[Solitary mast cell tumor. A case comunication]. / Mastocitoma solitario. Comunicación de un caso.

BACKGROUND: The solitary cutaneous mastocytoma is a variant of cutaneous mastocytosis which carries a good prognosis. It may develop at a very early age, during the first weeks of life, or even be congenital. Typically, they present as red-brownish lesions that may be asymptomatic or present systemic manifestations associated with histamine release. CASE REPORT: A 19-year-old female patient who attended a medical consultation for a pigmented lesion, slightly raised in the left antecubital fold, asymptomatic, of recent appearance and progressive growth. Dermoscopy reported a fine symmetrical network, yellowish-brown in color and randomly distributed black dots. The pathology report and immunohistochemical findings were consistent with mast cell tumor. CONCLUSIONS: The solitary cutaneous mastocytoma should not be considered as an exclusive entity in the pediatric population. Acknowledgment of its atypical clinical presentation with its dermatoscopic features, is useful for diagnosis.

ANTECEDENTES: El mastocitoma solitario es una variante de mastocitosis cutánea de buen pronóstico, congénita, que aparece durante las primeras semanas de vida. Las manifestaciones clínicas incluyen: lesiones de color rojo-marrón, que pueden ser asintomáticas o generar lesiones sistémicas asociadas con la liberación de histamina. REPORTE DE CASO: Paciente femenina de 19 años, que acudió a consulta médica por una lesión pigmentada, ligeramente sobreelevada en el pliegue antecubital izquierdo, asintomática, de reciente aparición y crecimiento progresivo. La dermatoscopia reportó una fina red simétrica, de color pardo-amarillenta, con puntos negros y distribución al azar. El informe de Anatomía patológica y los hallazgos de inmunohistoquímica fueron compatibles con mastocitoma. CONCLUSIONES: El mastocitoma solitario no es exclusivo de la población pediátrica y su manifestación en la población adulta suele ser atípica. El conocimiento de las características dermatoscópicas es útil para establecer el diagnóstico certero.

Mutations of the c-KIT gene in canine mast cell tumors and respective nodal metastases classified according to mast cell infiltration / Mutações no gene c-KIT em mastocitomas caninos e respectivas metástases nodais classificados segundo a infiltração de mastócitos

The molecular background of canine mast cell tumors (MCT) has been extensively investigated; however, the dynamic molecular changes that occur during carcinogenesis and metastasis are not fully understood. This study aimed to evaluate the incidence of mutations in the c-KIT proto-oncogene in canine MCTs and relative draining regional lymph nodes. Suspected or confirmed lymph node metastasis was classified accordingly to the HN Weishaar classification. The study included 34 dogs diagnosed with MCT; 19 patients were enrolled prospectively. These dogs had the primary MCT and regional lymph node resected and analyzed simultaneously. The second group was evaluated retrospectively and included fifteen patients resectioning the primary MCT without evaluation of regional lymph node. Analyzes of c-KIT mutation were performed for all primary MCTs and, in the first group, compared between primary MCT and HN-classified metastasis. Internal tandem duplications (ITD) in exon 11 of the c-KIT gene were detected in 20% of patients. Ten of the nineteen patients (52%) in the first group presented mast cell infiltration in the regional lymph node, and ITD in exon 11 of the c-KIT gene was detected in five and two dogs from Groups 1 and 2, respectively. ITD c-KIT mutations are common in canine MCT and may be found in the draining lymph node metastases/mast cell infiltrates in the absence of mutation of the primary tumor. Evaluation of c-KIT mutation in the primary tumor and metastases may be informative for defining both prognosis and therapeutic options in MCT cases.

O perfil molecular do mastocitoma (MCT) tem sido bastante investigado, no entanto as dinâmicas moleculares que ocorrem durante a carcinogênese e metástase desta neoplasia não estão bem esclarecidas. O objetivo desse estudo foi avaliar a incidência de mutações no proto-oncogene c-KIT em MCTs caninos e respectivos linfonodos regionais. Os casos suspeitos ou confirmados de metástase para os linfonodos, foram classificados de acordo com a classificação HN de Weishaar. O estudo incluiu 34 cães diagnosticados com MCT e, desses, 19 pacientes foram avaliados de maneira prospectiva, em que o tumor primário e o linfonodo regional foram ressecados e analisados simultaneamente. O segundo grupo foi avaliado retrospectivamente e incluiu quinze pacientes que tiveram ressecção do MCT primário sem avaliação de linfonodo regional. A análise da mutação c-KIT foi realizada para todos os MCTs primários e, no primeiro grupo, comparados entre MCT primário e metástase classificada pelo sistema HN. Duplicações internas em tandem (DIT), no exon 11 do gene c-KIT, foram detectadas em um total de 20% dos pacientes. Dez dos dezenove pacientes (52%) do primeiro grupo apresentavam infiltração de mastócitos no linfonodo regional, e DIT no exon 11 do gene c-KIT foram identificadas em cinco e dois cães dos Grupos 1 e 2, respectivamente. Mutações do tipo DIT no gene c-KIT são comuns no MCT canino e podem estar presentes nas metástases/infiltrados de mastócitos na ausência de mutação do tumor primário. A avaliação da mutação no gene c-KIT no tumor primário e metástases pode ser informativa para definir tanto o prognóstico quanto as opções terapêuticas em casos de MCT.

