Tyrosine kinase inhibitors as an alternative treatment in canine mast cell tumor.

The current gold standard treatment for canine mast cell tumors (MCT) uses vinblastine sulfate (VBL) as chemotherapy, although tyrosine kinase inhibitors (TKI) have recently been shown to be worthy candidates for treatment. This systematic review aimed to analyze the overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and complete (CR) or partial response (PR) in dogs with MCT treated with TKI compared to standard VBL treatment. The systematic review was registered in the Open Science Framework (OSF) database under the identifier 10.17605/OSF.IO/WYPN4 (https://osf.io/). An electronic search was performed in nine databases. References from eligible studies were also selected to find more registers. A total of 28 studies met the eligibility criteria, and one more was recovered from the references of eligible studies, totaling 29 selected studies. The overall response rate, complete response, and partial response were higher in dogs treated with tyrosine kinase inhibitors than in dogs treated with vinblastine. The overall survival and progression-free survival of vinblastine-treated dogs were higher compared to tyrosine kinase inhibitors-treated dogs. Dogs with mutated KIT treated with tyrosine kinase inhibitors have longer overall survival and progression-free survival compared to those treated with vinblastine. It is important to consider the limitation of the study which should temper the interpretation of the results, videlicet, the extracted data lacked sample standardization and included variables such as animal characteristics, mutation detection methods, tumor characteristics, and treatment types which may have influenced the outcome of the study. Systematic review registration: https://osf.io/, identifier: 10.17605/OSF.IO/WYPN4.

Clinical Implications of Immune Checkpoints and the RANK/RANK-L Signaling Pathway in High-Grade Canine Mast Cell Tumors.

Mast cell tumors (MCTs) are the most common malignant cutaneous tumors in dogs, and they present extremely variable biological behavior. The interaction between RANK, RANK-L, and immune checkpoints is frequently detected in the tumor microenvironment, and, together, they participate in every stage of cancer development. Thus, the aim of this study was to characterize the molecular profiles of PD-L1, CTLA-4, RANK/RANK-L signaling pathway, and IFN-γ in primary tumors and lymph node metastases. Formalin-fixed, paraffin-embedded slides of MCTs and metastatic lymph nodes of ten dogs were submitted to immunohistochemical investigations. The results demonstrated that the tumor microenvironment of the high-grade mast cell tumors showed moderate or intense immunolabeling of all proteins, and the lymph node metastases also showed moderate or intense immunolabeling of checkpoint proteins. In addition, MCTs larger than 3 cm were associated with intensified PD-L1 (p = 0.03) in metastatic lymph nodes and RANK-L (p = 0.049) immunoreactivity in the tumor. Furthermore, dogs with a survival time of less than 6 months showed higher PD-L1 immunoreactivity (p = 0.042). In conclusion, high-grade MCT is associated with an immunosuppressive microenvironment that exhibits elevated RANK/RANK-L signaling and enhanced immune checkpoint immunoreactivity, potentially facilitating intratumorally immune escape. These biomarkers show promise as clinical indicators of disease progression and might response to immunotherapy in dogs with high-grade MCTs, thus emphasizing their importance for guiding treatment decisions and improving outcomes.

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.

Cytological grading of canine mast cell tumors: correlation with histologic grading and survival time / Graduação citológica de mastocitomas caninos: correlação com graduação histológica e sobrevida

ABSTRACT: Mast cell tumors are one of the most common neoplasia in dogs and cytopathology and/or histopathology examinations are used for diagnosis. Histologic grading is considered the gold standard test to predict the prognosis of this neoplasia. However, studies have been conducted using the cytological grading system to provide similar information in a faster, less invasive, and more accessible way. This study aimed to investigate cytological graduation and correlate it with histological grading and the survival time of dogs diagnosed with cutaneous mast cell tumors at the Veterinary Hospital of "Universidade Federal de Uberlândia" over five years. For that, cytological and histological slides from 72 animals were reviewed. The statistical methods used were the kappa test for agreement between grading systems, the Kaplan-Meier for survival time, Cox regression for comparison of cytological and histological grades and survival time. The cytological grading when compared to the two-tier histologic grading, high and low grades, had a moderate agreement (kappa 0.566). When the correlation between survival time and the cytological grade was evaluated, there was a higher death rate in the group with high-grade mast cell tumors compared to low grade, pointing to a correlation between survival time and cytological grade (p=0.009). In conclusion, the cytological grade is useful to treatment planning and providing prognostic information that precedes tumor removal, showing a good correlation with the two-tier histologic grading and with the survival time of the animals.

