Osteosarcoma Arising from Iliac Bone Lesions of Hereditary Multiple Osteochondromas: A Case Report

Osteochondroma is the most common benign bone tumor, accounting for approximately 20–40% of all benign bone tumors [1]. Osteochondroma includes two phenotypes, solitary and hereditary multiple osteochondromas (HMO). These cartilage-capped bony projections typically arise on the metaphyses of long bones during skeletal development. Though about 85% of osteochondromas present as solitary and nonhereditary lesions, 15% of osteochondromas occur as multiple hereditary lesions [1]. Often asymptomatic, osteochondromas can lead to complications such as pain, fracture, neurovascular compression, and growth disturbance [2]. HMO has a wider symptom spectrum, frequently resulting in more significant physical deformities and functional impairments than solitary osteochondromas [3].

Exostosin (EXT)1 and EXT2-encoding glycosyltransferases are tumor suppressor genes. Osteochondromas are related to genetic abnormalities in EXT1 or EXT2. In particular, germline mutations in EXT1 or EXT2 were found to be associated with HMO. The risk of malignant transformation in osteochondromas occurs in approximately 10% of hereditary lesions. It is also estimated to be less than 1% in solitary osteochondromas and 1–3% in multiple osteochondromas [4]. A sign of malignant transformation is cartilage cap thickness greater than 2 cm, and 94% of the histological types are chondrosarcomas [5]. However, transformation to osteosarcoma is very rare. A rare case of HMO causing osteosarcoma in the ilium is reported along with a review of the literature on malignant tumors forming osteochondromas other than chondrosarcomas.

A 66-year-old woman presented with recurrent right abdominal pain. She had a family history of multiple bony lesions affecting her father, brother, and a niece. Computed tomography (CT) showed a mass protruding into the pelvic cavity, 9 cm × 7 cm × 7 cm, with bone destruction and internal calcification in the right iliac bone (Fig. 1a, c). Other osteochondromas were present on the knees, ilium, both scapulae, and the right fifth rib (Fig. 1e–i). Magnetic resonance imaging showed a mass with T2-low and T2-high aneurysm-like changes (Fig. 1b, d). The cartilage cap was not evident. Because of the rapid growth, a CT-guided biopsy was performed, and the diagnosis was osteosarcoma. There was no evidence of metastasis on whole-body CT. One course of chemotherapy with doxorubicin and ifosfamide was performed, but the patient refused to continue chemotherapy, so wide resection of the tumor was performed. The specimen was 8.5 cm × 6.5 cm × 6.5 cm of bony tissue with elasticity protruding from the bony surface (Fig. 2a). It was easily detached from the peritoneum. The fascia of the iliopsoas muscle was attached to the tumor, and the osteotomy resected 3 cm above the hip joint from the iliac crest and medially beyond the sacroiliac joint, partially including the sacral wing. The distal 1/2 of the sacroiliac joint was preserved (Fig. 2b). The pathological diagnosis of osteosarcoma arising from the osteochondroma was made. The resection site showed that the margins were negative, and postoperative chemotherapy was not performed. Three years after surgery, there was no evidence of recurrence or metastasis, and the patient was able to walk unassisted.

The pathology specimen showed tumor-like cartilage tissue without atypical cells, suggesting osteochondroma (Fig. 3a). The cartilage cap was about 6 mm. Histologically, tumor-like cartilage tissue without dysplastic cells was observed at the margins of the mass, which was considered to be osteochondroma (Fig. 3b, c). Inside the tumor, just below the osteochondroma, there was proliferation of highly pleomorphic dysplastic cells with bone formation, consistent with osteosarcoma (Fig. 3d, e). The resection margins of bone and soft tissues were free of tumor.

Malignant transformation arising in an osteochondroma occurs in 1–3% of cases, especially in HMOs. Overall, 94% of the histologic types are chondrosarcomas, and other types are osteosarcomas, fibrosarcomas, and malignant fibrous histiocytomas [6]. Reports of malignant transformation from osteochondroma to osteosarcoma are very rare, and malignant transformation to osteosarcoma arising in an osteochondroma in the ilium is described in the present report.

There have been 11 cases of osteochondromas developing secondary osteosarcomas since 1966, with 5 cases reported in teenage patients, and the overall average age of onset was 29.5 years, older than that of conventional osteosarcoma [7]. Unlike the development of chondrosarcoma, it arises from the neck of the osteochondroma, and a higher percentage of patients with solitary osteochondroma than with multiple osteochondromas develops secondary osteosarcoma [4]. In our review, there were also 8 cases of solitary osteochondroma and 3 cases of multiple osteochondromas. In the solitary cases, the femur and tibia were the most common site of occurrence (Table 1). The histological grade is often high, and extensive resection is often performed. Chemotherapy has also often been given to patients under 55 years of age in recent years (Table 1).

Osteochondromas tend to transform to malignancy in the thickened cartilaginous cap and initially into low-grade chondrosarcomas. In contrast, in high-grade sarcomas, there are no neoplastic cartilaginous elements present [2, 6, 7, 10]. In the present study, imaging suggested that the proliferating tumor tissue did not include cartilaginous components. Tumor growth devoid of cartilaginous tissue should raise suspicions of malignant progression toward a high-grade tumor. From our review, 2 cases showed low-grade osteosarcoma [4, 9]. The prognosis is good for a short period of time, with a maximum survival of more than 4 years [6]. One patient with lung metastases died within 7 months after surgery, and lung metastasis is considered to be a factor associated with a poor prognosis [11].

The present patient was 66 years old, had a family history of multiple osteochondromas, and had a very rare case of malignant transformation of an osteochondroma of the iliac bone into osteosarcoma. Histologically, there was lobulated formation of cartilage without atypical cells consistent with a white area at the limbus. Bone tissue was found directly beneath the cartilage, and highly polymorphous atypical cells proliferated with synostosis in the bone tissue, leading to the diagnosis of osteosarcoma arising from osteochondroma. However, the pathological differences from conventional osteosarcoma are not fully elucidated and unknown.

A case of osteosarcoma arising from an iliac lesion of HMO was described. Although no recurrence or metastasis has been observed 3 years after surgery, further follow-up is necessary due to the short time after surgery.

Written, informed consent was obtained from the patient for publication of the details of her medical case and any accompanying images. This study protocol was reviewed and the need for approval was waived by the Ethics Committee of Mie University Hospital due to the retrospective nature of this case report.

The authors have no conflicts of interest to declare.

There was no funding support for this study.

Writing: Tadamasa Handa; conceptualization and review and editing: Kunihiro Asanuma; investigation: Hiroto Yuasa and Katsunori Uchida; formal analysis: Tomohito Hagi; data curation: Tomoki Nakamura; supervision: Kunihiro Asanuma and Akihiro Sudo. All authors have read and agreed to the published version of the manuscript.

All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author. The CARE Checklist has been completed by the authors for this case report, and is attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000541480).