Mixed Type of Malignant Mesothelioma in an Aged Male ICR Mouse

Multiple whitish nodules in the thoracic cavity at the site of the thymus were observed in a 101-week-old male ICR mouse. In a histopathological examination, the neoplastic cells were predominantly fusiform in shape and proliferated in sarcomatoid growth patterns. Some neoplastic cells showed epithelial growth patterns, such as the ductal structures. Mitotic figures were frequently seen, and small necrotic foci and invasion to adjacent thoracic organs were noted. In Alcian blue staining, bluish materials were observed between fusiform-shaped cells and in some of the lumens of the ductal structures. In immunohistochemistry, both fusiform-shaped and ductal structure-forming cells were positive for vimentin and weakly positive to positive for cytokeratin. Based on the aforementioned findings, the thoracic nodules were diagnosed as a mixed type of malignant mesothelioma. This case was thought to be rare because of the very low occurrence of spontaneous mesothelioma in mice.     

Pleural mesothelioma in a young cat

A mesothelioma was seen as an incidental finding in the thoracic cavity of an eleven-month old female cat. At necropsy, the pale nodular lesions were spread over the ventral parts of the lungs and their corresponding parts of the diaphragm and the thoracic wall. Microscopically, the tumor consisted of mesenchymal tissue with large amounts of collagenous fibers covered by a mainly unilayered, polymorphic, partly vacuolated line of cells with large nuclei. Mitotic figures were rare. Based on morphological appearance the lesion was classified as an early mesothelioma.     

Malignant Peritoneal Mesothelioma with a Sarcomatoid Growth Pattern and Signet-Ring-Like Structure in a Female F344 Rat

We report a biphasic malignant mesothelioma in an aged female F344/DuCrlCrlj rat. Macroscopically, multiple pale brown nodules were observed in the abdominal cavity with retention of bloody ascites. Histopathologically, the tumor cells spread over the peritoneum and formed masses on the surface and underlying adipose tissues. The tumor cells dominantly proliferated in a solid, nodular or nest-like pattern with modest amount of fibrillar connective tissues, which contained hyaluronan. The tumor consisted of ovoid, polygonal or spindle-shaped cells that possessed eosinophilic cytoplasms including glycogen; some tumor cells showed a signet-ring-like structure. Multinucleated cells and mitosis were found frequently, and direct invasion to intra-abdominal organs and intravascular metastasis to the liver were observed. Immunohistochemically, keratin and mesothelin were strongly positive in most of tumor cells, while vimentin was mainly positive in spindle-shaped cells. Podoplanin was also positive, particularly in the cell membrane of tumor cells. Electron microscopically, tumor cells showed an intercellular desmosome-like structure, basement membrane and microvillus. We diagnosed the case as a malignant peritoneal mesothelioma with a sarcomatoid growth pattern and signet-ring-like structure.     

Canine cardiac mesothelioma with granular cell morphology

Cardiac mesothelioma with granular cell features was diagnosed in a 10-year-old Golden Retriever presenting with pericardial and abdominal effusions. The diagnosis was based on gross, morphologic, and immunohistochemical features. The immunohistochemical profile of the neoplasm was pancytokeratin positive, vimentin positive, and S-100 negative; most gross and morphologic features were consistent with both mesothelioma and granular cell tumor. To the authors' knowledge, the prognosis for either primary cardiac mesothelioma or granular cell tumor in the dog is unknown. At 4 months after thoracotomy, pericardectomy, and mass excision, this dog was alive and without clinical evidence of pericardial or abdominal effusions. We describe a granular morphologic variant of cardiac mesothelioma in a dog.     

