Immunohistochemical features of canine ovarian papillary adenocarcinoma and utility of cell block technique for detecting neoplastic cells in body cavity effusions.

Dogs with ovarian papillary adenocarcinoma occasionally present with ascites and/or pleural effusion. These aspirated fluids often contain a large number of cells, and distinction between neoplastic cells and activated mesothelial cells can be difficult. In this study, 7 cases of canine ovarian papillary adenocarcinoma, including 3 with ascites and pleural effusion, were immunohistochemically examined. Ovarian tumor cells were positive for cytokeratin CAM5.2 (CAM5.2), Wilms' tumor 1 (WT-1) and progesterone receptor (PR) in all 7 cases. A metastatic lesion of the mediastinum in one case was also positive for CAM5.2, WT-1 and PR. Immunohistochemistry on cell blocks obtained from ascites and/or pleural effusion of 2 cases revealed the presence of PR-positive epithelial cells. Whereas, activated mesothelial cells in ascites or pleural effusion collected from dogs without neoplastic lesions were negative for PR. In addition, surface epithelium and subsurface epithelial structures (SES) of normal canine ovaries, that are considered to be the cell of origin for ovarian papillary adenocarcinoma, were also positive for CAM5.2, WT-1 and PR. These results indicate that, together with CAM5.2, WT-1 and PR is a useful diagnostic marker for canine ovarian papillary adenocarcinoma. Expression of PR may be associated with progesterone-dependent nature of canine ovarian papillary adenocarcinoma.

Diagnostic utility of measuring lactate dehydrogenase levels and its isoenzyme activities for the evaluation of malignancy in feline pleural effusion and ascitic fluid.

Background: Lactate dehydrogenase (LDH) isoenzymes may be useful in the differential diagnosis of pleural effusion (PE) and ascitic fluid (AF) etiologies in cats since tissue damage induces their release, changing the pattern of their activity. Aim: This study aimed to determine the diagnostic utility of measuring LDH levels and isoenzyme activities in PE or AF in cats with malignancy. Methods: LDH levels and isoenzyme activities in the serum, PE, and AF were compared among cats in the malignant, infectious, and non-malignant, non-infectious groups. A receiver operating characteristic (ROC) analysis was performed to assess the accuracy in diagnosing feline malignancy. Results: Significant differences in LDH level and LDH isoenzyme activities in the PE and AF were observed among the three groups. The combination of LDH level and LDH-1 activity in PE or AF had the highest area under the ROC (AUC) values for discriminating malignant effusion from non-malignant effusion. The AUC of the combination of LDH level and LDH-1 activity in PE or AF was 0.874. The sensitivity and specificity of using the combination of LDH level (cut-off: <2,269 U/l) and LDH-1 activity (cut-off: <4.8%) in PE or AF for predicting malignancy with the highest AUC value were 94.4% and 72.7%, respectively. Conclusion: Our results suggest that the combination of LDH level and LDH-1 activity in PE or AF is a potential factor for diagnosing malignancy. Considering that LDH isoenzymes can be measured inexpensively and easily, LDH tests can be readily accommodated in veterinary clinical practice.

Long-Term Treatment Results for Ovarian Tumors with Malignant Effusion in Seven Dogs.

Surgery and platinum-based chemotherapy are highly efficacious for treating advanced ovarian cancers in humans, but their efficacy is less known in dogs. We evaluated the long-term treatment outcomes of seven dogs with malignant ovarian tumors with malignant abdominal effusion. Ovariohysterectomies (OVHs) were performed on all dogs; four had ovarian adenocarcinoma (AC) with gross dissemination in the peritoneum (two with pleural effusion), and three had a granulosa cell tumor (GCT) with no gross dissemination in the peritoneal cavity, although one showed pleural effusion. Effusion resolved after the OVH in all dogs. Six dogs (three ACs, three GCTs) received postoperative IV carboplatin therapy. Two dogs with GCT had no postoperative recurrence or metastasis, and one dog with GCT had recurrence 1811 days postoperatively. All dogs with AC developed recurrent effusion 171-584 days postoperatively, which resolved after intracavitary administration of cisplatin or carboplatin, with a subsequent disease-free interval of 155-368 days. Overall survival was longer for dogs with GCTs (822-1840 days) than for those with ACs (617-841 days). These results suggest that dogs with ovarian tumors with malignant effusion can survive relatively long after platinum-based chemotherapy in addition to OVH, with a more favorable prognosis for GCT than AC.

