Mastocytosis in the skin in dogs: A multicentric case series.

Canine cutaneous mastocytosis (CM) is rare in contrast to canine mast cell tumours. In humans, CM commonly affects children and is usually indolent with possible spontaneous resolution. Systemic mastocytosis (SM) with bone marrow involvement typically affects adults, can have a poor outcome, and often includes skin lesions. 'Mastocytosis in the skin' (MIS) is the preferred term of skin lesions, if bone marrow evaluations are not available, which is often the cases in dogs. In human SM and CM, KIT mutations are often detected. The veterinary literature suggests clinical resemblances between human and canine MIS, but data is limited, and KIT mutations are rarely assessed. This retrospective study describes clinicopathological findings, treatment and outcome of 11 dogs with suspected MIS. Dogs with multiple mast cell tumours were excluded. Histopathology reports (n = 5) or slides (n = 6) were reviewed. KIT mutation analysis including exons 8, 9, 11, 14 and 17 were analysed in eight dogs. Median age at diagnosis was 4 years (range, 1-12). Typical clinical signs included multifocal to generalised nodules and papules. Histologically, skin lesions were characterised by dermal infiltration of well-differentiated mast cells. KIT mutations were detected in 3/8 dogs (exon 9: n = 2; exon 11: n = 1). One dog had mastocytaemia suggesting possible SM. Glucocorticoids were mostly successful with lesion improvement in all treated dogs (n = 8). This cohort highlights resemblances between human and canine MIS. Further studies are required to confirm these findings and establish diagnostic criteria for CM and MIS associated with SM in dogs.

Evaluation of Ki67, Bax, Bcl-2 and KIT in canine cutaneous mast cell tumours and their relationship with histopathology and prognosis.

Canine cutaneous mast cell tumours (CCMCTs) are common in dogs and exhibit many unpredictable behaviors. This study aimed to encourage pathology laboratories in developing countries to routinely assess prognosis by applying commonly used histopathological grading systems and immunohistochemistry (IHC) markers. We performed histological grading according to both the Patnaik and Kiupel systems, determined the mitotic count (MC) and carried out IHC for the detection of Ki67, Bax, Bcl-2 and KIT in 54 CCMCT cases. MC was associated with both grading systems in terms of survival following diagnosis and prognostic factors differed among cases categorized by the cut-off value of 5. KIT patterns were associated with grading systems and MC. The cohort with pattern II had a lower survival rate than those with patterns I and III. Ki67 was associated with survival when evaluated over the cut-off value of 0.018. Bax expression was associated with both grading systems. Median survival time was longer in patients with lower Bax expression level. Immunohistochemical detection of KIT, Ki67 and Bax improves histopathology in predicting the prognosis. If IHC is unavailable, reports regarding MC and values from both grading systems are the most effective, convenient and cost-effective way to provide the most reliable prognostic data and guidance for the clinicians.

Cutaneous mastocytosis in 8 young dogs and review of literature.

Cutaneous mastocytosis (CM) is a rare condition in young dogs characterized by multicentric cutaneous proliferation of neoplastic mast cells. Clinical data from 8 dogs that met inclusion criteria (age of onset less than 1.5 years, greater than 3 lesions) were obtained via a standardized survey. Biopsy samples were classified by the Kiupel/Patnaik grading systems and analyzed for c-KIT mutations. The median age of onset was 6 months (range: 2-17 months). Dogs had 5 to more than 50 lesions characterized as nodules, plaques, and papules. Seven dogs were pruritic. Clinical staging in 2 dogs did not reveal visceral involvement. No dogs had systemic illnesses at diagnosis. Histologically, CM was similar to cutaneous mast cell tumor (cMCT). Two dogs had neoplasms classified as high-grade/grade II while 6 dogs had low-grade/grade II neoplasms. No dogs had mutations in c-KIT exons 8 and 11. Treatment included antihistamines (8/8), corticosteroids (7/8), lokivetmab (3/8), and toceranib (1/8). Six dogs were alive with lesions at the end of the study with a median follow-up time of 898 days, while 2 dogs were euthanized. In dogs with high-grade/grade II neoplasms, one continued to develop lesions at 1922 days post-diagnosis, while the other dog was euthanized at 56 days post-diagnosis. One dog was euthanized 621 days post-diagnosis due to rupture of a neoplasm. CM occurs in young dogs and is histologically indistinguishable from cMCT. Current histologic grading systems did not apply uniformly to the dogs of the study and further studies are needed.

