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A 12‐year‐old male domestic cat with multiple subcutaneous mast cell tumours (MCTs) presented with a 2‐week history of pruritus and raw/bleeding skin from self‐trauma at Kagoshima University Veterinary Teaching Hospital. Polymerase chain reaction (PCR) and histopathological analyses revealed intertumoral heterogeneity among tumour locations based on the mutation status of KIT. In addition, the expression pattern of KIT was characterized. After failed treatment with vinblastine (2.0–2.2 mg/m2, intravenous administration, two doses in total) or nimustine (25 mg/m2, intravenous administration, two doses in total), toceranib (2.2–2.6 mg/kg, orally administered, every other day) was administered to treat recurrent MCTs harbouring the KIT exon eight internal tandem duplication mutation, achieving a complete response. However, toceranib resistance developed 2 months after treatment initiation. Subsequent PCR analysis was conducted to identify the mutational status of KIT in each MCT and to detect the presence of secondary mutations associated with the acquisition of toceranib resistance. Secondary KIT mutations (c.998G>C and c.2383G>C), which were not initially detected in tumour cells at diagnosis, were identified after the development of resistance to toceranib. This indicates that the tumour cells in feline MCTs in the same case have diverse characteristics. Our findings encourage further investigation into the development of therapeutic strategies for feline MCTs, particularly focusing on the heterogeneous nature of KIT/KIT and overcoming acquired resistance to toceranib. [ABSTRACT FROM AUTHOR]

Abstract A 12‐year‐old male domestic cat with multiple subcutaneous mast cell tumours (MCTs) presented with a 2‐week history of pruritus and raw/bleeding skin from self‐trauma at Kagoshima University Veterinary Teaching Hospital. Polymerase chain reaction (PCR) and histopathological analyses revealed intertumoral heterogeneity among tumour locations based on the mutation status of KIT. In addition, the expression pattern of KIT was characterized. After failed treatment with vinblastine (2.0–2.2 mg/m2, intravenous administration, two doses in total) or nimustine (25 mg/m2, intravenous administration, two doses in total), toceranib (2.2–2.6 mg/kg, orally administered, every other day) was administered to treat recurrent MCTs harbouring the KIT exon eight internal tandem duplication mutation, achieving a complete response. However, toceranib resistance developed 2 months after treatment initiation. Subsequent PCR analysis was conducted to identify the mutational status of KIT in each MCT and to detect the presence of secondary mutations associated with the acquisition of toceranib resistance. Secondary KIT mutations (c.998G>C and c.2383G>C), which were not initially detected in tumour cells at diagnosis, were identified after the development of resistance to toceranib. This indicates that the tumour cells in feline MCTs in the same case have diverse characteristics. Our findings encourage further investigation into the development of therapeutic strategies for feline MCTs, particularly focusing on the heterogeneous nature of KIT/KIT and overcoming acquired resistance to toceranib.

Medical records from a single referral hospital (Davies Veterinary Specialists, Hitchin, UK) were reviewed to identify dogs (n = 8) with preputial cutaneous mast cell tumours (CMCT) that underwent surgical excision and primary preputial reconstruction, preserving the penis and urethra, after clients declined alternatives such as penile amputation and urethrostomy, from June 2017–June 2022. Tumours had a median diameter of 21.5 (min 15, max 30) mm, were located cranioventrally (3/8), caudoventrally (1/8), laterally (2/8) and dorsally (2/8) relative to the prepuce and were diagnosed as CMCT based on cytology. No dogs had hepatic or splenic metastasis on cytology but inguinal lymph node metastasis was identified in 3/4 dogs sampled. The owners of all dogs had declined penile amputation and scrotal urethrostomy. The CMCT were excised and primary reconstruction of the prepuce performed. Surgical lateral margins of 10, 20 or 30 mm were used and the deep margin excised the inner preputial lamina or underlying muscular fascia. The deep margin for caudoventral CMCT involved excision of the underlying SC adipose tissue. Preputial advancement was performed in 3/8 dogs to achieve adequate penile coverage. Histopathology confirmed all CMCT were Kiupel low grade, Patnaik grade II with complete margins in 6/8 dogs but identified metastasis only in one inguinal lymph node from one dog. Two dogs encountered minor complications (infection and a minor dehiscence) and one dog had a major complication (infection with major dehiscence). Median follow-up duration was 125 weeks, excluding one dog with 4 weeks of follow-up. None of the dogs experienced local recurrence or died of mast cell disease during the available follow-up period. This clinical study evaluated a surgical alternative to penile amputation and advanced reconstructive techniques for Kuipel low/Patnaik grade II preputial CMCT when these procedures were declined by owners. Surgical excision of preputial CMCT with lateral margins of 10, 20 or 30 mm with primary preputial reconstruction is achievable with low morbidity and a good outcome when penile amputation and scrotal urethrostomy is not an option. [ABSTRACT FROM AUTHOR]

Early diagnosis of nodal metastasis has been shown to impact prognosis for dogs with mast cell tumours (MCT). The objective of this retrospective study was to determine the correlation between computed tomographic characteristics of lymph nodes and histologic nodal metastasis using the HN classification system, in dogs with cutaneous or subcutaneous MCT and regional lymph node(s) removal. Dogs that had removal of MCT and regional lymphadenectomy within 31 days of the initial staging computed tomography (CT) were enrolled. Subjective lymph node characteristics used included margination, loss of fat at hilus, shape of margin, perinodal fat pattern, increase in number of nodes, and pre‐ and post‐contrast heterogeneity. Enhancement, heterogeneity, and short‐long axis ratio were calculated. Seventy‐one lymph nodes from 37 dogs were included. Generalised linear mixed model of assessment of lymph node was performed twice, with binary outcome [non‐metastatic (HN0/1) versus metastatic (HN2/3)] and 4‐point scales (HN0–HN3). After blind assessment of 7 characteristics described above, a final subjective interpretation of each lymph node as non‐metastatic or metastatic was assigned. A significant correlation was found between final interpretation and prediction of metastasis. Higher HN classification was also significantly correlated with the increased number of nodes and pre‐ and post‐contrast heterogeneity. No correlation was found in short‐long axis ratio, calculated heterogeneity, or degree of enhancement. Sensitivity of CT was 35.7%, specificity was 96.6%, and accuracy was 60.5% for nodal metastasis. CT alone cannot be recommended for assessment of metastasis. The use of multiple computed tomographic characteristics may increase accuracy of nodal metastasis detection. [ABSTRACT FROM AUTHOR]

An 11‐year‐old, female‐neutered beagle was presented with a growing soft tissue mass arising within the deep tissues of the left cranial cervical region. At presentation, facial asymmetry was evident along with palpable lymphadenomegaly. Magnetic resonance imaging demonstrated a locally invasive cervical mass with intracranial invasion through focal osteolysis of the occipital bone. After antihistamine administration, cytology confirmed mast cell tumour (MCT) with metastasis to local lymph nodes and liver. The owner chose to pursue lomustine and prednisolone, which were dispensed, but, before home administration, prolonged seizures/status epilepticus occurred prompting euthanasia. Postmortem examination confirmed a high‐grade MCT associated with, and infiltrating through, muscle, calvarium, dura mata, leptomeninges and the underlying brain. We present the clinical, imaging, and pathological findings of an unprecedented case of extracranial MCT tumour causing osteolysis of an imperforate flat bone (occipital bone) and intracranial invasion. [ABSTRACT FROM AUTHOR]

Mast cell tumours (MCTs) arise in the dermis and subcutaneous tissues in animals and humans and are one of the most common neoplasms of the skin in dogs. Cannabinoid type 2 receptor (CB2R), cyclin-dependent kinase inhibitor (p21) and matrix metalloproteinase 1 (MMP-1) are potential targets for novel anti-tumour therapeutic strategies. This study evaluated by immunohistochemical means the reactivity of p21, MMP-1 and CB2R proteins in association with a three-tier grading system in cutaneous canine MCTs.

