Search

Variation in nuclear size and shape is an important criterion of malignancy for many tumor types; however, categorical estimates by pathologists have poor reproducibility. Measurements of nuclear characteristics can improve reproducibility, but current manual methods are time-consuming. The aim of this study was to explore the limitations of estimates and develop alternative morphometric solutions for canine cutaneous mast cell tumors (ccMCTs). We assessed the following nuclear evaluation methods for accuracy, reproducibility, and prognostic utility: (1) anisokaryosis estimates by 11 pathologists; (2) gold standard manual morphometry of at least 100 nuclei; (3) practicable manual morphometry with stratified sampling of 12 nuclei by 9 pathologists; and (4) automated morphometry using deep learning-based segmentation. The study included 96 ccMCTs with available outcome information. Inter-rater reproducibility of anisokaryosis estimates was low (k = 0.226), whereas it was good (intraclass correlation = 0.654) for practicable morphometry of the standard deviation (SD) of nuclear size. As compared with gold standard manual morphometry (area under the ROC curve [AUC] = 0.839, 95% confidence interval [CI] = 0.701-0.977), the prognostic value (tumor-specific survival) of SDs of nuclear area for practicable manual morphometry and automated morphometry were high with an AUC of 0.868 (95% CI = 0.737-0.991) and 0.943 (95% CI = 0.889-0.996), respectively. This study supports the use of manual morphometry with stratified sampling of 12 nuclei and algorithmic morphometry to overcome the poor reproducibility of estimates. Further studies are needed to validate our findings, determine inter-algorithmic reproducibility and algorithmic robustness, and explore tumor heterogeneity of nuclear features in entire tumor sections., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Detection of metastatic mast cell tumors (MCTs) in lymph nodes is a critical factor for treatment, prognosis, and clinical management. Presence/absence of mast cells in the lymph nodes cannot be used as a sole parameter to determine metastasis due to the inability to differentiate neoplastic from non-neoplastic/inflammatory mast cells. While cytologic and histopathologic classifications for assessment of metastatic MCTs based on the numbers and distribution of mast cells have been developed, inconsistency between the clinical interpretation of these grading schemes and actual metastatic status occurs. The aim of this study is to identify a novel diagnostic tool to accurately predict overt metastatic mast cell tumors in lymph nodes. We investigated the possibility of using RT-qPCR to detect mRNA expression of mast cell-specific genes in lymph nodes with different stages of MCT metastatic classification. We are able to establish a highly sensitive and discriminating RT-qPCR measuring Carboxy peptidase A3 (CPA3) and tryptase mRNA expression and identify the cut-off values with high sensitivity and specificity for overt metastatic MCTs in lymph nodes. An area of future interest would be to expand our analysis of the extent to which cut-off values for these markers in correctly identifying disease status, as well as predicting clinical outcomes and survival times. This would offer valuable information regarding the practical applicability of this technique and may enable us to improve our standards of detection metastasis, including possibility of molecular analysis of cytologic specimens obtained from suspicious nodes subjected to surgical excision.

A male Malayan tiger cub developed well-circumscribed, erythematous, alopecic lesions on the face, torso, and paws when 1-wk-old. Biopsies of a torso lesion and a right front paw lesion at 1-mo-old confirmed cutaneous mast cell tumors (MCTs). MCTs on the paws grew into pendulous masses up to 6.5 cm in diameter by 3-mo-old, but those on the face and torso regressed. Fine-needle aspiration of the spleen at 3-mo-old revealed marked mast cell infiltration. The spleen and the right paw cutaneous MCT were removed; the paw MCT recurred within 7 d. A 12-bp tandem duplication, suggesting a somatic mutation, was identified in exon 8 of c-KIT in DNA extracted from the cutaneous MCT on the right paw and from one over the torso, but not from the spleen. Remaining MCTs on the paws regressed slowly following splenectomy and had completely regressed by 1-y-old. At 7-y-old, there was no recurrence of any mast cell disease. Mast cell disease in this tiger cub is similar to a report in a domestic kitten and to pediatric mastocytosis in humans, which commonly begins in infancy, improves by adolescence, and is associated with somatic c-kit mutations. To our knowledge, mastocytosis has not been reported previously in a juvenile exotic felid. [ABSTRACT FROM AUTHOR]

Mast cell tumors (MCTs) are one of the most common cutaneous malignancies in dogs. Previous studies have reported expression of mast cell–specific proteases chymase and tryptase in canine cutaneous MCTs and in connective tissue and mucosal mast cells. In humans and rodents, mast cells express an additional specific protease, carboxypeptidase A3 (CPA3). In this article, we describe CPA3 immunoreactivity in connective tissue, visceral, mucosal, and neoplastic mast cells in dogs. Positive immunolabeling for CPA3 was observed in nonneoplastic mast cells in 20/20 formalin-fixed paraffin-embedded normal tissues (skin, liver, spleen, intestine), and in 63/63 MCTs irrespective of their histological grade. CPA3 protein expression was comparable to that of c-kit in both the nonneoplastic and neoplastic mast cells. Three distinct labeling patterns (membranous, diffuse, and focal cytoplasmic) were observed for CPA3 in MCTs. The focal cytoplasmic labeling pattern was associated with high-grade MCTs staged with the Kiupel 2-tier grading criteria. We propose CPA3 as a novel immunohistochemical marker for canine mast cells in health and disease. [ABSTRACT FROM AUTHOR]