Comparison of serum tryptase as a diagnostic oncological marker in canine versus human mast cell neoplasms.

Canine mast cell tumors (MCTs) are a promising translational model for human mast cell neoplasms with striking similarities such as the Darier's sign and mutations in the KIT gene. Whereas mast cell neoplasms are rare in humans, MCTs are the most frequent malignant neoplasms of the skin in dogs. In human systemic mastocytosis, serum tryptase is an important diagnostic criterion. Surprisingly, serum tryptase levels were not yet investigated in dogs with MCTs. Therefore, the aim of this study was to investigate whether serum tryptase levels in dogs with cutaneous MCTs were elevated compared to those of a non-MCT control group. As a secondary aim, it was investigated whether surgical manipulation caused an increase in serum tryptase in canine MCT patients. A total of 48 serum samples were collected from dogs with different grades of cutaneous MCTs (n = 24) and non-MCT controls (n = 24). In dogs with cutaneous MCTs, blood was collected prior to and within 1 h after surgery. Serum tryptase levels were measured using a commercially available canine-specific ELISA kit. No significant difference in serum tryptase levels was found between cutaneous MCT patients and non-MCT controls, nor in these levels before versus after surgery. Our findings in canine cutaneous MCTs are in accordance with human cutaneous mastocytosis, where serum tryptase levels tend to remain within the normal range. However, despite various similarities between aggressive mast cell tumors in dogs and humans, serum tryptase cannot be considered a diagnostic biomarker in dogs with cutaneous MCTs as part of a comparative oncologic strategy.

A case of cutaneous bullous mastocytosis in a Yorkshire terrier puppy.

BACKGROUND: Cutaneous bullous mastocytosis (CBM) is a rare disease characterised by erythroderma, bullae formation on trunk, scalp and extremities which evolve to erosions. OBJECTIVE: To describe a rare variant of cutaneous mastocytosis and treatment options. ANIMAL: A 7-month-old Yorkshire terrier puppy with erythroderma and bullae formation. METHODS: Clinical examination (including haematological, biochemical and radiographic), skin biopsy, histopathological and immunohistochemical evaluation. CONCLUSION AND CLINICAL RELEVANCE: The case fulfills the criteria of CBM, representing a rare entity that is reported to be associated with spontaneous regression. However, in severe cases treatment with systemic corticosteroids, H1 and H2 antihistamines, and masitinib can be performed.

Contexte - La mastocytose cutanée bulleuse (CBM) est une maladie rare caractérisée par une érythrodermie, la formation de bulles sur le tronc, le cuir chevelu et les extrémités qui évoluent vers des érosions. Objectif - Décrire une variante rare de la mastocytose cutanée et les options de traitement. Animal - Un chiot Yorkshire terrier de 7 mois avec formation d'érythrodermie et de bulles. Méthodes - Examen clinique (y compris hématologique, biochimique et radiographique), biopsie cutanée, évaluation histopathologique et immunohistochimique. Conclusion et pertinence clinique - Le cas remplit les critères de CBM, représentant une entité rare rapportée comme étant associée à une régression spontanée. Cependant, dans les cas graves, un traitement avec des corticostéroïdes systémiques, des antihistaminiques H1 et H2 et du masitinib peut être effectué.

