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Objectives The primary goal of this study was to characterize the clinical presentation of feline cutaneous lymphoma. The secondary aims included determining if treatment or initial response to treatment affected the overall survival of patients, and understanding if disease characteristics such as immunophenotype, cell size or the presence of epitheliotropism influenced response to treatment. Methods Veterinary medical oncologists at four academic veterinary teaching hospitals submitted cases of feline patients with cutaneous lymphoma diagnosed by histopathology or cytology. Signalment, feline leukemia virus (FeLV)/feline immunodeficiency virus (FIV) status, physical examination findings, clinical signs, diagnostic tests, therapy, response and outcome, and necropsy findings, when available, were recorded. Results Forty-one patients were identified and described. The majority of patients were domestic shorthair cats (n = 29). The median age at diagnosis was 12.3 years. Males were over-represented in the population (n = 30). In the majority of patients (n = 33), the FIV/FeLV status was unknown. Twenty patients were fully staged. Thirty-four patients were treated with a variety of modalities, including surgery, radiation, single-agent or combination chemotherapy, or prednisolone only. In multiple patients, surgery or radiation was combined with a systemic therapy. Of 34 patients treated with some form of therapy, 20 responded (achieving either a partial response or complete remission). Conclusions and relevance Clinical signs and physical examination findings varied among patients. Response to therapy appeared to be associated with survival (P = 0.0025); however, this population was highly censored. Immunophenotype, cell size and the presence of epitheliotropism did not influence treatment response. Results were limited by small numbers of patients, heterogeneous disease manifestations and treatment protocols. Further studies are necessary to evaluate the effect of specific treatment modalities and disease subtype on prognosis.

Background B‐cell chronic lymphocytic leukemia (BCLL) in dogs generally is considered an indolent disease, but previous studies indicate a wide range in survival times. Objectives We hypothesized that BCLL has a heterogeneous clinical course, similar to chronic lymphocytic leukemia in humans. We aimed to assess presentation and outcome in dogs with BCLL and evaluate the prognostic relevance of clinical and flow cytometric factors. Animals One hundred and twenty‐one dogs with BCLL diagnosed by flow cytometry. Three breed groups were represented: small breed dogs (n = 55) because of increased risk of BCLL; Boxers (n = 33) because of preferential use of unmutated immunoglobulin genes; and other breeds (n = 33). Methods Retrospective study reviewing signalment, clinicopathologic data, physical examination findings, treatment, and survival of dogs with BCLL. Cellular proliferation, determined by the percentage of Ki67‐expressing CD21+ B‐cells by flow cytometry, was measured in 39 of 121 cases. Clinical and laboratory variables were evaluated for association with survival. Results The median survival time (MST) for all cases was 300 days (range, 1‐1644 days). Boxers had significantly shorter survival (MST, 178 days) than non‐Boxers (MST, 423 days; P 40% Ki67‐expressing B‐cells) had significantly shorter survival (MST, 173 days) than did cases with 60 000 lymphocytes/μL) or clinical signs at presentation had significantly shorter survival. Conclusions and Clinical Importance B‐cell chronic lymphocytic leukemia had a variable clinical course and Boxer dogs and cases with high Ki67 had more aggressive disease.

Background Epidemiologic studies suggest residential radon exposure might increase the risk of primary lung cancer in people, but these studies are limited by subject mobility. This limitation might be overcome by evaluating the association in pets. Hypothesis Primary pulmonary neoplasia (PPN) rate is higher in dogs and cats residing in counties with a high radon exposure risk (Environmental Protection Agency [EPA] zone 1) compared to zones 2 (moderate radon exposure risk) and 3 (low radon exposure risk). Animals Six hundred ninety client-owned dogs and 205 client-owned cats with PPN. Methods Retrospective review of medical records at 10 veterinary colleges identified dogs and cats diagnosed with PPN between 2010 and 2015. Each patient's radon exposure was determined by matching the patient's zip code with published county radon exposure risk. County level PPN rates were calculated using the average annual county cat and dog populations. The PPN counts per 100 000 dog/cat years at risk (PPN rates) were compared across radon zones for each species. Results The PPN rate ratio in counties in high radon zone (1) was approximately 2-fold higher than in counties in lower radon zones for dogs (rate ratio zone 1 to 2, 2.49; 95% confidence interval [CI], 1.56-4.00; rate ratio zone 1 to 3, 2.29; 95% CI, 1.46-3.59) and cats (rate ratio zone 1 to 2, 2.13; 95% CI, 0.95-4.79; zone 1 to 3, 1.81; 95% CI, 0.9-3.61). Conclusions and clinical importance Exposure to household radon might play a role in development of PPN in dogs and cats.

