Postradiation Sarcoma Workup

• No specific laboratory blood tests are used to diagnose postradiation sarcoma (PRS). 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.

• Plain radiographs

  • Obtain plain radiographs in 2 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.
• CT scan and MRI

  • If plain radiograph findings are normal and the patient has significant pain, these scans 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 to detect soft-tissue involvement in PRS.
  • CT scan of the chest is performed to detect pulmonary metastases.
• Technetium bone scan is performed to detect bone metastases.

• Biopsy

  • Fine-needle aspiration biopsies or Tru-Cut core biopsies can be obtained from the lesion for histopathologic/cytopathologic confirmation of diagnosis and to type and grade 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 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, as 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.

Postradiation sarcoma (PRS) in bone and soft tissue usually is a high-grade lesion, which partly accounts for the almost uniformly grim prognosis.^{[4, 7]} In a study of 130 patients with PRS of bone and soft tissue from the Mayo Clinic, 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 histologic type of PRS was demonstrated between the 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.^[20]

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.

See the image below.

Microscopically, while specific characteristics such as osteoid production (in osteosarcomas) may be seen, in general, these tumors show pleomorphic high-grade spindle cell features with marked nuclear pleomorphism, mitotic activity, and variable necrosis (see Image above).

Careful staging is a prerequisite for appropriate management of postradiation sarcoma (PRS).

The marrow extent and soft-tissue involvement of PRS should be gauged using radiologic modalities, of which MRI is the best choice. Biopsies may be obtained to confirm the diagnosis and to type and grade the lesion.

A CT scan of the chest is obtained to detect pulmonary metastases. A technetium bone scan is performed to detect bone metastases.

Based on 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.

• The AJCC staging system is based on the TNM staging system and uses the following categories:

  • Size and extension of primary tumor (T)
  • Involvement of lymph nodes (N)
  • Presence of metastases (M)
  • Type and grade of sarcoma (G)
• Definitions of the TNMG staging system are as follows:

  • T - Primary tumor
    • T1 - Tumor smaller than 5 cm
    • T2 - Tumor 5 cm or larger
  • N - Regional lymph nodes
    • N0 - No histologically verified regional node metastasis
    • N1 - Histologically verified regional node metastasis
  • M - Distant metastasis
    • M0 - No distant metastasis
    • M1 - Distant metastasis
  • G - Histologic grade of malignancy
    • G1 - Well differentiated
    • G2 - Moderately well differentiated
    • G3 - Poorly differentiated
    • G4 – Undifferentiated
• The MSTS staging system classifies tumors as follows:

  • Stage IA - Low grade, intracompartmental
  • Stage IB - Low grade, extracompartmental
  • Stage IIA - High grade, intracompartmental
  • Stage IIB - High grade, extracompartmental
  • Stage III - Systemic or regional metastases
• In the MSTS staging system, the margins are classified as follows:

  • Intralesional - Margin through tumor tissue
  • Marginal - Margin through reactive zone around tumor consisting of edema, inflammatory cells, fibrous tissue, and tumor cell satellites
  • Wide - Margin through normal tissue outside reactive zone
  • Radical – Removal of entire compartment containing tumor