Introducción - la mastocitosis bullosa cutánea (CBM) es una enfermedad rara caracterizada por eritroderma, formación de bullas en el tronco, cabeza y extremidades que evolucionan a erosiones. Objetivo - describir una variante rara de mastocitosis cutánea y opciones de tratamiento. Animal- un cachorro Yorkshire terrier de 7 meses con eritroderma y formación de bullas. Métodos - examen clínico (incluyendo hematológico, bioquímico y radiográfico), biopsia de piel, evaluación histopatológica e inmunohistoquímica. Conclusión y relevancia clínica- el caso descrito cumple con los criterios de CBM, lo que representa una entidad rara que se describe como asociada con regresión espontánea. Sin embargo, en casos graves se puede realizar tratamiento con corticoides sistémicos, antihistamínicos H1 y H2 y masitinib.

Contexto - A mastocitose cutânea bolhosa (MCB) é uma doença rara caracterizada por eritrodermia, formações bolhosas no tronco, cabeça e extremidades que evoluem para erosões. Objetivo - Descrever uma variante rara de mastocitose cutânea e as opções de tratamento. Animal - Um filhote de Yorkshire terrier de sete meses de idade com eritrodermia e formações bolhosas. Métodos - Exame clínico (incluindo avaliação hematológica, bioquímica e radiográfica), biópsia de pele, histopatologia e avaliação imunohistoquímica. Conclusão e relevância clínica - Esse caso preenche os critérios de MCB, representando uma entidade rara em que a regressão espontânea é relatada. Entretanto, em casos graves, tratamento com corticosteroides, anti-histamínicos H1 e H2 e masitinib podem ser realizados.

Canine cutaneous and subcutaneous mast cell tumours: a narrative review.

Cutaneous and subcutaneous mast cell tumours are common neoplasms in the dog. While the majority can be treated with adequate local therapy alone, a subset demonstrates a biologically aggressive behaviour associated with local recurrence or metastasis. This article reviews the diagnosis and tumour staging of canine mast cell tumours alongside treatment options and the evidence supporting their use. In addition, prognostic markers are evaluated to highlight how one can recognise mast cell tumours that may behave in a biologically aggressive manner as well as the challenges of tumours that are large, infiltrative or in locations not amenable to wide surgical excision.

Prognostic value of immunohistochemical markers in canine cutaneous mast cell tumours: A systematic review and meta-analysis.

Histological grading systems remain cornerstones in the prognosis of canine cutaneous mast cell tumours (MCTs), but the distinct biological behaviour of each tumour often necessitates the use of complementary markers. Although a plethora of immunohistochemical markers have been proposed as prognostic factors, few are presently applied in routine diagnosis. This systematic review and meta-analysis was designed to establish which immunohistochemical markers have verifiable prognostic value for cutaneous MCTs in dogs. A Boolean search of five databases identified 200 articles for screening, of which 73 were selected for full-text assessment and 24 ultimately included in the systematic review. Odds Ratio (OR) was adopted as the summary measure for subsequent meta-analysis but only 15 articles, relating to the immunomarkers Ki-67 (9), KIT (5), and BAX (2), provided either a value for OR or sufficient data to calculate this statistic. Meta-analysis verified that canine cutaneous MCTs with elevated expression of Ki-67 or BAX, as well aberrant immuno-expression of KIT, showed an increased odds of death, with respective OR values of 11.2 (95% CI 6.3-20.0; p < .01), 9.9 (95% CI 1.3-73.6; p = .03), and 4.1 (95% CI 1.1-15.3; p = .03). Despite KIT, Ki67, and BAX arise as suitable prognostic factor for canine MCTs, this study highlighted the lack of important clinical and statistical data in many published articles, rendering it impossible to complete the meta-analysis of several potentially valuable immunohistochemical markers.

Long-term postsurgical outcomes of mast cell tumors resected with a margin proportional to the tumor diameter in 23 dogs.

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.

Histologically low-grade, yet biologically high-grade, canine cutaneous mast cell tumours: A systematic review and meta-analysis of individual participant data.

