Thymic carcinosarcoma with melanocytic differentiation in a dog.

Carcinosarcomas are very rare tumors in dogs. Although carcinosarcomas with melanocytic differentiation arising from organs other than the thymus have been described in humans, this type of tumor has not been reported in dogs in any part of the body. We observed such a tumor in the cranial mediastinum of an 11-year-old spayed female dachshund. The dog was admitted to the clinic because of coughing, sporadic regurgitation, and dyspnea. Thoracic ultrasonography and computed tomography revealed a large mediastinal mass that was surgically removed via sternotomy. The tumor was of thymic origin and demonstrated 3 distinct components: an epithelial component positive for pancytokeratin (AE1/AE3) and high molecular weight cytokeratin (CK5/CK6) with some cystic spaces; a mesenchymal component positive for vimentin; and in association with the epithelial part, a minor melanocytic component positive for Melan A. Histologic metastasis of the epithelial and melanocytic components was present within a tracheobronchial lymph node. The dog died 105 d after surgery, after an episode of acute dyspnea. Key clinical message: To the authors' knowledge, this is the first report of thymic carcinosarcoma with melanocytic differentiation.

Carcinosarcome thymique avec différenciation mélanocytaire chez un chienLes carcinosarcomes sont des tumeurs très rares chez le chien. Bien que des carcinosarcomes avec différenciation mélanocytaire provenant d'organes autres que le thymus aient été décrits chez l'homme, ce type de tumeur n'a été rapporté chez le chien dans aucune partie du corps. Nous avons observé une telle tumeur dans le médiastin cránien d'une femelle teckel stérilisée de 11 ans. Le chien a été admis à la clinique en raison de toux, de régurgitations sporadiques et de dyspnée. L'échographie thoracique et la tomodensitométrie ont révélé une masse médiastinale importante qui a été retirée chirurgicalement par sternotomie. La tumeur était d'origine thymique et présentait 3 composantes distinctes : une composante épithéliale positive pour la pancytokératine (AE1/AE3) et la cytokératine de haut poids moléculaire (CK5/CK6) avec quelques espaces kystiques; un composant mésenchymateux positif à la vimentine; et en association avec la partie épithéliale, un composant mélanocytaire mineur positif pour Melan A. Des métastases histologiques des composants épithéliaux et mélanocytaires étaient présentes dans un ganglion lymphatique trachéobronchique. Le chien est décédé 105 jours après l'intervention chirurgicale, à la suite d'un épisode de dyspnée aiguë.Message clinique clé :À la connaissance des auteurs, il s'agit du premier cas de carcinosarcome thymique avec différenciation mélanocytaire.(Traduit par Dr Serge Messier).

Thyroid carcinosarcoma masquerading as a paraesophageal abscess in a Cane Corso dog.

A 12-year-old castrated male Cane Corso dog was presented with cervical swelling, lethargy, anorexia, and cough. An extensive neck mass with necrotic cysts was observed, severely adherent to surrounding tissues. Based on diagnostic imaging including ultrasound, computed tomography, and fine-needle aspiration cytology, paraesophageal abscess was tentatively diagnosed. However, after the mass was surgically removed, a diagnosis of thyroid carcinosarcoma composed of neoplastic cell populations with epithelial and mesenchymal origins was made via histopathology and immunohistochemistry. The dog died of a recurrent mass with pulmonary metastasis 105 d after surgery. This report describes a rare type of canine thyroid cancer, thyroid carcinosarcoma, preoperatively masquerading as an abscess and postoperatively confirmed by histopathology. Key clinical message: Thyroid carcinosarcoma, despite its rarity in dogs, should be included in the differential diagnoses of cervical mass especially with an aggressive progression.

Carcinosarcome thyroïdien déguisé en abcès paraoesophagien chez un chien Cane Corso. Un chien Cane Corso mâle castré de 12 ans a été présenté avec de l'enflure cervicale, de la léthargie, de l'anorexie et une toux. Une masse étendue du cou avec des kystes nécrotiques a été observée, adhérente fortement aux tissus environnants. Sur la base de l'imagerie diagnostique comprenant l'échographie, la tomodensitométrie et la cytologie par aspiration à l'aiguille fine, un abcès paraoesophagien a été provisoirement diagnostiqué. Cependant, après l'ablation chirurgicale de la masse, un diagnostic de carcinosarcome thyroïdien composé de populations de cellules néoplasiques d'origine épithéliale et mésenchymateuse a été posé par histopathologie et immunohistochimie. Le chien est décédé d'une masse récurrente avec métastase pulmonaire 105 jours après la chirurgie. Ce rapport décrit un type rare de cancer de la thyroïde canine, le carcinosarcome thyroïdien, se faisant passer pour un abcès en préopératoire et confirmé en postopératoire par histopathologie.Message clinique clé:Le carcinosarcome thyroïdien, malgré sa rareté chez le chien, doit être inclus dans les diagnostics différentiels de masse cervicale surtout à évolution agressive.(Traduit par Dr Serge Messier).

