Malignant giant cell tumor of soft parts in a mare

Abstract

Two subcutaneous masses were removed from the elbow of a mare. Histologically they were composed of islands of polygonal to plump spindlelioid cells with large nuclei, coarsely stippled chromatin, and eosinophilic cytoplasm. Findings were diagnostic for a malignant giant cell tumor of soft parts, a rare tumor with a fair prognosis.

A 4-year-old, Clydesdale cross mare was presented to the Atlantic Veterinary College (AVC) Teaching Hospital for the evaluation of 2 masses on the lateral aspect of the right elbow. The masses had been noted 7 mo previously and had remained unchanged since that time. The referring veterinarian had performed an initial fine needle aspirate and subsequent biopsy, which were sent to the AVC for interpretation. The aspirate was suggestive of a sarcoid, but the material provided was considered insufficient for a definitive diagnosis. Most of the biopsy contained normal dermal and subcutaneous (SC) tissues, with the exception of a small area in the deep dermis that yielded mesenchymal cells, predominantly spindle-shaped cells, multinucleated cells, hemosiderin-laden macrophages, lymphocytes, plasma cells, neutrophils, eosinophils, and a fibrovascular stroma. Anisokaryosis of these cells was moderate. Interpretation of the biopsy was that it was probably from an equine malignant giant cell tumor of soft parts.

On physical examination at the AVC, the presence of the masses was confirmed. No other abnormalities were diagnosed. The caudal mass was firm, nodular, approximately 5 cm in diameter, and freely moveable, with no apparent attachments to underlying structures. The cranial mass was approximately 10 cm long and more linear or cord-like. Its caudal part was soft and freely moveable, while its cranial part appeared to be firmly attached to the underlying musculature, with a palpable stalk running craniomedially. Potential differential diagnoses for the nodular lesions included sarcoid, scar tissue, foreign body reaction, fibroma or fibrosarcoma, chondroma or chondrosarcoma, leiomyoma or leiomyosarcoma, malignant giant cell tumor, and lipoma or liposarcoma. Differential diagnoses that were considered less likely were squamous cell carcinoma, melanoma, hemangiopericytoma, neurofibroma or neurofibrosarcoma, and lymphoma or lymphosarcoma.

In order to determine the extent of involvement of the underlying tissues and joint, an ultrasonograph of the right elbow was obtained. Detomidine HCl (Dormosedan; Pfizer, London, Ontario), 0.01 mg/kg bodyweight (BW), IV, was administered. Results showed that the caudal mass was SC and superficial, with a hypoechoic center. The cranial mass contained multifocal areas of hyperechogenicity, was encapsulated, and varied from being superficial caudally to being infiltrative cranially with involvement of the underlying muscle belly. There was no evidence of involvement of the joint or surrounding bone.

The day after presentation, the mare was prepared for surgery to resect the masses. Due to financial constraints, a standing procedure was elected. A 14-gauge jugular catheter was placed, and detomidine HCl, 0.015 mg/kg BW, and butorphanol tartrate (Torbugesic; Ayerst, Guelph, Ontario), 0.015 mg/kg BW, were administered, IV, for sedation, along with 4 mg/kg BW of phenylbutazone (Phenylbutazone; Univet, Milton, Ontario). A line block of lidocaine (Lurocaine; Vetoquinol, Lavaltrie, Quebec) was injected to desensitize the region over the right elbow. A further intraoperative dose of detomidine HCl, 0.015 mg/kg BW, and butorphanol tartrate, 0.015 mg/kg BW, was administered, IV, 45 min after the initial dose, to allow completion of the standing procedure. The masses were excised to include ~ 5-cm margins of apparently healthy tissue, and the incision was continued into the deep SC layers, where possible. Due to the infiltrative nature of the cranial mass, a 3-cm segment of the affected muscle belly was also excised in an attempt to achieve clean margins. The excised tissue was fixed in 10% formalin and submitted for histopathologic examination.

Removal of the masses and surrounding tissue produced a large rectangular defect approximately 20 cm × 15 cm. Two rows of tension relieving incisions were made in the skin, dorsal and ventral to the defect, to allow primary closure of the skin. The wound was closed in 2 layers by using a combination of mattress sutures for tension relief and a simple interrupted pattern for apposition. Drainage was accomplished with the aid of a Penrose drain that was sutured into place at the dorsocranial aspect of the wound to exit caudoventrally. A stent bandage was placed over the incision site to allow for daily wound management.

Postoperative complications were encountered 3 h after surgery, when repetitive pawing by the mare led to dehiscence of the caudal 2/3 of the incision. Initially, the stent bandage was repositioned to cover the drain and the open wound, and butorphanol tartrate, 0.015 mg/kg BW, was administered, IV, for postoperative analgesia. Eventually, the stent bandage was removed entirely, due to failure of the umbilical tape sutures. The mare was again sedated with 0.015 mg/kg BW, IV, each of detomidine HCl and butorphanol tartrate, the wound was lavaged with sterile saline, 10-cm × 10-cm gauze sponges were placed over the open wound, and a huck towel was sutured into place with large mattress sutures to cover the wound. When the gauze 10-cm × 10-cm sponges became saturated with drainage fluid, they were removed and replaced by loosening and retying the caudalmost mattress sutures. Phenylbutazone, 2.3 mg/kg BW, was administered, PO, on the evening after surgery and then q12h for the next 48 h. The dose was tapered from 2.3 mg/kg BW on the 1st day to 1.5 mg/kg BW on the 2nd day, and then discontinued.

