The 2-tier grading system identifies canine cutaneous and/or subcutaneous mast cell tumors with aggressive biological behavior regardless of growth model.

Histologic grading of canine cutaneous mast cell tumors (cMCTs) has prognostic and therapeutic implications, yet validation for subcutaneous MCTs (scMCTs) is lacking. For scMCTs with or without dermal invasion, determining their biological behavior remains poorly standardized and sometimes sparks controversy. This prospective study aimed to assess the prognostic utility of the 2-tier histologic grading system in MCTs with different growth models (GMs) and explore the prognostic impact of the GM itself. We assessed 6 histologic GM categories: solely cMCT (C-SC0), cMCT with superficial (C-SC1) or deep subcutaneous (C-SC2) involvement, solely scMCT (SC-C0), and scMCT with deep (SC-C1) or superficial (SC-C2) infiltration of the dermis. Ninety-one MCTs from 76 dogs undergoing excision and regional/sentinel lymphadenectomy were examined. GM classification identified 11 (12%) C-SC0 tumors, 12 (13%) C-SC1, 15 (16%) C-SC2, 21 (23%) SC-C0, 15 (16%) SC-C1, and 17 (19%) SC-C2. Mitotic count, 2-tier grade, nodal involvement, surgical margins, and outcome were stratified according to GM. scMCTs lacking dermal invasion, historically associated with a benign clinical course, had a poor prognosis in 10% of cases. cMCTs exhibiting deep subcutaneous involvement included the largest percentage of high-grade tumors (33%), had the highest occurrence of overt nodal metastases (33%), and had the lowest 1-year survival rate (86%). Histologic grade was confirmed as a relevant prognostic factor, surpassing nodal involvement and histologic margin status. The 2-tier histologic grading enabled the identification of all MCTs with aggressive biological behavior, regardless of their cutaneous or subcutaneous location.

Comparison of sonographic and CT findings for the identification of renal nodules in dogs and cats.

Ultrasonography (US) and computed tomography (CT) are used to diagnose neoplastic and non-neoplastic focal renal lesions in dogs and cats; however, comparative studies between these two diagnostic tools are lacking. The aim of this retrospective, methods comparison study was to evaluate and compare the performance of US compared to CT in identifying at least one renal nodule in animals with confirmed focal renal lesions. Imaging studies of animals with uni- or bilateral renal nodules smaller than 3 cm that underwent both US and CT and that had a pathologically confirmed diagnosis were reviewed. Animals with renal cysts and infarcts were excluded. Recorded features for both modalities included the following: shape, size, number, localization, margins, renal profile. For CT only, recorded features also included attenuation (HU) and pattern of enhancement.  For US only, recorded features also included echogenicity, echostructure, and rate of visibility. Final diagnosis was obtained by cytology or histopathology. Using CT, lesions were identified in all 39 (100%) kidneys of 18 dogs and seven cats. Most lesions were multiple, cortical, well-defined, iso-attenuating (precontrast), hypo-attenuating, and moderately enhancing (postcontrast). Using US, lesions were identified in 29 of 39 (74%) kidneys. Overall, nine (31%) lesions were poorly visible; 10 (26%) kidneys appeared normal; in 17 (59%) organs, lesions' number was underestimated. Isoechoic, non-protruding lesions were difficult to identify by US. Ultrasonography underestimated renal lesions compared to CT in 59% of the kidneys (P = 0.001). Final diagnoses included metastatic disease (n = 16), infiltration by feline lymphoma (n = 4), primary neoplasia (n = 3), and non-neoplastic benign lesions (n = 2).

Ultrasonographic features of intestinal lipogranulomatous lymphangitis in 10 dogs.