Morphological and Immunohistochemical Characterization of an Oral Metastatic Carcinosarcoma in a Cat.

A 15-year-old neutered male mixed breed Domestic Shorthair cat was presented for a rapidly growing, intraoral soft gingival mass on the left mandibular region. The neoplastic tissue consisted histologically of two distinct malignant cell populations: spindle cells arranged in bands and epithelioid cells arranged in cords. A few multinucleated giant cells were scattered among the neoplastic cells. Spindle cells and multinucleated giant cells strongly expressed vimentin while epithelial cells strongly expressed pancytokeratins. On the basis of the histological and immunohistochemical results, a diagnosis of oral carcinosarcoma was made. After 2 months, due to the extent of disease and poor prognosis, the cat was euthanized. Necropsy revealed a markedly enlarged, multilobulated white-pink neoplastic mass that had originated from the left side of the sublingual region and involved the coronoid process of the left mandibular bone. The cut surface of the enlarged left submandibular lymph node was glistening, whitish-tan in colour with a multinodular appearance, suggestive of metastasis and confirmed by histological examination. Oral carcinosarcoma is uncommonly recorded in humans and dogs and, to the best of our knowledge, this is the first reported case in a cat.

Feline uterine carcinosarcoma infiltrated with osteoclast-like giant cells.

A 12-year-old female Himalayan cat underwent an ovariohysterectomy to remove an intra-abdominal mass. Histologic examination using immunohistochemical staining revealed that the mass was comprised of epithelial and mesenchymal components. Within the lesion, multinucleated giant cells (MGCs) were observed diffusely. MGCs were positive for vimentin and Iba-1 and negative for cytokeratin AE1/AE3 and CD204. In addition, MGCs were negative for Ki-67, indicating nonneoplastic cells. Osteoclast-like MGC (OLMGC) phenotype with tartrate-resistant acid phosphatase positivity was also seen. These findings suggested that the uterine tumor was carcinosarcoma with OLMGCs. Uterine tumors in humans, such as leiomyosarcoma and carcinosarcoma, with OLMGC infiltration, are well-known pathologic entities; however, they are rare in animals and to our knowledge, have not been previously reported in cats.

Biphasic Feline Mammary Carcinomas Including Carcinoma and Malignant Myoepithelioma.

Feline mammary tumors are usually malignant and aggressive carcinomas. Most cases are simple monophasic carcinomas (1 epithelial population), and additional phenotyping is usually not needed. In this study, we describe 10 malignant mammary tumors from 9 female cats that had unusual histomorphology: they appeared biphasic, with 2 distinct cell populations. Initially, they were morphologically diagnosed as either carcinosarcoma (1/10) or malignant pleomorphic tumor (9/10) of the mammary gland, as the latter did not match any previously described histological subtype. Immunohistochemistry (IHC) was performed for pancytokeratin, cytokeratins 8 and 18, cytokeratin 14, cytokeratins 5 and 6, vimentin, p63, calponin, alpha-smooth muscle actin, Ki-67, ERBB2, estrogen receptor alpha, and progesterone receptor. In 7 of 10 cases, the biphasic nature was confirmed and, on the basis of the IHC results, they were classified as carcinoma and malignant myoepithelioma (4/10), ductal carcinoma (1/10), and carcinosarcoma (2/10). The other 3 of 10 cases were monophasic based on IHC. In the cases of carcinoma and malignant myoepithelioma, the malignant myoepithelial cells were 100% positive for vimentin (4/4) and variably positive for p63, calponin, and cytokeratins (4/4). These findings show that, although rare, biphasic mammary carcinomas do occur in cats. In dogs and humans, tumors composed of malignant epithelial and myoepithelial cells have a less aggressive behavior than certain simple carcinomas, and therefore, their identification might also be clinically significant in the cat.

Bilateral Thyroid Carcinosarcoma in a Cat.