Mesothelioma in horses

Pleural mesothelioma and pericardial mesothelioma with spread to the pleural cavity were diagnosed in 2 horses. Clinical signs included respiratory distress, depression and pleural pain. The affected body cavities contained copious, serous effusions containing very large neoplastic mesothelial cells with densely-staining cytoplasm, hyperchromic nuclei and prominent, often multiple, nucleoli. Ultrastructurally, the neoplastic cells appeared as solid aggregates, with profuse microvillous borders and neolumen formation. Cytological examination, together with confirmative ancillary diagnostic tests, including electron microscopy and immunocytochemistry, may be used to obtain an ante-mortem diagnosis of mesothelioma.     

Lipid-rich pleural mesothelioma in a dog

An 11-year-old, neutered, male Golden Retriever cross dog was euthanized following a history of recurrent pericardial effusions. At necropsy, blood-tinged pericardial and intrathoracic effusions were seen along with numerous firm to hard plaque-like masses that studded the epicardial, pericardial, mediastinal, and costal pleural surfaces. Within the right thorax, the lesions coalesced into a large mass that occupied most of the cavity. Histologically, the masses were composed of solid sheets and papillary aggregates of medium-sized polygonal cells that contained abundant vacuolated to clear cytoplasm. Some of the cytoplasmic vacuoles stained positive with oil red O. The stroma contained metaplastic trabeculae of woven and lamellar bone. Immunohistochemically, the neoplastic cells expressed vimentin, pancytokeratin, and S-100 protein. Transmission electron microscopy corroborated the presence of intracytoplasmic vacuoles and demonstrated prominent intercellular junctional complexes and apically located microvilli. These findings are consistent with a lipid-rich variant of mesothelioma. To the authors' knowledge, this is the first report of a lipid-rich mesothelioma in a dog.     

A case of biphasic mesothelioma with osseous and chondromatous differentiation in a cat

An 11-year-old domestic short hair cat with dyspnea, cyanosis, and pleural effusion died. Necropsy revealed several nodules and masses on the parietal pleura, pericardium, and diaphragm. The tumor contained epithelial and mesenchymal components and displayed osseous and chondromatous differentiation. Tumors cells were positive for pancytokeratin and vimentin. This is the first report of a biphasic mesothelioma with osseous and chondromatous differentiation in this species.     

Histological comparison of malignant epithelioid mesothelioma in young and adult cattle

The histology and immunohistochemistry of pleomorphic and conventional epithelioid mesotheliomas were examined. The former was detected in two young calves aged 2 and 4 months and was characterized by pleomorphic and atypical cells with decreased expression of cytokeratin 7 (CK7). In contrast, the latter was found in a 31-month-old heifer, consisting of tumor cells uniform in size and shape with CK7 expression in nearly all cells. Production of collagen by tumor cells was demonstrated in both histological types, and was considered to be characteristic of bovine epithelioid mesothelioma. Pleomorphic mesothelioma is far more pleomorphic and mitotically active than conventional mesothelioma, and its normal counterpart may be immature mesothelial cells with high proliferation potential, which exist in fetal life and early calfhood.     

Pericardial mesothelioma in a neonatal calf

We encountered an extremely rare tumor, a pericardial mesothelioma, in a neonatal calf. The patient calf showed severe abdominal distention, and died immediately after birth. The thoracic cavity was contained a huge heart with a large amount of pericardial fluid. A number of granular and cobblestone-like nodules were dispersed over the epicardium and pericardium. The nodules consisted of papillary proliferations of neoplastic cells, and the neoplasm occasionally showed mesenchymal proliferations. Immunohistochemistry revealed that they had the characteristics of mesothelial cells (cytokeratin-and vimentin-positive), and the neoplasm was diagnosed as mesothelioma.     

Deciduoid peritoneal mesothelioma in a dog

Deciduoid mesothelioma is a rare variant of epithelial mesothelioma, up to now only described in human pathology, which bears remarkable cytomorphologic resemblance to the endometrium of pregnancy, termed decidua. A case of peritoneal mesothelioma with deciduoid features in a 10-year-old, female dog is reported. Multiple whitish-gray nodules (1-5 mm in diameter) in parietal peritoneum and mesentery were histologically composed of large, proliferating, polygonal or ovoid cells with an abundant eosinophilic, glassy cytoplasm. Immunohistochemical evaluation indicated that the neoplastic cells coexpressed cytokeratin and vimentin with strong and diffuse cytoplasmic staining, and ultrastructural analysis showed long and slender mesothelial-type microvilli; these findings confirmed the mesothelial origin of the tumor.     

