Extraskeletal Osteosarcoma Induced by a Foreign Body Granuloma
An 8 yr old spayed female Italian greyhound was presented with a mass in the cranial abdomen. Preliminary evaluation of the dog revealed a large, cavitary, irregularly shaped mass with no definitive association with any abdominal organs. During an exploratory celiotomy, a 16 cm × 12 cm × 6 cm mass was removed. On subsequent histopathology, extraskeletal osteosarcoma induced by a foreign body granuloma was diagnosed. The foreign body granuloma, based on histopathological findings, was suspected to be secondary to a retained surgical sponge from her routine ovariohysterectomy performed 7 yr prior to presentation. Animals with granulomas induced by foreign bodies can remain asymptomatic for years; however, those granulomas can progress to extraskeletal osteosarcomas, which carry a poor prognosis.
Introduction
Extraskeletal osteosarcomas (OSAs) are malignant soft-tissue mesenchymal neoplasms that are not associated with either a periosteal or bony matrix.1–5 Extraskeletal OSAs are rare in the dog if mammary involvement is excluded.1,3,4,6–12 They are aggressive neoplasms that readily metastasize. Extraskeletal OSAs have been reported secondary to retained surgical sponges in both humans and dogs.9–12 Retained surgical sponges may remain asymptomatic for years; however, there is a risk that malignant transformation can occur.10 Previous reported canine cases of extraskeletal OSAs induced by retained surgical sponges had relatively short survival times (2–3 mo) postoperatively.9–11 This report describes a case of extraskeletal OSA induced by a foreign body granuloma with an extensive disease-free interval.
Case Report
An 8 yr old spayed female Italian greyhound weighing 6.4 kg was referred to the Internal Medicine Service at Iowa State University with a 10 day history of a painful abdomen, prior fever, lethargy, and for further evaluation of a mass in the cranial abdomen. Initially, the patient was examined by the referring veterinarian for pain in her abdomen and was subsequently prescribed tramadol HCla [3.6 mg/kg per os (PO) q 8 hr]. Two days later, the patient was re-presented to her referring veterinarian with signs of lethargy, pyrexia (body temperature was 40°C), and anorexia. No physical examination abnormalities were documented in the medical record. A complete blood cell count (CBC), serum biochemical analysis, and free-catch urinalysis were performed by the referring veterinarian. Results revealed a moderate leukocytosis (34.61 × 109/L; reference range, 5.5–16.9 × 109/L), neutrophilia (30.49 × 109/L; reference range, 2–12 × 109/L), proteinuria (4+; reference range, 1+ to 4+), and hematuria (3+; reference range, 1+ to 4+). The patient was prescribed amoxicillin trihydrate/clavulanate potassiumb (18 mg/kg PO q 12 hr) for a presumed urinary tract infection. According to the owners, the patient did well for a few days but then became increasingly lethargic and inappetent 1 wk after starting the antibiotics. The patient re-presented to the referring veterinarian. On physical examination, the patient's cranial abdomen was firm and full on abdominal palpation. Subsequent abdominal radiographs revealed a large round mass in the cranial abdomen.
On presentation to Iowa State University, the patient was bright, alert, and responsive. Her respiratory rate, heart rate, and body temperature were within normal limits. On physical examination, a large cranial abdominal mass was noted with no peripheral lymphadenopathy. Blood was obtained for a CBC, serum biochemical analysis, and clotting times. Blood pressure measurement and urinalysis were also performed. Results of the CBC revealed a moderate leukocytosis (29.21 × 109/L; reference range, 6–17 × 109/L), neutrophilia (25.7 × 109/L; reference range, 3–11.4 × 109/L), mild anemia (36%; reference range, 37–55%), and monocytosis (1.46 × 109/L; reference range, 0.15–1.35 × 109/L). Serum biochemical analysis identified hypokalemia (3.4 mEq/L; reference range, 3.9–5.3 mEq/L), hypocalcemia (9.3 mg/dL; reference range, 9.7–11.3 mg/dL), and hypophosphatemia (1.9 mg/dL; reference range, 3.2–6 mg/dL). Initially, her blood pressure was 215 mm Hg, but several hours later had decreased to 140 mm Hg (by Doppler). The urinalysis revealed no abnormalities, and the prothrombin and partial prothrombin times were normal.
