MRI ischemic and hemorrhagic lesions in arterial and venous territories characterize central nervous system intravascular lymphoma in dogs.

Intravascular lymphoma (IVL) is characterized by the proliferation of large malignant lymphocytes within the lumen of blood vessels. This retrospective, multi-center, case series study aimed to describe the MRI features of confirmed central nervous system IVL in dogs and compare them with histopathological findings. Medical record databases from seven veterinary centers were searched for cases of histologically confirmed IVL. Dogs were included if an MRI was performed. The MRI studies and histopathology samples were reviewed to compare the MRI changes with the histopathological findings. Twelve dogs met the inclusion criteria (12 brains and three spinal cords). Imaging of the brains revealed multifocal T2-weighted/FLAIR hyperintense and T1-weighted iso-hypointense lesions, with variable contrast enhancement; areas of abnormal diffusion both in arterial and venous territories in diffusion-weighted imaging; and meningeal enhancement. On gradient echo images (GRE), the changes comprised tubular susceptibility artifacts, consistent with the "susceptibility vessel sign", and additional variably sized/shaped intraparenchymal susceptibility artifacts. Spinal cord lesions presented as fusiform T2-weighted hyperintensities with scattered susceptibility artifacts on GRE and variable parenchymal and meningeal contrast enhancement. On histopathology, subarachnoid hemorrhages and neuroparenchymal areas of edema and necrosis, with or without hemorrhage, indicating ischemic and hemorrhagic infarctions, were found. These lesions were concurrent with severely dilated meningeal and parenchymal arteries and veins plugged by neoplastic lymphocytes and fibrin. Due to the unique angiocentric distribution of IVL, ischemic and hemorrhagic infarcts of variable chronicity affecting both the arterial and venous territories associated with thrombi formation can be detected on MRI.

A case of colonic-colonic intussusception in a dog secondary to lymphoma treated with colonic resection and anastomosis.

A 2-year-old castrated male Great Dane crossbreed dog was presented with a history of diarrhea and suspected intussusception. Abdominal ultrasound revealed a colonic-colonic intussusception. The gastrointestinal tract was explored, and an approximately 5-cm intussusception was discovered mid-colon. All other gastrointestinal structures were normal in appearance. The intussusception could not be reduced manually. A colonic resection and anastomosis were performed together with a left-sided incisional colopexy. The dog recovered from surgery and histopathology revealed the intussusception to be secondary to large cell transmural lymphoma. Sections from the surgical margins revealed proliferation of fibrovascular tissue along the serosal surface segmentally, but no neoplastic cells were identified. The dog was subsequently treated with chemotherapy consisting of doxorubicin and prednisone. No evidence of disease recurrence was noted on ultrasound 9 months after surgery. Approximately 2 years after surgery, the dog is noted to be clinically normal at home with no abnormal findings on physical examination. A complete blood (cell) count and chemistry obtained at this time revealed no significant abnormalities besides mild azotemia. Additional restaging was declined by the owner.

Un cas d'intussusception colon-colon chez un chien secondaire à un lymphome traité par résection c olonique et anastomose. Un grand danois croisé mâle castré âgé de 2 ans a été présenté avec des antécédents de diarrhée et une suspicion d'intussusception. L'échographie abdominale a révélé une intussusception colon-colon. Le tractus gastro-intestinal a été exploré et une intussusception d'environ 5 cm a été découverte au milieu du côlon. Toutes les autres structures gastro-intestinales avaient un aspect normal. L'intussusception n'a pas pu être réduite manuellement. Une résection colonique et une anastomose ont été réalisées avec une colopexie incisionnelle du côté gauche. Le chien a récupéré de la chirurgie et de l'histopathologie a révélé que l'intussusception était secondaire à un lymphome transmural à grandes cellules. Des sections des marges chirurgicales ont révélé une prolifération de tissu fibrovasculaire le long de la surface séreuse de manière segmentaire, mais aucune cellule néoplasique n'a été identifiée. Le chien a ensuite été traité par une chimiothérapie composée de doxorubicine et de prednisone. Aucun signe de récidive de la maladie n'a été noté à l'échographie 9 mois après la chirurgie. Environ 2 ans après la chirurgie, le chien est cliniquement normal à la maison sans résultats anormaux à l'examen physique. Une numération sanguine (cellule) complète et l'analyse chimique obtenues à ce moment n'ont révélé aucune anomalie significative outre une légère azotémie. Une nouvelle restadification a été refusée par le propriétaire.(Traduit par Dr Serge Messier).