Fasting has been shown to decrease chemotherapy‐associated adverse events (AEs), in part through insulin‐like growth factor (IGF‐1) reduction, and may induce a protective effect on normal cells during chemotherapy treatment in mice and people. The purpose of this study was to evaluate the effect of fasting on constitutional, bone marrow and gastrointestinal (GI) AEs, and serum glucose, IGF‐1 and insulin levels in dogs receiving vincristine. The study was a prospective, crossover clinical trial in tumour‐bearing dogs. Dogs were randomized to be fasted for 24 to 28 hours prior to and 6 hours following their first or second vincristine treatment, and fed normally for the alternate dose. A significant reduction in nausea, anorexia, lethargy and serum insulin was observed when dogs were fasted; however, no significant differences were found in other GI symptoms, neutrophil count, serum glucose or IGF‐1. Fasting prior to vincristine therapy is a safe and effective treatment modality that helped mitigate constitutional and GI AEs in tumour‐bearing dogs.

Background Metastasis of appendicular osteosarcoma is most common to the lungs and is generally considered a terminal event in dogs. Behavior and prognosis associated with cutaneous or subcutaneous metastases (CSM) is poorly defined. Objective Describe the population and gather prognostic information regarding appendicular osteosarcoma with CSM in dogs. Animals Twenty dogs with appendicular osteosarcoma and CSM. Methods Retrospective case series. Medical records were searched to identify dogs diagnosed with appendicular osteosarcoma that developed CSM. Demographic data, order of metastatic events, and CSM clinical features were evaluated. Kaplan‐Meier survival curves were constructed and log‐rank tests were used to compare survival between groups of dogs. Results In 19 dogs (95%), CSM was an incidental finding. Seventeen dogs (85%) developed pulmonary metastasis, and 1 dog (5%) developed bone metastasis. No other metastatic sites were detected before euthanasia. The median CSM‐free interval and CSM survival time were 160 days (range: 0‐542 days) and 55 days (range: 5‐336 days), respectively. The median CSM survival time was significantly longer for dogs treated with surgery and chemotherapy (94 days) or chemotherapy only (64 days) than for dogs that did not receive these treatments (11 days) (P = .002 and P = .03, respectively). No other factors were associated with survival after diagnosis of CSM. Conclusion and Clinical Importance The skin or subcutaneous tissue can be the first osteosarcoma metastatic site detected. After CSM diagnosis, the prognosis is grave with median survival

Purpose: The mTOR pathway has been identified as a key nutrient signaling hub that participates in metastatic progression of high-grade osteosarcoma. Inhibition of mTOR signaling is biologically achievable with sirolimus, and might slow the outgrowth of distant metastases. In this study, pet dogs with appendicular osteosarcoma were leveraged as high-value biologic models for pediatric osteosarcoma, to assess mTOR inhibition as a therapeutic strategy for attenuating metastatic disease progression. Patients and Methods: A total of 324 pet dogs diagnosed with treatment-naïve appendicular osteosarcoma were randomized into a two-arm, multicenter, parallel superiority trial whereby dogs received amputation of the affected limb, followed by adjuvant carboplatin chemotherapy ± oral sirolimus therapy. The primary outcome measure was disease-free interval (DFI), as assessed by serial physical and radiologic detection of emergent macroscopic metastases; secondary outcomes included overall 1- and 2-year survival rates, and sirolimus pharmacokinetic variables and their correlative relationship to adverse events and clinical outcomes. Results: There was no significant difference in the median DFI or overall survival between the two arms of this trial; the median DFI and survival for standard-of-care (SOC; defined as amputation and carboplatin therapy) dogs was 180 days [95% confidence interval (CI), 144–237] and 282 days (95% CI, 224–383) and for SOC + sirolimus dogs, it was 204 days (95% CI, 157–217) and 280 days (95% CI, 252–332), respectively. Conclusions: In a population of pet dogs nongenomically segmented for predicted mTOR inhibition response, sequentially administered adjuvant sirolimus, although well tolerated when added to a backbone of therapy, did not extend DFI or survival in dogs with appendicular osteosarcoma.