RESUMO: O mastocitoma é uma das neoplasias cutâneas mais comum nos cães e os exames citopatológicos e/ou histopatológicos são utilizados para diagnóstico. A graduação histológica é considerada padrão ouro para prever o prognóstico dessa neoplasia. Contudo, estudos têm sido realizados visando utilizar graduação citológica para fornecer informações semelhantes de maneira rápida, menos invasiva e mais acessível. Esse trabalho objetivou realizar graduação citológica e correlacionar com as graduações histológicas e com a sobrevida de cães diagnosticados com mastocitoma cutâneo no Hospital Veterinário da Universidade Federal de Uberlândia durante 5 anos. Para isso, lâminas de citologia e histologia de mastocitomas de 72 animais foram revisadas. Os métodos estatísticos utilizados foram teste kappa para concordância entre os sistemas de graduação, método Kaplan-Meier para tempo de sobrevida dos animais, e análise pela regressão de Cox para comparação do grau citológico e grau histológico e o tempo de sobrevida global. A graduação citológica quando comparada com a histológica de dois níveis, alto grau e baixo grau, obteve uma concordância moderada (kappa 0,566). Na avaliação da correlação entre sobrevida e grau citológico, houve maior taxa de óbito no grupo de cães com mastocitoma de alto grau, comparado aos de baixo grau, sendo observada correlação entre a sobrevida e o grau citológico (p=0,009). Esse estudo concluiu que o grau citológico é útil para o planejamento do tratamento e para fornecer informações prognósticas que antecedem a exérese do tumor, tendo boa correlação com a graduação histológica de dois níveis e com a sobrevida dos animais.

Pathological aspects of cutaneous mast cell tumors with metastases in 49 dogs.

Cutaneous mast cell tumor (MCT) is one of the most frequent cutaneous neoplasms of dogs and may vary from well-differentiated to aggressive tumors with metastasis. The authors retrospectively described the gross and histologic aspects of metastatic MCT in 49 dogs. Primary MCT was most commonly identified in the inguinal region (14/35; 40%), and at necropsy multiple, cutaneous nodules were frequently reported (23/49; 47%). All primary MCT were classified as high-grade neoplasms, and metastases involved the lymph nodes (47/49; 96%), spleen (33/49; 67%), liver (29/49; 59%), bone marrow (20/49; 41%), kidneys (16/49; 33%), and heart (14/49; 29%), while the lungs were less commonly affected (9/49; 18%). The main gross findings included lymphadenomegaly in 47 cases; splenomegaly in 28 cases, with splenic nodules in 13 dogs; hepatomegaly in 28 cases, with white pinpoint foci in 9 cases; nodules on the capsular surface of the kidneys in 9 dogs; and epicardial nodules in 6 cases. Histologically, the lymph nodes were largely obliterated by neoplastic mast cells, while in the spleen, neoplastic cells were multifocally scattered (16/33; 48%), arranged in nodules (10/33; 30%), or obliterated the parenchyma (9/33; 27%). In the liver, the neoplastic cells mainly infiltrated the sinusoids (24/29; 83%), but were also arranged in random nodules (10/29; 34%). Interstitial and nodular metastases were observed in the kidneys and the heart. Grossly unapparent metastases were common in the heart (6/14; 43%), kidneys (4/16; 25%), and lungs (6/9). KIT III and KIT II staining patterns were observed in 29 and 20 cases, respectively.