After 2 d, the bandage and drain were removed and the surgical site was managed as an open wound. Saline-soaked 10-cm × 10-cm sponges were used twice daily to clean the wound and distal part of the limb of debris and accumulated exudate, and petroleum jelly was placed on the limb distal to the wound to reduce scalding due to drainage fluids. The wound bed appeared to be normal during hospitalization; the exudate remained serosanguinous with no evidence of malodor or pus. The mare was discharged 5 d after surgery with instructions to the owner to continue stall rest for 3 wk and limit exercise to hand walking to promote wound contraction and reduce excess motion during healing. It was recommended that the wound should then be reassessed in order to alter the exercise protocol appropriately. Cleansing of the wound with saline twice daily and application of petroleum jelly to reduce scalding of skin distal to the wound was recommended.

Results of the histopathologic examination were diagnostic for a malignant giant cell tumor of soft parts. The caudal tumor was well defined and restricted to the deep dermis. The cranial mass arose from the deep dermis but extended deep to the underling skeletal muscle. The tumors were similar histologically and were surrounded by a dense collagen capsule that was infiltrated in various areas by small nests of tumor cells. Both tumors were composed of islands of polygonal to plump spindleloid cells with large nuclei, coarsely stippled chromatin, various small nucleoli, and moderate eosinophilic cytoplasm. These cells resembled histiocytes or fibroblasts in appearance (Figure 1). Few mitotic figures were seen (approximately 1 per 400 × field), but those noted often had a bizarre appearance. Multinucleated cells with 4 to 20 nuclei were present in large numbers and were characterized by moderate eosinophilic cytoplasm. Clusters of lymphocytes, plasma cells, and many macrophages containing hemosiderin were also noted. Cells were supported by a collagenous stroma that thickened to form bands that dissected throughout the neoplasm dividing it into incomplete lobules. Many small foci of hemorrhage were present. The tumor did not appear to extend beyond the margins of the sections examined.

Figure 1. Histologic appearance of equine malignant giant cell tumor of soft parts. Note multinucleated giant cells (arrow). Hematoxylin and eosin. Bar = 25 μm.

The giant cell tumor of soft parts, also referred to as a malignant fibrous histiocytoma, is more commonly seen in the cat and is considered rare in the horse (1,2,3). To date, the neoplasm has been reported in the quarter horse, the standardbred, the Arabian horse, and the mule (1,2). The mean age of diagnosis is 6.8 y (range 3–12 y) with no apparent gender bias (2). The tumors appear in horses as firm, raised masses that are often solitary and firmly adhered to the superficial SC tissue (1). The tumors are slow growing and do not appear to have a predilection for a specific region of the body (2). Masses have been identified in the jugular groove, as well as on the thigh, stifle, elbow, thorax, and shoulder (2). Metastatic potential for this tumor in horses appears to be very low (1,4,5,6). However, in cats, it tends to involve deeper structures, grow faster, be more invasive, and, commonly, recur or metastasize (1,5,6).

Compared with other reports of equine giant cell tumors, the current case had both typical and atypical features (1,2,5,6). The age of the mare was below the usual mean age of detection, and is the first report of such a tumor in this breed (2). The presence of multiple tumors instead of the usual solitary mass, and the grossly infiltrative nature of the cranial mass are also uncommon (1,2,5,6). Tumors of this type are typically characterized as being slow growing and appearing creamy white on cut surface with evidence of a fibrous capsule and lobulation, as in this horse (2). Multifocal areas of hemorrhage and necrosis are often present (2,6), but necrosis was not observed on gross or histologic examination in this case. Erythrocytes and hemosiderin-containing macrophages were common findings, suggestive of previous episodes of hemorrhage. The current histopathologic results were consistent with reported characteristic features of this equine tumor, including numerous multinucleated giant cells surrounded by whorls of spindleloid cells and mononuclear cells, a low mitotic index, minimal anaplastic features, and a supporting fibrovascular stroma (1,2,6). In one report, giant cells isolated from the tumor contained a ruffled or irregular surface due to the presence of microvilli (6), but this was not a feature in this case. As observed in the current case, these tumors are usually confined to the deep dermal tissues, but small nests of multinucleated giant tumor cells are often found to invade the surrounding tissues. Such nests of cells may explain why this tumor often demonstrates local recurrence after surgical excision, and illustrate why wide surgical margins are important (2). Due to the locally infiltrative nature of this type of tumor, current recommendations are to achieve margins of at least 2 to 3 cm or to remove the tumor en bloc, if it is firmly adhered to underlying structures (4).

The histiogenesis of the malignant giant cell tumor is currently unknown, although its histologic characteristics suggest a mesenchymal origin (1,3,6). It is generally accepted that it represents a soft tissue sarcoma, with some authors claiming a likely histiocytic origin and others citing a fibroblastic lineage (1,3,5). A similar tumor of bone (giant cell tumor of bone, osteoclastoma) has been reported to occur in dogs, cats, and, rarely, horses (7,8). In these species, such tumors develop in the region of the epiphyses of long bones and appear to arise from mesenchymal cells of the bone marrow to produce lytic lesions (7). The only histologic similarity observed between the skeletal and nonskeletal tumors was the presence of multinucleated giant cells, mononuclear cells, spindle cells, and areas of hemorrhage (7,8). The appearance of the giant cells differs from those seen in the soft tissue tumors. It is unlikely that the skeletal and nonskeletal masses represent the same tumor type, although a common mesenchymal origin with subsequent variations in histiogenesis is possible.

Based on the limited reports on this tumor, the prognosis associated with the treatment of malignant giant cell tumors is fair (1,2,4), depending on the degree of cellular differentiation, the number of mitotic figures, the location of the tumor, the degree of involvement of surrounding tissues, and the success of surgical excision (4). In the current case, surgical excision appeared to be successful up to the time of the 8-month follow-up, but the infiltrative nature of this type of tumor and the abnormal mitotic figures indicated that the area should be carefully monitored for recurrence.