Laboratory Studies
No specific laboratory blood tests are used to diagnose postradiation sarcoma (PRS; also referred to as radiation-induced sarcoma [RIS]). Routine laboratory investigations may be ordered.
Cytogenetic studies on PRS tumor cells do not have much value, because the tumor cells can have numerous quantitative (numerical) and qualitative abnormalities that lack specificity. However, the value of cytogenetic analysis lies in excluding other conditions that may have specific anomalies and that may present a challenge in light-microscopic examination.
Imaging Studies
Plain radiographs should be obtained in two planes. Cortical bone destruction is the most common finding. A mineralized soft-tissue mass is seen in most patients. Changes such as osteopenia and sclerosis are seen in a minority of patients.
If plain radiography yields normal findings and the patient has significant pain, computed tomography (CT) and magnetic resonance imaging (MRI) are useful for identifying abnormal areas in the medullary cavity, cortical bone destruction, and the presence of an extramedullary soft-tissue mass. MRI is the best modality for detecting soft-tissue involvement in PRS. Chest CT is performed to detect pulmonary metastases.
Technetium bone scanning is performed to detect bone metastases.
Biopsy
Fine-needle aspiration (FNA) biopsies or Tru-Cut core biopsies can be obtained from the lesion for histopathologic/cytopathologic confirmation of diagnosis and for typing and grading of the lesion. In the case of a deep-seated lesion, CT-guided biopsies can be obtained. The biopsy should be the final diagnostic procedure because it can distort the findings from imaging studies, especially MRI.
Careful preoperative planning is required before biopsy is attempted. Imaging studies aid the surgeon in selecting the best site for tissue diagnosis. Usually, the best diagnostic site is at the interface between the tumor and adjacent normal tissue; this also prevents the occurrence of fracture at the biopsy site, in that biopsy in this location usually does not violate cortical bone.
A frozen section can be obtained to determine whether adequate representative tissue has been obtained. A definitive diagnosis usually is delayed until permanent sections are analyzed.
Olson et al conducted a retrospective review of 13 patients (median age, 61 years) who underwent FNA in the treatment of PRS. [24] Patients generally presented with large tumors (median, 8 cm; range, 3-12 cm), and median survival was 14 months (range, 6-46 months). Nine of the 13 patients died of their disease, and one was lost to follow-up. The tumors were morphologically heterogeneous. The researchers concluded that PRS can be diagnosed by means of FNA and that immunohistochemistry is often required to rule out locally recurrent malignancy.
Histologic Findings
PRS in bone and soft tissue usually is a high-grade lesion, and this partly accounts for the almost uniformly grim prognosis. [4, 7] In a study of 130 patients with PRS of bone and soft tissue, osteosarcoma was the most common type, constituting 61.5% of all cases. [10] This was followed by fibrosarcoma (23.7%), malignant fibrous histiocytoma (MFH; 9.6%), chondrosarcoma (3.7%), and rare cases of angiosarcoma and Ewing sarcoma. No difference in the histologic type of PRS was demonstrated between orthovoltage and megavoltage groups.
Among soft-tissue PRS lesions, the most common histologic type is MFH (70%), followed by osteosarcoma, fibrosarcoma, malignant peripheral nerve sheath tumor (MPNST), chondrosarcoma, and angiosarcoma. [25]
Grossly, these tumors are soft and fleshy, with extension into adjacent soft tissue and formation of a soft-tissue mass. Hemorrhagic/necrotic foci and matrix production (osteoid/chondroid) may be seen. Degenerative calcific changes also may be noted. Microscopically, whereas specific characteristics such as osteoid production (in osteosarcomas) may be seen, these tumors generally show pleomorphic high-grade spindle cell features with marked nuclear pleomorphism, mitotic activity, and variable necrosis. (See the image below.)
Light-microscopic appearance of postradiation osteosarcoma; tumor is composed of pleomorphic plump spindle cells with focal presence of neoplastic osteoid (pink areas) in between tumor cells. This meningeal tumor occurred 10 years after radiation therapy in patient who had received such therapy for recurrent pituitary neoplasm.
Staging
Careful staging is a prerequisite for appropriate management of PRS. The marrow extent and soft-tissue involvement of PRS should be gauged by using diagnostic imaging modalities, of which MRI is the best choice. Biopsies may be obtained to confirm the diagnosis and to type and grade the lesion. CT of the chest is obtained to detect pulmonary metastases. A technetium bone scan is performed to detect bone metastases.
On the basis of the results of imaging and histopathologic/cytopathologic studies, the lesion may be staged. The American Joint Committee on Cancer (AJCC) and Musculoskeletal Tumor Society (MSTS) staging systems generally are used.
AJCC staging system
The AJCC staging system is based on the TNM staging system and uses the following categories:
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Size and extension of primary tumor (T)
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Involvement of lymph nodes (N)
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Presence of metastases (M)
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Type and grade of sarcoma (G)
T categories in the AJCC TNMG staging system are as follows:
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T1 - Tumor smaller than 5 cm
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T2 - Tumor 5 cm or larger
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T3 - Discontinuous tumors in the primary bone site (skip metastases)
N categories in the AJCC TNMG staging system are as follows:
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N0 - No histologically verified regional node metastasis
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N1 - Histologically verified regional node metastasis
M categories in the AJCC TNMG staging system are as follows:
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M0 - No distant metastasis
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M1 - Distant metastasis
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M1a - Isolated pulmonary metastasis
G categories in the AJCC TNMG staging system are as follows:
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G1 - Well differentiated
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G2 - Moderately well differentiated
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G3 - Poorly differentiated
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G4 – Undifferentiated
With the eighth edition of the AJCC cancer staging manual, the prognostic stage groups are no longer defined for spine and pelvic primaries.
MSTS staging system
The MSTS staging system classifies tumors as follows:
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Stage IA - Low grade, intracompartmental
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Stage IB - Low grade, extracompartmental
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Stage IIA - High grade, intracompartmental
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Stage IIB - High grade, extracompartmental
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Stage III - Systemic or regional metastases
In the MSTS staging system, the margins are classified as follows:
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Intralesional - Margin through tumor tissue
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Marginal - Margin through reactive zone around tumor consisting of edema, inflammatory cells, fibrous tissue, and tumor cell satellites
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Wide - Margin through normal tissue outside reactive zone
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Radical – Removal of entire compartment containing tumor
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Light-microscopic appearance of postradiation osteosarcoma; tumor is composed of pleomorphic plump spindle cells with focal presence of neoplastic osteoid (pink areas) in between tumor cells. This meningeal tumor occurred 10 years after radiation therapy in patient who had received such therapy for recurrent pituitary neoplasm.
