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Several studies evaluating Ki67 in canine cutaneous mast cell tumors (cMCTs) have reported its prognostic value when tumors of all histological grades are included. This study aims to evaluate whether the Ki67 index has a predictive value in a homogeneous cohort of G2/LG cMCTs with HN2 lymph nodes (LNs) and to describe the clinical outcome. The second goal was to explore the correlation between the Ki67 index and MC. The medical databases of three institutions were retrospectively searched for dogs undergoing surgical treatment for cMCT and LN extirpation, with a histological diagnosis of G2/LG with HN2 LNs. Information about histological margins, MC, Ki67 index, local recurrence, nodal relapse, distant metastasis, de novo cMCT occurrence and date and cause of death were included. A total of 39 cases were identified. None of these developed local and nodal relapse or metastatic distant disease. Median MC was 1 (0–2). Median Ki67 index was 3.5 (0.7–14.3). Ki67 and MC were not significantly correlated. At the end of the study, 32 (82%) dogs were alive, 7 (18%) dogs were dead from unrelated causes and 4 (10.2%) dogs were lost to follow-up. The median ST was not reached, and the mean was 893 days (104–2241 days). Considering the strict inclusion criteria, dogs affected by G2/LG with HN2 LNs treated with surgery alone may have a good oncologic outcome; the Ki67 index does not have prognostic impact.

Methylene Blue (MB) is combined with radiopharmaceutical for intraoperative sentinel lymph node (SLN) mapping, but its role during SLN extirpation has not been investigated yet in veterinary medicine. The aim of this study was to assess whether MB increased surgical detection of SLN beyond the use of intraoperative gamma-probe (IGP) alone in clinically node-negative dogs with mast cell tumors (MCTs) following the detection of sentinel lymphocentrums (SLCs) via preoperative planar lymphoscintigraphy. Dogs enrolled underwent MCT excision and SLC exploration guided by both MB and IGP. Data recorded for each SLN were staining (blue/non-blue), radioactivity (hot/non-hot), and histopathological status (HN0-1 vs. HN2-3). A total of 103 dogs bearing 80 cutaneous, 35 subcutaneous, and 1 mucocutaneous MCTs were included; 140 SLCs were explored, for a total of 196 SLNs removed. Associating MB with IGP raised the SLNs detection rate from 90% to 95%. A total of 44% of SLNs were metastatic: 86% were blue/hot, 7% were only blue, 5% were only hot, and 2% were non-blue/non-hot. All HN3 SLNs were hot. Combining MB with IGP can increase the rate of SLN detection in dogs with MCTs; nonetheless, all lymph nodes identified during dissection should be removed, as they might be unstained but metastatic.

In canine cutaneous mast cell tumours (cMCTs), histologic grade and clinical stage are the most important prognostic factors, with high-grade tumours and metastatic lymph nodes (LNs) significantly influencing the evolution of disease. However, it is uncertain whether histologic grade and clinical stage should be given equal weighting value in patient prognostication and management. Dogs with low- and high-grade cMCTs and at least one overtly metastatic sentinel LN undergoing standardized treatment, consisting of surgical excision of the cMCT, lymphadenectomy and chemotherapy, were retrospectively included. The aim was to determine whether, at the same clinical stage, histologic grade retained prognostic relevance. Sixty dogs were included: 26 had a high-grade cMCT tumour and 34 had a low-grade cMCT. Median follow-up was 367 days (range, 187-748) in the high-grade group, and 1208 days (range, 180-2576) in the low-grade group. Median time to progression was significantly shorter in the high-grade group than in the low-grade group (214 days versus not reached; p .001), as well as tumour-specific survival (545 days versus not reached; p .001). On multivariable analysis, a high histologic grade and incomplete margins retained prognostic significance for both tumour progression and tumour-specific death. In dogs with cMCT and at least one overtly metastatic LN undergoing multimodal treatment, histologic grade significantly correlated with outcome. Overall prognosis was not unfavourable, even in the high-grade group, further supporting that a multimodal therapeutic approach, addressing primary tumour and sentinel LN, should be offered. Whether chemotherapy should be incorporated in the therapeutic planning of low-grade cMCTs remains to be defined.