Intranasal mast cell tumors: Clinical, immunohistochemical, and molecular features in 20 dogs.

Mast cell tumors (MCTs) are an uncommon primary neoplasm of the nasal cavity in dogs for which there is a paucity of existing literature regarding their clinical behavior and molecular features. The objectives of this retrospective study were to examine the clinical findings, histopathologic and immunohistochemical features, and c-KIT mutation status of primary intranasal MCTs in dogs and identify potential prognostic factors. Canine biopsies submitted to a diagnostic laboratory in Colorado between 2010 and 2019 with intranasal neoplasms diagnosed as MCTs and no history of cutaneous or oral MCT were considered. Immunohistochemistry for CD117 and Ki67 and polymerase chain reaction (PCR) for internal tandem duplications at exons 8 and 11 of the c-KIT gene were performed. Twenty out of 1849 (1%) primary intranasal neoplasms were MCTs. Metastases were reported in 11/20 cases (55%), with the mandibular lymph node representing the most common site. One case had distant metastases to abdominal viscera. Of the cases with available outcome data, 6/14 (43%) died or were euthanized from MCT-related disease within 1 year of the onset of clinical signs. Only one case had a c-KIT mutation at exon 11. In our study, intranasal MCTs were prone to metastasize and had a generally poor prognosis, resembling the behavior of MCTs arising in other mucosal locations. While dogs with metastatic disease and survival times of <1 year tended to have atypical KIT localization, moderate to high Ki67 indices, and mitotic counts ≥8, definitive prognosticators could not be identified due to the limited number of cases with favorable clinical outcomes.

Abordagem diagnóstica de mastocitoma cutâneo metastático em canino / Diagnostic approach of metastatic cutaneous mastocytoma in dog

O mastocitoma é uma das neoplasias cutâneas mais comuns que acometem cães. O diagnóstico da doença é baseado em aspectos clínicos e laboratoriais, sendo a citologia e a histopatologia os métodos de eleição. Diante disso, o objetivo deste estudo é relatar a importância da ampla abordagem diagnóstica de mastocitoma cutâneo metastático em uma fêmea canina castrada, atendida no Hospital Veterinário da Universidade Estadual do Ceará, com uma neoformação em membro compatível com mastocitoma. O estadiamento da paciente foi feito através de exames laboratoriais de hemograma completo, e citologia aspirativa de linfonodo regional e medula óssea, que evidenciaram a presença de focos de metástase; bem como do exame de ultrassom abdominal, que evidenciou alterações no parênquima hepático e linfoadenomegalia ilíaco medial direita. Diante das suspeitas, optou-se pela eutanásia da paciente, cujo corpo foi enviado para os exames de necropsia e histopatologia, os quais confirmaram o diagnóstico de mastocitoma cutâneo de alto grau, com metástase em fígado, pulmão, medula e linfonodos. Desta forma pode-se concluir que o mastocitoma cutâneo metastático é uma neoplasia de diagnóstico multifatorial, em que a realização de exames hematológicos associados às análises citológicas, histopatológicas e de imagem são indispensáveis para estabelecer o diagnóstico definitivo para que seja determinada uma melhor conduta terapêutica e prognóstico de pacientes caninos.

Mast cell tumors are one of the most common skin neoplasms that affect dogs. The diagnosis is based on clinical and laboratory aspects, with cytology and histopathology being the preferred methods. Therefore, this study aims to report the importance of the broad diagnostic approach of metastatic cutaneous mastocytoma in a castrated a female dog attended at the Veterinary Hospital of the State University of Ceará, with a neoformation in a member compatible with mast cell tumor. The patient's staging was performed through laboratory tests of complete blood count, aspiration cytology of regional lymph nodes and bone marrow, which showed the presence of focus of metastasis, as well as the abdominal ultrasound examination, which showed changes in the liver parenchymas and right medial iliac lymphadenopathy. Given the suspicions, the patient was euthanized and the body was sent for necropsy and histopathological examination, which confirmed the diagnosis of high-grade cutaneous mast cell tumor, with metastasis in the liver, lung, bone marrow, and lymph nodes. Thus, it can be is concluded that mast cell tumor is a neoplasm of multifactorial diagnosis, where hematological tests associated with cytology, histopathological, and imaging analyses are essential to establish the definitive diagnosis to determine a better therapeutic behavior and prognosis of canine patients.