Immunohistochemical characterization of mesothelioma in 6 large felids

Mesothelioma has been reported frequently in large felids. These neoplasms present a diagnostic challenge given their highly variable morphology that mimics carcinomas or sarcomas at different locations. Our goal was to characterize mesotheliomas morphologically and immunohistochemically to determine if a panel of antibodies could be used to more accurately support the diagnosis of these neoplasms in large felids. Mesotheliomas from 6 large felids, including 4 clouded leopards, 1 Bengal tiger, and 1 cheetah, were immunohistochemically labeled for vimentin, E-cadherin, pancytokeratin, Wilms tumor 1 (WT1), MUC-1, and calretinin. The mesotheliomas of the 4 clouded leopards and the tiger were of the epithelial subtype; the mesothelioma from the cheetah was biphasic. All 6 mesotheliomas had strong immunohistochemical labeling for vimentin, E-cadherin, and pancytokeratin. All cases had cytoplasmic labeling for WT1, and 2 also had nuclear labeling. The 3 mesotheliomas with distinct papillary fronds were weakly positive for MUC-1. These and one other epithelial mesothelioma were also positive for calretinin. Our study demonstrates that the morphologic and immunohistochemical phenotypes of mesothelioma that have been identified in humans and domestic species can occur in large felids, and a panel of pancytokeratin, vimentin, WT1, and calretinin can be utilized to support the diagnosis of these neoplasms.     

Malignant mesothelioma in urban dogs

Clinical and postmortem materials from six dogs with a diagnosis of malignant mesothelioma were studied retrospectively. The dogs were urban pets with clinical signs of malignant effusions. Two mesotheliomas were pleural, one pericardial, and one peritoneal. Both pleura and pericardium were involved in one dog, and the pleura and peritoneum in another. On gross examination at necropsy, diffuse granular or velvety plaques covering mesothelial surfaces were found in all dogs; firm discrete pleural nodules also were present in two dogs. Neither distant metastases nor areas of deep lung invasion were found. The tumors varied histologically, but the most common type was epithelial with a papillary pattern. Ultrastructurally, the neoplastic cells had prominent surface microvilli, numerous desmosomes, and tonofilaments. Lung tissue from these dogs and from control dogs was evaluated for the presence of ferruginous bodies. Asbestos bodies were found in three of five dogs with mesotheliomas but rarely were found in control dogs. As a group, the mesothelioma cases had significantly more asbestos bodies and total ferruginous bodies than controls. The clinical and morphologic appearance of canine mesothelioma is similar to human mesothelioma and also may be associated with exposure to airborne fibers.     

Morphology and classification of 96 primary cardiac neoplasms in Fischer 344 rats

Ninety-six primary cardiac neoplasms were identified from 79,971 Fischer 344 (F344) rats used in chronic toxicity and carcinogenicity studies by the National Toxicology Program (NTP) and National Cancer Institute (NCI), for an overall incidence of 0.1%. Neoplasms were classified as: 60 endocardial schwannomas, 23 intramural schwannomas, eight atriocaval mesotheliomas, three paragangliomas, one pericardial mesothelioma, and one hemangioma. Metastases occurred in four rats with endocardial schwannoma. Histological appearance of the endocardial and intramural schwannomas was consistent with origin from nerve sheath. Two of six endocardial schwannomas available for immunohistochemical staining were weakly positive for S-100 antigen. The atriocaval mesotheliomas, while morphologically resembling adenocarcinoma, were positive for vimentin and keratin, indicating mesothelial origin. Seventy of the 96 cardiac neoplasms occurred in rats 2 years of age or older at time of death. There were no sex or treatment-related differences in the incidence of these neoplasms, with the exception of atriocaval mesothelioma, which was more common in males.     