Epididymal primary mast cell tumor in a dog

Background: In the literature, there are a few descriptions of epididymis neoplasia in domestic animals, especially considering primary tumors. In the few reports found in literature, the lesions were a consequence of the invasion of testicular or paratesticular neoplasia, as a papillar carcinoma in a dog's and a bull's epididymis, and mesenchymal tumors - fibrome/ fibrosarcoma, leiomyoma/leiosarcome. On the other hand, mast cell tumors are the second most prevalent neoplasia in dogs in Brazil, affecting especially the skin. The aim of this report is to describe for the first time a low malignancy mast cell tumor in a mixed-breed dog's epididymis, without metastasis or recurrence in a 2-year follow-up period. Case: A 10-year-old male mixed-breed dog was presented for pre-surgical evaluation for elective orchiectomy. In the physical examination, an increase in the volume of approximately 2 cm with an irregular appearance was identified on palpation in the cranial pole of the left testis. In the trans surgical period, an increase in testicular volume (4 cm long x 2 cm wide) was observed, with a firm consistency in the region of the vas deferens with macroscopic changes in the region. The testis was sectioned, and the fragments were sent for histopathological evaluation in 10% buffered formaldehyde. There was a fairly cellular circumscribed neoplastic infiltrate, distributed in a sheet and separated by fibrovascular stroma, and rounded neoplastic cells with a moderate amount of basophilic cytoplasmic granulation, and discrete anisocytosis and anisokaryosis. The nuclei were rounded with vesicular chromatin with 1 or 2 distinct nucleoli. No mitosis figures were observed in 10 high power fields (400x). Few eosinophils were distributed throughout the neoplastic cell population. Immunohistochemistry demonstrated immunostaining for KIT protein with perimembranous staining in 95% of neoplastic mast cells, giving a KIT 1 pattern. There was no positive nuclear staining for Ki67 in any cell of the histological sections examined. A grade II mast cell tumor (low grade of malignancy) was diagnosed. After diagnosis, the animal underwent radiographic evaluation of the chest and abdominal ultrasound, and a new physical inspection in search of nodules, plaques, skin lesions, or subcutaneous masses. There were no metastases in the thorax and abdominal cavity, nor physical alterations, and it can be inferred that the epididymis was the primary site of the mast cell tumor. After 2 years of orchiectomy, there were no recurrences, and no chemotherapy treatment was performed. Discussion: Extracutaneous mast cell tumors are uncommon in animals, but have been reported in oral and nasal mucosa, nasopharynx, larynx, trachea, intestine, visceral lymph nodes, spleen, liver, spinal cord, intestine, ureter, conjunctiva, lung and more recently in tear gland of the third eyelid. However, in the authors' assessment, this is the first description of mast cell tumor in the epididymis in dogs. The diagnosis was established by histopathological examination, which revealed a grade II epididymal mast cell tumor and immunohistochemical evaluation (KIT and Ki-67) as being of low aggressiveness. The diagnosis of a primary tumor was confirmed since the staging was established after the histopathological diagnosis, involving chest radiography, abdominal ultrasound, cutaneous evaluation in search of nodules, plaques, cutaneous and subcutaneous lesions, and did not reveal other abnormalities or metastases not identified in the preoperative evaluation. In addition, immunostaining with KIT and Ki-67 reaffirmed the low degree of malignancy and the potential for metastases, which can be observed by the asymptomatic follow-up of the patient 2 years after the surgical excision.

Metastatic intranasal mastocytoma in a dog

Background: Mast cell tumors (MCTs) are neoplasms originating from mast cells, which can be well or poorly differentiated. They are considered the most commonly diagnosed malignant cutaneous neoplasm in dogs; however, intranasal forms are still little reported. Thus, this study seeks to report a case of unilateral intranasal MCT exhibiting submandibular lymph node metastasis. Case: A 11-year-old-and-4-month-old dog of undefined breed (UB), weighing 41 kg, was referred to the Veterinary Medical Teaching Hospital of the University of Passo Fundo (UPF), in the state of Rio Grande do Sul, Brazil. Presenting a clinical history of bilateral purulent nasal secretion, accompanied by sneezing in the two months prior to admission, in addition to vomiting and diarrhea. Auxiliary tests were requested, including skull X-ray, cytology of the nasal cavity with a swab, and collection of material from the submandibular lymph node directly through cytology with a needle. Cytological findings from the right nasal cavity were consistent with mast cell tumors (MCTs). Cytological analysis of the left nasal cavity was compatible with dysplasia/cellular reactivity. A heterogeneous population of cells was detected on cytology of the right submandibular lymph node. These findings were consistent with MCT lymph node metastasis. Skull radiography showed an increase in both opacity and soft tissue extension, surpassing the palate, from the canine tooth through the caudal region of the maxillary sinuses to the last molar, without bone destruction. The dog was then admitted for an abdominal ultrasound, which showed no changes in the spleen or liver. The leukocyte count showed mild lymphopenia and the presence of reactive lymphocytes. Through the buffy coat, the presence of rare round cells, compatible with circulating mast cells, was detected. Due to the biological behavior of the neoplasm and its anatomical location, the established therapy was based on the use of vinblastine and prednisolone. The patient did not show any clinical improvements. In a joint decision with the patient's guardian, the dog was euthanized. Discussion: Intranasal MCTs commonly present progressive and intermittent unilateral epitaxis, mucopurulent nasal discharge, dyspnea, and ocular discharge. Several anatomical sites were associated with more aggressive neoplastic phenotypes; those with an unfavorable prognosis were mainly those present in the oral and intranasal mucosa. Cytopathological examination is considered a highly sensitive method for the diagnosis of MCTs. Metastases are present in more than 90% of mucosal MCTs, usually affecting regional lymph nodes and associated with a poor prognosis. Radiography is considered a useful test in determining the size and location of tumors in the nasal cavity. Chemotherapy plays an important role in the treatment, especially in cases like the one described in this report, in which surgical excision is not possible due to the anatomical location of the neoplasm. Intranasal MCTs are uncommon in dogs. In this case, he presented aggressive, metastatic behavior and a poor response to antineoplastic therapy. Furthermore, due to the location of these tumors, they may be clinically similar to a number of other upper respiratory tract diseases, posing a diagnostic challenge. Therefore, it is essential that the search for differential diagnoses be carried out through auxiliary tests, such as cytology and imaging.

