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Spaying female and castrating male dogs, hereinafter referred to as neutering, is a US convention for the first year in the dogs life. Research on 35 breeds of dogs revealed that early neutering increases risks of joint disorders, such as hip dysplasia (HD), elbow dysplasia (ED), or cranial cruciate ligament (CCL) tear, or cancers, such as lymphosarcoma (LSA), mast cell tumor (MCT), hemangiosarcoma (has), or osteosarcoma (OSA), for some breeds. Joint disorder risks are heightened for some larger breeds and for mixed-breed dogs weighing more than 20 kg. Some breeds had elevated risks for cancers. Several other research teams have reported health complications associated with neutering. The study goal includes using the same methodology for data collection and analyses as in the study on 35 breeds for five additional dog breeds weighing at least 20 kg. The breeds were: German Short/Wirehaired Pointer, Mastiff, Newfoundland, Rhodesian Ridgeback, and Siberian Husky. Major differences among breeds appeared in vulnerability to joint disorders and cancers with early neutering: male and female Pointer breeds had elevated joint disorders and increased cancers; male Mastiff breeds had increased CCL and LSA and females had non-significant elevated CCL risks; female Newfoundland breeds had heightened risks for joint disorders and males had non-significant elevated risks; female Ridgeback breeds had heightened MCT with very early neutering; and Siberian Huskies showed no significant effects on joint disorders or cancers, but female breeds showed a non-significant but elevated CCL. Updated guidelines cover 40 dog breeds. These results further emphasize the importance of personalized decisions regarding the neutering of dogs, considering the dogs breed, sex, and context.

Abstract Background Lymphoma has been implicated as a possible cause of proteinuria in dogs. However, information about the potential importance of proteinuria in dogs with lymphoma is limited. Hypothesis To determine if the presence of proteinuria at diagnosis was associated with median survival times in dogs with lymphoma and if lymphoma stage (I‐V) or type (B vs T) were associated with the presence of proteinuria. Animals Eighty‐six client‐owned dogs with a new diagnosis of lymphoma between 2008 and 2020. Methods This was a retrospective cross‐sectional study with dogs divided into proteinuric or nonproteinuric groups based on dipstick urine protein (protein ≥30 mg/dL classified as proteinuric) or a ratio of dipstick protein to urine specific gravity (ratio ≥1.5 classified as proteinuric). Dogs were excluded for: (1) treatment within 2 months with glucocorticoid, anti‐neoplastic, or anti‐proteinuric therapies, (2) diagnosed hypercortisolism or renal lymphoma, (3) active urine sediment, or (4) urine pH >8. Survival analysis utilized a Kaplan‐Meier estimator and log‐rank testing. Results There was a significant difference in median survival between proteinuric and nonproteinuric dogs classified by urine dipstick (245 days [91, 399] vs 335 days [214, 456]; P = .03) or UP : USG (237 days [158, 306] vs 304 days [173, 434]; P = .03). No difference in prevalence of proteinuria was identified between stages (I‐V) or types (B and T). Conclusions and Clinical Importance Proteinuria appears to be negatively associated with survival time in dogs newly diagnosed with lymphoma.

Background: Lymphoma has been implicated as a possible cause of proteinuria in dogs. However, information about the potential importance of proteinuria in dogs with lymphoma is limited. Hypothesis: To determine if the presence of proteinuria at diagnosis was associated with median survival times in dogs with lymphoma and if lymphoma stage (I‐V) or type (B vs T) were associated with the presence of proteinuria. Animals: Eighty‐six client‐owned dogs with a new diagnosis of lymphoma between 2008 and 2020. Methods: This was a retrospective cross‐sectional study with dogs divided into proteinuric or nonproteinuric groups based on dipstick urine protein (protein ≥30 mg/dL classified as proteinuric) or a ratio of dipstick protein to urine specific gravity (ratio ≥1.5 classified as proteinuric). Dogs were excluded for: (1) treatment within 2 months with glucocorticoid, anti‐neoplastic, or anti‐proteinuric therapies, (2) diagnosed hypercortisolism or renal lymphoma, (3) active urine sediment, or (4) urine pH >8. Survival analysis utilized a Kaplan‐Meier estimator and log‐rank testing. Results: There was a significant difference in median survival between proteinuric and nonproteinuric dogs classified by urine dipstick (245 days [91, 399] vs 335 days [214, 456]; P =.03) or UP : USG (237 days [158, 306] vs 304 days [173, 434]; P =.03). No difference in prevalence of proteinuria was identified between stages (I‐V) or types (B and T). Conclusions and Clinical Importance: Proteinuria appears to be negatively associated with survival time in dogs newly diagnosed with lymphoma. [ABSTRACT FROM AUTHOR]

IntroductionLymphoma is the most common hemopoietic neoplasia in horses. Common clinicopathologic abnormalities in equine lymphoma include hyperglobulinemia, hypoalbuminemia, hyperfibrinogenemia, anemia, thrombocytopenia and lymphocytosis. Hypoglobulinemia has been reported in other species with lymphoma, however it has not been well-described in horses. The objectives of this study were to examine the prevalence of hypoglobulinemia in equine lymphoma, and to identify prognosis and clinicopathological abnormalities associated with serum globulin concentrations.MethodsNinety-six horses with lymphoma were investigated in this retrospective study. Patients were allocated into groups based on serum globulin concentration. Survival analysis was performed to determine risk factors associated with globulin concentration and outcome.ResultsNineteen horses were hypoglobulinemic (≤2.1 g/dL), 63/98 were normoglobulinemic (2.2-4.3 g/dL), and 16/98 were hyperglobulinemic (≥4.4 g/dL). Hyperglobulinemia was associated with a higher anion gap (P = 0.0005), lower bicarbonate (P = 0.006), sodium (P = 0.03) and chloride concentrations (P = 0.002), and higher total protein than hypoglobulinemic horses (P < 0.0001). For location, 37% of horses with mucocutaneous lymphoma were hypoglobulinemic, compared to none in the hyperglobulinemic group (P = 0.02). Survival times were significantly different between low, normal and high globulin groups (P = 0.0002, median [range] survival times: 333 [1-3792], 43 [1-4,001] and 4 [1-129] days, respectively). Significant risk factors for shortened time to death were hyperglobulinemia (HR 2.4, P = 0.02), T cell lymphoma (HR 3.5, P < 0.0001), and multicentric (HR 3.1, P = 0.0008) and mediastinal (HR 6.4, P = 0.006) forms of lymphoma. Lack of chemotherapy was associated with shortened survival time (HR 4.5, P < 0.0001). B cell lymphomas (P < 0.0001) and mucocutaneous lymphoma location (P < 0.0001) were associated with longer survival times.DiscussionSerum globulin concentrations are associated with location of lymphoma, clinicopathologic abnormalities, and survival times in equine lymphoma.

Despite an initial strong response in most dogs with multicentric lymphoma treated with chemotherapy, relapse remains common. There is no clearly superior first rescue protocol described either for resistant or relapsed canine multicentric lymphoma. The objectives of this study were to assess clinical response and outcomes for canine multicentric lymphoma treated with first rescue protocols. The secondary objective was to assess prognostic variables for dogs undergoing these protocols. This was a bi‐institutional retrospective cohort study. Two hundred and sixty‐five dogs were treated with first rescue chemotherapy, including anthracycline‐based combination chemotherapy (CHOP‐like, n = 50), nitrosourea alkylating agent‐rich chemotherapy (n = 45), anthracycline‐based or related compound chemotherapy (n = 34), or nitrosourea single‐agent chemotherapy (n = 136). The overall median progression free survival time of first rescue protocol was 56.0 days (0–455 days). Important prognostic factors identified for first rescue protocol included the attainment of a complete response to the first rescue chemotherapy (p <.001), the use of a CHOP‐like first rescue protocol (p =.009), duration of first remission (HR 0.997, p =.028), and if prednisolone was included in the first rescue protocol (HR 0.41, p =.003). Adverse events (AE) were common, with 81.1% of dogs experiencing at least one AE during first rescue chemotherapy. This study highlights the need for improved first rescue therapies to provide durable remission in canine resistant or relapsed lymphoma. [ABSTRACT FROM AUTHOR]

