Canine lymphoma is a major clinical burden, accounting for roughly 7 to 24 percent of all cancers in dogs, with T-cell tumors representing 10 to 38 percent of high-grade, multicentric cases. The standard of care for decades has been CHOP chemotherapy, a multi-drug combination of vincristine, cyclophosphamide, doxorubicin, and prednisone. While CHOP achieves an overall response rate of about 96 percent in T-cell lymphoma, dogs respond less well and relapse sooner than their B-cell counterparts, with a median progression-free survival of just 133 days and a median survival time of around 235 days. The T-cell immunophenotype itself is a recognized negative prognostic indicator, making protocol selection a pressing clinical question.

The biological rationale for turning to alkylating agents lies in the mechanics of drug resistance. T-cell lymphomas in both humans and dogs carry more chromosomal aberrations than B-cell neoplasms, suggesting a greater capacity for acquired drug resistance. Overexpression of ATP-binding cassette transporter proteins, which pump drugs such as doxorubicin and vincristine out of tumor cells, has been documented in canine lymphoma. Crucially, alkylating agents are not substrates for these efflux pumps and show no cross-resistance with them, which has driven interest in alkylator-heavy combinations like LOPP, comprising lomustine, vincristine, procarbazine, and prednisone, and MOPP, which substitutes mechlorethamine for lomustine.

Historically, both protocols have reported response rates comparable to CHOP when used as first-line therapy. LOPP has been associated with overall response rates of 94 to 97 percent and complete response rates of 83 to 90 percent, while MOPP has shown a 98 percent overall response rate and a 78 percent complete response rate in earlier reports. Median survival times have ranged from about 9 months for MOPP to 10 to 17 months for LOPP, both figures generally exceeding the roughly 8 months historically attributed to CHOP in T-cell disease. Until now, however, no study had directly compared the two protocols head to head in dogs with T-cell or hypercalcemic lymphoma, leaving the choice largely to clinician experience, practicality, owner preference, and cost.

The new study included dogs with confirmed intermediate to large cell T-cell lymphoma of multicentric distribution, excluding T-zone lymphoma and cases with gastrointestinal or cutaneous involvement because of their distinct prognoses. Thirty-seven dogs received LOPP and 34 received MOPP, each given on a 28-day cycle for up to six cycles. Diagnosis was established through cytology, histopathology, flow cytometry, and polymerase chain reaction for antigen receptor rearrangement, with immunophenotyping completed in every dog. Flow cytometry, performed in nearly 86 percent of cases, revealed that the dominant immunophenotype was CD4-positive CD8-negative, present in 49 of the 71 dogs. More than half of the dogs were hypercalcemic at diagnosis, and among those undergoing thoracic imaging, just over half harbored a cranial mediastinal mass.

The headline results favored LOPP decisively on two of the four key endpoints. Complete response was achieved in 86 percent of LOPP-treated dogs versus 65 percent of MOPP-treated dogs, a statistically significant difference. Median progression-free survival was 208 days under LOPP compared with 102 days under MOPP, also significant, and multivariable analysis confirmed that LOPP reduced the risk of progression or death by more than two-thirds. Overall response rates, at 97 percent versus 91 percent, did not differ significantly, and median overall survival times were statistically indistinguishable at 298 days for LOPP and 231 days for MOPP. The authors suggest that the survival equivalence likely reflects the wide variety of rescue chemotherapies used after relapse and differing decisions about when to discontinue treatment.

Toxicity profiles were broadly similar between the groups, though the details matter for practicing clinicians. Grade III or higher adverse events occurred in 45.9 percent of LOPP-treated dogs versus 20.6 percent of MOPP-treated dogs, driven largely by myelosuppression, which affected 35.1 percent of LOPP patients. Febrile neutropenia was more frequent with LOPP at 8.1 percent compared with 2.9 percent for MOPP, consistent with lomustine’s dose-limiting toxicity being neutropenia. Hospitalization was required in 18.9 percent of LOPP dogs and 11.8 percent of MOPP dogs, and notably, prophylactic antibiotics, given to more than 62 percent of LOPP patients, did not appear to prevent febrile neutropenia. Treatment delays and dose reductions were common in both arms, and the authors caution that the lower-than-historical doses used in this cohort may explain why survival figures fell short of some earlier LOPP reports.

The study also yielded prognostic insights specific to T-cell disease. Dogs with a cranial mediastinal mass and those with the CD4-positive CD8-negative immunophenotype were more likely to achieve complete remission, an intriguing reversal of the mediastinal mass’s usual status as a negative prognostic marker in mixed-immunophenotype lymphoma populations. Achieving any response, and especially a complete response, strongly prolonged progression-free survival, and complete response also extended overall survival on univariate analysis. Stage V disease emerged as an independent negative prognostic factor for progression-free survival in multivariable analysis. Notably, more MOPP-treated dogs had stage V disease, 47 percent versus 22 percent, which the authors acknowledge could partly account for that protocol’s weaker performance, alongside schedule modifications and the possibility of type II error.

Perhaps the most encouraging finding is the existence of a long-surviving subgroup. A quarter of the dogs treated with these alkylator-rich protocols were still alive at 487 days with LOPP and 389 days with MOPP, echoing historical reports of 25 to 35 percent two-year survival with LOPP and a quarter of MOPP-treated dogs alive at 939 days. Such prolonged survival has not been reported with CHOP in T-cell lymphoma, and identifying which dogs belong to this favorable subset is now a priority. The authors conclude that clinicians considering alkylator-rich multi-drug chemotherapy should favor LOPP over MOPP for its higher complete response rate and longer progression-free survival, while stressing that prospective randomized trials are needed to confirm the result. For now, the median outlook for dogs with multicentric T-cell lymphoma remains a guarded 8 to 9 months, but these data sharpen the treatment algorithm and offer a concrete reason for hope in a meaningful fraction of patients.

Subject of Research: Comparison of LOPP and MOPP alkylator-based chemotherapy protocols for first-line treatment of canine multicentric T-cell lymphoma

Article Title: Retrospective comparison of MOPP versus LOPP for first-line treatment of canine multicentric T-cell lymphoma

Article References: Lounsberry, C., Lindley, S. S., Bergman, N., LaRue, M., Haas-Linden, S., & Smith, A. A. (2025). Retrospective comparison of MOPP versus LOPP for first-line treatment of canine multicentric T-cell lymphoma. Veterinary Oncology, 2(1), Article 22. https://doi.org/10.1186/s44356-025-00039-y

Image Credits: AI Generated

DOI: 10.1186/s44356-025-00039-y

Keywords: canine lymphoma, T-cell lymphoma, LOPP, MOPP, chemotherapy, veterinary oncology, lomustine, mechlorethamine, alkylating agents, complete response, progression-free survival, drug resistance

Canine diffuse large B-cell lymphoma is far more than a veterinary curiosity. It accounts for roughly 50 to 60 percent of all lymphoid cancers in dogs and mirrors human diffuse large B-cell lymphoma, which makes up about 40 percent of non-Hodgkin lymphomas in people. Because pet dogs develop the disease spontaneously, live in the same environments as their owners, and possess intact immune systems, they offer a clinically relevant model that laboratory mice cannot match. Drugs such as venetoclax, ibrutinib, and acalabrutinib have already been explored through this comparative framework, and the typical time to relapse in dogs, six to eight months, is far shorter than in humans, allowing therapeutic studies to move at an accelerated pace.