Canine mast cell tumour lomustine's sensitization by tyrosine kinase inhibitors

Background: Tyrosine kinase inhibitors (TKIs) may sensitize neoplasms to conventional antineoplastic agents, however such studies are scarse in the veterinary literature and there is no in vivo study about this subject. Although the literature recommend consensual about the use of masitinib for unresectable or metastatic MCTs, the potential of tumour sensitization to chemotherapeutic agents exerted by the drug is poorly explored in veterinary medicine. The objective of this paper was to report, for the first time, the sensitization of 2 canine mast cell tumours (MCTs) to lomustine, with the use of 2 tyrosine kinase inhibitors: masitinib and toceranib. Cases: Two dogs were referred due tumour recurrence in the left pelvic limb (dog 1), and unilateral mass in the right nasal mucocutaneous region (dog 2). The first case was a 8-year-old female Pinscher, and the second case refers to a 8-year-old male mixed-breed dog. Fine needle aspiration of both lesions was performed, and the cytological analysis were compatible with high grade canine MCT. In the first case, it was started a chemotherapeutic treatment with intravenous vinblastine (2 mg/m² ), associated with prednisolone (40 mg/m2 , every 24 h for 7 days), followed by 25 mg/m2 every 24 h, for more 30 days, tramadol (4 mg/kg every 8 h, until new recommendations) and gabapentin (3 mg/kg every 12 h, until new recommendations). However, there was no objective response, and vinblastine was substituted by lomustine (60 mg/m2 every 21 days), however there was also no response after 2 doses. After masitinib importation, the same was started at 12.5 mg/kg orally every 24 h, but there was also no objective response. However, after new lomustine administration the lesion showed complete remission. The second dog initiated its treatment with toceranib, recently licensed in Brazil, at a dosage of 2.7 mg/kg every 48 h, and after 30 days, there was partial remission. However, the remaining lesion still deemed unresectable, and systemic chemotherapy with lomustine (50 mg/m2 ) was initiated along with continuous toceranib. After 3 weeks of the first chemotherapy complete remission was noted and a second dose was administered. Once the patient remained in complete clinical remission, only toceranib was maintained at the same dose. After 11 months using the toceranib, there was sign of disease recurrence and lomustine was re-initiated resulting in complete remission. Discussion: The TKIs masitinib and toceranib might be considered the first-line therapy for unresectable and/or metastatic canine MCT, but also for those cases with confirmed internal tandem duplications in the exon 11 of the c-KIT protooncogene. Masitinib appears to be more selective than others TKI, such as toceranib, imatinib, dasatinib and sunitinib, because it causes weak inhibition of BCR/ABL (breakpoint cluster region-Abelson), Fms (macrophage colony-stimulating factor receptor), Flt-3 (FMS-like tyrosine kinase-3) and VEGFR (vascular endothelial growth factor receptor), which may partially explains its increased safety and lower risk of cardiotoxicity. In the first case, the animal has been treated with lomustine associated to masitinib and showed a progression-free interval of 33 days, however, the response reported may have been lower, due previously exposition to chemotherapeutic agents, which might compromise the response to TKI. The second case, with the association of lomustine and toceranib, was followed up for 365 days, presenting only one recurrence in the final third of the follow-up, however, with subsequent new complete remission. Sensitization of canine MCT to lomustine with TKIs increases the therapeutic possibilities for this neoplasm, mainly in patients with advanced stage and high-grade tumours.

Hemangiossarcoma associado a quimiodectoma em cadela Pit Bull idosa / Hemangiosarcoma associated with chemodectoma in an old Pit Bull bitch

Background: The prevalence of neoplasms in domestic animals has been augmenting over the years. Hemangiosarcoma, which most frequently affects large breed dogs, is a neoplasm with high metastatic power and corresponds to 5% of malignant neoplasms. Chemodectoma, a neoplasm that can have malignant or benign behavior, is uncommon, corresponding to less than 8% of all cardiac tumors, and originates from cardiac chemoreceptor cells and involves mainly the aortic and carotid bodies. The aim of this study is to describe the case of an elderly Pit Bull dog with hepatic hemangiosarcoma and chemodectoma associated with four other different tumors: hemangioma, papilloma, mastocitoma and melanoma. Case: A 14-year-old female Pit Bull, castrated, was presented to Veterinary Clinic of the Federal University of Santa Catarina (UFSC), Curitibanos Campus, Brazil. The owner referred apathy, hyporexia, and increased abdominal volume for two weeks. Physical examination showed emaciation and abdominal effusion. Abdominocentesis was performed, three liters of serosanguineous fluid was drained and a sample was sent for analysis. Complementary tests were requested and showed mild hypoalbuminemia, normocytic normochromic anemia, and lymphopenia. The ultrasound examination revealed thickening of vessels and hepatomegaly, in addition to the presence of an oval structure containing hyperechogenic cavitations. Diagnostic exploratory laparotomy was indicated, but the owner refused. Drug therapy was prescribed in a palliative manner and, during the clinical follow-up period, two abdominocentesis procedures and one thoracentesis procedure were performed, both resulting in simple transudate. Finally, the patient developed severe apathy, edema in all limbs, and died at home. Necroscopic examination was done and revealed hemoperitoneum and hemothorax...(AU)

