Case Report: Gingival Fibrosarcoma in a Horse
Summary
A four-year-old Thoroughbred cross mare was referred to the University of Edinburgh Veterinary School Equine Hospital for treatment of a soft tissue tumor on the buccal gingival margin of the rostral right maxillary cheek teeth. The lesion which was initially surgically excised was subsequently diagnosed as fibrosarcoma by histopathology and adjunctive treatment with intra-lesional cisplatin chemotherapy was begun. The tumor recurred and was repeatedly treated with intra-lesional cisplatin injections along with additional surgical resection over the course of 14 weeks. Despite the initial poor response to treatment, no further re-growth of the tumor occurred three months following its final treatment. The horse remained free of visible evidence of tumor nearly five years later.
Introduction
Oral tumors, especially gingival tumors, are relatively uncommon in horses compared to other domestic species. Consequently, case reports with histological confirmation of tumor type and long term follow-up information following treatment are rare. Equine oral tumors often remain undetected until they have reached an advanced state, and clinical signs are often first noted when facial swellings, dysmastication, or unilateral nasal discharge occur1. Due to usual their late detection, equine oral tumors are often difficult to treat effectively, and surgical treatment is also often limited by the poor anatomical access to the equine oral cavity, because of the limited jaw opening of herbivores. The limited documentation of equine oral tumors, other than cases of oral squamous cell carcinoma, means that it is difficult to give an accurate prognosis when treating these cases. Some equine oral tumors respond unexpectedly to treatment, with some aggressive and invasive tumors regressing completely, or alternatively, some apparently benign tumors becoming invasive and refractory to treatment1.
In general, it appears that equine oral growths are under-reported2. Equine oral tumors of dental or bone origin are rare, and although usually benign, they can lead to malformation of the supporting bones and airway obstruction in some cases. Such tumors can include ameloblastoma, cementoma, odontoma, and osteoma/osteosarcoma1. Soft-tissue tumors in contrast are more common, with squamous cell carcinoma being the most commonly reported equine oral tumor2. Other soft tissue tumors including melanoma, haemangiosarcoma and fibroma/fibrosarcoma have been less commonly documented in the equine oral cavity.
Fibrosarcoma been rarely reported in any site in horses, with just a few reports of fibrosarcomas of the subepithelial connective tissue of the head and trunk, and synovial structure linings published3. This is in contrast to equine sarcoids, which are the most common tumor in horses, and are often histologically diagnosed as fibrosarcoma. Sarcoids contain a fibrosarcoma-like stromal component, but are generally differentiated from fibrosarcoma by the relationship between the spindle cells and the overlying epidermis, which is often hyperplastic with prominent rete pegs4. Consequently, true equine fibrosarcomas should be considered separately from sarcoids, although both tumor types can be classified as soft tissue sarcomas5. In contrast to horses, fibrosarcomas are frequently found in the oral cavity of dogs6, 7.
Fibrosarcomas have been identified in the paranasal and premaxillary regions in limited numbers of equine cases8, but have not been reported caudal to the premaxilla in the oral cavity. No metastases have been reported for fibrosarcomas of oral or paranasal origin in horses. In other species, fibrosarcomas are reported to often recur following surgical excision due to tumor cells invading deeper fascial planes (up to 30% in canine patients9 ), but metastasis is rare7.
The overall prevalence of oral tumors in horses appears low with a prevalence of 1.8% in 400 consecutive referred cases of dental disorders at this clinic, all of which were odontogenic or osteogenic in origin, including ameloblastoma, osteoma, and osteosarcoma10. Only two horses were treated successfully with lesional excision, while the remaining five were euthanized either immediately following diagnosis or following unsuccessful attempts at lesional excision. It is interesting that no gingival growths (neoplastic or non-neoplastic) were reported in this case series 10 .
This case report describes a fibrosarcoma of the buccal gingiva of the maxillary cheek teeth that was successfully treated by repeated surgical excision and intra-lesional cisplatin.
Case Report
A four-year-old Thoroughbred cross mare was presented to the University of Edinburgh Equine Hospital due to an acute onset swelling rostral to the right facial crest, first noted five weeks prior to presentation. Oral examination by the referring veterinarian identified an exudate-covered, firm, pink soft tissue mass located on the buccal gingival margin of the 107 cheek tooth. The horse was treated with oral potentiated sulphonamides, but the mass continued to grow and the horse was referred for investigation of a suspected oral tumor.