Neoplastic melanocytic pleural effusion in a Portuguese water dog.

A 9-year-old castrated male Portuguese water dog was presented following incomplete excision of a malignant melanoma at the left lip commissure by the referring veterinarian. Physical examination was otherwise unremarkable. The patient was staged using thoracic radiographs, abdominal ultrasound, and fine-needle aspirates of the mandibular lymph nodes and spleen. Given the absence of any definitive evidence of metastasis, the malignant melanoma was surgically completely removed. The dog then received four melanoma vaccine doses as an adjuvant therapy and remained clinically healthy for more than 3 months after the last immunization. However, 232 days after the initial discovery of the lip mass, the dog was euthanized due to deterioration and a poor prognosis based on the presence of lung metastases and neoplastic melanocytic pleural effusion. The latter has been rarely reported in dogs, despite the high prevalence of oral malignant melanomas and the tendency of these tumors to metastasize to the lungs.

Evaluation of intracavitary carboplatin chemotherapy for treatment of pleural carcinomatosis in cats: a retrospective study of eight cases.

OBJECTIVES: The aim of this study was to evaluate the benefit of intracavitary carboplatin chemotherapy in cats with malignant pleural effusion of epithelial origin. METHODS: The medical records of cats with a cytological diagnosis of neoplastic pleural effusion of epithelial origin were reviewed at three referral institutions between January 2013 and June 2018. Only cats treated with intracavitary carboplatin chemotherapy were enrolled. Data collection included signalment, medical history, clinical signs, pleural effusion analysis, diagnostic imaging findings, intracavitary carboplatin chemotherapy protocol, adverse events, response to chemotherapy, outcome and underlying primary tumour, if possible. RESULTS: Eight cats met the inclusion criteria. Three cats had previous surgical removal of a tumour, including a poorly differentiated primary lung carcinoma, a uterine adenocarcinoma and a benign mammary tumour. The main clinical signs were tachypnoea and/or dyspnoea, inappetence and weight loss. Thoracic radiographs revealed marked bilateral pleural effusion in all cats. Pleural fluid analysis was consistent with a modified transudate, with malignant epithelial cells on cytology, leading to a diagnosis of pleural carcinomatosis. All cats received only one cycle of intracavitary carboplatin chemotherapy at a dose of 200-240 mg/m2. Recurrence of pleural effusion was reported in 7/8 cats within 4-15 days of chemotherapy, and death was recorded in all cats within 5-16 days, owing to recurrent pleural effusion or poor general condition. The primary cancer was suspected to be of pulmonary, mammary and pancreatic origin in four cats, two cats and one cat, respectively, and of unknown origin in the remaining cat. CONCLUSIONS AND RELEVANCE: In this study, intracavitary carboplatin chemotherapy seems ineffective in managing neoplastic pleural effusion of epithelial origin in cats with pleural carcinomatosis. Other cytotoxic drugs and/or techniques should be investigated in the future to improve the quality of life and survival of cats with pleural carcinomatosis.

Growth of adenocarcinoma from canine pleural fluid on aerobic bacterial culture.

We report a case of canine adenocarcinoma with multi-organ metastasis in which colonies of adenocarcinoma cells grew upon aerobic bacterial culture of pleural effusion. Stained agar colonies were highly similar to rare suspicious cells seen on cytologic examination of the pleural effusion, as well as rare cells seen on cytologic examination of pancreatic and gastric wall fine-needle aspirates. Cells from colonies growing on agar media were mildly immunoreactive for cytokeratin. Histologic examination of tissues obtained at autopsy revealed pancreatic adenocarcinoma with vascular invasion and nodal, gastric, pulmonary, and pleural metastasis.

Nodules and masses are associated with malignant pleural effusion in dogs and cats but many other intrathoracic CT features are poor predictors of the effusion type.