A neutered female domestic shorthaired cat was presented for a rapidly growing left cervical mass and a 6-month history of primary hyperthyroidism. Cytological examination of the mass was consistent with a sarcoma. Due to poor clinical response the cat was humanely destroyed and a post-mortem examination was performed. This revealed a markedly enlarged, irregularly shaped left thyroid gland with signs of infiltration of the trachea. The contralateral (right) thyroid was also moderately enlarged and irregularly shaped. Histopathological examination of the cervical masses indicated bilateral thyroid carcinosarcomas, evidenced by positive immunohistochemical labelling for vimentin, pan-cytokeratin and thyroid transcription factor-1 of the appropriate cell populations. The cat also had a concurrent pulmonary adenocarcinoma (papillary-lepidic type), unrelated to the thyroid neoplasm. Thyroid carcinosarcoma is an uncommonly recorded canine and human neoplasm and this is the first case of this entity to be reported in a cat.

Cutaneous Pilomatrical Carcinosarcoma in a Dog.

Malignant pilomatricomas are uncommon cutaneous neoplasms in veterinary and human medicine. Pilomatrical carcinosarcoma is a rare subset of malignant pilomatricoma that has been described in man. This article reports a neoplasm with morphological features of pilomatrical carcinosarcoma in a dog. The nodular neoplasm occurred on the left lateral hock and was partially alopecic. Microscopically, the tumour was composed of a cystic carcinomatous component surrounding areas of abrupt keratinization and a sarcomatous component exhibiting bundles of spindle cells and irregular, scalloped areas of mineralized and non-mineralized osteoid matrix. The carcinomatous and sarcomatous areas were immunoreactive for pan-cytokeratin and vimentin, respectively, while immunoreactivity for e-cadherin was restricted to the carcinomatous component of the neoplasm. The unique morphological features of this tumour were similar to those described in human pilomatrical carcinosarcoma.

Carcinosarcoma mimicking a feline injection-site sarcoma in a cat.

A 15-year-old spayed female domestic short-haired cat with cutaneous/subcutaneous well-circumscribed, alopecic mass approximately 25 × 30 mm in diameter, localized to the left shoulder region was brought to the veterinary surgery department. Despite the suggestive location and macroscopic appearance, feline injection-site sarcoma was not suspected based on the cytologic examination of fine-needle aspirates. The tumor was surgically resected, and tissue sections were evaluated microscopically. The tumor was found to be nonencapsulated with a distinct border between the neoplastic parenchyma and surrounding connective tissue. The neoplastic tissue consisted of 2 cell populations: elongated to spindle-shaped cells arranged in bands and cords and malignant epithelial-like cells. Both populations showed microscopic features of malignancy. Multinucleate giant cells with irregular cytoplasm were scattered among the neoplastic cells. The spindle-shaped cells strongly expressed vimentin but did not express α-smooth muscle actin (α-SMA) or cytokeratin. Desmin was strongly expressed in about 0-5% of cells. Epithelial-like cells expressed cytokeratin, but not vimentin, desmin, or α-SMA. Multinucleate giant cells expressed vimentin, but did not α-SMA, desmin, or cytokeratin. Based on microscopic observations and IHC results, the final diagnosis was carcinosarcoma with histologic features compatible with feline injection-site sarcoma, but without the clinical aggressiveness of this tumor.

Cytogenetic aspects of a canine breast carcinosarcoma - a case report.

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.

VEGFR-2 expression in malignant tumours of the canine mammary gland: a prospective survival study.

Vascular endothelial growth factor receptor-2 (VEGFR-2) is the main receptor activated by vascular endothelial growth factor -A (VEGF-A) to promote tumour angiogenesis. Its clinical prognostic value has not been studied in canine mammary tumours (CMTs). Dogs with mammary cancer were enrolled in a survival study and the immunohistochemical expressions of VEGFR-2 and VEGF-A were analysed and associated with clinicopathological features. VEGFR-2 expression was associated with VEGF immunoreactivity in cancer cells, supporting the presence of an autocrine loop that may be involved in CMTs growth and survival. VEGFR-2 was also expressed by endothelial cells from tumour vasculature and positively associated with stromal matrix metalloproteinase-9 (MMP-9), suggesting the existence of a link between endothelial cells activation and up-regulation of matrix degrading proteins. Carcinosarcomas exhibited high VEGFR-2 expression suggesting that it may be one of the activated molecular pathways in this aggressive histological type and that VEGFR-2 inhibitors may constitute a potential treatment to improve the prognosis of these patients. Both VEGF and VEGFR-2 immunoreactivities were independent of patients' overall survival (OS) and disease-free survival (DFS).

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.

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.