Spaying female and castrating male dogs, hereinafter referred to as neutering, is a US convention for the first year in the dog's life. Research on 35 breeds of dogs revealed that early neutering increases risks of joint disorders, such as hip dysplasia (HD), elbow dysplasia (ED), or cranial cruciate ligament (CCL) tear, or cancers, such as lymphosarcoma (LSA), mast cell tumor (MCT), hemangiosarcoma (has), or osteosarcoma (OSA), for some breeds. Joint disorder risks are heightened for some larger breeds and for mixed-breed dogs weighing more than 20 kg. Some breeds had elevated risks for cancers. Several other research teams have reported health complications associated with neutering. The study goal includes using the same methodology for data collection and analyses as in the study on 35 breeds for five additional dog breeds weighing at least 20 kg. The breeds were: German Short/Wirehaired Pointer, Mastiff, Newfoundland, Rhodesian Ridgeback, and Siberian Husky. Major differences among breeds appeared in vulnerability to joint disorders and cancers with early neutering: male and female Pointer breeds had elevated joint disorders and increased cancers; male Mastiff breeds had increased CCL and LSA and females had non-significant elevated CCL risks; female Newfoundland breeds had heightened risks for joint disorders and males had non-significant elevated risks; female Ridgeback breeds had heightened MCT with very early neutering; and Siberian Huskies showed no significant effects on joint disorders or cancers, but female breeds showed a non-significant but elevated CCL. Updated guidelines cover 40 dog breeds. These results further emphasize the importance of personalized decisions regarding the neutering of dogs, considering the dog's breed, sex, and context. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to determine response rates, median progression-free intervals (PFIs) and median survival times (MSTs) for cats with intermediate–large cell lymphoma treated with a vincristine, cyclophosphamide, mitoxantrone and prednisolone (CMOP) protocol. A secondary objective was to determine the tolerability of mitoxantrone used within this multiagent protocol. Methods: The medical records of 31 cats treated at a single institution between 2009 and 2022 were reviewed to identify suitable cases. Cats were included in the study if they had a confirmed diagnosis of intermediate–large cell lymphoma, had received a CMOP protocol as first-line treatment and had completed at least one 4-week cycle of this protocol. Modifications allowed in the protocol included the use of l-asparaginase, vinblastine substitution for vincristine, chlorambucil substitution for cyclophosphamide and dexamethasone or methylprednisolone substitution for prednisolone. Results: The overall response rate was 74% (n = 23), with 45% (n = 14) achieving complete remission (CR), 29% (n = 9) achieving partial remission (PR) and 26% (n = 8) achieving stable disease (SD). The Kaplan–Meier median PFI and MST were 139 days and 206 days, respectively. Responders (CR or PR) had a significantly longer (P <0.001) median PFI and MST compared with non-responders (SD) (176 days vs 62 days, and 251 days vs 61 days, respectively). Cats that achieved CR had a significantly longer median PFI and MST (P <0.001) at 178 days and 1176 days, respectively. The 6-month and 1- and 2-year survival rates in cats with CR were 64%, 57% and 35%, respectively. Treatment with mitoxantrone was generally well tolerated, with no cats experiencing Veterinary Cooperative Oncology Group adverse effects above grade 2. Conclusions and relevance: The CMOP protocol is an alternative and well-tolerated treatment for cats with intermediate–large cell lymphoma. As demonstrated with previous chemotherapy protocols, cats that respond to treatment, particularly those that achieve CR, are likely to have more durable responses. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinomas (HCC) represent approximately 50% of primary liver neoplasms and can be localized or distributed throughout the parenchyma. Lymphoma is the clonal proliferation of lymphocytes, with the multicentric form being the most common in dogs. Metronomic chemotherapy consists of the administration of low-dose antineoplastic agents at short, regular intervals. However, no effective treatment for nodular or disseminated HCC nor reports of metronomic chemotherapy in dogs with lymphoma exist. Thus, this study aimed to report the use of antineoplastic therapies in 2 dogs diagnosed with inoperable nodular HCC and multicentric lymphoma. Cases: The 1st patient was a 16-year-old bitch mixed breed weighing 7.4 kg that was treated at the Veterinary Hospital of the Federal University of Santa Maria (HVU-UFSM). Ultrasound examination revealed nodular structures measuring approximately 1 cm throughout the hepatic parenchyma, with the largest one measuring approximately 4.48 x 3.07 cm located in the left lateral lobe. An increased uterine volume was also observed. Exploratory celiotomy showed pyometra and hepatic nodules. Liver biopsy confirmed the diagnosis of HCC. Owing to the impossibility of surgical resection, the treatment of choice was metronomic chemotherapy with cyclophosphamide at 15 mg/mm2 every 48 h with follow-up imaging and blood tests. Nine months after diagnosis, a nodular area of approximately 1.5 x 1.3 cm was identified in the greater curvature of the stomach. The patient remained clinically stable, with stable neoplasm progression. However, at the age of 19 years, the bitch died 2 years and 5 months after the metronomic administration of cyclophosphamide, and the causa mortis was elderliness. The 2nd patient was a 10-year-old bitch Shih Tzu weighing 3.7 kg, referred for suspected lymphoma and also examined at the HVU-UFSM. The patient manifested with enlarged mandibular and popliteal lymph nodes and lymphocytic leukocytosis. A multicentric lymphoma was confirmed via fine-needle aspiration cytology (FNAC) and through clinical signs and blood tests. Chemotherapy treatment was initiated with the CHOP regimen, which included cyclophosphamide [200 mg/m2], vincristine [0.6 mg/m2], doxorubicin [25 mg/m2], and prednisone [5 mg/kg]. However, this regimen was not effective and changed to chlorambucil [3 mg/m2), VO, SID, for 4 days] and prednisone [1 mg/kg, VO, SID]. However, this protocol was not feasible due to the unavailability of the drug on the market; therefore, metronomic chemotherapy was initiated. The bitch received cyclophosphamide 15 mg/m2 every 48 h, showing clinical improvement in the lymphocytic leukocytosis. Chronic anemia, weight loss, leukemia, and chronic kidney disease occurred as complications and were treated accordingly. The bitch lived for 3 years and 6 months after the diagnosis and eventually died due to years of treatment and worsening general condition due to the acquired complications. Discussion: Veterinary Medicine is faced with several challenges in designing effective metronomic chemotherapy regimens, including the selection of appropriate drugs and the establishment of effective doses. Both patients in this report received cyclophosphamide [15 mg/m2, every 48 h]. In human medicine, metronomic chemotherapy is considered a safe and potentially useful treatment, which was observed in the reported patients since it presented few side effects and an increased survival period of 880 days in the patient with HCC and 1,275 days in the patient with multicentric lymphoma. This regimen can be considered for inoperable tumors and in cases of refractory to conventional regimens. [ABSTRACT FROM AUTHOR]

Bovine leukosis is a disease caused by an oncogenic retrovirus that belongs to the Retroviridae family and is known for its worldwide distribution, causing great economic losses, especially in dairy farming. Few studies on the disease have been reported in Risaralda (Colombia). The objective was to determine the prevalence of the bovine leukosis virus and its association with some risk/protection factors in cattle herds from Risaralda. Blood samples were taken from 145 individuals from 6 herds in the Risaralda region, during the year 2018. DNA extraction was carried out by salting out and PCR was used to detect the provirus DNA. For each animal, the racial composition, sex, age group, origin and herd were taken in order to evaluate possible factors associated with the presence of the virus. A descriptive analysis of the information was performed, the prevalence was estimated with the 95% confidence interval, and the effect of risk/protection factors on leukosis positivity was determined by logistic regression and the odds ratio was estimated. All analyzes were done using R software. A general prevalence of 6.90% was estimated. Statistically significant differences were found for age group one (Under 5 years) and two (5 to 10 years) with respect to age group three (Over 10 years) (OR = 0.19 in both cases), indicating a higher frequency with age. This work is one of the first carried out in the department of Risaralda and provides surveillance of the disease in Colombia. [ABSTRACT FROM AUTHOR]

Spaying female and castrating male dogs, hereinafter referred to as neutering, is a US convention for the first year in the dog's life. Research on 35 breeds of dogs revealed that early neutering increases risks of joint disorders, such as hip dysplasia (HD), elbow dysplasia (ED), or cranial cruciate ligament (CCL) tear, or cancers, such as lymphosarcoma (LSA), mast cell tumor (MCT), hemangiosarcoma (has), or osteosarcoma (OSA), for some breeds. Joint disorder risks are heightened for some larger breeds and for mixed-breed dogs weighing more than 20 kg. Some breeds had elevated risks for cancers. Several other research teams have reported health complications associated with neutering. The study goal includes using the same methodology for data collection and analyses as in the study on 35 breeds for five additional dog breeds weighing at least 20 kg. The breeds were: German Short/Wirehaired Pointer, Mastiff, Newfoundland, Rhodesian Ridgeback, and Siberian Husky. Major differences among breeds appeared in vulnerability to joint disorders and cancers with early neutering: male and female Pointer breeds had elevated joint disorders and increased cancers; male Mastiff breeds had increased CCL and LSA and females had non-significant elevated CCL risks; female Newfoundland breeds had heightened risks for joint disorders and males had non-significant elevated risks; female Ridgeback breeds had heightened MCT with very early neutering; and Siberian Huskies showed no significant effects on joint disorders or cancers, but female breeds showed a non-significant but elevated CCL. Updated guidelines cover 40 dog breeds. These results further emphasize the importance of personalized decisions regarding the neutering of dogs, considering the dog's breed, sex, and context.