A firm, non-mobile mass within the oral cavity adjacent to cheek tooth 107 was palpable through the cheeks. Oral examination revealed an ulcerated, red, soft tissue growth, approximately 20 mm wide and 40 mm long on intraoral measurement, which was attached to the buccal gingiva of the 106 cheek tooth by a small pedicle and extensively to the gingiva of the 107 and the rostral aspect of the 108 (Fig. 1).
Under standing sedation, (0.04 mg/kg romifidine hydrochloride[a] and 0.025 mg/kg butorphanol[b] IV) an excisional biopsy (approximately 5 mm diameter and 5 mm deep) was sharply dissected from the mass to include both the gingival epithelium and subepithelial tissue. Cryostat histopathology was performed to quickly determine the nature of the mass to plan treatment for the following day. Histology showed fibroplasia, neovascularization, and fibrosis indicating that the mass was compatible with exuberant granulation tissue,. There was also surface ulceration with a superimposed exudate of fibrin and neutrophils.
The following day, the mass and its gingival attachments were sharply excised as deeply as possible per os under (the previously described) standing sedation (Fig. 2), removing a 45x25x25 mm growth. Due to the location and depth of the mass, the excision was incomplete however, with some soft tissue appearing to remain deep to the plane of excision. There was minimal post-operative hemorrhage or discomfort following surgery. Perioperative broad-spectrum antibiosis was provided along with intravenous flunixin meglumine[c] (1.1 mg/kg), and the horse was discharged from the hospital on the following day, on a seven-day course of oral phenylbutazone[d] (2.2 mg/kg PO twice daily).
Histology of paraffin embedded sections of the excised growth showed its subepithelial tissue was extensively effaced and the gingiva elevated into broad-based polypoid projections by a multilobulated, non- encapsulated, ill-defined proliferation of fusiform spindle cells arranged in swirling streams and bundles supported by a collagenous stroma and extracellular matrix. Some of of the streams and bundles were quite short. There was occasional nuclear palisading, creating a herringbone pattern. Individual cells had indistinct cell borders, a moderate amount of fibrillar, pale eosinophilic cytoplasm and oval to elongated hypochromatic nuclei, often with at least one prominent nucleolus. There was moderate anisokaryosis and mitotic figures averaged 5 per 10 hpf (400X). In one or two areas, the spindle cells were more densely packed and florid, with increased nuclear pleomorphism and mitoses (up to 6 per hpf). No surgical margins were apparent with spindle cells present at the excised border. The gingival epithelium was variably hyperplastic and ulcerated, with superimposed fibrin, necrotic neutrophils and bacterial cocci. The histological features and infiltrative growth pattern were compatible with an oral sarcoma, most likely a fibrosarcoma (Fig. 3). Given the diagnosis, it was considered likely that this tumor would have the potential to be locally invasive and recurrent, especially as excision did not appear to be complete. More accurate prognostication was difficult, due to the rarity of reports of such tumors in horses.
The mare remained comfortable with a good appetite and had no apparent difficulty in eating following surgery. Due to the suspicion of incomplete excision, intralesional cytotoxic therapy was recommended as soon as feasible as an adjunctive treatment to surgical resection. The horse returned to the R(D)SVS four weeks after the initial surgery for its first intralesional treatment. The facial swelling had not significantly reduced although only minimal regrowth of the mass was visible intraorally, with small nodules beginning to appear on the gingival surface. Following sedation, 1 mg cisplatin[e] suspended in 2 ml sesame oil was administered intralesionally at multiple sites, particularly at the margins and attachments to grossly normal tissues. The horse was discharged from the hospital on the same day, on a 14-day course of oral phenylbutazone (2.2 mg/kg PO twice daily).
At examination four weeks later (eight weeks after the initial surgery), the external swelling was smaller although further regrowth of the tumor on the gingiva on the buccal aspect of teeth 106 and 107 was visible intraorally as compared to the previous examination, (Fig. 4). Following sedation, 2 mg cisplatin suspended in sesame oil was administered intralesionally as previously described, and the horse was discharged into the owner’s care with a seven-day course of oral phenylbutazone.
Fourteen weeks following initial surgical treatment, the horse was observed to be uncomfortable during eating and had marked halitosis. Repeat evaluation revealed that the external swelling rostral to the right facial crest was similar in size to the previous examination. However, significant regrowth of the tumor was seen intraorally when compared to the eight-week reexamination. The mass had developed several pedunculated portions adjacent to the 106 and 107 cheek teeth with entrapment of feed material and marked inflammation of the adjacent gingiva and oral mucosa dorsal to the growth. Under sedation, two pedunculated portions of the mass were sharply resected as deeply as possible, and 4.5 mg cisplatin suspended in sesame oil was administered intralesionally into the affected gingiva with postoperative oral phenylbutazone prescribed as before. The mass was not submitted for subsequent histopathological evaluation as it was highly unlikely deeper margins were obtained during this second surgical procedure.
