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The article covers two clinical cases of domestic cats suffering from a mediastinal form of lymphoma and provides their cytological, immunohistochemical, and pathohistological verification. The lymphoma immunophenotyping method using the B-cell markers CD79a and CD3 was used to identify T-cells. The mediastinal type of lymphoma in cats is usually rarely registered and statistically, the number of cases does not exceed 20%, which is consistent with our observations. Shortness of breath, difficulty with swallowing, lack of appetite, cyanotic mucous membranes, lymphadenomegaly of the mediastinal lymph nodes and effusion in the chest cavity were found in the clinically ill cats. An X-ray examination of the chest cavity revealed an increased contrast in the mediastinal area and displacement of the lungs towards the spine. A complete blood count revealed lymphopenia. Cytological smears of the chest cavity transudates revealed mostly monomorphic lymphoblasts with large rounded hyperchromic nuclei and narrow cytoplasm stained in light blue. The karyoplasm was somewhat granular, the nucleoli were visible, and the mitoses were atypical and numerous. The cytological picture in biopsy samples of mediastinal lymph nodes was characterized by a monomorphic population of lymphoblasts with an eccentrically located nucleus and moderately basophilic karyoplasm. The cell cytoplasm was vacuolated in some places, with presence of atypical mitotic figures. Most of the cells had two nuclei. Diffuse tumoral lesions of the chest cavity tissues, focal tumorous lesions of the lung parenchyma, and lymphadenopathy of the mediastinal lymph nodes were found during the autopsy in the first case. The second clinical case demonstrated the massive lymphadenopathy of the mediastinal lymph nodes. Histologically, a diffuse lesion by a monomorphic population of lymphoblasts was revealed in preparationsfrom the soft tissues of the chest wall. The lymphoblasts’ insignificant cytoplasm, with nuclei from round to elliptical shape, infiltrated the chest wall’s soft tissues. It was found immunohistochemically that the blast cells showed reactivity to CD79a, and were mostly negative to CD3. This indicates the development of a large diffuse B-cell lymphoma. The immunohistochemical picture of lymph node necropsies from another cat was somewhat similar. However, it was also characterized by lymphoblasts with eccentrically placed nuclei, increased number of cells with mitotic figures, somewhat intensive CD3 antibodies expression (especially in the paracortical area of lymph nodes), and significant CD79a marker expression. [ABSTRACT FROM AUTHOR]

Summary: This case report describes the diagnosis and treatment of an aryepiglottic tumour in a 19‐year‐old Paint gelding. Diagnostic work‐up included physical examination, endoscopic evaluation of the upper airway, and histopathology of the mass following removal. Treatment consisted of surgical excision of the aryepiglottic mass under endoscopic guidance followed by a 100 Gy dose of radiation delivered with strontium‐90 plesiotherapy to the surgical bed at 72 h post‐operatively. The radiation applicator was passed through the left nostril and the application area was confirmed via endoscopic evaluation. Histopathology, including immunohistochemistry, confirmed that the aryepiglottic tumour was T cell lymphoma. Recheck examination, including physical examination and upper airway endoscopy, was performed 1, 3 and 6 months following treatment and local recurrence was not observed. Local control with minimal morbidity can be achieved with surgical excision of equine lymphoma followed by strontium‐90 plesiotherapy. [ABSTRACT FROM AUTHOR]

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Copyright of Veterinarski Glasnik is the property of Veterinarski Glasnik and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In this report, T-cell lymphoma in the atrium of a 1.5-year-old Holstein bull is described. Macroscopically, a large white to a yellow tumour mass with a size of 4.5×3.5×2 cm was observed in the left atrium. Histopathological examination revealed extensive infiltration of medium- to large-sized lymphocytic cells with round to oval nuclei and stippled chromatin, surrounded by a narrow rim of pale eosinophilic cytoplasm. Immunohistochemically, the tumour cells indicated positivity with CD3 and Ki-67, but negativity with CD79α, CD20 and S100. On the basis of the histologic and immunohistochemical findings, this tumour was diagnosed as a T-cell lymphoma. [ABSTRACT FROM AUTHOR]

This report characterized seven cases of canine retrobulbar lymphoma that have been diagnosed during 2008 to 2014 by immunophenotyping of CD3 and Pax5. Classification of lymphoma were performed according to the revised WHO guidelines. Four retrobulbar lymphomas were of T-cell origin, while the others were of B-cell. Out of 7 cases, four subtypes were diagnosed in this study; T-cell-rich large B-cell lymphoma (3/7), T-cell lymphoblastic lymphoma (2/7), peripheral T-cell lymphoma (1/7), and cutaneous nonepitheliotropic lymphoma (1/7). T-cell-rich large B-cell lymphoma was found to be the most frequent subtype found. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Veterinary Journal / Revue Vétérinaire Canadienne is the property of Canadian Veterinary Medical Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The standard of care treatment for canine lymphoma is multi‐agent chemotherapy containing prednisolone, cyclophosphamide, vincristine and an anthracycline such as doxorubicin (CHOP) or epirubicin (CEOP). Lomustine, vincristine, procarbazine, and prednisone (LOPP) has been evaluated as a rescue, with encouraging results; however, resistance to vincristine is likely in patients relapsing on CHOP/CEOP, and this agent may enhance LOPP toxicity without improving efficacy. The aim of this study was to evaluate responses to a modified‐LOPP protocol that does not include vincristine (LPP) and is administered on a 21‐day cycle. Medical records of dogs with high‐grade multicentric lymphoma from 2012 to 2017 were reviewed. Dogs with relapsed lymphoma that received LPP as a rescue protocol were enrolled. Response, time from initiation to discontinuation (TTD) and toxicity of LPP were assessed. Forty‐one dogs were included. Twenty‐five dogs (61%) responded to LPP including 12 complete responses (CR) and 13 partial responses (PR). Responders had a significantly longer TTD (P < .001) compared to non‐responders with 84 days for CR and 58 days for PR. Neutropenia was documented in 20 dogs (57%): 12 grade I to II, 8 grade III to IV. Thrombocytopenia was infrequent (20%): 5 grade I to II, 2 grade III to IV. Twelve dogs developed gastrointestinal toxicity (30%): 10 grade I to II and 2 grade III. Nineteen dogs had elevated ALT (59%): 9 grade I to II, 10 grade III to IV. Treatment was discontinued due to toxicity in 8 dogs (19%). The LPP protocol shows acceptable efficacy and toxicity‐profile and minimizes in‐hospital procedures. [ABSTRACT FROM AUTHOR]