Mast cell tumors (MCTs) are the most common skin tumor of the dog, and accurately predicting their clinical behavior is critical in directing patient therapy, as they range from benign lesions to a fatal systemic disease. Grading is useful for prognosis, but it cannot predict the behavior of all MCTs. We hypothesized that biomarker immunolabeling in tumor tissues would correlate with patient morbidity and mortality. A clinically annotated tissue microarray (TMA) of primary, recurrent, and metastatic (to lymph node) canine dermal and subcutaneous MCTs was created. Some dogs whose MCTs were included in the TMA did not receive adjunctive treatment after surgical excision of the MCT, whereas others were treated with one or a combination of chemotherapy, radiation, or oral toceranib. Immunohistochemistry for beclin-1, an autophagy protein, was performed followed by digital image analysis. Beclin-1 immunolabeling was higher in recurrent tumors (mean H -score 110.8) than primary MCTs (mean H -score 73.5), and highest in lymph node metastases (mean H -score 138.5) with a significant difference in means (P <.001). While beclin-1 level was not prognostic, it was strongly predictive for survival after adjunctive treatment; dogs with high beclin-1-expressing tumors showed poorer survival compared to those with low beclin-1-expressing tumors (HR = 5.7, P =.02), especially in Kiupel high-grade tumors (HR = 16.3, P =.01). Beclin-1 immunolabeling was the only significant predictive factor by multivariable analysis (P =.04). These findings may improve our ability to predict the response to adjunctive therapy. Importantly, these data suggest that autophagy inhibitors may be useful in improving response to treatment for dogs with high-grade MCTs. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Skin tumors are the most frequently diagnosed lesions, of which 7%-21% are mast cell tumors (MCTs). There is a great effort to identify factors that can influence the prospective course of MCTs. Although, the histological grade is considering an important predictor helping to determine the malignancy and metastatic potential of MCTs. Aim: In this study, an epidemiological analysis of risk factors (breed, age, sex, and anatomical site) for dogs having MCTs was evaluated considering the respective MCTs histological grade in comparison to other skin tumors. Methods: The study included 244 dogs affected by cutaneous MCTs from a universe of 1,185 dogs diagnosed with skin tumors. A univariable analysis with Fisher exact test was performed to determine the odds ratios (ORs) with 95% confidence intervals (CIs). Results: Boxers had a higher predisposition to Patnaik's grade I (OR = 5.9, 95% CI 2.648-13.152) and to Kiupel's low-grade MCTs (OR = 2.6, 95% CI 1.539-4.447). Labrador retrievers (OR = 2.1, 95% CI 1.423-3.184), and pugs (OR = 12.9, 95% CI 2.336-70.931) had a predisposition for Patnaik's grade II MCTs and Kiupel's low-grade lesions (OR = 2.3, 95% CI 1.478-3.597; OR = 17.1, 95% CI 3.093-94.377, respectively). French bulldogs had a higher risk to grade III MCTs (OR = 7.9, 95% CI 2.381-26.072). Pit bulls had a predisposition to grade III MCTs and Kiupel's highgrade tumors (OR = 4.4, 95% CI 1.221-16.1 and OR = 4.962, 95% CI 1.362-18.077, respectively). Bull terriers (OR = 12.7, 95% CI 2.098-76.818) presented higher risk for having low-grade MCTs. The perigenital area and trunk exhibit a greater risk for high grading lesion (OR = 6.6, 95% CI 2.679-16.334; OR = 1.9, 95% CI 1.028-3.395, respectively) and the limbs had a predisposition to grade II tumor (OR = 1.6, 95% CI 1.134-2.395). A decreased risk of having MCT was seen in older dogs (from 7-10 years to 11-18 years) compared to that in the reference group (4-6 years). Conclusion: When comparing to canine skin tumors, this study showed a relationship between MCT histological grading and the risk factors, age, breed, and topography of canine MCTs. The variations noted in the clinical presentation of MCTs amongst predisposed dog breeds reinforces the relevance of the genetic background in MCTs carcinogenesis. [ABSTRACT FROM AUTHOR]

Abstract Background Traditionally, wide lateral surgical margins of 3 cm and one fascial plane deep have been recommended for resection of canine cutaneous mast cell tumor (MCT). Several studies have been published assessing surgical margins of less than this traditional recommendation. The objective of this systematic review was to determine if resection MCT with lateral surgical margins

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.

One of the primary objectives of the Oncology Pathology Working Group (OPWG), a joint initiative of the Veterinary Cancer Society and the American College of Veterinary Pathologists, is for oncologists and pathologists to collaboratively generate consensus documents to standardize aspects and provide guidelines for oncologic pathology. Consensus is established through review of relevant peer-reviewed literature relative to a subgroup's particular focus. In this article, the authors provide a critical review of the current literature for grading of canine cutaneous mast cell tumors, suggest guidelines for reporting, and provide recommendations for its clinical interpretation. The article mainly focuses on histologic grading, but relevant information on mitotic count and cytological grading are also discussed. This document represents the opinions of the working group and the authors but does not constitute a formal endorsement by the American College of Veterinary Pathologists or the Veterinary Cancer Society. [ABSTRACT FROM AUTHOR]

Tumor grading is a method to quantify the putative clinical aggressiveness of a neoplasm based on specific histological features. A good grading system should be simple, easy to use, reproducible, and accurately segregate tumors into those with low versus high risk. The aim of this review is to summarize the histological and, when available, cytological grading systems applied in veterinary pathology, providing information regarding their prognostic impact, reproducibility, usefulness, and shortcomings. Most of the grading schemes used in veterinary medicine are developed for common tumor entities. Grading systems exist for soft tissue sarcoma, osteosarcoma, multilobular tumor of bone, mast cell tumor, lymphoma, mammary carcinoma, pulmonary carcinoma, urothelial carcinoma, renal cell carcinoma, prostatic carcinoma, and central nervous system tumors. The prognostic relevance of many grading schemes has been demonstrated, but for some tumor types the usefulness of grading remains controversial. Furthermore, validation studies are available only for a minority of the grading systems. Contrasting data on the prognostic power of some grading systems, lack of detailed instructions in the materials and methods in some studies, and lack of data on reproducibility and validation studies are discussed for the relevant grading systems. Awareness of the limitations of grading is necessary for pathologists and oncologists to use these systems appropriately and to drive initiatives for their improvement. [ABSTRACT FROM AUTHOR]