Objectives: The present study aimed to investigate pegylated- l -asparaginase monotherapy for feline large cell lymphoma as a potential alternative to palliative corticosteroids treatment in animals whose owners declined cytotoxic chemotherapy. Methods: A retrospective, descriptive case series of cats treated initially with pegylated- l -asparaginase as a sole therapy for feline large cell lymphoma is reported. The treatment protocol consisted of 12 intramuscular injections of pegylated- l -asparaginase with increasing intervals. If cats were unresponsive to pegylated- l -asparaginase monotherapy, a second-line treatment was initiated. Signalment, origin of lymphoma, staging, treatment, possible adverse events and follow-up data were extracted from the medical records. Responses and survival data were analysed. Results: Eighty-two cats with lymphoma of five different anatomic types were included: alimentary, abdominal extra-alimentary, peripheral nodal, nasal/nasopharyngeal and other (mediastinal, renal [solitary] and miscellaneous combined in one group for analytical purposes). The response rate was 74.1% (95% confidence interval = 63.4–83.5) with 38.3% (95% confidence interval = 27.8–48.8) in complete remission. The median disease-free period and calculated overall survival time were 70 days (12–1702+) and 79 days (1–1715+), respectively. The response rate was significantly correlated with the origin of the lymphoma and the combined group had a significantly lower response rate (P = 0.035). Twenty-four cats were also treated with corticosteroids. There was no significant difference in outcomes between the group treated with or without corticosteroids. Adverse events were present in a small number of cats (14/82). The majority of these adverse events were mild to moderate in 5/14 cats; however, the adverse events were severe enough to cause discontinuation of therapy. Conclusions and relevance: Based on the response rate and median disease-free period, treatment with pegylated- l -asparaginase is inferior when compared with historical chemotherapy protocols. However, some cats demonstrated an exceptional long disease-free period. Therefore, pegylated- l -asparaginase could be offered as an alternative to corticosteroid therapy alone. Further studies are needed to evaluate the additional benefit over palliative corticosteroid monotherapy. [ABSTRACT FROM AUTHOR]

Introduction: Cancer is a global health concern, with a significant impact on mortality rates. Despite advancements in targeted antitumor drugs, the development of new therapies remains challenging due to high costs and tumor resistance. The exploration of novel treatment approaches, such as combined chemotherapy, holds promise for improving the effectiveness of existing antitumor agents. Cold atmospheric plasma has demonstrated antineoplastic effects in preclinical studies, but its potential in combination with specific ions for lymphosarcoma treatment has not been investigated. Methods: An in vivo study was conducted using a Pliss lymphosarcoma rat model to evaluate the antitumor effects of composite cold plasma and controlled ionic therapy. Groups of rats were exposed to composite cold plasma for 3, 7, and 14 days, while the control group received no treatment. Additionally, a combination of chemotherapy with cold plasma therapy was assessed, with doxorubicin hydrochloride administered at a dosage of 5 mg/kg. PERENIO IONIC SHIELD™ emitted a controlled ionic formula during the treatment period. Results: The in vivo study demonstrated tumor growth inhibition in groups exposed to composite cold plasma for 3, 7, and 14 days compared to the control group. Furthermore, combining chemotherapy with cold plasma therapy resulted in a threefold reduction in tumor volume. The most significant antitumor effects were observed when doxorubicin hydrochloride at a dosage of 5 mg/kg was combined with 14 days of PERENIO IONIC SHIELD™ ionic therapy. Discussion: The use of composite cold plasma therapy, in conjunction with a controlled ionic formula emitted by PERENIO IONIC SHIELD™, in the complex treatment of lymphosarcoma in rats showed promising antitumor effects. The combination therapy, particularly when combined with doxorubicin hydrochloride, demonstrated enhanced efficacy. These findings suggest the potential for utilizing cold atmospheric plasma and controlled ions as an adjunctive treatment approach in lymphosarcoma therapy. Further research is warranted to explore the mechanisms underlying these effects and to evaluate the safety and efficacy in human clinical trials. [ABSTRACT FROM AUTHOR]

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BackgroundEvolution of indolent to aggressive lymphoma has been described in dogs but is difficult to distinguish from the de novo development of a second, clonally distinct lymphoma. Differentiation of these scenarios can be aided by next generation sequencing (NGS)-based assessment of clonality of lymphocyte antigen receptor genes.Case presentationAn 8-year-old male intact Mastiff presented with generalized lymphadenomegaly was diagnosed with nodal T zone lymphoma (TZL) based on cytology, histopathology, immunohistochemistry and flow cytometry. Thirteen months later, the dog re-presented with progressive lymphadenomegaly, and based on cytology and flow cytometry, a large B cell lymphoma (LBCL) was diagnosed. Sequencing-based clonality testing confirmed the de novo development of a LBCL and the persistence of a TZL.ConclusionsThe occurrence of two distinct lymphoid neoplasms should be considered if patient features and tumor cytomorphology or immunophenotype differ among sequential samples. Sequencing-based clonality testing may provide conclusive evidence of two concurrent and distinct clonal lymphocyte populations, termed most appropriately "composite lymphoma".

IntroductionCancer is a global health concern, with a significant impact on mortality rates. Despite advancements in targeted antitumor drugs, the development of new therapies remains challenging due to high costs and tumor resistance. The exploration of novel treatment approaches, such as combined chemotherapy, holds promise for improving the effectiveness of existing antitumor agents. Cold atmospheric plasma has demonstrated antineoplastic effects in preclinical studies, but its potential in combination with specific ions for lymphosarcoma treatment has not been investigated.MethodsAn in vivo study was conducted using a Pliss lymphosarcoma rat model to evaluate the antitumor effects of composite cold plasma and controlled ionic therapy. Groups of rats were exposed to composite cold plasma for 3, 7, and 14 days, while the control group received no treatment. Additionally, a combination of chemotherapy with cold plasma therapy was assessed, with doxorubicin hydrochloride administered at a dosage of 5 mg/kg. PERENIO IONIC SHIELD™ emitted a controlled ionic formula during the treatment period.ResultsThe in vivo study demonstrated tumor growth inhibition in groups exposed to composite cold plasma for 3, 7, and 14 days compared to the control group. Furthermore, combining chemotherapy with cold plasma therapy resulted in a threefold reduction in tumor volume. The most significant antitumor effects were observed when doxorubicin hydrochloride at a dosage of 5 mg/kg was combined with 14 days of PERENIO IONIC SHIELD™ ionic therapy.DiscussionThe use of composite cold plasma therapy, in conjunction with a controlled ionic formula emitted by PERENIO IONIC SHIELD™, in the complex treatment of lymphosarcoma in rats showed promising antitumor effects. The combination therapy, particularly when combined with doxorubicin hydrochloride, demonstrated enhanced efficacy. These findings suggest the potential for utilizing cold atmospheric plasma and controlled ions as an adjunctive treatment approach in lymphosarcoma therapy. Further research is warranted to explore the mechanisms underlying these effects and to evaluate the safety and efficacy in human clinical trials.

