Chondroblastic osteosarcoma of the middle ear in a guinea pig (Cavia porcellus)

Abstract

A 3-year-old intact female guinea pig (Cavia porcellus) was presented for acute anorexia. Medical and surgical treatments for cystitis and ovarian cysts, respectively, did not prevent continuous weight loss. Computed tomography and histopathological analysis revealed a chondroblastic osteosarcoma of the right middle ear, which has not been reported in this species.

Case description

A 3-year-old intact female guinea pig (Cavia porcellus) was presented to the Exotic Animal Clinic of the University of Montreal with a 1-week history of partial anorexia with decreased urine and fecal output. The owner did not report any recent changes in the guinea pig’s environment, or any stressful event. The diet consisted of commercial guinea pig pellets and timothy hay ad libitum. Fresh fruits, vegetables, and herbs were offered daily and a water-soluble vitamin C supplement was added to the drinking water once weekly.

On physical examination, the guinea pig weighed 920 g with a body condition score of 3/5. Subtle enophthalmos of the right eye, without any other ocular abnormalities, was noticed. Oral examination revealed an abnormal occlusal plane of the last mandibular molars (M3) bilaterally without dental spicules. The caudal abdominal region was distended and painful on palpation. It was not possible to distinguish abdominal structures due to abdominal wall contraction from discomfort. The remainder of the physical examination was unremarkable and the guinea pig urinated while being palpated.

Initial differential diagnosis for gastrointestinal stasis and painful caudal abdomen included disorders of the urinary (urolithiasis, cystitis) or genital (ovarian cysts, neoplasia) tracts or less likely disorders of the digestive tract (fecal impaction). Initial diagnostic plan included urinalysis and abdominal ultrasound. Due to financial constraints, the owner elected to donate the animal to the Small Mammal Shelter of the University of Montreal.

Partial urinalysis was performed on a urine sample collected following micturition. Urine dipstick was positive for proteins (0.3 g/L), glucose (2.8 mmol/L), and bilirubin (1+). On examination of the sediment, 10 to 25 leucocytes were observed per high-power field (hpf ), which was suggestive of cystitis.

The initial treatment plan consisted of subcutaneous fluids [100 mL/kg body weight (BW) per day], Lactate Ringer’s Solution (Rafter 8 Products, Calgary, Alberta) (1), meloxicam (Metacam; Apotex, Toronto, Ontario), 0.5 mg/kg BW, PO, q12h, trimethoprim-sulfamethoxazole (Novo-Trimel; Teva Canada, Toronto, Ontario), 30 mg/kg BW, PO, q12h and buprenorphine (Vetergesic; Alstoe Animal Health, Whitby, Ontario), 0.03 mg/kg BW, SC, q6h (2). The guinea pig was force-fed with Critical care powder (Critical care; Oxbow Animal Health, Murdock, USA), 60 mL/kg BW per day, q6h (1). As part of the routine admission protocol to the Shelter, a treatment for parasites (Selamectine, Revolution; Pfizer, Animal Health, Kirkland, Quebec), 16 mg/kg BW, was administered topically once.

On day 1, an abdominal ultrasound was conducted and showed changes consistent with mild cystitis. Bladder sludge and 1 bladder stone ventrally measuring 1.1 mm diameter were confirmed. Ultrasound also revealed the presence of ovarian cysts bilaterally and the appearance of the uterus was compatible with cystic hyperplasia. Mild gallbladder distension without concurrent signs of obstruction was also noted. Bacterial culture of the urine was not performed since antibiotic therapy had been initiated.

After 24 h of hospitalization, the guinea pig produced feces in small amounts and urinated normally. The guinea pig showed persistent dysorexia during the first week of medical management, although mild improvement in food consumption was observed. On day 7, the guinea pig weighed 975 g and assisted feeding was progressively decreased. The right enophthalmos initially observed appeared to have resolved.

On day 8, a recheck analysis on a urine sample collected by natural urination was within reference limits. From days 8 to 14, progressive weight loss was observed daily with a body weight decreasing to approximately 800 g. The patient remained alert, showed some interest in fresh food items but was not eating sufficiently on her own so assisted-feedings were adjusted.

On day 15 following initial presentation, a recheck ultrasound was performed without sedation. The mineralized calculus within the bladder was adhered to the ventral wall causing a mild focal deformation of the wall at the adhesion site. Other previous findings were unchanged. Although the guinea pig was alert and had an improved appetite that day, abdominal palpation was still painful. In order to address abdominal discomfort related to the ovarian cysts and fulfill the Shelter’s mission, an ovariectomy was scheduled. Prazosin (Teva-Prazosin; Teva), 0.5 mg/kg BW, PO, q24h, and tramadol (Summit Veterinary Pharmacy, Aurora, Ontario), 4 mg/kg BW, PO, q12h, were added to the previous treatments to reduce potential urethral hyperreflexia and improve analgesia with a multimodal approach, respectively (2).

