Equine sinonasal anaplastic sarcoma infected with multi-drug resistant Escherichia coli

Abstract

A 5-year-old Hanoverian horse was presented for a palpable and visible mass over the frontal and maxillary sinuses. Following endoscopy and radiography surgical excision was attempted. The horse was euthanized during surgery and samples of the mass were identified as malignant anaplastic sarcoma, a seldom reported sinonasal tumor in equids.

Sinonasal tumors in horses are rare and generally present as maxillary sinus cysts, progressive ethmoid hematomas, or inflammatory nasal polyps (1,2). Neoplasms are most commonly found in the caudal maxillary sinus, unlike in humans, in whom tumors are more likely to develop in the nasal passages (2). In equids, neoplasms usually present as squamous cell carcinomas (1); adenocarcinoma, osteomas, dental tumors, fibrosarcomas, and hemangiosarcomas are also found (1,3). One case report details an anaplastic sarcoma in the right caudal maxillary sinus of a 10-year-old horse (3). Anaplastic neoplasms are solid masses of undifferentiated cells that are commonly round or pleomorphic epithelial cells, making them most commonly carcinomas.

Communication between the paranasal sinuses, nasal passages, and nasopharynx allows for easy spread of tumor cells throughout the region by invasion or expansion (1). Tumors most commonly develop in the caudal maxillary sinus from which neoplastic cells are able to pass into the frontoconchal sinus through the frontomaxillary opening (1,4) and invade the rostral maxillary sinus by eroding the maxillary septum (1,4). The rostral maxillary sinus is divided into lateral and medial compartments by the infraorbital canal; from the medial portion a neoplasm could invade the ventrochonchal sinus, which communicates with the dorsochoncal sinus, through the conchomaxillary opening (4). The rostral maxillary sinus also communicates with the middle meatus via the nasomaxillary opening which allows neoplasms to expand into the nasopharynx (4). The close anatomic location of the nasal cavity and paranasal sinus to vital structures, such as the meninges, great vessels, and skull base, results in sinonasal tumors having a poor prognosis (5).

Growth of a tumor puts pressure on the surrounding tissues and blood vessels, resulting in increased rate of bone resorption, while surrounding unaffected areas with intact blood vessels lay down excessive new bone, causing facial swelling (1). In expansile growth, thinner bones, such as the concha and ethmoids, are destroyed as the tumor expands into them, while more flexible tissues, such as cartilage, are distorted (1). With invasive growth there is increased pressure on tissues as the tumor cells invade between layers of calcaneous bone (1). This allows for further spread of the neoplasia into regions such as the cribriform plate and orbit. The neoplasm can also occlude the blood and lymphatic vessels which exacerbates swelling of the head (1).

Metastasis of sinonasal tumors is infrequently reported (1,6,7) but can occur to local lymph nodes and other areas of the head (1,3). Clinical signs of sinonasal neoplasia are similar to those of non-neoplastic tumors, trauma, and infectious lesions (6). Nasal and ocular discharge, facial deformities and swelling, mastication problems, and neurologic signs have all been reported (1,3,6). Treatment is difficult because diagnosis often occurs in the late stages of disease (2).

Case description

A 5-year-old Hanoverian mare was presented with a 3-week history of facial swelling and the owners had noticed blood on the stall walls. The horse appeared normal before presentation. The referring veterinarian had treated the horse with IM ceftiofur and penicillin G. Radiographs showed fluid in the frontal and right caudal maxillary sinuses. Nasal discharge began on the left side and progressed to bilateral discharge. A week before referral the horse was started on 2 g of phenylbutazone once a day. The horse was being treated with omeprazole before initial presentation to the referring veterinarian.

On examination, the horse had persistent left-sided mucopurulent nasal discharge and the left frontoconchal and caudal maxillary sinuses were swollen. External palpation found the swelling to be firm and boney. Percussion of the left maxillary and frontal sinuses was dull. Epiphora was observed in the left eye. There was swelling in the mid-neck near the trachea, attributed to the IM injections of ceftiofur.

The horse was sedated for upper airway endoscopy using xylazine (Rompun; Bayer Animal Health, Mississauga, Ontario), 0.3 mg/kg body weight (BW), IV, and butorphanol (Torbugesic; Mérial Canada, Baie d’Urfé, Québec), 0.01 mg/kg BW, IV. Endoscopy showed occlusion of the left nasomaxillary opening and mucopurulent discharge with hemorrhagic mucous membranes. The region’s normal anatomy was distorted, including the left dorsal meatus and conchae. The right side of the nasomaxillary opening was within normal limits as well as both guttural pouches, larynx, epiglottis, and dorsal pharynx.

Radiographs of the skull were taken (Figure 1). The left lateral view showed fluid lines in the rostral and caudal maxillary sinus and the dorsochoncal and frontoconchal sinuses, along with a mass of soft tissue with rounded margins in what was assumed to be the left frontoconchal and central maxillary sinuses. The nasal septum was deviated to the right in the ventral-dorsal view; an area of soft tissue or fluid opacity was observed on the left. The coronal view showed boney deformities in the left frontal sinus and a soft tissue mass in the left caudal maxillary sinus. The tooth roots were within normal limits. Based on the initial examination a differential list included neoplasia, paranasal sinus cyst, or an ethmoid hematoma. The owner elected a sinus lavage and surgery to explore the sinus to determine the cause of the mass. The horse was admitted to hospital for surgery.

