Clinical presentation, histological findings, and prognosis in female dogs with mixed mammary neoplasms / Apresentação clínica, achados histológicos e prognóstico em cadelas com neoplasias mamárias mistas

The aim of this study was to describe the clinical and morphological characteristics of mixed mammary neoplasms and verify what characteristics affect the prognosis of female dogs with carcinomas in mixed tumors and carcinosarcomas. This was a retrospective study of 67 female dogs that underwent mastectomies and were diagnosed with benign mixed tumors (n=13), carcinomas in mixed tumors (n=44) and carcinosarcomas (n=10). Data regarding the clinical and histological aspects of the neoplasms were collected and the relation with specific survival times, and hazard ratios (HR) in 24 months was calculated. In univariate analysis, the diagnosis of carcinosarcoma (HR 8.26, p=0.006), carcinomatous areas with micropapillary or solid patterns (HR 17.49; p=0. 001) and lymph node metastasis (HR 7.07;p=0.020) were associated with specific survival. In multivariable analysis, only micropapillary or solid pattern (HR=16.34; p=0.007) remained independent factor associated with lower specific survival. Micropapillary or solid carcinomatous patterns were associated with shorter specific survival time (p=0.002) among animals with carcinomas in mixed tumors. Among the carcinosarcomas, lymph node metastasis (p=0.010) was associated with a shorter specific survival time. In conclusion, carcinomas in mixed tumors and carcinosarcomas vary in prognosis depending on the carcinomatous proliferation patterns and spread of the disease.

O objetivo deste estudo foi descrever as características clínicas e morfológicas das neoplasias mamárias mistas e verificar quais características interferem no prognóstico de cadelas com carcinomas em tumores mistos e carcinossarcomas. Este foi um estudo retrospectivo de 67 cadelas, que foram submetidas a mastectomias e diagnosticadas com tumores mistos benignos (n = 13), carcinomas em tumores mistos (n = 44) e carcinossarcomas (n = 10). Foram coletados dados sobre os aspectos clínicos e histológicos das neoplasias e a relação com o tempo de sobrevida específica e a razão de risco (OR) em 24 meses foram calculadas. Na análise univariada, o diagnóstico de carcinossarcoma (HR 8,26; p=0,006), as áreas carcinomatosas com padrão micropapilar e sólido (HR 17,49; p= 0,001) e metástase linfonodal (HR 7,07; p=0,020) foram associadas à menor sobrevida específica. Na análise multivariável, apenas o padrão micropapilar ou sólido (HR=16,34; p=0,007) permaneceu como fator independente associado à sobrevida. Proliferações carcinomatosas micropapilares ou sólidas (p = 0,002) foram associadas a tempos de sobrevida específica mais curtos entre os animais com carcinomas em tumor misto. Entre os pacientes com carcinossarcoma, metástases em linfonodos (p = 0,010) foram associadas a um menor tempo de sobrevida específica. Em conclusão, os resultados mostraram que os carcinomas em tumores mistos e os carcinossarcomas podem ter prognóstico variável, dependendo do padrão de proliferação carcinomatosa e da disseminação linfática da doença.

A comparative analysis of anatomopathological features and COX-2 expression of mammary neoplasms with malignant mesenchymal components in female dogs / Análise comparativa das características anatomopatológicas e expressão de COX2 em neoplasias mamárias com componentes mesenquimais malignos em cadelas

ABSTRACT: Canine mammary neoplasms with malignant mesenchymal components, such as carcinosarcomas and sarcomas, belong to an uncommon and histologically heterogeneous group. Little is known about the biological behavior of these histogenic variants. This study aimed to compare the clinicopathological characteristics and the COX-2 immunohistochemical expression of different histologic subtypes of carcinosarcomas and sarcomas. Samples of 23 carcinosarcomas and 15 sarcomas from the mammary glands of female dogs were studied. Medical records were reviewed to obtain clinical data. Subsequently, histology microscope slides were analyzed to assess for mesenchymal subtypes, necrosis, vascular invasion, histologic grades, and lymph node metastasis. Immunohistochemistry was used to assess the COX-2 expression. The malignant mesenchymal proliferation was categorized into osteosarcomas (23/40), fibrosarcomas (5/40), liposarcomas (6/40) and chondrosarcomas (4/40). The osteosarcomatous differentiation was the most predominant type among the sarcomas and carcinosarcomas and was associated with vascular invasion (P=0.010) and lymph node metastases (P=0.014). High COX-2 expression was detected in 14.3% of the carcinosarcomas (carcinoma and/or sarcoma cells) and 27.3% of the sarcomas. The carcinosarcomas and sarcomas had similar clinical and pathological characteristics and developed as large tumors, with intratumoral necrosis and a predominance of high histologic grades, although the frequency of vascular invasion and lymph node metastasis was low. Osteosarcoma subtypes presented more aggressive characteristics than non-osteosarcoma subtypes.

RESUMO: Neoplasias mamárias caninas com componentes mesenquimais malignos, como carcinossarcomas e sarcomas, são um grupo de neoplasias pouco frequentes e histologicamente heterogêneas e pouco se sabe sobre o comportamento biológico das variantes histogênicas. O objetivo desse estudo é comparar as características anatomopatológicas e a expressão imunoistoquímica de COX-2 de diferentes subtipos histológicos de carcinossarcomas e sarcomas. Foram estudados 23 carcinosarcomas e 17 sarcomas da glândula mamária de cadelas. Os prontuários médicos foram revisados para obtenção de dados clínicos. Posteriormente, as lâminas histológicas foram avaliadas para acessar os subtipos mesenquimais, necrose, invasão vascular, grau histológico, metástase linfonodal. A imunoistoquímica foi realizada para avaliar a expressão de COX-2. Os tipos encontrados de proliferação mesenquimal maligna foram osteossarcoma (23/40), fibrossarcoma (7/40), lipossarcoma (6/40) e condrossarcoma (4/40). A diferenciação osteossarcomatosa foi predominante entre os sarcomas e carcinossarcomas e foi associado com invasão vascular (P=0,006) e metástase linfonodal (P=0,014). Uma expressão alta de COX-2 foi detectada em 14,3% dos carcinossarcomas (células carcinomatosas e/ou sarcomatosas) e 27,3% dos sarcomas. Os carcinossarcomas e sarcomas apresentaram características clínicas e patológicas semelhantes e se desenvolveram como tumores grandes, com necrose intratumoral e predomínio de alto grau histológico, mas com baixa frequência de invasão vascular e metástase distante. Os subtipos osteossarcomatosos apresentaram características mais agressivas quando comparados com subtipos não osteossarcomatosos.