The study aimed at morphological and immunohistochemical analysis of 53 mast cell tumors in dogs. Immunohistochemical studies included determination of cell markers for CD2, CD25, mast cell tryptase and mast cell chymase in canine MCTs and comparison of their expression levels with parameters of malignancy (grade, mitotic index, Ki-67 labelling index and CD117 staining pattern). Patnaik grading system identified 20 dogs with grade I MCTs, 17 with grade II and 16 with grade III. According to Kiupel grading, 34 dogs had low-grade MCT and 19 high-grade tumors. Mitotic index was between 0 and 2.4 (mean 0.4). The CD2 expression was high in 32 of 53 cases, CD25 in 20, tryptase in 44, and chymase in 15. The Ki-67 labelling index ranged between 0 and 55% (mean 11%). Majority of MCTs revealed the second staining pattern of CD117 (n=21). We found that expression of CD2 is linked with tumor malignancy, while CD25 determined tumor development. The tumor division into MCTT and MCTTC may be used as prognostic factor. MCT tryptase positive and chymase positive are less malignant than tryptase positive and chymase negative ones. [ABSTRACT FROM AUTHOR]

Copyright of Revista Brasileira de Reprodução Animal is the property of Revista Brasileira de Reproducao Animal and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Clinical staging is a fundamental step in the clinical assessment of canine cutaneous mast cell tumor (cMCT), and it is recommended to evaluate the tumor draining lymph node (eTDLN), perform diagnostic imaging, and fine needle aspiration (FNA) of the spleen and liver to determine the presence of metastatic disease, thereby refining the prognosis. The aim of this retrospective study was to evaluate the prevalence of splenic and hepatic involvement in newly diagnosed canine low-grade cMCT (Patnaik grade I–II, Kiupel low-grade). Medical records of dogs that underwent a clinical staging work-up and surgical excision for a low-grade cMCT between December 2019 and December 2021 were reviewed at five veterinary centers. Only dogs with a histological diagnosis of low-grade cMCT, FNA or histology of the eTDLN, FNA of the spleen and liver, and one year of follow up were included. One hundred and thirty-six dogs met the inclusion criteria. Only 1 out of 136 dogs (0.7%) had the presence of visceral metastases at diagnosis, suggesting that the prevalence of visceral metastases in low-grade cMCT is extremely low. The results of this study are consistent with previous literature and suggest that after a diagnosis of low-grade cMCT, cytology of visceral organs may not represent an essential step in the clinical staging work-up.

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

Mast cell tumors (MCTs) are well-known neoplasms derived from either mucosal or connective tissue mast cells. While well studied in several domestic species, MCTs are rarely documented in rodents. A three-year-old, male African dormouse (Graphiurus sp.) presented with a history of vomiting and anorexia for 3 months. Sonography revealed thickened gastric mucosa and hyperperistalsis. The patient died after receiving symptomatic treatment for 2 months. At necropsy, locally extensive, pale, thickened mucosal foci obscuring the first half of the stomach lumen was noted. Histological examination revealed moderately polymorphic, round, oval to spindle cells with amphophilic cytoplasmic granules infiltrating the mucosa to tunica muscularis, with moderate numbers of eosinophils. The mucosa was severely ulcerated with the proliferation of granulation tissue. The granules in most tumor cells exhibited metachromasia with the toluidine blue stain. Neoplastic cells revealed positive membranous immunoreactivity to KIT. Herein, we report the first case report of MCT in dormouse but also the first gastrointestinal MCT in a rodent species.

Cutaneous round cell tumors in goats present a diagnostic challenge. In this article, we provide a description of caprine cutaneous mast cell tumors (MCT) and histiocytomas, and report on the validation of anti-human antibodies to CD117/KIT and Iba1 by immunohistochemistry on a range of caprine tissues. Cells immunolabeled for CD117/KIT included resident mast cells in normal lung and skin, interstitial cells of Cajal (intestine), and neuronal cell bodies (brain). Cells immunolabeled for Iba1 included resident macrophages in many tissues including normal lung, dendritic cells (hemolymphatic tissues), Kupffer cells, and microglia. Of 5 cutaneous MCT, only one had metachromasia of cytoplasmic granules; however, neoplastic cells of all 5 MCT had positive immunolabeling for CD117/KIT. The CD117/KIT immunolabeling pattern was predominately focal paranuclear in 3 cases, and cytoplasmic or membranous in 1 case each. Two histiocytomas were identified and had strong positive immunolabeling for Iba1 but not CD117/KIT. All 7 cutaneous round cell tumors described herein occurred in goats less than 4 years of age; the 2 cutaneous histiocytomas were in goats less than 14 months of age. Neither of the cutaneous histiocytomas recurred within 24 months of surgical removal. [ABSTRACT FROM AUTHOR]

Canine cutaneous mast cell tumors (ccMCTs) are currently graded according to Patnaik and Kiupel grading schemes. The qualitative and semiquantitative parameters applied in these schemes may lead to inter- and intraobserver variability. This study investigates the prognostic value of volume-weighted mean nuclear volume ( v v ¯ ), a stereological estimation that provides information about nuclear size and its variability. v v ¯ of 55 ccMCTs was estimated using the "point-sampled intercept" method and compared with histological grade and clinical outcome. The clinical history of dogs treated with surgical excision alone was available for 30 ccMCTs. Statistical differences in v v ¯ were found between grade II ( x ¯ = 115 ± 29 µm3) and grade III ccMCTs ( x ¯ = 197 ± 63 µm3), as well as between low-grade ( x ¯ = 113 ± 28 µm3) and high-grade ccMCTs ( x ¯ = 184 ± 63 µm3). An optimal cutoff value of v v ¯ ≥ 150 µm3 and v v ¯ ≥ 140 µm3 was determined for grade III and high-grade ccMCTs, respectively. In terms of prognosis, v v ¯ was not able to predict the clinical outcome in 42% of the cases; however, cases with v v ¯ <125 µm3 had a favorable outcome. These results indicate that, despite having limited prognostic value when used as a solitary parameter, v v ¯ is highly reproducible and is associated with histological grade as well as with benign behavior. [ABSTRACT FROM AUTHOR]

