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An 8-y-old spayed female Beagle dog was presented with peripheral lymphadenomegaly. Lymph node cytology and flow cytometry led to the diagnosis of large B-cell lymphoma (LBCL). We detected minimal percentages of LBCL cells in peripheral blood and bone marrow samples. However, a monomorphic population of neoplastic cells different from those found in the lymph node was found in the bone marrow. T-cell acute lymphoblastic leukemia was suspected based on flow cytometric immunophenotyping. PCR for antigen receptor rearrangement (PARR) revealed clonal rearrangement of both B-cell and T-cell receptors, and the presence of both neoplastic clones in the lymph node, peripheral blood, and bone marrow. The dog was treated with multi-agent chemotherapy but died 46 d following diagnosis. Tumor staging and patient classification are needed to accurately establish a prognosis and select the most appropriate therapeutic protocol.

Background Oral malignant melanoma is the most common, but aggressive oral cancer in dogs with poor prognosis. Electrochemotherapy (ECT) has therapeutic potential in such tumors as effective local treatment. Therefore, the aim of this prospective clinical study was to evaluate treatment effectiveness of ECT in as first line treatment for canine oral malignant melanoma, and search for factors influencing treatment outcome. Methods Sixty-seven canines with primary oral malignant melanoma, non-candidates for first-line therapy, were enrolled. All dogs received ECT and follow-up exams for the span of two years. Results Based on RECIST criteria, the objective response rate was 100%, 89.5%, 57.7%, and 36.4%, in stage I, II, III and IV, respectively. Only patients in stage I, II and III with partial or complete response improved their quality of life. The median time to progression was 11, 7, 4 and 4 months, and median survival time after the treatment was 16.5, 9.0, 7.5 and 4.5 months, for patients in stage I, II, III and IV, respectively. Significantly better was local response in stage I and II disease (p = 0.0013), without the bone involvement (p = 0.043) Conclusions Electrochemotherapy is effective local treatment of oral canine malignant melanoma when no alternative treatment is available. Better response is expected in stage I and II patients with tumors without bone involvement.

Feline mammary carcinomas are highly malignant tumors usually associated with poor outcome. Nevertheless, survival times can differ significantly according to various prognostic factors. The Elston and Ellis (EE) histologic grading system, originally developed for human breast cancer, is commonly used to grade feline mammary carcinomas, although it is not really adapted for this species, hence the need of a more relevant grading system. Although few veterinary studies attempted to validate previously published results in an independent cohort, the aim of our study was to evaluate the prognostic value of different histologic grading systems in feline invasive mammary carcinomas, including the EE grading system applicable to human breast cancers and the modified and newly designed histologic grading systems recently proposed by Mills et al. Survey data and histologic features of 342 feline invasive mammary carcinomas were analyzed with respect to overall and cancer-specific survival. The histological grading system with best prognostic value was the mitotic-modified Elston and Ellis (MMEE) grading system: grade III carcinomas ( P = .04, hazard ratio [HR] = 1.46, 95% CI, 1.01-2.11), grade II ( P = .03, HR = 1.39, 95% CI, 1.03-1.88), and grade I carcinomas (HR = 1.00, reference), with decreasing hazard ratios significantly were associated with a worse overall survival, independently from the pathologic tumor size (pT ≥ 20 mm: P = .002, HR = 1.45, 95% CI, 1.15-1.83) and positive nodal stage ( P = .001, HR = 1.51, 95% CI, 1.18-1.94). This retrospective study validates Mills et al's proposal to adapt the thresholds for mitotic counts to better assess the histological grade of the highly proliferative mammary carcinomas encountered in the cat.

Background: Cyclooxygenase 2 (COX-2) is an inducible isoform by cellular activation, proinflammatory cytokines and growth factors. The aims of the current study were to evaluate COX-2 immunoexpression in epithelial and lamina propria (LP) of cats with inflammatory bowel disease (IBD) and low grade alimentary lymphoma (LGAL), as well as to correlate them with clinical signs and histopathological scoring. Cats diagnosed with IBD and LGAL (2007-2013) were included in the current study. Feline chronic enteropathy activity index (FCEAI) was calculated for all cases. Control group was composed by 3 healthy indoor cats and 5 sick cats died or were euthanized (non-gastrointestinal illness). Diagnosis and classification of IBD and LGAL was established according to the WSAVA gastrointestinal standardization group template and the National Cancer Institute formulation, respectively. Furthermore, a modified WSAVA template was applied for LGAL evaluation. Immunolabelling for COX-2 (polyclonal rabbit anti-murine antibody) was performed on biopsy samples. Epithelial and LP (inflammatory or neoplastic cells) COX-2 immunolabelling was calculated according to the grade and intensity. The most representative segment scored by the WSAVA and the modified WSAVA were used for statistical analysis., Results: Significant difference was found regarding COX-2 intensity overexpression in the epithelial cells of IBD and LGAL groups when compared to control cats, but not between the groups of sick cats, whereas no differences were found regarding the grade of immunoreactivity between groups. No difference was found for COX-2 immunoexpression at the LP between all groups. However, 3 cats from LGAL group showed COX-2 expression in neoplastic cells at the LP. There were no correlations between epithelial or LP COX-2 expression and FCEAI and histological alterations., Conclusions: Increased COX-2 intensity at the epithelial cells observed in cats with IBD and LGAL may be secondary to the inflammatory response or a protective function in the intestinal reparation. COX-2 expression at the LP was presented in 33% of LGAL. This result provides a reason for further investigation concerning the role of COX-2 expression in feline alimentary lymphoma.

Nephroblastomas are uncommon embryonal tumors in dogs. We report herein a blastema-predominant nephroblastoma with gingival metastasis in an 8-y-old Miniature Pinscher dog. Histologically, the mass was composed mainly of blastemal elements with minor epithelial and mesenchymal differentiation. Metastatic masses in the gingiva had histologic and immunohistochemical features similar to those of the primary renal nephroblastoma. Neoplastic cells were extensively positive for both vimentin and PAX8, and scattered positive for cytokeratin. Using the clinical staging of human Wilms tumor, we staged our case as stage IV with <4 mo of survival time. We summarized previous studies of canine renal and spinal nephroblastomas, and analyzed the correlations among clinical staging, histologic classification, and mean survival time of dogs with renal nephroblastomas. Clinical staging was significantly correlated with survival time, as shown in humans. In dogs, however, additional factors can potentially influence the outcome of treatment and disease development.