In the new study, the researchers analyzed lymph node samples from 15 dogs with multicentric DLBCL and two healthy control animals treated at the Governador Laudo Natel Veterinary Hospital at UNESP in Jaboticabal. Tissue fragments were snap-frozen and stored at minus 80 degrees Celsius before total RNA was extracted and converted into sequencing libraries using the Illumina TruSeq protocol. The team sequenced the libraries on an Illumina HiScanSQ platform with paired-end chemistry, then aligned the resulting reads against the canine reference genome CanFam6 using the STAR aligner. Differential expression analysis was carried out with the EdgeR package, modeling read counts with a negative binomial distribution and controlling the false discovery rate through the Benjamini-Hochberg procedure.

The results were striking in their asymmetry. The analysis identified 410 differentially expressed genes, of which 408 were downregulated in the tumor samples compared with normal lymph nodes, while only two genes, CPLX3 and a poorly characterized locus, were upregulated. Most of the silenced genes are involved in immune function, the very machinery that healthy tissue uses to police malignant cells. The researchers then cross-referenced their findings with four previous RNA-sequencing studies of canine B-cell lymphoma, comparing the overlapping gene lists to identify candidates of highest biological relevance. From this convergence, five genes emerged as the focus of the study: STOM, TBC1D8, HMOX1, ABCB1, and CTLA4.

Each of these five genes tells a distinct mechanistic story. STOM encodes stomatin, an integral membrane protein that organizes ion channels and helps structure the immunological synapses through which immune cells communicate; its disruption has been linked to gastric MALT lymphoma, colorectal cancer, and altered glucose transport via GLUT1. TBC1D8 encodes a GTPase-activating protein that regulates Rab-mediated vesicular trafficking, a process essential for antigen presentation, and in human colorectal and ovarian cancers it has been tied to invasiveness and poor prognosis through metabolic reprogramming toward aerobic glycolysis, the Warburg effect. HMOX1, or heme oxygenase 1, plays a paradoxical role in tumor biology, acting cytoprotectively at moderate levels while promoting lipid peroxidation and ferroptotic cell death when overexpressed.

The remaining two genes connect the signature directly to therapy. ABCB1 encodes P-glycoprotein, the ATP-dependent efflux pump responsible for multidrug resistance, which exports chemotherapeutic agents from tumor cells and undermines treatment efficacy; inhibiting it has been shown to restore drug sensitivity in lymphoma models. CTLA4 is one of the most famous targets in modern immunology, an immune checkpoint receptor that dampens T-cell activation by competing with CD28 for binding to CD80 and CD86. Its dysregulation enables tumors to escape immune surveillance, and checkpoint inhibitors targeting CTLA4, often combined with anti-PD-1 therapy, have transformed human cancer treatment. The enrichment analysis and protein-protein interaction networks built with the STRING database and Enrichr tool further connected these genes to the nuclear receptor meta-pathway, anion transport regulation, and xenobiotic transport across the blood-brain barrier, hinting at how drug metabolism and tumor stress responses converge.

When the team correlated expression of the five-gene signature with clinical outcomes, the picture was suggestive but not definitive. All 15 lymphoma patients had been treated with the CHOP chemotherapy protocol, and their survival times ranged from just 2 weeks to 160 weeks, with a mean of 48.8 weeks. Kaplan-Meier analysis showed a trend toward reduced overall survival in dogs with lower expression of the individual genes and of the composite signature, but none of these associations reached statistical significance, likely reflecting the small cohort size. The authors note that a priori power analysis was performed, and that the study was designed as a vanguard investigation capable of detecting very large effect sizes, but they acknowledge that larger, multicentric validation studies will be needed before these markers enter clinical practice.

Beyond the gene expression data, the study offers one of its most vivid insights into the tumor microenvironment itself. Using three independent computational deconvolution methods, CIBERSORT, quanTIseq, and EPIC, the researchers estimated the proportions of immune cell types within each sample. Tumor tissue was overwhelmingly dominated by neoplastic B cells, as expected in a B-cell malignancy, but the effector arm of the immune system was conspicuously depleted: cytotoxic CD8-positive T cells and macrophages were markedly reduced compared with healthy lymph nodes, which displayed a diverse repertoire of macrophages, monocytes, CD4-positive T cells, and neutrophils. This immunosuppressive architecture suggests active evasion of immune detection by the tumor. Intriguingly, an age-stratified analysis found that younger dogs tended to show higher CD4-positive T-cell infiltration, a trend the authors interpret as possibly reflecting preserved antitumor immunity before age-related immunosenescence takes hold.

The Brazilian setting of the study adds an important dimension to the global picture. Transcriptomic data from South American canine populations had been largely absent from the literature, despite evidence that environmental factors shape cancer biology. Previous case-control studies in São Paulo and the metropolitan region of Recife found that dogs living near high-traffic roads or exposed to solvents and paints faced substantially elevated risks of developing lymphoma, with one study reporting a nearly fivefold increase in risk, positioning pet dogs as sentinels for environmental carcinogens that may also affect humans. The authors also highlight a methodological point with consequences for the entire field: because earlier studies aligned their reads against the older CanFam3.1 or even CanFam2 reference genomes, while this study used the more complete and accurately annotated CanFam6, discrepancies in the numbers and identities of differentially expressed genes across studies are partly artifacts of genome assembly rather than true biological differences.

The study is not without limitations, and the authors are candid about them. The cohort comprised only 15 tumor samples and two controls, drawn from multiple breeds, and breed predispositions were not incorporated into the power analysis. Yet the consistency of the normal-sample expression profiles across all comparable published studies supports the validity of the small control group, and the magnitude of the transcriptional differences observed lent the analysis statistical footing despite its scale. What the work ultimately delivers is a framework: five interconnected genes governing membrane dynamics, vesicular transport, oxidative stress, immune regulation, and drug resistance, set against a tumor microenvironment that has lost its cytotoxic defenders. If validated in larger cohorts, these signatures could guide individualized treatment decisions in veterinary oncology, from checkpoint inhibitor combinations to strategies for reversing multidrug resistance, while reinforcing the dog’s standing as one of the most valuable spontaneous models for advancing human lymphoma research.