Sentinel lymph node biopsy (SLNB) is an accepted veterinary surgical procedure given the impact of early detection of nodal metastases on staging of several canine malignancies. This study aims at reporting the incidence and risk factors for surgical complications of SLNB in tumour-bearing dogs. A total of 113 client-owned dogs that underwent tumour excision and SLNB guided by γ-probing and blue dye were retrospectively enrolled. Recorded variables included: signalment, location and number of extirpated lymphocenters and nodes, time for SLNB, histopathological status of excised nodes. Incidence of SLNB complications was calculated. They were classified as minor and major based on severity and required treatment, and as short-term (0-30 days) and long-term (31-90 days). Univariate analysis with generalized linear model with binomial error estimated the association between variables and incidence of SLNB complications. Significance was set at 5%. Median overall time for SLNB was 25 min. Surgeons excised one node in 38% of dogs and multiple nodes in 62% of cases, belonging to one (62%) or multiple (38%) lymphocenters. Metastases were detected in 45% of nodes. No intraoperative complications occurred. The overall incidence of postoperative complications of SLNB was 21,24%, the majority of which (91.67%) were minor. Only increasing dogs' weight was associated with an increased incidence of SLNB complications (p = .00976). Sentinel lymphadenectomy was associated with a relatively low incidence of complications, most of which were self-limiting. The low morbidity and previously reported impact on staging of SLNB justify its implementation to collect data for prognostic studies.

Canine mammary tumours represent a hard-prognostic task for veterinary clinicians. TNM staging and grading systems refer to a single tumour. Significant limits come to light when these systems are applied to multiple mammary tumours due to the arbitrary criterion in determining which single tumour is representative of the patient's prognosis. This study explored some clinical features of 50 dogs affected by at least one malignant mammary tumour. Clinical features and staging, together with histological classification and grading, have been related to disease-free survival (DFS) with the purpose to evaluate their impact on prognosis. The prognosis was worse in 10-11-year-old dogs (P 0.05), in dogs affected by complex carcinoma (P 0.05), and in patients assigned to Peña grade I (P 0.05). The bodyweight was not linearly related to DFS (P 0.01), and patients with a low number of neoformations (n ≤ 2) showed a better prognosis than dogs with 3-5 tumours (P 0.05). Both the average and the total size of malignant tumours were related to DFS (P 0.05). Dogs assigned with stage I had the best DFS (P 0.05). In conclusion, the Peña grade I alone would not seem to guarantee a favourable prognosis when applied to mammary tumours in dogs affected by multiple simultaneous presentations. Different characteristics, besides tumour grading, such as tumour immunophenotype and expression of hormonal receptors, could in the future, contribute to elucidate the clinical behaviour of multiple canine mammary tumours.

OBJECTIVE: To report the outcomes associated with sentinel lymph nodes (SLN) detection and extirpation guided by radionuclide and methylene blue injections in dogs with cutaneous and subcutaneous mast cell tumors (MCT). STUDY DESIGN: Clinical prospective cohort study. ANIMALS: Thirty client‐owned dogs with MCT amenable to wide‐margin excision, without evidence of distant metastasis and abnormal regional lymph nodes (RLN). METHODS: Technetium‐99 m and methylene blue were injected peritumorally. Dogs underwent preoperative γ‐camera scintigraphy and an intraoperative γ‐probe‐guided SLN extirpation. Outcomes included technical and surgical complications, number of SLN, SLN location respecting the expected RLN, and histopathology results. RESULTS: Sentinel lymph node mapping was applied to 34 MCT in 30 dogs without any complication. Sentinel lymph nodes were not identified in three of 34 tumors, all with previous scar tissue. Sentinel lymph nodes did not correspond to expected RLN in 19 of 30 (63%) tumors. Histological examination confirmed an early or overt metastasis in 32 of 57 (56%) SLN extirpated. CONCLUSION: Sentinel lymph node mapping and biopsy with radionuclide and injection of methylene blue was associated with low morbidity and allowed detection of SLN in dogs with MCT at first presentation without scar tissue. CLINICAL SIGNIFICANCE: Incorporation of SLN mapping and extirpation allows for a personalized staging approach in dogs with MCT. The presence of scar tissue in dogs with recurrent tumors seems to be a limitation for SLN mapping with this technique.