OBJECTIVE To evaluate factors for associations with duration of first remission and survival time in dogs ≥ 14 years of age with stage III to V multicentric lymphoma. DESIGN Retrospective cohort study. ANIMALS 29 dogs ≥ 14 years of age with multicentric lymphoma treated with a chemotherapy protocol at dosages used for younger dogs (n = 22) or with prednisolone alone (7). PROCEDURES Various data were collected from the medical records, including treatment response and related adverse events. Survival analysis was performed to determine duration of first remission and survival time (from start of chemotherapy), and these outcomes were compared between various groupings. RESULTS The 7 (24%) dogs that received prednisolone alone had a median survival time of 27 days and were excluded from further analysis. Complete clinical remission was achieved in 21 of the 22 (95%) remaining dogs; 1 (5%) achieved partial remission. Median duration of first remission was 181 days. Anemic dogs had a briefer remission period (median, 110 days) than nonanemic dogs (median, 228 days). Median survival time for all 22 dogs was 202 days, with estimated 1- and 2-year survival rates of 31% and 5%, respectively. Six (27%) dogs had adverse events of chemotherapy classified as grade 3 or worse. CONCLUSIONS AND CLINICAL RELEVANCE Survival time was substantially longer in dogs treated with a chemotherapy protocol versus prednisolone alone. Findings suggested that the evaluated chemotherapy protocols for lymphoma were beneficial for and tolerated by very elderly dogs, just as by younger dogs, and need not be withheld, or dosages adjusted, because of age alone.

OBJECTIVE To evaluate the safety and efficacy of intralesional triamcinolone administration, as a sole or adjuvant treatment, in dogs with mast cell tumors. DESIGN Retrospective case series ANIMALS 23 dogs with mast cell tumors. PROCEDURES Medical records of dogs treated for a confirmed diagnosis of a mast cell tumor between 2005 and 2011 were reviewed. Patients with a confirmed diagnosis and measurable disease (tumor longest dimension ≥ 0.5 cm) that had received ≥ 1 intralesional treatment with triamcinolone, regardless of prior, concurrent, or adjuvant treatments, were eligible for inclusion. Data collected included patient characteristics, results of cytologic and histologic testing and tumor staging, triamcinolone dosage, treatment response, and adverse events. RESULTS 23 dogs with 24 tumors were included. Tumors were treated by means of intralesional triamcinolone administration alone (n = 5), intralesional triamcinolone administration with concurrent oral administration of glucocorticoids (6), and intralesional triamcinolone administration with concurrent cytotoxic chemotherapy, with or without oral administration of corticosteroids and radiation therapy (13). Of 5 dogs treated with intralesional triamcinolone administration alone, 1 achieved a complete response, 3 achieved a partial response, and 1 maintained stable disease. The response rate for all 24 tumors (23 dogs) was 67% (16/24), including 4 with a complete response and 12 with a partial response. The median time to progression was 63 days (range, 6 to 447 days). Three dogs experienced adverse events (local hemorrhage [n = 1]; suspected gastrointestinal ulceration [2]). CONCLUSIONS AND CLINICAL RELEVANCE Intralesional triamcinolone administration may be well tolerated and effective for treatment of nonresectable mast cell tumors in dogs.

Mast cell tumors (MCTs) are commonly encountered in dogs and have been reported in cutaneous, conjunctival, oral mucosal, and gastrointestinal locations, but not in an intramuscular location. Medical records at 2 referral centers in the UK were examined to find cases of MCTs in this location. Seven dogs were identified as having an intramuscular MCT by a combination of fine-needle aspirate cytology and computed tomography or ultrasound. None of the dogs had evidence of local lymph node metastasis. Six dogs had no evidence of distant metastasis and surgery was carried out as the primary treatment option. Three of those dogs also had adjunctive chemotherapy due to a high Ki67 value or high mitotic index. All 6 dogs that had had surgery were alive at follow-up with a minimum elapsed time of 7 months. One dog had a course of chemotherapy due to the location, size, and evidence of biological activity of the tumor and died 23 days afterwards. The prognosis of intramuscular mast cell tumors appears to be favorable in most cases.

The medical records of 4 dogs with histologically confirmed intranasal mast cell tumors (MCTs) were retrospectively evaluated to determine their biological behavior. Information on signalment, presenting clinical signs, tumor grade, treatment administered, and survival times was obtained from the medical record. All 4 patients had high grade tumors and received chemotherapy. Survival times ranged from 27 to 134 days. All 4 dogs showed signs of local or distant disease progression, suggestive of an aggressive behavior of intranasal MCTs.

Positron Emission Tomography-Computed Tomography (PET-CT) is routinely used for staging and monitoring of human cancer patients and is becoming increasingly available in veterinary medicine. In this study, 18-fluorodeoxyglucose (18FDG)-PET-CT was used in dogs with naturally occurring splenic hemangiosarcoma (HSA) to assess its utility as a staging and monitoring modality as compared to standard radiography and ultrasonography. Nine dogs with stage-2 HSA underwent 18FDG-PET-CT following splenectomy and prior to commencement of chemotherapy. Routine staging (thoracic radiography and abdominal ultrasonography) was performed prior to 18FDG-PET-CT in all dogs. When abnormalities not identified on routine tests were noted on 18FDG-PET-CT, owners were given the option to repeat a PET-CT following treatment with eBAT. A PET-CT scan was repeated on Day 21 in three dogs. Abnormalities not observed on conventional staging tools, and most consistent with malignant disease based on location, appearance, and outcome, were detected in two dogs and included a right atrial mass and a hepatic nodule, respectively. These lesions were larger and had higher metabolic activity on the second scans. 18FDG-PET-CT has potential to provide important prognostic information and influence treatment recommendations for dogs with stage-2 HSA. Additional studies will be needed to precisely define the value of this imaging tool for staging and therapy monitoring in dogs with this and other cancers.

