Miscellaneous Malignant Primary Bone Tumors

Rosanna Wustrack, MD, FAAOS

Melissa Zimel, MD, FAAOS

Neither of the following authors nor any immediate family member has received anything of value from or has stock or stock options held in a commercial company or institution related directly or indirectly to the subject of this chapter: Dr. Wustrack and Dr. Zimel.

This chapter is adapted from McKeown D, Boland PJ: Miscellaneous malignant primary bone tumors, in Biermann JS, ed: Orthopaedic Knowledge Update^®: Musculoskeletal Tumors 3. American Academy of Orthopaedic Surgeons, 2014, pp 195-201.

ABSTRACT

Osteosarcoma, Ewing sarcoma, and chondrosarcoma account for most primary malignant bone tumors. Chordoma almost exclusively arises in the axial skeleton in older adults. Surgery is the mainstay of treatment with novel forms of radiation commonly used in the adjuvant setting. Both high-grade undifferentiated pleomorphic sarcoma of bone and fibrosarcoma of bone are diagnoses of exclusion. They present in older individuals and are managed using an approach similar to that used for osteosarcoma. Primary leiomyosarcoma of bone can be diagnosed with immunohistochemistry, displaying smooth muscle markers. Following appropriate staging studies and biopsy, a definitive surgery with negative margins can be curative. Malignant vascular tumors of bone include the intermediate-grade epithelioid hemangioendothelioma and the very aggressive angiosarcoma. Wide resection allows only potential for cure. Adamantinoma is a low-grade malignant epithelioid tumor of bone with a predilection for the anterior tibial cortex. Osteofibrous dysplasia-like adamantinoma is a locally aggressive variant without metastatic potential. Wide resection is the treatment of choice for adamantinoma. Long-term follow-up of more than 10 years after treatment is recommended because late metastases can occur.

INTRODUCTION

Osteosarcoma, chondrosarcoma, and Ewing sarcoma account for more than 75% of all primary bone tumors. Rare bone tumors include chordoma, undifferentiated pleomorphic sarcoma (UPS; previously known as malignant fibrous histiocytoma), fibrosarcoma, leiomyosarcoma, malignant vascular tumors, and adamantinoma. Diagnostic modalities, staging, and management of these primary bone sarcomas follow the same principles as those for the more common tumors.

CHORDOMA

Chordoma is a slow-growing, locally destructive, malignant bone tumor thought to arise from vestigial or ectopic notochordal tissue.¹^,²

Epidemiology

Analysis of data collected by the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program from 1973 to 1987 shows that osteosarcoma, chondrosarcoma, and Ewing sarcoma account for 77% of all primary bone tumors.³ Chordoma accounts for 8.4% of all primary bone tumors, making it the fourth most common.³ The overall incidence is 0.084 per 100,000 people.² Although chordoma occurs almost
exclusively in the axial skeleton, rare cases are reported in the appendicular skeleton and soft tissues. Anatomically, the sacrococcygeal, spheno-occipital, and mobile spine are involved, in that order of frequency.²

Chordoma is rare in children and adolescents. The overall incidence increases with age, and the median age at diagnosis is 57 years with a slight male predominance (57.9%).¹^,³ Spheno-occipital tumors are more common in younger patients, whereas sacral involvement predominates in older age groups. Like Ewing sarcoma, chordoma is extremely rare among populations of African origin globally and most patients are White (86.9%).²^,³ A familial form has been described. The association between intraosseous benign notochordal tumors (IOBNCTs) and chordoma is currently under debate. The literature includes several reports of the two entities coexisting in the spine, but definitive transformation of IOBNCTs to chordoma has not been confirmed.⁴

Patients with spheno-occipital lesions may have headaches, cranial nerve palsies, dysphagia, and secondary endocrinopathies from pituitary destruction. Long-standing low back pain or poorly localized gluteal pain is common in sacrococcygeal tumors; however, up to 30% of patients will present with radiculopathy;⁵ bowel or bladder dysfunction usually indicates advanced disease.¹^,²^,⁵ It is not uncommon for patients to present with locally advanced disease because of the slow-growing nature of chordomas and nonspecific symptoms.

Imaging

Radiographically, chordomas are lytic, with an epicenter in the midvertebral body. Sacrococcygeal tumors are difficult to see on plain radiographs and thus are frequently overlooked. Bone scintigraphy may show reduced or normal radioisotope uptake.

MRI is the most useful imaging modality; however, routine lumbar MRI to evaluate low back pain or sciatica may not extend caudal past the S2 level and miss very distal tumors. Chordomas are predominantly bright on T2-weighted sequences with some internal T1 hyperintensity and heterogeneous enhancement. Central vertebral body lysis and anterior and posterior cortical destruction are common features in chordoma but are rarely seen in IOBNCTs (Figure 1). In sacral lesions, extension into the piriformis muscles and sacroiliac ligaments is common and important to note when planning for surgery. CT shows bone lysis and bone destruction in chordoma, whereas sclerosis without cortical destruction are more common radiographic features of IOBNCTs⁴^,⁶ (Figure 2). A 2021 study that examined 23 patients with chordoma found an average maximum standardized uptake value of 5.8 ± 3.7 and concluded that positron emission tomography-CT may be useful in the initial staging of chordomas, to assess treatment response and local or distant recurrence.⁷

FIGURE 1 Sagittal magnetic resonance image of the sacrum shows typical chordoma with bony destruction and soft-tissue extension both anteriorly and posteriorly.