Prognostic role of lymphocyte to monocyte ratio in feline high-grade lymphomas.

The lymphocyte to monocyte ratio (LMR) is a useful prognostic marker of various cancers in human and canine patients. This study aimed to determine whether this ratio could predict disease outcomes in cats with high-grade lymphoma. Medical records of 33 cats diagnosed with high-grade lymphoma were retrospectively analyzed. The prognostic influence of LMR and other clinicopathological data on the time to progression (TTP) and overall survival (OS) was studied using the Kaplan-Meier curves. The optimal cutoff value of this ratio was 3.4, which corresponded to the maximum sensitivity (1.000) and specificity (0.611) of the LMR for predicting median OS days, using receiver operating characteristic analysis. A univariate analysis demonstrated that cats with a low LMR had significant reductions in both TTP [hazard ration (HR) = 3.403, 95% confidence interval (CI): 1.502 to 8.720; P = 0.003] and OS (HR = 3.418, 95% CI: 1.433 to 9.449, P = 0.005). In multivariate analysis, independent predictors of OS included LMR (HR = 2.889, 95% CI: 1.048 to 8.843, P = 0.040), clinical stage (HR = 0.330, 95% CI: 0.118 to 0.960, P = 0.042), and age (HR = 4.151, 95% CI: 1.574 to 11.888, P = 0.004).

Rôle pronostique du rapport lymphocytes sur monocytes dans les lymphomes félins de grade élevé. Le rapport lymphocyte sur monocytes (LMR) est un marqueur pronostique utile de divers cancers chez les patients humains et canins. Cette étude visait à déterminer si ce rapport pouvait prédire l'issue de la maladie chez les chats atteints d'un lymphome de grade élevé. Les dossiers médicaux de 33 chats diagnostiqués avec un lymphome de grade élevé ont été analysés rétrospectivement. L'influence pronostique de la LMR et d'autres données clinicopathologiques sur le temps de progression (TTP) et la survie globale (OS) a été étudiée à l'aide des courbes de Kaplan-Meier. La valeur seuil optimale de ce rapport était de 3,4, ce qui correspondait à la sensibilité (1,000) et à la spécificité maximales (0,611) du LMR pour prédire les jours de OS médians, en utilisant l'analyse des caractéristiques de fonctionnement du récepteur. Une analyse univariée a démontré que les chats avec un faible LMR présentaient des réductions significatives du TTP [rapport de risque (HR) = 3,403, intervalle de confiance (IC) à 95 % : 1,502 à 8,720; P = 0,003] et de la OS (HR = 3,418, IC à 95 % : 1,433 à 9,449, P = 0,005). Dans l'analyse multivariée, les prédicteurs indépendants de la OS comprenaient le LMR (HR = 2,889, IC à 95 % : 1,048 à 8,843, P = 0,040), le stade clinique (HR = 0,330, IC à 95 % : 0,118 à 0,960, P = 0,042) et l'âge (HR = 4,151, IC à 95 % : 1,574 à 11,888, P = 0,004).(Traduit par Dr Serge Messier).

RNA disruption indicates CHOP therapy efficacy in canine lymphoma.

BACKGROUND: Assessment of the efficacy of a multi-agent chemotherapy protocol in which cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) are administered in canine lymphoma is generally performed by physical measurement of lymph node diameter. However, no consistent correlation has been made with prognostic indicators and the length or absence of clinical remission based on lymph node size. RNA disruption measured mid-therapy has been correlated with increased disease-free survival in recent studies of human cancer and was assessed in this study of canine lymphoma patients. Fine needle aspirate samples were taken before treatment and at weeks 3, 6, and 11 of CHOP therapy. RNA was isolated from these samples and assessed using an Agilent Bioanalyzer. RNA disruption assay (RDA) analysis was performed on the data from the resulting electropherograms. RESULTS: An increased RNA disruption index (RDI) score was significantly associated with improved progression-free survival. CONCLUSIONS: Predicting the risk of early relapse during chemotherapy could benefit veterinary patients by reducing ineffective treatment and could allow veterinary oncologists to switch earlier to a more effective drug regimen.