Breast tumors are the most common tumors in dogs and the study of disease prognostic factors is important for establishing the appropriate treatment protocols. The purpose of this study was to clinically stage mammary tumors of bitches and correlate the stages with histological type and grade. The tumors of 63 dogs were clinically staged based on the findings of tumor sizing, lymph node evaluation, and radiographic examination. After surgical excision, the tumors were classified histologically and graded. The relationship between the tumor grade, stage, and histological type was evaluated using a binomial test. Stage I tumors were the most numerous (31.75%), followed by tumors at stages II, III, IV, and V. Animals with histological grade I carcinomas presented stage I, II, or III tumors more frequently and stage IV and V tumors less frequently. The number of animals with simple carcinomas that were at stage I of the disease was greater than that at stage V. Carcinomas in the mixed tumors were less aggressive; however, the small number of animals in stage V of the disease made any statistical association impossible. The complex carcinomas presented with the invasion of the lymph nodes and less cellular differentiation in a larger number of animals than did simple carcinomas. Histological grading proved to be the best parameter for the prognostic evaluation of the breast carcinomas.

Objectives: The purpose of this study was to investigate the disease-free interval, survival time and adverse events of a combined treatment approach in cats with mammary malignant tumors using radical mastectomy and adjuvant mitoxantrone., Methods: All cats underwent surgery to remove the mammary chain containing the tumors. A 3 cm margin was obtained around removed tumors. For staging purposes, regional inguinal lymphadenectomy was performed in all cases. After histopathology, cats were staged according to the World Health Organization's (WHO) staging system. Chemotherapy with mitoxantrone was started 15-30 days after surgery (6 mg/m(2) IV every 21 days for four cycles) with the objective of delaying metastasis., Results: Three cats were intact, one cat was early spayed, four cats were late spayed and four cats were spayed at an unknown age. Based on the WHO's staging system, six cats were classified as stage I and six cats as stage III. The median disease-free interval and survival time were 360 and 480 days, respectively. Four (33%) cats received four doses of mitoxantrone, four (33%) cats received three doses and four (33%) cats received only one dose. The most frequent adverse effects of chemotherapy were azotemia, anorexia, leukopenia and vomiting., Conclusions and Relevance: Adjuvant mitoxantrone chemotherapy may be an option for feline mammary tumors. Further, sufficiently powered, randomized prospective trials are necessary to determine if mitoxantrone is superior, inferior or equivalent to doxorubicin in the adjuvant setting., (© ISFM and AAFP 2015.)

Canine lymphoma is the neoplasm most often treated by chemotherapy, yet there are few data to correlate response to therapy with its different subtypes. This study is based on biopsy specimens from 992 dogs for which lymphoma was the clinical diagnosis. All cases were phenotyped by immunohistochemistry for CD3 and CD79alpha. Cases with histiocytic proliferation were evaluated immunohistochemically for CD18. Clonality was verified in 12 cases by polymerase chain reaction (PCR). Survival (event time) data and complete survival information (cause of death or time to last follow-up) were available on 456 dogs. Additional covariate information when available included size, age, sex, phenotype, stage and grade of lymphoma, mitotic index, and treatment protocol. Because of the many subtypes of B- and T-cell lymphoma, the cases were grouped into 7 diagnostic categories: (1) benign hyperplasia; (2) low-grade B-cell; (3) high-grade B- and T-cell; (4) low-grade T-cell; (5) centroblastic large B-cell of all mitotic grades (subdivided by clinical stage); (6) immunoblastic large B-cell of all mitotic grades, and (7) high-grade peripheral T-cell. Grouping was determined by histological grade (based on mitotic rate/400× field, with low-grade 0-5, intermediate 6-10, and high-grade >10) and stage for survival function estimation. No association with survival was found for size (based on breed of dog) or sex. All diagnostic categories of indolent or low-grade type had low mitotic rates, whereas those with clinically high grades had high mitotic rates. The diagnostic category with the most cases was centroblastic large B-cell lymphoma. Compared with dogs in this largest represented group of lymphomas, dogs with high-grade lymphomas had significantly higher mortality rates, and dogs with low-grade T-cell lymphomas had significantly lower mortality rates. Treatments for high-, intermediate-, and low-grade lymphomas were divided into 4 groups: absence of treatment, chemotherapy with or without hydroxydaunorubicin, and only prednisone. Dogs with low-grade T-cell (T-zone) lymphomas had the longest median survival (622 days), whereas the shortest median survival was in dogs with T-cell high-grade (peripheral T-cell) subtype (162 days). The dogs with centroblastic large B-cell lymphomas had a median survival of 127 days with low stage, 221 days with intermediate stage, and 215 days with advanced stage. Dogs with T-zone lymphoma were probably diagnosed in later stages of disease because of the lack of signs associated with progression. As with human lymphomas, a histological diagnosis with immunophenotyping is a minimal requirement for diagnosis of a specific subtype.

Background: The utility of whole body magnetic resonance imaging (MRI) in detecting bone marrow infiltration in dogs with cancer has not been investigated., Objectives: To assess the feasibility of 3T body MRI for bone marrow assessment in dogs with hematopoietic neoplasia., Animals: Seven dogs with B-cell lymphoma, 3 dogs with myelodysplastic syndrome (MDS), and 2 clinically normal dogs., Methods: A prospective study of dogs with hematopoetic cancer was conducted using T1W, T2W, In-Phase, Out-of-Phase and STIR pulse sequences of the body excluding the head prior to bone marrow sampling. The relative signal intensity of a midlumbar vertebral body and a midshaft femoral bone marrow was compared by visual and point region of interest analysis to regional skeletal muscle., Results: Similarity of femoral diaphyseal and vertebral body marrow signal intensity to that of skeletal muscle on the Out-of-Phase sequence was useful in distinguishing the 3 dogs with hypercellular marrow because of MDS from the 7 dogs with B-cell lymphoma and from the 2 clinically normal dogs. 1/7 dogs with lymphoma had proven bone marrow involvement but normal cellularity and less than 5% abnormal cells. Unaffected midfemoral marrow had greater signal intensity than skeletal muscle and unaffected vertebral marrow had less signal intensity than skeletal muscle on the Out-of-Phase sequence., Conclusions and Clinical Importance: 3T, Out-of-Phase MR pulse sequence was useful in distinguishing diffuse bone marrow infiltrate (MDS) from minimally or unaffected marrow using skeletal muscle for signal intensity comparison on whole body MRI., (Copyright © 2013 by the American College of Veterinary Internal Medicine.)