A very guarded prognosis was given due to the repeated regrowth of the tumor despite three cytotoxic and two surgical treatments. The horse was discharged with the understanding that further significant regrowth of the tumor accompanied by dysmastication and discomfort might necessitate euthanasia. However, the horse returned to our clinic three months after the final surgical and cisplatin treatments with no recurrence of the facial swelling detected and no discomfort observed when eating. Intraoral examination revealed that the mass had fully regressed, with only scarring of the retracted gingival margin visible where the mass had been (Fig. 5). No treatment was performed at that time.
Eight months following the final treatment, the owner reported that the horse was asymptomatic other than intermittent food accumulation at the site of tumor excision. Clinical examination confirmed the absence of facial swelling, with no tumor regrowth visible on oral examination. A small amount of calculus had accumulated on the buccal aspect of tooth 107, due to its retracted gingival margin following surgical resection and intra-lesional therapy of the growth. The calculus was easily removed using a dental pick, revealed moderate gingivitis of the underlying tissue (Fig. 6). Biannual dental evaluation was recommended following discharge from the hospital. The final follow through information was obtained four years later, when it was reported that the horse continued to be asymptomatic and in full work.
Discussion
Fibrosarcoma falls under the general category of soft tissue sarcoma. These tumors are generally non-encapsulated and have poorly defined borders and consequently, recurrence is common following excision. They are also reported to respond poorly to chemotherapy or radiotherapy7. The tumor in this case report repeatedly recurred after both surgical excision and intralesional cisplatin therapy, but eventually responded to further surgical debulking and intra-lesional chemotherapy.
The initial histopathological diagnosis of granulation tissue on the cryostat preparations in this case most likely reflects the presence of surface granulation tissue, possibly secondary to ulceration and trauma of the mass and on retrospect, a deeper biopsy would have been better. Regardless of the biopsy depth, cryostat sections can be difficult to interpret and it is possible that a combination of tumor cells and reactive fibrous tissue were present in the original biopsy. Interestingly, Findley et al (2013) reported that it can be difficult to histologically differentiate equine fibrosarcomas from hyperplastic granulation tissue, particularly when samples are small, poorly oriented or fragmented3. Clinically, the most likely differential diagnoses for the tumor reported here include fibrous gingival hyperplasia or gingival fibroma, commonly termed oral fibroma in clinical literature, both which are infrequently diagnosed in horses1,2. Fibrous hyperplasia tends to be self-limiting, usually does not require treatment, and is not a precursor to malignancy. Oral fibromas can appear clinically similar to fibrous hyperplasia and have been recorded in horses, but are likely under-reported. They tend to be slow growing, but could feasibly develop into fibrosarcomas, which could have been the possible pathogenesis in this case due to its location1.
In general, fibrosarcomas are histologically characterized by variably pleomorphic spindle cells arranged in interlacing bundles and supported by a collagenous stroma. There are varying degrees of anisokaryosis, anisocytosis, nuclear pleomorphism and mitotic activity, depending on tumor grade3,9. Most fibrosarcomas are likely to recur, especially if not widely excised. Metastases have also been reported in cases of equine fibrosarcoma, most frequently to the lungs and liver. Primary tumor locations include the subcutis, bone, pleura, skeletal muscle and peritoneum11 12although not, as previously noted, the oral cavity,.
There are various differentials to consider for soft tissue sarcomas including, peripheral nerve sheath tumors and perivascular wall tumors. Histopathologically, a diagnosis of peripheral nerve sheath tumor was considered, particularly given that some areas were composed of more slender fusiform cells in a cleared, looser stroma. These tumors have been described in other species, most commonly associated with spinal nerves or the autonomic nervous system13. However, in this case the more predominant interlacing pattern indicated a more likely fibrosarcoma as opposed to nerve sheath tumor. Additionally, perivascular wall tumors derived from the mural wall of blood vessels share the ‘spindle-cell’ characteristic with fibroma/fibrosarcoma and peripheral nerve sheath tumors. However, they also typically exhibit a whirling, bundled pattern of growth which was not seen in this tumor as described14Another differential diagnosis for a similar gingival mass in dogs is a peripheral odontogenic fibroma. These masses histologically contain stroma of periodontal ligament origin along with odontogenic epithelium, which may appear as bone, cementum, or dentine. Fibromatous epulides may not extend to the gingival surface however, and they are always continuous with the periodontal ligament proper. The treatment of choice for these tumors is local excision as well, which is typically curative15.