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Abstract
A 10-year-old, female, pot-bellied pig (Sus scrofa) experienced a 3-month history of reduced appetite, dysphagia, and weight loss. Clinical examination revealed a mass in the left part of the oral cavity extending from the hard to the soft palate. At necropsy, a firm, white, poorly demarcated ulcerated mass at the left hard and soft palate with metastases to the left retropharyngeal lymph node and the lung was observed. Additional findings included a uterine adenocarcinoma, a hepatocellular adenoma, and nodular hyperplasias in spleen and adrenal glands. Histologically, the poorly demarcated, infiltrative growing oral mass consisted of islands, cords, and single epithelial cells with moderate squamous differentiation. Cells were strongly positive for cytokeratin by immunohistochemistry. Similar cells were found in the left retropharyngeal lymph node and the lung. The present findings represent the first report of a metastasizing oral squamous cell carcinoma in a pig.
Key words: Hepatocellular adenoma; immunohistochemistry; pot-bellied pig; oral squamous cell carcinoma; uterine adenocarcinoma.
Neoplasms in pigs have been reported only infrequently and include uterine leiomyoma and fibroma, malignant lymphoma, melanoma, hemangiosarcoma, hepatocholangioadenoma, hepatocellular carcinoma, and osteoma in decreasing frequency.1,4,10,11 Squamous cell carcinoma represents a common neoplasm in some domestic species including dogs and cats. In addition, it has been described in cows and horses but not in pigs.6,7,12 This tumor entity can be observed in various locations including eyelid, conjunctiva, pinna, oral cavity, vulva, stomach, and skin.12 However, there are specific preferential locations for each species.12 Although the cause triggering development of squamous cell carcinomas remains undetermined in most cases, chronic physical irritation (i.e., chronic epidermal injury), UV light, and virus infection have been shown to play a causative role in most cases.12 In addition, carcinogens contained in tobacco, coal tar, and soot as well as arsenic and smegma have been shown experimentally or by epidemiologic data analysis to play an important role as promotor.12 Uterine adenocarcinoma, a common finding in rabbit and cattle, has been described only rarely in other domestic animals including the sow.8 Metastases can be found frequently in regional lymph nodes and lung.8
A 10-year-old pot-bellied pig (Sus scrofa) showed a 3-month history of weight loss and dysphagia. Clinical examination revealed an ulcerated, infiltrative growing mass in the hard and soft palate of the left oral cavity. Owing to poor prognosis, the animal was killed and submitted for necropsy. Tissue samples from various organs including the mass of the oral cavity and the left retropharyngeal lymph node were collected at necropsy, fixed in 10% buffered formalin, and embedded in paraffin wax.9 Tissue sections were stained with hematoxylin and eosin (HE) and used for immunohistochemistry by applying the ABC-method using primary antibodies directed against cytokeratin (DakoCytomation, Glostrup, Denmark), and vimentin (DakoCytomation, Glostrup, Denmark).9 In brief, sections were dewaxed and antigens were demasked by Pronase E and Tween treatment (cytokeratin; 20 minutes), Triton treatment (vimentin; 0,25%, 30 minutes) as described.9
Gross pathology revealed a multifocal, firm, white, ulcerated, poorly demarcated mass measuring 15.0 x 7.2 x 2.4 cm in size, in the left side of the oral cavity in the hard and soft palate (Fig. 1). The neoplasm reached from the ethmoid bone and the left internal pterygoid muscle to the rostral palate with subpalatinal extension to the canines. Furthermore, a diffuse infiltration into the left cheek was noticed. All premolars and molars of the left side and the third molar of the right side were missing. An abscess at the ethmoid bone, adjacent to the neoplasm was detected. In addition, a tumor mass, measuring 8.0 x 4.0 x 4.0 cm, was found in the region of the left lateral retropharyngeal lymph node. The lung was slightly increased in size, firm, and reddish with prominent interlobular septae.
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Histologic examination of the oral cavity revealed a densely cellular, poorly demarcated, unencapsulated mass consisting of a moderate fibro-vascular stroma and numerous neoplastic epithelial cells arranged in sparsely-packed islands, cords, or as single cells, infiltrating into the submucosa. The tumor cells, round to oval, sometimes polygonal, between 10 x 20 µm and 15 x 30 µm in size, with distinct cell borders, exhibited a moderate amount of a pale eosinophilic cytoplasm and possessed a centrally located round to oval nucleus (Fig. 2). Tumor cells were further characterized by a finely stippled chromatin pattern, two to five nucleoli and one to two mitoses per high power field (HPF). Prominent squamous cell differentiation was found in a few locations. A few bizarre mitotic figures were also found. Additional findings included loss of preexisting bone tissue as a result of tumor-cell infiltration, crater-like ulcerations with secondary superficial bacterial infection, multifocal areas of necrosis, and a moderate, diffuse, lympho-histiocytic, neutrophilic, focal granulomatous inflammation with few multinucleated giant cells. In the left retropharyngeal lymph node and most frequently in the interlobular pulmonary septae, tumor-cell infiltration, similar to the one described in the oral cavity, was associated with lymphocytes and plasma cells (Fig. 3).
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Squamous cell carcinoma may also have an extension to the nasal cavity, and ulcerations are frequently complicated by secondary bacterial infections similar to the present case.7 Lymphatic metastasis of feline and canine oral squamous cell carcinomas may occur by massaging tumor cells into vessel by the tongue.7 Only 510% of canine gingival squamous cell carcinomas metastasize into regional lymph nodes and only 3% to distant sites.7 In contrast, tonsillar squamous cell carcinoma of the dog metastases frequently and very early in the course of the disease into the mandibular lymph node. Ninety-eight percent spread to the regional lymph nodes, and 63% show distant metastases in lung, liver, and spleen.7 In this 10-year-old, female, pot-bellied pig, spatial distribution of the primary tumor and metastases, ulcerations, and extension into ethmoidal structures are reminiscent of metastasizing oral squamous cell carcinoma of tonsillar origin in cats and dogs. The cause of the present case remains undetermined.
Though genital tract tumors including uterine leiomyomas and fibromas are frequently noted in aging pigs, endometrial adenocarcinomas have been described only rarely.1,5,11 The latter is a rare tumor in many domestic animals except for cattle and rabbits.8 The incidence of endometrial adenocarcinomas is more frequent in older animals compared with younger.8 Squamous cell metaplasia as observed in the uterine adenocarcinoma of the present pot-bellied pig has also been described in humans.2 Unfortunately, immunohistochemical results did not allow to distinguish between a carcinoma of endometrial or oral cavity origin, therefore a metastasis of the squamous cell carcinoma within the uterine adenocarcinoma cannot be ruled out completely.
Hepatocellular adenomas are described in dogs, cattle, sheep, cats, and pigs.3 The occurrence of benign hepatocellular neoplasms is less frequently reported than the malignant counterpart.3 Some authors reported an increased incidence of hepatocellular adenoma in younger pigs in contrast to other species.3 In the present pot-bellied pig, the adenoma was differentiated from nodular hyperplasia and carcinoma by lack of infiltrative growth and anisokaryosis as well as the presence of a capsule. In conclusion, this report describes for the first time a metastasizing oral squamous cell carcinoma in a 10-year-old pot-bellied pig.
Acknowledgements
We would like to thank Mrs. P. Grünig for excellent technical assistance and Mrs. B. Behrens for photographic support.
References
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