Elsevier

Mayo Clinic Proceedings

Volume 82, Issue 11, November 2007, Pages 1409-1432
Mayo Clinic Proceedings

SYMPOSIUM ON SOLID TUMORS
Sarcoma

https://doi.org/10.4065/82.11.1409Get rights and content

Sarcomas comprise a heterogeneous group of mesenchymal neoplasms. They can be grouped into 2 general categories, soft tissue sarcoma and primary bone sarcoma, which have different staging and treatment approaches. This review includes a discussion of both soft tissue sarcomas (malignant fibrous histiocytoma, liposarcoma, leiomyosarcoma, synovial sarcoma, dermatofibrosarcoma protuberans, angiosarcoma, Kaposi sarcoma, gastrointestinal stromal tumor, aggressive fibromatosis or desmoid tumor, rhabdomyosarcoma, and primary alveolar soft-part sarcoma) and primary bone sarcomas (osteosarcoma, Ewing sarcoma, giant cell tumor, and chondrosarcoma). The 3 most important prognostic variables are grade, size, and location of the primary tumor. The approach to a patient with a sarcoma begins with a biopsy that obtains adequate tissue for diagnosis without interfering with subsequent optimal definitive surgery. Subsequent treatment depends on the specific type of sarcoma. Because sarcomas are relatively uncommon yet comprise a wide variety of different entities, evaluation by oncology teams who have expertise in the field is recommended. Treatment and follow-up guidelines have been published by the National Comprehensive Cancer Network (www.nccn.org).

Section snippets

HISTORY

Sarcomas have played an important role in the understanding of the nature of cancer. In 1909, Rous13 was given a Plymouth Rock hen bearing a spindle cell sarcoma. Rous found that he could transfer the tumor from one chicken to another, but not to all types of chickens. In his studies of the nature of the transmissible agent, Rous found that extracts of tumors that passed through a Berkefeld filter (which did not allow passage of particles of the size of known bacteria) could also transfer the

CYTOGENETIC CHANGES

Cytogenetic changes are common in sarcomas15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28 (Table 1) and can be divided into 2 broad categories. One group has specific characteristic cytogenetic changes and relatively simple karyotypes, such as a fusion gene or point mutation. The other group has nonspecific changes, often with very complex karyotypes.16, 29, 30, 31 In several cases, the observed genetic changes have been exploited as targets of therapy. A better understanding of the

ETIOLOGIC AGENTS AND RISK FACTORS

Although most sarcomas arise spontaneously, some risk factors have been identified. Exposure to ionizing radiation increases the incidence of sarcomas, typically more than 7 to 10 years after exposure, most commonly in patients treated with radiation therapy for breast and cervical cancer as well as lymphoma.32, 33 Patients treated with ionizing radiation for cancer have developed both osteosarcoma and STS, including angiosarcoma.34, 35, 36, 37, 38 Other risk factors include chronic lymphedema,

SOFT TISSUE SARCOMAS

Soft tissue sarcomas, which represent fewer than 1% of malignancies, may arise in skin or other organs as well as soft tissue. Because the Surveillance, Epidemiology, and End Results data on STS only include those arising in soft tissue, they underestimate their true incidence.54 For example, the 1993 US national estimate increases from approximately 6000 STS cases per year to approximately 11,400 cases after the inclusion of STSs that originated in organs.54, 55 Similarly, GIST, which was

PRIMARY SARCOMAS OF BONE

The most common primary bone tumors are osteosarcoma, EWS, and MFH of bone. Management of primary sarcomas of bone has improved dramatically in the past 3 decades. Most patients are able to undergo limb-sparing procedures, and survival has improved dramatically.