Intestinal lipogranulomatous lymphangitis (ILL) is a granulomatous inflammation of the lymphatic vessels of the intestinal wall and mesentery characterized by lipogranulomas. The purpose of this retrospective, multi-center, case series study is to report the ultrasonographic features of canine ILL. Ten dogs with a histologically confirmed ILL undergoing preoperative abdominal ultrasound were retrospectively included. Additional CT was available in two cases. Lesion distribution was focal in eight dogs and multifocal in two. All dogs presented with intestinal wall thickening and two had a concomitant mesenteric mass adjacent to the intestinal lesion. All lesions were in the small intestine. Ultrasonographic features were altered wall layering with predominantly muscular and to a lesser extent submucosal layer thickening. Other findings included hyperechoic nodular tissue within the muscular, serosa/subserosal, and mucosal layers, hyperechoic perilesional mesentery, enlarged submucosal blood/lymphatic vessels, mild peritoneal effusion, intestinal corrugation, and mild lymphadenomegaly. The two intestinal to mesenteric masses presented heterogeneous echostructure, predominantly hyperechoic with multiple hypo/anechoic cavitations filled with mixed fluid and fat attenuation content on CT. Histopathological findings included lymphangiectasia, granulomatous inflammation, and structured lipogranulomas affecting mainly submucosa, muscularis, and serosa. The intestinal to mesenteric cavitary masses revealed severe granulomatous peritonitis with steatonecrosis. In conclusion, ILL should be considered as a differential diagnosis for dogs with this combination of ultrasonographic features.

Longitudinal lymph node step-sectioning for the identification of metastatic disease in canine mast cell tumor.

Lymph node (LN) metastasis in canine mast cell tumor (MCT) can affect prognosis and postsurgical treatment recommendations; however, routine histological single-section examination may underestimate the incidence of metastases. This prospective study aimed at determining whether longitudinal step-sectioning of the entire LN allows for a more reliable detection of metastases. Dogs with MCT undergoing resection of the primary tumor and regional lymphadenectomy were enrolled. Formalin-fixed LNs were bisected longitudinally, both halves were embedded in paraffin and histological sections prepared at 200 µm steps. The nodal mast cells were classified according to the Weishaar classification. First-section evaluation (FSE; ie, examination of the first section obtained from the blocks) and whole LN step-section evaluation (SSE) were compared. Fifty-eight LNs were included. The median number of sections per LN was 6 (range, 3-28). FSE with toluidine blue (TB) revealed 27 (47%) nonmetastatic (HN0), 14 (24%) premetastatic (HN1), 9 (15%) early metastatic (HN2), and 8 (14%) overtly metastatic (HN3) LNs. SSE with TB resulted in upgrading the LN status in 2 cases (HN2 to HN3; HN0 to HN1). Evaluation of the first section plus an additional step-section resulted in 100% accuracy. Compared with SSE with TB, the accuracy of FSE with HE was 98% for HN3 LNs and 74% for HN2 LNs. FSE appears to reliably allow for the detection of LN metastasis in MCT, although examination of a further parallel section at a 200 µm step may increase the accuracy. A metachromatic stain is recommended for the identification of early metastases.

A retrospective study on prophylactic regional lymphadenectomy versus nodal observation only in the management of dogs with stage I, completely resected, low-grade cutaneous mast cell tumors.

BACKGROUND: While lymphadenectomy of metastatic lymph nodes (LNs) has been associated with improved outcome, the clinical utility of prophylactic lymphadenectomy in dogs with stage I cutaneous mast cell tumors (cMCTs) remains a controversial topic. To assess the therapeutic role of lymphadenectomy of uninvolved regional LNs, the long-term outcome of cMCT-bearing dogs with cytologically negative and surgically unresected regional LNs (observation only, OO) was compared with that of dogs with surgically resected and histologically negative regional LNs (prophylactic regional lymphadenectomy, PRL). RESULTS: A retrospective analysis of 64 dogs with a low-grade, completely resected stage I cMCT was performed: 35 (54.7%) dogs were subjected to OO and 29 (45.3%) underwent PRL. Dogs were monitored for a median of 813 and 763 days in the OO group and PRL group, respectively. The number of dogs undergoing MCT progression was significantly higher in the OO group (P = 0.028) and curve comparison revealed a tendency to a better time to progression in the PRL group (P = 0.058). No significant difference in survival time (P = 0.294) was observed between dogs in the OO and PRL groups. CONCLUSIONS: Our results showed that lack of immediate lymphadenectomy was associated with a higher risk for tumor progression. This preliminary judgement, reinforced by the findings that lymphadenectomy was well tolerated in all cases, and that histopathology provides the definitive assessment of the nodal pathological status, may suggest that prophylactic lymphadenectomy is indicated in the management of stage I MCTs. Larger prospective studies are warranted for generating clinical evidence of this latter hypothesis.

