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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.

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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)

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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)

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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.

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This study searched a rare and aggressive type of cancer in dogs and humans, the breast carcinosarcoma. Both clinical and pathological traits of mammary carcinosarcomas in dogs are similar to humans, such as infrequent occurrence, fast tumor growth, and unfavorable prognosis when compared to carcinomas. Other possible alterations include chromosomal abnormalities that can be useful for the identification of tumoral cells and diagnosis. The aim of this study was to compare the chromosomal features of peripheral lymphocytes and tumor cells in a mammary carcinosarcoma of a 14-year-old female Poodle. Chromosomes were analyzed from 210 metaphases by conventional Giemsa staining, C-banding, and base-specific fluorochrome staining with chromomycin A3 (CMA3+) and DAPI. Of the 105 blood cells, 56.3% followed the standard karyotype of dogs (2n = 78). In contrast, the carcinosarcoma cells showed high chromosomal numbers (104 to 153), divided into 80% hypertriploid (118 to 136 chromosomes), 10.5% hypotetraploid (137 to 153 chromosomes), 5.7% hypotriploid (104 to 116 chromosomes), and 3.8% triploid cells (117 chromosomes). Among the aneuploid cells identified, we highlighted the trisomy of pair 1 and X chromosome once these elements were easily recognized in karyotype because of their size (pair 1) or differential morphology. Heterochromatin in normal cells was restricted to the pericentromeric region of all chromosomes while few C-bands were observed in tumor cells. This apparent loss of heterochromatin in neoplastic cells was supposed to favor centric fusion among formerly acrocentric chromosomes. Fluorochrome staining reinforced this hypothesis once GC-rich segments (CMA3+) were identified on 10 chromosomes from normal cells (2n = 78) whereas carcinosarcoma metaphases had up to 11 chromosomes bearing CMA3 signals in spite of their remarkable high chromosomal numbers. We concluded that, like in humans, the carcinosarcoma in dogs caused genome instability that eventually led to structural and numerical chromosomal aberrations. Besides, this study reinforced the importance of cytogenetic studies in dogs as a reference material for human cancer studies, especially in rare cases, since it is possible to increase knowledge about the characteristics of breast neoplasms in which there is a little availability of similar cases for comparative studies.

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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.

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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.

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.

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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)

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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.

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O carcinossarcoma é um tumor maligno, pouco frequente em cães, composto por células do tecido epitelial e mesenquimal. Constatar alterações bioquímicas, hematológicas e determinar um possívelmarcador tumoral circulante (MTC) seria de extrema importância para avaliar a resposta do organismofrente ao tumor e ao tratamento. Marcadores tumorais permitem conhecer a presença, evoluçãoou resposta terapêutica de um tumor maligno. Neste trabalho, relata-se o caso de uma cadela da raça poodle de 12 anos de idade que apresentava carcinossarcoma na mama torácica com metástase para linfonodos e pulmão, sendo submetida à mastectomia radical. Como proposta de identifi car marcadores tumorais confi áveis para acompanhar a evolução da doença, realizou-se testes laboratoriais dehemograma completo, LDH (desidrogenase láctica), fosfatase alcalina, cálcio, fósforo e CEA (AntígenoCarcinoembrionário MTC). Foi possível evidenciar uma elevada concentração sorológica de CEAem coleta realizada no pré- cirúrgico, sugerindo sua utilização como possível marcador tumoral paraauxiliar no diagnóstico do câncer de mama avançado em cadelas(AU)

The carcinosarcoma is a malignant tumor, uncommon in dogs, composed of cells of mesenchymaland epithelial tissue. Search for biochemical and hematological changes, and determine a possibletumor marker (TM) would be extremely important to assess the bodys response against the tumorand treatment. Tumor markers allow us to know the presence, progression or therapeutic response ofa malignant tumor. Here we report a case of a female dog, poodle 12 year-old that had mammary carcinosarcomawith metastasis to thoracic lymph nodes and lungs, and underwent radical mastectomy.As a proposal to identify reliable tumor markers for monitoring disease progression, we carried outlaboratory tests hemogram, LDH (lactic dehydrogenase), alkaline phosphatase, calcium, phosphorusand CEA (Carcinoembryonic Antigen -TM). The results showed a high concentration of CEA in serologicalsamples were collected pre-surgery, suggesting its possible use as a tumor marker for thediagnosis of advanced mammary cancer in female dog(AU)

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O carcinossarcoma é um tumor maligno, pouco frequente em cães, composto por células do tecido epitelial e mesenquimal. Constatar alterações bioquímicas, hematológicas e determinar um possívelmarcador tumoral circulante (MTC) seria de extrema importância para avaliar a resposta do organismofrente ao tumor e ao tratamento. Marcadores tumorais permitem conhecer a presença, evoluçãoou resposta terapêutica de um tumor maligno. Neste trabalho, relata-se o caso de uma cadela da raça poodle de 12 anos de idade que apresentava carcinossarcoma na mama torácica com metástase para linfonodos e pulmão, sendo submetida à mastectomia radical. Como proposta de identifi car marcadores tumorais confi áveis para acompanhar a evolução da doença, realizou-se testes laboratoriais dehemograma completo, LDH (desidrogenase láctica), fosfatase alcalina, cálcio, fósforo e CEA (AntígenoCarcinoembrionário – MTC). Foi possível evidenciar uma elevada concentração sorológica de CEAem coleta realizada no pré- cirúrgico, sugerindo sua utilização como possível marcador tumoral paraauxiliar no diagnóstico do câncer de mama avançado em cadelas