Presença da mutação do gene BRCA1 em cadelas com tumores mamários malignos / Presence of BRCA1 gene mutation in bitches with malignant mammary tumors

Mammary tumors (MTs) in bitches are similar to breast cancers in women. Thus, they can be used as a model for human breast cancer and findings can be extrapolated for use in human medicine. BRCA1 is a tumor suppressor gene. When the gene has a mutation, it cannot repair damaged DNA, which causes genetic instability and tumorigenesis. Therefore, we aimed to study the frequency of single nucleotide polymorphisms (SNPs) in the BRCA1 gene that are associated with distinct histological types of malignant MT in bitches. The study population consisted of 91 bitches, including a control group of 6 animals with healthy mammary glands and 85 animals with MTs. All animals underwent a presurgery evaluation consisting of a questionnaire administered to the person responsible for the animal, a physical examination, collection of peripheral blood for hematological and serum biochemistry evaluations, an electrocardiogram, and a preanesthesia evaluation. In addition, distant metastasis was studied via chest radiography and abdominal ultrasound. After evaluations were complete, the animals that could undergo surgery were administered general anesthesia and underwent a mastectomy or mammary gland sample collection. Histopathological examination and molecular analysis were performed to identify mutations in the BRCA1 gene. Histopathological examinations found 10 different types of malignant tumors in 36 sick animals. Tumor samples plus samples from the 6 control animals were subjected to DNA extraction, polymerase chain reaction (PCR) analysis, and genetic sequencing. The tumor with the highest incidence (33.33%) was a complex carcinoma, followed by carcinoma in mixed tumor (13.88), tubular carcinoma (13.88) and carcinosarcoma (13.88). Molecular analysis revealed 3 different SNP points in 5 samples (4006G>A, 3619A>G, and 3761C>T). The allelic variant 4006G>A (1/36) resulted in the alteration of the amino acid valine by isoleucine (V1336 I). The mutation 3619A>G (2/36) inserted the amino acid alanine instead of threonine (T1207 A). The mutation 3761C>T (2/36) led to the alteration of the amino acid serine by phenylalanine (S1254 F), a mutation for which there are no published reports. The histological types that showed BRCA1 mutations were complex carcinoma (1/5), carcinoma in mixed tumor (1/5), papillary carcinoma (1/5) and tubular carcinoma (2/5). Software analysis identified the new SNP (nucleotide 3761) in BRCA1 and 2 point mutations in nucleotides 4006 and 3619 and responsible for genetic instability. The development of breast cancer is caused by many endogenous and exogenous factors. The results of our study show that these factors have a greater presence in female, mixed breed, uncastrated, and older dogs, confirming the data in the veterinary literature. In the present study, we found different histological types of malignant breast tumors with mutations in the BRCA1 gene, as other authors have reported. However, we also found the mutation 3761C>T, which, to the best of our knowledge, has not been reported in the literature. This shows the need for studies in veterinary medicine that assess mutations in the BRCA1 gene and the most common histological types. In conclusion, SNPs in the BRCA1 gene cause genetic instability, resulting in additional mutations that lead to the development of breast tumors. They are point mutations that affect transcription, resulting in truncated proteins. These proteins may have a loss of function, leading to carcinogenesis.(AU)

Effects of ovarian pathologies and uterine inflammations on adenomyosis in bitches

Background: Adenomyosis is a non-neoplastic condition, characterized by the presence of endometrial glands or cells in the myometrium. Adenomyosis is defined by post-operative microscopic examination of uterine tissue and a rarely seen infertility problem in bitches. The process of transformation of healthy uterus into adenomiotic uterus is still a mystery. We aimed to determine role of ovarian pathologies and uterine inflammations on pathogenesis of uterine adenomyosis in bitches.Cases: After ovariohysterectomy, the uteri were fixed and processed by routine methods. Sections were stained with HematoxylinEosin, Massons trichrome and Periodic-Acid-Schiff and immunohistochemically; with p53 protein, Ki-67, α-smooth-muscle actin, cytokeratin-CK 8, 14, 19 antibodies, estrogen and progesterone receptors by Avidin-Biotin-Complex-Peroxidase method. Histopathologically, 7 of the collected tissue samples (n = 38) were diagnosed as adenomyosis. There were unilateral (n = 6) or bilateral (n = 1) adenomyosis in which endometrial glands had broken through the myometrium, and in some cases there were fibromyoma, inflammation, papillary hyperplasia and cysts in glands. Vaginal fibroma, fibromyoma and benign mix tumor (n = 1), simple carcinoma (n = 3), carcinosarcoma (n = 3) in mammary gland were determinated histopathologically. In addition to these findings, follicular cysts (n = 4), parovarian cyst (n = 1), adenocarcinoma and Rete ovarii adenoma were diagnosed in some ovaries. The CK 19 was scored at endometrial glands (n = 2) positively and also, muscle fibers were stained positively with α-smooth-muscle actin antibody (n = 7).Discussion: Adenomyosis is an infertility problem in adult dogs and is hard to detect with routine gynecological examinations. Adenomyosis can be seen unaccompanied by other gynecological problems such as endometritis or leiomyomas, while mammary tumors with adenomyosis have been previously reported in women and in only one case of a bitch.[...](AU)

Effects of ovarian pathologies and uterine inflammations on adenomyosis in bitches

Background: Adenomyosis is a non-neoplastic condition, characterized by the presence of endometrial glands or cells in the myometrium. Adenomyosis is defined by post-operative microscopic examination of uterine tissue and a rarely seen infertility problem in bitches. The process of transformation of healthy uterus into adenomiotic uterus is still a mystery. We aimed to determine role of ovarian pathologies and uterine inflammations on pathogenesis of uterine adenomyosis in bitches.Cases: After ovariohysterectomy, the uteri were fixed and processed by routine methods. Sections were stained with HematoxylinEosin, Masson’s trichrome and Periodic-Acid-Schiff and immunohistochemically; with p53 protein, Ki-67, α-smooth-muscle actin, cytokeratin-CK 8, 14, 19 antibodies, estrogen and progesterone receptors by Avidin-Biotin-Complex-Peroxidase method. Histopathologically, 7 of the collected tissue samples (n = 38) were diagnosed as adenomyosis. There were unilateral (n = 6) or bilateral (n = 1) adenomyosis in which endometrial glands had broken through the myometrium, and in some cases there were fibromyoma, inflammation, papillary hyperplasia and cysts in glands. Vaginal fibroma, fibromyoma and benign mix tumor (n = 1), simple carcinoma (n = 3), carcinosarcoma (n = 3) in mammary gland were determinated histopathologically. In addition to these findings, follicular cysts (n = 4), parovarian cyst (n = 1), adenocarcinoma and Rete ovarii adenoma were diagnosed in some ovaries. The CK 19 was scored at endometrial glands (n = 2) positively and also, muscle fibers were stained positively with α-smooth-muscle actin antibody (n = 7).Discussion: Adenomyosis is an infertility problem in adult dogs and is hard to detect with routine gynecological examinations. Adenomyosis can be seen unaccompanied by other gynecological problems such as endometritis or leiomyomas, while mammary tumors with adenomyosis have been previously reported in women and in only one case of a bitch.[...]