Grading Cutaneous Mast Cell Tumors in Cats.

Cutaneous mast cell tumors (cMCTs) account for approximately 20% of skin neoplasms in cats. As there is no grading system for these tumors, prognosis is difficult to estimate. Although the typical presentation is a benign tumor that can be cured by surgical excision, a small but important proportion of feline cMCTs is biologically aggressive and can spread to local lymph nodes, precede the onset of disseminated cutaneous disease, or be associated with visceral involvement. A number of macroscopic and histologic features were retrospectively evaluated in cases of feline cMCTs treated with surgical excision with or without medical therapy. Cats were divided into 2 groups based on the clinical outcome. Group 1 included cats alive with no mast cell tumor-related disease at 1000 days from surgery; group 2 included cats developing histologically confirmed metastatic or cutaneous disseminated disease. The criteria allowing the best differentiation between the groups were used to develop a grading scheme. Groups 1 and 2 were composed by 48 (76%) and 15 (24%) cases, respectively. Tumors were classified as high grade if there were >5 mitotic figures in 10 fields (400×) and at least 2 of the following criteria: tumor diameter >1.5 cm, irregular nuclear shape, and nucleolar prominence/chromatin clusters. According to this scheme, the 15 (24%) high-grade cMCTs had significantly reduced survival time (median, 349 days; 95% CI, 0-739 days) as compared with the 48 low-grade tumors (median not reached; P < .001). Further studies are warranted to validate this grading system and test reproducibility on a larger case series.

Evaluation of Ki-67 expression in feline non-ocular melanocytic tumours.

BACKGROUND: Melanomas are rare in cats. The eye is the most commonly involved site, whereas few data are available about feline non-ocular melanomas (NOMs). Ki-67 thresholds with prognostic relevance have been established for canine melanomas, but not in cats. This study was undertaken to investigate the relationship between Ki-67 index, tumour characteristics, and clinical outcome in feline NOMs. Histologic samples were retrospectively reviewed. Amelanotic tumours were admitted upon immunohistochemical positivity for Melan A or S100. Evaluated parameters included morphological diagnosis, histotype, junctional activity, degree of pigmentation, vascular invasion, lymphocytic infiltrate, necrosis, mitotic count (MC) and Ki-67 index. Pigmented tumours were bleached before evaluation. Clinical and follow-up information were retrieved via telephone interviews with the referring veterinarians. RESULTS: Fifty tumours located in skin (n = 33) and mucosae (n = 17) were included. Forty-eight percent and 95% of amelanotic tumours (n = 21) stained positive for Melan A and S100, respectively. Most achromic tumours were mucosal (P < 0.001, Fisher's exact test) and presented a spindle cell morphology (P = 0.002; Fisher's exact test). MC and Ki-67 index were significantly correlated (P < 0.001; R = 0.67; Spearman's rank correlation); median values were 15 (range, 0-153) and 28% (range, 1-78%), respectively. Both were significantly higher in spindle cell melanomas, in tumours lacking junctional activity and in poorly-pigmented tumours. Follow-up information was available for 33 cats (66%). Variables related with a poor clinical outcome included mucosal location, tumour size, spindle, balloon and signet ring cell histotypes, low pigmentation, MC > 5, Ki-67 > 20% and lack of treatment administration. On multivariable analysis, only tumour histotype and treatment retained prognostic significance. CONCLUSIONS: Although the majority of feline NOMs behave aggressively, Ki-67 index, together with other parameters, may contribute to prognostic assessment. Prospective studies on homogeneous populations are warranted to identify reliable threshold values for this marker.