The carcinosarcoma is a malignant tumor, uncommon in dogs, composed of cells of mesenchymaland epithelial tissue. Search for biochemical and hematological changes, and determine a possibletumor marker (TM) would be extremely important to assess the body’s response against the tumorand treatment. Tumor markers allow us to know the presence, progression or therapeutic response ofa malignant tumor. Here we report a case of a female dog, poodle 12 year-old that had mammary carcinosarcomawith metastasis to thoracic lymph nodes and lungs, and underwent radical mastectomy.As a proposal to identify reliable tumor markers for monitoring disease progression, we carried outlaboratory tests hemogram, LDH (lactic dehydrogenase), alkaline phosphatase, calcium, phosphorusand CEA (Carcinoembryonic Antigen -TM). The results showed a high concentration of CEA in serologicalsamples were collected pre-surgery, suggesting its possible use as a tumor marker for thediagnosis of advanced mammary cancer in female dog

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A case of mammary carcinosarcoma is reported in a 13-year-old, mixed breed female cat, which was not spayed and had not received contraceptives. The patient presented extensive and coalescent nodules in all mammary glands. Based on the histological and immunohistochemical findings, the diagnosis of mammary carcinosarcoma was confirmed.

Descreve-se um caso de carcinossarcoma mamário em uma gata, sem raça definida, de 13 anos de idade. A gata não era castrada e não recebeu anticoncepcionais. A paciente apresentou extensivos e coalescentes nódulos em todas as glândulas mamárias. Com base nos achados histológicos e imunoistoquímicos, firmou-se o diagnóstico de carcinossarcoma da glândula mamária.

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A case of mammary carcinosarcoma is reported in a 13-year-old, mixed breed female cat, which was not spayed and had not received contraceptives. The patient presented extensive and coalescent nodules in all mammary glands. Based on the histological and immunohistochemical findings, the diagnosis of mammary carcinosarcoma was confirmed.(AU)

Descreve-se um caso de carcinossarcoma mamário em uma gata, sem raça definida, de 13 anos de idade. A gata não era castrada e não recebeu anticoncepcionais. A paciente apresentou extensivos e coalescentes nódulos em todas as glândulas mamárias. Com base nos achados histológicos e imunoistoquímicos, firmou-se o diagnóstico de carcinossarcoma da glândula mamária.(AU)

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A la Clínica Veterinaria de la Universidad de los Llanos, llegó un canino hembra de 9 años de edad raza Chow Chow, cuyo motivo de consulta fue epistaxis bilateral 4 meses atrás y una masa en la región nasal. Según lo reportado por el propietario, la masa había comenzado a salir 1 mes atrás del día de la consulta. Al examen clínico presentaba una masa subdérmica en la región nasal superior de 2 cm de diámetro. Se realizó una citología de la misma y se encontraron células inflamatorias sin presencia de células neoplásicas. El paciente volvió al mes y la masa con un diámetro de 5cm, estaba ubicada en la región nasal superior y región zigomática. El can presentaba disnea, anorexia, deshidratación del 6 por ciento, secreción mucopurulenta nasal y ocular, midriasis bilateral, reflejo corneal bilateral negativo, aumento de la presión infraocular del ojo derecho. En la glándula mamaria inguinal derecha presentaba una masa de 2cm de diámetro dura y móvil. Se realizó una citología por aspirado con aguja fina, de distintas zonas de las masas, tanto de la nariz, como de la glándula mamaria. Se valoró la citología permitiéndose definir el origen tumoral del proceso. Se realizó biopsia por incisión de la región sinonasal, diagnosticándose tumor mesenquimal maligno grado tres condrosarcoma sinonasal, conformado por células cartilaginosas pleomórficas con anisocariosis. Se realizaron radiografías de la región nasal y del pulmón, encontrándose una zona radiopaca a nivel del seno maxilar con osteolisis del hueso, se evidenciaba la masa de aproximadamente 4 cm de ancho por 2 cm de largo en el lado derecho. En el pulmón no se evidenció metástasis. Después del diagnóstico de histopatología se decide realizar la eutanasia, encontrándose histopatológicamente metástasis en pulmón, confirmación del condrosarcoma mesenquimal y un carcinosarcoma de glándula mamaria.

To the Veterinary Clinic of the Universidad de los Llanos, come a 9 years old Chow Chow female canine, whose consultation reason was a bilateral epistaxis occurred 4 months ago, sudden loss of the vision and a mass in the nasal region of 2cm of diameter approximately, according to the report of the owner, the mass showed up 1 month the day of the consultation. To the clinical exam they were the following abnormal discoveries. Hirsute hair, opaque, presented a subdermic mass approximately in the nasal region superior of 2 cm. diameter that grew to 5 cm. diameter after 1 month of the consultation, located in the nasal region superior and zigomatic region, of hard consistency, the animal had dysnea, bilateral mydriasis, the bilateral corneal reflection was negative, increase of the infraocular pressure of the right eye, the realized test of obstacles in the clinic was negative, that which showed us a blindness. Besides a complete clinical exploration and taking of the advantages of the cytology, she was carried out an aspired with fine needle of different areas of the masses so much neoplastic of the nose and of the region of the mammary gland, being obtained two types of samples. The cytology was evaluated to define origin of the tumors of the process. She was carried out biopsy for incision of the sinunosal region being diagnosed wicked tumor mesenchymal Chondrosarcoma sinunasal that commits bone. After having carried out the autopsy they took samples for histopathology. Being diagnosed mesenchymal chondrosarcoma sinunasal grade 3, with metastasis to lung, and a carcinosarcoma of mammary gland.

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