OBJECTIVE To determine an optimal time interval between amputation and initiation of adjuvant chemotherapy (TIamp-chemo) in dogs with appendicular osteosarcoma without distant metastases and whether TIamp-chemo was associated with outcome. ANIMALS 168 client-owned dogs treated at 9 veterinary oncology centers. PROCEDURES Data were collected from the dogs’ medical records concerning potential prognostic variables and outcomes. Dogs were grouped as to whether they received chemotherapy within 3, 5, 7, 10, 15, 20, 30, or > 30 days after amputation of the affected limb. Analyses were performed to identify variables associated with time to tumor progression and survival time after limb amputation and to determine an optimal TIamp-chemo. RESULTS Median TIamp-chemo was 14 days (range, 1 to 210 days). Median time to tumor progression for dogs with a TIamp-chemo ≤ 5 days (375 days; 95% CI, 162 to 588 days) was significantly longer than that for dogs with a TIamp-chemo > 5 days (202 days; 95% CI, 146 to 257 days). Median overall survival time for dogs with a TIamp-chemo ≤ 5 days (445 days; 95% CI, 345 to 545 days) was significantly longer than that for dogs with a TIamp-chemo > 5 days (239 days; 95% CI, 186 to 291 days). CONCLUSIONS AND CLINICAL RELEVANCE Findings indicated that early (within 5 days) initiation of adjuvant chemotherapy after limb amputation was associated with a significant and clinically relevant survival benefit for dogs with appendicular osteosarcoma without distant metastases. These results suggested that the timing of chemotherapy may be an important prognostic variable.

The recent literature supports the sentinel lymph node (SLN) biopsy in dogs with MCT due to discrepancy with the regional lymph node and the high percentage of occult metastasis. However, the SLN biopsy includes additional anesthesiologic, diagnostic, and surgical procedures, and additional costs. The study aimed to assess the association between clinicopathological variables and SLN status, determining the identification of dogs at lower risk of SLN metastases. Dogs with integumentary MCT were admitted to the lymphoscintigraphic mapping and subsequent biopsy of SLN. The association between clinicopathological variables of MCT and SLN status was statistically tested, both considering occult and overt metastasis together (HN2-HN3) and overt metastasis (HN3) alone. Fifty low-grade cutaneous MCT and 16 subcutaneous MCT were included. A small to moderate association between integumentary MCT ≥ 3 cm and HN2-HN3 SLN was found. A strong association of integumentary MCT dimension and subcutaneous MCT with HN3 SLN occurred. Dimension of low-grade cutaneous and subcutaneous MCT seems to correlate with SLN status, but additional study should confirm this data before excluding small MCT to the SLN biopsy. On the contrary, the study results induce a solid suggestion for mapping and biopsy of the SLN in MCT &gt, 3 cm and subcutaneous MCT.

Treatment options for dogs with metastatic (stage III) splenic hemangiosarcoma are limited. A doxorubicin-based chemotherapy regimen is commonly administered; however, there are no published data to support this practice. The aim of this study was to investigate the impact of maximum-tolerated-dose chemotherapy (MTD), metronomic chemotherapy (MC) and no adjuvant treatment on outcome in dogs with stage III splenic hemangiosarcoma undergoing splenectomy. Medical records of dogs with stage III splenic hemangiosarcoma that underwent splenectomy followed by MTD chemotherapy, MC or no adjuvant treatment were retrieved. Time to progression (TTP), survival time (ST) and toxicity were evaluated. One hundred three dogs were identified: 23 received adjuvant MTD, 38 MC and 42 were not medically treated. Overall median TTP and ST were 50 (95% confidence interval [CI], 39-61) and 55 days (95% CI, 43-66), respectively. Dogs treated with adjuvant MTD had a significantly longer TTP and ST compared with dogs receiving MC (median TTP, 134 vs 52 days, P = .025; median ST, 140 vs 58 days, P = .023, respectively). Dogs treated by splenectomy only had the shortest median TTP (28 days) and ST (40 days). However, treatment-related adverse events (AEs) were significantly more frequent in the MTD group (P = .017). The outcome for dogs with metastatic splenic hemangiosarcoma is poor. While MTD showed greater efficacy compared to MC, toxicity was higher in this group. Treatment-related AEs need to be carefully balanced against this modest survival prolongation when offering adjuvant MTD to dogs with advanced stage hemangiosarcoma.