Canine Splenic Nodular Lymphoid Lesions: Immunophenotyping, Proliferative Activity, and Clonality Assessment.

Canine splenic lymphoid nodules are currently classified as indolent lymphomas (marginal zone lymphoma [MZL], mantle cell lymphoma [MCL]) or nodular hyperplasia (lymphoid [LNH] or complex [CNH] type). Their differentiation can be difficult on morphology, because of similar histologic appearance and poorly defined diagnostic criteria. Thirty-five surgical samples of splenic lymphoid nodules were reviewed in order to assess the diagnostic contribution of immunophenotyping, proliferative activity and clonality (PARR) in differentiating between hyperplastic and neoplastic lesions. Proliferative activity was evaluated by double immunolabeling for Ki-67 and CD79a, in order to separately assess the proliferative activity of B cells and non-B cells. Definitive diagnoses were MZL ( n = 11), MCL ( n = 4), LNH ( n = 10), and CNH ( n = 10). The overall concordance between histology and PARR was above 90%. Lymphomas had a significantly higher percentage of CD79a-positive areas (mean, 36.30%; P = .0004) and a higher B-cell proliferative activity (median Ki-67 index, 5.49%; P = .0012). The threshold value most accurately predicting a diagnosis of lymphoma was ≥28% of B-cell areas, with a Ki-67 index above 3%. Dogs were monitored for a median follow-up time of 870 days (IQR, 569-1225), and no relapses were documented. Overall median survival time was 1282 days. The combination of histology, immunohistochemistry and PARR can improve the diagnostic accuracy for canine splenic lymphoid nodules, although the long-term behavior of these lesions appears similar.

COMPARISONS AMONG COMPUTED TOMOGRAPHIC FEATURES OF ADIPOSE MASSES IN DOGS AND CATS.

A better understanding of the CT features of different forms of canine and feline adipose tumors would be valuable for improving patient management and treatment. The purpose of this retrospective, cross-sectional study was to describe and compare the CT features of pathologically confirmed lipomas, infiltrative lipomas, and liposarcomas in a sample of canine and feline patients. A total of 50 animals (46 dogs, four cats) and a total of 60 lesions (23 lipomas, 20 infiltrative lipomas, and 17 liposarcomas) were included in the study. Lipomas appeared as round to oval-shaped (n = 21), well-marginated (n = 20) fat-attenuating lesions. Infiltrative lipomas appeared as homogeneous, fat-attenuating masses but, unlike lipomas, they were most commonly characterized by an irregular shape (75%; P < 0.001), and linear components, hyperattenuating relative to the surrounding fat (100%; P < 0.05). Liposarcomas were represented exclusively by heterogeneous lesions with soft tissue attenuating components with a multinodular appearance (76.5%; P < 0.05). Regional lymphadenopathy (n = 10) and amorphous mineralization (n = 4) were also observed in association with liposarcomas. Computed tomography can provide useful information regarding disease location, extent, and involvement of the adjacent structures. Tumor definition and shape were the most useful parameters to differentiate between lipomas and infiltrative lipomas. The presence of a heterogeneous mass, with a multinodular soft tissue component and associated regional lymphadenopathy and mineralization, were features favoring a diagnosis of liposarcoma.

Combination of radiation therapy and firocoxib for the treatment of canine nasal carcinoma.

