Cytological lymph node evaluation in dogs with mast cell tumours: association with grade and survival*

The purpose of this retrospective cohort study is to describe the association of cytological assessment of lymph node metastasis with survival and tumour grade in dogs with mast cell tumours. Regional lymph node aspirates of 152 dogs diagnosed with a mast cell tumour were reviewed and classified according to specific cytological criteria for staging. 97 dogs (63.8%) had stage I tumours, and 55 (36.2%) had stage II tumours. Stage II dogs had a significantly shorter survival time than dogs with stage I disease (0.8 and 6.2 years, respectively; P < 0.0001). Dogs with grade III mast cell tumours were more likely to have stage II disease (P = 0.004). These results suggest that cytological evaluation of lymph nodes in dogs with mast cell tumours provides useful and valuable clinical information, and the results correlate with tumour grade and outcome thus providing a practical and non‐invasive method for staging.     

Association of prognostic features and treatment on survival time of dogs with systemic mastocytosis: A retrospective analysis of 40 dogs

Systemic mastocytosis is a rare phenomenon, with limited information regarding prognostic features and effective treatment of canine patients with this disease. The objective of this study is to determine the impact of certain features and treatments on dogs with systemic mastocytosis. The medical records of 40 dogs from 4 northeastern US veterinary hospitals, with evidence of systemic mast cell disease, were evaluated retrospectively. Variables analysed with relation to overall survival and prognostic significance included treatment protocol used, substage, presence of a cutaneous or visceral tumour, presence of multiple cutaneous Mast cell tumours, grade of the primary tumour and metastatic site(s). Dogs with metastatic disease confined to distant lymph nodes lived longer than those with circulating mast cells in the blood (P = .001), and those with metastatic disease evident in more than 2 sites had a worse prognosis than those with disease in a single location (P = .005). Additionally, administration of chemotherapeutic agents led to increased survival over prednisone therapy alone (P = .008), with the combination of lomustine, vinblastine and prednisone prolonging survival over the tyrosine kinase inhibitor, toceranib phosphate (P = .002). Presence of mast cells in the blood and/or evidence of disease in more than 2 sites indicate widespread dissemination suggesting their use as negative prognostic features. Furthermore, a chemotherapy protocol including combination lomustine and vinblastine therapy may be more effective than toceranib phosphate for the treatment of dogs with disseminated mast cell disease. Overall, patients with systemic mastocytosis have a grave prognosis and more effective treatment options are needed.     

Use of CD9 and CD61 for the characterization of AML‐M7 by flow cytometry in a dog*

Acute megakaryoblastic leukaemia (AML‐M7) is a rare myeloproliferative disorder in domestic animals. Recently, thanks to the greater availability of immunophenotype techniques, precise diagnosis is more easily made. The morphological evaluation has its limitations, especially in the study of poorly differentiated cells. Few reports have described AML‐M7 in dogs using flow cytometry. This clinical case points out the utility of flow cytometry in the characterization of AML‐M7 in a 3‐year‐old German Shepherd dog. Flow cytometry investigation has established megakaryocytic lineage involvement by showing the presence of two megakaryocyte/platelet associated antigens (CD9 and CD61). In human medicine CD9 may be used as a platelet and megakaryocyte marker. There is an evidence of cross‐reactivity of human anti‐CD9 monoclonal antibody with canine samples. To our knowledge, the use of CD9 has never been described before, for this purpose in the dog.     

Gastric carcinoma in canines and humans,a review

Gastric carcinoma (GC) is the most common neoplasm in the stomach of dogs. Although incidence in the general population is reported to be low, breed‐specific GC has a high incidence. Median age at presentation ranges from 8 to approximately 10 years. The disease is mostly located in the lesser curvature and antropyloric region of the stomach. Unfortunately, diagnosis is usually made when the disease is at an advanced stage and, therefore, prognosis is poor. Due to similarities in clinical presentation, diagnosis, histology and prognosis, canine GC may serve as a valuable model for human GC. Extensive pedigrees of canine gastric carcinoma cases could reveal insights for human gastric carcinoma. Putative species differences include the role of Helicobacter in pathogenesis, the wide array of genetic data and screening available for humans, and treatment protocols that are available for human GC.     

