Tumors of the Respiratory Tract.

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.

Association of proteinuria at time of diagnosis with survival times in dogs 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.

Evaluation of a multiagent chemotherapy protocol combining vincristine, cyclophosphamide, mitoxantrone and prednisolone (CMOP) for treatment of feline intermediate-large cell lymphoma.

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.

Evaluation of clinical response and prognostic factors in canine multicentric lymphoma treated with first rescue therapy.

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.

Assisting decision-making on age of neutering for German Short/Wirehaired Pointer, Mastiff, Newfoundland, Rhodesian Ridgeback, Siberian Husky: associated joint disorders, cancers, and urinary incontinence.

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.

Pegylated-l-asparaginase therapy for feline large cell lymphoma: 82 cases (2017-2020).

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.

Adjuvant composite cold atmospheric plasma therapy increases antitumoral effect of doxorubicin hydrochloride.

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.

Lymphosarcoma Incidence in Kazakhstan: A Retrospective Survey (2010-2019).

OBJECTIVE: The aim is to study the trends of lymphosarcoma incidence in the regional context in Kazakhstan. METHODS: The retrospective study was done using descriptive method of oncoepidemiology. The extensive, crude and age-specific incidence rates are determined according to the generally accepted methodology used in statistics. The data were used to calculate the average percentage change (APС) using the Joinpoint regression analysis to determine the trend over the study period. RESULTS: 3,987 new cases of lymphosarcoma were registered in the country (50.7% in men, 49.3% in women). During the studied years the average age of patients was 54.2±0.8 years. The highest incidence rates per 100,000 in the entire population were found in the age groups 65-69 years (10.4±0.6), 70-74 years (10.7±0.8), and 75-79 years (10.3±0.8). The highest tendency to increase in age-related incidence rates was at the age over 85 (APC=+8.26) and to decrease at the age under 30 (APC=-6.17). The average annual standardized incidence rate was 2.3 per 100,000, and in dynamics tended to increase (APC=+1.43). It was found that the downward trend was observed in five regions (Akmola, Atyrau, Karaganda, North and South Kazakhstan), and the most pronounced decline was in the Karaganda (APC=-3.61) and South Kazakhstan (APC=-2.93) regions. When compiling thematic maps, incidence rates were determined based on standardized indicators: low - up to 1.97, average - from 1.97 to 2.60, high - above 2.60 per 100,000 for both sexes. CONCLUSION: Trends in the incidence of lymphosarcoma in Kazakhstan are growing and have geographical variability, and a high incidence is observed in the eastern and northern regions of the country. Sex differences have been established the incidence in men is higher than in female population, but the rate of increase in the incidence in women is more pronounced.

Prognostic significance of CD25 expression in dogs with a noninvasive diagnosis of B-cell lymphoma treated with CHOP chemotherapy.

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.

Dendritic Cell-Derived Artificial Microvesicles Inhibit RLS40 Lymphosarcoma Growth in Mice via Stimulation of Th1/Th17 Immune Response.

Cell-free antitumor vaccines represent a promising approach to immunotherapy of cancer. Here, we compare the antitumor potential of cell-free vaccines based on microvesicles derived from dendritic cells (DCs) with DC- and cationic-liposome-based vaccines using a murine model of drug-resistant lymphosarcoma RLS40 in vivo. The vaccines were the following: microvesicle vaccines­cytochalasin B-induced membrane vesicles (CIMVs) obtained from DCs loaded with total tumor RNA using cholesterol/spermine-containing cationic liposomes L or mannosylated liposomes ML; DC vaccines­murine DCs loaded with total tumor-derived RNA using the same liposomes; and liposomal vaccines­lipoplexes of total tumor-derived RNA with liposomes L or ML. Being non-hepatotoxic, CIMV- and DC-based vaccines administered subcutaneously exhibited comparable potential to stimulate highly efficient antitumor CTLs in vivo, whereas liposomal vaccines were 25% weaker CTL inducers. Nevertheless, the antitumor efficiencies of the different types of the vaccines were similar: sizes of tumor nodes and the number of liver metastases were significantly decreased, regardless of the vaccine type. Notably, the booster vaccination did not improve the overall antitumor efficacy of the vaccines under the study. CIMV- and DC- based vaccines more efficiently than liposome-based ones decreased mitotic activity of tumor cells and induced their apoptosis, stimulated accumulation of neutrophil inflammatory infiltration in tumor tissue, and had a more pronounced immunomodulatory activity toward the spleen and thymus. Administration of CIMV-, DC-, and liposome-based vaccines resulted in activation of Th1/Th17 cells as well as the induction of positive immune checkpoint 4-1BBL and downregulation of suppressive immune checkpoints in a raw PD-1 >>> TIGIT > CTLA4 > TIM3. We demonstrated that cell-free CIMV-based vaccines exhibited superior antitumor and antimetastatic activity in a tumor model in vivo. The obtained results can be considered as the basis for developing novel strategies for oncoimmunotherapy.