Simple Summary: This study focused on identifying and evaluating the use of selected potential biomarkers in predicting the treatment response of mast cell tumours (MCT) in dogs using a combination of electrochemotherapy (ECT) and interleukin 12 gene electrotransfer (IL-12 GET). In the study of 48 patients with 86 MCTs, blood samples were taken before, one month and six months after treatment to identify reliable biomarkers that predict response to treatment. An increased plasma nucleosome concentration and increased serum lactate dehydrogenase (LDH) activity one month after treatment correlated with a more effective local response, such as necrosis and swelling. These biomarkers proved to be potential early indicators of treatment success. However, the serum ferritin concentration did not prove to be meaningful. The results of this study provide crucial insights into the use of the plasma nucleosome concentration and serum LDH activity as potential indicators of treatment efficacy in veterinary oncology. Ultimately, this study emphasises the need to identify and validate predictive biomarkers to improve treatment outcomes in dogs with MCT and other malignancies treated similarly. Electrochemotherapy (ECT) in combination with the gene electrotransfer of interleukin 12 (IL-12 GET) has been successfully used in veterinary medicine for the treatment of mast cell tumours (MCT), but the biomarkers that could predict response to this treatment have not yet been investigated. The aim of this study was to determine the plasma nucleosome and serum ferritin concentrations, as well as the lactate dehydrogenase (LDH) activity, in the serum of treated patients before and one and six months after treatment to evaluate their utility as potential biomarkers that could predict response to the combined treatment. The study was conducted in 48 patients with a total of 86 MCTs that we treated with the combined treatment. The blood samples used for analysing the potential predictive biomarkers were taken before treatment and one and six months after treatment, when the response to treatment was also assessed. The Nu. Q® Vet Cancer Test, the Canine Ferritin ELISA Kit, and the RX Daytona+ automated biochemical analyser were used to analyse the blood samples. The results showed that the plasma nucleosome concentration (before treatment (BT): 32.84 ng/mL (median); one month after treatment (1 M AT): 58.89 ng/mL (median); p = 0.010) and serum LDH activity (BT: 59.75 U/L (median); 1 M AT: 107.5 U/L (median); p = 0.012) increased significantly one month after treatment and that the increase correlated significantly with the presence of a more pronounced local reaction (necrosis, swelling, etc.) at that time point for both markers (nucleosome: BT (necrosis): 21.61 ng/mL (median); 1 M AT (necrosis): 69.92 ng/mL (median), p = 0.030; LDH: BT (necrosis): 54.75 U/L (median); 1 M AT (necrosis): 100.3 U/L (median), p = 0.048). Therefore, both the plasma nucleosome concentration and serum LDH activity could serve as early indicators of the effect of the treatment. In this context, the serum ferritin concentration showed no significant predictive potential for treatment response (p > 0.999 for all comparisons). In conclusion, this study provides some new and important observations on the use of predictive biomarkers in veterinary oncology. Furthermore, it emphasises the need for the continued identification and validation of potential predictive biomarkers in dogs with MCT and other malignancies undergoing ECT treatment in combination with IL-12 GET to ultimately improve treatment outcomes. [ABSTRACT FROM AUTHOR]

Abstract An 11‐year‐old, female‐neutered beagle was presented with a growing soft tissue mass arising within the deep tissues of the left cranial cervical region. At presentation, facial asymmetry was evident along with palpable lymphadenomegaly. Magnetic resonance imaging demonstrated a locally invasive cervical mass with intracranial invasion through focal osteolysis of the occipital bone. After antihistamine administration, cytology confirmed mast cell tumour (MCT) with metastasis to local lymph nodes and liver. The owner chose to pursue lomustine and prednisolone, which were dispensed, but, before home administration, prolonged seizures/status epilepticus occurred prompting euthanasia. Postmortem examination confirmed a high‐grade MCT associated with, and infiltrating through, muscle, calvarium, dura mata, leptomeninges and the underlying brain. We present the clinical, imaging, and pathological findings of an unprecedented case of extracranial MCT tumour causing osteolysis of an imperforate flat bone (occipital bone) and intracranial invasion.

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Neoadjuvant chemotherapy can be used in canine mast cell tumours (MCTs) to optimise surgical margins or to enable marginal excision in challenging locations. The objective of this study was to describe the outcome of dogs with cutaneous and subcutaneous MCTs treated with neoadjuvant vinblastine‐prednisolone (NA‐VP). Records of treatment‐naïve dogs with cutaneous/subcutaneous MCT that received NA‐VP were reviewed including signalment, indication for NA‐VP, staging results, clinical response, surgical data and histopathology reports. For dogs with post‐operative follow‐up ≥365 days, predictive factors for local recurrence (LR) were evaluated. Forty‐four dogs were included. NA‐VP was indicated to optimise surgical margins (group MARG) in 19 dogs (43.2%) and to enable surgery (group MORB) in 25 dogs (56.8%). Complete and partial response were documented in 40.9% of dogs and 30 dogs (68.2%) underwent surgery. The indication for NA‐VP was significantly associated with undergoing surgery (p <.001) on multivariable analysis. Twelve (48%) and 18 dogs (94.7%) underwent surgery in the group MORB and MARG, respectively. Five dogs (16.7%) experienced wound dehiscence. Complete excision was achieved in 14 dogs (46.7%). In dogs undergoing surgery with ≥365 days of follow‐up, LR was documented in five cases (20.8%). None of the factors analysed including mitotic count, completeness of excision and response to NA‐VP were associated with LR; notably, LR occurred in 3/11 (27.2%) completely excised MCTs. In a pre‐operative setting, NA‐VP appears safe and could be beneficial in selected cases. Prognostic factors such as clinical response, mitotic count and completeness of excision should be interpreted with caution following NA‐VP. [ABSTRACT FROM AUTHOR]

In this study we undertook a comprehensive analysis of a Pet Tumour Registry of the Canary Archipelago (PTR‐CA) in Spain to investigate the epidemiology of canine cutaneous round cell tumours. From a database of 2526 tumours collected from 2003 to 2020, we conducted a longitudinal analysis of the main trends in diagnosis, age, multiplicity and anatomical distribution as well as a case–control study comparing these cases with the contemporaneous canine population of the Canary Archipelago to analyse breed distribution. In line with former studies, we found histiocytomas mostly affect young dogs (2, IQR 1–5) and mast cell tumours affect middle‐to‐old dogs (8, IQR 6–10) with grade 1 affecting at younger ages (6.5, IQR 6–8) than both grade 2 (8, IQR 6–10 years) and grade 3 (9, IQR 7–11). Histiocytomas and plasmacytomas showed a similar anatomical distribution appearing mainly on the face, head and neck regions while mast cell tumours occur mainly on limbs and trunk. Higher risk for mast cell tumours and histiocytomas were found for Bulldog‐related breeds such as Boxer (ORMCT = 23.61, CI95%: 19.12–29.15, ORHCT = 10.17, CI95%: 6.60–15.67), Boston Terrier (ORMCT 19.47, CI95%: 7.73–49.05, ORHCT 32.61, CI95%: 11.81–90.07) and Pug (ORMCT 8.10, CI95%: 5.92–11.07, ORHCT 7.87, CI95%: 4.66–13.28) while Chihuahua dogs showed significantly less risk (ORMCT 0.18, CI95%: 0.09–0.33, ORHCT 0.41, CI95%: 0.21–0.78). Notably, the Canarian Mastiff, a local breed, had a low risk of suffering from a mast cell tumour which raises the question of whether this relates to a genetic peculiarity of this breed or some husbandry and environmental factor. [ABSTRACT FROM AUTHOR]