Clinical pathological and epidemiological assessment of morphologically and immunologically confirmed canine leukaemia

Traditionally, classification of leukaemia in dogs has relied on morphological examination and cytochemical staining patterns, but aberrant cellular morphology and stain uptake often curtails accurate categorization, and historical data based on this classification may be unreliable. Immunophenotyping is now the gold standard for classification of leukaemias. The purpose of this prospective study was to assess the clinical pathological and epidemiological features of a population of dogs with morphologically and immunologically confirmed leukaemia and to compare them within categories: acute and chronic lymphoid leukaemia (ALL and CLL), and acute and chronic myeloid leukaemia (AML and CML). There were 64 cases of morphologically and immunologically confirmed leukaemia: 25 cases of ALL, 17 cases of CLL and 22 cases of AML. Prevalence of B and T immunophenotypes in ALL and CLL was not statistically different. Dogs with AML were significantly younger than those with ALL at presentation (P = 0.04). Golden Retriever dogs in the study population were overrepresented in comparison with a control population of dogs (6/25 ALL cases, 8/64 leukaemia cases). No sex was overrepresented. Dogs with ALL had significantly more severe neutropenia (P = 0.001) and thrombocytopenia (P = 0.002) than those with CLL and had significantly more cytopenias. The severity and numbers of cytopenias seen in ALL and AML were not significantly different. Twenty‐one of the leukaemia cases showed one cytopenia, fourteen had two cytopenias and twenty‐one cases had pancytopenia. Anaemia was the most common cytopenia seen in isolation (17/21). No dogs had neutropenia without anaemia and/or thrombocytopenia. Total white blood cell counts were not different between the groups. The atypical cell counts within the peripheral blood were significantly higher in ALL than AML; both in isolation and as a percentage of the total white blood cell count (P = 0.03). This study strengthens the hypothesis that acute leukaemias give rise to more profound cytopenias, affecting more cell lines, than chronic leukaemias.     

Long‐term survival in dogs with localized histiocytic sarcoma treated with CCNU as an adjuvant to local therapy*

Histiocytic sarcoma (HS) is associated with a poor prognosis owing to the presence of metastasis at the time of diagnosis in most dogs. Improved outcome has been reported in several dogs with localized HS following local therapy, however, distant metastasis occurs in 70–91% of dogs suggesting that adjuvant systemic therapy is necessary. The purpose of this retrospective study was to describe clinical characteristics and outcome in dogs with localized HS treated with aggressive local therapy plus adjuvant CCNU chemotherapy. Data from 16 dogs were evaluated. The median disease‐free interval was 243 days. Two dogs had local recurrence and eight dogs developed metastatic disease with a median time to relapse of 201 days in these 10 dogs. The median survival time for all 16 dogs was 568 days. These results support the recommendation for aggressive local therapy combined with adjuvant CCNU chemotherapy in dogs with localized HS.     

Angiofibroma of the nasal cavity in 13 dogs

This case series describes a rare entity, nasal angiofibroma, in 13 dogs that were presented to the University of Wisconsin, School of Veterinary Medicine from 1988 to 2000. All dogs in this case series presented with clinical signs and radiographic changes that were strongly suggestive of a locally invasive neoplasm. However, histopathology completed on transnostral core biopsy samples revealed benign appearing vascular proliferation with secondary lymphosuppurative inflammation was established despite cytologic criteria of malignancy present in five dogs. On the basis of the outcomes in this case series, nasal angiofibroma should be considered a differential for dogs presenting with clinical signs consistent with a malignant nasal tumour.     