Osteopatia hipertrófica associada à metástase intratorácica de tumor mamário canino: relato de dois casos / Hypertrophic osteopathy associated with intrathoracic metastasis of mammary tumor canine: two cases report / Osteopatía hipertrófica asociada con metástasis intratorácica canina de tumor de mama: dos casos de informe

A osteopatia hipertrófica é um distúrbio de osteoprodução generalizada do periósteo que acomete os ossos longos, sendo geralmente secundária a alguma doença intratorácica, como doença cardiopulmonar ou neoplasia. A maioria das lesões são bilaterais e simétricas, podendo ocorrer nos quatro membros. O presente trabalho tem como objetivo relatar dois casos de osteopatia hipertrófica associada à metástase pulmonar de carcinoma mamário e os achados clínico patológicos destes cães foram estudados.(AU)

Hypertrophic osteopathy is a generalized bone production disorder the periosteum that affects the long bones, usually secondary to some intrathoracic disease, such as cardiopulmonary disease or cancer. Most lesions are bilateral and symmetrical and can occur in all four limbs. This study aims to report two cases of hypertrophic osteopathy associated pulmonary metastasis of breast carcinoma and the clinical and pathological findings of these dogs were studied.(AU)

Osteopatía hipertrófica es un trastorno generalizado osteoproducción del periostio que afecta a los huesos largos, generalmente secundaria a alguna enfermedad intratorácica, como la enfermedad cardiopulmonar o cáncer. La mayoría de las lesiones son bilaterales y simétricas, que se producen en las cuatro extremidades. Este estudio tiene como objetivo reportar dos casos de la osteopatía hipertrófica asociada con se estudiaron las metástasis pulmonares de carcinoma de mama hallazgos clínicos y patológicos de estos perros.(AU)

Osteopatia hipertrófica associada à metástase intratorácica de tumor mamário canino: relato de dois casos / Hypertrophic osteopathy associated with intrathoracic metastasis of mammary tumor canine: two cases report / Osteopatía hipertrófica asociada con metástasis intratorácica canina de tumor de mama: dos casos de informe

A osteopatia hipertrófica é um distúrbio de osteoprodução generalizada do periósteo que acomete os ossos longos, sendo geralmente secundária a alguma doença intratorácica, como doença cardiopulmonar ou neoplasia. A maioria das lesões são bilaterais e simétricas, podendo ocorrer nos quatro membros. O presente trabalho tem como objetivo relatar dois casos de osteopatia hipertrófica associada à metástase pulmonar de carcinoma mamário e os achados clínico patológicos destes cães foram estudados.

Hypertrophic osteopathy is a generalized bone production disorder the periosteum that affects the long bones, usually secondary to some intrathoracic disease, such as cardiopulmonary disease or cancer. Most lesions are bilateral and symmetrical and can occur in all four limbs. This study aims to report two cases of hypertrophic osteopathy associated pulmonary metastasis of breast carcinoma and the clinical and pathological findings of these dogs were studied.

Osteopatía hipertrófica es un trastorno generalizado osteoproducción del periostio que afecta a los huesos largos, generalmente secundaria a alguna enfermedad intratorácica, como la enfermedad cardiopulmonar o cáncer. La mayoría de las lesiones son bilaterales y simétricas, que se producen en las cuatro extremidades. Este estudio tiene como objetivo reportar dos casos de la osteopatía hipertrófica asociada con se estudiaron las metástasis pulmonares de carcinoma de mama hallazgos clínicos y patológicos de estos perros.

Consensus regarding the diagnosis, prognosis and treatment of canine mammary tumors: benign mixed tumors, carcinomas in mixed tumors and carcinosarcomas

Mammary neoplasms are the most frequent tumors in female dogs. Of these neoplasms, benign mixed tumors (BMTs) and carcinomas in mixed tumors (CMTs) represent a large proportion of small animal oncology diagnoses. Together with carcinosarcomas (CSs), these three neoplastic entities are characterized by the proliferation of benign or malignant epithelial, myoepithelial, and mesenchymal cells, depending on their histological types. This histological heterogeneity, in addition to their molecular heterogeneity, confers these tumors with distinct biological behavior, which results in the need for different clinical and therapeutic approaches. The present consensual document elucidates the oncological issues related to the diagnosis, prognosis, and treatment of BMTs, CMTs, and CSs of the canine mammary gland.

Consensus regarding the diagnosis, prognosis and treatment of canine mammary tumors: benign mixed tumors, carcinomas in mixed tumors and carcinosarcomas

Mammary neoplasms are the most frequent tumors in female dogs. Of these neoplasms, benign mixed tumors (BMTs) and carcinomas in mixed tumors (CMTs) represent a large proportion of small animal oncology diagnoses. Together with carcinosarcomas (CSs), these three neoplastic entities are characterized by the proliferation of benign or malignant epithelial, myoepithelial, and mesenchymal cells, depending on their histological types. This histological heterogeneity, in addition to their molecular heterogeneity, confers these tumors with distinct biological behavior, which results in the need for different clinical and therapeutic approaches. The present consensual document elucidates the oncological issues related to the diagnosis, prognosis, and treatment of BMTs, CMTs, and CSs of the canine mammary gland.(AU)

Antioxidant effects of açaí seed ( Euterpe oleracea ) in anorexia-cachexia syndrome induced by Walker-256 tumor

PURPOSE: To assess antioxidant effects of açaí seed extract on anorexia-cachexia induced by Walker-256 tumor. METHODS: A population of 20 lab rats were distributed into four groups (n=5): Control Group (CG), which only received tumor inoculation. Experimental Group-100 (EG-100), with animals submitted to tumor inoculation and treated with seed extract in a 100 mg / ml concentration through gavage. Experimental Group-200 (EG-200), with animals submitted to tumor inoculation and treated with seed extract in a 200 mg / ml concentration. Placebo Group (GP), which received tumor inoculation and ethanol-water solution. We analyzed proteolysis, lipid peroxidation, tumor diameter and weight. RESULTS: Lipid peroxidation was representative only in the cerebral cortex, where there was more oxidative stress in rats treated with the extract (p = 0.0276). For proteolysis, there was less muscle damage in untreated rats (p = 0.0312). Only tumor diameter in treated rats was significantly lower (p = 0.0200) compared to untreated ones. CONCLUSIONS: The açaí seed extract showed no beneficial effect on the general framework of the cachectic syndrome in lab rats. However, some anticarcinogenic effects were observed in the tumor diameter and weight.(AU)

ESTUDO RETROSPECTIVO DE 973 NEOPLASIAS EPITELIAIS EM CÃES

Neoplasias acometem humanos e animais desde os tempos da Pré-História e, na atualidade, estão entre as enfermidades de maior impacto na saúde dessas espécies. Há séculos, estudiosos procuram desvendar o processo de oncogênese, buscando determinar fatores desencadeantes associados à doença, a fim de preveni-la e melhor combatê-la. Na espécie canina, dentre as neoplasias de maior ocorrência figuram aquelas de origem epitelial, as quais representam 50% dos tumores diagnosticados na espécie. Destes, a grande maioria apresenta comportamento maligno, comprometendo a qualidade de vida dos animais acometidos e, frequentemente, cursando com o óbito. Diante disso, este estudo retrospectivo teve por objetivo analisar o arquivo de dados do Setor de Patologia Animal da Escola de Veterinária e Zootecnia da Universidade Federal de Goiás (SPA-EVZ-UFG), no período de janeiro de 2006 a dezembro de 2018, selecionando os diagnósticos de neoplasias epiteliais em cães. Dessa forma, foram catalogados 973 casos, compreendendo 66 diagnósticos distintos, dos quais tumores malignos (73,8%) prevaleceram. Tumores nas glândulas mamárias obtiveram maior frequência (72,7%), seguidos dos cutâneos (20,5%) e demais regiões (6,8%). Cadelas representaram 85,9%dos animais, enquanto os machos 14,1%. Houve predominância de animais idosos (68,6%) e cães sem raça definida (SRD) (30,2%). Contudo, entre cães de raça definida, destacaram-se aqueles das raças Poodle (15,4%) e Dachshund (10,1%). Dentre os tumores mamários, carcinoma em tumor misto (14,9%), carcinoma complexo (12,6%), carcinossarcoma (11,9%), tumor misto benigno (9,8%) e carcinoma sólido (8,9%) foram os de maior representatividade. O carcinoma de células escamosas (CCE) (34,7%) e o adenoma de glândula sebácea (11,6%) se destacaram entre os tumores cutâneos, e o ameloblastoma (38,8%), por sua vez, apresentou maior frequência entre as demais neoplasias epiteliais. Em conclusão, neoplasias de glândula mamária e pele obtiveram maior representatividade entre os tumores epiteliais, com maior incidência daqueles de comportamento maligno, sendo os cães sem raça definida os mais acometidos.