Subject of Research: Transcriptomic profiling and immune microenvironment analysis of canine diffuse large B-cell lymphoma

Article Title: Transcriptomic profiling reveals prognostic gene signatures and immune landscape alterations in canine diffuse large B-cell lymphoma

Article References: Anai, L. A., Cavalca, A. M. B., Xavier, P. L. P., Semolin, L. M. S., Jark, P. C., Senhorello, I. L. S., Fukumasu, H., Demarchi Munhoz, T., Figueiredo, M. L., Fernandes, C. C., Costa, M. T., Kobayashi, P. E., Santana, Á. E., & Fonseca-Alves, C. E. (2026). Transcriptomic profiling reveals prognostic gene signatures and immune landscape alterations in canine diffuse large B-cell lymphoma. Veterinary Oncology, 3(1), Article 1. https://doi.org/10.1186/s44356-025-00051-2

Image Credits: AI Generated

DOI: 10.1186/s44356-025-00051-2

Keywords: canine lymphoma, diffuse large B-cell lymphoma, RNA sequencing, transcriptomics, tumor microenvironment, CTLA4, ABCB1, HMOX1, STOM, TBC1D8, immune evasion, comparative oncology

Lymphoma is one of the most common malignancies in dogs, and its diagnosis typically begins with fine needle aspiration of an enlarged peripheral lymph node. Cytology, the microscopic examination of cells harvested in this minimally invasive way, is fast and generally reliable, but it is not always definitive. Confirming a diagnosis of lymphoma and characterizing it as B-cell or T-cell disease usually requires histopathology with immunophenotyping through PCR for antigen receptor rearrangement, flow cytometry, or immunohistochemistry. Those ancillary tests add cost, time, and logistical complexity, and they are not uniformly available across veterinary practices. Because microscopic evaluation demands trained pathologists, high-quality optics, and consistent staining reagents, diagnostic delays can affect clinical decisions and outcomes for canine patients.

The Florida team asked whether a convolutional neural network, the class of deep learning architecture that has transformed medical image classification, could shoulder part of this diagnostic burden. They selected ResNet-50, a fifty-layer residual network pretrained on the ImageNet database, and fine-tuned it through transfer learning on cytological photomicrographs captured at 1,000-fold magnification with immersion oil. The researchers assembled their dataset from cases submitted between 2017 and 2024 to the University of Florida Small Animal Hospital, drawing on the archive of the Clinical Pathology Service and cross-checking electronic medical records to verify each diagnosis.

Strict inclusion and exclusion criteria shaped the final cohort. Lymphoma cases required a cytological diagnosis of intermediate or large-cell lymphoma confirmed by PARR or flow cytometry, while reactive lymphoid hyperplasia cases required a predominance of small mature lymphocytes with plasma cells and no concern for a neoplastic population. Three board-certified clinical pathologists independently reviewed every selected slide to ensure consensus. The resulting dataset comprised 260 lymph node slides from 184 dogs, from which 2,600 images were captured: 1,070 images of B-cell lymphoma from 72 dogs, 490 images of T-cell lymphoma from 35 dogs, and 1,040 images of reactive lymphoid hyperplasia from 77 dogs. Most slides were stained with Wright-Giemsa, with a small number stained with Diff-Quick to reflect real-world staining variation.

A critical design decision was that the dataset was partitioned at the patient level rather than the image level. This meant that no images from a dog in the test set ever appeared in the training or validation pools, preventing information leakage from inflating performance. Approximately 20 percent of patients were held out for final testing, while the remaining 80 percent were used for 10-fold cross-validation, with hyperparameter tuning and early stopping applied within each fold. Images were standardized to 1920 by 1080 pixels, normalized using ImageNet channel statistics computed without reference to the validation or test data, and augmented on the fly with random horizontal and vertical flips during training.

The first task was binary classification: lymphoma versus reactive lymphoid hyperplasia. Across ten independently trained models, test accuracy ranged from 85.4 percent to 95.4 percent, with a mean of 90.3 percent, and the area under the receiver operating characteristic curve ranged from 0.943 to 0.988. The best-performing model achieved an accuracy of 0.954 with a Matthews correlation coefficient of 0.904, sensitivity of 0.950, specificity of 0.958, and an F1 score of 0.957. The authors note that this level of sensitivity matches or slightly exceeds the roughly 93 percent sensitivity reported for clinical pathologists distinguishing lymphoma from non-lymphoma in cytology, and it clears the 94 percent threshold proposed for decision-rule validation in this domain. Training, validation, and test performance remained closely aligned across folds, suggesting minimal overfitting.

The second task was far harder: distinguishing B-cell from T-cell lymphoma using cytological appearance alone. This is notoriously difficult even for experienced pathologists, because both immunophenotypes often present as morphologically similar populations of large or intermediate lymphocytes, with only subtle clues such as occasional uropods in some T-cell cases. Unsurprisingly, the models performed more modestly here, with test accuracies between 66.2 percent and 79.8 percent, a mean of 74.3 percent, and area under the curve values between 0.653 and 0.748. The representative model achieved an accuracy of 0.743, though confidence intervals were wide given the limited number of T-cell patients. The authors point out that some discordance may stem from the reference standards themselves, since PARR and flow cytometry do not always agree, especially in samples with low tumor burden.

The study also carries important caveats that the authors address directly. The entire dataset came from a single veterinary teaching hospital, raising questions about geographic and equipment-related bias. Images were manually captured from representative fields chosen by pathologists rather than from whole-slide imaging, confirming high image quality but simplifying the task relative to real diagnostic workflows. Cases of small-cell lymphoma, which account for fewer than two percent of canine lymphomas and are extremely difficult to separate from reactive hyperplasia on cytology alone, were deliberately excluded, meaning the model’s scope is limited to the most cytologically distinct presentations. Class imbalance and the predominance of one imaging system may also have influenced performance, and the researchers emphasize that robust external validation on prospectively collected, multi-institutional data is essential before any clinical deployment.

Transparency was a stated priority throughout. Unlike conventional practice, where a hold-out test set is evaluated once, the team reported results from all ten cross-validation folds and identified the best-performing model, providing a detailed suite of metrics including confidence intervals derived from patient-level bootstrapping with 1,000 iterations. The source code for preprocessing, training, and evaluation will be released publicly on GitHub, and the anonymized image dataset is available from the corresponding author upon reasonable request under a data use agreement. The authors argue that this openness stands in contrast to the proprietary opacity that often surrounds commercial AI diagnostic tools, such as the cytology-triage platforms already entering veterinary practice.

