eMedicine Specialties > Orthopedic Surgery > Neoplasms

Postradiation Sarcoma: Differential Diagnoses & Workup

Author: Nagarjun Rao, MD, FRCPath, Assistant Professor, Department of Pathology, Medical College of Wisconsin
Coauthor(s): Donald A Hackbarth Jr, MD, FACS, Professor of Clinical Orthopedic Surgery, Division Chief, Musculoskeletal Oncology, Department of Orthopedic Surgery, Medical College of Wisconsin; Stuart Wong, MD, Assistant Professor, Department of Medicine, Section of Hematology/Oncology, Froedert Memorial Lutheran Hospital; Vivek Panikkar, MBBS, MS, MCh, FRCS, Consulting Surgeon, Departments of Trauma and Orthopedics, Doncaster Royal Infirmary, UK; Vinod B Shidham, MD, FRCPath, FIAC,, Professor, Director of Cytopathology Fellowship Training Program, FNAB Service, and International Cytopathology Fellowship, Department of Pathology, Medical College of Wisconsin; Co-Editor-in-Chief and Executive Editor, CytoJournal
Contributor Information and Disclosures

Updated: Jul 14, 2009

Differential Diagnoses

Bursitis
Calcifying Tendonitis
Gout
Non-neoplastic Conditions Simulating Bone Tumors
Osteoarthritis
Rotator Cuff Pathology

Other Problems to Be Considered

Differential diagnoses for bone pain in a patient with a history of irradiation include the following:

  • Metastatic bone disease
  • Radiation osteopathy
  • Nonneoplastic causes of bone pain, such as rotator cuff impingement syndrome, osteoarthritis, bursitis/tendonitis, gout, and pseudogout

The pain in postradiation sarcoma (PRS) is worse at night. The pain usually is not relieved with aspirin or NSAIDs. Patients with arthritis also complain of worsening pain at night, but it usually is positional and only occasionally severe enough to wake the patient. Arthritic pain also usually is exacerbated by activity and relieved by rest.

Workup

Laboratory Studies

  • 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.

Imaging Studies

  • 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.

Procedures

  • 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.

Histologic Findings

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.18

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.

Light microscopic appearance of postradiation ost...

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 postradiation in a patient who had received radiation for a recurrent pituitary neoplasm.

Light microscopic appearance of postradiation ost...

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 postradiation in a patient who had received radiation for a recurrent pituitary neoplasm.


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).

Staging

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

More on Postradiation Sarcoma

Overview: Postradiation Sarcoma
Differential Diagnoses & Workup: Postradiation Sarcoma
Treatment & Medication: Postradiation Sarcoma
Follow-up: Postradiation Sarcoma
Multimedia: Postradiation Sarcoma
References
Further Reading

References

  1. Cahan WG. Radiation-induced sarcoma--50 years later. Cancer. Jan 1 1998;82(1):6-7. [Medline].

  2. Smith LM, Cox RS, Donaldson SS. Second cancers in long-term survivors of Ewing''s sarcoma. Clin Orthop. Jan 1992;(274):275-81. [Medline].

  3. Cahan WG, Woodard HQ, Higinbotham NL, et al. Sarcoma arising in irradiated bone: report of eleven cases. 1948. Cancer. Jan 1 1998;82(1):8-34. [Medline].

  4. Debeer P, Van de Meulebroucke B, Stuyck J, Sciot R, Samson I. Postradiation soft tissue sarcoma of the shoulder: a case report. Acta Orthop Belg. Aug 2007;73(4):521-4. [Medline].

  5. Nicolas MM, Nayar R, Yeldandi A, De Frias DV. Pulmonary metastasis of a postradiation breast epithelioid angiosarcoma mimicking adenocarcinoma. A case report. Acta Cytol. Nov-Dec 2006;50(6):672-6. [Medline].

  6. Hanasono MM, Osborne MP, Dielubanza EJ, Peters SB, Gayle LB. Radiation-induced angiosarcoma after mastectomy and TRAM flap breast reconstruction. Ann Plast Surg. Feb 2005;54(2):211-4. [Medline].

  7. Fang Z, Matsumoto S, Ae K, Kawaguchi N, Yoshikawa H, Ueda T. Postradiation soft tissue sarcoma: a multiinstitutional analysis of 14 cases in Japan. J Orthop Sci. 2004;9(3):242-6. [Medline].

  8. Fangman WL, Cook JL. Postradiation sarcoma: case report and review of the potential complications of therapeutic ionizing radiation. Dermatol Surg. Aug 2005;31(8 Pt 1):966-72. [Medline].

  9. Mullah-Ali A, Ramsay JA, Bourgeois JM, Hodson I, Macdonald P, Midia M, et al. Paraspinal synovial sarcoma as an unusual postradiation complication in pediatric abdominal neuroblastoma. J Pediatr Hematol Oncol. Jul 2008;30(7):553-7. [Medline].

  10. Inoue YZ, Frassica FJ, Sim FH, et al. Clinicopathologic features and treatment of postirradiation sarcoma of bone and soft tissue. J Surg Oncol. Sep 2000;75(1):42-50. [Medline].

  11. Neuhaus SJ, Pinnock N, Giblin V, Fisher C, Thway K, Thomas JM, et al. Treatment and outcome of radiation-induced soft-tissue sarcomas at a specialist institution. Eur J Surg Oncol. Dec 27 2008;[Medline].

  12. Bjerkehagen B, Smeland S, Walberg L, Skjeldal S, Hall KS, Nesland JM, et al. Radiation-induced sarcoma: 25-year experience from the Norwegian Radium Hospital. Acta Oncol. 2008;47(8):1475-82. [Medline].