Practical Relevance: To safely and effectively treat cats with cancer it is important to understand the drugs being used and some species-specific concerns in relation to chemotherapy., Clinical Challenges: While many of the same principles in treating cats with chemotherapy and targeted agents hold true as for other species, including dogs, cats display altered metabolism of drugs and species-specific toxicities that can present particular challenges for veterinarians., Audience: This article is aimed at practitioners who treat feline cancer or who help manage cats undergoing cancer therapy., Evidence Base: The article reviews the known literature regarding species differences between dogs and cats relating to the use of chemotherapy and targeted therapies. For many of the drugs mentioned there are limited studies and caution must be exercised when using drugs that have a low therapeutic index.

Background: The frequency of mammary malignancies in canine patients is even three times over than in human. In various types of cancer different intracellular signalling pathways are perturbed, thus the patients with pathologically the same type of cancer often have dissimilar genetic defects in their tumours and respond in a heterogeneous manner to anticancer treatment. That is why the objective of the hereby study was to assess the gene expression profiles in canine mammary carcinomas (in unsupervised manner) classified by pathologists as grade 1 (well differentiated), grade 2 (moderately differentiated) and grade 3 (poorly differentiated) and compare their molecular and pathological classifications., Results: Our unsupervised analysis classified the examined tissues into three groups. The first one significantly differed from the others and consisted of four carcinomas of grade 3 and one carcinoma of grade 2. The second group consisted of four grade 1 carcinomas. The very heterogeneous (based on their pathological parameters) group was the last one which consisted of two grade 1 carcinomas, two grade 3 carcinomas and five grade 2 carcinomas. Hierarchical dendrogram showed that the most malignant tumour group had significantly distinct gene expression., Conclusions: Molecular classification of canine mammary tumours is not identical with pathological classification. In our opinion molecular and pathological characterization of canine mammary malignancy can complement one another. However, furthers studies in this field are required.

We performed a preliminary study involving 10 dogs to assess the applicability of body MRI for staging of canine diffuse hematopoietic neoplasia. T1-weighted (before and after intravenous gadolinium), T2-weighted, in-phase, out-of-phase, and short tau inversion recovery pulse sequences were used. By using digital region of interest (ROI) and visual comparison techniques, relative parenchymal organ (medial iliac lymph nodes, liver, spleen, kidney cortex, and kidney medulla) signal intensity was quantified as less than, equal to, or greater than that of skeletal muscle in 2 clinically normal young adult dogs and 10 dogs affected with either B-cell lymphoma (n = 7) or myelodysplastic syndrome (n = 3). Falciform fat and urinary bladder were evaluated to provide additional perspective regarding signal intensity from the pulse sequences. Dogs with nonfocal disease could be distinguished from normal dogs according to both the visual and ROI signal-intensity relationships. In normal dogs, liver signal intensity on the T2-weighted sequence was greater than that of skeletal muscle by using either the visual or ROI approach. However in affected dogs, T2-weighted liver signal intensity was less than that of skeletal muscle by using either the ROI approach (10 of 10 dogs) or the visual approach (9 of 10 dogs). These findings suggest that the comparison of relative signal intensity among organs may have merit as a research model for infiltrative parenchymal disease (ROI approach) or metabolic effects of disease; this comparison may have practical clinical applicability (visual comparison approach) as well.

Practical Relevance: Feline mast cell tumors (MCTs) are frequently encountered in general practice. MCTs are the most common splenic tumor, second most common skin tumor and third most common intestinal tumor in cats. Treatment and prognosis can vary dramatically with location and histologic classification., Clinical Challenges: While a cytologic or histologic diagnosis is often easy to obtain, the various histologic classifications, lack of a relevant grading scheme, and disparity in behavior depending on anatomic location make prognostication for cases of feline MCTs confusing. This is quite different from canine MCTs, where there is an established grading system which correlates clinically with prognosis and an accepted standard of care., Audience: Due to its prevalence, general practitioners encounter MCTs regularly. In many instances, referral for diagnosis and treatment is not necessary., Evidence Base: Historically, there has been limited clinical evidence upon which to determine optimal treatment of MCTs in cats. Most recommendations are based on limited case reports or retrospective studies. With the recent introduction of receptor tyrosine kinase inhibitors to the veterinary market, there has been new research on the use of these drugs in cats, and new treatment options are on the horizon.

The purpose of this study was to elucidate the relationship between plasma free amino acid (PFAA) levels and the clinical stages of mammary gland tumors (MGT) in dogs. PFAA levels in canines with malignant mammary tumors were decreased compared to those of healthy animals. The levels of aspartate and ornithine, in the dogs with tumor metastasis were significantly decreased when compared to those of dogs that did not have metastases. Results of this study indicate that PFAA levels could be a risk factor or biomarker for canine MGT metastasis.