Background: Nephrotic syndrome (NS) is rare in dogs and is characterized by concurrent clinical findings of proteinuria, hyperlipidemia, hypoalbuminemia, and edema. NS has been reported in humans receiving tyrosine kinase inhibitors (TKI) and in dogs receiving masitinib. This is the first report of NS in a dog receiving toceranib phosphate. Case presentation: An 8-year-old, female, spayed Labrador retriever was diagnosed with a 10 cm mast cell tumor on the left lateral abdomen. After completion of a 12-week vinblastine and prednisone protocol, she began treatment with toceranib phosphate (2.6 mg/kg by mouth, every other day). Proteinuria was documented prior to starting toceranib. On day 426 after diagnosis (day 328 of toceranib phosphate treatment), the dog was evaluated for diarrhea, lethargy and anorexia. On physical examination, dependent edema was noted on the ventral chest and abdomen, and sterile neutrophilic inflammation was aspirated from a 2.3 cm splenic nodule. The following laboratory values were reported: albumin < 1.5 g/dL; cholesterol 378 mg/dl and urine protein to creatinine ratio of 3.79. The patient was diagnosed with NS, and treatment with toceranib phosphate was discontinued. Low-dose aspirin was started in addition to an increased dosage of enalapril (0.47 mg/kg q12hr). No other therapy was instituted. The dog improved clinically, and laboratory values returned to near normal over the 8-week follow-up. She was euthanized 1399 days after discontinuing toceranib phosphate with progressive disease. Conclusions: Nephrotic syndrome is a potential adverse event associated with the drug toceranib phosphate which may be reversible with discontinuation of treatment. Careful monitoring of urine protein, serum biochemistry, blood pressure and patient weight is advisable during treatment with toceranib phosphate. [ABSTRACT FROM AUTHOR]

Neutering (including spaying) of male and female dogs in the first year after birth has become routine in the U.S. and much of Europe, but recent research reveals that for some dog breeds, neutering may be associated with increased risks of debilitating joint disorders and some cancers, complicating pet owners' decisions on neutering. The joint disorders include hip dysplasia, cranial cruciate ligament tear or rupture, and elbow dysplasia. The cancers include lymphoma, mast cell tumor, hemangiosarcoma, and osteosarcoma. In previous studies on the Golden Retriever, Labrador Retriever and German Shepherd Dog, neutering before a year of age was associated with increased risks of one or more joint disorders, 2–4 times that of intact dogs. The increase was particularly seen with dogs neutered by 6 months of age. In female Golden Retrievers, there was an increase in one or more of the cancers followed to about 2–4 times that of intact females with neutering at any age. The goal of the present study was to expand and use the same data collection and analyses to cover an additional 29 breeds, plus three varieties of Poodles. There were major breed differences in vulnerability to neutering, both with regard to joint disorders and cancers. In most cases, the caregiver can choose the age of neutering without increasing the risks of these joint disorders or cancers. Small-dog breeds seemed to have no increased risks of joint disorders associated with neutering, and in only two small breeds (Boston Terrier and Shih Tzu) was there a significant increase in cancers. To assist pet owners and veterinarians in deciding on the age of neutering a specific dog, guidelines that avoid increasing the risks of a dog acquiring these joint disorders or cancers are laid out for neutering ages on a breed-by-breed and sex basis.

Glucocorticoid administration is a common clinical practice that attempts to decrease the inflammation associated with and improve the resectability of canine mast cell tumors (MCTs). However, the impact of neoadjuvant glucocorticoids on the histological features and proliferation indices of canine MCTs is unknown. The objective of this study was to evaluate changes in tumor grade, mitotic count, Ki67, AgNOR, and AgNORxKi67 scores following short-course anti-inflammatory neoadjuvant prednisone in canine patients with MCTs. This was a prospective single-arm pilot study. Client-owned dogs with treatment-naïve cytologically confirmed MCTs were enrolled. Patients underwent an initial incisional biopsy followed by a 10–14-day course of anti-inflammatory prednisone and surgical resection. All histological samples were randomized, masked, and evaluated by a single pathologist. Unstained paired pre- and post-treatment samples were submitted to a commercial laboratory for Ki67 and AgNOR immunohistochemical analysis. There were 11 dogs enrolled with 11 tumors. There were no statistical differences between the pre- and post-treatment histological parameters of mitotic index, Ki67, AgNOR, or Ki67xAgNOR. There were no clinically significant alterations between pre-treatment and post-treatment in the assignment of tumor grades. A short course of anti-inflammatory prednisone does not appear to alter the histological parameters that affect grade determination or significantly alter the proliferation indices in canine MCTs.