The abdominal radiographs obtained by the referring veterinarian the day prior to referral were reviewed by the Iowa State University Radiology Department and the presence of a large soft-tissue midabdominal mass was confirmed. Differential diagnoses for the abdominal mass included a mass of splenic, hepatic, or mesenteric origin. Three-view thoracic radiographs were obtained, and no evidence of metastatic disease was seen. Abdominal ultrasonography was performed to further differentiate the organ of origin of the mass. The liver and spleen appeared normal in size, shape, and echotexture. The gastrointestinal tract had a normal appearance and thickness. The abdominal mass was visible from the caudal margin of the liver border to the urinary bladder. The mass appeared large, cavitary, and irregularly shaped with no definitive association with any organs identified. The tissues immediately surrounding the mass were hyperechoic. There was neither abdominal effusion present nor any abnormal lymph nodes identified.
The top differential diagnoses for the cause and source of the abdominal mass included a neoplastic process; granuloma; or an abscess from the mesentery, omentum, or intestine. An abdominal computerized tomographic scan was offered for further assessment of the origin of the mass but declined by the owners. Ultrasound-guided fine-needle aspirates of the mass were also offered but declined by the owners.
The owners did consent to an exploratory celiotomy. The patient was monitored and maintained on IV fluids in the intensive care unit overnight prior to surgery. The following morning, ionized Ca was measured and found to be normal (1.3 mmol/L; reference range, 1.25–1.45 mmol/L). The dog was premedicated and anesthetized with no complications. During the exploratory celiotomy, a large 16 cm × 12 cm × 6 cm mass was removed from the abdomen (Figure 1). The mass did not appear to originate from any abdominal organ but did have adhesions to the pancreas, cecum, jejeunum, and stomach. Following removal of the mass, the abdomen was further explored and examined. No other gross abnormalities were seen. The patient recovered uneventfully after surgery. She remained on maintenance IV fluid administration and a fentanylc constant rate infusion (2 µg/kg/hr) for 24 hr. The next morning, the patient's medications were changed to oral tramadold (1.8 mg/kg PO q 8–12 hr) and carprofene (1.8 mg/kg PO q 12 hr) because she was eating well and appeared comfortable. Those medications were prescribed and sent home with the owner for 1 wk postsurgically. She remained in the intensive care under observation until her owners could pick her up 2 days postoperatively with instructions to limit activity to leash walks only for 2 wk and to ice the incision for 2 days (2–3 times/day for 10–15 min). The patient was also discharged with an Elizabethan collar to prevent licking of the incision.
Citation: Journal of the American Animal Hospital Association 51, 5; 10.5326/JAAHA-MS-6224
Sections of the abdominal mass were submitted for fungal and bacterial culture as well as histopathology. The bacterial and fungal cultures were negative. Histopathology revealed a mass that was composed of spindle to pyriform to stellate cells aligned in sheets of intersecting bundles. The neoplastic cells were aligned along trabecula of osteoid. The neoplastic cells had a central oval to elongate nucleus, 1–2 nucleoli, a moderate amount of eosinophilic cytoplasm and discernible cell borders. Anisocytosis and anisokaryosis were moderate to marked, and the mitotic index was high (40 mitotic figures/10 fields at a magnification of 400×). There were large foci of necrosis associated with pockets of purulent exudate throughout the mass. In addition, there was a substantial amount of uniform refractile fibers of acellular foreign material, which were about 15 microns in diameter, surrounded by granulomatous inflammation and scattered throughout the neoplasm, between neoplastic cells (Figure 2). Neoplastic tissue extended to the surgical margins, indicating incomplete removal of the mass. The diagnosis was an extraskeletal OSA. The mass was associated with granulomatous peritonitis containing abundant foreign material. The foreign material was suspected to be either a cloth or surgical sponge.