Objective: To assess the usefulness of histologic evaluation of surgical margins to predict local recurrence of cutaneous malignant tumors in dogs and cats treated by means of surgical excision., Design: Prospective case series., Animals: 40 dogs and 20 cats., Procedures: 60 surgically excised tumors (20 soft tissue sarcomas [STSs], 20 mast cell tumors [MCTs], and 20 carcinomas) were examined histologically. Margins were classified as clean, close, or infiltrated; histologic grade was assessed in STSs and MCTs. Recurrence rates and recurrence-free intervals (RFIs) during a 24-month follow-up period were recorded, and method accuracy was calculated., Results: Surgical margins were clean in 29 of 60 (48%) tumors, close in 11 (18%), and infiltrated in 20 (33%). Tumors recurred in 27 of 60 (45%) animals, with a mean ± SD RFI of 229 ± 173 days. Recurrence rates for animals that had tumors with infiltrated (16/20) or close (8/11) margins were significantly higher than recurrence rate for animals that had tumors with clean margins (3/29). Margin classification was a significant predictor of RFI. Accuracy of the method to predict recurrence was 94% for carcinomas, 87% for STSs, and 76% for MCTs., Conclusions and Clinical Relevance: Histologic assessment of margin status was useful for predicting local recurrence of cutaneous malignant tumors in dogs and cats treated by means of excision alone. Method accuracy varied among tumor types and grades. Recurrence times suggested postsurgical follow-up should continue for ≥ 2 years. Results were similar for animals with infiltrated and close tumor margins, and careful postsurgical management is recommended for both.

Objective: To evaluate the safety and efficacy of a vaccine containing plasmid DNA with an insert encoding human tyrosinase (ie, huTyr vaccine) as adjunctive treatment for oral malignant melanoma (MM) in dogs., Animals: 111 dogs (58 prospectively enrolled in a multicenter clinical trial and 53 historical controls) with stage II or III oral MM (modified World Health Organization staging scale, I to IV) in which locoregional disease control was achieved., Procedures: 58 dogs received an initial series of 4 injections of huTyr vaccine (102 μg of DNA/injection) administered transdermally by use of a needle-free IM vaccination device. Dogs were monitored for adverse reactions. Surviving dogs received booster injections at 6-month intervals thereafter. Survival time for vaccinates was compared with that of historical control dogs via Kaplan-Meier survival analysis for the outcome of death., Results: Kaplan-Meier analysis of survival time until death attributable to MM was determined to be significantly improved for dogs that received the huTyr vaccine, compared with that of historical controls. However, median survival time could not be determined for vaccinates because < 50% died of MM before the end of the observation period. No systemic reactions requiring veterinary intervention were associated with vaccination. Local reactions were primarily limited to acute wheal or hematoma formation, mild signs of pain at the injection site, and postvaccination bruising., Conclusions and Clinical Relevance: Results support the safety and efficacy of the huTyr DNA vaccine in dogs as adjunctive treatment for oral MM., Impact for Human Medicine: Response to DNA vaccination in dogs with oral MM may be useful in development of plasmid DNA vaccination protocols for human patients with similar disease.

Objective: To evaluate the relationship between width and depth of surgical margins, amount of edema within and around the tumor, and degree of demarcation between the tumor and surrounding tissues with the clinical outcome following surgical removal of cutaneous mast cell tumors (cMCTs) in dogs., Design: Retrospective cohort study., Animals: 100 dogs with 115 resectable cMCTs., Procedures: Information about the dogs' clinical outcomes following cMCT removal was obtained from primary care veterinarians. Histologic sections of excised tumors were assessed retrospectively for tumor grade and measurement of the narrowest lateral and deep margins of nonneoplastic tissue excised with the tumors; edema within the tumor and surrounding tissues was assessed as minimal, moderate, or severe. Tumors were classified as poorly, moderately, or well demarcated on the basis of the degree of mast cell infiltration into the adjoining connective tissue., Results: Following tumor excision (with no additional postsurgery treatment), 96 dogs had no local recurrence or metastatic disease for 27 to 31 months; 4 metastatic disease-related deaths (dogs with grade II or III tumors) occurred within 3 to 9 months. Histologically, mean lateral and deep surgical margins around the tumors were 8.9 and 5.3 mm, respectively. No recurrence of tumor or metastatic disease developed following excision with lateral margins ≥ 10 mm and deep margins ≥ 4 mm. Edema and degree of demarcation were not correlated with outcome., Conclusions and Clinical Relevance: Results suggested that most grade I and II cMCTs in dogs can be successfully treated by complete surgical removal with margins smaller than those currently recommended.

Objective: To determine factors predicting survival in dogs with high-grade multicentric lymphoma. Design-Retrospective cohort study. Animals-127 dogs with high-grade multicentric lymphoma evaluated at 4 veterinary hospitals from 2000 to 2009., Procedures: Records were reviewed to identify dogs with completely staged high-grade multicentric lymphoma treated with chemotherapy. Data collected included signalment, history, hematologic findings, tumor characteristics, treatment, and outcome. Long-term survival was defined as surviving > 2 years after diagnosis. Variables were analyzed for associations with dogs living > 2 years., Results: Among the 127 enrolled dogs, 13 (10%) survived > 2 years with a median survival time of 914 days (range, 740 to 2,058 days). Survival rates at 3, 4, and 5 years were 4%, 3%, and 1 %, respectively. At diagnosis, 11 of the 13 long-term survivors had a body weight ≥ 10 kg, PCV ≥ 35%, absence of ionized hypercalcemia, centroblastic lymphoma, immunophenotype B, absence of bone marrow involvement, and lymphoma stages I through IV and were not previously treated with corticosteroids. The same combination of factors was present in 26 of 114 (23%) dogs surviving ≤ 2 years, yielding a negative predictive value of 97.8% for long-term survivors. Four of the 6 long-term survivors that died during the study died of another cancer; 3 of them had osteosarcoma., Conclusions and Clinical Relevance: Absence of the aforementioned combination of variables at diagnosis may help identify dogs with lymphoma that will not survive > 2 years. Other types of neoplasia, in particular osteosarcoma, may develop in long-term-surviving dogs.