Imatinib Mesylate for the Treatment of Canine Mast Cell Tumors: Assessment of the Response and Adverse Events in Comparison with the Conventional Therapy with Vinblastine and Prednisone.

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.

Diagnosis, Prognosis and Treatment of Canine Cutaneous and Subcutaneous Mast Cell Tumors.

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.

Epidemiology of Canine Mast Cell Tumors in Uruguay

We examined in the present study main epidemiological features of canine mast cell tumors in Uruguay, principal breeds of occurrence, age, gender, anatomical distributions, and associated differences of pathological grading. During a three-year period, eighty four out of 405 skin specimens of dogs mainly received at the Veterinary Faculty of Montevideo from private clinics were mast cell tumors. Mix-breed dogs were mostly affected, followed by Labrador Retrievers, Boxers, Pit bulls and Golden Retrievers. Age of patients ranged from 3 to 15 years (median 7.9), and the incidence in females was slightly higher than in males. Tumors were more frequent in the trunk, followed by extremities, scrotum and neck. The majority of specimens were of high malignancy.

Epidemiology of Canine Mast Cell Tumors in Uruguay

We examined in the present study main epidemiological features of canine mast cell tumors in Uruguay, principal breeds of occurrence, age, gender, anatomical distributions, and associated differences of pathological grading. During a three-year period, eighty four out of 405 skin specimens of dogs mainly received at the Veterinary Faculty of Montevideo from private clinics were mast cell tumors. Mix-breed dogs were mostly affected, followed by Labrador Retrievers, Boxers, Pit bulls and Golden Retrievers. Age of patients ranged from 3 to 15 years (median 7.9), and the incidence in females was slightly higher than in males. Tumors were more frequent in the trunk, followed by extremities, scrotum and neck. The majority of specimens were of high malignancy.(AU)

Comparison of two different vinblastine dosages for treatment of cutaneous mast cell tumor in dogs

Background: Mast cell tumors (MCT) are among the most common malignant cutaneous neoplasm in dogs with variable biologic behavior and remain a therapeutic challenge in high-grade cases. Surgery remains the primary treatment for canine MCT; however, chemotherapy and radiation therapy are commonly used to treat aggressive cases. The combination of vinblastine (VBL) at a dose of 2 mg/m² and prednisone is the classically described protocol for MCT treatment. Studies have shown the safety of higher VBL doses for dogs with MCT, but there is a lack of information regarding dose intensity and outcome as a goal after chemotherapy. This study aimed to evaluate the impact of a higher dose of VBL on MCT treatment outcome. Materials, Methods & Results: This was an observational and comparative study conducted in two different Veterinary Teaching Hospitals. Client-owned dogs with histopathological diagnosis of grade II or III MCT were selected and underwent at least four chemotherapy sessions with VBL and prednisone. The experimental group (EG) consisted of 18 dogs that received a dose of 3 mg/m² VBL treated in one institution. The control group (CG) included 31 dogs that received a dose of 2 mg/m² VBL treated at the other institution. All dogs treated in both groups had a clinical and complete blood count (CBC) evaluation performed previous the start of chemotherapy (T0) and before each weekly treatment (T1, T2, T3, and T4). After treatment, dogs in both groups were followed-up for the recurrence rate and overall survival time after diagnosis. There was no significant difference in clinical variables between EG and CG. During treatment, dogs of EG showed a significant reduction in erythrocyte, hemoglobin, and hematocrit values between T0 and T1, T2, T3, and T4 (P < 0.001). Comparatively, the CG showed significant reduction in hemoglobin (P = 0.02) and total leucocytes (P = 0.001) values in the same period. Despite these findings, these hematological...