Several sentinel lymph node (SLN) mapping techniques, to detect nodal metastasis in canine tumours have been investigated in the last 10 years in veterinary oncology. The purpose of this prospective study was to describe a reliable, quick, and inexpensive technique for SLN mapping in canine patients affected by cutaneous and subcutaneous mast cell tumours (MCT). Eighty dogs were enrolled in this study for a total of 138 cytologically diagnosed MCTs. Sentinel lymph node mapping was performed by injecting iomeprole peritumorally followed by serial radiographs at 1, 3, 6 and 9‐min post injection. A total of 168 SLNs were detected, 90% at first radiograph, 1 min after the peritumoral iomeprole injection, while in the rest of the cases SLN was identified at 3 min. Sentinel lymph nodes detected by the preoperative radiographic indirect lymphography with iomeprole (PRILI) differed from regional lymph nodes in 57% of cases. The PRILI technique detected simultaneously multiple SLNs in the 26% of cases and multiple lymph centers in the 31% of MCTs. To allow the surgical identification of the SLNs, a peritumoral injection of methylene blue was performed at the time of surgery. This study reports a widely available technique for SLN mapping using digital radiographs in combination with a water‐soluble medium, representing a cost‐effective alternative to other SLN mapping procedures. Based on our results, this technique can be effective for SLNs mapping in dogs with MCTs but further comparative studies are needed to assess its reliability and efficacy in different tumours. [ABSTRACT FROM AUTHOR]

It is known that the regional lymph node (RLN) may not correspond to the sentinel lymph node (SLN) (the first lymph node draining the tumour), and many diagnostic techniques have recently been aimed at its detection. Although lymphoscintigraphy is the gold standard in both human and veterinary medicine for SLN mapping, it is relatively unavailable in veterinary medicine due to costs and difficult management of the radiotracer. This prospective study evaluated, as a first aim, the feasibility and sensitivity of the computed tomography lymphography (CTL) in detecting the SLN in 62 mast cell tumours (MCTs). The second aim was to evaluate the accuracy of the CTL in identifying the most representative lymph node of the patient's lymphatic status; the histological status of the SNL was compared with that of the RLN, to see in how many cases the patient's stage would have changed according to the RLN. When the RLN turned out to be also the SLN it was decided to excise, as a control LN, the one localised in the neighbourhood of the MCT (neighbouring lymph node; NLN). The detection rate was 90%, with failure of SLN identification in six cases. In 18 (32%) of 56 MCTs with a diagnostic CTL, the SLN did not correspond to the RLN. Forty‐five MCTs were surgically removed, together with their corresponding SLN and RLN/NLN. Since the clinical stage of the patient would have changed in only 7% of cases, CTL is a reliable method of detecting the SLN and, for staging purposes, there is no need to remove other LNs. [ABSTRACT FROM AUTHOR]

Summary: A 15‐year‐old pony gelding was presented with a history of dyspnoea with inspiratory and expiratory noise for 1 week. An upper airway respiratory endoscopic examination revealed two tracheal masses, the largest one being located on the distal third of the neck, occupying almost all of the tracheal diameter. Surgical removal undertaken was in two steps under endoscopic guidance. First, scissors and Babcock forceps inserted through a tracheotomy incision were used to sever the masses. Then, a diode laser was used to cauterise the resection sites. Gross examination and histopathology confirmed a diagnosis of tracheal mastocytoma. [ABSTRACT FROM AUTHOR]

Electrochemotherapy (ECT) in combination with the gene electrotransfer of interleukin 12 (IL-12 GET) has been successfully used in veterinary medicine for the treatment of mast cell tumours (MCT), but the biomarkers that could predict response to this treatment have not yet been investigated. The aim of this study was to determine the plasma nucleosome and serum ferritin concentrations, as well as the lactate dehydrogenase (LDH) activity, in the serum of treated patients before and one and six months after treatment to evaluate their utility as potential biomarkers that could predict response to the combined treatment. The study was conducted in 48 patients with a total of 86 MCTs that we treated with the combined treatment. The blood samples used for analysing the potential predictive biomarkers were taken before treatment and one and six months after treatment, when the response to treatment was also assessed. The Nu. Q® Vet Cancer Test, the Canine Ferritin ELISA Kit, and the RX Daytona+ automated biochemical analyser were used to analyse the blood samples. The results showed that the plasma nucleosome concentration (before treatment (BT): 32.84 ng/mL (median); one month after treatment (1 M AT): 58.89 ng/mL (median); p = 0.010) and serum LDH activity (BT: 59.75 U/L (median); 1 M AT: 107.5 U/L (median); p = 0.012) increased significantly one month after treatment and that the increase correlated significantly with the presence of a more pronounced local reaction (necrosis, swelling, etc.) at that time point for both markers (nucleosome: BT (necrosis): 21.61 ng/mL (median); 1 M AT (necrosis): 69.92 ng/mL (median), p = 0.030; LDH: BT (necrosis): 54.75 U/L (median); 1 M AT (necrosis): 100.3 U/L (median), p = 0.048). Therefore, both the plasma nucleosome concentration and serum LDH activity could serve as early indicators of the effect of the treatment. In this context, the serum ferritin concentration showed no significant predictive potential for treatment response (p > 0.999 for all comparisons). In conclusion, this study provides some new and important observations on the use of predictive biomarkers in veterinary oncology. Furthermore, it emphasises the need for the continued identification and validation of potential predictive biomarkers in dogs with MCT and other malignancies undergoing ECT treatment in combination with IL-12 GET to ultimately improve treatment outcomes.