Canine cutaneous neoplasms in the metropolitan region of Goiânia, Goiás state, Brazil / Neoplasias cutâneas caninas na região metropolitana de Goiânia, Goiás, Brasil

The present study aimed to describe the occurrence and epidemiological features of skin neoplasms diagnosed in dogs in the metropolitan region of Goiânia, Goiás state, Brazil. Diagnoses from dog biopsies from 2011 to 2016 provided by a private veterinary pathology laboratory were analyzed. The main diagnoses were mast cell tumor, hemangiosarcoma, squamous cell carcinoma, malignant melanoma, and hemangioma. Highest frequency of neoplasms was found in female dogs, dogs aged > 8 years, and purebred dogs, particularly the American Pit Bull Terriers and the Poodles. Most common sites affected by the neoplasms were the limb and the head. Using multiple correspondence analysis, groups of neoplasms were found to be associated with different epidemiological features and the size of the neoplasms was associated with the biological behavior. The results of this study described predispositions and verified the importance of different types of skin neoplasms in dogs in the region being studied.(AU)

O objetivo deste estudo foi determinar a prevalência e as características epidemiológicas das neoplasias cutâneas em cães na região metropolitana de Goiânia, Goiás. Foram analisados os diagnósticos de um laboratório do setor privado de 2011 a 2016. Mastocitoma, hemangiossarcoma, carcinoma de células escamosas, melanoma maligno e hemangioma representaram os principais diagnósticos. A maioria dos casos ocorreram em cães de raças definidas, fêmeas e com idade >8 anos. American Pit Bull Terrier e Poodle foram as raças mais encontradas. As neoplasias acometeram principalmente regiões de membros e cabeça. Pela análise de correspondência múltipla, associou-se os grupos de neoplasias com diferentes características epidemiológicas e o tamanho da neoplasia com o comportamento biológico. A comparação dos resultados com pesquisas prévias possibilitou confirmar predisposições previamente descritas e verificar a importância dos diferentes tipos de neoplasias cutâneas em cães na região estudada.(AU)

Mastocitoma felino. Reporte de caso / Feline mastocytoma. Case report

RESUMEN Los mastocitomas son tumores originarios de los mastocitos que usualmente afectan a los perros y los gatos. Pueden llegar a tener un comportamiento benigno, sin embargo, esto dependerá del grado de la neoplasia y su estadiaje. En felinos, clínicamente se han descrito dos patrones: visceral y cutáneo, de los cuales el cutáneo es el más frecuente, llegando a causar metástasis a órganos adyacentes e incluso afectar el bazo y/o intestino en estadios más diferenciados. Se presenta un caso de mastocitoma felino correspondiente a un ejemplar mestizo con cuadro clínico de inicio de más de dos meses de evolución, consistente en la aparición de una placa alopécica ulcerada y elevada en región interescapular, acompañada de prurito que presentó resolución espontánea. Mediante el curso clínico se imnunizó contra el virus de la rabia, posteriormente, se observó la aparición de una lesión nodular subcutánea de características inusuales de 2cm de diámetro. Acorde con el tiempo de evolución y el antecedente vacunal se decidió la realización de biopsia y resección quirúrgica. El reporte de la biopsia confirmó diagnóstico de mastocitoma grado histológico 3 de Patnaik, teniendo en cuenta las características histológicas, estructurales y su comportamiento clínico. Se realizó seguimiento del caso pasados ocho meses, donde se evidenció mejoría del cuadro clínico, sin aparición de nueva masa sugestiva de neoplasia, sin hallazgos de metástasis a otras estructuras, con cicatrización exitosa de herida quirúrgica y evolución satisfactoria.

ABSTRACT Mast cells are tumors originating from mast cells which usually affect cats and dogs. They may have benign behavior, however, this will depend on the degree of the neo-plasm and its staging. In cats, two patterns have been described clinically: visceral and cutaneous, of which the cutaneous form is the most frequent, reaching metastasis to adjacent organs and even affecting the spleen and / or intestine in more differentiated stages. A case of a mastocytoma is presented, a feline corresponding to a mongrel specimen with a clinical picture of onset of more than two months of evolution, consisting of the appearance of an allopecal plaque, ulcerated and elevated in the interscapular region, accompanied by pruritus that presented spontaneous resolution. Through the clinical course, he was immunized against the rabies virus, later the appearance of a nodular lesion of unusual subcutaneous characteristics, 2 cm in diameter, was observed. According to the evolution time and the vaccination history, it was decided to perform a biopsy and surgical resection. The biopsy report confirmed the diagnosis of Patnaik's histological grade 3 mastocytoma, taking into account the histological and structural characteristics and its clinical behavior. The case was followed up after eight months, where an improvement in the clinical picture was evident, without the appearance of a new mass suggestive of neoplasia, without metastatic findings to other structures, with successful healing of the surgical wound and satisfactory evolution.