Neoplasms have afflicted humans and animals since Prehistorical times and are now among the illness of major impact on the health of both species. For centuries, scholars have been trying to unravel the oncogenesis process seeking to determine the triggering factors associated to the disease in order to better fight it and prevent it. In the canine species, among the neoplasms of major occurrence are those of epithelial origin which represent 50% of all the diagnosed tumors of the specie. Of these tumors, the majority present aggressive behavior, compromising the life quality of the afflicted animals and, frequently , leading to death. Before that, this retrospective study aimed analyze the data files of Setor de Patologia Animal da Escola de Veterinária e Zootecnia da Universidade Federal de Goiás (SPA-EVZ-UFG), in the period of January, 2006 to December, 2018, selecting all the epithelial neoplasm diagnoses in dogs. Thus, were cataloged 973 cases, comprehending 66 distinct diagnoses from which malignant tumors prevailed (73,8%) . Tumors of the mammary gland obtained higher frequency (72,7%), followed by the cutaneous tumors (20,5%) and tumors in other regions (6,8%). Bitches represented 85,9% of all animals, while only 14,1% corresponded to males. There was prevalence of elderly animals (68,6%) and dogs without defined breed (30,2%). However, among the dogs with defined breed, the Poodle (15,4%) and the Dachshund (10,1%) highlighted. Among the mammary tumors the carcinoma in mixed tumor (14,9%), complex carcinoma (12,6%), carcinosarcoma (11,9%), benign mixed tumor (9,8%) and the solid carcinoma (8,9%) had major representativity. The squamous cell carcinoma (34,7%) and sebaceous adenoma (11,6%) featured between the cutaneous tumors, in its turn the ameloblastoma (38,8%) presented higher frequency among the other epithelial neoplasms observed. In conclusion, skin and mammary gland neoplasms obtained higher representativity between the epithelial tumors observed, with higher incidence of those with malignant behavior, being dogs without defined breed more afflicted.

Avaliação da imunomarcação de células-tronco tumorais em carcinossarcomas mamários e carcinomas em tumores mistos em cadelas / Evaluation of immunostaining of tumor stem cells in mammary carcinosarcomas and carcinomas in mixed tumors in bitches

As células-tronco tumorais (CTTs) pertencem a uma pequena população de células dentro do tumor com propriedades de autorrenovação e diferenciação em outros tipos celulares. Neste estudo avaliou-se o comportamento tanto das porções mesenquimais quanto das epiteliais de seis carcinossarcomas (CSs), 11 carcinomas em tumores mistos (CTMs) grau I, 11 grau II e 10 grau III. Nas porções epiteliais dos CS e CTM foram observadas imunomarcações para os anticorpos CD44, CD24, Oct-4 e ALDH-1. Nas porções mesenquimais dos CS, nas porções epiteliais dos CTMs graus II e III não houve imunomarcação para o ALDH-1. Concluiu-se que as CTTs são expressas em proporções iguais tanto nas porções mesenquimais quanto nas epiteliais dos CSs e ausentes nas porções mesenquimais bem diferenciadas de CTMs.(AU)

Cancer stem cells belong to a small population of cells within the tumor with properties of self-renewal and differentiation into other cell types. In this study, the behavior of both portions, mesenchymal and epithelial, was evaluated. Six carcinosarcomas (CSs), 11 carcinomas within mixed tumors (CWMTs) grade I, 11 grade II, and 10 grade III were evaluated. In the epithelial portions of the CS and CWMTs was observed immunostaining for antibodies CD44, CD24, Oct-4 and ALDH-1. In the mesenchymal portions of the CS, in the epithelial portions of CMTs grades II and III no immunostaining for ALDH-1 was found. It was concluded that the tumor stem cells are expressed in equal proportions in the epithelial and mesenchymal portions of the CS. No immunostaining in the mesenchymal portions of well-differentiated CWMTs was seen.(AU)

PESQUISA DE CÉLULAS NEOPLÁSICAS EM MEDULA ÓSSEA DE CADELAS COM TUMOR DE MAMA

A glândula mamária é o segundo sítio mais comum de desenvolvimento tumoral em cadelas. Uma das formas de estadiamento destes tumores é avaliar a presença ou ausência de metástase à distância, inclusive na medula óssea. Este achado, na Medicina, associa-se a baixa sobrevida de mulheres com tumores mamários, porém na Medicina Veterinária esse estadiamento clínico é mais utilizado para pacientes com linfomas e mastocitomas. Estudos que utilizem a biópsia de medula óssea como método de pesquisa de estadiamento em tumores mamários são escassos. Desta forma o presente estudo teve como objetivo avaliar lesões mamárias e a medula óssea de 36 cadelas, buscando-se células tumorais disseminadas ou focos metastáticos. Para isso realizou-se a análise histopatológica dos tumores de mama, linfonodos e medula óssea dessas cadelas, corados com Hematoxilina e Eosina. Na medula óssea também foram utilizadas a coloração com Tricrômio de Masson, para avaliação de fibrose medular, e a imunohistoquímica, para a pesquisa de micrometástase. O carcinoma em tumor misto grau I fora o mais observado (18,08%), não havendo diferença estatística com relação ao tamanho tumoral e a presença de metástase em linfonodos. Na medula óssea de uma cadela com carcinossarcoma (4,35%) houve marcação citoplasmática de uma provável célula tumoral disseminada, de origem epitelial, com o anticorpo citoqueratina-19 pela imunohistoquímica. Nenhuma das cadelas que apresentou diminuição da celularidade ou fibrose medular (Tricrômio de Masson) ou tiveram marcação celular para citoqueratina. Conclui-se então que a avaliação da medula óssea pode ser utilizada como um método de estadiamento do tumor de mama em cadelas, pois células tumorais disseminadas apresentam potencial de se tornarem lesões secundárias bem como se disseminarem para focos distantes, causando metástases terciárias num período de tempo indeterminado.

The mammary glands are the second most common site of tumour development in female dogs. One way of staging these tumours is evaluate the presence or absence of distant metastasis, including those in the bone marrow. In Medicine, this finding is associated with the low survival of women with breast tumours, but in Veterinary Medicine this clinical staging is more used for patients with lymphomas and mast cells tumours. Studies using bone marrow biopsy as a method of staging research in breast tumours are scarce. Thus, the present study aimed to evaluate mammary lesions of 36 female dogs, as well as the bone marrow of them, searching for disseminated tumour cells or metastatic foci. For this, we performed histopathological analysis of mammary gland tumours, lymph node and bone marrow of these dogs, stained with Hematoxylin and Eosin. The Masson's trichrome staining was also used for the evaluation of bone marrow fibrosis and immunohistochemical technique for a micrometastasis research. Carcinoma in grade I mixed tumour was the most observed (18.08%), with no statistical difference between tumour size and lymph-node metastasis. In the bone marrow of a bitch with carcinosarcoma (4.35%) a probable disseminated tumor cell of epitelial origin was found using cytokeratin-19 antibody by immunohistochemistry technique. None of the female dogs presented decreased cellularity or bone marrow fibrosis (Masson's trichrome) or had cell labeling for cytokeratin. It is concluded that bone marrow evaluation can be used as a method of staging mammary tumour in female dogs, since disseminated tumor cells have the potential to become secondary lesions as well as spread to distant foci, causing tertiary metastases in an undetermined period of time.