Background: Malignant melanoma of dogs is a highly aggressive neoplasm and is the 2nd most common digit tumor. Metastatic disease is a common sequela for which few effective treatment options exist. Studies show that xenogeneic tyrosinase DNA vaccination yields immune responses and prolongation of survival in dogs with oral malignant melanoma., Objectives/hypothesis: Describe clinical findings and tumor characteristics of a cohort of dogs with digit malignant melanoma, and evaluate the prognostic utility of a proposed staging system. Determine if a novel xenogeneic DNA vaccine is safe and potentially effective for treatment of dogs with digit melanoma., Animals: Fifty-eight dogs with digit malignant melanoma treated at the Animal Medical Center between 2004 and 2007., Methods: Retrospective, medical records review of dogs with digit melanoma treated with xenogeneic DNA vaccine., Results: Overall median survival time (MST) for dogs treated with loco-regional control and xenogeneic DNA vaccine was 476 days with a 1-year survival rate of 63%. MST for dogs presenting with metastasis was 105 days versus 533 days for dogs presenting without metastasis (P < .0001). Forty-eight percent of the dogs in the latter group were alive at 2 and 3 years. A proposed staging system proved prognostic with stages I-IV dogs surviving >952, >1,093, 321, and 76 days, respectively., Conclusions and Clinical Importance: The xenogeneic murine tyrosinase DNA vaccine was safe and appears effective when used in conjunction with local and regional disease control. The proposed staging system was prognostic in this study and future studies might benefit from utilizing this staging system., (Copyright © 2010 by the American College of Veterinary Internal Medicine.)

Mammary neoplasms are the most common neoplasm in female dogs. Two histologic classification systems for canine mammary tumors and dysplasias have been published: the first in 1974 and a modification in 1999. This article provides a brief overview of the two histologic classification systems. Since the publication of the second system, several new histologic subtypes of canine mammary neoplasms have been described. These have been incorporated into the proposed new classification system. This article also compares the grading systems for canine mammary carcinomas and their use for prognosis, along with the histologic classification.

The present study aimed to objectively evaluate the adverse events after the administration of chemotherapeutic agents used in the University of Wisconsin (UW)-Madison chemotherapy protocol (UW-25) for canine lymphoma, using the Veterinary Co-operative Oncology Group common terminology criteria for adverse events (VCOG-CTCAE). The medical records of 40 dogs with multicentric high-grade lymphoma that underwent UW-25 were reviewed. Gastrointestinal adverse events of grade 2 and above and blood/bone marrow adverse events of all grades were evaluated. Gastrointestinal adverse events occurring at least once during the entire period of UW-25 were observed in 50% (20/40), 17.9% (7/39), and 8.1% (3/37) of the dogs after the administration of vincristine (VCR), cyclophosphamide (CPA), and doxorubicin (DXR), respectively. Blood/bone marrow adverse events occurring at least once during UW-25 were observed in 57.5% (23/40), 41% (16/39), and 8.1% (3/37) of the dogs after the administration of VCR, CPA, and DXR, respectively. The rate of patients that experienced gastrointestinal adverse events was higher after the first administration of VCR than after the first administration of DXR. Findings obtained in this study will be helpful in predicting the adverse events that could occur when dogs with lymphoma are treated with UW-25.

The objective of this paper was to evaluate the efficacy of a hypofractionated radiation protocol for feline facial squamous cell carcinoma (SCC). Twenty-five histologically confirmed SCCs in 15 cats were treated with four fractions of 7.6-10Gy each, with 1 week intervals. The equipment used was a linear accelerator Clinac 2100 delivering electron beam of 4 or 6MeV, and a bolus of 5 or 10mm was used in all lesions. Of the lesions, 44% were staged as T4, 16% as T3, 8% as T2 and 32% as T1. Of the irradiated lesions, 40% had complete response, 12% had partial response and 48% had no response (NR) to the treatment. For T1 tumors, 62.5% had complete remission. Mean overall survival time was 224 days. Owners requested euthanasia of cats having NR to the treatment. Mean disease free time was 271 days. Side effects observed were skin erythema, epilation, ulceration and conjunctivitis, which were graded according to Veterinary Radiation Therapy Oncology Group (VRTOG) toxicity criteria. Response rates found in this study (52%) were lower when compared to other protocols, probably due to technique differences, such as fractionation schedule, bolus thickness and energy penetration depth. However, the hypofractionated radiation protocol was considered safe for feline facial SCC. Modifications of this protocol are being planned with the objective of improving the cure rates in the future., (Copyright 2009 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.)

Aims: This article reviews the incidence, etiology, diagnosis, treatment and prognosis of mammary tumors in cats., Practical Relevance: Approximately 80% of feline mammary masses are malignant, with adenocarcinoma being the most common tumor type. Early diagnosis is, therefore, essential to improve the prognosis and quality of life of affected cats., Treatment Approaches: Surgery is the most widely used treatment for malignant tumors. However, as mammary tumors are often advanced and metastasis has already occurred by the time of diagnosis, surgery routinely does not provide a cure. Ovariohysterectomy or hormonal therapy are the treatments of choice for fibroadenomatous hyperplasia (the most common benign mass) and usually lead to a successful outcome., (Copyright 2010. Published by Elsevier Ltd.)

Twenty-nine canine cutaneous mast cell tumors (MCTs) were morphometrically analyzed with regard to mean nuclear area (MNA) using cytopathology smears. The results showed a correlation between MNA and survival. When graded into 2 morphometrically different groups, there were statistically significant differences among high- and low-grade MCTs, regarding both Romanowsky-type stain and hematoxylin and eosin. Cytomorphometry could also separate histologic grade II tumors with better prognosis from the more aggressive MCTs. The results indicated that nuclear morphometry on cytopathology preparations can predict the biological behavior of cutaneous MCTs in dogs in an independent manner, yielding a rapid and reproducible diagnosis, which renders the method useful for veterinary oncology.