Looking forward, the researchers frame their models as triage and decision-support tools rather than replacements for pathologists, insisting that a board-certified clinical pathologist must retain final diagnostic responsibility and interpret model outputs alongside clinical history and ancillary tests. Future work will explore whole-slide imaging pipelines that could mirror the way pathologists actually examine slides, explainable AI techniques such as Gradient-weighted Class Activation Mapping to reveal which cellular features drive predictions, other CNN architectures, and multi-institutional datasets spanning diverse stains, scanners, and patient populations. The moderate success of B-cell versus T-cell classification, despite the well-known morphological overlap between these immunophenotypes, hints that deep networks may be extracting genuinely subtle cytomorphological patterns. For now, the study establishes a careful, reproducible performance baseline and an explicit methodological roadmap for bringing AI-assisted cytology from the research bench toward the veterinary clinic, where faster answers could mean earlier treatment for dogs with lymphoma.

Subject of Research: Deep learning classification of canine lymphoma in lymph node cytology images

Article Title: Deep learning-assisted cytological image analysis for canine lymphoma

Article References: Deep learning-assisted cytological image analysis for canine lymphoma. (n.d.). https://doi.org/10.1186/s44356-026-00056-5

Image Credits: AI Generated

DOI: 10.1186/s44356-026-00056-5

Keywords: canine lymphoma, deep learning, cytology, ResNet-50, veterinary pathology, convolutional neural networks, B-cell lymphoma, T-cell lymphoma, reactive lymphoid hyperplasia, image classification, veterinary oncology, artificial intelligence

Lymphoma accounts for the majority of hematopoietic malignancies in dogs, and more than 80 percent of cases present as multicentric disease, with tumors distributed across multiple lymph nodes. Accurate staging matters: knowing whether the spleen, liver, or bone marrow is involved determines the World Health Organization stage, shapes prognosis, and guides treatment decisions. Yet the standard approach is cumbersome. Veterinarians typically combine a physical examination, complete blood count with blood smear analysis, serum biochemistry, three-view thoracic radiographs, abdominal ultrasound, and cytologic evaluation of the liver, spleen, and bone marrow. Each test carries its own costs, procedural risks, and dependence on operator skill, and inconsistencies between protocols produce what researchers call stage migration, complicating comparisons between clinical studies.

In human medicine, the gold standard for lymphoma staging is positron emission tomography combined with computed tomography, PET/CT, a functional imaging technique that reveals metabolically active tumor tissue throughout the body. But PET/CT has drawbacks even in humans: up to 30 percent of non-Hodgkin lymphoma cases show low or absent tracer uptake, indolent subtypes may escape detection, post-treatment inflammation can trigger false positives, and repeated scans deliver cumulative ionizing radiation, a concern highlighted by recent evidence linking diagnostic CT exposure in children to a mildly increased incidence of hematopoietic cancers. In veterinary medicine, PET/CT is largely inaccessible due to high costs and limited availability, leaving an obvious gap that whole-body diffusion-weighted MRI may be able to fill.

DWI exploits a subtle physical phenomenon: the random Brownian motion of water molecules within tissue. By applying magnetic field gradients, the technique measures how freely water diffuses, which in turn reflects cellular density and tissue architecture. Tumors, packed with densely clustered cells, restrict water movement and appear bright on diffusion-weighted images with corresponding dark signal on apparent diffusion coefficient, or ADC, maps. The Lyon team acquired images on a 1.5 Tesla scanner in three overlapping fields of view covering head, thorax, and abdomen, using single-shot echo-planar sequences at five different b-values ranging from 0 to 1400 s/mm². Merging the 3D T1-weighted Dixon images with diffusion-weighted and ADC maps via alpha-blending post-processing produced whole-body images that allowed a single 77-minute anesthetized session to survey lymph nodes, liver, spleen, and bone marrow simultaneously.

Five dogs with treatment-naïve, cytologically or histologically confirmed multicentric high-grade lymphoma were enrolled prospectively between September 2022 and December 2023, spanning breeds from German Shepherd to Jack Russell Terrier with a median age of nine years. Each animal underwent conventional comprehensive staging and WB-DWI at diagnosis, then received a month of induction chemotherapy with either L-COP or L-CHOP before the entire evaluation was repeated. A board-certified veterinary radiologist, blinded to the conventional results and to whether a scan was taken before or after treatment, interpreted every MRI. A lesion was called positive if it showed hyperintense signal on diffusion-weighted images with matching hypointensity on ADC maps.

The results were encouraging but imperfect. Conventional methods classified three dogs as stage IV and two as stage V due to bone marrow infiltration. WB-DWI staged one dog as stage III, three as stage IV, and one as stage V, agreeing with conventional staging in three of five cases and achieving 72 percent overall agreement across all anatomical sites. Cohen’s Kappa statistics indicated moderate agreement for peripheral lymph nodes (κ = 0.531) and bone marrow (κ = 0.545), but only slight agreement for liver and spleen (κ = 0.0). Notably, WB-DWI failed to detect liver involvement in all five patients, despite cytology confirming hepatic infiltration in each case.

In some respects, the MRI outperformed the traditional toolkit. Enlarged lymph nodes were readily distinguishable by their marked hyperintensity, and the technique exposed retropharyngeal involvement in four patients and inguinal involvement in one that physical examination had missed. Retropharyngeal nodes can be hard to palpate, and inguinal nodes are often masked by adjacent mammary tissue or fat. The modality also seemed advantageous for intrathoracic and cranial abdominal node beds, which radiographs and ultrasound frequently obscure due to superimposition, small size, or gastrointestinal contents. Conversely, mesenteric lymph nodes proved difficult to evaluate, likely because of signal interference from adjacent intestinal loops, and a microchip artifact blocked assessment of one dog’s superficial cervical nodes. Most challenging of all were the liver and spleen, organs known in human studies to be susceptible to respiratory and cardiac motion artifacts and to display inherently high signal on diffusion-weighted sequences even when healthy.

The treatment-monitoring results were striking. By the end of induction chemotherapy, all five dogs had achieved complete clinical remission by conventional criteria, and WB-DWI independently confirmed the resolution of lymph node and bone marrow disease in every animal, with post-treatment scans showing no sites of abnormal hyperintensity. The two methods were completely concordant for post-treatment follow-up. WB-DWI also flagged bone marrow infiltration in one of the two cytologically positive patients; the detected case had 20 percent marrow involvement versus 8 percent in the missed case, hinting that sensitivity depends on the degree of infiltration. Because bone marrow aspirates are not consistently performed in veterinary staging despite the prognostic weight of stage V disease, a non-invasive whole-body surrogate could meaningfully change practice.

The authors are careful to emphasize the study’s limitations. With only five dogs, limited stage variability, and no confirmed non-lymphoid organ involvement, the cohort cannot establish true diagnostic accuracy. Diffusion hyperintensity is not specific for cancer: increased cellularity, inflammation, or ischemia can all restrict water diffusion, and normal spleen and lymph nodes may share imaging characteristics with diffuse neoplastic infiltration. Quantitative ADC analysis was not performed because standardized reference ranges do not yet exist for dogs, although small studies have begun characterizing ADC values in healthy canine organs. Future work incorporating healthy controls, patients with inflammatory diseases, and PET/CT as a comparative reference standard will be essential to define the modality’s specificity and reliability across institutions.