Man's best friend: what can pet dogs teach us about non-Hodgkin's lymphoma?

Animal models are essential for understanding lymphoma biology and testing new treatments prior to human studies. Spontaneously arising lymphomas in pet dogs represent an underutilized resource that could be used to complement current mouse lymphoma models, which do not adequately represent all aspects of the human disease. Canine lymphoma resembles human lymphoma in many important ways, including characteristic translocations and molecular abnormalities and similar therapeutic responses to chemotherapy, radiation, and newer targeted therapies (e.g. ibrutinib). Given the large number of pet dogs and high incidence of lymphoma, particularly in susceptible breeds, dogs represent a largely untapped resource for advancing the understanding and treatment of human lymphoma. This review highlights similarities in molecular biology, diagnosis, treatment, and outcomes between human and canine lymphoma. It also describes resources that are currently available to study canine lymphoma, advantages to be gained by exploiting the genetic breed structure in dogs, and current and future challenges and opportunities to take full advantage of this resource for lymphoma studies.

Enzooty of non-Hodgkin's malignant lymphoma of Papio hamadryas in Sukhumi monkey colony. Clinical and morphological signs of pre-lymphoma.

Inoculation of hamadryas baboons with blood of leukemia ill people-induced malignant non-Hodgkin's lymphoma in experimental animals for a very considerable latency period. At close contact of inoculated baboons with healthy non-inoculated animals, the lymphoma spread between them. The epidemiological analysis, postmortem examination, histological analysis, tissue culturing, and PCR were used for the diagnostics of lymphoma and pre-lymphoma, purification, identification of STLV-1, and HVP viruses. Characteristic clinical and morphological signs designated by us as pre-lymphoma often precede the lymphoma development. In some cases, pre-lymphoma does not develop in lymphoma because animals die from various diseases and do not reach the point of the lymphoma development. The horizontal transmission of lymphoma arising with the participation of T-lymphotropic retrovirus STLV-1 is shown.

Feline low-grade alimentary lymphoma: an emerging entity and a potential animal model for human disease.

BACKGROUND: Low-grade alimentary lymphoma (LGAL) is characterised by the infiltration of neoplastic T-lymphocytes, typically in the small intestine. The incidence of LGAL has increased over the last ten years and it is now the most frequent digestive neoplasia in cats and comprises 60 to 75% of gastrointestinal lymphoma cases. Given that LGAL shares common clinical, paraclinical and ultrasonographic features with inflammatory bowel diseases, establishing a diagnosis is challenging. A review was designed to summarise current knowledge of the pathogenesis, diagnosis, prognosis and treatment of feline LGAL. Electronic searches of PubMed and Science Direct were carried out without date or language restrictions. RESULTS: A total of 176 peer-reviewed documents were identified and most of which were published in the last twenty years. 130 studies were found from the veterinary literature and 46 from the human medicine literature. Heterogeneity of study designs and outcome measures made meta-analysis inappropriate. The pathophysiology of feline LGAL still needs to be elucidated, not least the putative roles of infectious agents, environmental factors as well as genetic events. The most common therapeutic strategy is combination treatment with prednisolone and chlorambucil, and prolonged remission can often be achieved. Developments in immunohistochemical analysis and clonality testing have improved the confidence of clinicians in obtaining a correct diagnosis between LGAL and IBD. The condition shares similarities with some diseases in humans, especially human indolent T-cell lymphoproliferative disorder of the gastrointestinal tract. CONCLUSIONS: The pathophysiology of feline LGAL still needs to be elucidated and prospective studies as well as standardisation of therapeutic strategies are needed. A combination of conventional histopathology and immunohistochemistry remains the current gold-standard test, but clinicians should be cautious about reclassifying cats previously diagnosed with IBD to lymphoma on the basis of clonality testing. Importantly, feline LGAL could be considered to be a potential animal model for indolent digestive T-cell lymphoproliferative disorder, a rare condition in human medicine.