Objective: To evaluate the prognostic potential of expression of hormone receptors in malignant mammary gland tumors of dogs. Design-Cohort study., Animals: 89 female dogs with malignant mammary gland tumors and 24 female dogs with benign mammary gland tumors., Procedures: Female dogs with malignant (n = 89 dogs) and benign (24) mammary gland tumors were evaluated to determine the prognostic value of the expression of estrogen receptor (ER)A or the progesterone receptor (PR), as determined by use of immunohistochemical methods., Results: In this study, 68 (60.2%) and 88 (77.9%) of the 113 dogs with mammary gland tumors had expression of ERA and PR, respectively. Expression of ERA and PR was detected proportionately more frequently in benign tumors (23/24 [95.8%] and 24/24 [100%], respectively) than in malignant tumors (45/89 [50.6%] and 64/89 [71.9%]). Percentage of tumors with positive results for ERA and PR was significantly higher in tumors < 5 cm in diameter; as clinical stage I, II, or III; and without metastasis to lymph nodes or distant metastasis. However, only PR expression in tumor cells was significantly associated with 1-year survival after surgical removal of the tumor. Moreover, dogs with malignant tumors expressing ERA and PR had a significantly higher survival rate, compared with the rate for dogs with malignant tumors expressing ERA but not PR., Conclusions and Clinical Relevance: These findings strongly suggested that expression of PR could be used as a prognostic factor for survival, especially in female dogs with malignant mammary gland tumors with ERA expression.

Canine inflammatory mammary carcinoma (IMC) is a rare, locally aggressive, highly metastatic tumor that is poorly responsive to treatment. The purposes of this study were to retrospectively evaluate the history, signalment, and clinical signs of dogs with IMC; compare the outcome of affected dogs treated with traditional chemotherapy with those treated with piroxicam; evaluate Cox-2 expression of IMC cells; and correlate Cox-2 expression with outcome based on treatment. Strong cyclooxygenase-2 expression was present in all tumors. Improvement in clinical condition and disease stability was achieved in all dogs treated with piroxicam, with mean and median progression-free survival of 171 and 183 days, respectively. Median survival time of 3 dogs treated with doxorubicin-based protocols was 7 days, which was significantly less than that of dogs treated with piroxicam (median, 185 days). In conclusion, piroxicam should be considered as a single agent for the treatment of dogs with inflammatory mammary carcinoma.

Photodynamic therapy uses nonthermal coherent light delivered via fiber optic cable to locally activate a photosensitive chemotherapeutic agent that ablates tumor tissue. Owing to the limitations of light penetration, it is unknown whether photodynamic therapy can treat large osseous tumors. We determined whether photodynamic therapy can induce necrosis in large osseous tumors, and if so, to quantify the volume of treated tissue. In a pilot study we treated seven dogs with spontaneous osteosarcomas of the distal radius. Tumors were imaged with MRI before and 48 hours after treatment, and the volumes of hypointense regions were compared. The treated limbs were amputated immediately after imaging at 48 hours and sectioned corresponding to the MR axial images. We identified tumor necrosis histologically; the regions of necrosis corresponded anatomically to hypointense tissue on MRI. The mean volume of necrotic tissue seen on MRI after photodynamic therapy was 21,305 mm(3) compared with a pretreatment volume of 6108 mm(3). These pilot data suggest photodynamic therapy penetrates relatively large canine osseous tumors and may be a useful adjunct for treatment of bone tumors.

Unlabelled: The aim of this study was to evaluate the effectiveness of local treatment electrochemotherapy (ECT) with cisplatin and to compare it with effectiveness of surgery for treatment of mast cell tumours (MCT) in dogs., Materials and Methods: In the present retrospective study, 25 dogs of different breeds with MCT were divided into two treatment groups: surgery (16 dogs with 16 tumours) and those whose owners refused surgery being included into the ECT group (9 dogs with 12 tumours). Response rate and duration of response to the treatment were evaluated and comparison between groups was made., Results: The clinical stages of the tumours were stage I in 4 (45%) and stage III in 5 (55%) dogs treated by ECT; 12 (75%) dogs treated by surgery were stage I and 4 (25%) dogs were in clinical stage III. The median size of the tumours was 5.2 cm3 and 2.9 cm3 of tumours treated by surgery and ECT, respectively. ECT resulted in as comparable antitumor effectiveness as surgical treatment. However, the estimated median duration of response in dogs treated with complete surgical excision was 31.5 months, while it was not reached for the ECT group at the time of writing., Clinical Significance: ECT is an easy, effective and safe local treatment of MCT. It can be an alternative treatment to surgery, specifically for smaller nodules in which a complete response with long duration can be obtained after only one treatment session, or when the nodule is unresectable because of the location.

Objective: To identify prognostic factors in cats with injection-site sarcomas (ISSs)., Design: Retrospective case series., Animals: 57 cats with ISSs., Procedures: Medical records of cats were reviewed with regard to sex, age, anatomic site of tumor, tumor size, histologic grade, excision of a primary tumor versus excision of a recurrent ISS, use of excision alone versus excision plus adjuvant therapy, local tumor recurrence, and development of distant metastasis to predict overall survival time (ie, time from tumor excision to death)., Results: In univariate analyses, local recurrence and development of distant metastasis were significantly associated with survival time in cats. On multivariate analysis, development of distant metastasis remained a significant prognostic factor. Histologic grade was associated with distant metastasis, with cats having grade 3 tumors being significantly more likely to develop metastasis than cats with grade 1 and 2 tumors. Factors associated with local recurrence of ISSs were not identified., Conclusions and Clinical Relevance: The development of distant metastasis, which may occur later during the course of the disease, was identified as a prognostic factor for overall survival time in cats with ISSs. In addition, cats with histologic grade 3 ISSs should be considered for further interventional studies with chemotherapy to prevent the high rate of distant metastasis.

Objective: To determine clinical activity and toxic effects of lomustine when used to treat cats with mast cell tumors (MCTs)., Design: Retrospective case series., Animals: 38 cats with measurable, histologically or cytologically confirmed MCTs treated with lomustine at a dosage > or = 50 mg/m(2)., Procedures: Medical records were reviewed to determine response to treatment and evidence of drug toxicoses. The Kaplan-Meier method was used to estimate remission duration., Results: 26 cats had cutaneous MCTs, 7 had MCTs of the mesenteric lymph nodes, 2 had gastrointestinal tract MCTs, 2 had hepatic MCTs, and 1 had MCTs involving multiple organs. Targeted lomustine dosage was 50 mg/m(2) in 22 cats and 60 mg/m(2) in 16 cats. Median administered dosage of lomustine was 56 mg/m(2) (range, 48 to 65 mg/m(2)), and median number of doses administered was 2 (range, 1 to 12). Seven cats had a complete response and 12 had a partial response, for an overall response rate of 50%. Median response duration was 168 days (range, 25 to 727 days). The most common toxicoses were neutropenia and thrombocytopenia., Conclusions and Clinical Relevance: Results suggested that lomustine had activity against MCTs in cats and was well tolerated. Further, findings suggested that treatment with lomustine should be considered for cats with MCTs for which local treatment is not an option.

