Retrospective evaluation of toceranib phosphate (Palladia) in the treatment of canine carcinomatosis and mesothelioma.

Canine carcinomatosis (CC) and mesothelioma (CM) are rare but aggressive neoplasms that historically have been associated with poor prognoses. There is limited information regarding treatment for CC and CM. The purpose of this retrospective study was to evaluate the efficacy and tolerability of toceranib phosphate (Palladia) in dogs with CC and CM. Cases were solicited from the American College of Veterinary Internal Medicine (ACVIM) Oncology listserv and retrospectively reviewed. For eligibility, a cytologic and/or histopathologic diagnosis of CC or CM was required. A total of 23 cases were included (CC = 14, CM = 8, both = 1). Eighty-two percent (19/23) of dogs presented with effusion. The best overall response rate (BORR) was 30.4% (13% complete response [CR], 17.3% partial response [PR]). Stable disease (SD) was appreciated in 14 dogs (60.8%) including the four dogs without effusion. The most common toceranib-related adverse events were either Grade 1 and 2 diarrhea or hyporexia. The median progression-free survival (PFS) was 171 days (range, 7-519 days) and overall median survival time (MST) was 301 days (range, 49-875 days) for all dogs. When evaluating dogs solely with effusion, the median PFS and overall MST were 171 days (range, 7-519 days) and 285 days (range, 49-875 days), respectively. This report demonstrates that toceranib is both well tolerated and a potential treatment for CC and CM. A randomised, controlled, prospective study would be needed to objectively assess the survival benefit of toceranib in the management of CC and CM, with and without effusion.

Localized pleural mesothelioma in a dog.

Malignant mesotheliomas with localized growth are extremely rare in dogs. A 9-year-old male dog presented with a localized tumour that originated from the parietal pleura and had polypoid growth in the thoracic cavity. Histological examination revealed that the tumour consisted of tubular formations with scattered cysts and minimal papillary growth pattern. Neoplastic cells were immunopositive for mesothelial markers (calretinin and Wilms' tumour gene 1) and negative for carcinoma markers (thyroid transcription factor 1 and tumour protein 63). The animal was alive with no recurrence or metastasis/dissemination 11 months after surgery. To the best of our knowledge, this is the first report of a localized mesothelioma in a dog without metastasis/dissemination and highlights the value of mesothelial markers for an accurate diagnosis.

Biphasic pleural mesothelioma in a goat.

An 8-year-old Saanen goat doe was seen for inappetence, tachycardia, and intermittent bluish-grey discoloration of the oral mucous membranes. On physical examination, the goat was mildly tachypneic and tachycardic, with reduced sounds auscultated on the left side of the thorax. Euthanasia was elected. Necropsy revealed an infiltrative, multinodular mass within the left thoracic cavity and innumerable small, tan nodules disseminated across the pleura of the lungs, thoracic walls, and diaphragm. Upon histologic examination, the mass was composed of highly pleomorphic, fusiform to polygonal cells. Neoplastic cells exhibited positive immunoreactivity for both cytokeratin and vimentin, consistent with a diagnosis of biphasic pleural mesothelioma. Key clinical message: Mesothelioma has rarely been described in the goat but should be considered as a differential diagnosis for thoracic masses in small ruminants, along with thymoma; metastatic neoplasia; carcinomatosis; and granulomatous lesions caused by parasites, bacteria, and fungi.

Mésothéliome pleural biphasique chez une chèvre. Une chèvre Saanen âgée de 8 ans a été vue pour de l'inappétence, une tachycardie et une décoloration gris bleuâtre intermittente des muqueuses buccales. À l'examen physique, la chèvre était légèrement tachypnéique et tachycardique, avec des sons réduits auscultés du côté gauche du thorax. Il a été décidé d'euthanasier l'animal. L'autopsie a révélé une masse multinodulaire infiltrante dans la cavité thoracique gauche et d'innombrables petits nodules brun clair disséminés à travers la plèvre pulmonaire, les parois thoraciques et le diaphragme. À l'examen histologique, la masse était composée de cellules hautement pléomorphes, fusiformes à polygonales. Les cellules néoplasiques ont présenté une immunoréactivité positive pour la cytokératine et la vimentine, compatible avec un diagnostic de mésothéliome pleural biphasique.Message clinique clé:Le mésothéliome a rarement été décrit chez la chèvre mais doit être considéré comme un diagnostic différentiel des masses thoraciques chez les petits ruminants, avec le thymome, la néoplasie métastatique, la carcinomatose et les lésions granulomateuses causées par des parasites, des bactéries et des champignons.(Traduit par Dr Serge Messier).