Citation: Journal of the American Animal Hospital Association 51, 5; 10.5326/JAAHA-MS-6224
The patient was presented for a consultation with the Oncology Department 2 wk following surgical discharge from the hospital to discuss prognosis and chemotherapeutic options. Given the paucity of literature on chemotherapeutic treatment of extraskeletal OSA, several options were discussed with the owners, including a course of IV carboplatin, metronomic chemotherapy consisting of piroxicam and cyclophosphamide, treatment with palladia, or no adjunct therapy. A guarded prognosis was given for all treatments because so little was known about chemotherapeutic response in patients with extraskeletal OSA. The owners elected palliative chemotherapy with piroxicamf (0.3 mg/kg PO q 24 hr) with instructions to return in 2 mo for re-evaluation and repeat thoracic radiographs. On follow-up evaluation with Iowa State University 4 mo postoperatively, there was no evidence of metastatic disease on either abdominal ultrasound or repeat thoracic radiographs. The patient was prescribed additional piroxicam therapy. Nine months postoperatively, the patient returned to Iowa State University for re-evaluation. The CBC and serum biochemical analysis revealed no abnormalities. Repeat thoracic radiographs and an abdominal ultrasound were recommended but declined at that time. One year postoperatively, the patient was reportedly doing well by the referring veterinarian and was still on daily piroxicam. The owners declined further bloodwork and radiographs, although they were offered by the referring veterinarian.
Discussion
In this report, a middle-aged dog underwent an exploratory celiotomy to remove a midabdominal mass of unknown etiology. Histopathology of the mass revealed an extraskeletal OSA suspected to be induced by a retained surgical sponge. The patient neither had any other abdominal surgery aside from a reportedly routine ovariohysterectomy at the age of 6 mo nor any history of foreign body ingestion.
OSAs are malignant mesenchymal neoplasms that produce osteoid.1–4 OSAs are the most common primary bone tumor in dogs and account for at least 80–85% of all bony tumors in dogs.2–4 They have been described in dogs, cats, rats, humans, and more rarely in horses, cattle and sheep.2,4 OSAs can be classified based on the type and amount of matrix and characteristics of the cells, including osteoblastic, chondroblastic, fibroblastic, poorly differentiated, and telangectatic.3,4 Typically, OSA is found in either the appendicular or axial skeleton.5
In dogs with OSA, the extraskeletal location is the least common region for this neoplasm to occur.1,3,4,6,7 Extraskeletal OSAs in dogs have been described in the urogenital tract, liver, spleen, mammary gland, skin, and gastrointestinal tract.1,6,7 It is difficult to differentiate extra-skeletal OSAs from other tumors or granulomas on routine imaging, especially if there is no calcification present.7–9
Extraskeletal OSAs are malignant soft-tissue mesenchymal neoplasms that produce either osteoid or cartilaginous matrix in soft tissues or visceral organs with no periosteal or bony involvement.1,6,8 They are rare in the dog if the mammary glands are excluded.1,6,7,10 In humans, extraskeletal OSAs occur infrequently in patients under the age of 30 years, with a slight male prevalence.8 In dogs, the diagnosis for extraskeletal OSA is dependent on (1) uniform morphological pattern of sarcomatous tissue; (2) production of malignant osteoid or bone; (3) high mitotic index; and (4) exclusion of osseous origin.7 To the authors' knowledge, there have only been three other known case reports of extraskeletal OSAs induced by a foreign body granuloma in the literature in the last 20 yr.9–11