Thoracic CT may be used in the workup of patients with pleural effusion. In humans, certain pleural features on CT aid in diagnosing an underlying cause for pleural effusion, whereas this is not well studied in veterinary medicine. This retrospective cross-sectional analytical study assessed pleural and other intrathoracic abnormalities on CT in dogs and cats with pleural effusion and explored potential discriminatory features between effusion types. Eighty-nine dogs and 32 cats with pleural cytology and/or histopathology were categorized into malignant pleural disease (15 dogs and 11 cats), pyothorax (34 dogs and 7 cats), chylothorax (20 dogs and 11 cats), transudative (11 dogs and 2 cats), and hemorrhagic effusion (9 dogs and 1 cat). Multivariable logistic regression analysis comparing malignancy to other effusions found that older patient age (dogs: odds ratio 1.28, P = 0.015; cats: odds ratio 1.53, P = 0.005), nodular diaphragmatic pleural thickening (dogs: odds ratio 7.64, P = 0.021; cats: odds ratio 13.67, P = 0.031), costal pleural masses (dogs: odds ratio 21.50, P = 0.018; cats: odds ratio 32.74, P = 0.019), and pulmonary masses (dogs: odds ratio 44.67, P = 0.002; cats: odds ratio 18.26, P = 0.077) were associated with malignancy. In dogs, any costal pleural abnormality (odds ratio 47.55, P = 0.002) and pulmonary masses (odds ratio 10.05, P = 0.004) were associated with malignancy/pyothorax, whereas any costal pleural abnormality (odds ratio 0.14, P = 0.006) and sternal lymphadenopathy (odds ratio 0.22, P = 0.040) were inversely associated with transudates. There were, however, many overlapping abnormalities between effusion types, so further diagnostic testing remains important for diagnosis.

Can malignant and inflammatory pleural effusions in dogs be distinguished using computed tomography?

Computed tomography (CT) is the primary imaging modality used to investigate human patients with suspected malignant or inflammatory pleural effusion, but there is a lack of information about the clinical use of this test in dogs. To identify CT signs that could be used to distinguish pleural malignant neoplasia from pleuritis, a retrospective case-control study was done based on dogs that had pleural effusion, pre- and postcontrast thoracic CT images, and cytological or histopathological diagnosis of malignant or inflammatory pleural effusion. There were 20 dogs with malignant pleural effusion (13 mesothelioma, 6 carcinoma; 1 lymphoma), and 32 dogs with pleuritis (18 pyothorax; 14 chylothorax). Compared to dogs with pleuritis, dogs with malignant pleural effusions were significantly older (median 8.5 years vs. 4.9 years, P = 0.001), more frequently had CT signs of pleural thickening (75% vs.44%, P = 0.04), tended to have thickening of the parietal pleura only (65% vs. 13%, P = 0.01) and had more marked pleural thickening (median 3 mm vs. 0 mm, P = 0.01). Computed tomography signs of thoracic wall invasion were observed only in dogs with malignant pleural effusions (P = 0.05). There were no significant differences in pleural fluid volume, distribution or attenuation, degree of pleural contrast accumulation, amount of pannus, or prevalence of mediastinal adenopathy. Although there was considerable overlap in findings in dogs with malignant pleural effusion and pleuritis, marked thickening affecting the parietal pleural alone and signs of thoracic wall invasion on CT support diagnosis of pleural malignant neoplasia, and may help prioritize further diagnostic testing.

Neoplastic pleural effusion and intrathoracic metastasis of a scapular osteosarcoma in a dog: a multidisciplinary integrated diagnostic approach.

A 10-year-old, female spayed mixed-breed or cross-bred dog was referred to the Small Animal Teaching Hospital of the University of Liverpool due to tachypnea, dyspnea, and pleural effusion not responding to diuretics and antibiotics. The chest was drained and cytology of the pleural fluid was consistent with a modified transudate with presence of atypical cells initially attributed to mesothelial hyperplasia and dysplasia. Computed tomography detected, in addition to the bilateral pleural effusion, diffuse pleural thickening, multiple pleural and pulmonary nodules, and a mineralized and lytic mass in the left scapula. Imaging findings were suggestive of a primary bone tumor with intrathoracic metastasis. Cytology of the left scapular and pleural masses revealed a malignant neoplasm highly suggestive of osteosarcoma. The diagnosis was confirmed by demonstration of a positive cytochemical reaction for alkaline phosphatase on prestained cytology slides. This finding prompted review of the initial interpretation of the pleural effusion cytology. The presence of neoplastic osteoblasts in the thoracic fluid was identified by a combination of cytochemistry, cell pellet immunohistochemistry, and transmission electron microscopy findings. In this report, a multidisciplinary integrated diagnostic approach was used to diagnose and confirm a neoplastic pleural effusion due to osteosarcoma metastasis in a dog.

Comparison of the efficacy of small and large-bore thoracostomy tubes for pleural space evacuation in canine cadavers.