Assessment of Canine Mast Cell Tumor Mortality Risk Based on Clinical, Histologic, Immunohistochemical, and Molecular Features.

Mast cell tumor (MCT) is a frequent cutaneous neoplasm in dogs that is heterogeneous in clinical presentation and biological behavior, with a variable potential for recurrence and metastasis. Accurate prediction of clinical outcomes has been challenging. The study objective was to develop a system for classification of canine MCT according to the mortality risk based on individual assessment of clinical, histologic, immunohistochemical, and molecular features. The study included 149 dogs with a histologic diagnosis of cutaneous or subcutaneous MCT. By univariate analysis, MCT metastasis and related death was significantly associated with clinical stage ( P < .0001, rP = -0.610), history of tumor recurrence ( P < .0001, rP = -0.550), Patnaik ( P < .0001, rP = -0.380) and Kiupel grades ( P < .0001, rP = -0.500), predominant organization of neoplastic cells ( P < .0001, rP = -0.452), mitotic count ( P < .0001, rP = -0.325), Ki-67 labeling index ( P < .0001, rP = -0.414), KITr pattern ( P = .02, rP = 0.207), and c-KIT mutational status ( P < .0001, rP = -0.356). By multivariate analysis with Cox proportional hazard model, only 2 features were independent predictors of overall survival: an amendment of the World Health Organization clinical staging system (hazard ratio [95% CI]: 1.824 [1.210-4.481]; P = .01) and a history of tumor recurrence (hazard ratio [95% CI]: 9.250 [2.158-23.268]; P < .001]. From these results, we propose an amendment of the WHO staging system, a method of risk analysis, and a suggested approach to clinical and laboratory evaluation of dogs with cutaneous MCT.

Ancillary techniques on the evaluation of canine cutaneous mast cell tumors from Brazil / Técnicas auxiliares avaliação de mastocitomas cutâneos caninos do Brasil

The use of histologic classification by a 2-tier grading system only, immunohistochemistry (IHC) for KIT and Ki-67 and polymerase chain reaction (PCR) for internal tandem duplications (ITD) on exon 11 has improved the prognostication of canine cutaneous mast cell tumors (CCMTs) particularly in the United States. However, these techniques are not commonly used in most Brazilian laboratories. Likewise, no studies, to date, have investigated the occurrence of ITD in CCMTs from the country. Thus, this study tested the 2-tier grading system, the immunohistochemistry for KIT and Ki-67 and the PCR for exon 11 in a group of Brazilian CCMTs with the goal of investigating the applicability of these tests in a Brazilian laboratory. Of the 39 CCMTs, 69.2% (27/39) were identified as low-grade and 30.8% (12/39) as high-grade by a 2-tier grading system. All tumors had a KIT expression pattern II, and 30.6% (11/36) had a high growth fraction (Ki-67). PCR amplification was successful in four of the 11 tumors examined. Two of these (50%) were positive for ITD. This study highlights the importance of using auxiliary techniques in the CCMT evaluation, identifies limitations and confirms the applicability of these methods on a routine diagnostic basis in Brazil. Our results will help to improve the prognostication of CCMTs in Brazilian diagnostic laboratories, encouraging the use of supplementary methods.(AU)