Canine cutaneous neoplasms in the metropolitan region of Goiânia, Goiás state, Brazil / Neoplasias cutâneas caninas na região metropolitana de Goiânia, Goiás, Brasil

ABSTRACT: The present study aimed to describe the occurrence and epidemiological features of skin neoplasms diagnosed in dogs in the metropolitan region of Goiânia, Goiás state, Brazil. Diagnoses from dog biopsies from 2011 to 2016 provided by a private veterinary pathology laboratory were analyzed. The main diagnoses were mast cell tumor, hemangiosarcoma, squamous cell carcinoma, malignant melanoma, and hemangioma. Highest frequency of neoplasms was found in female dogs, dogs aged > 8 years, and purebred dogs, particularly the American Pit Bull Terriers and the Poodles. Most common sites affected by the neoplasms were the limb and the head. Using multiple correspondence analysis, groups of neoplasms were found to be associated with different epidemiological features and the size of the neoplasms was associated with the biological behavior. The results of this study described predispositions and verified the importance of different types of skin neoplasms in dogs in the region being studied.(AU)

O objetivo deste estudo foi determinar a prevalência e as características epidemiológicas das neoplasias cutâneas em cães na região metropolitana de Goiânia, Goiás. Foram analisados os diagnósticos de um laboratório do setor privado de 2011 a 2016. Mastocitoma, hemangiossarcoma, carcinoma de células escamosas, melanoma maligno e hemangioma representaram os principais diagnósticos. A maioria dos casos ocorreram em cães de raças definidas, fêmeas e com idade >8 anos. American Pit Bull Terrier e Poodle foram as raças mais encontradas. As neoplasias acometeram principalmente regiões de membros e cabeça. Pela análise de correspondência múltipla, associou-se os grupos de neoplasias com diferentes características epidemiológicas e o tamanho da neoplasia com o comportamento biológico. A comparação dos resultados com pesquisas prévias possibilitou confirmar predisposições previamente descritas e verificar a importância dos diferentes tipos de neoplasias cutâneas em cães na região estudada.(AU)

Hemangiossarcoma associado a quimiodectoma em cadela Pit Bull idosa / Hemangiosarcoma associated with chemodectoma in an old Pit Bull bitch

Background: The prevalence of neoplasms in domestic animals has been augmenting over the years. Hemangiosarcoma, which most frequently affects large breed dogs, is a neoplasm with high metastatic power and corresponds to 5% of malignant neoplasms. Chemodectoma, a neoplasm that can have malignant or benign behavior, is uncommon, corresponding to less than 8% of all cardiac tumors, and originates from cardiac chemoreceptor cells and involves mainly the aortic and carotid bodies. The aim of this study is to describe the case of an elderly Pit Bull dog with hepatic hemangiosarcoma and chemodectoma associated with four other different tumors: hemangioma, papilloma, mastocitoma and melanoma. Case: A 14-year-old female Pit Bull, castrated, was presented to Veterinary Clinic of the Federal University of Santa Catarina (UFSC), Curitibanos Campus, Brazil. The owner referred apathy, hyporexia, and increased abdominal volume for two weeks. Physical examination showed emaciation and abdominal effusion. Abdominocentesis was performed, three liters of serosanguineous fluid was drained and a sample was sent for analysis. Complementary tests were requested and showed mild hypoalbuminemia, normocytic normochromic anemia, and lymphopenia. The ultrasound examination revealed thickening of vessels and hepatomegaly, in addition to the presence of an oval structure containing hyperechogenic cavitations. Diagnostic exploratory laparotomy was indicated, but the owner refused. Drug therapy was prescribed in a palliative manner and, during the clinical follow-up period, two abdominocentesis procedures and one thoracentesis procedure were performed, both resulting in simple transudate. Finally, the patient developed severe apathy, edema in all limbs, and died at home. Necroscopic examination was done and revealed hemoperitoneum and hemothorax...

Identification of two molecular subtypes in canine mast cell tumours through gene expression profiling.

Mast cell tumours (MCTs) are common neoplasms in dogs and are usually regarded as potentially malignant. Several studies have attempted to identify biomarkers to better predict biological behaviours for this tumour. The aim of this study was to identify pathways connected to clinical and histopathological malignancies, shorter survival times, and poor prognoses associated with MCTs. We performed genome-wide gene expression analyses on tissues obtained from 15 dogs with single MCTs, and identified two distinct tumour subtypes-high-risk and low-risk-associated with differences in histological grades, survival times, Ki67 indices, and occurrence of death due the disease. Comparative analyses of RNA sequence profiles revealed 71 genes that were differentially expressed between high- and low-risk MCTs. In addition to these analyses, we also examined gene co-expression networks to explore the biological functions of the identified genes. The network construction revealed 63 gene modules, of which 4 were significantly associated with the more aggressive tumour group. Two of the gene modules positively correlated with high-risk MCTs were also associated with cell proliferation and extracellular matrix-related terms. At the top of the extracellular matrix module category, genes with functions directly related to those of cancer-associated fibroblasts (CAFs) were identified. Immunohistochemical analyses also revealed a greater number of CAFs in high-risk MCTs. This study provides a method for the molecular characterisation of canine MCTs into two distinct subtypes. Our data indicate that proliferation pathways are significantly involved in malignant tumour behaviours, which are known to be relevant for the induction and maintenance of MCTs. Finally, animals presenting high-risk MCTs overexpress genes associated with the extracellular matrix that can be robustly linked to CAF functions. We suggest that CAFs in the MCT stroma contribute to cancer progression.