Low-grade canine cutaneous mast cell tumour (cMCT) with metastasis at the time of treatment is uncommonly reported, with few studies focusing on this specific clinical entity. The specific objective of this study was to systematically review the veterinary literature and perform a meta-analysis summarizing the clinical presentation, treatments reported and clinical outcomes from dogs with histologically low-grade cMCT and metastasis present at initial treatment. A total of 980 studies were screened with eight publications providing data on 121 dogs ultimately included. The most common treatments were surgery with adjuvant chemotherapy in 83/121 (69%) dogs; combined surgery, radiation and chemotherapy in 17/121 (14%) dogs; chemotherapy alone in 12/121 (10%) dogs and surgery alone in 7/121 (6%) dogs. Dogs with distant metastasis (n = 22) experienced significantly shorter survival compared with those with regional lymph node (RLN) metastasis (n = 99; median 194 vs 637 days; P < .01). Two variables were significantly associated with increased risk of death: presence of distant (vs RLN) metastasis (hazard ratio = 2.60; P < .01) and not receiving surgery as a component of treatment (hazard ratio = 3.79; P < .01). Risk of bias was judged to be low in terms of selection and performance bias but high in terms of detection and exclusion bias. In conclusion, dogs with cMCT and RLN metastasis can be expected to live significantly longer than those with distant metastasis, and surgery appears to have a role in extending survival of metastatic low-grade cMCT.

The secondary KIT mutation p.Ala510Val in a cutaneous mast cell tumour carrying the activating mutation p.Asn508Ile confers resistance to masitinib in dogs.

BACKGROUND: Gain-of-function mutations in KIT are driver events of oncogenesis in mast cell tumours (MCTs) affecting companion animals. Somatic mutations of KIT determine the constitutive activation of the tyrosine kinase receptor leading to a worse prognosis and a shorter survival time than MCTs harbouring wild-type KIT. However, canine MCTs carrying KIT somatic mutations generally respond well to tyrosine kinase inhibitors; hence their presence represents a predictor of treatment effectiveness, and its detection allows implementing a stratified medical approach. Despite this, veterinary oncologists experience treatment failures, even with targeted therapies whose cause cannot be elucidated. The first case of an MCT-affected dog caused by a secondary mutation in the tyrosine kinase domain responsible for resistance has recently been reported. The knowledge of this and all the other mutations responsible for resistance would allow the effective bedside implementation of a deeply stratified and more effective medical approach. CASE PRESENTATION: The second case of a canine MCT carrying a different resistance mutation is herein described. The case was characterised by aggressive behaviour and early metastasis unresponsive to both vinblastine- and masitinib-based treatments. Molecular profiling of the tumoural masses revealed two different mutations; other than the already known activating mutation p.Asn508Ile in KIT exon 9, which is tyrosine kinase inhibitor-sensitive, a nearly adjacent secondary missense mutation, p.Ala510Val, which had never before been described, was detected. In vitro transfection experiments showed that the secondary mutation did not cause the constitutive activation by itself but played a role in conferring resistance to masitinib. CONCLUSIONS: This study highlighted the importance of the accurate molecular profiling of an MCT in order to improve understanding of the molecular mechanism underlying tumourigenesis and reveal chemoresistance in MCTs for more effective therapies. The detection of the somatic mutations responsible for resistance should be included in the molecular screening of MCTs, and a systematic analysis of all the cases characterised by unexpected refractoriness to therapies should be investigated in depth at both the genetic and the phenotypic level.

Retrospective outcome evaluation for dogs with surgically excised, solitary Kiupel high-grade, cutaneous mast cell tumours.

Published outcomes for dogs with specifically high-grade mast cell tumours (MCTs), controlled for clinical stage, are few. Clinical outcomes for 49 dogs with Kiupel high-grade, clinical stage I, cutaneous MCTs were evaluated. Median survival time (MST) was 1046 days; 1 and 2-year survival rates were 79.3% and 72.9%, respectively. At study end 24 dogs had died, 23 dogs were alive (median follow-up 980 days) and 2 dogs were lost to follow-up. Death was considered MCT-related in 14 of 20 dogs with a known cause of death. Local tumour recurrence developed in nine dogs (18.4%); regional lymph node metastasis occurred in six dogs (12.2%); and a new MCT developed in 15 dogs (30.1%). Tumour location, histologic margin size and use of chemotherapy did not affect MST; increasing mitotic count (P = .001) and increasing tumour diameter (P = .024) were independently negatively prognostic. Six dogs that developed lymph node metastasis after surgery had worse MST (451 days) than 42 dogs that did not develop metastasis (1645 days); (P < .001). Our study suggests that dogs with local surgical control of clinical stage I histologically high Kiupel grade cutaneous MCT may have a long survival time; especially those with smaller tumours and a lower mitotic count. Our results suggest that evaluation of staging information and mitotic count may be equally helpful as histologic grading when making a prognosis; and highlight the importance of not relying on histologic grade alone when predicting survival for dogs with MCT.