Pleural mesothelioma in a California sea lion (Zalophus californianus).

A 25-year-old female California sea lion (Zalophus californianus) reared in an aquarium died following a history of anorexia, lethargy, abnormal protrusion of the skin, and oral respiration. At necropsy, multiple yellowish-white nodules with diameters of 0.1-0.5 cm were disseminated in the thoracic cavity and lungs. Histopathologically, the nodules were continuous with normal mesothelium and were characterized by the proliferation of spindle-shaped to polygonal neoplastic cells with prominent atypia. The neoplastic cells exhibited diffuse, strong staining for vimentin and partial, weak to moderate staining for cytokeratin AE1/AE3. Based on these findings, the lesions were diagnosed as pleural mesothelioma. This study reports the first case of pleural mesothelioma in California sea lion.

Pericardial malignant mesothelioma diagnosed in a dog by immunocytochemistry of the pericardial fluid: a case report.

BACKGROUND: Pericardial effusions are one of the most common cardiac diseases in dogs. Common causes of haemorrhagic pericardial effusions include neoplasia, such as hemangiosarcoma, mesothelioma, chemodectoma, and ectopic thyroid tumours, and benign idiopathic pericardial effusion. Distinguishing among reactive mesothelial cells, malignant mesothelioma, and adenocarcinoma in body effusions is a diagnostic challenge. Therefore, the author aimed to discover whether the observed cells were reactive mesothelial, mesothelioma, or adenocarcinoma cells through immunocytochemistry using five markers (cytokeratin, vimentin, desmin, E-cadherin, and calretinin) in a canine patient. CASE PRESENTATION: A 2.1 kg, spayed female, 10-year-old Yorkshire Terrier dog presented to a local hospital with dyspnoea and was evaluated for pericardial effusion. The presence of pericardial fluid was confirmed, and she was referred to our hospital for further evaluation. In cytological evaluation, cells shed individually or in clusters were observed, along with numerous non-degenerative neutrophils and macrophages. The cells showed binucleation, anisocytosis, anisokaryosis, abnormal nucleoli, abundant basophilic cytoplasm, high nuclear-cytoplasmic ratio, and coarse chromatin. Large atypical multinucleate cells were also observed. Erythrophagia was observed, indicating chronic haemorrhage. Immunocytochemistry using pericardial fluid was positive for cytokeratin, vimentin, desmin, E-cadherin, and calretinin. Therefore, malignant mesothelioma was diagnosed. CONCLUSIONS: Immunocytochemistry is a very useful diagnostic technique because it can determine whether several fluorescent markers are simultaneously expressed in the same cell. Further, E-cadherin and calretinin can be used for the differential diagnosis of reactive mesothelial cells, malignant mesothelioma, and adenocarcinoma in dogs.

Echocardiographic, thoracic ultrasonographic, and CTA diagnosis of pericardial neoplasia in a dog.

A 12-year-old male neutered Yorkshire Terrier presented for coughing and respiratory distress. Transthoracic echocardiography initially misdiagnosed the patient with pericardial effusion; repeat echocardiography increased suspicion for neoplasia. A definitive diagnosis was not apparent. Findings on thoracic computed tomography and thoracic ultrasound were consistent with a diffusely thickened, heterogenous, hypoechoic soft tissue structure surrounding the heart. Fine needle aspirates were obtained using ultrasound guidance and routine cytology of the intrapericardial mass was consistent with neoplasia, with pericardial mesothelioma most likely. These novel findings highlight the importance of thoracic ultrasound and potential limitations of echocardiography in diagnosis of pericardial neoplasia.

Mediastinal Serous Cavity Mesothelioma in Two Dogs.