Prior studies have identified high CD25 expression in canine diffuse large B‐cell lymphoma as a negative prognostic indicator. The objective of this retrospective study was to evaluate CD25 expression as a prognostic indicator in dogs with B‐cell lymphoma (BCL) diagnosed with commonly used noninvasive diagnostics (cytology and flow cytometry [FC]) and treated with CHOP chemotherapy. Lymph node aspirates from 57 dogs with cytologic diagnosis of lymphoma composed of intermediate to large lymphocytes were analysed with FC. Percentage of neoplastic B‐cells expressing CD25 and median fluorescence intensity (MFI) of CD25 were measured. Relationships of CD25 percent positivity and MFI to progression free survival (PFS) and survival time were evaluated. Median survival time (MST) of all dogs was 272 days (95% CI, 196–348 days) and median PFS was 196 days (95% CI, 172–220 days). Higher percentage of B‐cells positive for CD25 was associated with decreased risk of death in multivariable analysis (p =.02). Dogs with higher CD25 positivity had longer MST and PFS than dogs with lower CD25 positivity (318 days versus 176 days and 212 days versus 148 days, respectively), but these differences were not significant. CD25 MFI was not significantly associated with outcome. Based on the results of this study, the association of CD25 expression and prognosis in dogs with BCL diagnosed using noninvasive methods should be interpreted with caution. Further evaluation, with studies that include histopathologic differentiation of lymphoma subtypes, is needed. [ABSTRACT FROM AUTHOR]

Abstract Background The safety and efficacy of stereotactic body radiation therapy (SBRT) in the treatment of localized nasal lymphoma in cats has not been described. Hypothesis Stereotactic body radiation therapy with or without adjuvant chemotherapy is an effective and well‐tolerated treatment for localized nasal lymphoma in cats. Animals Thirty‐two client owned cats referred to Colorado State University for the treatment of nasal lymphoma. Methods Retrospective study of cats treated with SBRT between 2010 and 2020 at Colorado State University. Diagnosis of nasal lymphoma was obtained via cytology or histopathology. Signalment, radiation protocol, concurrent treatments, adverse effects, and survival were recorded. Results Progression free survival was 225 days (95% CI 98–514) and median survival time (MST) was 365 days (95% CI 123–531). No significant difference in survival was identified between cats that received 1 versus greater than 1 fraction (MST 427 vs. 123 days, P = 0.88). Negative prognostic factors included cribriform lysis (MST 121 vs. 876 days, P = 0.0009) and intracalvarial involvement (MST 100 vs. 438 days, P = 0.0007). Disease progression was noted in 38% (12/32), locally in 22% (7/32), and systemically in 16% (5/32). No cats developed acute adverse effects. Ten cats developed late adverse effects: keratitis/keratitis sicca (n = 2), alopecia (n = 4), and leukotrichia (n = 4). Twenty‐four cats (75%) had signs consistent with chronic rhinitis. Conclusions SBRT is effective and well tolerated for treating localized nasal lymphoma in cats. Outcomes for cats with lower stage disease (canine modified Adam's stage 3 and lower) are comparable to historic data of cats treated with fractionated radiation therapy.

Abstract Background Lymphoma is the most common spinal cord neoplasm and second most common intracranial tumor in cats, but description of specific magnetic resonance imaging (MRI) features is lacking. Objective Describe the clinical and MRI features of lymphoma affecting the central (CNS) or peripheral (PNS) nervous system or both in cats. Animals Thirty‐one cats with confirmed cytological or histopathological diagnosis or both of lymphoma involving the CNS or PNS or both, and MRI findings of the lesions. Methods Multicenter retrospective descriptive study. Signalment and medical information were recorded. Magnetic resonance imaging findings were reviewed by 3 observers following a list of predefined criteria and consensus was sought. Frequency distributions of the different categorical data were reported. Results Median duration of clinical signs at time of presentation was 14 days (range, 1‐90). Neurological examination was abnormal in 30/31 cats. On MRI, lesions affecting the CNS were diagnosed in 18/31 cats, lesions in both CNS and PNS in 12/31, and lesions in the PNS only in 1/31. Intracranial lesions were diagnosed in 22 cats (extra‐axial, 7/22; intra‐axial, 2/22; mixed, 13/22), and spinal lesions were diagnosed in 12 (6/12 involving the conus medullaris and lumbosacral plexuses). Infiltration of adjacent extra‐neural tissue was present in 11/31 cases. Contrast enhancement was seen in all lesions, being marked in 25/30. Meningeal enhancement was present in all but 2 cases. Several distinct MRI patterns were observed. Conclusions and Clinical Importance Nervous system lymphoma in cats has a wide range of MRI features, of which none is pathognomonic. However, together with clinical data and cerebrospinal fluid (CSF) analysis, MRI may provide a strong tentative antemortem diagnosis.

IntroductionLymphoma is the most common hemopoietic neoplasia in horses. Common clinicopathologic abnormalities in equine lymphoma include hyperglobulinemia, hypoalbuminemia, hyperfibrinogenemia, anemia, thrombocytopenia and lymphocytosis. Hypoglobulinemia has been reported in other species with lymphoma, however it has not been well-described in horses. The objectives of this study were to examine the prevalence of hypoglobulinemia in equine lymphoma, and to identify prognosis and clinicopathological abnormalities associated with serum globulin concentrations.MethodsNinety-six horses with lymphoma were investigated in this retrospective study. Patients were allocated into groups based on serum globulin concentration. Survival analysis was performed to determine risk factors associated with globulin concentration and outcome.ResultsNineteen horses were hypoglobulinemic (≤2.1 g/dL), 63/98 were normoglobulinemic (2.2–4.3 g/dL), and 16/98 were hyperglobulinemic (≥4.4 g/dL). Hyperglobulinemia was associated with a higher anion gap (P = 0.0005), lower bicarbonate (P = 0.006), sodium (P = 0.03) and chloride concentrations (P = 0.002), and higher total protein than hypoglobulinemic horses (P < 0.0001). For location, 37% of horses with mucocutaneous lymphoma were hypoglobulinemic, compared to none in the hyperglobulinemic group (P = 0.02). Survival times were significantly different between low, normal and high globulin groups (P = 0.0002, median [range] survival times: 333 [1–3792], 43 [1–4,001] and 4 [1–129] days, respectively). Significant risk factors for shortened time to death were hyperglobulinemia (HR 2.4, P = 0.02), T cell lymphoma (HR 3.5, P < 0.0001), and multicentric (HR 3.1, P = 0.0008) and mediastinal (HR 6.4, P = 0.006) forms of lymphoma. Lack of chemotherapy was associated with shortened survival time (HR 4.5, P < 0.0001). B cell lymphomas (P < 0.0001) and mucocutaneous lymphoma location (P < 0.0001) were associated with longer survival times.DiscussionSerum globulin concentrations are associated with location of lymphoma, clinicopathologic abnormalities, and survival times in equine lymphoma.

Thoracic neoplasia often presents with generalized and nonspecific clinical signs and should be considered as a differential especially when patients are nonresponsive to therapeutic intervention for more common differential diagnoses of respiratory disease (such as equine asthma) and where there is evidence thoracic and/or abdominal effusion upon examination. Antemortem diagnosis can be challenging and working closely with a pathologist to differentiate the respective neoplasia is helpful. Early recognition and appropriate management of thoracic neoplasia are vital for patient welfare as rapid disease progression can be relatively quick, and/or the relatively advanced stage of disease in which these patients frequently present., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Abstract A 7‐year‐old spayed female Scottish Fold cat presented with a 4‐week history of anorexia, weight loss and vomiting. Abdominal ultrasonography revealed a jejunal mass and a slightly enlarged jejunal lymph node. A fine‐needle aspiration of the mass revealed many round cells with multiple small intracytoplasmic magenta granules. The mass was diagnosed as a large granular lymphocyte (LGL) lymphoma based on cytology. The LGL lymphoma was completely resected via open surgery. The histologic and cytologic evaluations showed no neoplastic findings in the jejunal lymph node, liver, spleen, kidney or bone marrow. The LGL lymphoma was localized to the jejunum. Postoperatively, the cat received chemotherapy with nimustine, L‐asparaginase and prednisolone. The cat is currently receiving nimustine every 6 weeks, without adverse events, and treatment has been administrated a total of 18 times up until day 552. The cat is in a good condition, and the LGL lymphoma has not recurred. Nimustine should be considered one of the effective chemotherapeutic agents in the treatment of feline LGL lymphoma cases in the future.