On day 16, the guinea pig was in good general condition with a stable body weight allowing her to undergo surgery. Bilateral ovariectomy was conducted using a lateral flank approach (3). Following a 2-hour fasting period, (4,5) the guinea pig was sedated with a combination of midazolam (Midazolam; Sandoz, Boucherville, Quebec), 0.5 mg/kg BW, IM, buprenorphine (Vetergesic; Alstoe Animal Health), 0.05 mg/kg BW, IM, and ketamine (Narketan; Vétoquinol, Lavaltrie, Quebec), 5 mg/kg BW, IM (2). Anesthesia was induced and maintained with isoflurane (Isoflurane, USP; Fresenius Kabi Animal Health, Toronto, Ontario), 1% to 3% in oxygen delivered by facemask (6) using a Bain anesthetic system and a 0.5-L reservoir bag (7). Oxygen flow rate was maintained at 2 L/min. Anesthesia was monitored with the aid of pulse oximeter, Doppler, and capnometer. Manual intermittent positive pressure ventilation was administered as needed. Temperature was maintained using a water-circulating pad and infrared light. The guinea pig was positioned in right lateral recumbency. The left lateral side of the abdomen was routinely prepared for surgery and draped with a transparent adhesive surgical drape (Veterinary Transparent Surgical Drape; Veterinary Specialty Products, Boca Raton, Florida, USA). The landmarks for the cutaneous incision were the edge of the last ribs cranially and the line of the lateral vertebral processes dorsally, as previously described (3). Both cystic ovaries were excised through the left lateral incision (3). Fine-needle aspiration of cysts before exteriorization of each ovary was not deemed necessary. Hemostasis was verified and the incision was closed routinely. Flumazenil (Flumazenil Injection USP; Pharmaceutical Partners of Canada, Toronto, Ontario), 0.01 mg/kg BW (3), was administered intramuscularly. Recovery from anesthesia was unremarkable. The guinea pig was alert, had a good appetite, and defecated and urinated normally the evening following surgery.

On day 19, a seromucous epiphora with mild ventral corneal opacification of the right eye was newly observed in addition to a mild enophthalmos. Tobramycin (Tobrex; Sandoz) was initiated every 8 to 12 h pending complete evaluation by an ophthalmologist. A corneal ulcer characterized by corneal degeneration associated with detachment of the ventral corneal epithelium was diagnosed in the right eye. Immature bilateral cataracts characterized by partial opacification of the periphery of the lens was also present. Ophthalmic treatment plan was changed to serum, artificial tears gel, and bacitracin-neomycin-polymyxin B (Vétoquinol) application every 6 h in the right eye.

At this time, 3 d after the ovariectomy, the guinea pig was clinically comfortable and there was no more abdominal pain. Although the animal was alert, had good appetite, and produced feces and urine normally, weight loss continued despite assisted feedings. On day 22, the guinea pig weighed 723 g.

The hypotheses for chronic weight loss in a guinea pig with an adequate appetite may include hyperthyroidism or neoplasia. No mass was palpable in the cervical region. In order to investigate these diseases, thyroxine (T4) hormone level was determined and a whole body tomodensitometric examination was performed.

The results of these tests indicated that the serum concentration of thyroxine hormone was low [6.2 nmol/L; reference interval (RI): 14.2 to 66.9 nmol/L], thus excluding hyperthyroidism (8).

Whole-body computed tomographic (CT) scan was performed using a third-generation, 16-slice helical CT scanner (HiSpeed ZXi; General Electric, Mississauga, Ontario). The following protocol was used to image the guinea pig: exposure 120 kVp and 250 mA, slice thickness 1.25 mm, slice interval 0.625 mm, pitch 0.938:1, display field-of-view (DFOV) 12 cm and including the entire reference phantom, speed 9.37 mm/rotation, number of rotations 1.0/s, matrix 512*512″. Images were reformatted with a detail algorithm in sagittal and dorsal planes and 3D. The guinea pig was fasted for 1 h before induction and was maintained with isoflurane delivered by facemask for the procedure. The CT imaging revealed a well-defined mineralized mass associated with the right tympanic bulla (Figure 1). This mass lesion extended from the tympanic bulla to the caudal aspect of the nasopharynx and displaced the soft tissues of the nasopharynx to the left. This mass was large (approximately 1.0 × 1.5 × 1.1 cm), well-circumscribed, and isolated. There was no visible soft tissue component with this mass. The right tympanic bulla contained fluid (Figure 1) and the left appeared normal. The external ear canals were unremarkable. There were no other significant findings.