Simple Summary: In cats, gastrointestinal masses appear in relevant numbers. Histopathology and immunohistochemistry are needed for a detailed diagnosis but require invasive sampling. Therefore, the improvement of presurgical diagnostics (e.g., biomarkers in serum) is of interest in feline medicine. The present analysis of pathology reports included 679 alimentary lymphomas, 122 carcinomas, 29 spindle cell tumours, 23 polyps and 7 mast cell tumours (MCT). Immunohistochemical characterisation was available from 91 lymphomas, 10 sarcomas and 7 MCTs. Carcinomas and polyps were most commonly found in the large intestine, lymphomas were most commonly found in the stomach and small intestine and MCTs only occurred in the small intestine. In 68%, the submitted lymph nodes were infiltrated by neoplasms, and surgical margins were often not free of tumour cells. The prognostic and therapeutic value of cell size, mitotic count and immunophenotype in lymphomas must be interpreted carefully. A pilot study on miRNA-20b and miRNA-192 concentration in 11 lymphomas, 5 carcinomas and 5 controls was performed. The values of miRNA-20b were found to be up-regulated in samples of all types of cancer, whereas miRNA-192 was up-regulated in carcinomas and B-cell lymphomas only. The diagnostic purpose of miRNAs as potential biomarkers used for the non-invasive diagnosis of intestinal cancer in cats should be further evaluated. Background: Gastrointestinal masses in cats are of clinical relevance, but pathological studies with larger case numbers are lacking. Biomarkers such as miRNA have not yet been investigated in feline intestinal neoplasms. Methods: A retrospective analysis of pathology reports included 860 feline gastrointestinal masses. Immunohistochemistry was performed on 91 lymphomas, 10 sarcomas and 7 mast cell tumours (MCT). Analyses of miRNA-20b and miRNA-192 were performed on 11 lymphomas, 5 carcinomas and 5 control tissues by ddPCR. Results: The pathological diagnosis identified 679 lymphomas, 122 carcinomas, 28 sarcomas, 23 polyps, 7 MCT and 1 leiomyoma. Carcinomas and polyps were most commonly found in the large intestine, lymphomas were most commonly found in the stomach and small intestine and MCT only occurred in the small intestine. Besides the well-described small-cell, mitotic count <2 T-cell lymphomas and the large-cell B-cell lymphomas with a high mitotic count, several variants of lymphomas were identified. The values of miRNA-20b were found to be up-regulated in samples of all types of cancer, whereas miRNA-192 was only up-regulated in carcinomas and B-cell lymphomas. Conclusions: The histopathological and immunohistochemical (sub-)classification of feline intestinal masses confirmed the occurrence of different tumour types, with lymphoma being the most frequent neoplasm. Novel biomarkers such as miRNA-20b and miRNA-192 might have diagnostic potential in feline intestinal neoplasms and should be further investigated. [ABSTRACT FROM AUTHOR]

Simple Summary: Mast cell tumour (MCT) is a common cutaneous and subcutaneous neoplasia in dogs. Recent studies describe that sentinel lymph node (SLN) assessment is more specific to stage MCT, while regional lymph node (RLN) evaluation is not as specific. SNL is the first site of drainage of a tumour and the first metastatic site in several tumours. The study aims to evaluate the SLN drainage mapping of MCT with indirect lymphography in dogs. The second objective of the study is to compare the SLN to the RLN. Survey radiographs followed by an indirect lymphography were obtained for SLN mapping. Twenty-six dogs with 29 MCTs were included. SLNs were detectable in 26 MCTs and radiographic indirect lymphangiography with Lipiodol was able to detect at least one SLN in 90% of MCTs in dogs. In conclusion, radiographic indirect lymphangiography with Lipiodol is a feasible technique to map SLNs and its draining system in MCTs. The lymph drainage pattern of the MCTs may be different for each MCT and more than one SLN can be involved. Mast cell tumour (MCT) is a common cutaneous and subcutaneous neoplasia in dogs. It can metastasise to lymph nodes (LNs), and this adversely affects the prognosis and treatment. The study aims to evaluate the SLN mapping of MCTs with radiographic indirect lymphography. Dogs that underwent clinical staging were prospectively enrolled. Lipiodol was injected around the MCT or the surgical scar. After 24 h, LNs that picked up contrast were radiographically assessed. Twenty-six dogs with 29 MCTs were included. MCTs were confirmed histologically, while SLNs were evaluated either by cytology and/or histology. SLNs were detectable in 23 dogs with 26 MCTs. Lymphatic vessels were visible in 19 MCTs. In nine MCTs, at least two SLNs picked up contrast. In particular, seven MCTs involved two SLNs, and two MCTs involved three different SLNs. In nine MCTs, at least a SLN was metastatic. This study indicates that the lymph drainage pattern of the MCTs may be different for each MCT, and more than one SLN can be involved. Indirect lymphangiography with Lipiodol allowed the detection of the SLN in 90% of MCTs. This provided clinically relevant information to remove the LN and stage the patient. [ABSTRACT FROM AUTHOR]

Mast cell tumours (MCTs) are common canine skin neoplasia. While they generally occur as single tumours, multiple synchronous MCTs (msMCTs) of de novo/non-metastatic origin are reported in a proportion of the patient population. Where there is no evidence of metastasis or lymphatic spread, MCTs are effectively controlled by surgery and other local therapies. However, treatment of de novo msMCTs can be more challenging, especially when they occur in surgically difficult locations. Here, we report the use of tigilanol tiglate, a novel small molecule registered as a veterinary pharmaceutical for the local treatment of non-metastatic MCTs, in the treatment of patients with msMCTs presenting at three Australian specialist referral centres. We also present a meta-analysis of the literature to provide a better understanding of the prevalence of canine msMCTs. Notably, nine patients with a total of 32 MCTs were treated during the study. A complete response was recorded in 26 (81%) of the individual MCTs on Day 28 after a single tigilanol tiglate injection. Of the 6 initially non-responsive MCTs, one achieved a complete response after a further tigilanol tiglate treatment. A complete response was reported at 6 months in all 22 of the tumours that were evaluable and that had recorded a complete response at Day 84. For the literature meta-analysis, 22 studies were found with prevalence estimates of msMCTs ranging from 3 to 40%; when combined, these studies yielded 3,745 patients with a prevalence of 13% (95% CI 10; 16). Overall, the results demonstrate the utility of intratumoural tigilanol tiglate as an option for the treatment of multiple MCTs where multiple surgical resections would have been required.

Optimal chemotherapy protocols for high-risk mast cell tumours (MCTs) are unknown. The purpose of this study was to determine the tolerability and toxicity profile of a rapidly escalating vinblastine and prednisolone protocol (VPP) in which 3.00 mg/m2 was administered once 7 days apart: at day 14 and at day 21. Dogs with chemotherapy-naïve MCTs presenting to the Oncology Service of a single institution were prospectively enrolled to receive escalating vinblastine, and haematology and a standardised quality-of-life questionnaire were assessed prior to each dosage. Thirty-four dogs were included: 30 with microscopic disease treated with adequate local therapy and four with macroscopic disease. Of 220 doses of vinblastine administered, 4% were associated with grade 3 and 4 toxicity. A total of 70% of dogs tolerated 3.00 mg/m2 given 7 days apart at day 14 and 21, although 29% of dogs developed dose-limiting toxicities and 8% discontinued the protocol due to toxicity. In conclusion, VPP was well-tolerated overall, although prior to further dose intensity optimisation, it is important to determine if dose intensity is linked to outcome in canine MCT to avoid unwarranted toxicity.

A two-year-old spayed female American shorthair cat presented with a rough, circular, exophytic mass on the genital area. The clinical findings and histopathological examination revealed that the mass contained neoplastic mast cells and, thus, was diagnosed as a mast cell tumour. The anatomical location of the mass was not easily accessible for surgical intervention. We administered a targeted therapy using oral imatinib mesylate for eight weeks to reduce the size of the lesion and to facilitate the successful surgical removal. The tumour mass eventually reduced by 21% and was surgically excised. This is possibly the first study to use imatinib mesylate as a tumour reduction neoadjuvant to therapeutically address a feline cutaneous mast cell tumour located in a surgically inaccessible part of the body.