T-zone lymphoma (TZL) is an indolent, nodal lymphoma that has been clinically characterized in detail in dogs, and T-zone hyperplasia (TZH) is a hyperplastic change in lymph nodes associated with antigen processing. In some cases, histopathological features of TZL and TZH are similar, and are difficult to differentiate by morphology alone. Since there have been few publications characterizing their immunohistochemical profiles, histological, immunohistochemical, and clonality examinations were performed using formalin-fixed paraffin-embedded samples of canine lymph nodes with TZL (14 cases) and canine lymph nodes with TZH associated with nonlymphocytic tumors (10 cases). Immunohistochemically, small- to medium-sized lymphocytes of TZL were immunopositive for CD3, CD5, and HLA-DR, and negative for CD45, FOXP3, and granzyme B (GRB) in all cases. Among these 14 cases, 11 were immunopositive for CD8 and 1 was CD20 positive. Paracortical lymphocytes in TZH were diffusely immunopositive for CD3, CD5, and CD45, with scattered immunopositivity for CD8, HLA-DR, FOXP3, and GRB, and negative for CD20 in all cases. A clonal TCR gene rearrangement was detected in 13/14 TZL and none of the TZH cases. The present study revealed that TZL is a clonal proliferation of monomorphic CD8+CD45-GRB- T cells, while TZH consists of an immunophenotypically heterogenous population of CD45+ T cells that are variably positive for CD8 and FOXP3. These results suggest that canine TZL is a clonal proliferation of naïve or premature cytotoxic T cells. Regarding TZH, variable immunopositivity for cytotoxic and regulatory T-cell antigens may reflect immune responses to a variety of regional neoplastic lesions. [ABSTRACT FROM AUTHOR]

Abstract Background Antemortem definitive diagnosis of lymphoma in horses is often difficult. Thymidine kinase 1 (TK1) assay is a potentially useful biomarker for lymphoma in horses. Hypothesis/objectives To report the clinical performance of a commercially available TK1 assay for diagnosis of lymphoma in horses. We hypothesized that there would be no association between serum TK1 activity and a diagnosis of lymphoma in horses. Animals Forty‐two hospitalized horses, 14 with a definitive diagnosis of lymphoma, 4 with other neoplasia, and 24 with inflammatory disease. Methods Retrospective medical record review, groups were compared via Kruskal‐Wallis and Mann‐Whitney tests, and logistic regression was performed. Results Median (range) TK1 was 3 U/L (0.4‐17.7 U/L) in horses with lymphoma and 3.9 U/L (0.8‐94 U/L) in horses without lymphoma (P = .59). There was no significant difference in total protein between horses with and without lymphoma (6.6 g/dL [5.5‐8.3 g/dL] vs 6.6 g/dL [4.7‐10.4 g/dL]; P = .83). There was no significant difference in fibrinogen between horses with and without lymphoma (447 [100‐1364] mg/dL vs 433 [291‐2004] mg/dL; P = .47). On logistic regression, serum TK1 activity was not associated with a diagnosis of lymphoma (odds ratio, 0.97; 95% confidence interval, 0.9‐1.05, P = .48). Conclusion and Clinical Importance Serum TK1 values were not predictive of lymphoma diagnosis in this cohort of horses.

Abstract Lymphoma is widely recognized in veterinary medicine. However, studies focused on secondary lymphoma after chemotherapy do not exist in veterinary medicine. An 11‐year‐old, spayed female Shih‐Tzu dog was diagnosed with mammary gland carcinoma. Twenty‐five months after carboplatin treatment, the dog developed generalized lymphadenopathy (GL), diagnosed as high‐grade T‐cell lymphoma by immunohistochemistry. Another spayed female Shih‐Tzu dog who was 15‐year‐old had biopsy‐induced gastrointestinal stromal tumour. Three months after being treated with Toceranib, the dog developed GL that was diagnosed by PCR for antigen receptor rearrangement as T‐cell lymphoma. An eight‐year‐old, castrated male Mongrel dog was diagnosed with mast cell tumour. The dog was treated with vinblastine, but 14 months later, GL was revealed. Fine‐needle aspiration indicated lymphoma. The owner declined to investigate the cell lineage. All three dogs developed GL after chemotherapy. We suggest that secondary lymphoma can develop in dogs after chemotherapy for a primary cancer, and thus long‐term follow‐up is necessary.

Background: The safety and efficacy of stereotactic body radiation therapy (SBRT) in the treatment of localized nasal lymphoma in cats has not been described. Hypothesis: Stereotactic body radiation therapy with or without adjuvant chemotherapy is an effective and well‐tolerated treatment for localized nasal lymphoma in cats. Animals: Thirty‐two client owned cats referred to Colorado State University for the treatment of nasal lymphoma. Methods: Retrospective study of cats treated with SBRT between 2010 and 2020 at Colorado State University. Diagnosis of nasal lymphoma was obtained via cytology or histopathology. Signalment, radiation protocol, concurrent treatments, adverse effects, and survival were recorded. Results: Progression free survival was 225 days (95% CI 98–514) and median survival time (MST) was 365 days (95% CI 123–531). No significant difference in survival was identified between cats that received 1 versus greater than 1 fraction (MST 427 vs. 123 days, P = 0.88). Negative prognostic factors included cribriform lysis (MST 121 vs. 876 days, P = 0.0009) and intracalvarial involvement (MST 100 vs. 438 days, P = 0.0007). Disease progression was noted in 38% (12/32), locally in 22% (7/32), and systemically in 16% (5/32). No cats developed acute adverse effects. Ten cats developed late adverse effects: keratitis/keratitis sicca (n = 2), alopecia (n = 4), and leukotrichia (n = 4). Twenty‐four cats (75%) had signs consistent with chronic rhinitis. Conclusions: SBRT is effective and well tolerated for treating localized nasal lymphoma in cats. Outcomes for cats with lower stage disease (canine modified Adam's stage 3 and lower) are comparable to historic data of cats treated with fractionated radiation therapy. [ABSTRACT FROM AUTHOR]

Background: Lymphoma is the most common spinal cord neoplasm and second most common intracranial tumor in cats, but description of specific magnetic resonance imaging (MRI) features is lacking. Objective: Describe the clinical and MRI features of lymphoma affecting the central (CNS) or peripheral (PNS) nervous system or both in cats. Animals: Thirty‐one cats with confirmed cytological or histopathological diagnosis or both of lymphoma involving the CNS or PNS or both, and MRI findings of the lesions. Methods: Multicenter retrospective descriptive study. Signalment and medical information were recorded. Magnetic resonance imaging findings were reviewed by 3 observers following a list of predefined criteria and consensus was sought. Frequency distributions of the different categorical data were reported. Results: Median duration of clinical signs at time of presentation was 14 days (range, 1‐90). Neurological examination was abnormal in 30/31 cats. On MRI, lesions affecting the CNS were diagnosed in 18/31 cats, lesions in both CNS and PNS in 12/31, and lesions in the PNS only in 1/31. Intracranial lesions were diagnosed in 22 cats (extra‐axial, 7/22; intra‐axial, 2/22; mixed, 13/22), and spinal lesions were diagnosed in 12 (6/12 involving the conus medullaris and lumbosacral plexuses). Infiltration of adjacent extra‐neural tissue was present in 11/31 cases. Contrast enhancement was seen in all lesions, being marked in 25/30. Meningeal enhancement was present in all but 2 cases. Several distinct MRI patterns were observed. Conclusions and Clinical Importance: Nervous system lymphoma in cats has a wide range of MRI features, of which none is pathognomonic. However, together with clinical data and cerebrospinal fluid (CSF) analysis, MRI may provide a strong tentative antemortem diagnosis. [ABSTRACT FROM AUTHOR]

We examined the efficacy and adverse events of continuous l‐asparaginase administration in dogs with large cell lymphoma of presumedgastrointestinal (GI) origin. We retrospectively reviewed medical records of dogs with large cell lymphoma of presumed GI origin treated with continuous l‐asparaginase administration from 2009 to 2018. We collected information on the signalment, lesion site, complete blood count, serum biochemical profile, diagnostic imaging findings, cytological and histopathological findings, immunophenotype, l‐asparaginase administration frequency, treatment response, adverse events, rescue protocol, and patient outcomes. Clinical outcomes were assessed using medical records or by contacting the owner or referring veterinarian. Thirty‐two dogs with large cell lymphoma of presumed GI origin received weekly l‐asparaginase administration. The median number of l‐asparaginase injections was seven (range: 1–30). Although two of the 32 dogs had GI toxicity of grade 3 or higher, none developed a hypersensitivity reaction. The response rate based on ultrasonographic findings was 18/32 (56%) and that based on clinical signs was 30/32 (94%). The median overall progression‐free survival was 50 days (range: 2–214 days), and median overall survival was 147 days (range: 2–482 days). Adverse events associated with continuous l‐asparaginase administration were rare. Clinical signs at diagnosis improved in most cases. Based on these results, continuous l‐asparaginase administration appears to be a reasonable treatment option for dogs with large cell lymphoma of presumed GI origin. [ABSTRACT FROM AUTHOR]

Background. Tumors of the small intestine are difficult to diagnose. Their preoperative detection is an exception rather than the rule.Materials and methods. We examined 15 patients preoperatively diagnosed with small bowel tumors. Patients were selected for two-stage enterography according to special criteria. Before examination, patients received prokinetic agents to enhance gastrointestinal motility. After placing the probe in the initial segment of the small intestine, we connected a special device for remote mechanical administration of contrast agent (0.1 kg/cm2, which is equal to 100 mL/min). To prevent overextension of the intestine, we administered contrast by portions. After reaching the middle part of the ileum, we introduced a portion of air. Monitoring of the diagnostic process was performed by short-term radiographic inspection and imaging.Results and discussion. Multislice computed tomography enterography is currently considered as one of the most informative methods. It is a highly sensitive method for the diagnosis of small bowel tumors. However, a tailored approach should be used during examination with the consideration of gastrointestinal motility.Conclusion. Multislice computed tomography enterography has a number of advantages over conventional enterography.Small bowel tumors that are not associated with clinical signs of acute intestinal obstruction may remain undiagnosed for a long time and treated as any other gastrointestinal diseases.Surgical treatment of small bowel tumors remains the main therapeutic measure for patients.