Single Shot vs. Cocktail: A Comparison of Mono- and Combinative Application of miRNA-Targeted Mesyl Oligonucleotides for Efficient Antitumor Therapy.

Rational combinations of sequence-specific inhibitors of pro-oncogenic miRNAs can efficiently interfere with specific tumor survival pathways, offering great promise for targeted therapy of oncological diseases. Herein, we uncovered the potential of multicomponent therapy by double or triple combinations of highly potent mesyl phosphoramidate (µ) antisense oligodeoxynucleotides targeted to three proven pro-oncogenic microRNAs-miR-17, miR-21, and miR-155. A strong synergism in the inhibition of proliferation and migration of B16 melanoma cells was demonstrated in vitro for pairs of µ-oligonucleotides, which resulted in vivo in profound inhibition (up to 85%) of lung metastases development after intravenous injection of µ-oligonucleotide-transfected B16 cells in mice. A clear benefit of µ-21-ON/µ-17-ON and µ-17-ON/µ-155-ON/µ-21-ON combination antitumor therapy was shown for the lymphosarcoma RLS40 solid tumor model. In vivo administration of the µ-17-ON/µ-155-ON/µ-21-ON cocktail into RLS40-bearing mice elicited fourfold delay of tumor growth as a result of strong inhibition of tumor mitotic activity. It was discovered that the cocktail of µ-21-ON/µ-17-ON/µ-155-ON led to a twofold decrease in total destructive changes in murine liver, which indicates both the reduction in toxic tumor burden and the absence of specific toxicity of the proposed therapy.

[Activity of the Russian antitumor compound chlonisol in models of eyelid tumors (experimental study)]. / Aktivnost' otechestvennogo protivoopukholevogo soedineniya khlonizol na modelyakh opukholei vek (eksperimental'noe issledovanie).

Eyelid tumors are the most common neoplasms in everyday ophthalmic practice and cover a wide range of benign and malignant lesions. Surgical methods, cryodestruction, laser therapy and radiation therapy are used in the treatment of malignant eyelid tumors. Chemotherapy does not occupy a prominent place in the treatment of malignant eyelid tumors, its use is limited to sensitive tumors. OBJECTIVE: To assess the antitumor activity of the Russian-developed chemical compound 2-[3-(2-chloroethyl)-3-nitrosoureido]-1.3-propandiol (chlonisol) on the models of transplantable tumors of various histogenesis implanted into the lower eyelid. MATERIAL AND METHODS: The study was carried out on 67 mice of lines 129/SN, BALB/c and C57BL/6 that had Ehrlich carcinoma, sarcoma 37, lymphosarcoma LIO-1 and B16 melanoma transplanted into the eyelid. Tumor transplantation was done by injecting 0.05 ml of sterile sodium chloride solution containing 106 cells of Ehrlich carcinoma, sarcoma 37, lymphosarcoma LIO-1, or 10% suspension of tumor tissue of B16 melanoma. The injection was performed into the right lower eyelid in the direction from the outer towards the inner corner of the eye using a thin needle (29G). Chlonisol was administered at the maximum tolerated dose of 20 mg/kg or at the lower dose of 15 mg/kg intraperitoneally 24 hours after tumor transplantation. RESULTS: In mice with Ehrlich carcinoma, sarcoma 37, lymphosarcoma LIO-1 and melanoma B16 transplanted under the skin of the lower eyelid, a single intraperitoneal injection of chlonisol at the dose of 20 or 15 mg/kg caused significant inhibition of tumor growth reaching 100%. Chlonisol significantly increased overall survival in animals with Ehrlich carcinoma (log rank test, p=0.0464), sarcoma 37 (log rank test, p<0.0001), lymphosarcoma LIO-1 (log rank test, p=0.0122) and B16 melanoma (log rank test, p<0.0001); the proportion of animals that were fully healed was 25, 78, 67 and 25%, respectively. CONCLUSION: Chlonisol has a pronounced antitumor effect in mice with Ehrlich carcinoma, sarcoma 37, lymphosarcoma LIO-1 and B16 melanoma transplanted into the eyelid.

Characteristics of cranial vault lymphoma from a systematic review of the literature.