AVALIAÇÃO DA SOBREVIDA DE CADELAS PORTADORAS DE NEOPLASIAS MAMÁRIAS SUBMETIDAS A MASTECTOMIA COM OU SEM TERAPIAS ADJUVANTES

A neoplasia mamária é o principal tumor que acomete as cadelas, sendo o estudo dessa afecção de alta importância clínica e científica devido à frequência com que é observada na rotina veterinária. Este estudo tem caráter retrospectivo e prospectivo, visando avaliar a sobrevida de cadelas portadoras de neoplasias mamárias submetidas à mastectomia terapêutica, a partir da caracterização epidemiológica, estadiamento clínico, avaliação histopatológica e terapêutica instituída de cadelas atendidas no Hospital Universitário de Medicina Veterinária Professor Firmino Mársico Filho (HUVET), da Universidade Federal Fluminense (UFF), em Niterói Rio de Janeiro, no período de março de 2013 a março de 2018. Obtiveram-se dados de 260 cadelas submetidas à mastectomia terapêutica, nas quais identificou-se 26 raças distintas, sendo as de maior frequência as raças puras (75,5%). A idade média foi de 10 ± 2,8 anos. A maioria das cadelas (178/260; 67%) não eram castradas, e 33% (86/260) foram castradas após os 2 anos de idade. Tumores malignos (97%) foram mais frequentes em relação aos benignos (3%). Carcinoma em tumor misto (140/260; 54%), seguido do carcinossarcoma (33/260; 13%) foram os tipos histológicos mais frequentes. A presença de tumores nas duas cadeias mamárias correspondeu à 60% (158/260) dos casos, e lesões múltiplas foram identificadas em 83% (216/260). Tumores menores do que 3 cm corresponderam à maior frequência (113/260; 44%), e o estádio da doença mais observado foi o estádio I (110/260; 42%). A sobrevida média global deste estudo foi superior a 3 anos. Estádios mais avançados da doença apresentaram tempo de sobrevida menor; cadelas que passaram por quimioterapia apresentaram tempo de sobrevida maior; quanto maior o grau histológico da neoplasia, menor o tempo de sobrevida; quanto maior o tamanho do tumor, menor o tempo de sobrevida; e em relação aos tipos histológicos mais frequentes, o carcinossarcoma apresentou o pior prognóstico, não atingindo a média de sobrevida global. Conclui-se que neoplasias malignas são mais frequentes; o estadiamento clínico e grau histológico do tumor influenciam o prognóstico e a sobrevida; mastectomia unilateral ou bilateral associada à quimioterapia adjuvante aumenta a sobrevida, e mais da metade das pacientes encontravam-se vivas até o final deste estudo.

Mammary neoplasm is the main tumor that affects bitches, in this way, the study of this condition of high clinical and scientific importance due to the frequency with which it is observed in the veterinary routine. This retrospective and prospective study aimed at evaluating the survival of bitches with breast cancer submitted to therapeutic mastectomy, based on the epidemiological characterization, clinical staging, histopathological and therapeutic evaluation of bitches attended at University Hospital of Veterinary Medicine Professor Firmino Mársico Filho (HUVET) of the Federal Fluminense University (UFF), in Niterói, Rio de Janeiro, from March 2013 to March 2018. Data were obtained from 260 dogs submitted to therapeutic mastectomy, in whith 26 different breeds with the highest frequency being pure breeds (75.5%). The mean age was 10 ± 2.8 years. Most bitches (178/260, 67%) were not castrated, and 33% (86/260) were castrated after 2 years of age. Malignant tumors (97%) were more frequent than benign tumors (3%). Carcinoma in mixed tumor (140/260; 54%), followed by carcinosarcoma (33/260; 13%) were the most frequent histological types. The presence of tumors in the two mammary chains corresponded to 60% (158/260) of the cases, and multiple lesions were identified in 83% (216/260). Tumors smaller than 3 cm corresponded to the highest frequency (113/260; 44%), and the most observed stage of the disease was stage I (110/260; 42%). The overall mean survival of this study was over 3 years. More advanced stages of the disease had a shorter survival time; bitches who underwent chemotherapy had a longer survival time; the greater the histological grade of the neoplasia, the shorter the survival time; the larger the tumor size, the shorter the survival time; and in relation to the most frequent histological types, the carcinossarcoma presented the worse prognosis, not reaching the mean of global survival. We conclude that malignant neoplasms are more frequent; the clinical staging and histological grade of the tumor influence the prognosis and the survival; Unilateral or bilateral mastectomy associated with adjuvant chemotherapy increases survival, and more than half of the patients were alive by the end of this study.

Mammary gland carcinosarcoma in a new zealand white rabbit (Oryctolagus cuniculus) / Mammary gland carcinosarcoma in a new zealand white rabbit (Oryctolagus cuniculus)

Background: Carcinosarcoma of the breast (metaplastic, biphasic metaplastic, metaplastic sarcomatoid carcinoma, sarcomatoid carcinoma) is an aggressive, rare neoplasm that has been reported to account for 0.08-0.2% of all breast malignancies. Mammary carcinosarcoma is rare in rabbits. Carcinosarcoma is a neoplasia composed of cells morphologically resembling malignant epithelial components and cells resembling malignant connective tissue elements. In spite of the rarity in rabbits, carcinosarcoma should always be considered in the different diagnoses of the mammary neoplasias, especially those of undifferentiated neoplasias.Case: An eight-month-old, female New Zealand white rabbit (Oryctolagus cuniculus) weighing 1.9 kg was referred to Tabriz university veterinary hospital for acute swelling on the abdomen and history of mammary mass. The complete blood count was within the reference ranges. The rabbit had been slightly depressed and anorectic. At clinical examination, the patient presented a huge lobulated mass in the mammary gland area. Clinical signs were included: emaciation and hardness in moving. Due to unfavorable prognosis the rabbit was euthanized and afterward complete mastectomy was performed. At necropsy, a non-infi ltrative multilobulated mass were observed in the chirurgic area. The mass didnt infi ltrate into the skin, subcutaneously and adjacent to the musculat

