Biphasic pleural mesothelioma in a goat

Abstract

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.

Thoracic masses in small ruminants are uncommon and can be either neoplastic or inflammatory in nature (1). In general, inflammatory etiologies are more commonly encountered. For instance, Echinococcus sp. infection can cause hydatid cysts in the pleura and peritoneum of small ruminants (2,3), and nematodes such as lungworms occasionally lead to granuloma formation throughout the lungs, pleural surfaces, and along airways (4). Bacteria such as Corynebacterium pseudotuberculosis and Mycobacterium sp. can lead to granulomatous pneumonia, lymphadenitis, and pleuritis (1,5,6), as can fungi such as Cryptococcus sp. and Coccidioides sp. (5,7).

Neoplasia involving the thoracic cavity of goats is comparatively rare (1). Thymomas are one of the most common neoplasms of goats and usually exhibit benign behavior (8–10). Many thymomas are discovered incidentally, and cases with clinical compromise are usually due to local expansion of the mass and compression of adjacent structures rather than to metastasis or tissue invasion (10). In a retrospective study of 100 goats with neoplasia, 8.8% of the tumors were thymomas (8); and in a second study of 67 dairy goats > 2 y old, 25.3% had thymomas at necropsy (9). Thymomas can be found in the cranial mediastinum, ventral cervical region, or both, and tend to occur in older goats (10).

Unfortunately, not all neoplasms of the caprine thoracic cavity exhibit benign behavior. It is rare to encounter malignant neoplasms in the thoracic cavity of goats, but when seen, these include primary pulmonary carcinoma, metastatic neoplasia, lymphosarcoma, and mesothelioma (1,8,11,12). Mesothelioma is an extremely rare malignant neoplasm in livestock species, but it has been documented in cattle, sheep, and goats, among others (11–16). As in humans, mesothelioma of domestic species can develop at any site lined by mesothelium, including the pleura, peritoneum, pericardium, and tunica vaginalis of the testes (17). Clinical signs seen are dependent on the affected site and are often secondary to effusion, local tumor expansion and infiltration, or distant metastasis (12). In livestock species, mesotheliomas of the pleura, peritoneum, and pericardium have been reported (11–13,15,18). Common clinical signs include dyspnea, tachypnea, tachycardia, ascites, and anorexia. The prognosis is extremely poor, with only minimal disease amelioration achieved by surgical, radiological, and chemotherapeutic interventions (17).

In this case report, we describe pleural mesothelioma in a goat, which, to our knowledge, has only once been previously described.

Case description

The 8-year-old Saanen goat doe described in this report served as a healthy control and breeding animal as part of a research project approved by the Washington State University Institutional Animal Care and Use Committee (approval #s 6665 and 6667). The goat was born and maintained in an indoor/outdoor animal housing facility in eastern Washington State, USA, and was current on annual immunization for the diseases caused by the toxins of Clostridium perfringens Types C and D and C. tetani (BarVac CD/T; Boehringer Ingelheim, Ridgefield, Connecticut, USA) and on endo-/ectoparasite control, when indicated by fecal and physical examinations [anthelmintics: fenbendazole (Panacur; Merck, Rahway, New Jersey, USA) or ivermectin (Ivomec; Boehringer Ingelheim); Eimeria control: amprolium (Corid; Merial, Duluth, Georgia, USA); chewing lice infestation: coumaphos (Co-Ral; Bayer, Shawnee Mission, Kansas, USA) or permethrin (Permectrin II; Bayer)]. Serology for Coxiella burnetii (last trimester of pregnancy) and small ruminant lentivirus were consistently negative over the life of this animal and herd. Prior to the illness described herein, the goat had experienced no major health problems.