Figure 1.

Radiographs of the head, showing the sinonasal tumor. A, B — left lateral view shows the mass (arrow) in the left rostral and caudal maxillary sinus, frontoconchal sinus, and the dorsoconchal and ventroconchal sinuses. C, D — Ventral-dorsal view shows the deviation of the nasal septum (arrow), to the right; there is a possibility of the mass extending into the right maxillary sinus (arrowhead). E, F — Coronal view shows that the right frontal sinus is unaffected (arrowhead), there are boney deformities in the left frontal sinus (large arrow). In the left maxillary sinus there is a soft tissue mass (thin arrow).

A standing sedated exploratory surgery was attempted, but the mare became fractious. It was decided that general anesthesia would be safer and less stressful for the horse and surgical team. The horse was in the hospital for 8 d before surgery under general anesthesia. During this time the horse was given a basic examination and treated with flunixin meglumine (Banamine; Intervet Canada, Kirkland, Quebec), 1 mg/kg BW, IV, and trimethoprim and sulfadiazine (TMS) (Tribrissen; Intervet Canada), 3.2 mg/kg BW trimethoprim and 16 mg/kg BW sulfadiazine, IV, q24h. The mare’s heart and respiration rates remained within normal limits for the first 5 d of hospitalization. At 8 am on day 5 the mare had copious white, frothy nasal discharge from the right nostril and increased swelling of the head and neck. The following day her heart rate was elevated at 60 beats/min (bpm), swelling was still present, ventral edema was noted, and she was having difficulty eating and drinking. The morning of surgery the mare’ s heart rate was 48 bpm and her respiration rate was 20 breaths/min. She was still having difficulty eating and there was some nasal discharge.

A frontoconchal sinusotomy flap procedure was performed. The horse was anesthetized with romifidine hydrochloride (Sedivet; Boehringer Ingelheim, Burlington, Ontario), 0.05 mg/kg BW, IV, butorphanol (Torbugesic; Mérial Canada), 0.02 mg/kg BW, IV, diazepam (Diazepam; Sandoz, Boucherville, Quebec), 0.04 mg/kg, IV, ketamine (Narketan; Vétoquinol, Lavaltrie, Québec), 2.4 mg/kg BW, IV, and guaifenesin (Trutina Pharmacy, Ancaster, Ontario) 5% in lactated ringers solution (Baxter, Mississauga, Ontario) IV and maintained on isoflurane inhalation anesthesia. The horse was placed in right lateral recumbency and then the forehead over the left maxillary and frontal sinuses was clipped and aseptically prepared. The horse was draped to expose the left frontoconchal sinus.

The rostral incision was 4 cm long and perpendicular to the midline at the level of the infraorbital foramen. The lateral incision was made along the axial aspect of the facial crest and the caudal incision extended from the axial to medial canthus to the midline. This created a 3-sided box with midline uninterrupted. The skin was then reflected 2 cm from the edges of the incisions, as was the periosteum. To access the left frontoconchal sinus, an oscillating saw was used to create a frontoconchal sinus bone flap. The flap was elevated using blunt dissection and force to hinge the flap on the axial portion of the flap. An irregular cartilaginous, friable mass was discovered in the left frontal conchal sinus. The mass extended into the left rostral and caudal maxillary, ventrochonchal and dorsochoncal sinuses, and invaded the nasopharynx ventrally. A lavage with 500 mL lactated Ringer’s solution impregnated with 10 million IU of sodium penicillin was carried out and the mass was resected to the point of invasion into the nasopharynx but could not be resected further. The owner opted to have the mare euthanized during surgery.

A necropsy was not performed. Samples of the mass were sent to Prairie Diagnostic Services for histology, cytology, and culture. The mass was a malignant anaplastic sarcoma. The neoplasia was composed of interlacing and irregularly arranged polygonal to spindle-shaped cells with oval to slender nuclei. The cells were highly pleomorphic with marked anisocytosis and anisokaryosis. Mitosis was marked, and multinucleated neoplastic cells were observed.

Bacterial culture from a swab of the sinus mass revealed the presence of Escherichia coli as the predominant microbe. Staphylococcus and Streptococcus species were also identified. The E. coli was multi-drug resistant, susceptible to amikacin and enrofloxacin, intermediately resistant to gentamicin, and resistant to all other antimicrobials tested.