SURGICAL RESECTION OF METASTASES

Given the heterogeneity in the biological behavior of sarcoma, resection of metastatic disease, which often occurs with osteosarcoma but may occur with any sarcoma, is a reasonable option. The most commonly resected metastases are those of the lung. Factors that are weighed when deciding whether to resect metastases include the length of the disease-free interval, the number of metastases, and the growth rate of the metastases. Clearly, a short disease-free interval, the presence of a large

FUTURE DEVELOPMENTS

The development of optimal treatment strategies for sarcoma has been greatly complicated by the large number of subtypes, the heterogeneity in their biological behavior, and the small number of patients with particular subtypes enrolled in trials. Molecular techniques such as microarray-based gene expression profiles promise to improve our ability to predict both the probability of metastasis and overall clinical course and the probability of response to a particular treatment.7, 8, 80 Recent

CONCLUSION

Sarcomas comprise a heterogeneous group of neoplasms that can be grouped into 2 general categories, STSs and primary bone sarcomas, each with different staging and treatment approaches. The approach to a patient with a sarcoma begins with a biopsy that obtains adequate tissue for diagnosis without interfering with subsequent optimal definitive surgery. Subsequent treatment depends on the specific type of sarcoma. Because sarcomas are relatively uncommon and yet comprise a wide variety of

REFERENCES (391)

  • L Requena et al.

    Cutaneous vascular proliferations, part III: malignant neoplasms, other cutaneous neoplasms with significant vascular component, and disorders erroneously considered as vascular neoplasms

    J Am Acad Dermatol

    (1998)
  • UR Hengge et al.

    Update on Kaposi's sarcoma and other HHV8 associated diseases, part 1: epidemiology, environmental predispositions, clinical manifestations, and therapy

    Lancet Infect Dis

    (2002)
  • D Whitby et al.

    Detection of Kaposi sarcoma associated herpesvirus in peripheral blood of HIV-infected individuals and progression to Kaposi's sarcoma

    Lancet

    (1995)
  • SM Schuetze

    Imaging and response in soft tissue sarcomas

    Hematol Oncol Clin North Am

    (2005)
  • B O'Sullivan et al.

    Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: a randomised trial

    Lancet

    (2002)
  • SS Bielack et al.

    Doxorubicin: effect of different schedules on toxicity and anti-tumor efficacy

    Eur J Cancer Clin Oncol

    (1989)
  • DS Alberts et al.

    Efficacy and safety of liposomal anthracyclines in phase I/II clinical trials

    Semin Oncol

    (2004)
  • I Judson et al.

    Randomised phase II trial of pegylated liposomal doxorubicin (DOXIL/CAELYX) versus doxorubicin in the treatment of advanced or metastatic soft tissue sarcoma: a study by the EORTC Soft Tissue and Bone Sarcoma Group

    Eur J Cancer

    (2001)
  • R Palumbo et al.

    Phase II study of continuous-infusion high-dose ifosfamide in advanced and/or metastatic pretreated soft tissue sarcomas

    Ann Oncol

    (1997)
  • OS Nielsen et al.

    Effect of high-dose ifosfamide in advanced soft tissue sarcomas: a multicentre phase II study of the EORTC Soft Tissue and Bone Sarcoma Group

    Eur J Cancer

    (2000)
  • SW Weiss et al.

    Enzinger and Weiss's Soft Tissue Tumors

    (2001)
  • M Brennan et al.

    Sarcomas of soft tissue and bone: soft tissue sarcoma

  • KM Skubitz et al.

    Differential gene expression in leiomyosarcoma

    Cancer

    (2003)
  • RB West et al.

    The role of microarray technologies in the study of soft tissue tumours

    Histopathology

    (2006)
  • K Baird et al.

    Gene expression profiling of human sarcomas: insights into sarcoma biology

    Cancer Res

    (2005)
  • PW Pisters et al.

    Analysis of prognostic factors in 1,041 patients with localized soft tissue sarcomas of the extremities

    J Clin Oncol

    (1996)
  • EC Borden et al.

    Soft tissue sarcomas of adults: state of the translational science

    Clin Cancer Res

    (2003)
  • MA Clark et al.