Mutation and methylation status of KIT and TP53 in canine cutaneous and subcutaneous mast cell tumours.

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.

Clinical, histopathological and immunohistochemical chacteristics of equine cutaneous mastocytoma: case report / Características clínicas, histopatológicas e imuno-histoquímicas do mastocitoma cutâneo equino: relato de caso

A 3 year-old mare, Arab, that belongs to the experimental herd of FMVZ-USP presented cutaneous tumor lesions on right and left posterior limb with approximately one year of evolution. A new formation with rapid growth was observed on the neck region, and since then, the limbs lesion gained inflammatory characteristics. Aspirative punction was performed on the neck formation in order to submit the sample to cytological analyses, in which eosinophilic infiltrate was identified. At this point, a conservative approach was chosen with three consecutive corticoid infiltrations. With lack of success of infiltrative therapy, neck, right and left posterior limbs lesions were surgically removed. The material obtained from surgical procedures were sent to histophatological and immunohistrochemical evaluation, that confirmed cutaneous mastocytoma diagnosis. The mare was discharged after all surgical wound were healed and after full remission of clinical signs, and did not show relapses or any other complication from tumor lesions. Some cutaneous tumors are well described and commonly occur in horses, such as sarcoids, melanoma, papilloma and squamous cell carcinoma. Cutaneous mastocytoma is considered a rare cutaneous tumor in this species. According to literature, equine mastocytoma do not have breed predilection, however, some authors mention a greater involvement in Purebreed Arabian horses. In order to establish a definitive diagnosis, it is important to associate physical exams to histophatological an immunohistochemical evaluation and, even though rare in horses, this neoplasm must be considered as a differential diagnosis.

Uma égua puro sangue árabe, com 3 anos de idade, pertencente ao rebanho experimental da FMVZ-USP apresentou lesões tumorais cutâneas nos membros pélvicos direito e esquerdo com aproximadamente um ano de evolução. Notou-se nova formação cutânea com crescimento rápido na região do pescoço, e desde então, as lesões dos membros ganharam características inflamatórias. Foi realizada punção aspirativa da lesão do pescoço para análise citológica, em que se identificou infiltrado eosinofílico. Optou-se pelo início de tratamento conservativo com três infiltrações intralesionais consecutivas com corticoesteroide. A partir da falta de sucesso das infiltrações foram realizadas as excisões cirúrgicas totais dos nódulos do pescoço, membro pélvico direito e esquerdo. Todos os materiais obtidos dos procedimentos cirúrgicos foram enviados para avaliação histopatológica e imuno-histoquímica, nas quais se confirmou o diagnóstico de mastocitoma cutâneo. O animal recebeu alta após a cicatrização das feridas cirúrgicas e remissão dos sinais, e não demonstrou recidivas ou outras complicações advindas das lesões tumorais. Algumas neoplasias cutâneas são bem descritas e de comum ocorrência na espécie equina, como o sarcoide, melanoma, papiloma e tumor de células escamosas. Já o mastocitoma cutâneo consiste em neoplasia cutânea rara nessa espécie. Segundo a literatura, não parece existir uma predileção racial para o aparecimento deste tumor, entretanto, alguns autores citam o acometimento maior nos animais Puro Sangue Árabe. Para o estabelecimento do diagnóstico definitivo é importante a associação dos exames físico, histopatológico e imuno-histoquímico e, apesar desta neoplasia ser de raro aparecimento nos equinos, deve ser sempre considerada como diagnóstico diferencial.