Abstract Background Non‐Hodgkin lymphoma in humans is associated with environmental chemical exposures, and risk is enhanced by genetic variants in glutathione S‐transferases (GST) enzymes. Objective We hypothesized that boxer dogs, a breed at risk for lymphoma, would have a higher prevalence of GST variants with predicted low activity, and greater accumulated DNA damage, compared to other breeds. We also hypothesized that lymphoma in boxers would be associated with specific environmental exposures and a higher prevalence of canine GST variants. Animals Fifty‐four healthy boxers and 56 age‐matched nonboxer controls; 63 boxers with lymphoma and 89 unaffected boxers ≥10 years old. Methods We resequenced variant loci in canine GSTT1, GSTT5, GSTM1, and GSTP1 and compared endogenous DNA damage in peripheral leukocytes of boxers and nonboxers using the comet assay. We also compared GST variants and questionnaire‐based environmental exposures in boxers with and without lymphoma. Results Endogenous DNA damage did not differ between boxers and nonboxers. Boxers with lymphoma were more likely to live within 10 miles of a nuclear power plant and within 2 miles of a chemical supplier or crematorium. Lymphoma risk was not modulated by known canine GST variants. Conclusions and Clinical Importance Proximity to nuclear power plants, chemical suppliers, and crematoria were significant risk factors for lymphoma in this population of boxers. These results support the hypothesis that aggregate exposures to environmental chemicals and industrial waste may contribute to lymphoma risk in dogs.

Abstract Background Rabacfosadine (RAB), a novel antineoplastic agent conditionally licensed for the treatment of lymphoma in dogs, is efficacious in both naïve and previously treated dogs. Its use in combination with L‐asparaginase (L‐ASP) has not been studied. Hypothesis/Objectives To evaluate the safety and efficacy of L‐ASP given concurrently with RAB in dogs with relapsed multicentric lymphoma. Animals Fifty‐two dogs with relapse of lymphoma after treatment with at least 1 doxorubicin‐based chemotherapy protocol. Methods Open‐label, multicenter, prospective single‐arm clinical trial. Dogs were treated with RAB at 1.0 mg/kg IV every 21 days for up to a total of 5 doses. L‐asparaginase was administered at 400 IU/kg SQ concurrently with the first 2 treatments of RAB. Results The overall response rate (ORR) for all dogs was 67%, with 19 dogs (41%) achieving a complete response (CR). The median progression‐free survival time (MPFS) was 63 days (range 5‐428 days). Dogs experiencing a CR as their best response had an MPFS of 144 days (range 44‐428 days). Adverse events were similar to previous studies evaluating single agent RAB. Failure to achieve a CR and having previously received L‐ASP were negative prognostic factors on multivariate analysis. Conclusions and Clinical Importance Concurrent RAB/L‐ASP appears to be both efficacious and safe for treating relapsed multicentric lymphoma in dogs. Adverse events were most often mild and no unexpected toxicoses were observed.

Cyclophosphamide is widely used in combination chemotherapy to treat dogs with lymphoma. The metabolite of cyclophosphamide, acrolein, can irritate the urinary bladder and cause sterile haemorrhagic cystitis. The divided administration of cyclophosphamide across multiple days may reduce the occurrence of the cystitis. However, the therapeutic effect of this modification has not been evaluated and compared to the traditional single maximum-tolerated dose. It is difficult to evaluate the cytotoxic effect by the single chemotherapeutic drug in dogs. In order to verify the effect of the single and divided treatment of cyclophosphamide in canine lymphoma, we used two canine lymphoma cell lines (CLBL-1, B-cell lymphoma and UL-1, T-cell lymphoma) to imitate the clinical conditions. The cell viability in the CLBL-1 and UL-1 cells treated by a single dosage of 4-hydroxycyclophosphamide after 48 h were 70.4% and 61.5%, respectively. The cell viability in the CLBL-1 and UL-1 cells treated by the divided dosage of 4-hydroxycyclophosphamide after 48 h were 109.4% and 50.8%. There were no significant differences between the two administration methods in the T-cell lymphoma cell line (P = 0.215). The single full dosage of 4-hydroxycyclophosphamide exhibited a significant cytotoxic effect rather than the divided dosage in B-cell lymphoma cell line (P = 0.007) did. The maximum-tolerated dose of cyclophosphamide is still recommended to be used in dogs with B-cell lymphoma.

A 7‐year‐old spayed female Scottish Fold cat presented with a 4‐week history of anorexia, weight loss and vomiting. Abdominal ultrasonography revealed a jejunal mass and a slightly enlarged jejunal lymph node. A fine‐needle aspiration of the mass revealed many round cells with multiple small intracytoplasmic magenta granules. The mass was diagnosed as a large granular lymphocyte (LGL) lymphoma based on cytology. The LGL lymphoma was completely resected via open surgery. The histologic and cytologic evaluations showed no neoplastic findings in the jejunal lymph node, liver, spleen, kidney or bone marrow. The LGL lymphoma was localized to the jejunum. Postoperatively, the cat received chemotherapy with nimustine, L‐asparaginase and prednisolone. The cat is currently receiving nimustine every 6 weeks, without adverse events, and treatment has been administrated a total of 18 times up until day 552. The cat is in a good condition, and the LGL lymphoma has not recurred. Nimustine should be considered one of the effective chemotherapeutic agents in the treatment of feline LGL lymphoma cases in the future. [ABSTRACT FROM AUTHOR]

Background: Antemortem definitive diagnosis of lymphoma in horses is often difficult. Thymidine kinase 1 (TK1) assay is a potentially useful biomarker for lymphoma in horses. Hypothesis/objectives: To report the clinical performance of a commercially available TK1 assay for diagnosis of lymphoma in horses. We hypothesized that there would be no association between serum TK1 activity and a diagnosis of lymphoma in horses. Animals: Forty‐two hospitalized horses, 14 with a definitive diagnosis of lymphoma, 4 with other neoplasia, and 24 with inflammatory disease. Methods: Retrospective medical record review, groups were compared via Kruskal‐Wallis and Mann‐Whitney tests, and logistic regression was performed. Results: Median (range) TK1 was 3 U/L (0.4‐17.7 U/L) in horses with lymphoma and 3.9 U/L (0.8‐94 U/L) in horses without lymphoma (P =.59). There was no significant difference in total protein between horses with and without lymphoma (6.6 g/dL [5.5‐8.3 g/dL] vs 6.6 g/dL [4.7‐10.4 g/dL]; P =.83). There was no significant difference in fibrinogen between horses with and without lymphoma (447 [100‐1364] mg/dL vs 433 [291‐2004] mg/dL; P =.47). On logistic regression, serum TK1 activity was not associated with a diagnosis of lymphoma (odds ratio, 0.97; 95% confidence interval, 0.9‐1.05, P =.48). Conclusion and Clinical Importance: Serum TK1 values were not predictive of lymphoma diagnosis in this cohort of horses. [ABSTRACT FROM AUTHOR]

The most common subtype of lymphoma in the dog is diffuse large B-cell lymphoma (DLBCL). The remaining forms of B-cell lymphoma in dogs are categorized as small-to-intermediate in size and include marginal zone, follicular, mantle cell, and small-cell lymphocytic lymphoma. Marginal zone lymphoma and follicular lymphoma have readily identifiable unique histologic features while other forms of small B-cell lymphoma in the dog are poorly described by histopathology. Forty-seven cases of nodal small B-cell lymphoma identified by flow cytometry (small cell size based on forward scatter) with concurrent histopathology were reviewed. These cases fell into 3 histologic subtypes: marginal zone lymphoma, follicular lymphoma, and a diffuse form of small B-cell lymphoma with consistent features. As a descriptive term, we refer to the latter subtype as diffuse small B-cell lymphoma (DSBCL) until it can be further characterized by gene expression profiling and other molecular tools. Clinical presentation of DSBCL was compared to cases of histologically confirmed DLBCL and clinical follow-up was obtained for 22 of the 27 cases of DSBCL. This subset of diffuse small B-cell lymphoma had an overall median survival of 140 days. The expression of CD21, class II MHC and CD25 by flow cytometry did not differ between DSBCL and the other histologic subtypes of small cell B-cell lymphoma making histopathology the only current method of classification. [ABSTRACT FROM AUTHOR]