Even so, the proof of concept lands at an interesting moment for comparative oncology. Canine multicentric lymphoma shares clinical and pathological features with human non-Hodgkin lymphoma, and advances in veterinary imaging often mirror and inform human practice. Human studies already report excellent agreement between WB-DWI and PET/CT for lymphoma staging, and a whole-body diffusion MRI atlas of healthy adults now provides benchmarks for quantitative interpretation. Building an equivalent canine atlas, refining protocols with additional sequences such as T2-weighted imaging, and validating findings in larger and more diverse populations are the logical next steps. If those efforts succeed, a single, radiation-free MRI examination could transform how veterinary oncologists stage and monitor one of the most common cancers in dogs, sparing patients multiple invasive procedures while delivering a more complete picture of disease in one session.

Subject of Research: Whole-body diffusion-weighted MRI for staging canine multicentric high-grade lymphoma

Article Title: Evaluation of whole-body diffusion-weighted magnetic resonance imaging for the staging of canine multicentric high-grade lymphoma: a proof-of-concept study

Article References: Barrett, L. E., Ségard-Weisse, E., Girard, R., Bernardo Marques, G., Chamel, G., Diop, N., Dimeglio, F., Lajoinie, M., Lincet, P., Eddin, J. N., Bandiera-Mezei, L., Genieis, D., Dorez, H., & Ponce, F. (2026). Evaluation of whole-body diffusion-weighted magnetic resonance imaging for the staging of canine multicentric high-grade lymphoma: a proof-of-concept study. Veterinary Oncology, 3(1), Article 7. https://doi.org/10.1186/s44356-026-00059-2

Image Credits: AI Generated

DOI: 10.1186/s44356-026-00059-2

Keywords: canine lymphoma, whole-body diffusion-weighted imaging, WB-DWI, cancer staging, veterinary oncology, magnetic resonance imaging, apparent diffusion coefficient, bone marrow infiltration, chemotherapy response, L-CHOP, non-invasive imaging, stage migration

The drug targets the phosphatidylinositol-4,5-bisphosphate 3-kinase, AKT, mechanistic target of rapamycin signaling cascade, a central growth and survival pathway that is frequently dysregulated in both canine and human cancers. When this pathway runs amok, it drives neoplastic cells to proliferate relentlessly, evade apoptosis, crank up metabolism, and, in the case of lymphoid malignancies, stimulate the production of vascular endothelial growth factor, a molecule that supports tumor neovascularization. Because single-node inhibitors of the pathway often deliver only brief or incomplete responses, likely due to well-known feedback loops within the signaling network, the researchers turned to VDC597, a compound that blocks PI3K along with both mTOR complexes, mTORC1 and mTORC2, thereby hitting the pathway at multiple points simultaneously.

In their experiments, the team tested VDC597 against two canine cell lines: 1771, derived from a spontaneously occurring B-cell lymphoma, and CLL1390, derived from chronic lymphocytic leukemia. Both lines had previously been documented to carry mutations in or constitutively express activated proteins of the PI3K-AKT-mTOR pathway, making them appropriate models for pathway-targeted therapy. Western blot analysis showed that a 24-hour treatment with the drug produced a clear, dose-dependent reduction in phosphorylated AKT at the serine 473 residue, the molecular signature of pathway activation. The leukemia line proved more sensitive, showing significant suppression at concentrations as low as 0.2 micromolar, while the lymphoma line required a full micromolar dose to achieve statistically significant inhibition.

Timing experiments revealed that the drug’s effects on signal transduction are both rapid and durable. Following a single 1 micromolar dose, phosphorylation of AKT dropped quickly and remained at roughly half of control levels for a full 24 hours. Downstream phosphorylation of 4EBP1, a translation-regulating target of mTORC1, fell even more sharply, with statistically significant suppression measurable from half an hour after treatment through the two-hour mark. The researchers verified these biochemical findings by immunohistochemistry on fixed cell pellets, observing reduced perinuclear and cytoplasmic staining for both phosphoproteins after drug exposure, an encouraging confirmation that the compound shuts down signaling across the entire pathway rather than just a single branch.

The functional consequences were equally striking. After 72 hours of exposure, VDC597 halved the viable cell population at concentrations within or near what is pharmacologically achievable, with mean half-maximal inhibitory concentrations of 1.41 micromolar for CLL1390 and 2.56 micromolar for 1771, values informed by an earlier phase I trial of the drug in tumor-bearing dogs. Live-cell imaging, tracking fluorescently labeled nuclei and dead-cell stains over 48 hours, showed that the drug did not merely slow proliferation: it actively killed the lymphoma cells, with cell death increasing in a dose-dependent manner and becoming significantly elevated at concentrations of 0.25 micromolar and above. Enzyme-linked immunosorbent assays further demonstrated that VDC597 suppressed vascular endothelial growth factor production in both cell lines, again in a dose-dependent fashion, suggesting the drug may undermine the angiogenic support system that lymphoid tumors rely upon.

Because combination therapy, not single agents, ultimately determines how well targeted drugs translate into clinical benefit, the team paired VDC597 with the three chemotherapy drugs most commonly used in canine lymphoma protocols: dexamethasone, doxorubicin, and vincristine. The results were revealing. Combining VDC597 with dexamethasone produced genuinely synergistic growth inhibition, quantified by combination indices below 1 using the Chou-Talalay method, with the effect strongest at lower drug concentrations. Pairing the drug with doxorubicin yielded additive to mildly synergistic effects at lower doses, though the highest doxorubicin concentration produced antagonism, possibly because PI3K inhibition dampens the reactive oxygen species generation through which doxorubicin promotes apoptosis. Vincristine, whose mechanism overlaps with the pathway’s role in microtubule function during mitosis, showed only additive to mildly antagonistic interactions.

The strong synergy with dexamethasone is mechanistically compelling. Glucocorticoids kill lymphoid cells through receptors whose nuclear translocation and downstream signaling are potentiated by PI3K-AKT-mTOR inhibition, a finding previously documented in human B-cell acute lymphoblastic leukemia. The Colorado State results thus support the hypothesis that adding a dual PI3K/mTOR inhibitor to standard chemotherapy could deepen responses or sensitize resistant tumors, particularly in lymphoma, where the clinical reservoir of effective options is thin.