Background: Cranial vault lymphomas are rare and their clinical features are often similar to those of cranial vault meningiomas. The objective of this review was to identify the features helpful for differentiating lymphomas of the cranial vault, from meningiomas which were the most common diagnosis before the definitive pathological diagnosis. Methods: The inclusion criterion was a histologically proven malignant lymphoma initially appearing in the calvarium. We conducted a literature search of the electronic PubMed and Ichushi-Web databases up to June 1, 2020. Cranial vault lymphoma that was diagnosed after an original diagnosis of lymphoma in a nodal or soft-tissue site was excluded from the study. Descriptive analyses were used to present the patient characteristics. Results: A total of 111 patients were found in 98 eligible articles. Almost all studies were case reports. The most common symptom was a growing subcutaneous scalp mass (84%) present for a mean duration of 5.9 months before the patient presented for treatment in analyzable cases; this fast growth may distinguish lymphomas from meningiomas. The tumor vascularization was often inconspicuous or poor, unlike well-vascularized meningiomas. A disproportionately small amount of skull destruction compared with the soft-tissue mass was observed in two-thirds of the analyzable cases. Conclusion: This qualitative systematic review identified several features of cranial vault lymphomas that may be useful in differentiating them from meningiomas, including a rapidly growing subcutaneous scalp mass, poor vascularization, and limited skull destruction relative to the size of the soft-tissue mass.

In Vivo Antitumoral Effects of Linseed Oil and Its Combination With Doxorubicin.

Linseed oil (LO) is known for its exceptional nutritional value due to the high content of alpha-linolenic acid (ALA), an essential omega-3 polyunsaturated fatty acid; its anticarcinogenic effect has been established in several experimental and epidemiological studies. As an adjuvant of chemotherapeutic agents, LO and other ALA-rich vegetable oils have been studied in only a handful of studies at the experimental level. However, the efficacy of antitumoral therapy using doxorubicin (Dox) in combination with ALA and ALA-rich substrates has not yet been investigated. In this work, the antitumor activity of LO in a wide dose range was studied with monotherapy and combined with Dox in animal models with Pliss lymphosarcoma (PLS) and Lewis lung adenocarcinoma (LLC). It was founded the daily oral administration of LO (1, 3, and 10 ml per 1 kg) to rats (PLS) and 6 ml/kg to mice (LLC) for 11-12 days from 7 days after subcutaneous transplantation of tumors has a stable statistically significant effect on the dynamics of tumor growth, reducing the intensity of tumor growth and increasing the frequency of complete tumor regressions (CR) compared with the control. LO showed high antimetastatic activity in the LLC model. Furthermore, LO at a dose of 3 ml/kg potentiates the antitumor effect of Dox in the PLS model, reducing the volume of tumors at the end of treatment by 2.0 times (p = 0.013), the value of the tumor growth index by 1.6 times (p < 0.03) and increasing the frequency of CR 60 days after the start of therapy by 3.5 times (p = 0.019) compared with the use of Dox alone. The combination of Dox and LO or fish oil allows growing efficiency therapy of LLC in comparison with Dox alone, increasing the frequency of CR to 73.68% and 94.4%, respectively, and reducing the frequency of metastasis to zero.

Nodal T-zone lymphoma and T-zone hyperplasia in dogs.

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.

Cutaneous epitheliotropic lymphosarcoma in a captive white catfish (Ameiurus catus Linnaeus).

A wild caught white catfish (Ameiurus catus Linnaeus) developed multiple cutaneous masses. Cytology revealed neoplastic lymphocytes and microscopy confirmed dermal infiltration with epitheliotropism in the epidermis, oral mucosa, and cornea, without internal organ involvement. Transmission electron microscopy did not identify viral particles. Histopathology supported cutaneous epitheliotropic lymphosarcoma, a condition most commonly reported in mammals. This is the first reported case of cutaneous epitheliotropic lymphosarcoma in an ictalurid and one of the few published cases of this condition in any fish species.

Outcome of stereotactic body radiation for treatment of nasal and nasopharyngeal lymphoma in 32 cats.

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.

Clinical and magnetic resonance imaging features of lymphoma involving the nervous system in cats.

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.

Association of globulin concentrations with prognosis in horses with lymphoma.

Introduction: Lymphoma 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. Methods: Ninety-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. Results: Nineteen 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. Discussion: Serum globulin concentrations are associated with location of lymphoma, clinicopathologic abnormalities, and survival times in equine lymphoma.

Efficacy and adverse events of continuous l-asparaginase administration for canine large cell lymphoma of presumed gastrointestinal origin.

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.