Ocorrência simultânea de hemangiossarcoma e mastocitoma de grau II em cão da raça Pitbull / Simultaneous occurrence of hemangiosarcoma and grade II mast cell tumor in a Pit Bull Terrier

Background: The incidence of cutaneous neoplasms in dogs is high and quite variable. Hemangiosarcoma (HSA) and mast celltumor (MCT) are commonly diagnosed neoplasms in isolation; however, reports of concomitant occurrence in a single patientare rare. HSA is a malignant mesenchymal neoplasm of endothelial origin; the spleen is the most commonly affected organ.MCT is a common neoplasm that may affect any region of the body, without predilection for sex, although some breeds haveshown higher incidence. This report describes a case of HSA and MCT in a Pit bull terrier.Case: A 5-year-old white male Pit bull was presented to the Small Animal Clinic of the Federal Rural University of Pernambucowith nodules in preputial region measuring 5.4 x 3.7 cm and an ulcerated nodule in the right lateral thoracic region measuring23.0 x 19.0 x 5.5 cm. The owner reported surgical excision of two previous nodules one year before the consultation, but neitherwere submitted for cytopathological or post-surgical histopathological examination. Two months after the procedure, the nodulesrecurred. Cytopathological examinations of preputial and lateral thoracic nodules were performed, with a suggestive diagnosisfor HSA and MCT, respectively. Due to the unfavorable prognosis and the weakness of the animal, euthanasia was elected.Necroscopic examination revealed an ideal body condition score (4/9), hypertrophy of right pre-scapular and axillary lymphnodes, red hepatization in the apical lobe of the right lung, with multiple, soft and pigmented nodules in the spleen, liver, pancreas and testis. Several tissue samples were collected, conditioned in 10% buffered formaldehyde solution, routinely processedfor histology, and stained with hematoxylin-eosin and toluidine blue. Microscopically, the lateral thoracic nodule consisted ofround cells in cordonal arrangement, with sparse basophilic and discretely granular cytoplasm...(AU)

H-plastia com flap de avanço para reconstrução de região nasal após exérese de nódulo em cão / H-plasty with advancement flap for reconstruction of nasal region after nodule excision in a dog

O uso da cirurgia reconstrutiva no campo da Medicina Veterinária vem crescendo cada vez mais, principalmente quando associado a ressecções tumorais. Este relatório descreve a reconstrução cirúrgica com o uso de retalhos de avanço nasais pela técnica da plastia H, após ressecção tumoral sugestiva de mastocitoma em um cão. O animal foi tratado no Hospital Veterinário do Departamento de Medicina Veterinária da Universidade Federal Rural de Pernambuco, onde foi realizada a avaliação física e solicitados exames complementares para posterior encaminhamento à cirurgia. O tutor relatou que o nódulo começou a crescer 15 dias antes do procedimento. A massa neoplásica estava localizada na porção dorsal do plano nasal, com diagnóstico citológico sugestivo de mastocitoma.(AU)

The use of reconstructive surgery in the field of Veterinary Medicine has been growing increasingly, specially when associated with tumor resections. This report describes the surgical reconstruction with the use of advancement flaps in the nasal using the H-plasty technique, after tumor resection suggestive of mastocytoma in a dog. The animal was treated at the Veterinary Hospital of the Department of Veterinary Medicine of the Federal Rural University of Pernambuco, where the physical evaluation was made and complementary exams were requested for subsequent referral to surgery. The tutor reported that the nodule started growing 15 days before the procedure. The neoplastic mass was located in the dorsal portion of the nasal plane, with a cytological diagnosis suggestive of mastocytoma.(AU)

H-Plastia com flap de avanço para reconstrução de região nasal após exérese de nódulo em cão / H-Plasty with advancement flap for reconstruction of nasal region after nodule excision in a dog

O uso da cirurgia reconstrutiva no campo da Medicina Veterinária vem crescendo cada vez mais, principalmente quando associado a ressecções tumorais. Este relatório descreve a reconstrução cirúrgica com o uso de retalhos de avanço nasais pela técnica da plastia H, após ressecção tumoral sugestiva de mastocitoma em um cão. O animal foi tratado no Hospital Veterinário do Departamento de Medicina Veterinária da Universidade Federal Rural de Pernambuco, onde foi realizada a avaliação física e solicitados exames complementares para posterior encaminhamento à cirurgia. O tutor relatou que o nódulo começou a crescer 15 dias antes do procedimento. A massa neoplásica estava localizada na porção dorsal do plano nasal, com diagnóstico citológico sugestivo de mastocitoma.

The use of reconstructive surgery in the field of Veterinary Medicine has been growing increasingly, specially when associated with tumor resections. This report describes the surgical reconstruction with the use of advancement flaps in the nasal using the H-plasty technique, after tumor resection suggestive of mastocytoma in a dog. The animal was treated at the Veterinary Hospital of the Department of Veterinary Medicine of the Federal Rural University of Pernambuco, where the physical evaluation was made and complementary exams were requested for subsequent referral to surgery. The tutor reported that the nodule started growing 15 days before the procedure. The neoplastic mass was located in the dorsal portion of the nasal plane, with a cytological diagnosis suggestive of mastocytoma.