Tanovea® (first named GS-9219, then VDC-1101, generic name: rabacfosadine) is a pro-prodrug or “double” prodrug of PMEG [9-(2-phosphonylmethoxyethyl)guanine], which has been conditionally approved by the US FDA (Food and Drug Administration) for the treatment of lymphoma in dogs. Tanovea has been demonstrated to be effective against non-Hodgkin’s lymphoma (NHL) in dogs, as well as canine cutaneous T-cell lymphoma, spontaneous canine multiple myeloma, naïve canine multicentric lymphoma and relapsed canine B-cell lymphoma. As a double prodrug of PMEG, GS-9219 is first converted intracellularly by hydrolysis to cPr-PMEDAP, then deaminated to PMEG, which is then phosphorylated twice to its active metabolite PMEGpp, acting at the level of the cellular DNA polymerases. [ABSTRACT FROM AUTHOR]

Canine lymphoma is a heterogeneous group of diseases and many previous studies have evaluated the response of a mixed population of lymphoma cases to one specific treatment protocol. The aim of this retrospective study was to describe the outcome and prognostic factors in 42 cases of multicentric centroblastic diffuse large B‐cell lymphoma treated with either a COP‐type (35%) or CHOP‐type (64%) induction chemotherapy. The objective response rate to induction therapy was 94%; entire dogs had a greater rate of complete vs partial remissions than neutered dogs (P = .017). Median progression‐free survival for the first remission (PFS1) was 182 days; absence of anaemia at diagnosis (P = .002) and pretreatment neutrophil:lymphocyte ratio (NLR) below 9.44 (P = .015) were independently predictive of longer PFS1. Fifty‐eight percent of dogs received rescue protocols with an objective response rate of 81%; 31% of dogs received further rescue protocols (up to a total of 5) and the median number of protocols administered were 2. Median overall survival (OS) was 322 days, the 1‐year survival rate was 38% and the 2‐year survival rate was 9%. Lymphocyte:monocyte ratio above 1.43 (P = .031), NLR below 11.44 (P = .009), the combination of induction and rescue therapy (P = .030) and the total number of doxorubicin doses used (P = .002) were independently predictive of longer OS. Use of a COP‐type protocol induction compared with CHOP did not undermine OS providing doxorubicin was used as rescue therapy. [ABSTRACT FROM AUTHOR]

It is well established that tumour cells have metabolic differences when compared with normal cells. This is particularly true for energy metabolism in which dogs with cancer have been reported to have higher blood insulin and lactate concentrations than control dogs. Moreover, some human and animal studies suggest that the insulin‐like growth factor 1 (IGF‐1) signalling pathway may play a role in tumorigenesis and tumour progression. At present, IGF‐1 has not been evaluated in dogs with multicentric lymphoma. In this prospective, cross‐sectional study, blood levels of IGF‐1, as well as other markers of energy metabolism—insulin, glucose, lactate, and β‐hydroxybutyrate—were measured in 16 dogs with histologically or cytologically confirmed treatment‐naïve lymphoma. These results were compared with 16 age‐, sex‐ and weight‐matched healthy controls. Dietary histories were collected, and protein, fat and carbohydrate intake were compared between groups. Results demonstrated that IGF‐1, insulin, glucose and insulin:glucose ratio were not different between groups. However, lactate and β‐hydroxybutyrate were higher in the dogs with lymphoma than that in the control dogs (1.74 ± 0.83 mmoL/L vs 1.08 ± 0.27 and 2.59 ± 0.59 mmol/L vs 0.77 ± 0.38 mmol/L, respectively). Median dietary protein, fat and carbohydrates did not differ between the groups. This preliminary study suggests that higher insulin and IGF‐1 levels relative to controls may not be a consistent finding in dogs with lymphoma. The significance of increased β‐hydroxybutyrate in dogs with lymphoma warrants further investigation in a larger prospective study. [ABSTRACT FROM AUTHOR]

Canine nodal marginal zone lymphoma (nMZL) is classified as an indolent lymphoma. Such lymphomas are typified by low mitotic rate and slow clinical progression. While the clinical behaviour of canine splenic MZL has been described, characterized by an indolent course and a good prognosis following splenectomy, there are no studies specifically describing nMZL. The aim of this study was to describe the clinical features of and outcome for canine nMZL. Dogs with histologically confirmed nMZL undergoing a complete staging work‐up (including blood analysis, flow cytometry [FC] on lymph node [LN], peripheral blood and bone marrow, imaging, histology and immunohistochemistry on a surgically removed peripheral LN) were retrospectively enrolled. Treatment consisted of chemotherapy or chemo‐immunotherapy. Endpoints were response rate (RR), time to progression (TTP) and lymphoma‐specific survival (LSS). A total of 35 cases were enrolled. At diagnosis, all dogs showed generalized lymphadenopathy. One‐third was systemically unwell. All dogs had stage V disease; one‐third also had extranodal involvement. The LN population was mainly composed of medium‐sized CD21+ cells with scant resident normal lymphocytes. Histology revealed diffuse LN involvement, referring to “late‐stage” MZL. Median TTP and LSS were 149 and 259 days, respectively. Increased LDH activity and substage b were significantly associated with a shorter LSS. Dogs with nMZL may show generalized lymphadenopathy and an advanced disease stage. Overall, the outcome is poor, despite the “indolent” designation. The best treatment option still needs to be defined. [ABSTRACT FROM AUTHOR]