Carcinomas represent two-thirds of canine nasosinal neoplasms. Although radiation therapy (RT) is the standard of care, the incidence of local recurrence following treatment is high. Cyclooxygenase-isoform-2 (COX-2) is expressed in 71-95% of canine nasal carcinomas and has been implicated in tumor growth and angiogenesis. Accordingly, COX-2 inhibition seems rational to improve outcome. Dogs with histologically confirmed, previously untreated nasal carcinomas were randomized to receive the combination of a selective COX-2 inhibitor (firocoxib) and palliative RT (Group 1) or RT and placebo (Group 2). Patients were regularly monitored with blood tests, urinalysis, and computed tomography. Pet owners were asked to complete monthly a quality-of-life questionnaire. Twenty-four dogs were prospectively enrolled. According to Adams modified system, there were five stage 1, five stage 2, three stage 3, and 11 stage 4 tumors. Two dogs had metastases to regional lymph nodes. Median progression-free interval and overall survival were 228 and 335 days in Group 1 (n = 12) and 234 and 244 days in Group 2 (n = 12). These differences were not statistically significant. The involvement of regional lymph nodes was significantly associated with progression-free interval and overall survival (P = 0.004). Quality of life was significantly improved in Group 1 (P = 0.008). In particular, a significant difference was observed for activity and appetite. Although not providing a significant enhancement of progression-free interval and overall survival, firocoxib in combination with RT is safe and improved life quality in dogs with nasal carcinomas.

Role of CT in the Staging of Colorectal Tumors: A Preliminary Study on 10 Dogs.

This study aimed to define the CT features of colorectal tumors in dogs and assess CT's role in tumor staging. It was a retrospective, multicenter, descriptive study involving dogs with a cyto-histopathological diagnosis of colorectal tumors and high-quality pre- and post-contrast CT scans of the abdomen. CT successfully identified colorectal lesions in all cases, showing variations such as wall thickening, presence of masses, and luminal stenosis. It also detected lymph node involvement. Overall, this study helps us to understand the CT features of both epithelial and mesenchymal colorectal tumors, emphasizing CT's importance in staging and surgical planning for affected dogs. Larger studies are needed to identify specific CT findings for different colorectal neoplasms.

Dysregulated miRNAs in a canine model of haemangiosarcoma metastatic to the brain.

Haemangiosarcoma is a highly metastatic and lethal cancer of blood vessel-forming cells that commonly spreads to the brain in both humans and dogs. Dysregulations in phosphatase and tensin (PTEN) homologue have been identified in various types of cancers, including haemangiosarcoma. MicroRNAs (miRNAs) are short noncoding single-stranded RNA molecules that play a crucial role in regulating the gene expression. Some miRNAs can function as oncogenes or tumour suppressors, influencing important processes in cancer, such as angiogenesis. This study aimed to investigate whether miRNAs targeting PTEN were disrupted in canine haemangiosarcoma and its corresponding brain metastases (BM). The expression levels of miRNA-10b, miRNA-19b, miRNA-21, miRNA-141 and miRNA-494 were assessed in samples of primary canine cardiac haemangiosarcomas and their matched BM. Furthermore, the miRNA profile of the tumours was compared to samples of adjacent non-cancerous tissue and healthy control tissues. In primary cardiac haemangiosarcoma, miRNA-10b showed a significant increase in expression, while miRNA-494 and miRNA-141 exhibited downregulation. Moreover, the overexpression of miRNA-10b was retained in metastatic brain lesions. Healthy tissues demonstrated significantly different expression patterns compared to cancerous tissues. In particular, the expression of miRNA-10b was nearly undetectable in both control brain tissue and perimetastatic cerebral tissue. These findings can provide a rationale for the development of miRNA-based therapeutic strategies, aimed at selectively treating haemangiosarcoma.

A retrospective Italian Society of Veterinary Oncology (SIONCOV) study of 56 cats with appendicular osteosarcoma.