Lymphoma is widely recognized in veterinary medicine. However, studies focused on secondary lymphoma after chemotherapy do not exist in veterinary medicine. An 11‐year‐old, spayed female Shih‐Tzu dog was diagnosed with mammary gland carcinoma. Twenty‐five months after carboplatin treatment, the dog developed generalized lymphadenopathy (GL), diagnosed as high‐grade T‐cell lymphoma by immunohistochemistry. Another spayed female Shih‐Tzu dog who was 15‐year‐old had biopsy‐induced gastrointestinal stromal tumour. Three months after being treated with Toceranib, the dog developed GL that was diagnosed by PCR for antigen receptor rearrangement as T‐cell lymphoma. An eight‐year‐old, castrated male Mongrel dog was diagnosed with mast cell tumour. The dog was treated with vinblastine, but 14 months later, GL was revealed. Fine‐needle aspiration indicated lymphoma. The owner declined to investigate the cell lineage. All three dogs developed GL after chemotherapy. We suggest that secondary lymphoma can develop in dogs after chemotherapy for a primary cancer, and thus long‐term follow‐up is necessary. [ABSTRACT FROM AUTHOR]

Abstract Background Evolution of indolent to aggressive lymphoma has been described in dogs but is difficult to distinguish from the de novo development of a second, clonally distinct lymphoma. Differentiation of these scenarios can be aided by next generation sequencing (NGS)-based assessment of clonality of lymphocyte antigen receptor genes. Case presentation An 8-year-old male intact Mastiff presented with generalized lymphadenomegaly was diagnosed with nodal T zone lymphoma (TZL) based on cytology, histopathology, immunohistochemistry and flow cytometry. Thirteen months later, the dog re-presented with progressive lymphadenomegaly, and based on cytology and flow cytometry, a large B cell lymphoma (LBCL) was diagnosed. Sequencing-based clonality testing confirmed the de novo development of a LBCL and the persistence of a TZL. Conclusions The occurrence of two distinct lymphoid neoplasms should be considered if patient features and tumor cytomorphology or immunophenotype differ among sequential samples. Sequencing-based clonality testing may provide conclusive evidence of two concurrent and distinct clonal lymphocyte populations, termed most appropriately “composite lymphoma”.

Introduction. Bovine leukemia is a widespread infection worldwide, the causative agent of which is the bovine leukemia virus (BLV) in structural structure and functional features similar to human T-cell leukemia virus (HTLV-1 and HTLV-2) and It is considered as an actual medical and social problem. The study of the immune response in experimentally infected calves at an early stage of the disease development, synthesis of specific antibodies of classes G and M (IgG and IgM), diagnostic informativeness of detection of IgM in cattle leukemia is relevant and determines the purpose of this study. Material and methods. Samples of blood and serum of cattle: animals experimentally infected with VLCRS, patients with cattle leukemia; control negative; specific to heterologous pathogens of cattle diseases. Indirect and sandwich variant enzyme-linked immunosorbent assay (ELISA); commercial ELISA kits (IDEXX, USA; Hema LLC, FKP Kursk Biofactory Firm BIOK, Russia) for the detection of specific IgG and IgM for BLV in the agar gel immunodiffusion reaction (RID). Results. The humoral immune response develops shortly after infection — by 1-8 weeks. IgM are detected starting from the 3rd day, and IgG from the 7th day after infection. Up to 97% of coincidence of positive results in RID and indirect variant of TF ELISA based on monoclonal antibodies to cattle IgM (IgMbovine ) were found. Discussion. The dynamics of the synthesis of antibodies of classes M and G to the glycoprotein gp 51 BLV has a dose- dependent wave-like character, is consistent with the levels of increase / decrease in the absolute and relative number of leukocytes / blood lymphocytes of infected calves. Findings. Serum specific IgM was detected starting 3 days after infection with BLV. Early detection of IgM in serum of cattle can be used as an additional test for the detection of sick animals.

We report a precision medicine platform that evaluates the probability of chemotherapy drug efficacy for canine lymphoma by combining ex vivo chemosensitivity and immunophenotyping assays with computational modelling. We isolated live cancer cells from fresh fine needle aspirates of affected lymph nodes and collected post‐treatment clinical responses in 261 canine lymphoma patients scheduled to receive at least 1 of 5 common chemotherapy agents (doxorubicin, vincristine, cyclophosphamide, lomustine and rabacfosadine). We used flow cytometry analysis for immunophenotyping and ex vivo chemosensitivity testing. For each drug, 70% of treated patients were randomly selected to train a random forest model to predict the probability of positive Veterinary Cooperative Oncology Group (VCOG) clinical response based on input variables including antigen expression profiles and treatment sensitivity readouts for each patient's cancer cells. The remaining 30% of patients were used to test model performance. Most models showed a test set ROC‐AUC > 0.65, and all models had overall ROC‐AUC > 0.95. Predicted response scores significantly distinguished (P <.001) positive responses from negative responses in B‐cell and T‐cell disease and newly diagnosed and relapsed patients. Patient groups with predicted response scores >50% showed a statistically significant reduction (log‐rank P <.05) in time to complete response when compared to the groups with scores <50%. The computational models developed in this study enabled the conversion of ex vivo cell‐based chemosensitivity assay results into a predicted probability of in vivo therapeutic efficacy, which may help improve treatment outcomes of individual canine lymphoma patients by providing predictive estimates of positive treatment response. [ABSTRACT FROM AUTHOR]

T-zone lymphoma (TZL) is an indolent nodal T-cell lymphoma most commonly observed in submandibular lymph nodes in dogs. The diagnosis is based on its distinct morphology and expression of CD3. TZL has been reported to have a low Ki67 index and to lack expression of CD45. The latter feature has been used to diagnose this type of lymphoma via fine needle aspirate and flow cytometry without confirmation of the characteristic tissue architecture. The goal of this study was to characterize the immunophenotype of canine nodal TZL in greater detail. Twenty-seven TZLs were selected based on their characteristic morphology. A tissue microarray was generated, and immunohistochemical expression of CD3, CD5, CD20, CD21, CD25, CD45, Bcl-6, and Ki67 was evaluated. Neoplastic T cells in all cases were positive for CD3, CD5, and CD25, and negative for CD20, CD21, and Bcl-6. Positive labelling for CD45 was detected in 2 of the 27 cases with the remaining 25 cases being negative. All cases had a low Ki67 index with an average index of 19.56%. For the CD45-positive TZLs, clonality of the T-cell antigen receptor gamma gene was confirmed in only one of these cases. The observed immunophenotype of canine TZL is similar to previous publications with the exception that 2 cases expressed CD45. Expression of CD45 in TZLs in this study emphasizes the importance of interpreting immunophenotypic findings in conjunction with histopathology to reach an accurate diagnosis and not to use lack of expression of a particular antigen as the sole diagnostic criterion. [ABSTRACT FROM AUTHOR]

A 6.2‐year‐old 28‐kg (61.7 lb) intact female Golden Retriever was referred due to persistent and multiple cytopenias noted on a routine CBC prior to a mature ovariohysterectomy procedure. The patient's physical examination was unremarkable, and staging of the thorax and abdomen identified no abnormalities. At the referral hospital, moderate hypercalcemia, borderline anemia, and neutropenia were noted. Assessment of bone marrow samples by cytology, histology, immunohistochemistry, and flow cytometry indicated a T‐cell neoplasm. The patient was treated with a multi‐agent chemotherapy protocol for 6 months, which induced remission. Nine months after diagnosis, she relapsed with recurrence of hypercalcemia, cytopenias, and clinical illness. Single‐agent anthracycline (mitoxantrone) in combination with prednisone therapy was initiated for 3 months. Two months after completion, the patient relapsed again, and palliative therapy with prednisone was elected. The patient was euthanized 16 months after diagnosis due to progressive disease. Post‐mortem histopathologic evaluation showed extensive replacement of bone marrow by neoplastic cells, and infiltrates in multiple organs. The neoplasm was diagnosed as lymphoma rather than leukemia due to the lack of abnormal circulating cells throughout the course of disease. The neoplasm was detected only in marrow at the time of initial diagnosis, and the marrow was the most extensively effaced organ at the time of death. Therefore, leukemia or stage V lymphoma was considered unlikely. In patients with a cytopenia and lack of neoplastic leukocytosis or solid tissue masses, primary bone marrow lymphoma should be considered among the differential diagnoses. [ABSTRACT FROM AUTHOR]

