Extraskeletal osteosarcoma is defined as a malignant osseous neoplasm arising from soft tissue without attachment to skeletal bones. This neoplasm is rare compared with bone osteosarcoma, accounting for 1-2% of all soft tissue sarcomas [5
], and has a calculated annual incidence of 2 to 3 per million population [5
]. Diagnosis rests on three criteria: (1) the presence of a uniform morphological pattern of sarcomatous tissues that excludes the possibility of mixed malignant mesenchymal tumor, (2) production by sarcomatous tissues of malignant osteoid or bone (or both), and (3) ready exclusion of an osseous origin [6
]. Extraskeletal osteosarcoma occurs in older adults compared with skeletal osteosarcoma (median ages of 55 and 20 years old, respectively) [5
] and may have an intramuscular or a superficial location, with the thigh being the most common site (42.3%–52%) [5
], followed by the upper extremities (11.5%) [7
], the retroperitoneum (11.5%) [7
], and the buttocks (7.7%) [7
]. The duration of the symptoms (enlargement of soft tissue mass, pain) varies from several weeks to several years [5
]. The pathogenesis of the tumor is unclear, but radiation-induced extraskeletal osteosarcoma [5
], a history of preceding trauma at the tumor site [5
], and malignant transformation of myositis ossificans to extraskeletal osteosarcoma [7
] have been proposed.
Extraskeletal osteosarcoma is generally a highly aggressive neoplasm with a grave prognosis, and its histology is basically high-grade, similar to most skeletal osteosarcomas. Most patients die from metastatic disease within 2 to 3 years of the initial diagnosis [5
], with a reported local recurrence rate of 45%–50% and distant metastasis in over 60% of cases [7
]. Metastasis within two years after surgery has been found in 80% of the cases, with a five-year survival rate of 13% to 37% [9
]. Bane et al. concluded that tumor size (<5 versus ≥5
cm) is the major predictor of survival [7
It is not always easy to distinguish extraskeletal osteosarcoma from other benign or malignant bone- and cartilage-forming soft tissue lesions [5
]. Differential diagnosis requires consideration of various soft tissue osteogenic lesions [2
], including myositis ossificans, heterotopic and metaplastic ossification, pseudosarcomatous proliferative lesions, dermatomyositis with ossification, ossifying fibromyxoid tumor of soft tissue, synovial sarcoma with calcification, and malignant fibrous histiocytoma with osteoid production. Among malignant tumors, metaplastic bone is often observed in synovial sarcoma, epithelioid sarcoma, malignant fibrous histiocytoma, liposarcoma, malignant melanoma, and other mesenchymal or epithelial neoplasms [5
]. The main histological differential diagnoses are soft tissue chondroma, chondrosarcoma in soft tissue, and myositis ossificans [3
]. Pathological findings of a “reverse zoning phenomenon” (central deposition of osteoid material and atypical spindle cell proliferation at the periphery) [5
] is especially common in sarcoma, while a “zoning phenomenon” is a characteristic of myositis ossificans [3
Treatment for extraskeletal osteosarcoma is usually restricted to local intervention, including surgery alone or a combination of surgery and radiation therapy. Systemic therapy including adjuvant chemotherapy has not been established. Patel et al. [13
] summarized the efficiency of neo- and adjuvant chemotherapy consisting of doxorubicin, cisplatin, ifosfamide, methotrexate, and etoposide in 12 cases, of which only 3 showed a minor response and 9 showed no change or progression. Thus, classical, high-grade extraskeletal osteosarcoma is a rare and very aggressive tumor with a poor prognosis.
Well-differentiated (low-grade) extraskeletal osteosarcoma is extremely rare. This tumor was first described in 1953 by Umiker [14
] and appears to represent a low-grade variant of osteosarcoma with better biological behavior than classical extraskeletal osteosarcoma [4
]. A PubMed search found only 6 cases of well-differentiated extraskeletal osteosarcoma in the English literature. Including our case, the clinical features of the 7 reported cases of this tumor are summarized in . The patients were 2 males (28.6%) and 5 females (71.4%), and ranged in age from 32 to 74 years old (mean age 49.1 years old, median age 53 years old). This suggests a tendency of more frequent occurrence in females, with a similar onset age to classical extraskeletal osteosarcoma (median age 53 versus 55 years old). Three cases (cases 1, 6, and the present case) recurred as high-grade malignancy. All cases had a poor prognosis, with widespread metastasis after the initial surgery or death. To our knowledge, our case is the first example of a well-differentiated extraskeletal osteosarcoma arising from the retroperitoneum that recurred as anaplastic sarcoma.
Summary of reported cases with well-differentiated extraskeletal osteosarcomas.
Well-differentiated extraskeletal sarcoma may have a better prognosis than classical extraskeletal sarcoma, but some cases may recur as a high-grade malignancy with rapid progression leading to death. In our case, regular Follow-up was performed only with a plain abdominal CT scan at 6-month intervals. Based on our experience, we recommend closer follow-up using a chest-abdominal CT scan, abdominal magnetic resonance imaging (MRI), or ultrasound enhanced with a contrast agent.
Our case suggests that careful observation for the recurrence of the tumor is necessary if the pathological diagnosis is well-differentiated extraskeletal osteosarcoma.