    Soft-tissue sarcomas in adults

    N Engl J Med

    (2005)
  • P Dileo et al.

    Update on new diagnostic and therapeutic approaches for sarcomas

    Clin Adv Hematol Oncol

    (2005)
  • P Rous

    Sarcoma of the common fowl

    J Exp Med

    (1910)
  • P Rous

    A sarcoma of the fowl transmissible by an agent separable from the tumor cells

    J Exp Med

    (1911)
  • M van de Rijn et al.

    Genetics of soft tissue tumors

    Annu Rev Pathol Mech Dis

    (2006)
  • C Sreekantaiah et al.

    Chromosomal aberrations in soft tissue tumors: relevance to diagnosis, classification, and molecular mechanisms

    Am J Pathol

    (1994)
  • BJ Quade et al.

    Molecular pathogenesis of uterine smooth muscle tumors from transcriptional profiling

    Genes Chromosomes Cancer

    (2004)
  • F Pedeutour et al.

    Structure of the supernumerary ring and giant rod chromosomes in adipose tissue tumors

    Genes Chromosomes Cancer

    (1999)
  • F Pedeutour et al.

    Complex composition and co-amplification of SAS and MDM2 in ring and giant rod marker chromosomes in well-differentiated liposarcoma

    Genes Chromosomes Cancer

    (1994)
  • YF Lee et al.

    Molecular classification of synovial sarcomas, leiomyosarcomas and malignant fibrous histiocytomas by gene expression profiling

    Br J Cancer

    (2003)
  • IS Jeon et al.

    A variant Ewing's sarcoma translocation (7;22) fuses the EWS gene to the ETS gene ETV1

    Oncogene

    (1995)
  • JA Fletcher et al.

    Diagnostic relevance of clonal cytogenetic aberrations in malignant soft-tissue tumors

    N Engl J Med

    (1991)
  • CD Fletcher et al.

    Correlation between clinicopathological features and karyotype in lipomatous tumors: a report of 178 cases from the Chromosomes and Morphology (CHAMP) Collaborative Study Group

    Am J Pathol

    (1996)
  • P Aman et al.

    Rearrangement of the transcription factor gene CHOP in myxoid liposarcomas with t(12;16)(q13;p11)

    Genes Chromosomes Cancer

    (1992)
  • JL Bennicelli et al.

    Chromosomal translocations and sarcomas

    Curr Opin Oncol

    (2002)
  • BE Amendola et al.

    Radiation-associated sarcoma: a review of 23 patients with postradiation sarcoma over a 50-year period

    Am J Clin Oncol

    (1989)
  • WG Cahan

    Radiation-induced sarcoma—50 years later [editorial]

    Cancer

    (1998)
  • M Arlen et al.

    Radiation-induced sarcoma of bone

    Cancer

    (1971)
  • CM Brenin et al.

    Radiation-induced sarcoma following treatment of breast cancer

    Cancer Control

    (1998)
  • DM Nanus et al.

    Radiation-induced angiosarcoma

    Cancer

    (1987)
  • WW Souba et al.

    Radiation-induced sarcomas of the chest wall

    Cancer

    (1986)
  • SA Vorburger et al.

    Angiosarcoma of the breast

    Cancer

    (2005)
  • AH Woodward et al.

    Lymphangiosarcoma arising in chronic lymphoedematous extremities

    Cancer

    (1972)
  • Cited by (247)

    View all citing articles on Scopus

    Dr Skubitz has received grant support from Amgen, Bristol Myers, Cell Therapeutics, Johnson & Johnson, and Pfizer; is on the speakers' bureaus of Johnson & Johnson, Novartis, and Pfizer; owns publicly traded stock in Genentech and Johnson & Johnson; and has consulted for Amgen, Johnson & Johnson, Keryx, Novartis, and OSI. Dr D'Adamo is on the speakers' bureaus of Bayer, Novartis, and Pfizer.

    View full text