Background: Carcinosarcoma of the breast (metaplastic, biphasic metaplastic, metaplastic sarcomatoid carcinoma, sarcomatoid carcinoma) is an aggressive, rare neoplasm that has been reported to account for 0.08-0.2% of all breast malignancies. Mammary carcinosarcoma is rare in rabbits. Carcinosarcoma is a neoplasia composed of cells morphologically resembling malignant epithelial components and cells resembling malignant connective tissue elements. In spite of the rarity in rabbits, carcinosarcoma should always be considered in the different diagnoses of the mammary neoplasias, especially those of undifferentiated neoplasias.Case: An eight-month-old, female New Zealand white rabbit (Oryctolagus cuniculus) weighing 1.9 kg was referred to Tabriz university veterinary hospital for acute swelling on the abdomen and history of mammary mass. The complete blood count was within the reference ranges. The rabbit had been slightly depressed and anorectic. At clinical examination, the patient presented a huge lobulated mass in the mammary gland area. Clinical signs were included: emaciation and hardness in moving. Due to unfavorable prognosis the rabbit was euthanized and afterward complete mastectomy was performed. At necropsy, a non-infi ltrative multilobulated mass were observed in the chirurgic area. The mass didnt infi ltrate into the skin, subcutaneously and adjacent to the musculat

Mammary gland carcinosarcoma in a New Zealand white rabbit (Oryctolagus cuniculus)

Background: Carcinosarcoma of the breast (metaplastic, biphasic metaplastic, metaplastic sarcomatoid carcinoma, sarcomatoid carcinoma) is an aggressive, rare neoplasm that has been reported to account for 0.08-0.2% of all breast malignancies. Mammary carcinosarcoma is rare in rabbits. Carcinosarcoma is a neoplasia composed of cells morphologically resembling malignant epithelial components and cells resembling malignant connective tissue elements. In spite of the rarity in rabbits, carcinosarcoma should always be considered in the different diagnoses of the mammary neoplasias, especially those of undifferentiated neoplasias. Case: An eight-month-old, female New Zealand white rabbit (Oryctolagus cuniculus) weighing 1.9 kg was referred to Tabriz university veterinary hospital for acute swelling on the abdomen and history of mammary mass. The complete blood count was within the reference ranges. The rabbit had been slightly depressed and anorectic. At clinical examination, the patient presented a huge lobulated mass in the mammary gland area. Clinical signs were included: emaciation and hardness in moving. Due to unfavorable prognosis the rabbit was euthanized and afterward complete mastectomy was performed. At necropsy, a non-infiltrative multilobulated mass were observed in the chirurgic area. The mass didn't infiltrate into the skin, subcutaneously and adjacent to the musculature and it was moved easily. The neoplasia was solid, firm, and yellowbrownish. Tissue samples of the tumor were fixed in 10% neutral buffered formalin, embedded in paraffin, cut at 5 µm, and stained with hematoxylin and eosin and masson trichrome. Microscopically, the neoplasm had a solid pattern and was composed of a heterogeneous cell population, mainly pleomorphics. Polyhedral cells showing ovoid or vesicular nuclei with prominent nucleoli and abundant lightly acidophilic cytoplasm resembling epithelial cells were observed. Cells with scant cytoplasm and elongated or oval nuclei containing inconspicuous nucleoli resembling mesenchymal cell were also observed. There were also neoplastic areas with a myxoide matrix. Some young cartilage pieces were observed in the tumor. In some parts of the tumor a very dense fibrous connective tissue was observed. Based on the histological findings, the diagnosis of mammary carcinosarcoma was confirmed. Other organs showed normal histological characteristics. Discussion: The carcinosarcoma is a neoplasia characterized as containing a mixed cell population with malignant proliferation of both mesenchymal and epithelial-like cells. Although the carcinosarcoma is rare in the domestic species, their origin has been discussed in two theories: 1) multiclonal theory suggests that the epithelial and the mesenchymal components originated from two or more stem cells; 2) the monoclonal theory suggests that the epithelial and the mesenchymal components originated from totipotential neoplastic cells play multiple potential pathways of terminal differentiation. Abnormal level of growth and Prolactin hormones is one cause to breast tumors. Recent evidence supports the speculation that prolonged hyperprolactinemia leads to malignancy, given the case of ductal carcinoma in one woman who, after incomplete pituitary adenomectomy, was hyperprolactinemic for 15 years. This physiologic relationship and disease progression are important to consider in clinical diagnosis and management of these cases in rabbits. Although some studies were not showed any difference in level of mentioned hormones. In spite of being rare in rabbit, the carcinosarcoma should always be considered in the different diagnoses of the mammary neoplasias, mainly of those undifferentiated neoplasias.

Growth inhibition of Walker carcinosarcoma 256 with alcoholic extract of green tea leaves (Camellia sinensis) / Inibição do crescimento do carcinossarcoma 256 de Walker pelo extrato alcoólico de folhas de chá verde(Camellia sinensis)

PURPOSE: To evaluate the antitumor activity of alcoholic extracts of green tea (Camella sinensis). METHODS: Four groups of six Wistar rats were inoculated intramuscularly with 10(6) Walker tumor cells/mL. During 10 days, the animals received by gavage either 0.9% saline solution (Group I; negative control), solution containing 20 mg/Kg of tamoxifen (Group II; positive control), solution containing 0.07 g/Kg alcoholic extract of C. sinensis (Group III), or solution containing 0.14 g/Kg alcoholic extract of C. sinensis (Group IV). Following euthanasia on the tenth day, the tumor, liver, kidneys and spleen were excised and weighed, and tumor volume and tumor growth inhibition were quantified. RESULTS: The average weight of the animals was greater in Group IV than in Group II (p=0.0107). Tumor weight was smaller in Group IV than in Group I (p=0.0062), but did not differ from Group II. Tumor volume was smaller in Groups II and IV than in Group I (p=0.0131). Tumor growth inhibition was observed in Groups II (44.67% ± 32.47), III (16.83% ± 53.02) and IV (66.4% ± 25.82) (p>0.05). The groups did not differ with regard to the weight of the excised organs. CONCLUSION: Alcoholic extracts of green tea have antitumor activity.(AU)

OBJETIVO: Avaliar a atividade antitumoral do extrato alcoólico do chá verde (C. sinensis). MÉTODOS: Quatro grupos de seis ratos Wistar foram inoculados com 1x10(6) células/mL do tumor de Walker por via intramuscular. Os grupos foram tratados durante 10 dias, por gavagem, com salina 0,9 % (Grupo I, controle negativo), 20 mg/Kg de tamoxifeno (Grupo II, controle positivo) e extrato alcoólico de C. sinensis nas doses de 0,07 g/Kg (Grupo III) ou 0,14 g/Kg (Grupo IV). O volume e a inibição do crescimento tumoral foram calculados. RESULTADOS: A média dos pesos dos animais foi maior no Grupo IV do que no Grupo II (p=0,0107). O peso tumoral do Grupo IV foi menor do que o Grupo I (p=0,0062), mas não houve diferença quando comparado ao Grupo II. O volume tumoral foi menor nos grupos II e IV quando comparados ao Grupo I (p=0,0131). Inibição tumoral foi observada nos Grupos II = 44,67 ± 32,47, III = 16,83 ± 53,02 e IV = 66,4 ± 25,82 (p>0,05). Não houve diferença no peso dos órgãos entre os grupos. CONCLUSÃO: O extrato alcoólico do chá verde possui ação antitumoral.(AU)

Estudo clínico, patológico, epidemiológico e de sobrevida dos tumores mamários em gatas atendidas no Hospital Veterinário da Universidade Estadual de Londrina