We present a case of an intact 14-year-old male dog with a prostate B-cell lymphoma recognized in the contents of an irreducible perineal hernia. The enlarged prostate was replaced after reducing its size by partial excision, and the perineal hernia was repaired using the tunica vaginalis communis. However, the pelvic cavity was largely occupied by the replaced prostate, and urinary retention developed. The prostate was resected on the next day via abdominal median incision, and a bladder-urethra anastomosis was performed. Lymphoma has rarely been demonstrated to develop in the prostate, with the lesion comprising the hernia contents. The present study suggests the necessity of early treatment for perineal hernias and the possibility that lymphoma may be present in the hernia contents. [ABSTRACT FROM AUTHOR]

An 18-year-old male castrated jaguar ( Panthera onca) was presented with anorexia and continuous bleeding from the oral cavity after a history of fighting with the partner animal. Clinical evaluation revealed ulcerating lesions on the gingiva and hard palate and a hematoma on the tongue. Computed tomography of the head and endoscopic examination of the esophagus and stomach were unremarkable. Hematology and clinical chemistry revealed severe nonregenerative anemia, mild thrombocytopenia, and moderate azotemia. Several PCRs for feline hemotropic mycoplasmas ( Mycoplasma haemofelis, M heamominutium, M turicensis), Babesia felis, and Bartonella spp., as well as an Fe LV antigen test were negative. The cytologic examination of a bone marrow aspirate was consistent with ineffective erythropoiesis, most likely due to immune-mediated destruction of the erythroid precursor cells. Prednisolone therapy was initiated (1.25 mg/kg/day), and the CBC returned to normal 16 days after the initiation of the therapy. Anemia relapsed after 4 months and severe splenomegaly was noted. A repeat bone marrow aspirate revealed active erythropoiesis in the presence of erythroid precursor phagocytosis suggesting an immune-mediated process. Splenic fine-needle aspiration and tissue biopsies were taken, and all findings including histology and immunohistochemistry were consistent with a diffuse large B-cell lymphoma (DLBCL). Five days later, the clinical condition deteriorated and the jaguar died. Histopathology following necropsy showed infiltration with neoplastic lymphoblasts in the spleen, liver, and abdominal lymph nodes. This case report describes a nonregenerative immune-mediated anemia associated with a DLBCL in a jaguar. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Veterinary Journal / Revue Vétérinaire Canadienne is the property of Canadian Veterinary Medical Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Although cytology is a rapid diagnostic procedure in dogs, the cytologic criteria of endoscopic biopsies for chronic enteritis and intestinal lymphoma are not well defined. An immediate diagnosis using cytology would benefit patients by enabling prompt initiation of therapy. The objective of this study was to investigate the correlation between the results of endoscopic cytology and histopathology. In this study, 167 dogs with clinical signs of chronic gastrointestinal disease were included. On the basis of histopathology, the following diagnoses were determined: lymphocytic-plasmacytic enteritis in 93 dogs; eosinophilic enteritis in 5 dogs; small cell intestinal lymphoma in 45 dogs; and large cell intestinal lymphoma in 24 dogs. Two clinical pathologists retrospectively evaluated the endoscopic cytology of squash-smear preparations. The cytologic diagnoses of inflammation, small cell lymphoma, and large cell lymphoma were based on the severity of lymphocyte infiltration, the size of infiltrated lymphocytes, and eosinophil/mast cell infiltration. The clinical severity score was significantly increased along with the degree of lymphocyte infiltration evaluated by cytology. The cytologic diagnosis was in complete agreement with the histopathologic diagnosis in 136 of 167 (81.4%) cases. For the differentiation between enteritis and lymphoma, endoscopic cytology had a sensitivity of 98.6%, a specificity of 73.5%, a positive predictive value of 72.3%, and a negative predictive value of 98.6%. The log-rank test and Cox regression analysis showed that the results of cytology predicted the prognosis. These results suggest that endoscopic cytology is a useful technique to aid diagnosis of intestinal inflammation and lymphoma in dogs. [ABSTRACT FROM AUTHOR]

Lymphoma has been described in individual cases for goats but not systematically characterized in a larger cohort. This study aimed to subtype caprine lymphoma based on topographic and subgross distribution, immunophenotype, and cellular morphology following the World Health Organization classification system for hematopoietic tumors in domestic animals. Fifteen caprine lymphoma cases were assessed with 6 submitted as biopsy and 9 for postmortem examination. Goats were predominantly young adult (median 3 years) and dwarf breeds (Pygmy and Pygora). The sexes were similarly represented. Nuclear size was measured relative to red blood cells (RBCs) and then adjusted for species-specific differences and designated small (<3× RBCs), intermediate (3–4× RBCs), or large (>4× RBCs). Using immunohistochemistry, 11 of 15 (73%) goats had T-cell lymphoma (TCL; CD3 positive, CD79α negative) and 4 of 15 (27%) had B-cell lymphoma (BCL; CD79α positive, CD3 negative). A multicentric distribution was most common. TCL generally involved the thoracic cavity and/or neck, suggestive of thymic origin or homing. TCLs were further classified as lymphoblastic lymphomas (3/11; 27%), large granular lymphocyte lymphoma (1/11; 9%), diffuse small lymphocytic lymphomas (3/11; 27%), or peripheral/mature T-cell lymphoma (PTCL) not otherwise specified (4/11 [36%], of which 3 were high grade and 1 intermediate grade). In 1 goat with PTCL, lymph nodes had either paracortical expansion or diffuse infiltrates suggesting transition from nodular to diffuse PTLC. BCLs were classified as diffuse large B-cell lymphoma (2/4; 50%) or B-cell lymphocytic lymphoma intermediate type (2/4; 50%). In contrast to dogs and horses, lymphomas in goats are predominantly TCL and frequently involve the mediastinum. [ABSTRACT FROM AUTHOR]