The mediastinal serous cavity (MSC)-well documented but seldom recognized in the caudal mediastinum-is embryologically derived from the omental bursa. Mesothelioma arising from the MSC in two dogs is described. Both dogs presented with acute life-threatening hemorrhagic pleural effusion. Contrast computed tomography revealed a large solitary spherical-to-cylindrical tumor in the caudal mediastinum with variably thick, contrast-enhancing walls with lobular to frond-like proliferations that arose circumferentially and projected internally into a single, variably sized, fluid-attenuating lumen. The wall and lumen corresponded to the serous membrane and serous cavity of the MSC. Surgical exploration confirmed that both tumors arose from the mediastinum. Both had similar histologic findings, and special stains were necessary for definitive diagnosis. The tumor was nonresectable in one dog, and it was euthanized intraoperatively. The other survived 7 mo. An MSC mesothelioma should be considered a possible cause of hemothorax in dogs that may be detected on thoracic radiography and computed tomography. Differential diagnoses include esophageal foreign body or neoplasm, paraesophageal diaphragmatic hernia, MCS empyema, and pulmonary adenocarcinoma, with thoracic computed tomography helping to rule out foreign body and diaphragmatic hernia. For confirmed neoplasms, histochemistry and immunohistochemistry should be performed to differentiate between mesothelioma and pulmonary adenocarcinoma.

Outcome of dogs treated with chemotherapy for mesothelioma: A retrospective clinical study on 40 cases and a literature review.

Mesothelioma is an uncommon cancer in dogs for which there is no established standard of care. Chemotherapy is often suggested despite no definitive proof of efficacy. The aim of this study was to evaluate the impact of chemotherapy on survival of dogs with mesothelioma. A retrospective multicentric study was carried out. To be included, dogs needed to present an evocative clinical evolution and a morphological diagnosis of mesothelioma. Exclusion of other cause of effusion and complete clinical follow-up were also required. Fourty dogs were included, 27 received chemotherapy (group 1) and 13 did not (group 2). Groups were heterogeneous regarding the proportion of animals undergoing surgery as part of their treatment (16 in group 1, 2 in group 2; p = .016) and homogeneous otherwise. Univariate analysis showed that dogs from group 1 survived significantly longer than dogs from group 2 (MST: 366 vs. 74 days; p < .001). Complete resolution of effusion after the first chemotherapy administration positively correlated with survival in group 1 (MST: 415 vs. 160 days; p < .01). All other variable tested had no significant impact on survival in univariate analysis, but dogs undergoing surgery and dogs having serous membranes' modification at medical imaging tended to survive longer. Multivariate analysis confirmed that chemotherapy was the sole variable independently associated with survival in our study (odds ratio 5.57-6.12; p < .01).

Comparison of effusion cell block and biopsy immunohistochemistry in mesothelial hyperplasia, mesothelioma, and carcinoma in dogs.

BACKGROUND: Determining the cause of effusions is challenging and might require a biopsy. Whether cell blocks from effusions are representative of biopsies requires investigation. A previously developed immunohistochemical panel aids in the differentiation of hyperplastic and neoplastic mesothelium in canine biopsies but has not been investigated in effusions. OBJECTIVES: The study aimed to assess cell blocks as an alternative to biopsies and determine whether immunohistochemistry helps distinguish hyperplastic mesothelium, mesothelioma, and carcinoma. METHODS: Effusions and biopsies were collected from five dogs with mesothelial hyperplasia (group MH), six with mesothelioma (group M), and five with carcinoma (group C). Immunohistochemistry (IHC) for cytokeratin, vimentin, Wilm's tumor protein 1 (WT1), desmin, glucose transporter 1 (GLUT1), and insulin-like growth factor II mRNA-binding protein 3 (IMP3) was performed. Sections were scored for staining intensity and the percentage of positively stained cells. RESULTS: In paired cell blocks and biopsies, vimentin and WT1 staining were positively correlated for intensity and the percentage of positive cells, although not all paired results were identical. The intensity of IMP3 staining in cell blocks was higher in group M than in group C (P = 0.012), and WT1 staining was higher in group MH than in group C (P = 0.020). For biopsies, the intensity of WT1 staining was higher in group MH than in group C (P = 0.031). In group C, WT1 was negative in all cell blocks and biopsies, and desmin was negative in four of five cases. CONCLUSIONS: IHC results for the cell blocks and biopsies were comparable for potentially useful markers, such as WT1, which helped discriminate between groups. IHC provided additional information, although results were not always definitive. Further studies on a larger population are required.