Background Renal lymphoma in dogs is rare and has a poor prognosis. Granular lymphocyte morphology is rarely reported in canine renal lymphoma. Mild to moderate polycythemia is reported in a number of canine renal lymphoma cases. Case presentation A 10-year-old Labrador retriever presented to a university veterinary teaching hospital after a 1-month history of polyuria, polydipsia, and pollakiuria and a 2-week history of abdominal distention, lethargy, and increased respiratory effort. Abdominal ultrasound showed a wedge-shaped to rounded, heterogeneously hypoechoic mass lesion in the left kidney. Cytologic analysis of a percutaneous aspirate of the mass was consistent with lymphoma of granular lymphocytes. Severe polycythemia (hematocrit 0.871) was noted on a complete blood cell count. Clonality analysis identified a clonally rearranged T-cell receptor (TCR) gene and immunohistochemical staining was CD3+, CD79a- and CD11d+, supporting cytotoxic T-cell lymphoma. Conclusions To our knowledge, this is the first report of renal cytotoxic T-cell lymphoma with severe polycythemia in a dog. Severe polycythemia and renal cytotoxic T-cell lymphoma are both rare in dogs; this report adds to the body of knowledge on these conditions.

Case summary A case of nasal adenocarcinoma as a suspected secondary malignant neoplasm following definitive radiation therapy and multiagent chemotherapy for nasal lymphoma is described. An 11-year-old spayed female domestic shorthair cat was presented for a 3-week history of progressive facial swelling located over the nasal planum and extending to the medial canthus of the right eye. The cat was previously diagnosed with nasal lymphoma and treated with chemotherapy and definitive radiation 2.5 years prior. Although a definitive diagnosis could not be obtained via cytology, recurrent lymphoma was suspected based on the cat’s history and recurrent clinical signs. A lymphoma-directed chemotherapy protocol was attempted, but no clinical response was achieved. The cat was euthanased owing to progressive clinical signs and a diagnosis of nasal adenocarcinoma was made on necropsy examination. Both the original diagnosis of nasal lymphoma and the secondary diagnosis of nasal adenocarcinoma were confirmed with immunohistochemistry. Relevance and novel information Secondary malignant neoplasm following radiation therapy is infrequently reported in the veterinary literature. In the few reports that exist, most have described sarcoma development in the dog following radiation therapy. In the present report, we describe a cat with a suspected radiation-induced nasal adenocarcinoma that developed 2.5 years after definitive radiation treatment for nasal lymphoma.

The role of epigenetic alterations during cancer has gained increasing attention and has resulted in a paradigm shift in our understanding of mechanisms leading to cancer susceptibility. Sulforaphane (SFN) is a naturally occurring isothiocyanate derived from the precursor glucosinolate, glucoraphanin (GFN), which is found in cruciferous vegetables such as broccoli. Sulforaphane has been shown to suppress tumour growth by several mechanisms including inhibiting histone deacetylases. The objective of this study was to provide a detailed analysis of sulforaphane absorption following a single oral dose of a broccoli sprout supplement in normal dogs. A single dose of broccoli sprout supplement (with active myrosinase) was orally administered to 10 healthy adult dogs. Blood and urine samples were collected prior to dosing, and at various time points post‐dosing. Plasma total SFN metabolite levels peaked at 4 h post‐consumption and were cleared by 24 h post‐consumption. Urinary SFN metabolites peaked at 4 h post‐consumption, and remained detectable at 24 and 48 h post‐supplement consumption. A trend for decrease in histone deacetylase activity was observed at 1 h post‐consumption and a significant decrease was observed at 24 h post‐consumption. The data presented herein indicate that oral SFN is absorbed in dogs, SFN metabolites are detectable in plasma and urine post‐dosing, and SFN and its metabolites have some effect on histone deacetylase activity following a single dose.