Most dogs with large B-cell lymphoma (LBCL) that undergo chemotherapy and achieve clinical complete remission (CR) eventually relapse. However, time to relapse (TTR) is unpredictable. The aims of this prospective study were to assess the influence of post-chemotherapy lymph node (LN) infiltration by large CD21+ cells using flow cytometry (FC) on TTR, and to establish a cut-off value of prognostic significance. Dogs with newly-diagnosed, completely staged LBCL in CR after treatment were enrolled. Minimal residual disease (MRD) analysis by FC was performed on LN aspirates. TTR was calculated between MRD and relapse. Thirty-one dogs were enrolled: 4% had stage V disease, and diffuse large B-cell lymphoma was the most common histotype (74%). Based on LN infiltration at MRD evaluation, three groups were created: (a) acellular samples, (b) 0.5% infiltration. Overall median TTR was 154 days (range, 31-1974): 22 (71%) dogs relapsed during the study period, whereas 9 (29%) dogs did not. The difference among the three groups was significant (P = 0.042 log-rank test): median TTR was not reached for dogs with LN infiltration 0.5%. These results demonstrate that MRD assessment by FC on LN aspirates in dogs with LBCL in clinical CR predicts TTR. LN infiltration by >0.5% large CD21+ cells after treatment is an unfavourable prognostic factor.

Tumour stage is a prognostic indicator for canine malignant head and neck tumours (MHNT). However, consensus is lacking on nodal staging in the absence of clinically apparent nodal disease (cN0 neck). This prospective observational study aims to determine the diagnostic accuracy of radiopharmaceutical and blue dye for sentinel lymph node biopsy (SLNB), to assess the correspondence between sentinel lymph node (SLN) and clinically expected regional lymph node (RLN) and the impact on staging of the procedure in dogs with MHNT and cN0 neck. Twenty-three dogs with MHNT and cN0 neck underwent tumour excision and SLNB guided by preoperative lymphoscintigraphy and intraoperative gamma-probe and blue dye. Diagnostic performances and detection rate were calculated. Correspondence between SLN and RLN, number of nodes excised, histopathological status of the SLN and complications related to the procedure were recorded. The mapping technique identified at least one SLN in 19/23 dogs, with a detection rate of 83%. The SLN did not correspond to the RLN in 52% of dogs. Multiple nodes were removed in 61% of dogs. At histopathology, eight (42%) dogs had SLN+, of which four differed from the RLN. Only minor self-limiting complications occurred in five (22%) dogs. Radiopharmaceutical and blue dye guidance is accurate (sensitivity 88.9%; specificity 100%) for SLNB in dogs with MHNT and cN0 and allowed the extirpation of unpredictable and/or multiple SLN with minimal morbidity. Incorporation of SLNB in the management of MHNT is desirable to correctly stage the cN0 neck, owing the unpredictability of the lymphatic drainage.

Sentinel lymph node (SLN) mapping is the current gold standard for the oncological staging of solid malignancies in humans. This prospective observational study describes the feasibility and the limits of preoperative lymphoscintigraphy for SLN detection in dogs with spontaneous malignancies and the improvements in staging accuracy. Client‐owned dogs with confirmed malignant neoplasia and absence of distant metastasis were prospectively enrolled. Lymphoscintigraphy was performed after the peritumoral injection of Technetium‐99m labeled nanocolloids. Regional dynamic and static images were acquired, with and without masking of the injection site with a lead shield. The dogs were then subjected to surgery for tumor excision and SLN extirpation. Intraoperative SLN detection was performed by combining methylene blue dye and a dedicated gamma probe. Overall, 51 dogs with a total of 60 solid malignant tumors were enrolled. Lymphoscintigraphy identified at least one SLN in 57 of 60 cases (95%). The SLN did not always correspond to the regional lymph node (35/57, 61.4%). The use of a lead shield, masking the injection site, markedly improved the SLN visibility. The median time of SLN appearance was 11.4 ± 9.3 min. No side effects were observed. Preoperative lymphoscintigraphy allows for SLN detection in dogs and can improve staging accuracy by either identifying the SLN in a different lymphosome than clinically expected or discriminating the draining node in uncertain cases. The combined use of preoperative and intraoperative techniques is recommended to increase the SLN detection rate.