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.

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.

Peritoneal Mesothelioma in a Free-Ranging American Black Bear (Ursus americanus).

We necropsied an American black bear (Ursus americanus) from central Utah, US and found several liters of cloudy fluid and multiple white nodules in the peritoneal cavity. Histopathologic examination and staining with pancytokeratin and vimentin markers identified a peritoneal mesothelioma. Mesothelioma has not been reported previously in black bears.

PERICARDIAL MESOTHELIOMA AND ASSOCIATED PERICARDIAL EFFUSION IN A TIGER RAT SNAKE (SPILOTES PULLATUS) TREATED WITH PERICARDIOCENTESIS.

A 1.5 kg, male, wild-caught tiger rat snake (Spilotes pullatus) presented with an externally visible distension of the body wall at the level of the heart. Ultrasound examination showed marked pericardial effusion. Pericardial fluid showed no bacterial or fungal growth, few leukocytes, and few suspected reactive mesothelial or neoplastic cells. Therapeutic pericardiocentesis was successfully performed, removing most of the fluid from the pericardial sac. The snake had mild lethargy and weakness immediately after the procedure but returned to normal behavior within 2 wk. Repeat pericardiocentesis was performed 6 mo after the initial presentation when moderate refilling of the pericardial sac was seen. The snake died 4 days after the second procedure with acute hemorrhage. Pericardial mesothelioma was diagnosed by histopathology after postmortem examination. This report provides the first documented case of mesothelioma in a tiger rat snake and the first description of the disease in colubrids.

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.

Multicystic peritoneal tumor in two layer hens.

In chicken, peritoneal cystic lesions have not been clearly categorized. In this study, diffuse peritoneal multiple cysts were observed in two layer hens. The cysts in the serosa were lined with single layers of squamous or cuboidal cells. The papillary proliferations of columnar cells were also observed in one case. The smooth muscle layer or mass were observed around the cysts in both cases. The cystic lining cells were positive for pan-cytokeratin, vimentin, S100 and Wilms tumor 1. Ultrastructurally, they had sparsely microvilli on the luminal surface. The histological results indicated the present cases were multicystic mesothelioma, but also had characteristics of Mullerian epithelium. This is the first report describing the detailed pathological feature of unique multicystic tumor in chicken.

Diagnostic efficacy of imaging and biopsy methods for peritoneal mesothelioma in a calf.

BACKGROUND: Peritoneal mesothelioma is a rare abdominal disease; that occasionally occurs congenitally in younger calves. Cytologic examination of peritoneal effusion (PE) was utilized to diagnose this disease, and was not diagnostic. Diagnostic accuracy has been elevated by recent use of ultrasonography (US), despite most diagnoses have been obtained post-mortem in slaughter houses or during clinical necropsy. In humans, ante-mortem diagnosis is highly associated with clinical use of computed tomography (CT) and laparoscopy together with imaging-assisted biopsy. The present report evaluates the diagnostic applicability of CT and laparoscopy as well as US via the practical application of these imaging modalities in an affected calf, and compares the cytologic and histologic findings among in PE, and specimens obtained from fine-needle aspiration and core-needle biopsy. In addition, the present results were reviewed in comparison with those of previous bovine and human reports. CASE PRESENTATION: A 58-day-old male Japanese black calf presented first with scrotal swelling, followed by progressive abdominal distention. Abnormalities of the case included: 1) accumulation of anechoic PE inside the swollen scrotum and abdomen; 2) formation of multiple echogenic nodules within the peritoneal membrane based on US images; 3) presence of hyper-dense spots (suspected calcification) along the margins of the nodules; 4) anatomic connections between intra-abdominal nodular lesions and the swollen tunica vaginalis via the inguinal region based on CT images; 5) serosanguineous-colored and less-turbid characteristics of PE; and 6) formation of multiple nodules over all of the serosa of the rumen as well as the peritoneal wall based on laparoscopic views. Fine-needle aspiration and core-needle biopsy were successfully performed under US and laparoscopic observations, respectively. Histology findings of the core-needle biopsy specimen appeared more indicative (characterization of tubular structures comprised of cubical or columnar abnormal mesothelial cell linings) diagnostically of peritoneal mesothelioma than did findings of the fine-needle aspiration specimen. CONCLUSIONS: To the best of our knowledge, this report is the first description of clinical applications of CT and laparoscopy to diagnose peritoneal mesothelioma in a calf. Laparoscopy enhanced the diagnostic accuracy due to clear gross visualization of the intra-abdominal abnormalities and applicability to imaging-guided core-needle biopsy.

