Postradiation Sarcoma Workup
- Author: Nagarjun Rao, MD, FRCPath; Chief Editor: Harris Gellman, MD more...
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 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.
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. 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.
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. 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.
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.)
Careful staging is a prerequisite for appropriate management of PRS. The marrow extent and soft-tissue involvement of PRS should be gauged by 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. 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:
Size and extension of primary tumor (T)
Involvement of lymph nodes (N)
Presence of metastases (M)
Type and grade of sarcoma (G)
T categories in the AJCC TNMG staging system are as follows:
T1 - Tumor smaller than 5 cm
T2 - Tumor 5 cm or larger
N categories in the AJCC TNMG staging system are as follows:
N0 - No histologically verified regional node metastasis
N1 - Histologically verified regional node metastasis
M categories in the AJCC TNMG staging system are as follows:
M0 - No distant metastasis
M1 - Distant metastasis
G categories in the AJCC TNMG staging system are as follows:
G1 - Well differentiated
G2 - Moderately well differentiated
G3 - Poorly differentiated
G4 – Undifferentiated
MSTS staging system
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
Cahan WG. Radiation-induced sarcoma--50 years later. Cancer. 1998 Jan 1. 82(1):6-7. [Medline].
Smith LM, Cox RS, Donaldson SS. Second cancers in long-term survivors of Ewing''s sarcoma. Clin Orthop. 1992 Jan. (274):275-81. [Medline].
Cahan WG, Woodard HQ, Higinbotham NL, et al. Sarcoma arising in irradiated bone: report of eleven cases. 1948. Cancer. 1998 Jan 1. 82(1):8-34. [Medline].
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. 2007 Aug. 73(4):521-4. [Medline].
Nicolas MM, Nayar R, Yeldandi A, De Frias DV. Pulmonary metastasis of a postradiation breast epithelioid angiosarcoma mimicking adenocarcinoma. A case report. Acta Cytol. 2006 Nov-Dec. 50(6):672-6. [Medline].
Hanasono MM, Osborne MP, Dielubanza EJ, Peters SB, Gayle LB. Radiation-induced angiosarcoma after mastectomy and TRAM flap breast reconstruction. Ann Plast Surg. 2005 Feb. 54(2):211-4. [Medline].
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].
Fangman WL, Cook JL. Postradiation sarcoma: case report and review of the potential complications of therapeutic ionizing radiation. Dermatol Surg. 2005 Aug. 31(8 Pt 1):966-72. [Medline].
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. 2008 Jul. 30(7):553-7. [Medline].
Inoue YZ, Frassica FJ, Sim FH, et al. Clinicopathologic features and treatment of postirradiation sarcoma of bone and soft tissue. J Surg Oncol. 2000 Sep. 75(1):42-50. [Medline].
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. 1989 Oct. 12(5):411-5. [Medline].
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. 1991 Jul. 21(2):361-7. [Medline].
Strauss PG, Schmidt J, Pedersen L, et al. Amplification of endogenous proviral MuLV sequences in radiation- induced osteosarcomas. Int J Cancer. 1988 Apr 15. 41(4):616-21. [Medline].
Mentzel T, Schildhaus HU, Palmedo G, Büttner R, Kutzner H. Postradiation cutaneous angiosarcoma after treatment of breast carcinoma is characterized by MYC amplification in contrast to atypical vascular lesions after radiotherapy and control cases: clinicopathological, immunohistochemical and molecular analysis of 66 cases. Mod Pathol. 2012 Jan. 25(1):75-85. [Medline].
Laé M, Lebel A, Hamel-Viard F, Asselain B, Trassard M, Sastre X, et al. Can c-myc amplification reliably discriminate postradiation from primary angiosarcoma of the breast?. Cancer Radiother. 2015 May. 19 (3):168-74. [Medline].
Pitcher ME, Davidson TI, Fisher C, et al. Post irradiation sarcoma of soft tissue and bone. Eur J Surg Oncol. 1994 Feb. 20(1):53-6. [Medline].
Smith J. Radiation-induced sarcoma of bone: clinical and radiographic findings in 43 patients irradiated for soft tissue neoplasms. Clin Radiol. 1982 Mar. 33(2):205-21. [Medline].
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. 2008 Dec 27. [Medline].
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].
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. 2007 Jun. 89(6):808-13. [Medline].
Mavrogenis AF, Pala E, Guerra G, Ruggieri P. Post-radiation sarcomas. Clinical outcome of 52 Patients. J Surg Oncol. 2012 May. 105 (6):570-6. [Medline].
Papalas JA, Wylie JD, Vollmer RT. Osteosarcoma after radiotherapy for prostate cancer. Ann Diagn Pathol. 2011 Jun. 15(3):194-7. [Medline].
Weaver J, Billings SD. Postradiation cutaneous vascular tumors of the breast: a review. Semin Diagn Pathol. 2009 Aug. 26(3):141-9. [Medline].
Olson MT, Wakely PE Jr, Weber K, Siddiqui MT, Ali SZ. Postradiation sarcoma: morphological findings on fine-needle aspiration with clinical correlation. Cancer Cytopathol. 2012 Oct 25. 120(5):351-7. [Medline].
Enzinger FM, Weiss SW. General considerations. Soft Tissue Tumors. 3rd ed. St Louis: Mosby; 1995.
Chan JY, Wong ST, Lau GI, Wei WI. Postradiation sarcoma after radiotherapy for nasopharyngeal carcinoma. Laryngoscope. 2012 Dec. 122(12):2695-9. [Medline].
Brown J, Byers T, Thompson K, Eldridge B, Doyle C, Williams AM, et al. Nutrition during and after cancer treatment: a guide for informed choices by cancer survivors. CA Cancer J Clin. 2001 May-Jun. 51 (3):153-87; quiz 189-92. [Medline].