A 21-year-old New Forest pony presented for evaluation of lethargy and colic. Transcutaneous abdominal ultrasonography revealed a cavitary, thick walled, mass-like lesion that appeared continuous with the small intestine. The thick walls of the mass-like lesion were of heterogeneous echogenicity with hyperechoic foci extending from the hyperechoic luminal surface to within the wall and there was loss of normal wall layering. These findings were confirmed grossly at exploratory celiotomy and histopathological examination of affected tissues confirmed lymphoma. The ultrasound findings facilitated a preoperative presumptive diagnosis that allowed informed decision-making and aided case management. [ABSTRACT FROM AUTHOR]

Background: The presence of lymphoma in buffaloes was first reported in India in the 1960s. The disease is similar to Enzootic Bovine Leucosis (EBL) caused by Bovine leukemia virus (BLV) in cattle; however, according to our results and those of other studies, the etiology of these lymphomas in buffalo do not appear to be associated with BLV. The objectives of this study are to describe four cases of the disease in buffaloes belonging to the same herd in the Amazon region of Brazil and to perform a clinical-anatomopathological, immunohistochemical, and etiological study of the lymphomas. Results: Over a period of ten years, four buffaloes were observed presenting progressive weight loss, swelling of peripheral lymph nodes, and nodules in the subcutaneous tissue. Upon necropsy, whitish-colored tumor masses were observed in the form of nodules in the subcutaneous tissue, along with miliary nodules on the serosal surfaces of abdominal and thoracic organs and tumors in lymph nodes and other organs. Neoplastic lymphocyte proliferation was observed through histopathology. An immunohistochemical study revealed that the neoplasias were formed by proliferation of predominantly B lymphocytes. The presence of BLV genome was not detected in the lymphomas when using the real-time PCR technique, nor was it detected through immunohistochemical staining using monoclonal antibodies against two viral proteins. Bovine herpesvirus 6 was not detected in the tumors. However, Bovine immunodeficiency virus (BIV) was detected in samples of lymphoma and in the lymph nodes and kidneys of one of the animals. Conclusions: The occurrence of lymphoma in buffaloes is reported for the first time in Brazil and is characterized by B-cell multicentric lymphoma. The etiology of the disease does not appear to be associated with BLV; however, the detection of BIV in samples of lymphoma from one sick animal deserves further study, considering the oncogenic potential of this virus. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 6-month-old sexually intact male Long-Evans rat which was presented with acute left hind limb lameness. Topics include the clinical and gross finding of the rat's condition which include ambulatory paraparesis, ataxic pelvic limb gait, and pronounced muscular atrophy, the findings on infiltration and expansion of neoplastic cells on the rat's bone marrow, and the morphologic diagnosis which conclude acute, progressive paraplegia due to B-cell lymphoma.

This study describes epidemiologic, clinical, macro- and microscopic tumour characteristics and outcome in 97 cats with subcutaneous lymphoma, an uncommon variant of feline extranodal lymphoma. Middle-aged (median 11 years), male (60.8%), Domestic Shorthair cats (89.7%) were commonly affected. Most tumours presented as a painless, firm, subcutaneous nodule or mass, with predilection to the lateral thoracic or abdominal wall, and the interscapular region. Deep subcutaneous invasion with extension into superficial or underlying tissues, extensive central areas of necrosis and peripheral inflammation were characteristic histopathological findings. Prevalence of retroviral infection was low. Local relapses after therapy were common (43.5%), and 32.2% had distant involvement later in course. Median overall survival was 148 days. Subcutaneous lymphoma should be considered a rare but important differential diagnosis for a subcutaneous mass in cats. Tumours show an aggressive biological behaviour. Treatment options including prognosis should be investigated in further studies. [ABSTRACT FROM AUTHOR]

The aim of this prospective clinical trial was to investigate the efficacy and toxicity of a short-term, maintenance-free chemotherapy protocol in feline lymphoma. Twenty-six cats with confirmed diagnosis of high-/intermediate-grade lymphoma were treated with a 12-week protocol consisting of cyclic administration of l-asparaginase, vincristine, cyclophosphamide, doxorubicin and prednisolone. Complete ( CR) and partial remission ( PR) rates were 46 and 27%, respectively. Median duration of first CR was 394 days compared with a median PR duration of 41 days. No factor was identified to significantly influence the likelihood to reach CR. Overall survival amounted to 78 days (range: 9-2230 days). Median survival in CR cats was 454 days and in PR cats was 82 days. Toxicosis was mainly low grade with anorexia seen most frequently. In cats achieving CR, maintenance-free chemotherapy may be sufficient to attain long-term remission and survival. Factors aiding in prognosticating the likelihood for CR, strategies enhancing response and targeting chemotherapy-induced anorexia need to be identified in future. [ABSTRACT FROM AUTHOR]

CHOP-based (cyclophosphamide, doxorubicin, vinca alkaloid, prednisolone) chemotherapy protocols are often recommended for treatment of feline lymphoma. While maintenance-free CHOP-based protocols have been published and readily used in dogs, there is limited literature regarding similar maintenance-free protocols in cats. The purpose of this study was to describe the outcome of cats with intermediate- to high-grade lymphoma that were prescribed a modified 25-week University of Wisconsin-Madison ( UW-25) chemotherapy protocol. A secondary objective was examination of potential prognostic factors. One hundred and nineteen cats from five institutions treated with a UW-25-based protocol were included. The Kaplan-Meier median progression-free interval ( PFI) and survival time ( MST) were 56 and 97 (range 2-2019) days, respectively. Cats assessed as having a complete response ( CR) to therapy had significantly longer PFI and MST than those with partial or no response ( PFI 205 versus 54 versus 21 days, respectively, P < 0.0001 and MST 318 versus 85 versus 27 days, respectively, P < 0.0001). [ABSTRACT FROM AUTHOR]