Dogs with acute myeloid leukemia or lymphoid neoplasms (large cell lymphoma or acute lymphoblastic leukemia) may have indistinguishable mediastinal masses on radiographs.

Acute myeloid leukemia is an uncommon hematopoietic neoplasm of dogs that should be differentiated from lymphoid neoplasms, such as lymphoma, because of different treatment protocols and a worse prognosis. Thoracic radiography is performed frequently in dogs with suspected hematopoietic neoplasia, and detecting a mediastinal mass often prioritizes lymphoma as the most likely diagnosis. However, we have observed a mediastinal mass in several dogs with acute myeloid leukemia and hypothesized that (1) the frequency of a mediastinal mass was higher and (2) the size of the mass was larger in dogs with acute myeloid leukemia compared to dogs with lymphoid neoplasms. In this analytical study (observational, retrospective, and cross-sectional), the sample population included 238 dogs with hematopoietic neoplasia. These dogs were divided into lymphoid (large cell lymphoma, acute lymphoblastic leukemia) and myeloid groups based on standard phenotyping tests. A mediastinal mass was detected during thoracic radiography in 73/218 (33%) and nine of 20 (45%) dogs in the lymphoid and myeloid groups (P = 0.21), respectively. The median size ratio of mediastinal mass to cardiac silhouette was 0.20 and 0.23 in the lymphoid and myeloid groups (P = 0.96), respectively. Additionally, we observed normal thoracic radiographs in 111/218 (51%) dogs in the lymphoid group and nine of 20 (45%) dogs in the myeloid group. In conclusion, acute myeloid leukemia should be considered when a mediastinal mass is detected during radiography in dogs with suspected hematopoietic neoplasia-but the presence or size of a mediastinal mass does not differentiate between myeloid and lymphoid neoplasms.

Hemoabdomen secondary to high grade lymphoma.

A 10-year-old castrated male Labrador retriever dog was presented for evaluation of a right elbow mass. Mandibular lymphadenopathy was noted on physical examination. Following sudden death after discharge, a necropsy was performed. Cause of death was determined to be due to hemoabdomen secondary to high grade lymphoma.

Hémoabdomen secondaire à un lymphome de haut grade. Un chien mâle Labrador retriever castré âgé de 10 ans a été présenté pour l'évaluation d'une masse au coude droit. Une lymphadénopathie mandibulaire a été observée à l'examen physique. Après une mort soudaine consécutive au congé, une nécropsie a été réalisée. La cause de la mort a été déterminée comme étant un hémoabdomen secondaire à un lymphome de haut grade.(Traduit par Isabelle Vallières).

[Recent advances in transmissible tumors].

Transmissible tumors are a class of tumor that can be transmitted between individuals through living cells. So far, four types of transmissible tumors including canine transmissible venereal tumor (CTVT),Tasmanian devil facial tumor disease (DFTD), soft-shell clams leukemia (SSCL), and hamsters reticulum cell sarcoma (HRCS)have been discovered and identified. In the last decades, these transmissible tumors have been proved to be transmitted through living cells by cytological, histological and genetic studies. CTVT, the oldest mammalian somatic cell line, and DFTD originated from Schwann cell have been reported to avoid immunological recognition by down-regulating MHC expression, while a high copy number of Steamer retrotransposon is commonly exist in SSCL. In recent years, the whole-genome sequencing of CTVT and DFTD have been completed which facilitates studies on the mechanisms of tumorigenesis, transmission and evolution of transmissible tumors at the whole-genome level. In this review, we summarize the recent advances in transmissible tumors and discuss the research focus in next decade.

Monoclonal hyperglobulinemia in lymphosarcoma in a cockatiel (Nymphicus hollandicus) and a blue and gold macaw (Ara ararauna).

A 15-yr-old cockatiel (Nymphicus hollandicus) presented with decreased activity and appetite. A presumptive diagnosis of lymphoproliferative disease was made because of a monoclonal band observed on plasma protein electrophoresis. The owner declined further diagnostics or treatment, and the bird died 2 yr later. In a second case, a 4-yr-old blue and gold macaw (Ara ararauna) presented with lethargy and anorexia. Despite supportive treatment, the bird died 7 days later. Blood studies also demonstrated a monoclonal band on plasma protein electrophoresis. The histologic review of tissues from both birds found extensive neoplastic lymphoplasmocytic cells in the liver and supported a diagnosis of lymphosarcoma.