O uso de classificação histológica por um novo sistema de graduação que utiliza apenas duas categorias, imuno-histoquímica (IHQ) para KIT e Ki-67 e reação de polimerase em cadeia (PCR) para mutações (duplicações internas) no éxon 11 tem melhorado a avaliação do prognóstico de mastocitomas cutâneos caninos (MCCs), particularmente nos Estados Unidos. No entanto, essas técnicas são ainda pouco utilizadas em laboratórios brasileiros e, até então, nenhum estudo investigou a prevalência de duplicações internas (DIs) em MCCs do país. Este estudo testou o novo sistema de graduação histológica de duas categorias, a imuno-histoquímica para KIT e Ki-67 e o PCR para exon 11 em um grupo de MCCs brasileiros, com o objetivo de investigar a aplicabilidade desses métodos em um laboratório brasileiro. De 39 MCCs, 69,2% foram identificados como sendo de baixo grau e 30,8% como de alto grau. Todos tiveram um padrão II de expressão de KIT, e 30,6% (11/36) tiveram uma alta contagem para Ki-67. A amplificação foi bem-sucedida em quatro dos 11 tumores examinados. Dois destes (50%) foram positivos para DIs. Este estudo ressaltou a importância do uso de técnicas auxiliares na avaliação de MCCs, identificou limitações e confirmou a aplicabilidade desses métodos em uma rotina de diagnósticos no Brasil. Esses resultados irão auxiliar na melhor avaliação prognóstica dos MCCs em laboratórios brasileiros, encorajando o uso de métodos suplementares neste processo.(AU)

Ancillary techniques on the evaluation of canine cutaneous mast cell tumors from Brazil / Técnicas auxiliares avaliação de mastocitomas cutâneos caninos do Brasil

ABSTRACT: The use of histologic classification by a 2-tier grading system only, immunohistochemistry (IHC) for KIT and Ki-67 and polymerase chain reaction (PCR) for internal tandem duplications (ITD) on exon 11 has improved the prognostication of canine cutaneous mast cell tumors (CCMTs) particularly in the United States. However, these techniques are not commonly used in most Brazilian laboratories. Likewise, no studies, to date, have investigated the occurrence of ITD in CCMTs from the country. Thus, this study tested the 2-tier grading system, the immunohistochemistry for KIT and Ki-67 and the PCR for exon 11 in a group of Brazilian CCMTs with the goal of investigating the applicability of these tests in a Brazilian laboratory. Of the 39 CCMTs, 69.2% (27/39) were identified as low-grade and 30.8% (12/39) as high-grade by a 2-tier grading system. All tumors had a KIT expression pattern II, and 30.6% (11/36) had a high growth fraction (Ki-67). PCR amplification was successful in four of the 11 tumors examined. Two of these (50%) were positive for ITD. This study highlights the importance of using auxiliary techniques in the CCMT evaluation, identifies limitations and confirms the applicability of these methods on a routine diagnostic basis in Brazil. Our results will help to improve the prognostication of CCMTs in Brazilian diagnostic laboratories, encouraging the use of supplementary methods.

RESUMO: O uso de classificação histológica por um novo sistema de graduação que utiliza apenas duas categorias, imuno-histoquímica (IHQ) para KIT e Ki-67 e reação de polimerase em cadeia (PCR) para mutações (duplicações internas) no éxon 11 tem melhorado a avaliação do prognóstico de mastocitomas cutâneos caninos (MCCs), particularmente nos Estados Unidos. No entanto, essas técnicas são ainda pouco utilizadas em laboratórios brasileiros e, até então, nenhum estudo investigou a prevalência de duplicações internas (DIs) em MCCs do país. Este estudo testou o novo sistema de graduação histológica de duas categorias, a imuno-histoquímica para KIT e Ki-67 e o PCR para exon 11 em um grupo de MCCs brasileiros, com o objetivo de investigar a aplicabilidade desses métodos em um laboratório brasileiro. De 39 MCCs, 69,2% foram identificados como sendo de baixo grau e 30,8% como de alto grau. Todos tiveram um padrão II de expressão de KIT, e 30,6% (11/36) tiveram uma alta contagem para Ki-67. A amplificação foi bem-sucedida em quatro dos 11 tumores examinados. Dois destes (50%) foram positivos para DIs. Este estudo ressaltou a importância do uso de técnicas auxiliares na avaliação de MCCs, identificou limitações e confirmou a aplicabilidade desses métodos em uma rotina de diagnósticos no Brasil. Esses resultados irão auxiliar na melhor avaliação prognóstica dos MCCs em laboratórios brasileiros, encorajando o uso de métodos suplementares neste processo.