Lymphoma is one of the most common malignant tumors in canine. Protein phosphatase 2A (PP2A), a well-conserved serine/threonine phosphatase, plays a critical role as a tumor suppressor. Perphenazine (PPZ) is one of the phenothiazines and widely used as an antipsychotic drug. Recently, it is reported that PPZ directly binds with scaffolding subunit of PP2A complex and exerts anti-tumor effects on human T cell acute lymphoblastic leukemia. However, the effect of PPZ on canine lymphoma has not been studied. Here, we investigated the potential therapeutic role of PPZ and its molecular mechanism in canine T-cell lymphoma. In canine T-cell lymphoma cell lines, UL-1 and Ema, PPZ decreased cell survival in a dose-dependent manner. Increased caspase 3 activity and Annexin V positive cells suggested that PPZ induced apoptosis. PPZ dephosphorylated Akt, MEK1/2 and ERK1/2. Akt inhibitor, but not MEK1/2 inhibitor and ERK1/2 inhibitor, induced cell death, indicating the importance of Akt dephosphorylation for the anti-tumor effect of PPZ. Finally, we observed enhanced PP2A activity by PPZ treatment. The present results for the first time revealed that PPZ induced canine lymphoma cells apoptosis through Akt dephosphorylation via PP2A activation. Our study suggests the possible therapeutic application of phenothiazines for canine T-cell lymphoma. [ABSTRACT FROM AUTHOR]

The article provides the clinical signs and macroscopic and microscopic features of a thymic lymphoma in an arowana with a brief review of the literature. It cites a 1 year old gold crossback arowana presented to the Prasu-Arthorn animal hospital with a history of a weeklong period anorexia and delayed or lack of response to external stimuli. It describes the pathological and histophathologic findings associated with spontaneous thymic lymphoma in a gold crossback arowana.

Background Dysregulated apoptosis is a hallmark of tumorigenesis, and is also involved in resistance to cytotoxic treatment, and might be relevant in lymphoma in dogs. Hypothesis/Objectives That Bcl-2/Bax expression patterns differ between lymphoma immunophenotypes, and that Bcl-2/Bax ratio is correlated with prognosis. Animals Fifty-five client-owned dogs with multicentric lymphoma and 5 healthy dogs. Methods Prospective, case-control study. We compared 3 methods (flow cytometry, qRT- PCR, Western blot) for Bcl-2 and Bax quantification in a subset of dogs. The effect of time on Bcl-2/Bax ratios measured by flow cytometry was assessed in lymphoma cell lines. Immunophenotype and Bcl-2/Bax expression by flow cytometry were determined in LN aspirates from all dogs with multicentric lymphoma compared to healthy dogs. Progression-free survival ( PFS) was retrospectively evaluated in a group of dogs all receiving similar treatment. Results Bcl-2/Bax ratios remain consistent for at least 5 days after sample collection. Bcl-2/Bax ratio was higher in dogs with T-cell lymphoma (TCL; median 0.97, range 0.37-1.36) compared to B-cell lymphoma (BCL; median 0.36, range 0.07-1.45) ( P < .0001) and normal dogs (median 0.36, range 0.21-0.48) ( P = .0006), respectively. Dogs with Bcl-2/Bax ratios higher than the median of the group experienced a median PFS of 101 days and dogs with ratios equal and lower than the median had PFS of 130 days ( P = .19). Conclusions and clinical importance Higher intrinsic resistance to apoptosis following cytotoxic treatment might contribute to the less favorable prognosis associated with multicentric TCL in dogs. Whether Bcl-2/Bax will be helpful to identify canine BCL and TCL with more aggressive and more indolent behavior, respectively, should be evaluated in larger prospective clinical studies. [ABSTRACT FROM AUTHOR]

Adoptive T cell therapy (ACT) with antitumor CTL is a promising and tailored treatment against cancer. We investigated the role played by the affinity and avidity of the interaction between the tumor and the CTL on the outcome of ACT against a mouse non-Hodgkin B cell lymphoma that expresses OVA as a model neoantigen. ACT was assessed under conditions where antitumor CTL expressed TCR of varying affinity for OVA. We also assessed conditions where the avidity of Ag recognition varied because the lymphoma cells expressed high or low levels of OVA. Efficient eradication of small tumor burdens was achieved by high- or low-affinity CTL. Tumors expressing low levels of OVA could also be eliminated. However, ACT against large tumor burdens was unsuccessful, accompanied by CTL deletion and functional impairment. This negative outcome was not prevented by lowering the affinity of the CTL or the expression of OVA in the lymphoma. Thus, tumor burden, rather than CTL affinity or avidity, appears to be the main determinant of ACT outcomes in our lymphoma model. Insofar as our results can be extrapolated to the clinical setting, they imply that the range of CTL and tumor-associated Ag combinations that may be effectively harnessed in ACT against lymphoma may be wider than generally assumed. CTL expressing low-affinity TCR may be effective against lymphoma, and lowly expressed tumor-associated Ag should be considered as potential targets, but tumor reduction should always be implemented before infusion of the CTL. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Veterinary Journal / Revue Vétérinaire Canadienne is the property of Canadian Veterinary Medical Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The present clinical report describes a rare sporadic clinical case of chronic diarrhea due to lymphosarcoma in a 7-yearold crossbred Holstein-Friesian cattle. Diarrhea occurred due to intestinal lymphoid tissue involvement. The clinical diagnosis of lymphosarcoma was derived from peritoneal fluid aspirate, lymph node enlargement, and absence of serological and fecal evidence of any parasitic or bacterial infection. Reactive proliferative mesothelial hyperplasia in peritoneal fluid examination confirmed lymphosarcoma. The cells form numerous 3-dimensional clusters in mesothelial lymphosarcoma. Postmortem examinations confirmed visceral lymph node enlargements. A hematological examination revealed leukocytosis and a marked decrease in hemoglobin level, which reflected a severe degree of anemia. A clinical diagnosis of bovine lymphosarcoma was made, with visceral lymph node enlargement resulting in consistent chronic diarrhea in the adult cow. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 1-year old 223-kg replacement crossbreed dairy heifer submitted for necroscopy. Topics discussed include diagnosis of bovine leukemia virus (BLV) infection, B-cell lineage present in associated lymphomas, and visualizing changes in airway through videofluoroscopy.