Copyright of Summa, Animali da Compagnia is the property of Point Veterinaire Italie s.r.l. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Canine cutaneous mast cell tumors (ccMCTs) have a highly variable biological behavior and accurate prognostication is essential for therapeutic intervention. Internal tandem duplications (ITD) of exon 11 are the most commonly detected c-kit mutation in ccMCTs and are associated with poor prognosis and increased cellular proliferation. The prognostic value of detecting mutations in other exons of c-kit has not been systematically examined. In this study, we analyzed the prognostic value of ITD mutations of exon 8 in c-kit of ccMCTs in comparison to ccMCTs with ITD mutations of exon 11 and ccMCTs without mutations of exon 8 or 11. The mutational status, histological grade, KIT expression pattern, Ki67 index, AgNOR (argyrophilic nucleolar organizing region) score, and Ag67 score were determined in 221 ccMCTs, and outcome was available for 101 dogs. ITD mutations of exon 8 were found in 73/221 (33%), of exon 11 in 100/221 (45%), and none of these mutations in 50/221 (22%) of ccMCTs. None of the dogs with mutations of exon 8 died due to suspected ccMCT-related cause, but 23% dogs with ccMCTs with mutations of exon 11 died due to suspected ccMCT-related cause. Prognostic parameters in ccMCTs with exon 11 mutations were commonly associated with a high proliferative activity and poor prognosis, while prognostic markers in ccMCTs with mutations of exon 8 had lower values similar to those observed in ccMCTs without mutations in exons 8 or 11 of c-kit. This study indicates that screening for ITD mutations in exon 8 in ccMCTs may be helpful to identify less aggressive ccMCTs and may be recommended as a supplementary prognostic test. [ABSTRACT FROM AUTHOR]

We evaluated the postsurgical outcomes of cutaneous or subcutaneous mast cell tumors (MCTs, n=25) in 23 dogs, resected with lateral surgical margins proportional to the widest tumor diameter, including at least one facial plane. The tumor diameter range was 0.3-2.6 cm (median: 0.9 cm), and all were histologically diagnosed as Kiupel's low-grade MCT. Resection was histologically complete in 20, close (deep margin) in three, and incomplete (deep margin) in two. No dogs developed local recurrence at the site of initial surgery during follow-up of 161-2,219 days (median: 976 days). These results suggest that resection of low-grade, relatively small MCTs with surgical margins proportional to the tumor diameter is a practical procedure with high success rates. [ABSTRACT FROM AUTHOR]

Mast cell tumors (MCTs) are the most common skin tumors in dogs. Laboratory diagnosis of MCTs has been established by many techniques. The dyes generally used for tissue staining, including MCTs, are synthetic dyes, however, the global interest in using eco-friendly natural dye has become a significant matter. We focused on the butterfly pea (Clitoria ternatea L.) which is locally available. Limited studies are known about their efficacy as a tissue stain. The aim of this study was to investigate the staining ability of butterfly pea flower extract in cytological canine MCTs. The dried petals were ground into powder and dissolved in acidified ethanol to obtain the crude extraction. After filtration, this was added with mordant, 2.5% aluminium chloride, before staining. The methanol-fixed cytological samples of diagnosed MCTs were stained with the dye extract for 30 minutes, washed with distilled water and observed under light microscope initially, and after the counterstaining, with hematoxylin. The slides were stained with Giemsa, Toluidine blue and Diff-Quick stains to compare with the dye extract. The other round cell tumors including canine transmissible venereal tumor (TVT) and melanoma were also stained with the dye extract to compare with the MCTs. The results revealed a bright pink color specifically stained in the MCT granules. However, Giemsa, Toluidine blue and Diff-Quick staining shown their specific stain colors in the granules in larger numbers. The dye extract staining was not detected in either TVT or melanoma. Improvement of the dye extraction and staining conditions may provide additional staining outcomes, thus it may be possible to serve as an alternative natural dye for future application in cytological canine MCT diagnostics. [ABSTRACT FROM AUTHOR]

Tumors of mesenchymal origin are rarely reported in the pancreas. Therefore, this study characterized 17 feline non-epithelial pancreatic tumors, including clinical data, histopathology, and immunohistochemistry. Seventeen feline pancreatic tissue samples were investigated histopathologically and immunohistochemically. Selected pancreatic and inflammatory serum parameters, e.g., feline pancreatic lipase immunoreactivity (fPLI), 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(60-methylresorufin) ester (DGGR) lipase and serum amyloid A (SAA), were recorded, when available. The neoplasms were characterized as round (n = 13) or spindle (n = 4) cell tumors. Round cell tumors included 12 lymphomas and one mast cell tumor in ectopic splenic tissue within the pancreas. Lymphomas were of T-cell (n = 9) or B-cell (n = 3) origin. These cats showed leukocytosis (3/3) and increased fPLI (5/5), DGGR lipase (3/5) and SAA(4/5) values. Spindle cell tumors included two hemangiosarcomas, one pleomorphic sarcoma and one fibrosarcoma. The cat with pleomorphic sarcoma showed increased SAA value. Overall survival time was two weeks to seven months. These are the first descriptions of a pancreatic pleomorphic sarcoma and a mast cell tumor in accessory spleens within feline pancreas. Although rare, pancreatic tumors should be considered in cats presenting with clinical signs and clinical pathology changes of pancreatitis. Only histopathology can certainly distinguish solitary pancreatitis from a neoplasm with inflammation. [ABSTRACT FROM AUTHOR]

Mast cell tumors (MCTs) are common neoplasms in dogs, and treatments for these diseases include surgery, polychemotherapy and targeted therapy with tyrosine kinase inhibitors. This study aimed to evaluate the response and the adverse events of treatment with imatinib mesylate (IM) compared to conventional therapy using vinblastine and prednisolone (VP) in canine cutaneous MCTs. Twenty-four dogs were included in the study; 13 animals were treated with IM and 11 with VP. Tumor tissue samples were submitted for histological diagnosis, grading and KIT immunostaining. The response to treatment was assessed by tomographic measurements according to VCOG criteria. Adverse events were classified according to VCOG-CTCAE criteria. The IM and VP groups had dogs with similar breeds, gender, ages, MCT localization, WHO stages and lymph node metastasis profiles. Most MCTs were grade 2/low and had KIT- patterns 2 and 3. The objective response rate (ORR) was significantly higher (30.79%) in the IM group then in VP group (9.09%). Adverse events (AE) in IM group were all grade 1, significantly different from VP. In conclusion, IM presented better ORR and less severe adverse events when compared to VP, representing a suitable option for the treatment of low-grade canine MCTs.