Oncologia veterinária - exames radiográficos e ultrassonografia na tomada de decisões / Veterinary oncology: radiology and ultrasonography exams in decision making / Oncología veterinaria - los exámenes radiográficos y ecográficos para la toma de decisiones

A solicitação de exames de imagem é comum durante a abordagem clínica de pacientes com neoplasia. Embora seja cada vez mais frequente a disponibilidade de técnicas avançadas de diagnóstico por imagem, os exames radiográficos e ultrassonográficos permanecem como base diagnóstica na oncologia veterinária. A presente revisão descreve considerações para melhorar a abordagem clínica de animais com neoplasias baseando-se na utilização desses exames. Aborda-se o uso dos exames para triagem do paciente, diagnóstico, estadiamento, decisão terapêutica e seguimento. Descreve-se o fluxo de trabalho diante de alguns tipos tumorais, como linfoma mediastinal em gastos e mastocitoma e osteossarcoma em cães, e citam-se os momentos em que outras técnicas de imagem poderão ser indicadas.

Imaging exams are frequently requested during assessment of oncological patients. Although advanced imaging techniques are already available in veterinary medicine, radiographic and ultrasonographic exams remain the basic diagnostic tools in veterinary oncology. This review describes some considerations to improve clinical approach to animals with neoplasic lesions based on the use of radiographic and ultrasonographic exams. The role of these modalities in screening, diagnosis, staging, treatment choice, and follow-up of cancers is discussed. Additionally, a workflow for some type of tumors is described, such as mediastinal lymphoma in cats, as well as mast cell tumors and osteosarcoma in dogs. Situations that require other techniques are also discussed.

El pedido de exámenes de imagen es parte de la rutina durante el manejo clínico de pacientes con neoplasias. A pesar de ser cada vez más frecuente la disponibilidad de técnicas avanzadas de diagnóstico por imágenes, los exámenes radiográficos y de ecografía continúan siendo la base diagnóstica de la oncología veterinaria. Esta revisión describe algunas consideraciones para mejorar el abordaje clínico de los animales con neoplasias, basándose en la utilización de dichos exámenes. Se relata el uso de estos exámenes para la selección del paciente, el diagnóstico, estadificación, decisión terapéutica y el control de los pacientes. Se hace la descripción del flujo de trabajo frente a algunos tipos tumorales, como el linfoma mediastinal en gatos, el mastocitoma y el osteosarcoma en perros, citando en que momento pueden ser utilizadas otras técnicas de imagen que podrían ser indicadas.

Ki67/KIT double immunohistochemical staining in cutaneous mast cell tumors from Boxer dogs.

Cutaneous mast cell tumors (MCTs) are among the most frequent malignant tumors in dogs and Boxer breed dogs have a higher incidence of this disease. Ki67 staining and KIT staining are widely used to predict natural behavior in canine MCT but no previous study has evaluated double staining of these proteins as a prognostic factor. Based on biological behavior predictors in canine MCT, the purpose of this study was to determine the Ki67 proliferative index in KIT positive cells using double stain immunohistochemistry technique. Sixty-nine MCTs from Boxer dogs were selected and a tissue microarray was constructed for the double stained immunohistochemistry. Double positivity (Ki67(+)/KIT(+)) was observed in 20/69 (29%) MCT, with a mean of 9.06 double positive cells per tissue core (range 0.48%-43.97%) and Ki67(-)/KIT(+) animals had a longer survival time than Ki67(+)/KIT(+) animals (p=0.03).