Background: Gastrointestinal masses in cats are of clinical relevance, but pathological studies with larger case numbers are lacking. Biomarkers such as miRNA have not yet been investigated in feline intestinal neoplasms. Methods: A retrospective analysis of pathology reports included 860 feline gastrointestinal masses. Immunohistochemistry was performed on 91 lymphomas, 10 sarcomas and 7 mast cell tumours (MCT). Analyses of miRNA-20b and miRNA-192 were performed on 11 lymphomas, 5 carcinomas and 5 control tissues by ddPCR. Results: The pathological diagnosis identified 679 lymphomas, 122 carcinomas, 28 sarcomas, 23 polyps, 7 MCT and 1 leiomyoma. Carcinomas and polyps were most commonly found in the large intestine, lymphomas were most commonly found in the stomach and small intestine and MCT only occurred in the small intestine. Besides the well-described small-cell, mitotic count

Mast cell tumour (MCT) is a common cutaneous and subcutaneous neoplasia in dogs. It can metastasise to lymph nodes (LNs), and this adversely affects the prognosis and treatment. The study aims to evaluate the SLN mapping of MCTs with radiographic indirect lymphography. Dogs that underwent clinical staging were prospectively enrolled. Lipiodol was injected around the MCT or the surgical scar. After 24 h, LNs that picked up contrast were radiographically assessed. Twenty-six dogs with 29 MCTs were included. MCTs were confirmed histologically, while SLNs were evaluated either by cytology and/or histology. SLNs were detectable in 23 dogs with 26 MCTs. Lymphatic vessels were visible in 19 MCTs. In nine MCTs, at least two SLNs picked up contrast. In particular, seven MCTs involved two SLNs, and two MCTs involved three different SLNs. In nine MCTs, at least a SLN was metastatic. This study indicates that the lymph drainage pattern of the MCTs may be different for each MCT, and more than one SLN can be involved. Indirect lymphangiography with Lipiodol allowed the detection of the SLN in 90% of MCTs. This provided clinically relevant information to remove the LN and stage the patient.

Canine high-grade mast cell tumours (HGMCT) are associated with a poor prognosis, are inherently more invasive, and have higher rates of local recurrence. The primary aim of this retrospective study was to assess the efficacy of intratumoural tigilanol tiglate (TT) as a local treatment option. Eighteen dogs with mast cell tumours (MCT) cytologically diagnosed by veterinary pathologists as either high-grade or suspected high-grade MCT were treated with TT. The TT dose was based on tumour volume (0.5 mg TT/cm3 tumour volume) and delivered intratumourally using a Luer lock syringe and a fanning technique to maximise distribution throughout the tumour mass. Efficacy was assessed on the presence/absence of a complete response (CR) to therapy at days 28 and 84 using response evaluation criteria in solid tumours (RECIST). For dogs not achieving a CR after 28 days, the protocol was repeated with a second intratumoural TT injection. Ten out of 18 dogs (56%) in this study achieved and maintained a CR to at least 84 days after their first or second treatment. Six patients were alive and available for evaluation at 2 years, three of those were recurrence free, and a further three patients were recurrence free following a second treatment cycle. Tigilanol tiglate shows efficacy for local treatment of HGMCT, with higher efficacy noted with a second injection if a CR was not achieved following the first treatment. In the event of treatment site recurrence (TSR), the tumour may be controlled with additional treatment cycles. Tigilanol tiglate provides an alternative local treatment approach to dogs with HGMCT that would either pose an unacceptable anaesthetic risk or the tumour location provides a challenge when attempting surgical excision.

Mast cell tumour (MCT) is the most frequent skin neoplasm in dogs. These tumours are characterised by variable behaviour and clinical presentation that make prognosis an important and challenging task in the veterinary practice. Galectin-3 (Gal-3) is known to influence several biological processes that are important in the cancer context and has been described as a prognostic marker for several human cancers. The aim of the present work was to characterise Gal-3 immunolabelling in canine cutaneous MCTs and to investigate its value as a prognostic marker for the disease. Thirty-four random cases of canine cutaneous MCT that were surgically treated with wide margins were included in this study. Gal-3 expression was evaluated using immunohistochemistry and the results were compared with the expression of apoptosis-related proteins, Ki67 index, histopathological grades, mortality due to the disease and post-surgical survival. The majority of the MCTs (65.8%) were positive for Gal-3. Gal-3 immunolabelling was variable among the samples (2.7%–86.8% of the neoplastic cells). The protein was located in the cytoplasm or in the cytoplasm and the nucleus. Gal-3 positivity was correlated with BCL2 expression (P < 0.001; r = 0.604), but not with Ki67 and BAX. No significant differences were detected between histological grades or in the survival analysis. Gal-3 expression correlates with BCL2 expression in MCTs. Although an efficient marker for several human neoplasms, the results presented herein suggest that Gal-3 immunolabelling is not an independent prognostic indicator for this disease. [ABSTRACT FROM AUTHOR]

Abstract Background Mast cell tumours are the most common cutaneous neoplasms in dogs. Other primary sites include visceral organs, such as the gastrointestinal tract, liver, or spleen, and the oral cavity. Frequent metastatic sites include the local lymph nodes, skin, spleen, liver and bone marrow. The thorax is rarely affected by metastatic disease and no such cases have been reported in dogs. Mast cell tumours are usually not considered as a differential diagnosis for lung and intrathoracic chest wall masses in dogs. Chest wall tumours can be primary tumours of the ribs and sternum, an invasion of adjacent tumours into the chest wall, and metastasis from distant tumours. Cases presentation A German Shepherd dog presented with a history of persistent cough and a large mass involving the thoracic wall and a small round pulmonary mass. The dog had a history of mammary tumours that were surgically excised. Thoracoscopy revealed a thoracic wall mass involving the internal intercostal muscle and a small mass in the left cranial lung lobe. Cytology and histopathology of the intrathoracic mass confirmed the large mass as a mast cell tumour and the small mass as a carcinoma. Cytology of the sternal lymph nodes showed no involvement. The dog received toceranib for 3 months, which failed to alleviate persistent cough. Radiology indicated that the large mass had a partial response to toceranib. The dog was euthanasied. A Maltese dog presented with a history of chronic regurgitation and cough, and a large mass involving the left caudal lung lobe. Cytology and histopathology of mass confirmed a mast cell tumour. The dog received toceranib for 2 months. Radiology indicated that the large mass had no response to toceranib. The dog was euthanasied. Confirmation of lungs mast cell tumour and the absence of any other Mast cell tumour was achieved by postmortem examination. Conclusions The cases discussed are two unusual presentations of intrathoracic mast cell tumours, in the absence of cutaneous mast cell tumours, in dogs.

Introduction: Breed predisposition to cutaneous mast cell tumours (MCT) in a population of dogs in Poland affected by various skin tumours was assessed, and the distribution of MCT characteristics such as histological grading, sex, age, and location, in predisposed breeds was evaluated.