A 9-year-old spayed female Curly Coated Retriever was referred for evaluation of generalized peripheral lymphadenomegaly. The dog was clinically healthy on presentation with no anomalies detected on complete blood count, serum biochemistry, urinalysis, or three-view thoracic radiographs. Fine-needle aspiration (FNA) and cytology of the peripheral lymph nodes were consistent with lymphoma with an intermediate-sized lymphoid population. Flow cytometry of peripheral lymph nodes was consistent with a homogeneous population of CD4+ T cells that had lost expression of the pan-leukocyte antigen CD45. Variable expression of CD21, CD25, and class II major histocompatibility complex (MHC) were also noted. This was considered consistent with T-zone lymphoma (TZL), although the T cells were noted to be larger than usual based on flow cytometry. Due to the suspected indolent nature of this patient's disease and clinical progression, a careful monitoring approach was initially discussed with the owner. However, additional diagnostic testing was performed to confirm the diagnosis. Bone marrow cytology did not show any significant anomalies. The largest lymph node (left mandibular) was extirpated and submitted for histopathology. Based on the lymph node architecture, cellular features, and high mitotic activity, an unexpected diagnosis of peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) was made. The dog was started on CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy. This case illustrates the limitations of using flow cytometry as the sole means of diagnosing TZL and highlights the importance of using complementary tests when subtyping canine lymphoma, which is significant when considering a patient's treatment plan and prognosis.

Feline exocrine pancreatic carcinoma has been reported to be an aggressive tumor with a high metastatic rate and poor prognosis. Studies reporting long-term outcome of cats after surgical removal of solitary pancreatic carcinomas are rare, due to the uncommon diagnosis and paucity of cats who undergo treatment. In this study, nine cases of feline exocrine pancreatic carcinoma from seven academic and private practice veterinary hospitals were reviewed to examine the outcome in cats undergoing surgical removal of the mass. The median postsurgical survival time for the nine cats was 316.5 days (range, 25–964 days), with three cats alive at a median follow-up time of 309 days. This study demonstrates that surgical removal of pancreatic exocrine tumors in cats with localized disease can result in survival times of over 300 days.

Background Lymphocytosis is relatively common in cats, but few studies describe lymphocyte populations or the clinical course associated with different immunophenotypic expansions. Hypothesis/objectives We hypothesized that cats frequently develop non-neoplastic lymphocytosis and that different neoplastic immunophenotypes have variable prognoses. We aimed to characterize the lymphocyte expansions in a large population of cats with lymphocytosis and to assess clinical presentation and outcome in a subset. Animals Three cohorts of cats older than 1 year with lymphocytosis (>6000/μL) were examined to define immunophenotypic categories (n = 146), evaluate outcome (n = 94), and determine prevalence of immunophenotypes (n = 350). Methods Retrospective study of cats with blood submitted for flow cytometry. Medical records (n = 94) were reviewed for clinical data, treatment, and survival information. Results Five major immunophenotypic categories were identified: B cell, heterogeneous (≥2 lineages expanded), CD4+ T cell, CD4-CD8- (double negative [DN]) T cell, and CD5-low-expressing T cell. B-cell and heterogeneous phenotypes were more consistent with a non-neoplastic process, having polyclonal antigen receptor gene rearrangements, younger age at presentation, lower lymphocyte counts, and prolonged survival. The neoplastic phenotypes, CD4+ T cell, DN T cell, and CD5 low T cell, had different median survival times (752 days [n = 37], 271 days [n = 7], 27.5 days [n = 12], respectively). Among CD4+ T-cell cases, cats with abdominal lymphadenopathy, intestinal involvement, or both and females had shorter survival. Among 350 cats with lymphocytosis, CD4+ T-cell lymphocytosis was most common, followed by heterogeneous and B-cell phenotypes. Conclusions and clinical importance Neoplastic CD4+ T-cell lymphocytosis is common in cats and has a prolonged clinical course compared to aberrant T-cell phenotypes. Cats with heterogeneous and B-cell lymphocyte expansions commonly have non-neoplastic disease.