Carcinosarcoma in a white Rhinoceros (Ceratotherium simum simum).

In Rhinocerotidae, there are very few reports of tumors and no reports of a mixed tumor. This paper reports the case of a male 33-year-old southern white rhinoceros. Grossly, there were two masses in the coelomic cavity and solid nodules in the liver. Histologically, all tumors had a biphasic pattern that consisted of malignant epithelial cells (cytokeratin- and E-cadherin-positive) and non-epithelial cells (vimentin-positive) with cartilage. In this case, the prostate could not be identified, and instead, the largest tumor mass was present at that site. Furthermore, since structures regarded as the prostate duct remained in this tumor, we considered that this tumor was very likely to be of prostate gland origin. This case is the first report of carcinosarcoma in Rhinocerotidae.

Carcinosarcoma of the biliary system in a cat.

A 12-year-old, mixed-breed domestic cat was diagnosed with a multicystic hepatic mass via ultrasonographic examination and computer tomography scan. The tumor associated with the left medial liver lobe, and connected by a thin stalk to the hilar region, was surgically removed. The mass was firm, encapsulated, mottled white to red black, multinodular, and cystic. Histologic diagnosis was carcinosarcoma supported by positive immunohistochemistry for cytokeratins and vimentin of atypical neoplastic cell populations. On the basis of morphology, the origin was considered to be in the biliary tract. Biliary carcinosarcoma is a rare neoplasm that occurs in people. The epidemiology and risk factors have not yet been determined, and the prognosis is poor except for cases in which curative resection is performed.

Thyroid carcino-sarcoma in a dog.

An adult male greyhound was diagnosed with a thyroid carcino-sarcoma by means of histopathology and positive immuno-histochemistry staining for cytokeratin and vimentin. Surgery and radiotherapy of the area were successful in local tumour control. Adjuvant chemotherapy was recommended to treat and prevent further metastasis. The use of carboplatin, metronomic cyclophosphamide chemotherapy and toceranib failed to control the progression of distant metastasis. The survival time was seven months from the time of diagnosis. This is the eighth case of carcino-sarcoma of the thyroid documented in veterinary medicine and the first one treated with a multimodal approach based on surgery, radiotherapy and chemotherapy. As documented in human medicine, chemotherapy appeared to be ineffective to prevent or delay the progression of the metastatic disease in this case.

Mucin 6 and Tn antigen expression in canine mammary tumours: correlation with pathological features.

Overexpression of mucins is known to decrease cell-to-cell adhesion and thus to facilitate the invasion of cancer cells through the extracellular matrix. Mucin 6 (MUC6) is overexpressed and aberrantly O-glycosylated in human breast cancer, serving as a carrier for one of the most specific cancer-associated antigens, Tn antigen. Despite its relevance in breast cancer, MUC6 expression has not yet been characterized in canine mammary tumours (CMTs). The aims of this study were to assess the expression of MUC6 and Tn antigen in 55 benign and 77 malignant CMTs of different histological types and to investigate possible correlations with pathological features. MUC6 and Tn antigen were found to be significantly overexpressed in malignant compared with benign CMTs. MUC6 was significantly overexpressed in simple and complex carcinomas compared with simple and complex adenomas, respectively. When considering only the epithelial population, significant MUC6 overexpression was observed in carcinosarcomas when compared with benign mixed tumours. In addition, MUC6 was significantly overexpressed in simple compared with complex carcinomas. Finally, double-labelling immunofluorescence performed on seven malignant CMTs showed MUC6 and Tn co-expression. Therefore, MUC6 and Tn antigen overexpression is associated with malignant phenotypes of CMTs.

Pancreatic carcinosarcoma in a cat.

A 10-year-old female American shorthair cat was presented for evaluation of weight loss. An intra-abdominal mass was found on ultrasonography and laparotomy was performed. The mass was located in the left uterine horn and further masses were found in the pancreas, greater omentum and diaphragm. Microscopical examination revealed that the pancreatic mass had epithelial and mesenchymal components, which on immunohistochemistry expressed cytokeratin and vimentin, respectively. In addition, some spindle cells expressed vimentin and E-cadherin, which might suggest epithelial to mesenchymal transition. In contrast, the uterine, omental and diaphragmatic masses had only mesenchymal composition. The pancreatic lesion is proposed to be a primary carcinosarcoma with metastasis of only the mesenchymal component to distant sites. This the first report of pancreatic carcinosarcoma in a cat.

Mammary carcinosarcoma in cat: a case report / Carcinossarcoma mamário em gata: relato de Caso

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.