Importantly, the study went beyond cell culture to examine pathway activation in actual patients. Using tissue microarrays built from 118 lymph node samples collected from 84 dogs with spontaneous B-cell lymphoma, the researchers scored phosphorylated AKT and phosphorylated 4EBP1 by immunohistochemistry, employing both traditional manual Allred scoring and artificial intelligence-assisted whole-slide analysis with Visiopharm software to generate finer-grained H-scores. The two approaches correlated well, validating the use of machine learning tools for quantitative pathology in veterinary specimens. The phosphorylation signals proved highly variable from tumor to tumor, underscoring that not every canine B-cell lymphoma is driven by an equally active PI3K-AKT-mTOR pathway.

Two clinically meaningful correlations emerged. First, tumors with lower expression of major histocompatibility complex class II, a known adverse prognostic marker measured by flow cytometry, showed significantly higher levels of phosphorylated AKT, linking aggressive immune phenotype to stronger pathway activity. Second, samples taken after relapse following CHOP chemotherapy showed higher phosphorylated 4EBP1 than matched pre-treatment samples, a result that retained significance in paired manual scoring. However, no correlation was found between either phosphoprotein and progression-free interval, overall survival, WHO stage or substage, or flow cytometric immunophenotypic markers, and phosphorylated AKT did not rise in parallel with phosphorylated 4EBP1 in the relapse samples. The authors caution against overinterpreting these limited associations and suggest several possible explanations, including AKT phosphorylation at sites not detected by the assay, alternative 4EBP1 kinases such as PIM2 or RAS/MAPK signaling, or mutations downstream of AKT.

The study has clear limitations that its authors acknowledge. Only one cell line each was tested for lymphoma and leukemia, so the full heterogeneity of canine lymphoid malignancies, including T-cell lymphoma and acute lymphoblastic leukemia, remains unexplored. No washout experiments were performed to determine how long signaling stays suppressed after the drug is withdrawn, information that would be essential for designing oral dosing schedules. And the finding of elevated phosphorylated 4EBP1 without corresponding phosphorylated AKT in relapsed tumors awaits mechanistic confirmation. Nevertheless, the core message is clear: VDC597 collapses PI3K-AKT-mTOR signaling, kills lymphoid cancer cells in vitro at achievable concentrations, synergizes with dexamethasone, and may sensitize tumors to standard chemotherapy. As dogs with spontaneous diffuse large B-cell lymphoma are increasingly recognized as valuable models for human non-Hodgkin lymphoma, these results position dual PI3K/mTOR inhibition as a strategy worth advancing toward larger cell line panels, animal studies, and ultimately clinical trials in both species.

Subject of Research: Evaluation of the dual PI3K/mTOR inhibitor VDC597 against canine B-cell lymphoma and chronic lymphocytic leukemia cells in vitro, with immunohistochemical assessment of PI3K-AKT-mTOR pathway activation in spontaneous canine B-cell lymphoma.

Article Title: In vitro effects of the PI3K/mTOR dual-inhibitor, VDC597, in canine lymphoma and leukemia

Article References: Meuten, T., Brill, S. A., Brady, R. V., Farrell, K. B., Rose, B. J., Schlein, L. J., & Thamm, D. H. (2026). In vitro effects of the PI3K/mTOR dual-inhibitor, VDC597, in canine lymphoma and leukemia. Veterinary Oncology, 3(1), Article 13. https://doi.org/10.1186/s44356-026-00065-4

Image Credits: AI Generated

DOI: 10.1186/s44356-026-00065-4

Keywords: canine lymphoma, canine leukemia, VDC597, PI3K, mTOR, AKT, 4EBP1, signal transduction, chemotherapy, immunohistochemistry, veterinary oncology, drug combination

Primary intramuscular lymphoma, meaning lymphoma that arises in or overwhelmingly involves skeletal muscle rather than lymph nodes or organs, is exceptionally rare across species. In humans, it accounts for less than 1.5 percent of extranodal lymphoma cases, with diffuse large B-cell lymphoma the most common form reported in muscle. Patients typically present with limb swelling, muscle pain, and rapidly worsening symptoms, and tumors have been described in muscles ranging from the sartorius and psoas to the gastrocnemius and soleus. In dogs, the literature is even thinner. Prior to this report, the authors could identify only eight cases of lymphoma with muscular involvement, and two of those lacked a definitive diagnosis. Strikingly, five of the confirmed canine cases were T-cell lymphomas, whereas B-cell disease dominates in human intramuscular cases, hinting at a genuine species difference in the biology of this rare tumor.

The Colorado State patient’s clinical course began deceptively. At the wellness visit, the focal tarsal edema was attributed to a soft tissue injury, and an ulcerated skin lesion on the right lateral neck yielded non-diagnostic cytology. Within hours, the dog was at an emergency clinic, where a 4 by 6 centimeter mass was found in the right inguinal region. Blood work, a chemistry profile, and a tick-borne disease panel were unremarkable. Three days later, diarrhea developed, the inguinal mass had grown to 7 centimeters, and the dog was started on metronidazole and anti-inflammatory prednisone. When he arrived at the oncology service, his right pelvic limb and inguinal region were severely edematous, the mass itself hidden beneath the swelling, and his peripheral lymph nodes were normal in size and texture, an important clue that this was not ordinary nodal lymphoma.

Computed tomography of the limb, abdomen, and thorax revealed the true extent of the disease. Multifocal, isoattenuating masses that enhanced strongly with contrast were scattered diffusely throughout the musculature of the body, involving the semimembranosus, adductor magnus, vastus lateralis, gluteal, gracilis, biceps femoris, epaxial, subscapularis, infraspinatus, and triceps muscles, with individual lesions ranging from 1 to 12 centimeters. Additional small masses sat near the caudal vena cava and adjacent to the ventricular free walls of the heart, though these were deemed too risky to sample. Angiography ruled out a thrombus as the cause of the edema. Ultrasound-guided fine needle aspirates of the thigh masses showed a population of individualized round cells with vacuolated cytoplasm and mild to moderate atypia, suggestive of a discrete cell neoplasm but not definitive. The differential list spanned lymphoma, embryonal rhabdomyosarcoma, extraosseous osteosarcoma, histiocytic sarcoma, and hemangiosarcoma.

Facing rapidly progressive edema, the team biopsied the left thigh masses with tru-cut needles and, before histopathology returned, began empirical chemotherapy with L-asparaginase and doxorubicin, chosen to cover both lymphoma and sarcoma differentials. The response was dramatic: the owners reported improvement within 24 hours and near-complete resolution of the edema within 72 hours. Histopathology, however, was perplexing. Sheets of neoplastic round cells infiltrated between myocytes, frequently isolating individual muscle fibers, with 25 mitoses counted in just two high-powered fields. Immunohistochemistry deepened the mystery. The cells were negative for CD3, CD20, Pax5, Desmin, CD204, and Iba1, but diffusely positive for vimentin, and roughly 75 percent showed strong nuclear reactivity for Mum-1, a marker typically associated with plasma cell tumors and certain B-cell lymphomas.