Discussion

Anaplastic sarcomas of the sinonasal region are rare in equids and other species (1–3,5,7). In horses only about 1% of all head and neck neoplasms are sarcomas (5). This neoplasm has clinical signs that are similar to those caused by neoplastic and non-neoplastic tumors, making definitive diagnosis difficult. Sinonasal tumors are most often diagnosed in the late stages of disease, once the tumor has infiltrated surrounding tissues, leading to clinical signs (2,5,6,8–10). As reported by Dixon et al (11), even after clinical signs are present 75% of patients with sinonasal tumors are initially treated with antibiotics. Nasal and ocular discharge and facial deformities are common clinical signs of sinonasal tumors (1,3,5), as are mastication problems (6). These clinical signs, however, are also all associated with traumatic or infectious lesions which are more common than neoplasia (6,8).

In the present case the horse had an infection with multi-drug resistant E. coli, Streptococcus spp., and Staphylococcus spp. The referring veterinarian initially treated the horse with ceftiofur and penicillin, which were ineffective. Considering the resistance reported, these antimicrobials would not have been effective in treating the E. coli infection. The bacterial infection was most likely secondary to the anaplastic sarcoma and had treatment of this secondary infection been successful it would not have resolved the clinical signs attributed to the growing neoplasm.

The neoplasm was present in the ventrochonchal, dorsochoncal, frontoconchal, and left caudal and rostral maxillary sinuses and extended into the nasopharynx. Sinonasal tumors most commonly originate in the caudal maxillary sinus (1); this is also seen in humans with sinonasal sarcomas (5). In the present case the mass most likely developed in the caudal maxillary sinus or the ventrochonchal sinus. From either location the mass would have been able to expand into all the affected structures. During surgery involvement of the sphenopalatine sinus was not detected, but this sinus could not be fully assessed. The mass did not appear to cross the nasal septum into the right side of the head, but this could not be confirmed.

Radiographs and endoscopy were used to identify the mass in the sinuses; however, the definitive diagnosis was reached following surgery, histopathology, and cytology. Another option for diagnosis was using the endoscope to biopsy the mass for pathology before surgery. This would have provided the definitive diagnosis of an anaplastic sarcoma and secondary bacterial infection. Had this approach been taken initially, it is likely that surgery would have still been performed to try to excise the sarcoma. Radiographs are currently the most common form of imaging used to diagnosis sinonasal tumors; however, radiographs do not provide as much information on location and extent of the lesion as computed tomography (CT) (6,8). The use of CT can improve surgical treatment of sinonasal tumors as better surgical plans can be devised (6,8) to obtain good excisional margins (2). However, good margins are difficult to obtain unless the neoplasm is caught very early on (2). In advanced cases, like this one in which the sarcoma spread extensively, surgical treatment yields poor outcomes (6,8,9). Computed tomography can be used to diagnose these more extensive lesions, such as cribriform plate erosion, invasion of the cranium, and aggressive osteolysis, before surgery or other forms of treatment (8). Cissell et al (8) also reported that radiographs do not allow for assessment of the retrobulbar region, sphenopalatine sinus, or intracranial involvement, whereas CT does. Had CT been done on this mare the outcome, euthanasia, would likely be the same as removing the sarcoma would have left the nasopharynx communicating with the sinuses.

In humans it is more common to use radiotherapy rather than surgery as treatment for sinonasal tumors (2). Combinations of surgery, radiation, and chemotherapy had the most success in reducing the rate of recurrence and increasing survival time in humans (5,9). In dogs, radiation has been found to be more effective than surgical excision, whereas surgical excision following radiotherapy yields similar survival times compared to using only radiotherapy to treat sinonasal neoplasia (10); there is evidence that this holds true for horses (9). Radiotherapy is not a prevalent treatment in horses, but there is a growing number of facilities offering radiotherapy (2). It is likely that radiotherapy would be more successful than surgical excision in treating sinonasal tumors in horses (2,10). However, had the sarcoma been treated with radiotherapy and/or complete surgical excision or any other multimodal form of treatment, a fistula would have been made connecting the ventral conchal sinus to the nasopharynx, allowing for passage of food and other ingesta into the sinuses which could then pass into the airways. Euthanasia, therefore, was the only viable option at this stage of the disease.

The present case is similar to the one other report of equine sinonasal anaplastic sarcoma (3). Clinical signs included facial swelling, unilateral nasal and ocular discharge, exophthalmos, blindness, lateral headshaking, facial pruritis, and self mutilation of the face (3). Endoscopy showed a distention of the right maxillary sinus and the mass was identified in the caudal maxillary sinus. Surgery was preformed to excise the mass, which extended from the caudal maxillary, ventrochonchal, and sphenopalatine sinuses. The horse was euthanized a few days after surgery due to increased neurologic signs. At necropsy, sclerosis and necrosis of the sinus walls, and loss of the bone separating the optic and trigeminal nerves at the optic chiasm were discovered. Histopathology showed plump spindle cells with pale ovoid nuclei such that the mass was deemed an anaplastic sarcoma. In the present case there were no neurologic signs, and the sarcoma did not infiltrate the optic chiasm or any other cranial nerves.

In the one other reported case of anaplastic sarcoma in the sinonasal region, the mare also had a secondary infection with E. coli that had a high level of antibiotic resistance. Both cases highlight the difficulty in treating sarcomas of the sinonasal region in horses.