Objective: To compare response rates and remission and survival times in dogs with lymphoma treated with a continuous, multiagent, doxorubicin-based chemotherapeutic protocol or with a short-term single-agent protocol incorporating doxorubicin., Design: Nonrandomized controlled clinical trial., Animals: 114 dogs with lymphoma., Procedures: Dogs were treated with a chemotherapeutic protocol consisting of L-asparaginase, vincristine, cyclophosphamide, doxorubicin, methotrexate, and prednisolone (n=87) or doxorubicin alone (27)., Results: 63 of 86 (73%) dogs treated with the multiagent protocol (data on response was unavailable for 1 dog) and 14 of 27 (52%) dogs treated with the single-agent protocol had a complete remission. Dogs with lymphoma classified as substage

To evaluate the efficacy of clinical staging based on computed tomography (CT) imaging over the World Health Organization (WHO) staging system based on radiography for nasal tumors in dogs, a retrospective study was conducted. This study used 112 dogs that had nasal tumors; they had undergone radiography and CT and had been histologically confirmed as having nasal tumors. Among 112 dogs, 85 (75.9%) were diagnosed as adenocarcinoma. Then they were analyzed for survival time according to each staging system. More than 70% of the patients with adenocarcinoma were classified as having WHO stage III. The patients classified under WHO stage II tended to survive longer than those classified under WHO stage III. Dogs classified under WHO stage III were further grouped into CT stages III and IV, and CT stage III patients had a significantly longer survival time than CT stage IV patients. In addition, patients treated with a combination of surgery and radiation had a significantly longer survival time than the patients who did not receive any treatment in CT stage III. On the other hand, different treatment modalities did not show a significant difference in the survival time of CT stage IV dogs. The results suggest that WHO stage III dogs may have various levels of tumor progression, indicating that the CT staging system may be more accurate than the WHO staging system.

Background: Various diagnostic tests have been used to assign a clinical stage to dogs with lymphoma. As more sensitive staging methods are introduced, dogs are reclassified as having a higher disease stage, thereby affecting comparisons of dogs across differently staged clinical trials, and possibly, prognosis., Hypothesis: The addition of more sensitive staging tests causes stage migration in dogs with lymphoma., Animals: Fifty-nine client-owned dogs with previously untreated cytologically or histologically confirmed lymphoma, Methods: For every dog, the World Health Organization stage classification (I-V) was based on 5 groupings of various diagnostic tests: A (physical examination [PE] and quantitative blood count [QBC]), B (PE, QBC, thoracic and abdominal radiographs), C (PE, complete blood count with blood-smear evaluation [CBC], thoracic and abdominal radiographs), D (PE, CBC, thoracic radiographs, abdominal ultrasound), and E (PE, CBC, thoracic radiographs, abdominal ultrasound, and bone-marrow cytology). Dogs were treated with doxorubicin-based protocols., Results: There was migration between all of the staging methods except D to E. However, the stage was not a predictor of remission rate, remission duration, or survival, regardless of staging method used., Conclusions and Clinical Importance: These data emphasized the need for standardized methods to determine the clinical stage in dogs with lymphoma.

A relatively new strategy to longitudinally monitor tumor load in intact animals and the effects of therapy is noninvasive bioluminescence imaging (BLI). The validity of BLIf or quantitative assessment of tumor load in small animals is critically evaluated in the present review. Cancer cells are grafted in mice or rats after transfection with a luciferase gene--usually that of a firefly. To determine tumor load, animals receive the substrate agent luciferin intraperitoneally, which luciferase converts into oxyluciferin in an ATP-dependent manner Light emitted by oxyluciferin in viable cancer cells is captured noninvasively with a highly sensitive charge-coupled device (CCD) camera. Validation studies indicate that BLI is useful to determine tumor load in the course of time, with each animal serving as its own reference. BLI is rapid, easy to perform, and sensitive. It can detect tumor load shortly after inoculation, even when relatively few cancer cells (2500-10,000) are used. BLI is less suited for the determination of absolute tumor mass in an animal because of quenching of bioluminescence by tissue components and the exact location of tumors because its spatial resolution is limited. Nevertheless, BLI is a powerful tool for high-throughput longitudinal monitoring of tumor load in small animals and allows the implementation of more advanced orthotopic tumor models in therapy intervention studies with almost the same simplicity as when measuring traditional ectopic subcutaneous models in combination with calipers.

Objective: To assess response rate, median duration of response, adverse effects, and prognostic factors associated with concurrent administration of lomustine and prednisone as a first-line treatment for dogs with multicentric lymphoma., Design: Retrospective case series., Animals: 17 dogs., Procedures: Medical records were reviewed. Information obtained included signalment, physical examination findings, results of diagnostic testing, stage and substage, initial lomustine and prednisone dosages, and total number of lomustine doses administered., Results: Lomustine was administered at a median starting dosage of 67 mg/m(2), PO, every 21 days until 5 doses were given or disease progression was observed. Prednisone was administered at a median starting dosage of 1.8 mg/kg/d (0.82 mg/lb/d), PO, with dosage tapered during the first month of treatment. Six dogs had a complete response, and 3 had a partial response. Mean and median durations of response were 48.8 and 39.5 days, respectively. Median survival time was 111.2 days. In multivariate analyses, female sex and higher total lomustine dose were significantly associated with a longer disease-free inter-val. Neutropenia was the dose-limiting factor, with 4 dogs developing clinically important neutropenia 1 week after administration of a dose of lomustine., Conclusions and Clinical Relevance: Results suggest that concurrent treatment with lomustine and prednisone was well tolerated in dogs with multicentric lymphoma, but findings did not support the use of this combination for first-line treatment of affected dogs.