Mast cell tumors (MCTs) are hematopoietic neoplasms composed of mast cells. It is highly common in dogs and is extremely important in the veterinary oncology field. It represents the third most common tumor subtype, and is the most common malignant skin tumor in dogs, corresponding to 11% of skin cancer cases. The objective of this critical review was to present the report of the 2nd Consensus meeting on the Diagnosis, Prognosis, and Treatment of Canine Cutaneous and Subcutaneous Mast Cell Tumors, which was organized by the Brazilian Association of Veterinary Oncology (ABROVET) in August 2021. The most recent information on cutaneous and subcutaneous mast cell tumors in dogs is presented and discussed.

The study was aimed to characterize tumor response after combined treatment employing electrochemotherapy with IL-12 gene electrotransfer in dogs with spontaneous mast cell tumors (MCT).

Mast cell tumor (MCT) is the most common cutaneous neoplasm in dogs and wide surgical resection is the current first-line treatment. However, recurrence is common and often requires more specialist and expensive therapies. Tigilanol tiglate is a novel small molecule drug delivered by intratumoral injection that is currently under development to provide a new option for treating MCT. The aim of this study was to characterize a safe and effective dose of tigilanol tiglate for canine MCT and to gather preliminary data on the drug's pharmacokinetics. A multicenter, open-label, uncontrolled, non-randomized, dose de-escalation design was used. Eligibility was MCT stage I/IIa and a tumor size of 0.1–6.0 cm3. Dosing was based on tumor size (50% v/v tumor) and 3 drug concentrations (1.0, 0.5, 0.2 mg/mL) were evaluated. Twenty-seven dogs were treated in 3 dose de-escalation cohorts (10, 10, and 7 dogs, respectively). Efficacy at 21 days was defined using international accepted solid tumor response criteria (RECIST). Greatest efficacy (90% complete response) was observed at the highest drug concentration (1.0 mg/mL) and adverse events were generally low grade, mild and transient, and directly associated with the mode of action of the drug. Hematological and serum biochemistry were generally unremarkable with plasma concentration curves typical of a non-intravenous parenteral medication. Intratumoral treatment of MCT with tigilanol tiglate at a concentration of 1.0 mg/mL was highly efficacious and well-tolerated. These results support the drug's further development for the treatment of MCT and other solid tumors.

New knowledge and data can influence the treatment options of dogs and cats affected by neoplasms. Partial limb amputation with the use of a prosthesis is possible in dogs. Newer studies attempt to define better and understand the complications and limb function associated with this approach. Limb sparing is an alternative to amputation, and three-dimensional printing allows the manufacturing of personalized endoprostheses. Finally, the recommended approach for the excision of cutaneous mast cell tumors (MCTs) is with proportional margins. In dogs, grade shifting might have occurred when removing a recurrent MCT or soft tissue sarcoma., Competing Interests: Disclosure B. Séguin has no commercial or financial conflict of interest to disclose. J.M. Liptak is on the board of QBiotics Group., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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 > 3 cm and subcutaneous MCT.

One of the potential mechanisms underlying acquired resistance to toceranib in canine mast cell tumor (MCT) is the emergence of a secondary mutation in the KIT gene. Here, genetic alterations of KIT during clonal expansion and subsequent acquisition of resistance to toceranib were investigated in the toceranib‐susceptible canine MCT cell line VI‐MC, which carries a KIT‐activating mutation resulting in a predicted p.(Asn508Ile) amino acid change in the receptor tyrosine kinase protein KIT. Two sublines were cloned from VI‐MC and toceranib‐resistant sublines then were established by continuous exposure to toceranib. The mutation status of KIT in parental VI‐MC and its sublines was investigated using next‐generation sequencing (NGS). Additionally, effects of secondary mutations on toceranib sensitivity in p.(Asn508Ile)‐mutant KIT were examined. KIT secondary mutations, including those encoding p.(Asn679Lys)‐, p.(Asp819Val)‐, and p.(Asp819Gly)‐mutant KIT, that confer toceranib insensitivity to p.(Asn508Ile)‐mutant KIT emerged only in toceranib‐resistant VI‐MCs. These mutations were not detected by NGS in the parental VI‐MC line or in the toceranib‐naive cloned VI‐MCs, although the parental line and sublines exhibited genetic heterogeneity in KIT that may have been caused by genetic evolution during clonal expansion. VI‐MC clones with these secondary mutations in KIT appear to have arisen from subclones during treatment with toceranib rather than being pre‐existing. However, further study using a higher resolution technique will be needed to confirm the developmental mechanism of KIT secondary mutation in canine MCT cells with acquired resistance to toceranib. [ABSTRACT FROM AUTHOR]

Although reovirus has reached phase II and III clinical trials in human cancers, the exact mechanism of reovirus oncolysis is still not completely understood. Previously, we have shown that canine mast cell tumor (MCT) cell lines were highly susceptible to reovirus, as compared with other kinds of canine cancer cell lines. In this study, we showed that reovirus infection not only led to the dephosphorylation but also downregulation of c-kit in four canine MCT cell lines, where c-kit activation is required for proliferation. Consistent with c-kit dysregulation, downstream signaling of c-kit, the level of Ras-GTP and phosphorylation of all the downstream effectors of Ras (Raf, MEK, and ERK) and Akt decreased in all the cell lines after reovirus infection, except for Akt in one of cell lines. Pro-apoptotic and anti-apoptotic proteins such as Bim, Bad and Mcl-1 were also altered by reovirus infection in these cell lines. In short, reovirus infection degraded c-kit in all the canine MCT cell lines, leading to the downregulation of downstream signaling of c-kit, which may relate to the cell death induced by reovirus. • C-kit is degraded after reovirus infection in canine mast cell tumor cell lines. • Ras/Raf/MEK/ERK and Akt pathway are downregulated after reovirus infection. • Phospho-Bad and Mcl-1 are regulated after reovirus infection. [ABSTRACT FROM AUTHOR]