OBJECTIVE: To determine if there is a difference in the amounts of air (A), low-viscosity fluid (LV), or high-viscosity fluid (HV) that can be aspirated from the pleural cavity of canine cadavers using small-bore (SB) or large-bore (LB) thoracostomy tubes. DESIGN: Prospective experimental ex vivo study. SETTING: University teaching hospital. ANIMALS: Thirty-six canine cadavers. INTERVENTIONS: Each cadaver was randomly assigned to 1 of 6 groups (SB-A, LB-A, SB-LV, LB-LV, SB-HV, LB-HV). In each cadaver bilateral thoracostomy tubes (either SB or LB) were placed and 20 mL/kg of air, LV fluid, or HV fluid was instilled via 1 thoracostomy tube. Both tubes were aspirated and the volume aspirated was recorded and analyzed as a percentage of instilled air or fluid volume. The procedure was repeated on the contralateral hemithorax. MEASUREMENTS AND MAIN RESULTS: There was no significant difference in air or fluid recovery when SB and LB groups were compared. Median (range) air recovery volumes in the SB-A and LB-A groups were 101.5% (94.4-115.8%) and 102.8% (94.1-107.8%), respectively (P = 0.898). Recovery of LV fluid was 93.5% (79.2-99.0%) for SB-LV and 85.8% (77.1-101.8%) for LB-LV cadavers (P = 0.305) and recovery percentages of HV fluid were 92.6% (86.1-96.2%) and 91.4% (74.2-96.4%) for SB-HV and LB-HV groups, respectively (P > 0.999). There was no significant difference between SB and LB groups when all substances were combined (94.1% [79.2-115.8%] and 93.5% [74.2-107.8%], respectively, P = 0.557). CONCLUSIONS: SB and LB thoracostomy tubes demonstrated similar efficacy in removing known amounts of air, LV fluid, and HV fluid from the pleural space of canine cadavers. Further study is necessary to determine if SB and LB thoracostomy tubes demonstrate similar efficacy in clinical veterinary patients.

Mucinous Pleural Effusion in a Dog with a Pulmonary Adenocarcinoma and Carcinomatosis.

An 11 yr old castrated male greyhound presented to the Washington State University's Veterinary Teaching Hospital (WSU VTH) for evaluation of a 4 day history of pleural effusion. The pleural effusion had a gelatinous appearance, suggestive of mucus, and was characterized cytologically as a pyogranulomatous exudate with some features suggestive of a carcinoma. Postmortem examination identified a pulmonary mass with evidence of carcinomatosis. Pulmonary papillary adenocarcinoma with carcinomatosis was the histologic diagnosis. Abundant mucin production was present, consistent with a mucinous pulmonary adenocarcinoma. To the authors' knowledge, this is the first report of a mucinous pulmonary adenocarcinoma with mucus pleural effusion in a dog.

Malignant melanoma in pleural effusion in a 14-year-old cat.

CASE DETAILS: A 14-year-old female cat presented with signs of respiratory distress. Pleural fluid was found on radiographic assessment. Cytologic evaluation of the fluid revealed malignant melanocytosis. The cat had a previous history of a recurrent malignant melanoma near the base of the right ear. Due to declining clinical condition, the cat was euthanized. CLINICAL SIGNIFICANCE: Cutaneous malignant melanomas (or melanosarcomas) are uncommon neoplasms in cats, and knowledge is limited. As far as the authors are aware, there are no previous reports in the veterinary literature of malignant melanocytes being identified in pleural effusion in cats, as they have in dogs. This report suggests that, despite conflicting information in the literature regarding the clinical behavior of cutaneous melanomas in cats, these tumors are capable of recurrence and metastasis. Aggressive treatment may be necessary even, as in this case, if the tumor is well differentiated on histopathology.

Bronchogenic adenocarcinoma in a cat: an unusual case of metastasis to the skin.

A 6-year-old, spayed, female, domestic shorthair cat was presented for decreased activity. A nodular lesion was found in the skin extending into the subcutaneous tissue of the right abdominal flank. On lateral and ventrodorsal radiographs of the thorax, an opacity involving the entire right caudal lung lobe and pleural effusion were noted. Cytologic evaluation of cells in the thoracic fluid and in the mass revealed a population of atypical epipthelial cells with marked anisocytosis and high N:C ratios, organized in acinar-like clusters. Multinucleated cells and several mitotic figures were found. The cytologic interpretation was carcinoma. Because of the progressive severity of clinical signs, the cat was euthanized. Histologic evaluation of tissues obtained at necropsy indicated a bronchogenic adenocarcinoma in the lung, with metastasis to the skin of the right flank, but no involvement of the digits. Based on immunohistochemical stains, the neoplastic cells strongly co-expressed cytokeratin and vimentin, and were negative for S-100 and actin-specific antigen. Bronchogenic adenocarcinoma is an uncommon neoplasm in cats, and the digits are the most common sites of metastasis. This case was unusual in that the skin of the abdominal wall was the primary site of metastasis, with no involvement of the digits.