Focal thoracolumbar spinal cord lymphosarcoma in a ferret (Mustela putorius furo).

A 6-year-old, castrated male domestic ferret (Mustela putorius furo) was euthanized following progressive hind limb paresis and atonia of the bladder of 1-year duration. Neurological evaluation localized the lesion to the thoracolumbar spinal region, and magnetic resonance imaging showed a focal intramedullary spinal cord lesion. Histopathology revealed an extensive, unencapsulated, poorly demarcated mass within the thoracolumbar spinal cord, diagnosed as lymphosarcoma.

Lymphosarcome thoraco-lombaire localisé dans la moelle épinière chez un furet(Mustela putorius furo) . Un furet domestique (Mustela putorius furo) mâle castré âgé de 6 ans a été euthanasié après une parésie progressive des membres postérieurs et une atonie de la vessie d'une durée de 1 an. L'évaluation neurologique a repéré la lésion dans la région de la moelle épinière thoraco-lombaire et une imagerie par résonance magnétique a indiqué une lésion intramédullaire localisée dans la moelle épinière. L'histopathologie a révélé une masse importante, acapsulée et faiblement démarquée dans la moelle épinière thoraco-lombaire qui a été diagnostiquée comme un lymphosarcome.(Traduit par Isabelle Vallières).

Cloacolithiasis and intestinal lymphosarcoma in an African black-footed penguin (Spheniscus demersus).

A 13-yr-old male African black-footed penguin (Spheniscus demersus) presented thrice over 7 mo with gastrointestinal obstruction secondary to cloacolithiasis. Clinical signs consistently resolved with cloacolith removal and supportive care. However, 10 mo after initial presentation, it presented with similar signs, plus significant weight loss. No cloacolith was found, and it subsequently died. Significant gross findings included bilateral cecal masses, colonic perforation, and marked secondary coelomitis, multifocal tan to pale hepatic nodules, and pale kidneys with miliary white foci. Histopathologic diagnoses were intestinal lymphosarcoma with hepatic and renal metastases, secondary intestinal rupture, and subacute severe bacterial coelomitis. To the authors' knowledge, this is the first full report of either cloacolithiasis or lymphosarcoma in a penguin.

Treatment of feline intermediate to high-grade alimentary lymphoma: A retrospective evaluation of 55 cats treated with the VAPC combination chemotherapy protocol (2017-2021).

The most commonly utilized protocols to treat lymphoma in cats employ vincristine, cyclophosphamide and prednisone; with additional drugs sometimes used including L-asparaginase and doxorubicin. Medical records were reviewed for 55 cats with alimentary lymphoma treated with a novel multiagent protocol using prednisolone, L-asparaginase, doxorubicin, vinblastine instead of vincristine, a higher dosage of cyclophosphamide and oral procarbazine (VAPC protocol). Outcomes evaluated were response to therapy, toxicity and progression-free survival (PFS). Grade 3 or 4 neutropenia was the most common treatment-related reason for chemotherapy dosage adjustment, occurring in 8 of 52 cats receiving vinblastine, 7 of 55 cats receiving cyclophosphamide and 1 of 40 cats receiving doxorubicin, but febrile neutropenia was identified in only two cats. Of 38 cats receiving chemotherapy for measurable disease, 26 (68.4%) achieved complete response (CR). Three cats achieved a partial response and 9 cats failed to achieve a remission. There were no identified factors influencing whether a cat was likely to achieve CR. For all 55 cats (including those receiving chemotherapy and surgery), median PFS was 184 days with 1, 2 and 3-year survival rates of 35.4%, 26.5% and 26.5%, respectively. On multivariate analysis, 40 cats that achieved CR had a median survival time of 341 days (78 days for PR, 45 days for NR); PFS times were also significantly affected by lymphocyte:monocyte L:M ratio (>3.4 = 700 days vs. ≤3.4 = 126 days) and B-cell versus T-cell phenotype (220 days vs. 42 days, respectively).

The dog as a possible animal model for human non-Hodgkin lymphoma: a review.