Figure 1.

Axial computed tomography images of the tympanic bullae of the guinea pig. Note the liquid in the right tympanic bulla and the well-defined mineralized mass (arrow) associated with the liquid.

Due to poor prognosis and unsuitability for adoption, the guinea pig was euthanized. Anesthesia was induced with isoflurane delivered by facemask until a surgical plane was reached and an overdose of barbiturate (Euthansol; Merck Animal Health, Kirkland, Quebec) was administered by the intracardiac route.

At necropsy, the animal was in good body condition. Grossly, significant lesions were limited to the right tympanic bulla, which was distorted and enlarged to twice the size of the left bulla (Figure 2). On cut section, it contained a firm white to tan mass, approximatively 2 cm in diameter, with a granular translucent appearance and a gritty texture. The mass was moderately well-demarcated and compressed the adjacent temporal bone and cochlea.

Figure 2.

Skull — ventral view. The right tympanic bulla is enlarged and distorted by a firm mass (arrow).

Samples from all organs/tissues, including both tympanic bullae, were fixed in 10% neutral-buffered formalin; tympanic bullae were decalcified in hydrochloric acid at 37°C for 12 h. Samples were then processed, embedded in paraffin, cut at 5 μm, and stained with hematoxylin, eosin, phloxine, and saffron (HEPS). Histopathologic examination of the right tympanic bullae revealed a proliferation of spindle-shaped to polyhedral cells arranged in bundles. Multifocally, neoplastic cells produced an amorphous pale pink to yellowish matrix (osteoid) (Figure 3A) with formation of immature bone trabeculae (Figure 3B) and mineralization. In some areas, neoplastic cells were surrounded by numerous aggregates of amorphous pale blue matrix that stained bright red with Safranin-O-fast green staining (cartilaginous matrix) (Figure 3 C, D). Neoplastic cells had poorly defined borders and moderate amounts of eosinophilic cytoplasm. Pleomorphism was moderate with presence of a few binucleated cells. Mitotic count was low with up to 1 mitosis in 10 HPF. The mass was diagnosed as an osteosarcoma based on the production of osteoid by neoplastic cells. It was classified as chondroblastic since the production of cartilaginous matrix was a prominent feature of the neoplasm (9). On histopathological analysis no other abnormality was detected in any organ, including the lungs.

Figure 3.

A — Neoplastic cells surrounded by pink amorphous matrix (osteoid) (asterisks). B — Bundles of spindle-shaped neoplastic cells forming irregular and immature bone trabeculae (arrow), surrounded by osteoid matrix (asterisks). C — Polyhedral to spindle-shaped neoplastic cells produced both osteoid matrix (asterisk), and aggregates of cartilaginous matrix (arrow). D — Aggregates of cartilaginous matrix (arrow) stain bright red with Safranine-O-Fast green staining.

Discussion

Data on tumors in guinea pigs are increasing in the literature. Trichofolliculomas are the most common tumors of guinea pigs (10). There are many reports of reproductive tract tumors in the guinea pig, such as leiomyomas and leiomyosarcomas of the uterus, and ovarian adenocarcinomas and adenocarcinomas of the mammary glands (10). Although digestive neoplasms are not common, a few cases have been reported, such as a case of gastric leiomyoma (11) and a case of gastrointestinal stromal tumor (GIST) (12). Tumors of the urinary system are also uncommon, but transitional cell carcinoma of the bladder, renal adenocarcinoma, and renal fibrosarcoma have been described (10). Several others case reports of tumors in guinea pigs have been published, such as a case of thyroid carcinoma (13) among others (14). Although few studies on the prevalence of tumors in guinea pigs have been reported, a recent study (15) described spontaneous tumors in guinea pigs. Of the 20 neoplasias examined, 5 were skin tumors (trichofolliculomas, trichoepitheliomas, malignant pilomatricoma), 5 were tumors of the mammary glands (adenocarcinoma and adenoma), 6 were subcutaneous tumors (lipomas, liposarcoma, ossifying fibroma), 3 were lymphatic leukemias, and 1 was hepatocellular adenoma. No osteosarcomas were observed in this study and guinea pigs’ age ranged from 2 to 7 y (15).