Ocorrência simultânea de hemangiossarcoma e mastocitoma de grau II em cão da raça Pitbull / Simultaneous occurrence of hemangiosarcoma and grade II mast cell tumor in a Pit Bull Terrier

Background: The incidence of cutaneous neoplasms in dogs is high and quite variable. Hemangiosarcoma (HSA) and mast celltumor (MCT) are commonly diagnosed neoplasms in isolation; however, reports of concomitant occurrence in a single patientare rare. HSA is a malignant mesenchymal neoplasm of endothelial origin; the spleen is the most commonly affected organ.MCT is a common neoplasm that may affect any region of the body, without predilection for sex, although some breeds haveshown higher incidence. This report describes a case of HSA and MCT in a Pit bull terrier.Case: A 5-year-old white male Pit bull was presented to the Small Animal Clinic of the Federal Rural University of Pernambucowith nodules in preputial region measuring 5.4 x 3.7 cm and an ulcerated nodule in the right lateral thoracic region measuring23.0 x 19.0 x 5.5 cm. The owner reported surgical excision of two previous nodules one year before the consultation, but neitherwere submitted for cytopathological or post-surgical histopathological examination. Two months after the procedure, the nodulesrecurred. Cytopathological examinations of preputial and lateral thoracic nodules were performed, with a suggestive diagnosisfor HSA and MCT, respectively. Due to the unfavorable prognosis and the weakness of the animal, euthanasia was elected.Necroscopic examination revealed an ideal body condition score (4/9), hypertrophy of right pre-scapular and axillary lymphnodes, red hepatization in the apical lobe of the right lung, with multiple, soft and pigmented nodules in the spleen, liver, pancreas and testis. Several tissue samples were collected, conditioned in 10% buffered formaldehyde solution, routinely processedfor histology, and stained with hematoxylin-eosin and toluidine blue. Microscopically, the lateral thoracic nodule consisted ofround cells in cordonal arrangement, with sparse basophilic and discretely granular cytoplasm...

Nanog Expression and Proliferation Indices in Canine Cutaneous Mast Cell Tumors.

Mast cell tumors are one of the most frequent skin tumors in dogs. Treatment decisions often depend on a wide range of clinical information and the main criteria for prognostic formulation are histological grade, mitotic count, Ki67 index, and KIT immunostaining pattern. NANOG is a pluripotency factor expressed by normal and cancer stem cells, which is a prognostic marker and a potential therapeutic target for several human tumors. In the present study, mast cell tumor samples from 41 dogs were evaluated for NANOG and Ki67 by immunohistochemistry. All samples were positive for NANOG but its expression was not correlated with Ki67 index and no significant differences were found with respect to histopathological grades, disease-related mortality, or survival. Our results suggest that, although related to pluripotency, NANOG expression does not correlate with proliferative activity, and is not a reliable prognostic factor for canine cutaneous mast cell tumors.

Achados citopatológicos e ultrassonográficos de mastocitoma na bolsa escrotal em cão / Cytopathological and ultrasonographic findings of mastocytoma in a scrotal pouch in a dog

Mast cell tumors are the most common skin cancer in dogs. They are characterized by excessive proliferation of neoplastic mast cells. The areas of higher incidence are posterior region of the animal body, scrotum and flank. The diagnosis of mastocytoma is may have the aid of imaging tests such as ultrasonography, but it is essentially based on cytology. A dog was admitted to VETCLINIC for ultrasonographic and cytological examination of the scrotal region, because it was enlarged after orchiectomy procedure. Ultrasonographic examination revealed a heterogeneous echogenic image measuring 3.93 cm by 2.76 cm, showing regular and defined contours and with evident internal vascularity in Doppler mode suggestive of inflammatory process. In cytology, the sample of low cellularity consists of individualized round cells. Round to oval nucleus presenting coarse chromatin and sometimes evident nucleoli (1-2). Moderate to large cytoplasm with intense presence of granules of pink coloration. Intense anisocytosis and anisocariasis. Background of hemorrhagic blade with marked presence of granules, being the suggestive report, being the findings compatible with mastocytoma.

Achados citopatológicos e ultrassonográficos de mastocitoma na bolsa escrotal em cão / Cytopathological and ultrasonographic findings of mastocytoma in a scrotal pouch in a dog

Mast cell tumors are the most common skin cancer in dogs. They are characterized by excessive proliferation of neoplastic mast cells. The areas of higher incidence are posterior region of the animal body, scrotum and flank. The diagnosis of mastocytoma is may have the aid of imaging tests such as ultrasonography, but it is essentially based on cytology. A dog was admitted to VETCLINIC for ultrasonographic and cytological examination of the scrotal region, because it was enlarged after orchiectomy procedure. Ultrasonographic examination revealed a heterogeneous echogenic image measuring 3.93 cm by 2.76 cm, showing regular and defined contours and with evident internal vascularity in Doppler mode suggestive of inflammatory process. In cytology, the sample of low cellularity consists of individualized round cells. Round to oval nucleus presenting coarse chromatin and sometimes evident nucleoli (1-2). Moderate to large cytoplasm with intense presence of granules of pink coloration. Intense anisocytosis and anisocariasis. Background of hemorrhagic blade with marked presence of granules, being the suggestive report, being the findings compatible with mastocytoma.(AU)

Outcome of adjuvant chemotherapy with lomustine, vinblastine and chlorambucil on management of canine mast cell tumour of high to intermediate risk / Resultado da quimioterapia adjuvante com lomustina, vimblastina e clorambucil no manejo do mastocitoma canino de risco alto a intermediário

