Malignant peripheral nerve sheath tumor as a cause of chronic cardiac insufficiency in cattle
© Pavarini et al.; licensee BioMed Central Ltd. 2013
Received: 3 August 2012
Accepted: 4 January 2013
Published: 31 January 2013
Chronic cardiac insufficiency was associated with a malignant peripheral nerve sheath tumor in a cow. An eight-year-old cow developed a progressive condition (over a period of three months) characterized by an enhanced abdominal volume, reluctance to move, a positive jugular pulse, watery diarrhea and death. At necropsy, moderate subcutaneous edema and an enhanced hepatic lobular pattern were observed. A 23x20x11 cm firm, grayish-white mass adhered to and infiltrated the right atrium. Multiple firm, yellowish-white nodules of 0.5 to 12 cm in diameter were diffusely scattered in the epicardium and parietal pericardium. Histologically, the tumor was poorly circumscribed with foci of infiltration of the myocardium. The neoplastic cells had two major histologic patterns, Antoni types A and B. Within occasional foci, pleomorphic cells with an epithelioid appearance were present in addition to multinucleated cells with periodic acid Schiff (PAS)-positive cytoplasmic globules. Foci of cartilaginous and granular differentiations were interspersed among the neoplastic cells. Multiple vessels presented wall hyalinization and tumoral embolus. Large necrotic foci with mineralization and cholesterol clefts were also observed. Immunohistochemically, the tumor was positive for S100 protein, vimentin and neuron-specific enolase labeling.
KeywordsCattle Immunohistochemical procedures Neoplasm Malignant schwannoma
Tumors of the peripheral nervous system are common in humans but comparatively rare in domestic animals, having been mostly reported in cattle, dogs, cats and horses [1–4]. Peripheral nerve sheath tumors (PNST) compose a heterogeneous group of neoplasms that includes schwannomas (neurilemomas), neurofibromas and perineuromas. These neoplasms may originate from Schwann cells, fibroblasts, perineural cells, or combinations thereof. In domestic animals, the distinction between schwannomas and neurofibromas is not clearly defined; therefore, both of these are classified as PNST according to the World Health Organization. Based on the morphology and biological behavior, PNST’s may be classified as benign or malignant [5, 6]. This type of neoplasm may occur in any location in the peripheral nervous system. In cattle, PNST are often found in autonomic nerves such as those from the epicardial and mediastinal plexus and from the thoracic and cervical sympathetic ganglia . In cattle, PNST are generally asymptomatic and considered to be incidental findings, mainly at the slaughter lines [7–9]. Only a few bovine PNST’s have been associated with clinical disease, and these have usually been linked to compression secondary to the adjacent tumor [10–13]. This paper describes the clinical, pathological and immunohistochemical findings recorded in a case of chronic cardiac insufficiency due to a peripheral nerve sheath malignant tumor infiltrating the heart of a cow.
Primary antibodies and immunohistochemical protocols applied in the study
3 min/125°C, 0,01M citrate buffer pH 6.0
Mouse anti-human neuron-specific enolase (NSE) a
3 min/125°C, 0,01M citrate buffer pH 6.0
Mouse anti-human cytokeratina
3 min/125°C, 0,01M citrate buffer pH 6.0
Mouse anti-human desmina
Microwave (700w), 3x 5min,0,01M citrate buffer pH 6.0
20 min/100°C, 0,01M citrate buffer pH 6.0
Rabbit anti-glial fibrillary acidic protein (GFAP) a
10 min/100°C, Tris-EDTA buffer Ph 9,0
Rabbit anti-bovine neurofilamentc
10 min/37°C Trypsin 0,1% and Microwave (700w), 2 min, 0,01M citrate buffer Ph 6.0
Rabbit anti-human Von Willebrand Factora
3 min/125°C, 0,01M citrate buffer Ph 6.0
Discussion and conclusions
The diagnosis of chronic cardiac insufficiency caused by a malignant peripheral nerve sheath tumor in the heart of a cow was based on findings such as type A and B Antoni patterns and immunolabeling (anti-vimentin, anti-S100, and anti-NSE), all of which are consistent with a PNST, specifically a schwannoma [12, 14–16]. The histological differentiation between malignant and benign PNST can be difficult because both may show undefined edges and some degree of cellular pleomorphism . It has been suggested that malignant PNST in cattle have invasive areas in the adjacent tissue, extensive necrotic areas and cellular pleomorphism [12, 18, 19]. All of these characteristics were observed in this case; however, the presence of neoplastic cells within the blood vessels was the main finding that determined the classification of malignancy. A high level of mitosis is also indicative of a malignant PNST [12, 19], but this finding may be absent , as was the case here. Granular and cartilaginous differentiations were observed in the neoplasm. In addition, schwannomas may also present bone, glandular and melanotic differentiations [20–24], because migratory cells from the neural crest can differentiate into melanocytes and Schwann, ganglionic and mesenchymal cells, which contribute to form muscle, bone and cartilage in the head and neck . In dogs and humans, divergent differentiation is usually associated with a poor prognosis [24, 25]. The S100 protein is the primary marker in the diagnosis of bovine PNST (schwannoma and neurofibroma) and may be used as a single diagnostic tool [13, 26–28] or in combination with other markers such as GFAP and NSE [7, 17, 19, 29, 30]. The neoplastic cells in this study showed multifocal positivity for S100 and NSE immunolabeling but were negative for GFAP. Not all neoplastic cells from occasional human malignant schwannomas demonstrate anti-S100 immunolabeling due to the particular differentiation stages of the nervous cells . Anti-GFAP immunolabeling is a characteristic more commonly found in benign than malignant PNST in the dog . Anti-cytokeratin immunolabeling is usually not observed in cases of bovine PNST , but it was observed in cells with an epithelioid pattern in the case reported here. Anti-cytokeratin immunolabeling has been associated with occasional malignant schwannomas, especially when the primary antibody is a pancytokeratin marker (AE1/AE3) . Multifocal distributions of malignant PNST in cattle have been described [13, 26, 27, 30]. It is believed that multicenter schwannomas result from a simultaneous neoplastic transformation, rather than a metastatic process derived from a single primary site [15, 27]. However, other authors suggested that the neoplastic cells may disseminate from a primary focus to other organs through metastasis . In the present tumor, multiple small nodules were detected in the visceral and parietal pericardium, in addition to a large mass adhering to and infiltrating the right atrium and associated with large numbers of neoplastic cells inside the blood vessels. Such tumoral emboli indicate the possibility that metastasis might have occurred from the tumoral mass.
PNST in cattle are usually incidental findings upon necropsy or slaughter [7–9]. Clinical manifestations in cattle affected by PNST are sporadic and include limited mobility caused by limb paresis or paralysis, cranial nerve- and brainstem-related disorders, vagal indigestion, dyspnea, recurrent ruminal bloat, and progressive wasting [10–13, 18, 26, 33]. The cow in this study showed clinicopathological chronic cardiac insufficiency expressed by a reluctance to move, engorged jugular veins with a positive pulse, cavity edema, and an enhanced hepatic pattern, clinical manifestations caused by the tumor expansion, which compressed the heart and prevented adequate cardiac output. Subsequent events included venous stasis and an increase of the hydrostatic pressure in the blood vessels. It has been suggested that because they are slow-growing neoplasms, PNST are common in old cattle . Information presented here is useful for the differential diagnosis of the bovine chronic cardiac failure.
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