Identification of prognostic factors for perivascular wall tumours (PWTs) is desirable to accurately predict prognosis and guide treatment. 100 and two dogs with surgically excised PWTs without distant metastasis were retrospectively enrolled in this multi-institutional study, and the impact of pre-treatment leukocyte parameters, clinical and histopathological variables on local recurrence (LR) and overall-survival time (OST) were evaluated. Increasing values of white blood cell count (WBCC), neutrophil count (NC) and neutrophil-to-lymphocyte ratio (NLR) were significantly correlated with the hazard of LR in univariate analysis. WBCC and NC remained prognostic when adjusted for margins, grade, tumour size, location and skin ulceration, but lost their significance when adjusted for mitotic index and necrosis, whilst NLR remained prognostic only when close margins where categorised as infiltrated. Castrated males had a higher hazard of LR than intact males in univariate analysis, but significance was lost in multivariate models. Ulcerated PWTs and those located on the distal extremities had a higher hazard of LR both in univariate and multivariate analysis. Histological grade, necrosis, mitotic count, and infiltrated margins were all associated with LR both in univariate and multivariate analysis. Boxer breed, older age, ulceration, grade III, necrosis >50% and higher mitotic count were correlated with shorter OST, although breed and age lost their significance in multivariate analysis. Prognostication of surgically excised PWTs should be based on both clinical and histopathological variables. If validated in further studies, leukocyte counts and NLR may aid the clinician in identifying dogs at higher risk of LR before treatment.

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.

Studies regarding the neoplastic infiltration of the skin overlying canine subcutaneous soft tissue sarcoma (sSTS) are lacking. In case of the absence of tumor infiltration, there would be the possibility of leaving this unaffected skin in place, thus simplifying surgery. The aim of the study was to investigate whether the skin overlying sSTSs is infiltrated by neoplastic cells. Dogs with sSTSs treated surgically were prospectively enrolled. After excision, the skin was dissected from the tumor along the natural surgical plane of cleavage and histologically evaluated. Twenty-nine dogs with an sSTS were included (22 grade I, 6 grade II, and 1 grade III). The sSTS-overlying skin was not tumor-infiltrated in 14/29 cases (48.3%). A higher frequency of infiltration was observed in higher grade sSTSs (grades II and III, 100%; P = .006); nevertheless, 8/22 grade I sSTSs (36%) also showed cutaneous infiltration. This infiltration involved the dermis of the skin directly in contact with the tumor (multifocal in 11 and diffuse in four cases). Although the cutaneous tumor infiltration is less frequent in grade I sSTSs and a wide excision may still be the safest treatment for any sSTS for a greater possibility of local control, this study opens the possibility to a less aggressive cutaneous excision, but still with a local curative intent, as only the skin directly in contact with the sSTS has been proven to be tumor-infiltrated. Additional studies are warranted to confirm that excision of only this skin may guarantee a complete local control, especially in lower-grade sSTSs.

Nano- and microsized extracellular vesicles (EVs) are naturally occurring cargo-bearing packages of regulatory macromolecules, and recent studies are increasingly showing that EVs are responsible for physiological intercellular communication. Nanoparticles encapsulating anti-tumor theranostics represent an attractive "exosome-interfering" strategy for cancer therapy. Methods: Herein, by labeling plasma-derived EVs with indocyanine green (ICG) and following their biodistribution by in vivo and ex vivo imaging, we demonstrate the existence of nanoparticles with a highly selective cancer tropism in the blood of colorectal cancer (CRC) patients but not in that of healthy volunteers. Results: In CRC patient-derived xenograft (PDX) mouse models, we show that transplanted EVs recognize tumors from the cognate nanoparticle-generating individual, suggesting the theranostic potential of autologous EVs encapsulating tumor-interfering molecules. In large canine breeds bearing spontaneous malignant skin and breast tumors, the same autologous EV transplantation protocol shows comparable safety and efficacy profiles. Conclusions: Our data show the existence of an untapped resource of intercellular communication present in the blood of cancer patients, which represents an efficient and highly biocompatible way to deliver molecules directly to the tumor with great precision. The novel EV-interfering approach proposed by our study may become a new research direction in the complex interplay of modern personalized cancer therapy.