The decisive tool was PARR, the polymerase chain reaction assay for antigen receptor rearrangements, which detects clonal immune cell populations by examining gene rearrangements. The assay revealed polyclonal immunoglobulin genes but a clonal T-cell receptor arrangement, directly contradicting the plasma cell tumor interpretation suggested by the Mum-1 staining. Additional immunohistochemistry for CD34 and CD30 came back negative, excluding myeloid neoplasms and anaplastic large cell lymphoma, both of which can express Mum-1. The final diagnosis was T-cell lymphoma with aberrant Mum-1 expression and loss of the pan-T-cell marker CD3. Aberrant Mum-1 expression has been described before in canine and feline T-cell lymphoma, and loss of CD3 occurs in roughly 22.8 percent of canine T-cell lymphomas assessed by flow cytometry, but the combination made this case diagnostically treacherous. In total, achieving a definitive diagnosis took 31 days from the first chemotherapy dose.

Treatment continued with single-agent doxorubicin every three weeks, but eleven days after the third dose the disease declared its aggression. A new 5.8 by 5.2 centimeter fixed mass appeared at the base of the left ear with facial swelling, concerning for progression and possible central nervous system involvement, while peripheral lymph nodes remained unaffected. Cytology confirmed the same neoplastic population. The protocol was switched to a combination of lomustine and L-asparaginase, and within two days the facial mass had nearly resolved, only to recur and progress within eight days, eventually surrounding the left eye. A palliative single 6 Gy fraction of radiation therapy was delivered to the left side of the head, followed by one cycle of an MVPP protocol combining mechlorethamine, vinblastine, procarbazine, and prednisolone. Radiation rapidly reduced the facial swelling, and the report notes this is the only documented use of radiation therapy for intramuscular lymphoma in a dog.

The reprieve was brief. One week after radiation and MVPP, the facial swelling had improved and ventral edema was stable, but eleven days later edema progressed along the limbs and ventrum, and for the first time the dog had trouble rising and appeared uncomfortable. His owners elected humane euthanasia 63 days after initial presentation. No necropsy was performed, leaving open the question of whether the intramuscular masses represented a true primary muscular lymphoma or systemic spread, though the authors argue the overwhelming muscle burden, mild lymphadenomegaly, and complete absence of peripheral lymphadenopathy or organomegaly throughout the course favor a primary muscular process. Even at 63 days, the survival represents one of the longest reported for an dog with an aggressive lymphoma and significant intramuscular involvement.

The case carries several lessons for veterinary oncology, and echoes for comparative medicine. Intramuscular lymphoma should be on the differential list for any animal presenting with acutely progressive limb edema and multifocal muscle masses, even when lymph nodes are normal. Diagnosis demands a multimodal arsenal: contrast-enhanced CT to map disease extent, cytology and histopathology to characterize the cells, immunohistochemistry to define the lineage, and PARR or flow cytometry to resolve clonality when marker expression is misleading. The authors acknowledge that, in hindsight, a multiagent protocol such as CHOP, or an alkylator-rich LOPP regimen given the T-cell phenotype, would likely have been the preferred first-line approach had the diagnosis been known earlier. Instead, the urgency of the edema forced empirical monotherapy before the diagnosis was secure, a common dilemma with this tumor type.

Ultimately, the report underscores both the promise and the limits of modern veterinary cancer care. This tumor responded, at least transiently, to L-asparaginase, doxorubicin, lomustine with L-asparaginase, MVPP chemotherapy, and focal radiation, yet every response was measured in days to weeks, and the prognosis remains guarded. With fewer than ten documented canine cases and only a scattering of human reports, no consensus exists on optimal diagnosis or treatment, and each carefully documented case materially expands the field. The Colorado State team hopes that complete reporting of future cases, including imaging, immunophenotyping, clonality testing, and outcomes, will eventually yield a shared framework for this rare and relentless disease, one that in dogs appears to favor T-cells, strike through muscle, and progress faster than clinicians can comfortably respond.

Subject of Research: A rare canine T-cell lymphoma with extensive intramuscular involvement and aberrant Mum-1 expression

Article Title: T-cell lymphoma with significant intramuscular involvement with Mum-1 expression in a dog

Article References: Gutwillig, M., Schaffer, P., Yoon, P., & Vickery, K. (2026). T-cell lymphoma with significant intramuscular involvement with Mum-1 expression in a dog. Veterinary Oncology, 3(1), Article 21. https://doi.org/10.1186/s44356-026-00075-2

Image Credits: AI Generated

DOI: 10.1186/s44356-026-00075-2

Keywords: canine lymphoma, T-cell lymphoma, intramuscular lymphoma, Mum-1, veterinary oncology, immunohistochemistry, PARR, doxorubicin, L-asparaginase, radiation therapy, computed tomography, extranodal lymphoma

The retrospective cohort study searched electronic patient databases for all dogs diagnosed with lymphoma or lymphosarcoma between 1 January 2000 and 31 December 2021, with case status reviewed in May 2023. To be included, dogs required a diagnosis confirmed by cytology or histology and consistent clinical findings, reviewed by a board-certified veterinary oncologist. Dogs that had received prior chemotherapy, radiation or immunotherapy were excluded, although those previously treated with glucocorticoids were retained. The final cohort of 1366 dogs represented 1.6 percent of the hospital population over the study period, with 451 cases from the university teaching hospital and 915 from a private referral centre. More than 105 breeds were represented, alongside crossbred dogs.

The demographics of the cohort revealed a disease of middle-aged and older dogs. Ages ranged from just over two months to 17.7 years, with a median of 8.5 years, and median body weight of 23.2 kilograms. Neutered animals dominated the population, accounting for 84.5 percent of cases. The overwhelming majority of dogs, 72 percent, presented with multicentric or nodal disease, and 93.7 percent of those were at stage III or higher at diagnosis, underscoring how frequently lymphoma is advanced by the time it is recognised. Cutaneous lymphoma was the next most common form at 10.2 percent, followed by gastrointestinal disease at 6.1 percent and mediastinal disease at 2.9 percent. Where immunophenotyping was performed, B-cell tumours slightly outnumbered T-cell tumours, 53 percent to 45 percent.

The researchers also mapped the interconnections between laboratory abnormalities and clinical presentation, uncovering a web of statistically significant associations. Anaemia was more frequent in dogs with advanced stage, gastrointestinal disease, substage b, thrombocytopenia, hypoalbuminaemia and reduced appetite. Hypercalcaemia clustered with mediastinal disease, T-cell immunophenotype and advanced stages. Reduced appetite, recorded consistently in the medical records independently of substage, was associated with nearly every adverse marker, including anaemia, thrombocytopenia, hypercalcaemia and hypoalbuminaemia. These patterns suggest that a constellation of systemic derangements travels together in canine lymphoma, and that appetite may serve as a simple bedside indicator of disease burden.