DNA amplification by PCR detects KIT exon 11 internal tandem duplications in canine mast cell tumors (MCTs). Tissue-specific inhibitors often contaminate DNA extracted from formalin-fixed, paraffin-embedded (FFPE) canine MCTs, blocking PCR amplification and, consequently, preventing mutation detection. We used a commercial kit to extract DNA from FFPE canine MCTs. Two independent PCR assays, each with one primer set, were used to amplify target genes (HPRT and KIT) directly after FFPE DNA extraction. PCR amplification failed with at least one primer set in 153 of 280 samples (54.6%, 95% CI: 48.8–60.5%). One or 2 DNA washing steps were required to remove PCR inhibitors in 130 of 280 (46.4%) and 23 of 280 (8.2%) of these cases, respectively. DNA concentration and quality (A260/A280 and A260/A230) either pre- or post-washing were not associated with ability of the samples to be amplified by PCR using both HPRT and KIT primer sets. Low-grade and subcutaneous MCTs were less likely to amplify directly after DNA extraction and without any washing steps compared to high-grade MCTs using KIT gene primers. [ABSTRACT FROM AUTHOR]

In this article, diffuse splenic enlargement, its etiology and diagnostics are presented and discussed. Often without clinical signs, it may be palpated during an examination, through the abdominal wall in dogs and cats. Diffuse splenomegaly may be caused by neoplastic or non-neoplastic pathological changes. Diffusely enlarged spleen may accompany some neoplasms, like visceral mast cell tumor in cats or high-grade multicentric lymphoma in dogs. Primary splenic lymphomas account for only 10% of lymphomas in dogs, leading in most cases to multiple nodular lesions and only 20% of them manifest as diffuse splenomegaly. Non-neoplastic diffuse splenomegaly may also result from inflammation (splenitis) caused by viral, bacterial, fungal or parasitic infection or from congestion, mainly as an effect of systemic diseases. [ABSTRACT FROM AUTHOR]

Histopathological examination, grading, immunohistochemical staining and molecular genetic examinations are the proposed criteria that should be used for cutaneous mast cell tumors (CMCTs) classification. The presence of aberrant CD117 expression and mutations of the c-kit proto-oncogene could be an indicative parameter for final histological grading. Determination of the connection between the localization of KIT receptor expression and the histological grade of CMCTs without c-kit proto-oncogene mutations was the main goal of this study. The study included twenty four CMCTs and six control skin samples from 30 dogs of different ages, breed and sex. Formalinfixed and paraffin-embedded tissue samples were stained with hematoxylin-eosin and toluidine blue and immunohistochemically tested for CD117 expression. DNA was extracted from the same paraffin blocks and subsequent polymerase chain reaction amplification was performed using PE1 and PE2 primers. Degree of malignancy was determined based on the presence of mitotic figures, multinucleated cells, bizarre nuclei and karyomegaly in 10 high power fields. Based on histological features, fourteen of 24 CMCTs were of a high histological grade, while ten were classified as a lowgrade malignancy. CD117 cytoplasmic expression was observed in nine of fourteen high-grade malignancy CMCTs, which confirms the link between the aberrant CD117 expression and increased cell proliferation.

Tumors of mesenchymal origin are rarely reported in the pancreas. Therefore, this study characterized 17 feline non-epithelial pancreatic tumors, including clinical data, histopathology, and immunohistochemistry. Seventeen feline pancreatic tissue samples were investigated histopathologically and immunohistochemically. Selected pancreatic and inflammatory serum parameters, e.g., feline pancreatic lipase immunoreactivity (fPLI), 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6′-methylresorufin) ester (DGGR) lipase and serum amyloid A (SAA), were recorded, when available. The neoplasms were characterized as round (n = 13) or spindle (n = 4) cell tumors. Round cell tumors included 12 lymphomas and one mast cell tumor in ectopic splenic tissue within the pancreas. Lymphomas were of T-cell (n = 9) or B-cell (n = 3) origin. These cats showed leukocytosis (3/3) and increased fPLI (5/5), DGGR lipase (3/5) and SAA (4/5) values. Spindle cell tumors included two hemangiosarcomas, one pleomorphic sarcoma and one fibrosarcoma. The cat with pleomorphic sarcoma showed increased SAA value. Overall survival time was two weeks to seven months. These are the first descriptions of a pancreatic pleomorphic sarcoma and a mast cell tumor in accessory spleens within feline pancreas. Although rare, pancreatic tumors should be considered in cats presenting with clinical signs and clinical pathology changes of pancreatitis. Only histopathology can certainly distinguish solitary pancreatitis from a neoplasm with inflammation.