Cutaneous mast cell tumours (MCTs) are common skin neoplasms in dogs. MicroRNAs (miRNAs) are post-transcriptional regulators involved in several cellular processes, and they can function as tumour promoters or suppressors. However, the role of miRNAs in canine MCTs has not yet been elucidated. Thus, the current study aimed to characterize miRNA profiles and to assess their value as biomarkers for MCTs. miRNA expression profiles were assessed in formalin-fixed, paraffin-embedded samples by next-generation sequencing. Ten samples were MCT tissues, and 7 were healthy adjacent tissues. Nine dysregulated miRNAs (DE-miRNAs) were then validated using RT-qPCR in a larger group of MCT samples, allowing the calculation of ROC curves and performance of multiple factor analysis (MFA). Pathway enrichment analysis was performed to investigate miRNA biological functions. The results showed that the expression of 63 miRNAs (18 up- and 45 downregulated) was significantly affected in MCTs. Five DE-miRNAs, namely, miR-21-5p, miR-92a-3p, miR-338, miR-379 and miR-885, were validated by RT-qPCR. The diagnostic accuracy of a panel of 3 DE-miRNAs—miR-21, miR-379 and miR-885—exhibited increased efficiency in discriminating animals with MCTs (AUC = 0.9854) and animals with lymph node metastasis (AUC = 0.8923). Multiple factor analysis revealed clusters based on nodal metastasis. Gene Ontology and KEGG analyses confirmed that the DE-miRNAs were involved in cell proliferation, survival and metastasis pathways. In conclusion, the present study demonstrated that the miRNA expression profile is changed in the MCT microenvironment, suggesting the involvement of the altered miRNAs in the epigenetic regulation of MCTs and identifying miR-21, miR-379 and miR-885 as promising biomarkers.

Lymph node (LN) metastasis is a negative prognostic factor in dogs with cutaneous mast cell tumours (cMCTs). While elective lymphadenectomy of metastatic LNs improves outcome, the benefit of adjuvant medical therapy in dogs with early metastatic (HN2) LNs is debated. The aim of this retrospective multicentre study was to evaluate the therapeutic benefit of adjuvant medical therapy following surgical removal of the primary low-grade cMCT (Patnaik grade 1-2 and Kiupel low-grade) and lymphadenectomy of HN2 LNs by analysing survival rates and patterns of recurrence. Seventy-three dogs were included: 42 received adjuvant medical treatment (chemotherapy and/or kinase inhibitors), and 31 did not. The median follow-up time for medically treated dogs was 619 days: two experienced local recurrence, three nodal relapse and four distant relapse. For dogs undergoing surgery only, the median follow-up time was 545 days. None of them experienced local recurrence, nodal, or distant relapse. Time to progression was significantly shorter in dogs receiving adjuvant medical treatment (P = .021). A similar tendency was observed for overall survival (P = .056). The current study shows that dogs with low-grade cMCTs, that undergo surgical excision of the primary tumour and elective lymphadenectomy of the HN2 regional LN harbour a good prognosis. The use of adjuvant medical treatment in these dogs does not seem to provide any benefit in terms of progression and survival.

Subcutaneous spindle cell tumours characterized by whorling growth patterns are common in dogs and are identified as a distinct entity. These tumours were misnamed as hemangiopericytomas (HPCs) because of some minor morphological parallels with their human counterparts. In veterinary medicine, the cell of origin of HPC has been under debate for a long time. Some authors have suggested a perivascular origin while others a perineural one. The evidence of the orientation of the neoplastic cells around the vessels and the expression of contractile proteins supported a perivascular origin while S100 expression and an inconsistent vascular connection supported a perineural origin. Despite the morphological similarities with peripheral nerve sheath tumours in humans, the perineural origin was supported mainly by the expression of markers with low specificity. On the contrary, the majority of studies have supported the perivascular origin of 'old' canine HPC. Since a variable degree of myoid-pericytic differentiation was described, the term perivascular wall tumours (PWTs) were suggested to substitute HPC. Once the diagnostic criteria of PWTs were defined, the clinical behaviour and prognostic variables were investigated, demonstrating differences as compared with the group of canine soft tissue sarcomas (STSs) in general. PWTs are less aggressive, mostly locally invasive, and rarely metastasizing. Their behaviour seems to be less influenced by histological grade, suggesting that canine STSs are heterogeneous. The study of the biological behaviour of specific STS tumour types may be valuable in detecting differences which have passed unnoticed when STSs have been studied concomitantly.