Diagnosis and Prognosis of Canine Cutaneous Mast Cell Tumors.

Canine cutaneous mast cell tumors (MCTs) are among the most common canine cutaneous tumors, with highly variable biological behavior. This review describes in detail current approaches for cytologic and histologic diagnosis and prognosis, including advantages and limitations of cytologic and histologic grading and utilization of molecular markers, for example, Ki67, AgNORs, KIT expression, and c-Kit mutations, for a more accurate detection of aggressive MCTs. Furthermore, the current approach to evaluate surgical margins and spread to local lymph nodes is discussed.

Prevalence and prognostic value of c-kit and TP53 mutations in canine mast cell tumours.

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.

Lokivetmab therapy for pruritus in a dog with cutaneous mastocytosis.

BACKGROUND: Cutaneous mastocytosis (CM) is a rare disease of dogs characterized by rash, pruritus and proliferation of mast cells in the skin. Oral H1 antihistamines are recommended as the treatment to control pruritus. HYPOTHESIS/OBJECTIVE: To describe the effective treatment of pruritus associated with CM with lokivetmab in one dog. ANIMAL: A 4-year-old, spayed female cross-bred dog presented with severely pruritic, erythematous to pigmented macules and papules involving the ventral abdomen, interdigital skin, perivulval area and both pinnae; the pruritus had been unresponsive to treatment with antihistamines, prednisone and ciclosporin. METHODS AND MATERIALS: Complete blood count and serum biochemistry, abdominal ultrasound, blood smear and skin cytological evaluation, PCR, histopathological and immunohistochemical examination of skin biopsies. RESULTS: Skin cytological evaluation revealed high numbers of uniform, heavily granulated mast cells; histopathological findings showed focal dermal proliferations of well-differentiated, uniform mast cells consistent with a low-grade mast cell tumour (MCT). Clinical staging revealed that the disease was confined to the skin. Mutations of c-kit exon 8 and 11 were not detected. Treatment was initiated with anti-canine-interleukin (IL)-31 monoclonal antibody lokivetmab; antihistamines were continued. The dog's pruritus resolved within seven days and was maintained in remission over 15 months with once monthly lokivetmab injections; the skin lesions improved but did not resolve. CONCLUSION AND CLINICAL IMPORTANCE: Lokivetmab treatment was effective in resolving and maintaining pruritus remission in this dog with widespread cutaneous mast cell disease. Whether CM in dogs represent a separate entity that should be distinguished from a low-grade MCT requires further investigation.

Evaluation of Histological, Immunohistochemical, Clinical and Genetic Prognostic Factors Associated with the Response of Canine Mast Cell Tumours to Glucocorticotherapy.

Mast cell tumours (MCTs) are one of the most frequent neoplasms in dogs. Glucocorticoids (GCs) are widely used in the management of this disease, although no guidelines for their use have been established. The aim of this study was to evaluate the correlation of MCT prognostic factors with measurable response to GCs. This retrospective study included 60 dogs treated with prednisone or prednisolone prior to surgical biopsy of MCT. Incisional or excisional biopsy was performed 7-14 days after initiation of GC therapy. Histopathology, immunohistochemical labelling for Ki67 and KITr, and polymerase chain reaction for the c-KIT gene were performed. Partial response occurred in 63.3% of cases (38/60), while 36.7% (22/60) did not respond. A response to GCs was correlated with lower stage of the disease, low histological grade, lower pattern of KITr expression and Ki67 score. Response to GCs was positively correlated with well-established favourable prognostic factors.

Comparison between May-Grünwald-Giemsa and rapid cytological stains in fine-needle aspirates of canine mast cell tumour: Diagnostic and prognostic implications.

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.

Comparison of minichromosome maintenance protein 7, Ki67 and mitotic index in the prognosis of intermediate Patnaik grade cutaneous mast cell tumours in dogs.

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.

Therapeutic impact of regional lymphadenectomy in canine stage II cutaneous mast cell tumours.

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.