Osteosarcoma is the most common malignant primary bone cancer, but it is infrequently reported in cats. Feline appendicular osteosarcoma typically exhibits good prognosis when treated with surgery alone. A retrospective multi-institutional study was conducted to identify possible prognostic factors. Cats diagnosed with appendicular osteosarcoma were included if initial staging and follow-up information were available. Data including signalment, tumour characteristics, treatment modalities, and survival outcomes were collected and analysed. Fifty-six cats were included; the femur was the most frequently affected bone. Eight cats had distant metastasis at admission and an additional 9 developed metastatic disease during follow-up, resulting in an overall metastatic rate of 30%. Forty-nine (87.5%) cats underwent surgery, and 4 also received adjuvant chemotherapy. Among operated cats, median time to local progression (TTLP), time to distant progression and tumour-specific survival (TSS) were not reached. One- and 2-year survival rates were 66% and 55%, respectively. Seven (12.5%) cats received no treatment; 1- and 2-year survival rates were 25% and 0%, respectively. Operated cats had significantly longer TTLP (P < .001) and TSS (P = .001) compared with non-operated cats. Among operated cats, young age negatively impacted local tumour progression, while the presence of distant metastasis at diagnosis was associated with a higher risk of tumour-related death. This study reaffirms the good prognosis for cats with appendicular osteosarcoma undergoing surgery, but sheds light on some additional factors to consider. Accurate initial staging is recommended, as the metastatic rate may exceed many previous estimations. Surgery substantially extends survival time, whereas the role of chemotherapy remains uncertain.

A Retrospective Clinico-Pathologic Study of 35 Dogs with Urethral Transitional Cell Carcinoma Undergoing Treatment.

Chemotherapy and cyclooxygenase inhibitors (COXi) are primary treatments for canine urethral transitional cell carcinoma (uTCC), a tumor known for its aggressiveness and poor prognosis. This retrospective study aimed to evaluate the clinico-pathological characteristics, treatment modalities, and prognostic factors of 35 dogs with confirmed uTCC that received chemotherapy and COXi. Upon admission, urethral obstruction (UO) and urinary tract infection (UTI) were observed in seven (20%) dogs each. Gemcitabine (n = 20; 57.1%) and vinblastine (n = 10; 28.6%) were commonly used as first-line therapies, with four dogs also receiving radiation therapy. Based on RECIST, one (2.9%) dog achieved complete remission, nine (25.7%) partial remission, 20 (57.14%) showed stable disease, and five (14.3%) progressed. Among dogs with UO, six (85.7%) showed resolution or improvement after the first chemotherapy dose. The median time to local progression was 171 days (range: 107-235), and the median survival time was 333 days (range: 158-508). Dogs with UO upon admission had a higher risk of local progression, while both UO and UTI were associated with an increased risk of overall disease progression and tumor-related death. Additionally, gemcitabine significantly improved metastatic control. This study identified UO and UTI as negative prognostic factors, highlighting the importance of a multimodal approach in managing uTCC.

Multiorgan metastases with massive bone involvement of a medullary thyroid carcinoma in a dog.

A 10-year-old mixed-breed male dog was referred for a subcutaneous mass on the ventral neck. Based on total-body computed tomography (TBCT), the mass was located in the left thyroid lobe. Further alterations included enlargement of the ipsilateral mandibular and prescapular lymph nodes (LNs). Surgical excision of the mass and enlarged LNs was performed. Histopathology and immunohistochemistry were consistent with a medullary (C-cell) thyroid carcinoma, with no evidence of nodal metastases. Surgery was considered curative, and no medical treatment was provided. Periodic follow-up rechecks were unremarkable. After 18 months, the dog exhibited lethargy, vomiting, anorexia, and hind leg stiffness. TBCT revealed polyostotic osteopathy, and cytology suggested a metastatic endocrine carcinoma. Due to the dog's poor clinical condition and prognosis, the owner elected euthanasia, and a necropsy was performed. Based on gross pathology, histopathology, and immunohistochemistry, multiple metastases of the previous thyroid carcinoma were diagnosed, involving the occipital bone, multiple vertebrae, left sacral wing, fourth right rib, left scapula, left humerus, intrathoracic LNs, lung, spleen, and adrenal glands. This report describes a case of medullary thyroid carcinoma with distant multiorgan metastases and massive bone involvement after a disease-free interval of 18 months.

A Phase 2, Single-Arm, Open-Label Clinical Trial on Adjuvant Peptide-Based Vaccination in Dogs with Aggressive Hemangiosarcoma Undergoing Surgery and Chemotherapy.