Objectives: The objective of this retrospective study was to evaluate the outcome of dogs when grade II mast cell tumour (MCT) with low mitotic index (MI) and high Ki67 were treated with adjuvant lomustine. Animals: Client owned dogs with spontaneously occurring disease treated with adjuvant chemotherapy for grade II mast cell tumour with low MI (≤5/10HPF) and high Ki67 (>1.8%) with no evidence of metastatic disease at presentation. Procedures: Lomustine was administered every 3 weeks with three or four planned cycles. Response to treatment was assessed by regular re‐staging ultrasound with or without cytopathological examination of liver and spleen or through medical records from the referring veterinarian. Disease‐free interval (DFI) and median survival time (MST) were calculated using Kaplan–Meier method. Results: Twenty‐one dogs were included. All dogs underwent surgical excision and two dogs received adjuvant radiotherapy. None of the patients developed local recurrence. Three dogs (14.3%) developed metastatic disease. The DFI of these dogs was 141, 186 and 223 days. Median follow‐up period of the whole study population was 1112 days (358–2619). MST for patients with metastatic disease was 417 days. MST of the whole group was not reached. One‐year and 2‐year survivals were 95.2% and 90.5%, respectively. Conclusions and clinical relevance: This study population had low rates of tumour recurrence and improved survival compared to previously published data of similar population of dogs with low MI/high Ki67 MCT without adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Genetic causes of canine mast cell tumours (MCTs), except for mutations in the KIT gene detected in some MCTs, are generally unknown. We used whole exome sequencing to reveal mutation spectra in canine MCTs. We detected somatic mutations in 87 genes including 10 genes recognized as human cancer drivers. Besides KIT, 14 other genes were recurrently mutated. Subsequently, we performed next generation sequencing of a panel of 50 selected genes in additional MCT samples. In this group, the most frequently altered gene was GNB1 showing a recurrent dinucleotide substitution at position of Gly116 in 30% of the MCT samples (n = 6/20) and Ile80 substitution accompanied by a splice region mutation in one case. We extended the study by analysis of the above mentioned GNB1 regions in additional MCT samples by Sanger sequencing, and assessed the overall prevalence of GNB1 mutations to 17.3% (n = 14/81), which is similar to the prevalence of KIT alterations. Our results indicate that GNB1 mutations are probably involved in canine MCT pathogenesis in both cutaneous and subcutaneous MCT cases. As opposed to KIT alterations, the presence of GNB1 mutations did not negatively affect survival times, and our data even showed a trend towards positive prognosis. If our results are confirmed in a larger number of MCTs, an extension of molecular testing of canine MCTs by GNB1 analysis would help to refine the molecular stratification of MCTs, and become useful for targeted treatment strategies. [ABSTRACT FROM AUTHOR]

A new combination of Toceranib (Toc; 5-[(5Z)-(5-Fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-N-[2-(pyrrolidin-1-yl)ethyl]-1H-pyrrole-3-carboxamide) with nanohydroxyapatite (nHAp) was proposed as an antineoplastic drug delivery system. Its physicochemical properties were determined as crystallinity, grain size, morphology, zeta potential and hydrodynamic diameter as well as Toceranib release. The crystalline nanorods of nHAp were synthesised by the co-precipitation method, while the amorphous Toceranib was obtained by its conversion from the crystalline form during nHAp–Toc preparation. The surface interaction between both compounds was confirmed using Fourier-transform infrared spectroscopy (FT-IR), ultraviolet-visible spectroscopy (UV–Vis) and scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDS). The nHAp–Toc showed a slower and prolonged release of Toceranib. The release behaviour was affected by hydrodynamic size, surface interaction and the medium used (pH). The effectiveness of the proposed platform was tested by comparing the cytotoxicity of the drug combined with nHAp against the drug itself. The compounds were tested on NI-1 mastocytoma cells using the Alamar blue colorimetric technique. The obtained results suggest that the proposed platform shows high efficiency (the calculated IC50 is 4.29 nM), while maintaining the specificity of the drug alone. Performed analyses confirmed that nanohydroxyapatite is a prospective drug carrier and, when Toceranib-loaded, may be an idea worth developing with further research into therapeutic application in the treatment of canine mast cell tumour.

An 8-year-old neutered male French Bulldog was presented with a 2-day history of intermittent vomiting, reduced appetite and recent rapid development of multiple cutaneous masses over the head and neck regions. On presentation, the patient had a moderate volume of pericardial and bilateral pleural effusion. Echocardiography demonstrated irregular, heterogeneous thickening of the walls of the right ventricle and right atrium, consistent with infiltrative intramyocardial disease. Cytological examination of fine needle aspirates from one of the cutaneous masses confirmed a mast cell tumour. Pericardial fluid analysis revealed a haemorrhagic neoplastic effusion due to mast cell neoplasia. Histopathological and immunohistochemical examination of tissues obtained post mortem confirmed a high-grade cutaneous mast cell tumour with metastasis to the heart, pericardium, mediastinum and spleen. No metastatic disease was present in the submandibular lymph nodes or liver. Immunohistochemistry demonstrated KIT staining pattern 2. There was strong nuclear Ki67 labelling in an average of 65.0 cells per grid and an average of three positive AgNORs per nucleus in neoplastic cells. Polymerase chain reaction for the activating duplication mutation in exons 8 and 11 of c-Kit were negative. To the authors' knowledge, this is the first report of a canine cutaneous mast cell tumour associated with neoplastic pericardial effusion and widespread intrathoracic metastasis. [ABSTRACT FROM AUTHOR]

Conflicting evidence exists regarding the importance of routine abdominal ultrasound (US) with hepatic and splenic fine needle aspiration (FNA) cytology during staging of canine mast cell tumours (MCT). The objective of this study was to correlate ultrasonographic and cytologic findings in dogs with strictly defined high‐risk MCTs and to determine the influence on outcome. Our hypothesis was that US poorly predicts visceral metastasis in high‐risk MCTs and that early metastasis is associated with improved outcome when compared to overt metastasis. US of liver and spleen correlated to cytologic results, categorized as no metastasis, early metastasis or overt metastasis. Of 82 dogs prospectively enrolled, 18% had early visceral metastasis and 7% had overt metastasis on cytology; 67% with visceral metastasis had regional LN metastasis. US was a poor predictor of metastasis with sensitivity, specificity, positive predictive value and negative predictive value for the spleen of 67%, 68%, 21% and 94%, respectively and for the liver of 29%, 93%, 56% and 82%, respectively. Median time to progression (TTP) for dogs with no metastasis, early metastasis and overt metastasis was not reached, 305 and 69 days, respectively (P <.001). Median survival time (MST) for the 3 groups were not reached, 322 and 81 days, respectively (P <.001). High Patnaik or Kiupel grade, early metastasis, overt metastasis and adequate local control were significantly associated with outcome. Early visceral metastasis was associated with poorer outcome compared to dogs without metastasis, however, a subset of dogs experienced long‐term control. [ABSTRACT FROM AUTHOR]

Cutaneous and subcutaneous mast cell tumours (MCTs) are counted among the most frequent cancers in dogs. However, the genetic aetiology of their development is still mostly unknown, with the exception of KIT and tumor protein p53 (TP53) mutations reported in less than a half of cutaneous MCTs. In subcutaneous MCTs, no gene alterations were previously detected. We analysed KIT and TP53 mutations in cutaneous and subcutaneous MCTs, and identified methylated CpG sites in KIT and TP53 promoters and adjacent exon 1 regions. The mutation analysis focused on KIT exons 8, 9 and 11, and TP53 exons 5‐8, and revealed mutations in 26% and 7% cutaneous MCT cases, respectively. Moreover, we report a first case of KIT mutation ever detected in subcutaneous MCTs. KIT exon 11 mutations and high Kiupel and Patnaik grades were associated with reduced survival in this study. Both KIT and TP53 gene were generally unmethylated in canine cutaneous MCTs. A sporadic methylation of the CpG positions in KIT promoter and adjacent exon 1 was detected in 70.4% of cutaneous and 82% of subcutaneous MCTs. A sporadic methylation of the CpG positions in the TP53 promoter and exon 1 was observed in 36.8% of the analysed cutaneous MCT samples. Only in two subcutaneous MCTs, we observed more than 30% of clones showing KIT methylation at the CpG positions 13 or 14. The CpG position 14 is involved in a predicted binding site for Sp1 transcription factor. However, the significance of KIT promoter methylation at this specific position needs further evaluation. [ABSTRACT FROM AUTHOR]