Treatment patterns reflected the realities of veterinary oncology practice. The most common initial approach was a CHOP-based combination protocol, built on cyclophosphamide, doxorubicin, vincristine and prednisolone, used in 480 dogs, with a further 62 dogs receiving T-cell specific regimens. Other dogs received single-agent doxorubicin, mitoxantrone or lomustine, glucocorticoids alone, surgery, or a variety of other combinations. Notably, 355 dogs, or 26 percent, received no recorded treatment, and 26 were euthanised at diagnosis, figures that highlight the difficult decisions owners face when confronted with an aggressive cancer and the cost and commitment that intensive chemotherapy demands.

The core outcome analysis focused on the 542 dogs treated with CHOP-based protocols, of which 532 had sufficient pre-treatment data. The overall response rate was 87.5 percent, with 67.4 percent achieving complete remission and 20 percent partial remission. The median progression-free survival time was 200 days, and the median overall survival time was 252 days, with one-year survival estimates of roughly 25.6 percent for progression-free survival and 37.2 percent for overall survival. These figures place Australian dogs squarely within, though at the lower end of, the ranges reported from large European and North American studies, a reassuring finding given concerns that quarantine-driven genetic isolation, different breed demographics and environmental factors might produce divergent outcomes.

Perhaps the most striking result was the identification of the treating hospital itself as an independent prognostic factor for both progression-free and overall survival, despite the two centres sharing similar climates, breed profiles and referral-based management. The researchers could not identify an obvious difference in clinical management, other than less frequent steroid use at one hospital, and speculate that unmeasured differences in case mix or unidentified biases may be responsible. The finding carries a practical message for the field: when multi-centre veterinary studies pool cases to boost numbers, the treating clinic should be treated as a variable in the analysis, something rarely done in veterinary oncology to date.

Two further novel or rarely reported prognostic variables emerged. Reduced appetite at diagnosis independently predicted shorter progression-free and overall survival, a factor that has been investigated in only two prior studies and confirmed in just one, possibly because appetite is usually folded into substage rather than analysed on its own. And in a subset analysis restricted to breeds with ten or more cases, breed significantly influenced overall survival: compared with crossbred dogs, boxers, golden retrievers and Labrador retrievers had significantly shorter survival, with hazard ratios of 1.98, 2.09 and 3.02 respectively. Intriguingly, all three breeds are also recognised as being at elevated risk of developing lymphoma in Australia, hinting that the genetic factors which predispose certain breeds to the disease may also shape how their tumours respond to treatment.

The study also weighed in on a long-running controversy: the role of glucocorticoids within combination chemotherapy. Prior glucocorticoid exposure before chemotherapy showed no significant effect on outcome in any group, allowing clinicians some reassurance that short-term palliative steroid use while awaiting chemotherapy is unlikely to compromise later results. However, dogs whose CHOP protocols included prednisolone had significantly shorter progression-free and overall survival and lower remission rates than those whose protocols omitted it, even after multivariate adjustment. Because steroid inclusion was at clinician discretion, bias towards treating sicker dogs with steroids cannot be excluded, and the authors caution that this finding requires independent confirmation before practice changes.

The consistent prognostic anchor across nearly all analyses was response to initial treatment, confirming its status as the most reliable predictor of survival in canine lymphoma, yet one that cannot be known before therapy begins. The authors argue that identifying an accessible, cost-effective predictor of response at diagnosis remains one of the field’s most pressing needs, and would transform the conversations veterinarians have with owners contemplating treatment. For Australian dogs and their veterinarians, the broader message is one of connection: outcomes in this isolated population mirror those reported internationally, meaning that evidence from global studies can be applied to Australian patients, and Australian data, now substantially richer, can inform the world.

The scale of the new study deserves emphasis in context. Large veterinary lymphoma cohorts exceeding 200 treatment-naïve dogs are rare in the global literature, and the Australian dataset of 1366 cases, accumulated over 22 years, now ranks among the most extensive regional collections published anywhere. This matters because most of what veterinarians know about canine lymphoma prognosis derives from North American and European institutions, where breed distributions, referral patterns and owner attitudes toward chemotherapy may differ substantially from those in an island continent with strict quarantine controls shaping its dog population for generations.

The methodological grounding of the work also strengthens its conclusions. Survival endpoints were calculated in alignment with the Veterinary Comparative Oncology Group consensus criteria, the standardised response framework adopted across veterinary oncology since 2010, with earlier records retrospectively mapped onto those definitions. Progression-free and overall survival were measured from the commencement of treatment, and dogs still in remission at last examination were right censored rather than counted as failures. Overall survival was chosen over lymphoma-specific survival because, even when another cause of death was recorded, the authors could not exclude lymphoma as a contributing factor, a conservative decision that avoids inflating favourable outcomes.

The definition of a modified CHOP protocol also clarifies how real-world practice diverges from textbook regimens. Substituting mitoxantrone for doxorubicin in dogs with cardiac disease, adding agents such as L-asparaginase, or extending protocols to 19 or 25 weeks all qualified, reflecting the clinical judgement that shapes individualised care. By analysing these dogs alongside standard CHOP recipients, the study captures the heterogeneity of referral practice that pure prospective trials often exclude, at the cost of some protocol standardisation.

Several limitations temper interpretation. As a retrospective cohort, the study depended on owner willingness and financial capacity to pursue complete staging, meaning some recorded stages represent minimum estimates, particularly for dogs clinically at stage III. Immunophenotyping was not performed in every case, and the glucocorticoid findings rest on clinician discretion rather than randomisation, leaving residual confounding by case severity an open possibility. The hospital effect, while statistically robust, remains biologically unexplained.

For practicing veterinarians, the practical takeaways are concrete. Appetite at diagnosis, already routinely recorded, merits attention as an independent prognostic marker rather than a mere component of substage. Multi-institutional studies should treat the treating hospital as an analytical variable. And the finding that Australian outcomes sit within international ranges, albeit at the lower end, provides a defensible evidence base for applying global trial results to Australian patients while encouraging local participation in future multi-centre studies.

Subject of Research: Presentation, treatment outcomes and prognostic factors for canine lymphoma in Australian dogs

Article Title: A retrospective study on the presentation and outcomes for Australian dogs with lymphoma: 1366 cases

Article References: Bennett, P., Williamson, P., & Taylor, R. (2026). A retrospective study on the presentation and outcomes for Australian dogs with lymphoma: 1366 cases. Veterinary Oncology, 3(1), Article 19. https://doi.org/10.1186/s44356-026-00070-7

Image Credits: AI Generated

DOI: 10.1186/s44356-026-00070-7

Keywords: canine lymphoma, dogs, chemotherapy, CHOP protocol, prognostic factors, veterinary oncology, survival, glucocorticoids, breed risk, Australia, B-cell lymphoma, T-cell lymphoma