To test the antitumor effect and safety of peptide-based anticancer vaccination in dogs with hemangiosarcoma undergoing the standard of care (SOC; surgery and doxorubicin), canine hemangiosarcoma cells were infected with Salmonella typhi Ty21a to release immunogenic endoplasmic reticulum stress-related peptides into the extracellular milieu via CX43 hemichannels opening. The infected tumor cell secretome constituted the vaccine. Following the SOC, dogs with biologically aggressive hemangiosarcoma were vaccinated a total of five times, once every 3 weeks, and were followed up with serial imaging. A retrospective population of dogs undergoing the SOC alone served as controls. The primary endpoints were the time to progression (TTP) and overall survival (OS), and the secondary endpoints were toxicity and immune responses. A total of 28 dogs were vaccinated along with the SOC, and 32 received only the SOC. A tumor-specific humoral response along with a vaccine-specific T-cell response was observed. Toxicity did not occur. The TTP and OS were significantly longer in vaccinated versus unvaccinated dogs (TTP: 195 vs. 160 days, respectively; p = 0.001; OS: 276 vs. 175 days, respectively; p = 0.002). One-year survival rates were 35.7% and 6.3% for vaccinated and unvaccinated dogs, respectively. In dogs with hemangiosarcoma undergoing the SOC, the addition of a peptide-based vaccine increased the TTP and OS, while maintaining a safe profile. Moreover, vaccinated dogs developed a tumor-specific response, supporting the feasibility of future phase three studies.

Timely adjuvant chemotherapy improves outcome in dogs with non-metastatic splenic hemangiosarcoma undergoing splenectomy.

Timely delivery of adjuvant chemotherapy has been shown to be advantageous in many human cancers and canine osteosarcoma. Adjuvant chemotherapy has been shown to improve outcome for canine splenic hemangiosarcoma. The aim of this retrospective study was to investigate whether timely adjuvant chemotherapy administration resulted in better outcome in dogs with non-metastatic splenic hemangiosarcoma undergoing splenectomy. Medical records were searched for dogs with non-metastatic, splenic hemangiosarcoma that received splenectomy and adjuvant chemotherapy. The number of days from surgery to the first chemotherapy dose (StoC) was evaluated to identify the cut-off value associated with the best survival advantage. StoC and other possible prognostic factors were tested for influence on time to metastasis (TTM) and overall survival (OS). Seventy dogs were included. Median StoC was 20 days (range: 4-70). The time interval associated with the greatest survival benefit was 21 days. Median TTM and OS of dogs with StoC ≤ 21 days were significantly longer than those with StoC >21 days (TTM: 163 vs. 118 days, p = .001; OS: 238 vs. 146 days, p < .001). On multivariable analysis, StoC >21 days was the only variable significantly associated with increased risk of tumour progression (HR 2.1, p = .010) and death (HR 2.3; p = .008). Starting adjuvant chemotherapy within 21 days of surgery may be associated with a survival benefit in dogs with non-metastatic splenic hemangiosarcoma, possibly due to the early targeting of newly recruited metastatic cells after surgery.

Subcutaneous mast cell tumours: A prospective multi-institutional clinicopathological and prognostic study of 43 dogs.

BACKGROUND: Canine subcutaneous mast cell tumours (ScMCTs) reportedly have a good prognosis. However, biomarkers that can be used to predict outcome are currently limited. METHODS: A multicentre prospective study was conducted to identify new prognostic markers. Dogs with a first occurrence of ScMCT were enrolled upon primary tumour removal and regional lymphadenectomy. In the absence of metastasis, dogs were monitored, while dogs with overtly metastatic lymph nodes (histological node 3, HN3) received adjuvant vinblastine. RESULTS: Forty-three dogs were enrolled: 15 (34.9%) had at least one HN3 lymph node and received vinblastine, and 28 (65.1%) were monitored. Three tumours harboured exon 8 and 9 c-kit mutations. Eight (18.6%) dogs experienced tumour progression, and five (11.6%) died of MCT-related causes. The 1- and 2-year survival rates were 90% and 77%, respectively. Variables significantly associated with an increased risk of progression included high cytograde, a mitotic count (MC) greater than 4/10 high-power fields (hpf) and Ki67-index greater than 23. An MC greater than 4/10 hpf was also associated with an increased risk of tumour-related death. LIMITATIONS: Regional rather than sentinel lymphadenectomy was performed in these dogs. Dogs were enrolled in oncology referral centres, constituting a different population compared to previous studies. CONCLUSIONS: ScMCTs have a good prognosis. However, the metastatic rate at admission was higher in this study than previously reported, and a subset of tumours were associated with a fatal outcome despite multimodal treatment. Proliferative activity and cytograding may predict more aggressive behaviour in ScMCTs.