Feline large granular lymphocyte (LGL) lymphoma is an uncommon subtype of lymphoma characterized by a grave prognosis and scarce response to chemotherapy. There are limited reports on clinico-pathological and prognostic factors. One-hundred and 9 cats with newly diagnosed LGL lymphoma that underwent initial staging (including hematology, serum biochemistry, thoracic radiographs and abdominal ultrasound), and followed-up were retrospectively evaluated. LGL lymphoma was localized within the gastrointestinal tract with or without extra-intestinal involvement in 91.7% of the cases, and at extra-gastrointestinal sites in 8.3%. Symptoms were frequent. Anemia (31.2%) and neutrophilia (26.6%) were commonly observed, and 14 (12.8%) cats had neoplastic circulating cells. Frequent biochemistry abnormalities included elevated ALT (39.4%) and hypoalbuminemia (28.4%). Twenty (54.1%) of 37 cats had elevated serum LDH. Treatment varied among cats, and included surgery (11%), chemotherapy (23%), corticosteroids (38.5%) and no treatment (27.5%). Median time to progression (MTTP) was 5 days, and median survival time (MST) 21 days. MST was significantly shorter in the case of substage b, circulating neoplastic cells, lack of chemotherapy administration, and lack of treatment response. A small subset of cats (7.3%) survived more than 6 months, suggesting that a more favorable clinical course can be found among LGL lymphoma patients.

Testicular seminoma is reported in the rabbit but data about the immunophenotype of these tumours are lacking. The classification of human testicular germ cell tumours includes spermatocytic tumour (ST) originating from the post-pubertal spermatogonia/spermatocytes, which metastasizes rarely, and seminoma (SE), originating from gonocytes, which is malignant and metastasizes frequently. Gonocytes express placental alkaline phosphatase (PLAP) and are stained with periodic acid-Schiff (PAS). We report five cases of seminoma in pet rabbits. Microscopically, all the cases were diffuse seminoma and in one case there was metastasis to a sublumbar lymph node. Immunohistochemical expression of PLAP was diffuse in this metastatic tumour, in two other cases it was multifocal, in another it was limited to rare cells and in the remaining case was negative. PAS-positive cells were detected only in the four cases that expressed PLAP. These four cases were therefore classified as SE and the tumour without PLAP labelling or PAS staining was defined as ST. Both forms of human germ cell tumour therefore occur in the rabbit. SE appears to be well represented and may show metastasis, paralleling the human counterpart. The results of this study provide a basis for further evaluations of the rabbit as a possible animal model for the study of human SE.

Local recurrence (LR) is the major concern in the treatment of feline injection-site sarcoma (FISS). Pretreatment leukocyte counts and ratios have been reported as diagnostic and/or prognostic markers in human and canine oncology. The aim of this retrospective study was to explore the prognostic impact on LR and overall survival time (OST) of pretreatment neutrophil-to-lymphocyte ratio (NLR), white blood cell count (WBCC), neutrophil count (NC) and lymphocyte count (LC) in cats with surgically excised FISS. Eighty-two cats with histologically confirmed FISS at first presentation, without distant metastases, and with available pretreatment haematological analyses were retrospectively enrolled. The correlation of NLR, WBCC, NC, LC with tumour variables and patient variables was explored. NLR was correlated with tumour size (P = .004), histological pattern of tumour growth (P = .024) and histotype (P = .029), while WBCC and NC were associated with ulceration (P = .007, P = .011) and pattern of growth (P = .028, P = .004). No significant relationships emerged between LC and any of the considered variables. The impact of NLR, WBCC, NC, LC on LR and OST was then estimated in univariate and multivariate analysis. In univariate analysis, NLR, WBCC and NC were significant prognostic factors for both LR and OST. NLR, WBCC and NC remained prognostic in multivariate analysis for LR but not for OST. When NLR, WBCC and NC were jointly analysed, WBCC was the marker with the greater impact on LR. Preoperative NLR, WBCC and NC may aid in identifying cats at higher risk of LR.