Veterinary evaluation was requested due to 2 d of reduced appetite, reduced fecal and urine output, increased HR, and intermittent bluish-grey discoloration of the mucous membranes. On clinical examination, the doe was bright, alert, and responsive, and had pink, but tacky, mucous membranes. The doe was thin in body condition and the abdominal contour appeared bilaterally sunken. The rectal temperature (39.9°C), HR (156 beats/min), and Rf (respiratory rate: 56 breaths/min) were initially elevated. The rectal temperature and Rf later returned to within normal limits (temperature: 39.1°C, Rf: 36 breaths/min), although an expiratory abdominal effort and tachycardia persisted (120 beats/min). There was mild, bilateral, dry nasal discharge, and thoracic auscultation revealed reduced sounds on the left side. The only other significant clinical abnormalities were reduced and firm rumen fill and reduced rumen contractility. The results of a complete blood (cell) count (CBC) and blood smear were within normal limits, apart from a PCV of 45% [reference range (RR): 22 to 38%], which was attributed to dehydration. The plasma fibrinogen was 2 g/L (RR: 1 to 4 g/L). A serum chemistry panel revealed mild hyperproteinemia at 76 g/L (RR: 61 to 71 g/L) characterized by a low normal albumin at 26 g/L (RR: 25 to 35 g/L) and mild hyperglobulinemia at 50 g/L (RR: 27 to 41 g/L). Also noted were mild hypocalcemia at 2.10 mmol/L (RR: 2.25 to 2.97 mmol/L) and hypomagnesemia at 0.78 mmol/L (RR: 1.11 to 1.44 mmol/L), and mildly elevated sorbitol dehydrogenase at 31.9 U/L (RR: 14 to 30 U/L). Because this was an aged research animal, euthanasia and postmortem workup were elected to rule out diseases of potential concern to the rest of the herd.

Necropsy revealed an infiltrative, multinodular, tan mass within the left thoracic cavity, with diffuse atelectasis of the left lung lobes (Figure 1). The mass contained variably sized pockets of viscous, brown-green fluid. Innumerable small, tan nodules were disseminated across the visceral pleura of the lungs and parietal pleura of the thoracic walls and diaphragm. The mass minimally extended into the subpleural pulmonary parenchyma in few areas, and in one focus, extended through the mediastinum into the right thoracic cavity. Apart from the mammary glands, which contained multiple areas of mild fibrocystic change, other tissues (brain, eyes, oral cavity, heart, trachea, esophagus, thyroid gland, gastrointestinal tract, spleen, liver, kidneys, adrenal glands, urinary bladder, musculoskeletal system, skin, uterus, and ovaries) were grossly normal.

Figure 1.

Dorsal aspect of the lungs of an 8-year-old goat doe, with the cranial aspect to the left of the image. Note that the left lung is almost entirely atelectatic (*). Numerous pale tan-colored nodules (arrowheads) are disseminated across the pleural surface.

Samples of the thoracic mass were collected, fixed for ~4 d in 10% neutral buffered formalin, trimmed into tissue cassettes, and submitted to the Histopathology Section of the Washington Animal Disease Diagnostic Laboratory (WADDL) for routine processing and generation of H&E-stained slides. Following evaluation of the H&E-stained slides, paraffin-embedded tissue blocks were resubmitted to the WADDL Histopathology Section for pancytokeratin and vimentin immunohistochemical staining. Slides were examined independently, by 2 ACVP Board-certified veterinary anatomic pathologists (LMF and LAW), using light microscopy.

Histologically and at several sites, the visceral pleura was expanded by an infiltrative, densely cellular, and poorly demarcated mass that effaced subjacent alveoli (Figure 2 A). The mass was composed of streams, bundles, nests, and papillary projections of spindloid to round to polygonal cells supported by a moderate fibrous stroma (Figure 2 B, C). Cells had a moderate amount of eosinophilic cytoplasm and variably distinct borders (Figure 2 B, C). Nuclei were ovoid to round, with finely stippled chromatin and 1 to 3 variably prominent, basophilic nucleoli (Figure 2 B, C). Anisocytosis and anisokaryosis were moderate to marked. There were 2 mitoses per 10 400× high-powered fields (HPF) in the spindloid cell population, and 3 mitoses per 10 400× HPF in the epithelioid population. In a few small, randomly scattered foci, neoplastic cells were necrotic. Low numbers of erythrocytes and mixed leukocytes were scattered throughout the sectional area. Both epithelioid and spindloid cell populations exhibited strong, intracytoplasmic immunoreactivity for pancytokeratin and vimentin (Figure 3 A, B).

Figure 2.

Pleural neoplasm in an 8-year-old goat. H&E staining. A — Sub-gross (2.5× magnification): The visceral pleura is expanded by a densely cellular mass that infiltrates into and effaces the lung. The mass is composed of nests, streams, bundles, and papillary projections of neoplastic cells supported by a fine to moderate fibrous stroma. B (20× magnification) and C (40× magnification) — Cells are round to polygonal to fusiform, with finely stippled chromatin and prominent nucleoli.

Figure 3.