Two cases of feline malignant craniopharyngioma

Tumors at the cranial base in 2 cats (a 9 1/2-year-old, castrated male Chinchilla and a 7-year-old, castrated male American Shorthair) were diagnosed as malignant craniopharyngioma. The tumor lesion was histopathologically divided into four parts: 1) a small acinus part, in which relatively large cells with a pale cytoplasm composed small acini; 2) a duct part, in which small cuboidal cells composed ducts; 3) a cyst part, in which there were large cysts lined with flat cells; and 4) a pavement part, in which large multi-angular-shaped cells proliferated in a pavement pattern. The epithelial cells of some parts were positive for keratin by immunohistochemistry. Histopathologic findings of the present feline cases were identical to those of malignant craniopharyngioma in other animal species.     

Angiotrophic intravascular lymphosarcoma presenting as bi-cavity effusion in a dog

A 9-year-old German Shepherd cross was presented with a history of dyspnoea, decreased activity, episodic collapse and abdominal distention. Cytological examination of thoracic and abdominal fluid demonstrated neoplastic cells, either round or mesenchymal in nature. The dog was found to have a mass in the heart-base region. Exploratory thoracotomy was performed to identify the exact nature of the mass histologically, and to determine if it was the source of neoplastic cells seen in the effusions. Histological diagnosis of the mass was mesothelioma. Postoperatively the dog developed thrombocytopenia, probably immune-mediated, which was treated with prednisone therapy. The dog developed signs of respiratory distress shortly before discharge and, due to its deteriorating condition, was euthanased. A necropsy was performed and tissues were collected for histological examination. The histological diagnosis was angiotropic intravascular lymphosarcoma. Diagnosis of mesothelioma was not confirmed.     

Spontaneous extraskeletal osteosarcoma with various histological growth patterns in the abdominal wall of an ICR mouse

Extraskeletal osteosarcoma is extremely rare in mice. This case report demonstrates a spontaneous murine extraskeletal osteosarcoma that exhibited various histological growth patterns in an ICR mouse. At necropsy, the tumor mass was located in the abdominal wall and was 45 × 30 × 25 mm in size. Histopathologically, the tumor showed the following four growth patterns: a solid pattern of polygonal cells embedded in an osteoid eosinophilic matrix with calcification, an irregular sheet pattern of short spindle cells accompanying some eosinophilic multinucleated cells, a fascicular pattern of spindle cells and a cystic pattern lined by short spindle cells. Immunohistochemically, most of the tumor cells were positive for vimentin, proliferating cell nuclear antigen and osterix. The multinucleated cells mentioned above were desmin positive and were regarded as regenerative striated muscles but not tumor cells. Since no clear continuity with normal bone tissues was observed, the tumor was diagnosed as an “extraskeletal osteosarcoma.”     

Identification of canine transmissible venereal tumor cells using in situ polymerase chain reaction and the stable sequence of the long interspersed nuclear element.

