotherapy and limited experience so far [1].
For relapse, the Animals review reports rescue response rates of 40% to 90%, with median durations of 1.5 to 2.5 months [2]. The 2023 review identified 27 groups with relapsed disease. In the 23 groups that reported an overall response rate, the median was 43% [3].
Prognosis and reported outcomes
Reported figures vary across the sources. Merck cites median survival of about 12 months for B-cell and 6 to 8 months for T-cell lymphoma with multidrug protocols [1]. The Blood Advances review reports median survival of 10 to 13 months with CHOP-based protocols. It gives relapse at 52 days versus 160 days, and survival at 150 days versus 330 days, for T-cell versus B-cell disease [4]. The Animals review reports that 20% to 25% of dogs on CHOP-based protocols survive two years [2].
The 2023 Veterinary Sciences review by Bennett and colleagues summarized 43 papers on multicentric or nodal lymphoma treated with CHOP-like protocols. Across those groups, it found a median complete remission rate of 77%, a median overall response rate of 91%, and median survival times ranging from 73 to 622 days [3]. The authors reported inconsistent response definitions and remission start dates across studies, and a lack of standardized reporting. They argued that "novel approaches for lymphoma therapy will be required to substantively improve outcomes" [3].
On prognostic factors, the Animals review names immunophenotype and WHO substage as the two most reliable [2]. The Bennett review looked only at multivariate studies. In that set, immunophenotype was prognostic for remission in 52% of papers, and substage was prognostic for survival in 35.1% [3]. Response to treatment was prognostic for survival in 88.9% of the papers that included it [3].
Client discussion points
The sources supply several facts that bear directly on the owner conversation. Without treatment, survival is 4 to 6 weeks [1]. Most dogs respond to chemotherapy, but relapse is expected in most [1]. Fewer than 10% of cases are curable, per the Animals review [2]. The 2023 review found wide variability in published outcomes and in study methods [3]. The Animals review names immunophenotype and WHO substage as the two most reliable prognostic factors [2].