Lymphoma represents the most frequent hematopoietic cancer in dogs, and it shows significant overlap with the human disease. Several environmental factors have been associated with canine lymphoma, suggesting that they may contribute to lymphomagenesis. Canine lymphoma often presents in advanced stage (III-V) at diagnosis and, most commonly, has an aggressive clinical course requiring prompt treatment, which relies on the use of polychemotherapy. In this review, we will summarize the state-of-the-art of canine lymphoma epidemiology, pathobiology, diagnostic work-up and therapy, and will highlight the links to the corresponding human disease, providing evidence for the use of dog as an animal model of spontaneous disease.

Pathology of tumors in fish associated with retroviruses: a review.

Thirteen proliferative diseases in fish have been associated in the literature with 1 or more retroviruses. Typically, these occur as seasonal epizootics affecting farmed and wild fish, and most lesions resolve spontaneously. Spontaneous resolution and lifelong resistance to reinfection are 2 features of some piscine retrovirus-induced tumors that have stimulated research interest in this field. The purpose of this review is to present the reader with the epidemiological and morphological features of proliferative diseases in fish that have been associated with retroviruses by 1 or more of the following methods: detection of C-type retrovirus-like particles or reverse transcriptase activity in tumor tissues; successful tumor transmission trials using well-characterized, tumor-derived, cell-free inocula; or molecular characterization of the virus from spontaneous and experimentally induced tumors. Two of the diseases included in this review, European smelt spawning papillomatosis and bicolor damselfish neurofibromatosis, at one time were attributed to a retroviral etiology, but both are now believed to involve additional viral agents based on more recent investigations. We include the latter 2 entities to update the reader about these developments.

Clinicopathologic significance of histologic grade, pgp, and p53 expression in canine lymphoma.

To characterize the expression of P-glycoprotein (Pgp) and p53 in different histologic grades of canine multicentric lymphosarcoma (LSA), 31 cases of LSA without prior treatment were studied. The expression levels of the Pgp and p53 proteins were evaluated for their clinicopathologic significance among standard histologic evaluation. Immunohistochemistry (IHC) was performed on formalin-fixed, paraffin-embedded archival samples of 31 previously untreated LSA cases to detect the expression of Pgp and p53. All dogs were subsequently treated with a combination chemotherapy protocol. Remission and survival durations were evaluated for correlation with histologic grade and presence of drug resistance markers. Of the 31 cases, 24 (80%) and 7 (22%) were positive for Pgp and p53, respectively. Overall, the median survival and duration of remission in the study was 246 days and 137 days, respectively. The National Cancer Institute working formulation histologic grade was not associated with either survival or duration of first remission (DOR). The Pgp protein expression and DOR and survival was not statistically significant. Expression of p53 was statistically correlated with survival.

[The dog as a model for comparative studies of lymphoma and leukemia in humans]. / Pies jako model do badan porównawczychnad ludzkimi chloniakami i bialaczkami.

Dogs have accompanied humankind for thousands of years. They share the same environment, and thus are exposed to the same environmental factors such as air pollution, tobacco smoke, and various chemicals. Recent development of veterinary care has led to a significant extension of dogs' lifespan and allowed the diagnosis and treatment of a growing number of different diseases in this species. Among all diseases in dogs, cancer is considered the main cause of mortality, with lymphoproliferative disorders accounting for up to 30% of all canine cancers. Some of them, such as non-Hodgkin lymphoma (NHL) and lymphocytic leukemia, are very similar in the etiology, pathogenesis and response to treatment to the diseases occurring in humans. Due to anatomical and physiological similarities to humans, the dog is a useful model for the study of new therapeutic strategies for humans. Studies on the canine neoplasia are currently limited by the lack of well-characterized and widely available cell lines; thus, recently obtained canine NHL cell lines may become a valuable model for such studies. Investigation of their sensitivity to the antiproliferative effects of different factors should allow the creation of a database similar to the existing classification of human leukemias and lymphomas. This should enable quick and accurate diagnosis and selection of appropriate treatment based on phenotypic analysis and histopathological examination of clinical samples. The cooperation between human and veterinary oncologists gives the opportunity to use the dog as a model for the study of certain types of cancers presenting a challenge for modern medicine.