The article presents abstracts on veterinary pathology which include canine hepatic copper content, T-zone lymphoma in dogs and canine chronic lymphocytic leukemia and lymphoma.

Lymphoma is the most common haematopoietic malignancy in dogs and it has been associated with hypercoagulability and subsequent thromboembolism. The objectives of this study were to serially characterize the haemostatic status of dogs with multicentric lymphoma. Thromboelastography, thrombin-antithrombin complex concentration and routine haematology and coagulation panels were measured. Twenty-seven dogs were included in the study and 15 completed the study in remission. At presentation, 81% (22/27) of dogs with multicentric lymphoma had altered haemostatic profiles consistent with hypercoagulability. Laboratory evidence of hypercoagulability did not resolve during treatment or for up to 1 month following attainment of clinical remission. Accelerated rate of clot formation at the time of chemotherapeutic protocol completion was associated with decreased survival time. We concluded that dogs with multicentric lymphoma were frequently hypercoagulable from presentation through 4 weeks after the completion of chemotherapy. Increased angle and shortened K in dogs that have successfully completed their chemotherapeutic protocol may be associated with shorter survival times. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinase-2 and -9 (MMP-2 and -9), gelatinases among MMPs, are associated with cell migration, invasion, metastasis and angiogenesis in human solid tumor. The prognostic value of gelatinases in canine lymphoma remains equivocal. To evaluate the relation between serum gelatinases and canine lymphoma, gelatin zymography was used to detect the levels of serum MMP-2 and MMP-9 gelatinase activities in lymphoma-bearing dogs. In this retrospective study, twenty-four canine patients with different subtypes of lymphoma were identified according to the histopathogical examination, and 10 healthy dogs were included as control. Serum samples from the lymphoma-bearing dogs were collected before and after chemotherapy. Results showed that the MMP-9 levels increased in the lymphoma-bearing dogs (median: 199.37, interquartile difference: 37.67) and decreased after a complete response was achieved (median: 140.64, interquartile difference 48.62); however, the MMP-2 levels among the controls and lymphoma-bearing dogs with treatment were similar (before: median: 138.42, interquartile difference: 35.7; complete response: median: 119.26, interquartile difference: 39.03). Both MMP-2 and MMP-9 levels were higher in T-cell lymphoma than in B-cell lymphoma patients. Compared with MMP-2, changes in the level of serum MMP-9 gelatinase activity could be a prognostic factor in canine lymphoma. [ABSTRACT FROM AUTHOR]

Background: Koala retrovirus (KoRV) is an endogenous and exogenous retrovirus of koalas that may cause lymphoma. As for many other gammaretroviruses, the KoRV genome can potentially encode an alternate form of Gag protein, glyco-gag. Results: In this study, a convenient assay for assessing KoRV infectivity in vitro was employed: the use of DERSE cells (initially developed to search for infectious xenotropic murine leukemia-like viruses). Using infection of DERSE and other human cell lines (HEK293T), no evidence for expression of glyco-gag by KoRV was found, either in expression of glyco-gag protein or changes in infectivity when the putative glyco-gag reading frame was mutated. Since glyco-gag mediates resistance of Moloney murine leukemia virus to the restriction factor APOBEC3, the sensitivity of KoRV (wt or putatively mutant for glyco-gag) to restriction by murine (mA3) or human APOBEC3s was investigated. Both mA3 and hA3G potently inhibited KoRV infectivity. Interestingly, hA3G restriction was accompanied by extensive G → A hypermutation during reverse transcription while mA3 restriction was not. Glyco-gag status did not affect the results. Conclusions: These results indicate that the mechanisms of APOBEC3 restriction of KoRV by hA3G and mA3 differ (deamination dependent vs. independent) and glyco-gag does not play a role in the restriction. [ABSTRACT FROM AUTHOR]

The article discusses a study on the relationship between serum ferritin concentration before treatment and survival time in dogs with multicentric lymphoma. Topics include the classification of the dogs into high and low ferritin groups, the median survival times for each group, and findings suggesting that the initial high level of serum ferritin indicates short survival time in dogs with multicentric lymphoma. Large-scale research is recommended to confirm the study's findings.

The article presents abstracts presented during the 7th Congress of the European College of Equine Internal Medicine including the importance of responsible antimicrobial use among equine practitioners in Great Britain, a survey of equine lymphoma population and severe hyponatraemia in hospitalized foals.

Background: Cats infected with exogenous feline leukemia virus (exFeLV) have a higher chance of lymphoma development than uninfected cats. Furthermore, an increased exFeLV transcription has been detected in lymphomas compared to non-malignant tissues. The possible mechanisms of lymphoma development by exFeLV are insertional mutagenesis or persistent stimulation of host immune cells by viral antigens, bringing them at risk for malignant transformation. Vaccination of cats against exFeLV has in recent years decreased the overall infection rate in most countries. Nevertheless, an increasing number of lymphomas have been diagnosed among exFeLV-negative cats. Endogenous feline leukemia virus (enFeLV) is another retrovirus for which transcription has been observed in cat lymphomas. EnFeLV provirus elements are present in the germline of various cat species and share a high sequence similarity with exFeLV but, due to mutations, are incapable of producing infectious viral particles. However, recombination between exFeLV and enFeLV could produce infectious particles. Results: We examined the FeLV expression in cats that have developed malignant lymphomas and discussed the possible mechanisms that could have induced malignant transformation. For expression analysis we used next-generation RNA-sequencing (RNA-Seq) and for validation reverse transcription quantitative PCR (RT-qPCR). First, we showed that there was no expression of exFeLV in all samples, which eliminates the possibility of recombination between exFeLV and enFeLV. Next, we analyzed the difference in expression of three enFeLV genes between control and lymphoma samples. Our analysis showed an average of 3.40-fold decreased viral expression for the three genes in lymphoma compared to control samples. The results were confirmed by RT-qPCR. Conclusions: There is a decreased expression of enFeLV genes in lymphomas versus control samples, which contradicts previous observations for the exFeLV. Our results suggest that a persistent stimulation of host immune cells is not an appropriate mechanism responsible for malignant transformation caused by feline endogenous retroviruses. [ABSTRACT FROM AUTHOR]