Os tumores mamários em felinos compreendem cerca de 39 a 85 % das neoplasias nesta espécie. As neoplasias mamárias ocorrem geralmente em gatas idosas, não castradas e estão associados ao uso de progestágenos sintéticos. A maioria dos tumores mamários são malignos, invasivos e agressivos. Apresentam prognóstico desfavorável e grande capacidade de ocorrer recidiva local e metástase a distância. Objetivou-se, com este trabalho, caracterizar, sob ponto de vista epidemiológico, clínico e histopatológico as neoplasias mamárias de ocorrência espontânea em gatas (Felis catus). Foram revisados os arquivos do Laboratório de Patologia Animal da Universidade Estadual de Londrina (UEL). Cinquenta e um exames histopatológicos relacionados aos tumores mamários de gatas, proveniente do tratamento cirúrgico, foram analisados, no período de tempo compreendido entre 2005 e 2016. As lâminas foram lidas novamente e colocados na mesma classificação histológica. A média da idade das gatas com tumores mamários foi de a 9,7 anos e a maior frequência eram animais sem raça definida 72,5% (37/51), seguido da raça Siamês 23,5% (12/51) e Persa 4% (2/51). Os carcinomas mamários corresponderam 74%, (38/51), lesões não neoplásicas representaram 19,6% (10/51) e os tumores benignos com 5,8% (3/51). As lesões benignas foram classificadas em 100% como papilomas ductais, as lesões não neoplásicas compreenderam os fibroadenomatose com 70% (7/10), hiperplasia lobular, ductal e cisto cada um com 10% (1/10). Dentre as neoplasias malignas foram observados carcinomas cribiformes 40% (15/38), túbulos papilares 30% (12/38), carcinomas in situ 13,8% (4/38), carcinomas tubulares 7,8% (3/38), carcinomas sólidos 5,2% (2/38), carcinoma em tumor misto e carcinossarcoma com 2,6% (1/38). As metástases distantes foram encontradas principalmente nos pulmões. A maioria das neoplasias das glândulas mamárias em gatas apresentaram características malignas, evidenciando um mau prognóstico e menor tempo de sobrevida.

Mammary tumors in felines comprise about 39 to 85% of neoplasms in this species. These neoplasms usually occur in elderly, uncastrated cats and are associated with the use of synthetic progestogens. Most mammary tumors are malignant, invasive and aggressive. They present an unfavorable prognosis and great capacity of local recurrence and distant metastasis. The objective of this study was to characterize, from an epidemiological, clinical and histopathological point of view, the spontaneous mammary neoplasms of cats (Felis catus). The files of the Laboratory of Animal Pathology of the Universidade Estadual de Londrina (UEL) were reviewed. Fifty-one histopathological exams related to mammary glands from the surgical treatment were analyzed in the period between 2005 and 2016. The slides were read again and placed in the same histological classification. The mean age of cats with mammary tumors was 9.7 years and the highest frequency were non-breed animals (72.5%) (37/51), followed by the 23.5% (12/51) Siamese and Persian 4% (2/51). Mammary carcinomas accounted for 74%, (38/51), non-neoplastic lesions represented 19.6% (10/51) and benign tumors with 5.8% (3/51). The benign lesions were classified as 100% as ductal papillomas; non-neoplastic lesions comprised fibroadenomatosis with 70% (7/10), lobular, ductal and cyst hyperplasia each with 10% (1/10). Cribiform carcinoma was found in 40% (15/38), tubulopapillary 30% (12/38), ductal carcinoma in situ 13.8% (4/38), tubular carcinoma 7.8% (3/38), solid carcinoma 5.2% (2/38), carcinoma in mixed tumor and carcinosarcoma with 2.6% (1/38). Distant metastases were found mainly in the lungs. Most of the glandular neoplasms of the mammary glands presented malignant characteristics, evidencing a poor prognosis and shorter survival time.

Experimental model of ultrasound thermotherapy in rats inoculated with Walker-236 tumor

PURPOSE: To develop a model to evaluate the effects of focal pulsed ultrasound (US) waves as a source of heat for treatment of murine subcutaneous implanted Walker tumor. METHODS: An experimental, controlled, comparative study was conducted. Twenty male Wistar rats (160-300 g) randomized in 2 equal groups (G-1: Control and G-2: Hyperthermia) were inoculated with Walker-256 carcinosarcoma tumor. After 5 days G-2 rats were submitted to 45ºC hyperthermia. Heat was delivered directly to the tumor by an ultrasound (US) equipment (3 MHz frequency, 1,5W/cm³). Tumor temperature reached 45º C in 3 minutes and was maintained at this level for 5 minutes. Tumor volume was measured on days 5, 8, 11, 14 e 17 post inoculation in both groups. Unpaired t-test was used for comparison. P<0.05 was considered significant. RESULTS: Tumor volume was significantly greater in day 5 and decreased in days 11, 14 and 17 in treated rats. Rats treated with hyperthermia survived longer than control animals. On the 29th day following tumor inoculation, 40 percent of control rats and 77.78 percent of hyperthermia-treated rats remained alive. CONCLUSION: The proposed model is quite simple and may be used in less sophisticated laboratory settings for studying the effects of focal hyperthermia in the treatment of malignant implanted tumours or in survival studies.(AU)

OBJETIVO: Desenvolver um modelo para avaliar os efeitos do ultra-som focal pulsado como fonte de calor para o tratamento de tumores de Walker subcutâneos implantados em ratos. MÉTODOS: Um estudo experimental, controlado, comparativo foi realizado. Vinte ratos Wistar machos (160-300 g) divididos em dois grupos (G-1: Controle e G-2: hipertermia) foram inoculados com tumor de Walker carcinossarcoma-256. Após cinco dias os ratos do grupo G-2 ratos foram submetidos a hipertermia (45ºC). O calor foi aplicado diretamente no tumor por um equipamento de ultrassonografia (3 MHz, 1,5 W/cm³). A temperatura no tumor atingiu 45ºC em 3 minutos e foi mantida nesse nível por 5 minutos. O volume do tumor foi medido nos dias 5, 8, 11, 14 e 17 após a inoculação, em ambos os grupos. Teste t não pareado foi utilizado para comparação. P <0,05 foi considerado significante. RESULTADOS: O volume do tumor foi significativamente maior no 5º dia e diminuiu nos dias 11, 14 e 17 nos ratos tratados. Animais submetidos à hipertermia sobreviveram mais tempo que os animais do grupo controle. Vinte nove dias após a inoculação do tumor, 40 por cento dos ratos do grupo controle e 77,78 por cento dos ratos tratados com hipertermia permaneceram vivos. CONCLUSÃO: O modelo proposto é bastante simples e pode ser utilizado em laboratórios menos sofisticados para estudar os efeitos da hipertermia focal no tratamento dos tumores malignos implantados ou em estudos de sobrevida.(AU)

Características clinicopatológicas e prognóstico das neoplasias mamárias produtoras de matriz em cadelas