A 13-year-old entire male Thai Ridgeback dog presented to Prasu-Arthorn Animal Hospital, Faculty of Veterinary Science, Mahidol University with a mass on the caudal right flank. Fine needle aspiration (FNA) revealed round cells with intracytoplasmic granules consistent with mast cell tumour (MCT). Surgical excision was performed. Histological grading revealed poorly-differentiated, high grade MCT with 18 mitotic figures per 10 high power-fields (HPFs) and KIT staining was consistent with KIT pattern II (focal or stippled cytoplasmic staining); both of which are associated with poor survival. This contrasted with the better survival time implicated by low argyrophilic nucleolar organiser region (AgNOR) and Ki-67 scores, which were all below the cut-off values, suggesting low cellular proliferation. A chemotherapy protocol of vinblastine and prednisolone was subsequently commenced. Distant recurrence at the neck occurred at 67 days, confirmed to be MCT by histopathology. The dog later died, with a total survival time of 90 days from diagnosis. The actual survival time closely aligned with the estimated survival time based on histological grading. With few multivariate survival analyses available, this case demonstrates the use of AgNOR, Ki-67, and KIT localisation to complement histological grading for further studies to compare different variables in a clinical setting in Thailand. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are membrane‐enclosed fragments shed from all cell types, including tumour cells. EVs contain a wide range of proteins, biolipids and genetic material derived from mother cells and therefore may be potential biomarkers for tumour diagnosis, disease progression and treatment success. We studied the effect of canine mast cell tumours (MCTs) on EV concentrations in blood isolates in association with MCT's histological grade, Ki‐67 proliferative index, KIT‐staining pattern and number of PLT. The average EV concentration in blood isolates from nine dogs with MCTs was considerably higher than that in blood from eight healthy dogs. But there were no statistically significant differences in EVs concentration in the population of dogs with MCT according to a different histological grade of malignancy (Patnaik, Kiupel), KIT‐staining pattern and Ki‐67 proliferation index. The results show that these variables statistically do not significantly predicted EV concentrations in blood isolates (P > .05), except the KIT‐staining pattern I which added statistically significantly to the prediction (P < .05). The results confirmed the impact of neoplasms on the morphological changes to cell membranes, which result in greater vesiculability and higher EV concentrations. [ABSTRACT FROM AUTHOR]

Introduction. Canine cutaneous round cell tumours (CCRCTs) include various benign and malignant neoplastic processes. Due to their similar morphology, the diagnosis of CCRCTs based on histopathological examination alone can be challenging, often necessitating ancillary immunohistochemical (IHC) analysis. This study presents a retrospective analysis of CCRCTs. Materials and methods. This study includes 60 cases of CCRCTs, including 55 solitary and 5 multiple tumours, evaluated immunohistochemically using a basic antibody panel (MHCII, CD18, Iba1, CD3, CD79a, CD20 and mast cell tryptase) and, when appropriate, extended antibody panel (vimentin, desmin, a-SMA, S-100, melan-A and pan-keratin). Additionally, histochemical stainings (May-Grünwald-Giemsa and methyl green pyronine) were performed. Results. IHC analysis using a basic antibody panel revealed 27 cases of histiocytoma, one case of histiocytic sarcoma, 18 cases of cutaneous lymphoma of either T-cell (CD3+) or B-cell (CD79a+) origin, 5 cases of plasmacytoma, and 4 cases of mast cell tumours. The extended antibody panel revealed 2 cases of alveolar rhabdomyosarcoma, 2 cases of amelanotic melanoma, and one case of glomus tumour. Conclusions. Both canine cutaneous histiocytoma and cutaneous lymphoma should be considered at the beginning of differential diagnosis for CCRCTs. While most poorly differentiated CCRCTs can be diagnosed immunohistochemically using 1--4 basic antibodies, some require a broad antibody panel, including mesenchymal, epithelial, myogenic, and melanocytic markers. The expression of Iba1 is specific for canine cutaneous histiocytic tumours, and more sensitive than CD18. The utility of CD20 in the diagnosis of CCRCTs is limited. [ABSTRACT FROM AUTHOR]

Summary: Equine mast cell tumours (MCT) have been reported to occur in the skin, respiratory tract, oral cavity, synovial structures and eye. These tumours are typically locally invasive and nonaggressive. In this case, a MCT was located in the extensor carpi radialis (ECR) and was highly infiltrative. Excision of the ECR and local corticosteroid injection was curative and resulted in a good functional outcome. A 12‐year‐old Thoroughbred gelding presented for lameness, swelling and pruritus associated with the right antebrachium. Sonographic changes were suggestive of severe tenosynovitis and purulent material in the ECR. Surgical exploration revealed maceration at the ECR musculotendinous junction. The extensor sheath contained a large quantity of caseous material and serosanguinous fluid. The ECR tendon and 75% of the muscle was excised. Cytology and histopathology were consistent with a MCT that infiltrated the surgical margins. Post‐operatively the horse was treated with multiple local corticosteroid injections along the incision. Right forelimb movement was initially limited, however, there was steady improvement over 3 months with increasing exercise. At 18 months post‐operatively, no lameness was detectable in the walk, trot or canter and no recurrence of MCT was apparent. The horse appeared to compensate for loss of the ECR by using the biceps during the swing phase. Partial excision and local corticosteroid treatment can be curative for cases of invasive MCT. Extensive excision of the ECR is a viable treatment option for neoplasia or other conditions affecting the ECR in the horse. [ABSTRACT FROM AUTHOR]

Case report A 7‐year‐old female‐neutered Maltese Terrier × Papillon dog was presented with tachypnoea and weight loss following 12 months of therapy with toceranib phosphate for a metastatic, histologically‐low‐grade mast cell tumour. The dog was diagnosed with Pneumocystis canis based on PCR with supportive clinical, radiographic and cytological findings. No other clinical evidence of immunocompromise was identified through assessment of haematology and immunoglobulin quantification. Clinical signs completely resolved with a short course of potentiated sulfonamides and discontinuation of the toceranib. Conclusion: To the authors' knowledge this represents the first case of Pneumocystis in a dog secondary to immunomodulatory drug therapy. It is also the first case of opportunist infection secondary to a tyrosine kinase inhibitor in dogs. [ABSTRACT FROM AUTHOR]