Presumptive seeding metastasis of pericardial mesothelioma following repeated pericardiocentesis in a dog.

A dog with a history of recurrent pericardial effusion that required repeated pericardiocentesis was presented to the surgical service at the Ontario Veterinary College Health Sciences Centre for thoracoscopic pericardiectomy. Physical examination revealed a subcutaneous mass in the right lateral thorax. Cytology of the subcutaneous mass and histopathology of the pericardium were consistent with mesothelioma. This article details the first reported case of pericardial mesothelioma with suspected extra-thoracic metastasis following pericardiocentesis in a dog.

Implantation métastasique présumée d'un mésothéliome péricardique à la suite de péricardiocentèses répétées chez un chien. Un chien avec une historique d'effusions péricardiques récurrentes qui nécessitaient des péricardiocentèses répétées fut présenté au service de chirurgie du Ontario Veterinary College Health Sciences Centre pour une péricardiectomie thoracoscopique. L'examen physique a révélé une masse souscutanée dans le thorax latéral droit. L'examen cytologique de la masse sous-cutanée et l'histopathologie du péricarde étaient cohérents avec un mésothéliome. Le présent article donne les détails du premier cas rapporté chez un chien de mésothéliome péricardique avec métastase extra-thoracique suspectée consécutive à la suite de péricardiocentèses.(Traduit par Dr Serge Messier).

Malignant Mesothelioma of the Vaginal Tunic and Peritoneum in a Young Stallion.

Mesothelioma is a rare malignancy in horses. This report describes a case in which marked hemoperitoneum, moderate anemia, and moderate dependent edema were the presenting clinical signs in a 2-year-old Standardbred stallion with mesothelioma of the vaginal tunic. On necropsy, approximately 40 L of dark red fluid distended the abdomen. A dark red mass infiltrated and effaced the right pampiniform plexus, and red nodular masses were present multifocally on the parietal and visceral peritoneal surfaces. Histopathologically, the masses were composed of malignant spindle cells with a sarcomatoid appearance. Using immunohistochemistry, tumor cells were cytokeratin and vimentin positive and factor VIII-related antigen negative: compatible with a diagnosis of mesothelioma. This is the first report of mesothelioma arising from the vaginal tunic of a horse with subsequent spread to the peritoneum. This case adds additional information regarding the clinical presentation and behavior of mesothelioma originating from the vaginal tunic in horses.

Peritoneal sarcomatoid mesothelioma in a sika deer.

A slaughtered 2-year-old female sika deer (Cervus nippon yesoensis) had diffusely distributed multinodular lesions on the serosal surface of the peritoneal cavity and several nodules in the pleural cavity. Histologically, they were composed of proliferating spindle-shaped neoplastic cells, arranged in a fascicular fashion. The cells in the invasive foci transitioned from a sarcomatoid to an epithelioid appearance. Immunohistochemically, both the spindle-shaped and epithelioid cells were at least focally positive for pancytokeratin, vimentin, calretinin, α-SMA, and desmin. From these findings, the deer was diagnosed with peritoneal sarcomatoid mesothelioma with metastasis to the pleural cavity. To our knowledge, this is the first reported case of peritoneal mesothelioma in a cervid species and the first case of mesothelioma in a sika deer.