Background: Canine mastocytomas (mast cell tumors) represent a common malignancy among many dog breeds. A typical treatment strategy for canine mastocytomas includes surgery, chemo- and radio-therapy, although in many cases the therapy fails and the disease progression resumes. New treatment approaches are needed.Aims: The goal of this pilot study was to examine safety and efficacy of oncolytic Sendai virus therapy administered to canine patients with cutaneous or subcutaneous mastocytomas.Materials and Methods: Six canine patients, with variable grades and stages of the disease, received virus therapy, either as a monotherapy, or in combination with surgery. The therapy included two or more virus applications administered weekly or biweekly. Each application of Sendai virus (107-108.6 EID50) consisted of multiple individual 0.01–0.1 ml injections delivered intratumorally, intradermally around a tumor, and under a tumor bed.Results: The treatment was well tolerated, with minor transitory side effects. Of the six dogs, two did not receive surgery or any other treatment besides the virus injections. The other four animals underwent radical or debulking surgeries, and in three of them the subsequent administration of Sendai virus completely cleared locally recurrent or/and remaining tumor masses. Five dogs demonstrated a complete response to the treatment, the animals remained disease free during the time of observation (2–3 years). One dog responded only partially to the virotherapy; its after-surgical recurrent tumor and some, but not all, metastases were cleared. This dog had the most advanced stage of the disease with multiple enlarged lymph nodes and cutaneous metastases.Conclusion: The results of the pilot study suggest that Sendai virus injections could be safe and efficient for the treatment of dogs affected by mastocytomas.They also suggest the need of further studies for finding optimal schemes and schedules for this kind of therapy.

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

Highlights • Flow cytometry (FC) immunophenotypic analysis was used to characterize canine mast cell tumors. • Draining lymph nodes (LN) were also assessed for mast cell infiltration. • FC was able to identify both mast cells and eosinophils in the tumor and to detect and quantify mast cells in LNs. Abstract Mast cell tumors (MCT) are among the most frequent tumors in dogs, but studies regarding canine mast cell immunophenotype are lacking. The aim of this study was to assess the feasibility of flow cytometric analysis of MCTs, to describe canine MCTs immunophenotype(s), and to evaluate the ability of flow cytometry to detect mast cells in lymph node aspirates. Thirty-four primary canine MCTs and 12 draining lymph nodes were evaluated regarding the expression of CD117, IgE, CD11b, CD18, CD44, CD34, CD25 and CD45. Distinct populations attributable to mast cells and eosinophils were recognized based on light scatters and CD117 positivity. Common antigens (CD18, CD45, CD44) and CD117 were detected in all cases; positivity for IgE and CD11b was found in 28 (82%) and 23 (68%) cases respectively, while CD34 and CD25 were occasionally expressed. A single multicolor tube (IgE/CD117/CD11b/CD21/CD5) allowed the identification of mast cells in lymph nodes, showing a high correlation with cytology in quantifying mast cells infiltration. In conclusion, flow cytometric analysis can be applied to characterize canine MCTs and can be used to detect the presence of mast cells in lymph nodes. The immunophenotype abnormalities observed may be useful to confirm the neoplastic nature of such mast cells but the diagnostic usefulness of atypical antigen expression remains to be clarified. [ABSTRACT FROM AUTHOR]

Background: No biomarkers for the early detection of gastrointestinal (GI) toxicosis secondary to antineoplastic treatment are recognized in veterinary medicine. Toceranib causes GI toxicosis in dogs. Hypothesis/Objective: To assess if changes in plasma cytokeratin 18 (CK18) concentration, measured in dogs being treated with toceranib phosphate, can predict the onset of GI toxicosis. We hypothesize that an increase in CK18 concentrations will be detected before the development of GI toxicosis in dogs treated with toceranib phosphate. Animals Twenty healthy client‐owned dogs and 25 client‐owned dogs with surgically excised mast cell tumor (MCT). Methods: Prospective cohort study. Dogs were treated with toceranib (2.75 mg/kg PO q48h). Plasma was collected weekly for 4 weeks. Plasma CK18 concentration was measured on days 0, 7, 14, 21, and 28. vascular endothelial growth factor was measured on days 0 and 28. Results: Mean plasma CK18 concentration on day 0 in dogs with MCT was not significantly different than healthy controls (313.5 ± 592.8 pg/mL, 119.7 ± 76.9 pg/mL, mean ± SD P = 0.27). Mean plasma CK18 concentration decreased by 98.69 pg/mL from day 0 to day 28 (P < 0.001). Plasma CK18 concentration was not a significant predictor of the development of signs of GI toxicosis. Conclusions and Clinical Importance: Plasma CK18 concentration was not a clinically useful biomarker for the early detection of GI toxicosis secondary to toceranib administration in dogs with MCTs. [ABSTRACT FROM AUTHOR]

Mast cell tumors (MCTs) are one of the most common neoplasms in dogs. They originate from the bone marrow. Several criteria have been proposed for their classification, including histological grading and cell proliferation markers. The mitotic index, multiple nuclei, cells with bizarre nuclei and karyomegaly are the most important parameters for the classification of MCTs on high and low-grade malignancy. For the confirmation of MCT malignancy grade it is also important to determine the expression of the transmembrane kinase (KIT) receptor that has a significant role in the growth and differentiation of mast cell tumors. In high-grade malignancy MCTs in addition to membrane expression of the KIT receptor, aberrant cytoplasmic expression can be also observed. Fifty-two MCTs and 12 control samples of skin from dogs without MCTs were examined. Routinely processed tissue samples were stained with hematoxylin-eosin. Expression of KIT receptor was tested immunohistochemically. The classification of MCTs on high and low-grade malignancy was performed according to the Kiupel's 2-tier classification and the expression of KIT receptors. Sixteen of 52 MCTs were of a low-grade malignancy, while thirty-six were classified as a high-grade malignancy of which 19 MCTs showed aberrant cytoplasm labelling of KIT receptor. All 16 low-grade malignancy MCTs had only membrane expression of KIT receptor. Most high-grade malignancy MCTs showed cytoplasmic KIT expression indicating the link between aberrant KIT expression and increased cell proliferation. The presence of mitotic figures, multinucleated cells, bizarre nuclei and karyomegaly, as well as KIT receptor expression pattern are the most important prognostic factors in dogs with mast cell tumor. [ABSTRACT FROM AUTHOR]