Immunohistochemical and Morphopathological Features of Multiple Cutaneous Mast Cell Tumor in a Cow

A 4 year old female Holstein cow with multiple skin lesions was referred for clinical examination. Grossly, approximately 60 discrete cutaneous nodules and masses with variable sizes ranging from 1 to 5 cm were observed on both sides of flunks, shoulders, neck, back, and mammary glands. Histopathologically, the masses were composed of non-encapsulated accumulation of neoplastic round cells contained moderate to abundant amounts of finely eosinophilic granules in the cytoplasm. Cellular or nuclear pleomorphism and mitotic figures were not remarkable. Metachromasia was seen in cytoplasmic granules stained with toluidine blue. In the immunohistochemical staining, the neoplastic cells were positive for vimentin and c-kit. No immunoreactivity was seen for cytokeratin and HMB - 45. Based on these findings, multiple cutaneous mast cell tumor was diagnosed. Immunohistochemical features of mast cell tumor have not been reported previously in cattle.(AU)

Immunohistochemical and Morphopathological Features of Multiple Cutaneous Mast Cell Tumor in a Cow

A 4 year old female Holstein cow with multiple skin lesions was referred for clinical examination. Grossly, approximately 60 discrete cutaneous nodules and masses with variable sizes ranging from 1 to 5 cm were observed on both sides of flunks, shoulders, neck, back, and mammary glands. Histopathologically, the masses were composed of non-encapsulated accumulation of neoplastic round cells contained moderate to abundant amounts of finely eosinophilic granules in the cytoplasm. Cellular or nuclear pleomorphism and mitotic figures were not remarkable. Metachromasia was seen in cytoplasmic granules stained with toluidine blue. In the immunohistochemical staining, the neoplastic cells were positive for vimentin and c-kit. No immunoreactivity was seen for cytokeratin and HMB - 45. Based on these findings, multiple cutaneous mast cell tumor was diagnosed. Immunohistochemical features of mast cell tumor have not been reported previously in cattle.

Frequência de neoplasias cutâneas em cães atendidos no hospital veterinário da Universidade Federal de Uberlândia durante os anos 2000 a 2010 / Frequency of skin cancer in dogs treated at the Federal University of Uberlândia veterinary hospital from 2000 to 2010

Foram analisados os arquivos do laboratório de Patologia Animal do Hospital Veterinário da UFU de janeiro de 2000 a dezembro de 2010, selecionando protocolos referentes a biopsias cutâneas de cães coletando-se as seguintes informações: diagnóstico morfológico, localização anatômica, idade, sexo e raça dos cães, com o objetivo de realizar um estudo epidemiológico. Foram diagnosticados 549 tumores cutâneos em 543 cães, sendo que 281 cães eram machos e 247 fêmeas. Cães adultos e idosos foram os mais acometidos, assim como os cães sem raça definida, Poodle, Boxer, Pit Bull e Dashchund. Os tumores malignos prevaleceram com 65,39% dos casos, sendo os de origem epitelial os mais frequentes. O carcinoma de células escamosas foi a neoplasia predominante, seguido pelo mastocitoma e histiocitoma. Com relação á localização anatômica prevaleceu as regiões do abdômen (19,49%), cabeça (16,40%) e membros (15,30%). Não houve diferença na probabilidade de apresentar tumor cutâneo com relação ao sexo, porém considerando-se os tipos de tumores há maior probabilidade da população canina apresentar carcinoma de células escamosas e mastocitomas em detrimento dos outros tipos de tumores cutâneos.

We analyzed the archives of the Animal Pathology Laboratory of the Federal University of Uberlândia Veterinary Hospital from 2000 to 2010 with the aim of conducting an epidemiological study. Protocols for skin biopsies of dogs were selected and the following information was collected: morphological diagnosis, anatomical location, age, gender, and breed. Five hundred forty-nine skin tumors were diagnosed in 543 dogs, of which 281 were males and 247 were females. Adult and older dogs were the most affected, and mongrel dogs, Poodles, Boxers, Pit Bulls, and Dashchunds were the most frequent breeds. Malignant tumors were present in 65.39% dogs, and most tumors were derived from epithelial cells. Squamous cell carcinoma was the predominant neoplasia, followed by mast cell tumors and histiocytoma. With respect to the anatomic location, the abdomen (19.49%), head (16.40%), and limbs (15.30%) were the most frequently affected. Gender did not influence the probability of having a cutaneous tumor. With regard to tumor type, the canine population was more susceptible to squamous and mast cell tumors than to other skin tumors.