Lymphomas are common spontaneous tumors in nonhuman primates but remain poorly characterized in Japanese macaques (Macaca fuscata). This study examined 5 cases of spontaneous malignant lymphoma in Japanese macaques, focusing on the immunophenotypes and presence of simian lymphocryptoviruses, which are Epstein-Barr virus-related herpesviruses in nonhuman primates. The macaques with lymphoma were 5 to 28 years old, indicating that lymphomas develop over a wide age range. The common macroscopic findings were splenomegaly and enlargement of lymph nodes. Histologic and immunohistochemical analyses revealed that all cases were non-Hodgkin type and exhibited a T-cell phenotype, positive for CD3 but negative for CD20 and CD79α. The lymphomas exhibited diverse cellular morphologies and were subdivided into 3 types according to the World Health Organization classification. These included 3 cases of peripheral T-cell lymphoma, not otherwise specified; 1 case of T-cell prolymphocytic leukemia; and 1 case of an unclassifiable T-cell lymphoma. Positive signals were detected by in situ hybridization in 2 of the 4 examined cases using probes for the Epstein-Barr virus-encoded small RNA (EBER). Furthermore, the presence of M. fuscata lymphocryptovirus 2, a macaque homolog of Epstein-Barr virus, was demonstrated in EBER-positive cases by polymerase chain reaction amplification followed by direct sequencing. Immunohistochemistry using antibody to the Epstein-Barr virus-encoded nuclear antigen 2 was negative, even in the EBER-positive cases. The present study suggests that T-cell lymphoma is more common than B-cell lymphoma in Japanese macaques and that M. fuscata lymphocryptovirus 2 is present in some cases. [ABSTRACT FROM PUBLISHER]

Bovine leukemia virus (BLV) infection is widespread in the US dairy industry and the majority of producers do not actively try to manage or reduce BLV incidence within their herds. However, BLV is estimated to cost the dairy industry hundreds of millions of dollars annually and this is likely a conservative estimate. BLV is not thought to cause animal distress or serious pathology unless infection progresses to leukemia or lymphoma. However, a wealth of research supports the notion that BLV infection causes widespread abnormal immune function. BLV infection can impact cells of both the innate and adaptive immune system and alter proper functioning of uninfected cells. Despite strong evidence of abnormal immune signaling and functioning, little research has investigated the large-scale effects of BLV infection on host immunity and resistance to other infectious diseases. This review focuses on mechanisms of immune suppression associated with BLV infection, specifically aberrant signaling, proliferation and apoptosis, and the implications of switching from BLV latency to activation. In addition, this review will highlight underdeveloped areas of research relating to BLV infection and how it causes immune suppression. [ABSTRACT FROM AUTHOR]

Background The antimetabolite 6-thioguanine (6-TG) has been used to treat both human and canine lymphoid malignancies. 6-TG has been shown to be epigenetically active as a demethylating agent in a human lymphoma cell line, causing downregulation of DNA methyltransferase 1 (DNMT1) through ubiquitin-targeted degradation. Zebularine (Zeb), a similar cytidine analog, also has demethylating activity as well as oral bioavailability. The hypothesis of the present study was that 6-TG and Zeb would cause downregulation of DNMT1 and globally demethylate the genomic DNA of canine lymphoma cells. The secondary hypothesis was that these agents would cause a dose-dependent decrease in cell proliferation in canine lymphoma cells. Canine CLGL-90 malignant T cells and CLL 17-7 cells were incubated in modified RPMI media. They were treated with 6-TG, Zeb, or control media at biologically relevant concentrations. Results Following treatment with each agent, DNMT1 protein and global DNA methylation were significantly decreased. A dose-dependent decrease in cell survival was also observed, with apoptosis being the primary mode of cell death in the CLGL-90 cell line. Conclusions These results confirm the demethylating action of 6-TG and Zeb in canine cells which is similar to that shown in human cell lines. Confirmation of this mechanism supports the clinical application of these compounds as demethylating drugs in veterinary patients. [ABSTRACT FROM AUTHOR]

The article presents a study which characterized the sonographic appearance of thymomas, the neoplasms that are typically located in the cranioventral mediastinum in domestic species. Topics discussed include medical records and sonograms of animals diagnosed with either mediastinal thymoma or lymphoma between January 2005 and February 2012, characteristics made on the masses, and sonographic findings in mediastinal masses.