Focal granulomatous inflammation, associated with either cloth or fibrous material derived from cotton (also called a gossypiboma or textiloma), which has been described in human and veterinary patients, many of which are the result of surgical sponges.9,10 The estimate of human cases of retained surgical sponges and instruments in the United States is approximately 1500 annually.10 Veterinary medical cases do not have a definitive number due to lack of reporting.10 It is theorized that gossypibomas can induce OSAs via chronic inflammation, but that is extremely rare, usually only a granuloma forms.10,11 Malignant transformation to OSA in long bones has been reported with metallic implants secondary to fracture fixation.11 There have even been published reports of foreign material, such as plastics, inducing neoplasms in rats when implanted subcutaneously.11 At this time, it is unknown what stimulates malignant transformation over time. Animals can be asymptomatic for years before showing clinical signs such as fever, inappetence, lethargy, and discomfort, as was likely the case in the dog described in this report.9–12
Extraskeletal OSAs are very aggressive and metastasize readily via the hematogenous route.3,4 Dogs with extraskeletal OSAs have a worse prognosis for survival and metastasis than either appendicular or axial OSA.1,6,7 Extraskeletal OSAs can locally infiltrate adjoining tissues near the tumor. They can also metastasize distally, most notably to the lungs.1,11 Reported survival times average 1–3 mo from the time of diagnosis.6,7 A retrospective study of extraskeletal OSAs in dogs by Langenbach et al. (1998) revealed median survival time of 25 days for soft-tissue OSAs.6 In another small case series by Kuntz et al. (1998), 5 out of 14 dogs diagnosed with extraskeletal OSAs, had surgery, and were treated with varying chemotherapy protocols had a median survival of 146 days.7 For the dogs that were not euthanized after diagnosis and received no chemotherapy, the median survival was 33 days.7 Treatment of extraskeletal OSAs, especially extraskeletal OSAs associated with gossypibomas, have not been well evaluated in the veterinary literature.6,7 There are only three reported cases of gossypiboma-induced extraskeletal OSA: two were in limbs where former cranial cruciate repair was performed and one was associated with a retained surgical sponge from a previous ovariohysterectomy involving the jejunum.10,11 Of those cases, surgical removal of the masses were performed, and chemotherapy was declined.10,11 The median survival time for those three cases was 2.5 mo due to recurrence of disease and metastasis.10,11 Based on the current limited literature, extraskeletal OSA carries a guarded prognosis.
Conclusion
This report describes a patient diagnosed with an extraskeletal OSA, a rare mesenchymal tumor suspected to be induced by a retained surgical sponge, with a prolonged disease-free interval. The study authors suspect that surgical removal followed by daily piroxicam administration contributed to the successful outcome of this patient. Perhaps extraskeletal OSAs induced by gossypibomas exhibit enhanced cyclo-oxygenase expression due to the prolonged inflammation in the body from a foreign substance. The extended use of the nonselective cyclo-oxygenase inhibitor, piroxicam, could be contributing to the extended disease-free interval.
Sarcomatous transformation of a retained surgical sponge can occur years after the initial surgery occurred.10 There are only a few reported veterinary cases of gossypibomas inducing extraskeletal OSAs in the literature.10,11 Traditionally, extraskeletal OSAs have a shorter median survival time than skeletal OSAs; however, this case highlights extended survival after surgical removal of an intra-abdominal OSA with a high mitotic index.1,6,7 It is important to count sponges immediately following surgical procedures and use radiopaque sponges to facilitate a radiologic diagnosis of a gossypiboma. Although animals with gossypibomas can remain asymptomatic for years and are often benign, there is a risk of sarcomatous transformation.
Photograph of the mass (16 cm × 12 cm × 6 cm) removed from the abdomen. Cranial is to the right, caudal to the left, ventral to the top, and dorsal to the bottom. The white arrow area indicates where adhesions to the jejunum were removed.
Neoplastic osteoblasts adjacent to and imbedded within eosinophilic extracellular matrix (osteoid). In addition, there are several cross-sections of refractile foreign fibers within the neoplastic tissue. Hematoxylin and eosin stain, original high magnification, black bar = 20 micrometers. Black arrow indicates the foreign fiber and the white arrow shows an osteoblast embedded in the extracellular matrix.
Contributor Notes