Pleural mass in an 8-year-old goat. Pancytokeratin (A) and vimentin (B) immunohistochemistry, 20× magnification. Neoplastic cells demonstrate strong immunoreactivity for both epithelial (A) and mesenchymal (B) cell markers. This finding, along with the gross appearance and location of the mass, is consistent with mesothelioma.

Discussion

The tachypnea, tachycardia, asymmetrically muffled cardiopulmonary auscultation results, and intermittent bluish-grey discoloration of mucous membranes noted during evaluation of the doe were suggestive of severe pathology of the thoracic cavity. These findings, coupled with the age of the animal, weight loss, and recent inappetence, were indicative of a poor prognosis. Due to the potential risk of an infectious etiology that could affect others in the herd, necropsy and histopathology were pursued to determine the definitive cause of clinical decline. The appearance of the mass at necropsy was consistent with malignant neoplasia, and our top differential diagnoses at that point were metastatic carcinoma, carcinomatosis, and mesothelioma. A thymoma was deemed unlikely based on the multinodular, infiltrative, and widely disseminated nature of the neoplasm. Blueish-grey discoloration of mucous membranes and unilaterally muffled cardiac and lung sounds appreciated during physical examination were likely the result of diffuse atelectasis of the left lung lobes coupled with the mass effect caused by neoplastic tissue and fluid-filled, cystic spaces within the pleural space.

Histologically, mesotheliomas are divided into epithelioid, sarcomatous, and biphasic (mixed) types (19). Epithelioid tumors are composed of polygonal to round cells that form nests and papillary projections, whereas sarcomatous tumors are composed of streams and bundles of fusiform cells (19). Biphasic tumors contain areas of both epithelioid and sarcomatous patterns, as shown in this case (19). Since mesotheliomas closely resemble many other tumor types histologically, immunohistochemistry is often necessary to reach a definitive diagnosis (12,17). Mesothelial cells are considered primitive mesodermal cells and have the capability to undergo both mesenchymal-to-epithelial and epithelial-to-mesenchymal transitions, depending on environmental cues (20). As such, mesotheliomas generally express both epithelial (e.g., pancytokeratin) and mesenchymal (e.g., vimentin) markers (12,17,20). The histomorphology, immunohistochemical labeling pattern, and gross appearance of the lesion were subsequently used to confirm a diagnosis of mesothelioma, as in this case.

To our knowledge, this is the second report of a pleural mesothelioma in a goat (11), and 3 other reports describe peritoneal mesotheliomas in goats (12,15,16). The other reported pleural mesothelioma (11) caused dyspnea, tachypnea, and inappetence. Pleural effusion was noted on radiographs, and mucinous fluid was obtained via thoracocentesis. The histologic description of that tumor was consistent with the epithelioid subtype. Two of the 3 peritoneal mesotheliomas in goats caused significant ascites and inappetence (15,16), and the 3rd (12) resulted in chronic weight loss, anemia, inappetence, lethargy, diarrhea, dyspnea, and mucous membrane pallor. The latter was reported to be a sarcomatous mesothelioma and exhibited widespread metastasis to the lungs and myocardium, as well as severe effacement of the liver, adrenal glands, kidneys, and uterus. One of the remaining 2 reported peritoneal mesotheliomas was of the biphasic subtype (15), and the subtype of the 3rd was unspecified (16).

In cattle, mesotheliomas are often congenital, and are primarily seen in the peritoneum of neonatal calves (21). Although 54 to 90% of mesotheliomas in humans are attributable to previous asbestos exposure (19,22) [likewise for some cases in dogs (23,24)], no definitive causation has been established for mesotheliomas of livestock and other veterinary species (12,17). However, as studies have documented accumulation of potentially carcinogenic particulates and fibers within the pleura, lungs, and lymph nodes of small ruminants (25), a similar pathogenesis is possible.

Although rare, thoracic cavity neoplasia should be considered as a differential diagnosis in middle-aged and geriatric small ruminants with evidence of respiratory compromise. In goats, thymoma is the most commonly encountered thoracic neoplasm; however, malignant tumors, including mesothelioma, should also be considered. In addition to neoplastic causes of thoracic cavity masses, cysts and granulomata caused by parasites, bacteria, and fungus can also cause severe mass effects in the thoraxes of small ruminants.

Funding Statement

This work was supported by the USDA-ARS CRIS project numbers 2090-32000-042-000-00D and 2090-32000-044-000-00D.