Identification of occult micrometastases and isolated tumour cells within regional lymph nodes of previously diagnosed non‐metastatic (stage 0) canine carcinomas

Metastatic dissemination of carcinomas to lymph nodes impacts prognosis and treatment recommendations in human and veterinary medicine. Routine histopathologic evaluation of regional lymph nodes involves haematoxylin and eosin (H&E) staining to identify intra‐nodal neoplastic cells; however, identification of small volume metastases (micrometastases and individual tumour cells) may be missed without the aid of immunohistochemistry or additional step‐sections. The aim of this study was to identify occult carcinoma metastases in previously diagnosed non‐metastatic lymph nodes using step‐sections and pancytokeratin (panCK) immunohistochemistry. Samples from 20 regional lymph nodes diagnosed as non‐metastatic were serially sectioned and evaluated with panCK. Of these, 25% (n = 5) contained micrometastases (n = 1) or isolated tumour cells (n = 4). This study demonstrates the increased efficacy of serial step‐sections combined with panCK immunohistochemistry to identify small volume metastases in regional lymph nodes. The prognostic significance of micrometastases and isolated tumour cells in regional lymph nodes warrants further investigation in veterinary medicine.     

Outcome following treatment of soft tissue and visceral extraskeletal osteosarcoma in 33 dogs: 2008–2013

Extraskeletal osteosarcoma (EOS) is a rare, highly malignant mesenchymal neoplasm arising from viscera or soft tissues characterised by the formation of osteoid in the absence of bone involvement. Owing to the rarity of these neoplasms very little information exists on treatment outcomes. The purpose of this study was to describe the outcome following surgical treatment of non‐mammary and non‐thyroidal soft tissue and visceral EOS in dogs. Thirty‐three dogs were identified; the most common primary tumour site was the spleen. Dogs that had wide or radical tumour excision had longer survival times compared with dogs that had only marginal tumour excision performed [median survival time of 90 days (range: 0–458 days) versus median survival time of 13 days (range: 0–20 days)]. The use of surgery should be considered in the management of dogs with non‐mammary and non‐thyroidal soft tissue and visceral EOS.     

Serum neopterin levels in female dogs with malignant mammary tumours

In this study, we have determined serum neopterin levels in female dogs with primary malignant mammary tumours. The study involved 50 female dogs which had a malignant mammary tumours removed surgically (32 animals with carcinoma, 12 animals with sarcoma and 6 animals with carcinosarcoma) and 10 clinically healthy female dogs. Serum neopterin levels were determined using a commercial ELISA kit. The mean neopterin levels were lower in the malignant tumour groups than in healthy animals but differences were statistically significant only in carcinoma and sarcoma groups. The decrease of neopterin levels in animals with malignant mammary tumours may suggest their decreased cellular immunity. Moreover, it might indicate that decreased activity of cellular mechanisms of the anti‐neoplastic response is one of the factors associated with the development and course of malignant mammary tumours in female dogs; however, further studies are necessary.     

Ultrasound and computed tomography of the iliosacral lymphatic centre in dogs with anal sac gland carcinoma

In this prospective study, we hypothesized that computed tomography (CT) would identify more normal and abnormal iliosacral lymph nodes (LNs) than abdominal ultrasound in dogs with anal sac gland carcinoma (ASGC). Twelve client‐owned dogs with ASGC but without distant metastasis were enrolled. Abdominal ultrasound and contrast‐enhanced CT scans of the abdomen were obtained. Iliosacral LNs were counted and assessed for location, laterality and size. Significantly (P < 0.00001) more iliosacral LNs were identified with CT (61) than ultrasound (30), including significantly (P = 0.00012) more medial iliac LNs with CT (33) than ultrasound (19). There was no difference in number of internal iliac LNs identified with CT versus ultrasound. Significantly (P = 0.000061) more sacral LNs were identified with CT (15) than ultrasound (0). Ultrasound identified slightly more (7) abnormal iliosacral LNs than CT (5). Contrast CT was able to identify more normal but not more abnormal LNs than ultrasound.     