  13. Amendola BE, Amendola MA, McClatchey KD, et al. Radiation-associated sarcoma: a review of 23 patients with postradiation sarcoma over a 50-year period. Am J Clin Oncol. Oct 1989;12(5):411-5. [Medline].

  14. Taghian A, de Vathaire F, Terrier P, et al. Long-term risk of sarcoma following radiation treatment for breast cancer. Int J Radiat Oncol Biol Phys. Jul 1991;21(2):361-7. [Medline].

  15. Strauss PG, Schmidt J, Pedersen L, et al. Amplification of endogenous proviral MuLV sequences in radiation- induced osteosarcomas. Int J Cancer. Apr 15 1988;41(4):616-21. [Medline].

  16. Pitcher ME, Davidson TI, Fisher C, et al. Post irradiation sarcoma of soft tissue and bone. Eur J Surg Oncol. Feb 1994;20(1):53-6. [Medline].

  17. Smith J. Radiation-induced sarcoma of bone: clinical and radiographic findings in 43 patients irradiated for soft tissue neoplasms. Clin Radiol. Mar 1982;33(2):205-21. [Medline].

  18. Enzinger FM, Weiss SW. General considerations. In: Soft Tissue Tumors. 3rd ed. St. Louis:. Mosby;1995.

  19. Brown J, Byers T, Thompson K, et al. A cancer journal for clinicians: nutrition during and after cancer treatment. In: A Guide for Informed Choices by Cancer Survivors. Vol 51. 2001.

  20. Kalra S, Grimer RJ, Spooner D, Carter SR, Tillman RM, Abudu A. Radiation-induced sarcomas of bone: factors that affect outcome. J Bone Joint Surg Br. Jun 2007;89(6):808-13. [Medline].

Further Reading

Related eMedicine topics

Ionizing Radiation Exposure, Medical Imaging

Radiation Necrosis

Intestinal Radiation Injury

Radiation Necrosis

Radiation Cystitis

Clinical guidelines

Improving outcomes for people with sarcoma. National Collaborating Centre for Cancer - National Government Agency [Non-U.S.].  2006 Mar.  138 pages.  NGC:004878

Keywords

postradiation sarcoma, PRS, postirradiation sarcoma, radiation-induced sarcoma, osteosarcoma, fibrosarcoma, malignant fibrous histiocytoma, MFH, chondrosarcoma, angiosarcoma, Ewing sarcoma, malignant peripheral nerve sheath tumor, MPNST

Contributor Information and Disclosures

Author

Nagarjun Rao, MD, FRCPath, Assistant Professor, Department of Pathology, Medical College of Wisconsin
Nagarjun Rao, MD, FRCPath is a member of the following medical societies: American Society for Clinical Pathology, College of American Pathologists, and Royal College of Pathologists
Disclosure: Nothing to disclose.

Coauthor(s)

Donald A Hackbarth Jr, MD, FACS, Professor of Clinical Orthopedic Surgery, Division Chief, Musculoskeletal Oncology, Department of Orthopedic Surgery, Medical College of Wisconsin
Donald A Hackbarth Jr, MD, FACS is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American Association of Tissue Banks, American College of Surgeons, Children's Oncology Group, Christian Medical & Dental Society, Clinical Orthopaedic Society, and Wisconsin Medical Society
Disclosure: Musculoskeletal Transplant Foundation Honoraria Board membership

Stuart Wong, MD, Assistant Professor, Department of Medicine, Section of Hematology/Oncology, Froedert Memorial Lutheran Hospital
Disclosure: Nothing to disclose.

Vivek Panikkar, MBBS, MS, MCh, FRCS, Consulting Surgeon, Departments of Trauma and Orthopedics, Doncaster Royal Infirmary, UK
Disclosure: Nothing to disclose.

Vinod B Shidham, MD, FRCPath, FIAC,, Professor, Director of Cytopathology Fellowship Training Program, FNAB Service, and International Cytopathology Fellowship, Department of Pathology, Medical College of Wisconsin; Co-Editor-in-Chief and Executive Editor, CytoJournal
Vinod B Shidham, MD, FRCPath, FIAC, is a member of the following medical societies: American Association for Cancer Research, American Society of Cytopathology, College of American Pathologists, International Academy of Cytology, Royal College of Pathologists, and United States and Canadian Academy of Pathology
Disclosure: Nothing to disclose.

Medical Editor

Miguel A Schmitz, MD, Consulting Surgeon, Department of Orthopedics, Klamath Orthopedic and Sports Medicine Clinic
Miguel A Schmitz, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American Orthopaedic Society for Sports Medicine, and Arthroscopy Association of North America
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Sean P Scully, MD, PhD, Professor, Department of Orthopedics, University of Miami
Sean P Scully, MD, PhD is a member of the following medical societies: American Academy of Orthopaedic Surgeons, International Society on Thrombosis and Haemostasis, and Society of Surgical Oncology
Disclosure: Nothing to disclose.

CME Editor

Dinesh Patel, MD, FACS, Associate Clinical Professor of Orthopedic Surgery, Harvard Medical School; Chief of Arthroscopic Surgery, Department of Orthopedic Surgery, Massachusetts General Hospital
Dinesh Patel, MD, FACS is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American Association of Physicians of Indian Origin, American College of International Physicians, and American College of Surgeons
Disclosure: Nothing to disclose.

Chief Editor

Harris Gellman, MD, Consulting Surgeon, Broward Hand Center; Voluntary Clinical Professor of Orthopedic Surgery and Plastic Surgery, Departments of Orthopedic Surgery and Surgery, University of Miami School of Medicine
Harris Gellman, MD is a member of the following medical societies: American Academy of Medical Acupuncture, American Academy of Orthopaedic Surgeons, American Orthopaedic Association, American Society for Surgery of the Hand, and Arkansas Medical Society
Disclosure: Nothing to disclose.

 
 
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