In spite of the many available protocols, the use of chemotherapy for the management of canine mast cell tumours (MCT) remains empirical, and there is lack of criteria for the choice of protocol and definition of patients who may benefit from treatment. The objective of this study was to evaluate the outcome of dogs with MCT after adjuvant chemotherapy according to the risk of recurrence or metastasis proposed on the literature. This prospective study included 89 followed up dogs with prognosis assesment including clinical, histological, immunohistochemical and genetic features of canine MCT. Patients were grouped according to risk of recurrence and metastasis and recommended treatment with lomustine followed by chlorambucil if considered at high-risk, or vinblastine followed by chlorambucil if a patient was at intermediate risk. Outcome was defined by disease-free interval (DFI) and overall survival (OS) estimated by Kaplan-Meier curve. Adjuvant lomustine was useful for control of canine MCT of high-risk of recurrence or metastasis, but only when sequentially associated to chlorambucil with a DFI of 686 days and not reached OS. There was no difference in outcome in the intermediate-risk group despite choosen treatment. Patients at intermediate-to-low risk may not require adjuvant treatments, even in the absence of free surgical margins.(AU)

Apesar dos inúmeros protocolos disponíveis, o uso da quimioterapia permanece empírico para o mastocitoma canino e faltam critérios para escolha do protocolo e da definição dos pacientes que poderiam se beneficiar do tratamento. O objetivo deste estudo foi avaliar o resultado de cães com mastocitoma após a quimioterapia adjuvante, de acordo com o risco de recorrência ou metástase proposto na literatura. Este estudo prospectivo incluiu 89 cães com acompanhamento clínico e avaliação prognóstica, incluindo características clínicas, histológicas, imuno-histoquímicas e genéticas dos mastocitomas. Os pacientes foram agrupados segundo o risco de recorrência ou metástase, sendo recomendado tratamento com lomustina seguida de clorambucila, se considerados sob alto risco, ou vimblastina seguida de clorambucila, se estivessem sob risco intermediário. O resultado final foi definido pelo intervalo livre de doença (ILD) e pela sobrevida global (SG), estimados pela curva de Kaplan-Meier. Na adjuvância, a lomustina foi útil no controle do mastocitoma canino de alto risco, mas apenas quando associada ao clorambucila, com um ILD de 686 dias, sem atingir a mediana para SG. Não houve diferença no grupo de risco intermediário, independentemente do tratamento escolhido. Pacientes de risco intermediário podem não necessitar de tratamentos adjuvantes, mesmo na ausência de margens cirúrgicas livres.(AU)

Outcome of adjuvant chemotherapy with lomustine, vinblastine and chlorambucil on management of canine mast cell tumour of high to intermediate risk / Resultado da quimioterapia adjuvante com lomustina, vimblastina e clorambucil no manejo do mastocitoma canino de risco alto a intermediário

In spite of the many available protocols, the use of chemotherapy for the management of canine mast cell tumours (MCT) remains empirical, and there is lack of criteria for the choice of protocol and definition of patients who may benefit from treatment. The objective of this study was to evaluate the outcome of dogs with MCT after adjuvant chemotherapy according to the risk of recurrence or metastasis proposed on the literature. This prospective study included 89 followed up dogs with prognosis assesment including clinical, histological, immunohistochemical and genetic features of canine MCT. Patients were grouped according to risk of recurrence and metastasis and recommended treatment with lomustine followed by chlorambucil if considered at high-risk, or vinblastine followed by chlorambucil if a patient was at intermediate risk. Outcome was defined by disease-free interval (DFI) and overall survival (OS) estimated by Kaplan-Meier curve. Adjuvant lomustine was useful for control of canine MCT of high-risk of recurrence or metastasis, but only when sequentially associated to chlorambucil with a DFI of 686 days and not reached OS. There was no difference in outcome in the intermediate-risk group despite choosen treatment. Patients at intermediate-to-low risk may not require adjuvant treatments, even in the absence of free surgical margins.(AU)

Apesar dos inúmeros protocolos disponíveis, o uso da quimioterapia permanece empírico para o mastocitoma canino e faltam critérios para escolha do protocolo e da definição dos pacientes que poderiam se beneficiar do tratamento. O objetivo deste estudo foi avaliar o resultado de cães com mastocitoma após a quimioterapia adjuvante, de acordo com o risco de recorrência ou metástase proposto na literatura. Este estudo prospectivo incluiu 89 cães com acompanhamento clínico e avaliação prognóstica, incluindo características clínicas, histológicas, imuno-histoquímicas e genéticas dos mastocitomas. Os pacientes foram agrupados segundo o risco de recorrência ou metástase, sendo recomendado tratamento com lomustina seguida de clorambucila, se considerados sob alto risco, ou vimblastina seguida de clorambucila, se estivessem sob risco intermediário. O resultado final foi definido pelo intervalo livre de doença (ILD) e pela sobrevida global (SG), estimados pela curva de Kaplan-Meier. Na adjuvância, a lomustina foi útil no controle do mastocitoma canino de alto risco, mas apenas quando associada ao clorambucila, com um ILD de 686 dias, sem atingir a mediana para SG. Não houve diferença no grupo de risco intermediário, independentemente do tratamento escolhido. Pacientes de risco intermediário podem não necessitar de tratamentos adjuvantes, mesmo na ausência de margens cirúrgicas livres.(AU)