Prognostic impact of neoadjuvant aglepristone treatment in clinicopathological parameters of progesterone receptor‐positive canine mammary carcinomas

Neoadjuvant treatment of canine mammary carcinomas with the progesterone receptor (PR) antagonist aglepristone has a PR expression‐related inhibiting effect on proliferation index (PI). The aim of this study was to evaluate the effect of the treatment in the disease‐free period (DFP) and overall survival (OS) of canine mammary carcinomas. Fifty female dogs with mammary carcinomas were treated with aglepristone (n = 34) or oil vehicle (n = 16) before surgery (day 15). PR expression and PI were analysed by immunohistochemistry in samples taken at days 1 and 15. Epidemiological and clinicopathological data were assessed. DFP and OS data were retrieved every 4–6 months for at least 24 months after surgery. Aglepristone treatment increased DFP of animals bearing PR+ tumours with size smaller than 3 cm, complex and mixed tumours, with histologic grades I and II, and with PI ≤ 10%. Although further studies are necessary, current evidence points to treatment with aglepristone as useful for the management of canine mammary tumours.     

The tyrosine kinase inhibitor toceranib in feline injection site sarcoma: efficacy and side effects

Because of their locally invasive growth and high recurrence rate despite of aggressive local therapy, treatment of feline sarcomas is challenging. The tyrosine kinase inhibitor (TKI) toceranib is currently licensed for the treatment of canine mast cell tumours. There are only few reports about TKI usage in cats. Previous studies indicated promising potential of TKI for the treatment of feline injection site sarcoma (FISS). In this prospective clinical trial, 18 cats with unresectable FISS were treated at a target dosage of 3.25 mg kg^?1 every other day to evaluate the clinical efficacy and toxicity of toceranib. There was no clinical response measurable. Adverse events were generally mild and temporary. Grade 3 or 4 adverse events developed infrequently and all resolved with drug holidays and dose reductions.     

Phase I clinical trial of oral rosiglitazone in combination with intravenous carboplatin in cancer‐bearing dogs

Rosiglitazone is an FDA‐approved peroxisome proliferator‐activated receptor gamma (PPARγ) agonist and antidiabetic agent in humans that has been investigated for its ability to reduce tumor cell growth. The purpose of this study was to determine the maximally tolerated dose, peak plasma concentrations and side effect profile of oral rosiglitazone when combined with carboplatin in dogs with cancer. Rosiglitazone was administered at 6 and 8 mg/m² to seven dogs. Carboplatin was administered at 240–300 mg/m² in combination with rosiglitazone. For toxicity evaluation, the toxicity data for the seven dogs in this study were combined with the toxicity data from three dogs previously reported in a methodology study. Peak plasma rosiglitazone concentrations varied with dose. The dose‐limiting toxicity was hepatic at a dose of 8 mg/m². Three dogs had mild to moderate alanine aminotransferase elevations but no changes in total bilirubin, alkaline phosphatase, blood glucose or γ‐glutamyltranspeptidase values were noted.     

A review of sentinel lymph node evaluation and the need for its incorporation into veterinary oncology

Being the first lymph node or nodes to which many primary tumours reliably drain, the disease status of the sentinel lymph node/s (SLN) is important in the prediction of survival. SLN identification and biopsy are critical in the staging of human cancers. The status of the SLN helps determine prognosis and shape treatment plans. SLN evaluation is currently not routinely performed in veterinary oncology, not even at specialty oncology practices. Given the prognostic importance of lymph node involvement in tumours such as mammary gland carcinoma, osteosarcoma, synovial cell sarcoma and mast cell tumours, SLN evaluation should be incorporated into routine clinical practice so as to improve our clinical assessment of veterinary oncologic patients.     

PCNA and grade in 13 canine oral squamous cell carcinomas: association with prognosis

This study evaluated the prognosis factors of age, tumour size, anatomic location, histological grade and proliferating cell nuclear antigen (PCNA) expression in 13 dogs with oral squamous cell carcinoma (OSCC) with bone invasion and without signs of lymph node or distant metastasis. All animals were treated with radical excision performed with at least 1 cm margin, based on computed tomography images. In the 2‐year follow‐up, median disease‐free survival was 138 days for dogs with grade 3 tumours and was not reached for those with grade 2 tumours. Grade 3 tumours and PCNA labelling index ≥65% were related with a shorter disease‐free survival time and consequently poor prognosis (p = 0.003 and p = 0.034, respectively). Mean PCNA labelling index was significantly higher in recurrent cases (p = 0.011). Histological grade and PCNA expression may be important prognosis factors in canine OSCC.