Highlights • The c-kit gene mutations known as drivers in canine mast cell tumours were detected in 19.5% (n = 8/41) samples. • TP53 mutations were detected in 14.6% (n = 6/41) of canine mast cell tumour specimens. • The presence of c-kit gene mutations was correlated with high histopathological grade (P = 0.038). • There was no correlation between TP53 mutations and histopathological grade or survival time (P > 0.05). Abstract Cutaneous mast cell tumours (MCT) are among the most frequent malignancies in dogs. Their clinical behaviour is highly variable and, with the exception of mutations in the c-kit gene, little is known about their genetic aetiology. The mutational status of the c-kit exons 8, 9 and 11, and exons 5–8 of the TP53 gene was analysed to find markers for molecular stratification of MCTs and predictors of clinical outcome. Mutations in the c-kit gene were detected in 19.5% (n = 8/41) samples and their presence was significantly associated with the high histopathological grade (P = 0.038). Mutations in the DNA binding domain of the TP53 gene were found in 14.6% (n = 6/41) of the analysed MCTs, and their frequency was similar in low and high grade MCTs (P > 0.05). TP53 mutations were not useful prognostic factors in this sample of canine cutaneous MCTs. [ABSTRACT FROM AUTHOR]

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Mast cell tumours (MCTs) are the most common skin tumours in dogs. Their clinical behaviour is variable and their aetiology remains largely unknown. We performed a metaphase fluorescence in situ hybridisation (FISH) with whole chromosome painting probes, and interphase FISH with BAC probes for 14 cancer-related genes to reveal clonal structural chromosome rearrangements and copy number variants (CNVs) in canine cutaneous MCTs. The metaphase FISH performed in three MCTs revealed several clonal monosomies and trisomies and two different chromosome rearrangements. No centric fusions were detected. The interphase FISH showed a variety of low frequency CNVs for the individual cancer-related genes. The heterogeneous character of the detected abnormalities indicates increased chromosome instability in canine MCTs. The clonal gain of chromosome 11 was detected in 81% (13/16) of the MCTs. Further research is needed to evaluate the significance of this abnormality as prognostic factor for the survival time or recurrence risk assessments in canine cutaneous MCTs. [ABSTRACT FROM AUTHOR]

Lymph node (LN) metastasis in canine cutaneous mast cell tumours (cMCTs) is a well‐known negative prognostic factor. The role of lymphadenectomy in the treatment of stage II disease remains controversial because of its uncertain therapeutic benefit. Aim of this retrospective study was to investigate the impact of lymphadenectomy on tumour control and survival for dogs with stage II cMCTs. Dogs with firstly occurring, histologically confirmed cMCT with LN metastasis undergoing resection of the primary tumour and medical treatment thereafter were retrospectively enrolled. Dogs were classified into two groups: LN sampling (LNS; diagnosis of metastasis obtained by cytology) and regional LN dissection (LND; diagnosis obtained by histopathology). To determine the therapeutic value of lymphadenectomy, the characteristics of recurrence (local, nodal and distant) and survival were compared between groups. Evaluated outcome variables included signalment, anatomic location, diameter, ulceration, substage, surgical margins, Patnaik grading, Kiupel grading and medical treatment. Overall, 152 dogs were included: 81 underwent LND as part of primary surgery and 71 LNS. The median follow‐up time was 409 days for LND group and 620 days for LNS group. On univariable analysis, the risk of developing local, nodal or distant relapse was significantly higher in the LNS group compared with LND (P < 0.001). On multivariable analysis, the risk of tumour progression and tumour‐related death were 5.47 and 3.61 times higher in the LNS group, respectively (P < 0.001). Regional lymphadenectomy may have therapeutic value and improve prognosis in dogs with stage II cMCTs undergoing surgical removal of the primary tumour and medical treatment. [ABSTRACT FROM AUTHOR]

A previous study found that minichromosome maintenance protein 7 (MCM7) score was associated with prognosis in dogs with cutaneous mast cell tumours (MCTs) independent of histological grade. The primary aim of this study was to validate this score in a different cohort of dogs focusing exclusively on patients with Patnaik intermediate grade MCTs treated with surgery alone and followed for a minimum of 1 year. A secondary aim was to evaluate the prognostic performance of MCM7 in relation to Kiupel histological grade, mitotic index (MI) and Ki67 index in the same cohort of dogs. Ninety dogs were identified, 82 were low Kiupel grade and 8 were high Kiupel grade. Seventy‐two dogs were alive after a median follow‐up of 1136 days and 18 dogs died of MCT‐related causes after a median of 116 days. A MI threshold of 5 was associated with a sensitivity of 0.39 and a specificity of 0.99 in predicting MCT‐related death; for Ki67 a threshold of 0.018 was associated with a sensitivity of 0.78 and a specificity of 0.83; and for MCM7 a threshold of 0.18 gave a sensitivity of 0.83 and a specificity of 0.86. Combining MI, Ki67 and MCM7 showed an improved accuracy of predicting death compared with each individual variable. Therefore, performing Ki67 and MCM7 in dogs with GII MCT, low Kiupel grade and low MI might be a consideration. [ABSTRACT FROM AUTHOR]

Mast cell tumours (MCTs) are often diagnosed by cytology based on the identification of purple intracytoplasmic granules with methanolic Romanowsky stains, including May‐Grünwald‐Giemsa (MGG). In clinical practice, aqueous rapid stains (RS) are commonly used, but mast cell granules may not stain properly. Aim of this prospective study was to investigate the frequency of MCT hypogranularity with RS and its potential implications in tumour identification, cytological grading assessment and recognition of nodal metastatic disease. Cytological preparations of canine primary MCTs and metastatic lymph nodes with subsequent histopathological confirmation were included. For each case, good‐quality smears were stained with both MGG and RS and comparatively assessed. Eleven of 60 (18.3%) primary MCTs were hypogranular with RS; 9 of them were histologically high‐grade tumours and in 3 cases (5%) a definitive MCT diagnosis could not be made. Accuracy in cytological grading assessment (85%) did not differ between RS and MGG. Thirteen of 28 (46.4%) metastatic lymph nodes were hypogranular with RS and 3 independent observers failed to identify nodal MCT metastases in 7% to 18% of RS‐stained smears. This study confirms that, in limited cases, RS can be ineffective in staining MCT granules, particularly in high‐grade tumours, thus making diagnosis more dependent on experience and quality of preparations. In dubious cases, methanolic stains should be applied. The use of RS is discouraged for the search of nodal metastases, as the identification of isolated mast cells can be more challenging. [ABSTRACT FROM AUTHOR]

Mast cell tumours (MCTs) are commonly treated with radiation therapy, most often in a microscopic disease setting. Poorer outcomes are expected in patients with gross disease, and irradiation of gross disease may be associated with greater toxicity. The aim of this study was to compare acute radiation adverse events (AE) in dogs with gross and microscopic MCTs receiving radiotherapy. Fifty‐seven dogs were included, 28 with gross disease and 29 with microscopic. In order to assess mucosal and skin toxicity, patients were assigned to 2 groups: head (29 patients, 14 patients with gross and 15 microscopic) and other sites (28 patients, 14 each). All were treated with external beam radiotherapy, and toxicity assessed at the end of treatment and 10 to 14 days later (first recheck). All patients developed some acute radiation toxicity by the end of the course. However, there was no difference in the severity of toxicity between gross and microscopic disease in either site group at either time point. The only variable associated with an increased frequency of grade 2 or 3 toxicity at the first recheck was the use of prednisolone prior to radiotherapy (P = .05). No other factors were identified which were associated with increased toxicity. For the head group, the site of highest grade toxicity was mucosa or, if included in the field, nasal planum, which was often more severely affected than the mucosa. No significant late toxicity was identified. Two dogs developed acute haematemesis during the radiotherapy course, but both completed the course without further events. [ABSTRACT FROM AUTHOR]