Tumores produtores de matriz são neoplasias caracterizadas pela presença de estroma mesenquimal com produção de matriz mixoide, condroide e/ou óssea. Essas neoplasias podem ocorrer na mama da cadela e são classificadas como tumores mistos (tumor misto benigno, carcinoma em tumor misto, carcinossarcoma, sarcomas em tumores mistos) e sarcomas. Apesar da frequência desses tipos histológicos, em especial dos tumores mistos benignos e carcinomas em tumores mistos, pouco se conhece a respeito do prognóstico, devido à escassez de estudos com seguimento clínico e diferentes nomenclaturas e critérios de classificação empregados ao longo do tempo, o que torna difícil a comparação dos trabalhos. O objetivo do presente estudo foi avaliar as implicações das características clinicopatológicas no prognóstico dos tumores mamários produtores de matriz que acometem as cadelas. Foram avaliadas cadelas admitidas para tratamento cirúrgico de rotina para remoção dos tumores de mama no Hospital de Clínicas Veterinárias da Universidade Federal do Rio Grande do Sul (HCV) no período de novembro de 2014 a março de 2016. Foram obtidas informações sobre apresentação clínica do tumor como tempo de percepção dos tumores, localização, tamanho, número de mamas afetadas e ulceração além da pesquisa de metástases por meio de exames de imagem por meio de consulta aos prontuários clínicos. Aspectos morfológicos do tumor como grau histológico, invasão linfática, necrose intratumoral e o subtipo histológico do componente epitelial maligno dos tumores mistos também foram avaliados pelo exame histopatológico. Após o término do tratamento foram obtidas informações sobre a saúde dessas cadelas durante retorno ao HCV ou por meio de contato telefônico com os tutores por um período mínimo de um ano para determinação da sobrevida e da recorrência e recidiva dos tumores. A possível associação entre as variáveis clínicopatológicas e os tipos tumorais foi avaliada por meio de análise de regressão logística multivariada. Durante o período de estudo foram admitidas 289 cadelas e dessas 156 (53,97%), foram diagnosticadas com algum tipo de neoplasia produtora de matriz, sendo 29 (18,58%) tumores mistos benignos, 82 (52,56%) carcinomas em tumores mistos, 20 (12,82%) carcinossarcomas, 9 (5,76%) sarcomas e 14 (8,97%) carcinomas em tumores mistos concomitante a outros tumores mamários não produtores de matriz. Para estudo de prognóstico foram incluídas 118 cadelas, que não haviam feito tratamento anterior para neoplasia mamária, não presentavam tumores de pele ou outros sistemas e nem outros tumores mamários de pior prognóstico. Destas, 12 (10,16%) apresentavam tumores mistos benignos, 64 (54,23%) carcinomas em tumores mistos, 20 (16,94%) carcinossarcomas, 8 (6,77%) sarcomas. Houve associação entre tamanho tumoral mensurado durante o exame clínico e a ocorrência de tumores mistos benignos ( = 0,004). Comparando-se todos os tumores malignos, os carcinossarcomas foram associados a um tamanho maior do que 5,0 cm ( = 0,001). Entre os tumores malignos, os carcinomas em tumores mistos apresentam maior sobrevida, em comparação com os carcinossarcomas ( = 0,034) sarcomas ( < 0,000). As cadelas que apresentavam tumores menores (< 3,0 cm) mensurado na patologia tiveram uma maior sobrevida ( = 0,017) e as que apresentavam metástase em linfonodo regional tiveram sobrevida menor ( = 0,043). Quando avaliados apenas os carcinomas em tumores mistos, as cadelas com tumores com tamanho menor na avaliação clínica (< 3,0 cm) apresentaram maior sobrevida, o mesmo acontecendo quando foi considerado o tamanho do tumor analisado na macroscopia durante o exame histopatológico ( = 0,045). As pacientes que apresentavam estadio mais avançado tiveram uma sobrevida mais curta ( = 0,036). Os carcinomas em tumores mistos com proliferação epitelial sólida, micropapilar ou anaplásica foram associados com graus histológicos mais altos quando comparados com aqueles com proliferação tubular, túbulo-papilar ou papilar, além de apresentarem uma tendência à sobrevida mais curta quando avaliada a curva de sobrevida. Tais aspectos devem ser levados em consideração para estabelecimento de prognóstico e escolha do tratamento mais efetivo para cadelas com tumores mamários produtores de matriz.

Matrix-producing tumors are characterized by the presence of mesenchymal stroma with production of myxoid, chondroid and / or bone matrix. These neoplasms may occur in the mammary gland of female dogs and are classified as mixed tumors (benign mixed tumor, carcinomas in mixed tumors, carcinosarcoma, sarcomas in mixed tumors) and sarcomas. Despite the frequency of these histological types, especially of benign mixed tumors and carcinomas in mixed tumors, little is known about the prognosis, due to the scarcity of studies evaluating the clinical follow-up of these tumors. In addition, the existing studies are difficult to compare due to the evaluation of few cases and the different histological classification systems used over time. The aim of this study was to evaluate the implications of the clinicopathological characteristics in the prognosis of the mammary tumors producing matrix that affect the female dogs. We assessed the female dogs admitted for routine surgical treatment for removal of mammary tumors at the Hospital of Veterinary Clinics of the Federal University of Rio Grande do Sul (HCV) from November 2014 to March 2016. In the pre-surgical clinical evaluation, information about clinical presentation of the tumor was obtained, such as time of tumor perception, location, size, number of affected mammary glands and ulceration, besides the metastasis search through imaging tests. Morphological aspects of the tumor such as histological grade, lymphatic invasion and intratumoral necrosis and the histological subtype of the malignant epithelial component of mixed tumors were also evaluated through histopathology. After end treatment, information on the health of these dogs was obtained through a return to HCV or telephone contact with the tutors for a minimum of one year to determine the survival, and recurrence or relapse of tumors. The possible association between clinical and morphological variables and tumor types was evaluated through multivariate logistic regression analysis. During the study period, 289 female dogs were admitted, and of these, 156 (53.97%) were diagnosed with some type of matrix-producing neoplasia, of which 29 (18.58%) were benign mixed tumors, 82 (52.56%) carcinomas in mixed tumors, 20 (12.82%) carcinosarcomas, 9 (5.76%) sarcomas and 14 (8.97%) carcinomas in mixed tumors concomitant with other non-matrix mammary tumors. For the prognostic study, 118 female dogs were included, which had not undergone previous treatment for mammary neoplasia, had no skin tumors or other systems and no other mammary tumor with a worse prognosis. Of these, 12 (10.16%) had mixed benign tumors, 64 (54.23%) carcinomas in mixed tumors, 20 (16.94%) carcinosarcomas, 8 (6.77%) sarcomas. The association between tumor size measured during the clinical examination and the occurrence of benign mixed tumors ( = 0.004) was verified. Comparing all malignant tumors, carcinosarcomas were associated with a size larger than 5 cm ( = 0.001). Among malignant tumors, carcinomas in mixed tumors had a longer survival compared to carcinosarcomas ( = 0.034) and sarcomas ( < 0.000). Female dogs with smaller tumors (<3.0 cm) measured in the pathology had a longer survival ( = 0.017) and those with regional lymph node metastasis had a shorter survival ( = 0.043). When only carcinomas in mixed tumors were evaluated, Tumors with a smaller size in the clinical evaluation (<3.0 cm) had a longer survival, as did the size of the tumor analyzed in the macroscopy during the histopathological examination ( = 0.045). Patients with more advanced stage had a shorter survival ( = 0.036). Carcinomas in mixed tumors with solid, micropapillary or anaplastic epithelial proliferation were associated with higher histological grades when compared to those with tubular, tubulopapillary or papillary proliferation, and presented a trend towards shorter survival when the survival curve was evaluated. Such aspects should be considered for establishing prognosis and choosing the most effective treatment for female dogs with matrix-producing mammary tumors.