The guinea pig herein had significant abdominal discomfort upon presentation. Abdominal discomfort often results in non-specific signs such as depression, gastrointestinal stasis, anorexia, and secondary weight loss. However, despite efforts to eliminate each cause of pain in this individual with the management of urinary and ovarian disorders diagnosed initially, the persistent weight loss in a 3-year-old individual warranted further investigation. Differential diagnoses for chronic weight loss in a guinea pig include dental diseases, endoparasites, ovarian cysts, renal diseases, neoplasms, and hyperthyroidism (16). Hyperthyroidism is most often reported in guinea pigs 3 y old and older, and generally secondary to thyroid tumors including adenoma and adenocarcinoma. Clinical signs of hyperthyroidism are variable, the most frequent being weight loss despite a normal to increased appetite and hyperactivity. However, low concentrations of thyroxine hormone excluded hyperthyroidism in the guinea pig presented here.

Results of the CT imaging revealed a mineralized mass extending from the tympanic bulla to the caudal aspect of the nasopharynx. The location of this mass caused displacement of the airway and proximal esophagus, which may have contributed to difficulty in swallowing although dysphagia was not observed.

Diseases of the middle and inner ear are common and well-described in rabbits (17); however, they are probably underdiagnosed in guinea pigs. Unlike bacterial otitis, ear neoplasias are uncommon in rodents. Fibropapillomas of the ear canal are occasionally found and aural polyps may occur in the tympanic bullae of guinea pigs (10). Diseases of the ear are often associated with clinical signs including head tilt, ataxia, circling, torticollis, and facial nerve paralysis with possible secondary ulcerative keratitis (10). In the present report, the guinea pig’s right eye exhibited enophthalmos and a corneal ulcer. Considering initial ophthalmologic examination, the enophthalmos may have been associated with radiating pain from the neoplastic process, which responded partially to analgesic therapy until an ulcer developed. The corneal lesions may have occurred secondary to lack of lubrication or trauma peri-ovariectomy or possibly secondary to facial nerve paresis although eyelid closure was complete when evaluated. No signs of vestibular disease were observed. Although poorly documented in the guinea pig literature, surgeries of the external, middle, and inner ear are well-described in rabbits (17). Total ear canal ablation and lateral bulla ostectomy would not have allowed a complete surgical resection of this mass.

To the authors’ knowledge, this is the first report describing a chondroblastic osteosarcoma of the middle ear in a guinea pig (18). Osteosarcomas are aggressive malignant bone tumors, with rapid local invasion and high potential for lung metastasis (19). Osteosarcomas have been well-described in humans (20,21), horses (22), dogs (19,23–26), and cats (27), and represent the most common type of bone tumors in dogs (19). In dogs, osteosarcomas most commonly develop in the appendicular skeleton (19,26), with a predilection for specific sites such as distal radius, proximal humerus, distal femur, and proximal tibia (24,26), but tumors of the axial skeleton are not uncommon, including spine, ribs, skull, cranium, oral, and maxillofacial osteosarcomas (24,26). Case reports of appendicular osteosarcoma have also been published in small mammals: osteosarcoma of the left proximal tibia (28) and of the femur (29) in guinea pigs, and osteosarcoma of the right forelimb in a rabbit (30). Considering that, to the authors’ knowledge, only 2 cases of osteosarcomas have been reported in guinea pigs, osteosarcomas are rarely described in this species. In humans and dogs, oral and maxillofacial osteosarcomas seem to be less aggressive than appendicular osteosarcomas, with slower progression and lower trend to metastasis, although locally aggressive (24). Clinical signs may be insidious (26). The guinea pig of this report showed non-specific signs of pain (dysorexia) and ocular signs related to the location of the mass. No pulmonary metastasis was detected on CT examination and on histology for this individual, although lung metastases have been described in this species (29). The chronic weight loss of this individual could be of 2 origins: a mechanical origin by extension of the mass to the pharynx, which impaired swallowing; and a catabolic origin by tumoral mediators (31). Since the individual was still able to eat, cancer cachexia is the more likely.

Presumptive diagnosis of osteosarcoma is based on clinical signs, imaging studies, and cytological evaluation (19,24), although the gold standard for definitive diagnosis remains histological evaluation (24,26). The recommended treatment of osteosarcomas in dogs includes free-margin surgical resection, radiotherapy, and chemotherapy (19,24,32). Given the local aggressive nature of osteosarcomas, 2 to 3 cm tumor-free surgical margins are recommended (33). While amputation is feasible in the cases of appendicular osteosarcomas, free-margin surgical resection may be more complicated in cases of axial osteosarcomas. Local recurrence is not uncommon in dogs and humans with axial osteosarcoma (24). Prognosis depends on the tumor location, presence of metastasis, surgical margins, clinical signs, and body weight of the patient. Tumor-free surgical margins are reported to be the most important prognostic factor in dogs and humans with maxillofacial osteosarcoma (24).

The present report describes the diagnosis of a chondroblastic osteosarcoma of the right middle ear in a guinea pig. Although no metastasis was present, prognosis was guarded due to the location of the tumor and the inability to perform margin-free surgical resection.