Acquisition of multidrug resistance (MDR) is a common cause of treatment failure during chemotherapy for dogs with lymphoma (lymphosarcoma). Overexpression of P-glycoprotein (P-gp), encoded by the ABCB1 gene, is associated with MDR. Perifosine, an Akt inhibitor, downregulates the expression of P-gp. In this study, the antitumour effect of perifosine and its ability to modulate ABCB1 expression were examined in four canine lymphoid tumour cell lines (GL-1, CLBL-1, UL-1 and Ema). GL-1 and CLBL-1 were inherently negative for P-gp, while UL-1 and Ema were inherently positive for P-gp. GL-1 and UL-1 were sensitive to perifosine, whereas CLBL-1 and Ema were resistant. The amount of ABCB1 mRNA significantly decreased after treatment with perifosine in UL-1, associated with activation of the c-Jun NH2-terminal kinase (JNK) pathway, but such an effect was not observed in Ema. In UL-1, perifosine decreased the efflux of rhodamine 123 dye and reduced the 50% inhibitory concentration of vincristine, but such effects were not observed in Ema. Perifosine had an antitumour effect in 2/4 canine lymphoid tumour cell lines. In 1/4 cell lines, perifosine downregulated ABCB1 gene expression through activation of the JNK pathway and increased sensitivity to vincristine. [ABSTRACT FROM AUTHOR]

The Silkie is a typical Chinese breed of chicken. In 2012, batches of Silkies were found to have diffuse tumor-like nodules on their skin after feather removal, when they were slaughtered at about 60 days old. Gross examination showed no visible neoplastic lesions on the visceral organs and peripheral nerves, except slight splenomegaly in individual chickens. The disease was prevalent, with high condemnation rates for skin lesions, which caused great economic losses to the company. Tissues, including skin, visceral organs, and peripheral nerves, were collected for histologic examination. Heparinized blood samples were collected for virus isolation and identification. Marek’s disease virus (MDV), Reticuloendotheliosis virus (REV), and Avian leukosis virus (ALV) were analyzed, using polymerase chain reaction (PCR) tests. Histologic examination showed that all of the tumor-like nodules on the skin were lymphomas. Lymphoproliferative lesions occurred mostly on the skin and only a few on the viscera, including the liver and proventriculus. Infected chick embryo fibroblasts showed clear cytopathic effects; indirect fluorescent antibody test for envelope glycoprotein B was positive. In addition, PCR indicated the presence of MDV serotype 1 infection without REV and ALV. A phylogenetic tree of the Meq gene showed that the isolate (SD121201) and Chinese reference strains, which are very virulent MDVs, are in the same clade. It was concluded that the Silkies tested were infected with MDV serotype 1. The Marek’s disease epidemic has been controlled using CVI988/Rispens vaccines. [ABSTRACT FROM PUBLISHER]

The prognostic significance of the inactivation of the p16, p15, and p14 genes has been reported in lymphoid malignancies in humans. To evaluate the relationship between inactivation of the p 16, p 15, and p 14 genes and prognosis in canine high-grade lymphoma, primary tumor cell samples obtained from 71 dogs with high-grade lymphoma were examined for the expression levels of these genes. Quantitative and conventional reverse transcriptase-polymerase chain reaction (RT-PCR) analyses were used to measure the amounts of p16, p15, and p14 mRNAs. The methylation status of the CpG island of the p16 gene was evaluated using methylation-specific PCR. Overall survival (OS) was compared using the Kaplan-Meier method. The log-rank test and Cox proportional hazard model were used to evaluate factors that influenced OS. Of 62 dogs examined, p 16, p 15, and p 14 mRNA levels were found to be undetectable in 21, 18, and 10 dogs, respectively. In 20/68 dogs analyzed, the CpG island of the p16 gene was shown to be methylated. The prognostic significance of inactivation of the p16, p15, and p14 genes as well as various conventional factors obtained from medical records was examined, p 16 expression status and anatomic form/immunophenotype were found to correlate with OS in the dogs with high-grade lymphoma, p 16 mRNA level over its cut-off value correlated with a poor prognosis; however, the expression levels of p 15 and p14 mRNAs and p16 methylation status did not influence the prognosis in dogs with high-grade lymphoma. [ABSTRACT FROM AUTHOR]

Summary: This report describes the pathological findings in an adult female short-beaked common dolphin (Delphinus delphis) stranded alive in the Canary Islands. Necropsy examination revealed the presence of a nodular neoplastic growth in the central nervous system (CNS) at the level of the thalamus. Microscopical examination revealed the mass to be a lymphoma and immunohistochemical labelling demonstrated a T-cell origin. No significant lesions were observed in other organs, including lymphoid organs. This is the first report of a primary T-cell lymphoma in the CNS in cetaceans. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 4 1/2-year-old, 3-months pregnant Holstein cow, diagnosed with laryngeal obstruction. It mentions that the cow was admitted to the Centre Hospitalier Universitaire Yeterinaire (CHUV) for inspiratory dyspnea. Topics discussed include swollen arytenoids and a presumptive diagnosis of bilateral arytenoidal chondritis by endoscopic evaluation, right arytenoid was submitted for histopathology, and a diagnosis of laryngeal lymphoma.

The article discusses the results of a research study which evaluates the difference between the retinoid receptor expression and the non-neoplastic lymph nodes and nodal lymphoma in dogs. It mentions the use of the immunohistochemistry as the process to detect the retinoid receptors in non-neoplastic canine lymph nodes and lymphoma. It also suggests that the use of immunohistochemistry shows the value of both diagnosis and treatment of canine lymphoma.

Overexpression of ABC-transporters including Pgp, MRP1, and BCRP has been associated with multidrug resistance ( MDR) in both human and canine oncology. Therapeutic interventions to reverse MDR are limited, but include multidrug protocols and the temporary concomitant use of inhibitors of ABC-transporters. Recently, the use of tyrosine kinase inhibitors has been proposed to overcome MDR in human oncology. One of the tyrosine kinase inhibitors, masitinib, is licensed for veterinary use in the treatment of canine mast cell tumors. Therefore, this study aimed to assess the potential of masitinib to revert MDR in canine malignant lymphoma using an in vitro model with canine lymphoid cell lines. Masitinib had a mild antiproliferative effect on lymphoid cells, inhibited Pgp function at concentrations equal to or exceeding 1 μ m and was able to reverse doxorubicin resistance. The current findings provide the rationale for a combined use of masitinib with doxorubicin in the treatment of dogs with doxorubicin-resistant malignant lymphoma but await confirmation in clinical trials. [ABSTRACT FROM AUTHOR]