Background To describe the efficacy of four-layer porcine small intestinal submucosa (Vetrix BioSIS plus+) as single scaffold for the treatment of deep corneal lesions in dogs and cats. Methods 10 dogs and 3 cats with deep or full thickness corneal defects were treated surgically with BioSIS plus graft. Corneal transparency scores and vision were evaluated. Results Lesions in dogs were four perforations, three descemetoceles, two limbal melanocytomas and one deep corneal ulcer. In cats, there were one limbal melanocytoma and two perforations. The average length of the follow-up was 86 days. In all, 12 out of 13 eyes treated were visual at last recheck (92.3 per cent). The scars were mild eight cases (66.7 per cent), but denser in four cases (33.4 per cent). Complication were partial collagenolysis in three cases (25 per cent), which resolved with medical therapy, mild corneal pigmentation in one case (8.4 per cent) and anterior synechia in one case (8.4 per cent). One case experienced severe collagenolysis and was enucleated 21 days postoperatively. Conclusions Four-layer porcine SIS graft was successfully used for surgical treatment of deep corneal lesions in selected corneal diseases in a small series of dogs and cats, with good results in terms of mechanic support and corneal transparency.

Dogs with Diffuse Large B-Cell Lymphoma (DLBCL) benefit from the addition of active immunotherapy to traditional chemotherapy. We hypothesized that immune cells within neoplastic lymph nodes (LNs) may play a role in the tumor pathobiology and treatment response. The present study describes the composition and prognostic role of non-neoplastic lymphocytes in LNs of 59 dogs with treatment-naive DLBCL receiving chemo-immunotherapy. The percentage of small non-neoplastic cells and of CD5+, CD21+, CD4+ and CD8+ small cells was recorded via flow cytometry. CD4+/CD8+ and CD5+/large CD21+ cell ratios were calculated. The likelihood of progression significantly diminished with increasing percentage of small cells, CD5+ and CD8+ small cells, and CD5+/large CD21+ cell ratio, with decreasing CD4+/CD8+ ratio and in non-anemic dogs. Active immunotherapy is more effective in dogs with higher percentage of non-neoplastic lymphocytes at diagnosis. We lay the ground for future studies assessing the role of the immune system in the pathobiology of canine DLBCL.

It is widely accepted that psychological stress and mental illness can compromise the function of the immune system. Clinical and epidemiological studies on humans recognized that specific psychosocial factors, such as stress, chronic depression and lack of social support are risk factors for the development and progression of cancer. Unfortunately, most of the animals studies on this subject are based on laboratory tests performed on mice. This retrospective cohort study aims to analyze the relation between stress and tumor in pet dogs, by evaluating and comparing the stress level in two groups of 69 dogs each, balanced for sex and age: the oncologic group consists of dogs diagnosed with cancer and the control group consists of healthy dogs. Our results show that, before the cancer diagnosis, more dogs in the oncologic group faced changes in their household and routine as opposed to the control group (p

Diagnostic methods used in the initial and post-treatment evaluation of canine lymphoma are heterogeneous and can vary within countries and institutions. Accurate reporting of clinical stage and response assessment is crucial in determining the treatment efficacy and predicting prognosis. This study comprises a systematic review of all available canine multicentric lymphoma studies published over 15 years. Data concerning diagnosis, clinical stage evaluation and response assessment procedures were extracted and compared. Sixty-three studies met the eligibility criteria. Fifty-five (87.3%) studies were non-randomized prospective or retrospective studies. The survey results also expose variations in diagnostic criteria and treatment response assessment in canine multicentric lymphoma. Variations in staging procedures performed and recorded led to an unquantifiable heterogeneity among patients in and between studies, making it difficult to compare treatment efficacies. Awareness of this inconsistency of procedure and reporting may help in the design of future clinical trials.