FIGURE 2 A, Sagittal CT scan of the sacrum demonstrates a sclerotic intraosseous benign notochordal tumor (arrow). B, Magnetic resonance image from the same patient shows no cortical destruction.

Pathology

Diagnosis can usually be made with a carefully planned core biopsy. Histologically, three types of chordoma are observed: classic, chondroid, and dedifferentiated.¹^,²

In classic chordoma, lobules containing cells arranged in cords or nests in myxoid stroma are identified (Figure 3). The cells typically have vacuolated cytoplasm (physaliferous cells). Mitotic figures and pleomorphism are present. Myxoid stroma, mitotic figures, and pleomorphism are features not seen in IOBNCTs.⁴^,⁶^,⁸

FIGURE 3 Photomicrograph showing classic chordoma, with typical vacuolated physaliferous cells (arrow).

The chondroid variant comprises 15% of chordomas. They primarily occur in the spheno-occipital area, and patients with these tumors have a better prognosis than those with other chordoma types.¹ The features of chondroid chordomas overlap with those of chondrosarcoma. Dedifferentiated chordomas are biphasic tumors and contain areas of high-grade malignant spindle cells juxtaposed to classic chordoma features and have a poor prognosis.⁸

Immunohistochemical staining for S-100 and epithelial markers is positive in classic chordoma and the chondroid variant but is lost in dedifferentiated chordomas. Brachyury, a T-box transcription factor expressed by notochordal cells, is a highly specific marker for chordomas. This immunoprofile helps distinguish chordoma from chondrosarcoma and most other tumors.¹^,⁴^,⁶^,⁸^,⁹ Loss of integrase interactor 1 (INI-1) expression is seen in a small number of chordomas and may guide systemic treatment.⁷

Treatment

It is important to distinguish benign notochordal tumors from chordomas. In addition to the radiographic and histologic distinctions discussed previously, the benign tumors typically exhibit asymptomatic, incidental clinical findings that require no further treatment. The rare symptomatic lesion may be managed with intralesional excision.

Chordomas, however, require more aggressive treatment. Surgery is the mainstay. Several series report significant improvement in local control and survival with wide resection when compared with intralesional or marginal excision.¹^,⁵ For sacrococcygeal tumors, complete resection is usually possible. Overall survival at 3, 5, and 10 years has been reported at 80.9%, 73.5%, and 58.7%, respectively. Cranial chordoma may have improved survival compared with other sites; patients aged 65 years or older at diagnosis tend to have worse outcomes.²

Wide resection of chordomas of the mobile spine is preferred but is not always possible, in which case incomplete resection and radiation therapy are recommended. Complete surgical resection of spheno-occipital tumors is rarely possible, but good results have been reported using marginal or intralesional surgery combined with radiation therapy. Endoscopic resection is commonly used for these lesions.¹ In cases of unresectable chordoma, durable local control and improved overall survival at 5 years has been demonstrated in selected patients with high-dose definitive radiation therapy.¹⁰^,¹¹ Advances in radiation oncology using image-guided photons have facilitated the administration of effective, high-dose radiation therapy in spinal tumors.¹ The use of protons and carbon ions (hadron therapy) has provided a means of administering greater biologic doses of radiation therapy to chordomas while sparing sensitive neural or visceral structures.¹²^,¹³ A 2020 review of the National Cancer Database found that adjuvant high-dose radiation therapy demonstrated improved overall survival among patients treated surgically who had negative margins, but did not improve overall survival among those with negative margins. The study authors also compared radiation modalities and found improved overall survival when advanced treatments such as proton beam radiation or intensity-modulated radiation therapy were used compared with standard external beam radiation.¹⁴

Metastases to the lungs, bone, and subcutaneous tissues are late manifestations of chordoma and occur in approximately 30% of patients.⁵ Chordomas are resistant
to conventional chemotherapy; new agents that target known molecular pathways are being investigated, although none has become part of first-line treatment to date.¹^,²^,⁸

UNDIFFERENTIATED HIGH-GRADE PLEOMORPHIC SARCOMA OF BONE

UPS (previously known as malignant fibrous histiocytoma) represents less than 2% of all primary malignant bone tumors and is defined as a high-grade pleomorphic malignant tumor that lacks a specific line of differentiation. Seventy percent to 75% of these bony tumors arise in the appendicular skeleton.

Epidemiology

Males are affected more commonly than females, and the incidence rises in patients older than 40 years. These malignant lesions can arise de novo in bone (approximately 70% of cases) or can occur secondary to irradiation, bone infarct, Paget disease, or chronic osteomyelitis.¹⁵^,¹⁶^,¹⁷^,¹⁸ The appendicular skeleton of the lower limb is the most frequent site of involvement, with a predilection for the distal femur and proximal tibial metaphysis.¹⁷

Clinical Features

Only gold members can continue reading. Log In or Register to continue