Patterns of nodal metastases, biological behaviour and prognosis of canine mast cell tumours of the pinna: A multi-institutional retrospective study.

Canine cutaneous mast cell tumours (cMCTs) of the pinna have been associated with an aggressive biological behaviour, although data remain scarce. The knowledge acquired over the past years on histologic gradings, and the value of lymph node (LN) staging, may help in better characterizing this anatomical presentation. The first aim was to describe the frequency, location, and histologic appearance of LN metastases in cMCT of the pinna. A second aim was to evaluate prognosis. Medical records of dogs with cMCT of the pinna, that underwent tumour and sentinel (SLN) or regional LN (RLN) excision, were reviewed. The influence of potential prognostic variables on time to progression (TTP) and tumour-specific survival (TSS) was investigated. Thirty-nine dogs were included: 19 (48.7%) had Kiupel high-grade (K-HG) and 20 (51.3%) had low-grade (K-LG) MCTs. Eighteen (46.1%) dogs underwent SLN mapping: the superficial cervical LN was at least one of SLN in 17 (94.4%) cases. Twenty-two (56.4%) dogs had LN metastases; the superficial cervical LN was always involved. On multivariable analysis, only K-HG was associated with increased risk of progression (p = .043) and tumour-related death (p = .021). Median TTP and TSS were 270 and 370 days in K-HG, respectively; these were not reached in dogs with K-LG tumours (p < .01). cMCTs of the pinna are often K-HG and are also associated with a higher frequency of LN metastasis; however, we confirmed the independent prognostic value of histologic grading. A multimodal treatment may lead to favourable long-term outcome. Moreover, the superficial cervical LN is most often the SLN.

Mutations in Exons 8 and 11 of c-kit Gene in Canine Subcutaneous Mast Cell Tumors and Their Association with Cell Proliferation.

The prognostic significance of internal tandem duplication (ITD) mutations in exons 8 and 11 of c-kit has been well-described for canine cutaneous mast cell tumors (MCTs), but c-kit mutations have rarely been reported in subcutaneous MCTs. The objective of this study was to identify the prevalence of ITD mutations in exons 8 and 11 of c-kit in canine subcutaneous MCTs and to investigate its association with histologic grade, KIT pattern, and proliferation markers. ITD mutations in exons 8 and 11 of c-kit, mitotic count, Ki67 index, AgNOR number, Ki67xAgNOR score, KIT pattern, and histologic grade (two-tier system) were retrospectively recorded for 216 dogs with subcutaneous MCTs. ITD mutations in exons 8 and 11 of c-kit were detected in 23 (10.6%) and 12 (5.56%) subcutaneous MCTs, respectively. Exon 11 mutations were significantly associated with Kiupel high grade (p < 0.001) and increased mitotic count (p < 0.001) compared to subcutaneous MCTs with no mutations in exons 8 or 11 (p = 0.002) or subcutaneous MCTs with a mutation in exon 8 (p = 0.001). There was no significant association of either c-kit mutation with KIT patterns or proliferation activity. This study identified a higher prevalence of ITD mutations in exons 8 and 11 of c-kit in subcutaneous MCTs than previously reported. Like their cutaneous counterpart, subcutaneous MCTs with exon 11 mutations were more likely to be histologically high grade and have a higher mitotic count, whereas such associations were not observed in subcutaneous MCTs with exon 8 mutations.