Palliative intracavitary carboplatin therapy in a cat with suspected pleural mesothelioma.

A 12-year-old neutered male oriental shorthair cat was referred to the Animal Health Trust for investigation of pleural effusion. Ultrasonography revealed marked irregular thickening of the pleural surface of the cranial and caudal mediastinum. Cytological examination of the pleural fluid and fine needle aspirates of the thickened pleura suggested a diagnosis of mesothelioma. Following complete drainage of the thoracic cavity under ultrasound guidance, 180 mg/m2 carboplatin diluted in 60 ml sterile water was infused into the pleural space (30 ml in each hemithorax). This resulted in complete resolution of clinical signs for 34 days (having required thoracocentesis on four occasions in the preceding 4 weeks). The procedure was repeated using 200 mg/m2 carboplatin, and there was a further 20-day period where the cat was free of clinical signs. Further treatment was declined and the cat was euthanased 120 days after initial presentation. This is the first report of successful palliative chemotherapy for suspected feline mesothelioma and suggests that intracavitary carboplatin could be considered in tumours affecting the pleural cavity.

Use of chemotherapy for treatment of a mixed-cell thoracic lymphoma in a horse.

A 4-year-old Oldenburg mare was evaluated because of signs of lower airway disease and subsequently developed bilateral pleural effusion. Neoplastic cells were not identified in the fluid sample obtained via the initial thoracocentesis. A thoracic mass was detected radiographically, but its location prevented collection of a tissue sample. A diagnosis of lymphoma was made on the basis of results of immunophenotyping of pleural fluid specimens. Treatment of thoracic lymphoma in horses has been attempted, but there are limited data regarding chemotherapeutic-induced remission. In this horse, remission was achieved by use of a chemotherapeutic protocol consisting of administration of cytarabine, cyclophosphamide, and prednisolone. No adverse drug reactions were encountered during treatment. Immunophenotyping of cells in specimens of pleural fluid could be used to determine lymphocyte lineage and may be a useful alternative diagnostic modality when morphologic and cytologic examination of tissue specimens obtained via invasive techniques is not feasible.

Pleural fluid from a dog with marked eosinophilia.

A 12-year-old neutered male Shar-Pei was presented to the North Carolina State University Veterinary Teaching Hospital cardiology service with a 2-week history of coughing and a 2-day history of lethargy and anorexia. Pleural effusion and a mediastinal mass were detected with thoracic radiographs. Ten mL of fluid were removed via thoracocentesis, and cytologic examination of the fluid revealed marked eosinophilic inflammation and few atypical mast cells. Mast cell neoplasia was suspected. Aspirates of the mediastinal mass, abdominal lymph nodes, and bone marrow contained similar pleomorphic mast cells and increased numbers of eosinophils. The dog was diagnosed with systemic (visceral) mastocytosis, a rare form of neoplasia in dogs, and was euthanized. These tumors carry a poor to grave prognosis and the etiology is uncertain.

[Cardiac tamponade due to pericardial mesothelioma in an 11-year-old dog: diagnosis, medical and interventional treatments]. / Herztamponade durch ein Perikardmesotheliom bei einem 11-jährigen Hund: Diagnose, medikamentelle und interventionelle Behandlungen.

In a dog presenting with the clinical signs of exercise intolerance and ascites, cardiac tamponade due to suspected idiopathic pericarditis was diagnosed based on thoracic radiographs, electrocardiogram (EKG) and cardiac ultrasound. Pericardial effusion recurred soon after pericardiocenteses, prescription of colchizine and again after balloon pericardiotomy. After partial pericardectomy by thoracoscopy and after obtaining a histological diagnosis of mesothelioma adjuvant intracavitary chemotherapy using cisplatin was performed. Already one week later the dog developed marked dyspnea due to severe pleural effusion. The dog was maintained at acceptable life quality judged based on playfulness and appetite using repeated pleuro-centeses for an additional two months, when the dog was euthanized due to uncontrollable pleural effusion. Despite extensive treatments life span from initial presentation to euthanasia was only 5 months. Necropsy revealed extensive mesothelioma metastases covering the whole pleura, epicardium and remaining pericardium. Diagnostic and therapeutic aspects of (recurrent) pericardial effusion are discussed based on this case.