Canine transmissible venereal tumor (CTVT) is a unique tumor that can be transplanted across the major histocompatibility complex (MHC) barrier by viable tumor cells. In dogs, CTVT grows progressively for a few months and then usually regresses spontaneously. A long interspersed nuclear element (LINE) insertion is found specifically and constantly in the 5' end of the CTVT cell c-myc gene, outside the first exon. The rearranged LINE-c-myc gene sequence has been used with polymerase chain reaction (PCR) to diagnose CTVT. However, in CTVT cells, the total length of the inserted LINE gene is not constant. In this experiment, variation in the inserted LINE gene was studied to determine which parts of the LINE sequence can be used as primers to identify CTVT cells with in situ PCR (IS PCR). The LINE gene was inserted between the TATA boxes in the promoter region of c-myc. In CTVT cells, deletions of different lengths are frequent in this gene. However, the 550-bp segment at the 5' end of the LINE-c-myc gene was stable. Thus, primers were designed to cover the stable 0.55-kb segment from the 5' end outside the first exon of the c-myc gene to the 5' end of LINE gene stable segment. With these primers and IS PCR, individual CTVT cells in formalin-fixed tissue sections and CTVT cultures were identified. Cells from other canine tumors were negative for this gene. In addition, the CTVT-specific, 0.55-kb segment was not found in any spindle-shaped cells from progressive or regressive phase CTVT. The IS PCR technique also did not detect any positive spindle-shaped cells in CTVT cell cultures. Thus, fibroblastic terminal differentiation is less likely to be a mechanism for spontaneous regression of CTVT cells.     

Malignant pleural mesothelioma in a female Lion (Panthera leo)

An 18-year-old female lion (Panthera leo) was referred to the Department of Animal Pathology of the University of Turin (Italy). At necropsy, multiple nodular, 4-20-mm, confluent white firm nodules were scattered throughout the pleural surfaces of the thoracic wall and of the lungs. Histological lesions were represented by proliferations of papillary structures lined by cuboidal basophilic mesothelial cells with large, oval nuclei and abundant granular eosinophilic cytoplasm. Immunohistochemistry revealed immunoreactivity for pancytokeratin and vimentin. None of the cells expressed calretinin antigen. Asbestos fibers and asbestos bodies were not detected respectively by light microscopy and by Scanning Electron Microscope-Energy Dispersive Spectrometer investigations. On the contrary, chrysotile asbestos were identified in samples from shelter material. Histological and immunohistochemical findings were consistent with the diagnosis of an epithelial malignant mesothelioma. To our best knowledge, this is the first report of a pleural mesothelioma in a lion.     

Systemic Listeria monocytogenes infection and concurrent pleural mesothelioma in a cat

Herein we describe a rare case of systemic Listeria monocytogenes infection with concurrent pleural mesothelioma in a stray cat that was found dead and submitted for autopsy. Gross pathology changes consisted of thoracic clear yellow fluid admixed with suspended fibrin strands; clear-to-tan, variably sized, <3 mm diameter pulmonary nodules; and enlargement of the submandibular, retropharyngeal, and prescapular lymph nodes. Histologic changes consisted of extensive areas of suppurative inflammation and necrosis with mineralization that partially effaced the pulmonary parenchyma and lymph nodes. Random, distinct necrotic foci were present throughout the hepatic parenchyma. Extending from the pleura, within perinecrotic alveolar spaces, and infiltrating the submandibular, retropharyngeal, and prescapular lymph nodes were dense sheets of neoplastic epithelioid cells with moderate pleomorphism and occasional karyomegaly and multinucleation. Neoplastic cells exhibited immunolabeling for pancytokeratin AE1/AE3 and vimentin, consistent with pleural mesothelioma. Aerobic bacterial culture of lung yielded heavy growth of L. monocytogenes. Immunohistochemistry (IHC) for L. monocytogenes revealed clusters of bacteria in the lung, lymph node, and liver. Pathologic changes were consistent with systemic listeriosis, confirmed by bacterial culture and IHC, and concurrent pleural mesothelioma.     

Cytology of diffuse mesothelioma in the thorax of a horse.

Examination of effusions from body cavities must include a search for neoplastic as well as inflammatory cells. Neoplastic cells found in the thorax are generally derived from adenocarcinomas or mesotheliomas. Mesotheliomas are relatively uncommon and the neoplastic cells found in effusions are difficult to differentiate from activated cells in inflammatory effusions. An ante-mortem diagnosis of mesothelioma was made in a mare on the basis of the large volume of fluid produced, the pleomorphic mesothelial cells, the polyp formation and the absence of PAS staining material after digestion of the cell impression with maltase diastase.