Lymphoma is among the most common cancer in dogs. Diffuse large B-cell lymphoma (DLBCL) is the predominant type, accounting for up to half of all cases. Definitive diagnosis of DLBCL relies on cytologic evaluation with immunophenotyping, or histopathology and immunohistochemistry when needed. A rapid and specific molecular test aiding in the diagnosis could be beneficial. Noncoding microRNAs (miRNAs) are regulators of gene expression involved in a variety of cellular processes, including cell differentiation, cell cycle progression, and apoptosis. Not surprisingly, miRNA expression is aberrant in diseases such as cancers. Their high stability and abundance in tissues make them promising biomarkers for diagnosing and monitoring diseases. This study aimed to identify miRNA signatures of DLBCL to develop ancillary molecular diagnostic tools. miRNA was isolated from formalin-fixed, paraffin-embedded lymph node tissue from 22 DLBCL and 14 nonneoplastic controls. Relative gene expression of 8 tumor-regulating miRNAs was achieved by RT-qPCR (reverse transcriptase quantitative polymerase chain reaction). The results showed downregulation of the let-7 family of miRNAs and miR-155, whereas miR-34a was upregulated in DLBCL compared to the controls. We demonstrated that the combination of expression levels of miR-34a and let-7f or of let-7b and let-7f achieved 100% differentiation between DLBCL and controls. Furthermore, let-7f alone discriminated DLBCL from nonneoplastic tissue in 97% of cases. Our results represent one step forward in search of a rapid and accurate ancillary diagnostic test for DLBCL in dogs. [ABSTRACT FROM AUTHOR]

Cyclophosphamide is widely used in combination chemotherapy to treat dogs with lymphoma. The metabolite of cyclophosphamide, acrolein, can irritate the urinary bladder and cause sterile haemorrhagic cystitis. The divided administration of cyclophosphamide across multiple days may reduce the occurrence of the cystitis. However, the therapeutic effect of this modification has not been evaluated and compared to the traditional single maximum-tolerated dose. It is difficult to evaluate the cytotoxic effect by the single chemotherapeutic drug in dogs. In order to verify the effect of the single and divided treatment of cyclophosphamide in canine lymphoma, we used two canine lymphoma cell lines (CLBL-1, B-cell lymphoma and UL-1, T-cell lymphoma) to imitate the clinical conditions. The cell viability in the CLBL-1 and UL-1 cells treated by a single dosage of 4-hydroxycyclophosphamide after 48 h were 70.4% and 61.5%, respectively. The cell viability in the CLBL-1 and UL-1 cells treated by the divided dosage of 4-hydroxycyclophosphamide after 48 h were 109.4% and 50.8%. There were no significant differences between the two administration methods in the T-cell lymphoma cell line (P = 0.215). The single full dosage of 4-hydroxycyclophosphamide exhibited a significant cytotoxic effect rather than the divided dosage in B-cell lymphoma cell line (P = 0.007) did. The maximum-tolerated dose of cyclophosphamide is still recommended to be used in dogs with B-cell lymphoma. [ABSTRACT FROM AUTHOR]

Background: Non‐Hodgkin lymphoma in humans is associated with environmental chemical exposures, and risk is enhanced by genetic variants in glutathione S‐transferases (GST) enzymes. Objective: We hypothesized that boxer dogs, a breed at risk for lymphoma, would have a higher prevalence of GST variants with predicted low activity, and greater accumulated DNA damage, compared to other breeds. We also hypothesized that lymphoma in boxers would be associated with specific environmental exposures and a higher prevalence of canine GST variants. Animals Fifty‐four healthy boxers and 56 age‐matched nonboxer controls; 63 boxers with lymphoma and 89 unaffected boxers ≥10 years old. Methods: We resequenced variant loci in canine GSTT1, GSTT5, GSTM1, and GSTP1 and compared endogenous DNA damage in peripheral leukocytes of boxers and nonboxers using the comet assay. We also compared GST variants and questionnaire‐based environmental exposures in boxers with and without lymphoma. Results: Endogenous DNA damage did not differ between boxers and nonboxers. Boxers with lymphoma were more likely to live within 10 miles of a nuclear power plant and within 2 miles of a chemical supplier or crematorium. Lymphoma risk was not modulated by known canine GST variants. Conclusions and Clinical Importance: Proximity to nuclear power plants, chemical suppliers, and crematoria were significant risk factors for lymphoma in this population of boxers. These results support the hypothesis that aggregate exposures to environmental chemicals and industrial waste may contribute to lymphoma risk in dogs. [ABSTRACT FROM AUTHOR]

Lymphoma or lymphosarcoma is considered the most common malignant tumor in cats, representing one third of all malignancies diagnosed in felines. Food lymphoma is the most common anatomical form in this species, followed by mediastinal and multicentric. Food lymphoma can be divided, histopathologically, between small cells, lymphocytic, low grade, well differentiated, or large cells, lymphoblastic, high grade. Large granule lymphoma is a subtype characterized by the presence of Natural Killer T lymphocytes, which have a characteristic presence of intracytoplasmic granules. The types of food lymphomas are distinct neoplasms, with different clinical presentations, therapies and prognosis. In addition, it is difficult to differentiate them from other non-neoplastic diseases, such as inflammatory bowel disease and other chronic inflammation of the feline gastrointestinal tract. [ABSTRACT FROM AUTHOR]

Background: Rabacfosadine (RAB), a novel antineoplastic agent conditionally licensed for the treatment of lymphoma in dogs, is efficacious in both naïve and previously treated dogs. Its use in combination with L‐asparaginase (L‐ASP) has not been studied. Hypothesis/Objectives: To evaluate the safety and efficacy of L‐ASP given concurrently with RAB in dogs with relapsed multicentric lymphoma. Animals Fifty‐two dogs with relapse of lymphoma after treatment with at least 1 doxorubicin‐based chemotherapy protocol. Methods: Open‐label, multicenter, prospective single‐arm clinical trial. Dogs were treated with RAB at 1.0 mg/kg IV every 21 days for up to a total of 5 doses. L‐asparaginase was administered at 400 IU/kg SQ concurrently with the first 2 treatments of RAB. Results: The overall response rate (ORR) for all dogs was 67%, with 19 dogs (41%) achieving a complete response (CR). The median progression‐free survival time (MPFS) was 63 days (range 5‐428 days). Dogs experiencing a CR as their best response had an MPFS of 144 days (range 44‐428 days). Adverse events were similar to previous studies evaluating single agent RAB. Failure to achieve a CR and having previously received L‐ASP were negative prognostic factors on multivariate analysis. Conclusions and Clinical Importance: Concurrent RAB/L‐ASP appears to be both efficacious and safe for treating relapsed multicentric lymphoma in dogs. Adverse events were most often mild and no unexpected toxicoses were observed. [ABSTRACT FROM AUTHOR]

Cyclophosphamide exhibits the weakest therapeutic effect compared with vincristine and doxorubicin in the CHOP (C, cyclophosphamide; H, doxorubicin; O, vincristine; and P, prednisolone) chemotherapeutic protocol for the treatment of canine lymphoma. Twenty dogs with multicentric lymphoma were treated using the LHOP protocol, which used l-asparaginase in place of cyclophosphamide, and the outcomes were historically compared with those of dogs that received CHOP chemotherapy in the same institution. No significant differences were found in age (p = 0.107), body weight (p = 0.051), sex (p = 0.453), clinical stage V (p = 1), substage b (p = 0.573), T-cell phenotype (p = 0.340), overall response (p = 1), and hypercalcaemia status (p = 1) between the LHOP and CHOP groups. The adverse effects of l-asparaginase were well tolerated and self-limiting. The median PFS (progression-free survival) and median ST (survival time) in the LHOP group were 344 days (range: 28–940 days) and 344 days (range: 70–940 days), respectively. The median PFS and median ST in the CHOP group were 234 days (range: 49–1822 days) and 314 days (range: 50–1822 days), respectively. The dogs that received LHOP chemotherapy had a significantly longer PFS than the dogs that received CHOP chemotherapy (p = 0.001). No significant difference was observed in ST between the LHOP and CHOP groups (p = 0.131). Our study findings thus indicate that the LHOP protocol can be used as a first-line chemotherapeutic protocol in canine multicentric lymphoma.