Background Myxosarcomas are known to be classified as soft tissue sarcomas. However, there is limited clinical characterization pertaining specifically to canine cutaneous myxosarcomas in the literature. The objective of this study is to evaluate the local recurrence rate, metastatic rate and prognosis of canine myxosarcoma. Results A total of 32 dogs diagnosed with myxosarcoma via histopathology were included in this retrospective study. All dogs had surgical resection. No adjunct treatments were performed in 9 dogs, while 22 dogs also received either radiation therapy or chemotherapy, or a combination of both. One dog received only NSAID after surgery. Overall median survival time (MST) was 730 days (range 20–2345 days). The MST of dogs with a tumor mitotic count

Background A doxorubicin (DOX)-based chemotherapy protocol, CHOP, is the most effective treatment for canine high-grade B-cell lymphoma; however, the cost and time requirements associated with this protocol are not feasible for many pet owners. An alternative treatment option is the use of DOX, the most effective drug, in combination with prednisone. Prior studies with single-agent DOX included dogs with T-cell lymphoma, a known negative prognostic factor, which may have resulted in shorter reported survival times than if dogs with B-cell lymphoma were analyzed separately. The purpose of this study was to evaluate the outcome of dogs with high-grade B-cell lymphoma when treated with DOX and prednisone with or without L-asparaginase (L-ASP). Identification of prognostic factors was of secondary interest. Results Thirty-three dogs were included in the study; 31 dogs were evaluable for response with an overall response rate of 84%. The median progression free survival (PFS) and overall survival (OS) were 147 days and 182 days, respectively. The one-year survival fraction was 23%. No variable other than protocol completion was found to be significant for either PFS or OS including historical prognostic factors such as substage, thrombocytopenia, and body weight. Conclusions Dogs with high-grade B-cell lymphoma treated with DOX and prednisone with or without L-ASP have similar response rates, PFS, and OS to prior studies that did not differentiate between lymphoma immunophenotype. This protocol is not a replacement for CHOP; however, it is an alternative if time and cost are factors, while providing therapeutic benefit greater than prednisone alone.

OBJECTIVE: Report clinical outcomes of dogs with surgically excised mast cell tumors (MCT) and soft tissue sarcomas (STS). STUDY DESIGN: Prospective clinical study. SAMPLE POPULATION: Fifty‐three dogs with 52 MCT (50 low grade, 2 high grade) and 19 STS (12 grade I, 6 grade II, 1 grade III). METHODS: All dogs were examined at 3, 6, 12, 18, and 24 months postoperatively, with cytologic or histopathologic evaluation of suspected local recurrences. Dogs euthanized because of study tumor‐related causes underwent necropsy. RESULTS: Median intraoperative margins were 20 mm and 30 mm wide for MCT and STS, respectively, with 1 fascial plane resected en bloc. The narrowest histologic tumor‐free margins measured

OBJECTIVE: Quantify changes in the circumferential lengths of surgical margins of resected canine mast cell tumors (MCT) and soft tissue sarcomas (STS) between the time of collection and histopathology. STUDY DESIGN: Prospective, hypothesis‐driven, clinical study. SAMPLE POPULATION: Two hundred and thirty‐seven margins from 69 excised tumors (50 MCT and 19 STS) in 51 client‐owned dogs. METHODS: The lengths of surgical margins were recorded (eg, cranial, caudal, dorsal, and ventral) for each tumor at 5 time points: intraoperatively (in vivo), immediately after excision (ex vivo), after formalin fixation (postfixation), once mounted on glass slides (subgross), and as histologically tumor‐free margins (HTFMs). RESULTS: Compared to in vivo dimensions, the length of surgical margins at each processing step (ie, ex vivo, postfixation, subgross, and HTFM) was reduced by a median of 3.0, 5.0, 6.0, and 8.8 mm for MCT; 2.5, 2.0, 5.0, and 5.0 mm for STS. All processing steps resulted in significant reductions among MCT samples (P