Sarcomas

Clinical Background

Sarcomas are a group of rare malignant tumors that arise in bone and soft tissue and have a wide range of histologic types and prognoses.

Epidemiology

Incidence
- 2-4/100,000
- <1% of all malignancies
Age - mean is 50s
- 15% in children <15 years
- 40% in adults >55 years

Classification

Most common subtypes (>50 subtypes)
- Fibrous histiocytoma (formerly call fibrosarcoma)
- Leiomyosarcoma
- Liposarcoma
- Synovial sarcoma
- Neurofibrosarcoma (malignant schwannoma)
- Osteosarcoma
- Chondrosarcoma
- Rhabdomyosarcoma
- Gastrointestinal stromal tumors
- Ewing sarcoma
- Epithelioid sarcoma
- Kaposi sarcoma

Risk Factors

Genetic
- Li Fraumeni
- Neurofibromatosis type 1
- t(18;X) mutation
- t(12;16) or t(12;22) mutation
- Inherited retinoblastomas
- Beckwith-Wiedemann syndrome
Previous scar tissue
Previous radiation treatment - increases incidence 8-50-fold
Viruses
- HIV
- HHV8
Paget’s disease of the bone
Chronic lymphedema (Steward Treves syndrome) - lymphangiosarcoma

Pathophysiology

Mesodermal derivation from musculo-skeletal tissues such as connective tissue, lymphatic vessels, smooth and skeletal muscle, fat, fascia and synovial structures

Clinical Presentation

60% arise in the extremities
- 3:1 ratio legs to arms
Soft tissue tumors
- Asymptomatic mass is most common presentation
- May have mechanical symptoms (eg, pain) due to entrapment, pressure or traction
Bony tumors
- Pain and swelling of the affected area

See Also

Ewing Sarcoma

Neuroblastoma

Tests

Tests generally appear in the order most useful for common clinical situations

Test name: Chromosome Analysis, FISH-Interphase

ARUP #: 0092615

Methodology: Fluorescence in situ Hybridization

Use:

Differential diagnosis of small cell neoplasms in fluid-based samples

Order SYT for determining presence of the synovial 18q11.2 translocation

Order EWSR1 for determining presence of 22q12 translocation

Limitations:

EWSR1 FISH does not identify the 22q12 translocation partner; therefore, this test cannot alone distinguish between sarcomas involving EWSR1 such as Ewing’s tumor family, desmoplastic small round cell tumor, clear cell sarcoma, and myxoid chondrosarcoma

Follow-up:

Test name: Chromosome Analysis, Solid Tumor

ARUP #: 0097778

Methodology: Giemsa-Band Analysis

Use:

Detect recurrent chromosome abnormalities in tumor biopsy consistent with the diagnosis of a sarcoma

Limitations:

Tumor cells may not grow well in culture and may not be present in the cells analyzed. Therefore, it is recommended this test be done in conjunction with interphase FISH when either a EWSR1 or SYT translocation is in the differential (0092616)

Test name: CHOP Gene Rearrangement by FISH

ARUP #: 0049378

Methodology: Fluorescence in situ Hybridization

Use:

Diagnosis of liposarcoma in paraffin-embedded tissue

Test name: Ewing Sarcoma by RT-PCR

ARUP #: 0051220

Methodology: Reverse Transcription Polymerase Chain Reaction/Fluorescence Monitoring

Use:

Detect the most common types of EWS-FLI1 translocations that occur in the Ewing sarcoma family of tumors

Distinguish between the EWS-FLI1 type 1 and type 2 fusions

Test name: EWSR1 Break Apart Rearrangement by FISH

ARUP #: 0049335

Methodology: Fluorescence in situ Hybridization

Use:

Differential diagnosis of small cell neoplasms in paraffin-embedded tissue

Diagnose members of the Ewing family of neoplasms

Test name: SYT-SSX t(X;18) Translocations by RT-PCR

ARUP #: 0040114

Methodology: Reverse Transcription Polymerase Chain Reaction/Fluorescence Monitoring

Use:

Diagnose synovial sarcoma

Test name: Immunohistochemistry Stain Offering

ARUP #: arup005

Methodology: Immunohistochemistry

Use:

For fixed tissue samples, consultative services as well as immunohistochemical staining for CD21, CD34 (QBEND10), CD56 (NCAM), CD99 (013), muscle specific actin, myo D-1, myogenin, myoglobin, myosin, p-glycoprotein, smooth muscle actin, Ulex Europaeus, Vimentin and Desmin are available

References

Cited References

Skubitz KM, D'Adamo DR. Sarcoma. Mayo Clin Proc. 2007;82(11):1409-1432.

General References

Adigun IA, Rahman GA. A review of soft tissue sarcoma. Niger J Med. 2007;16(2):94-101.

Dang TA, Man TK. Classification of sarcomas using bioinformatics and molecular profiling. Curr Pharm Biotechnol. 2007;8(2):83-91.

de Alava E. Molecular pathology in sarcomas. Clin Transl Oncol. 2007;9(3):130-144.

Pisters PW. Treatment of localized soft-tissue sarcoma: lessons learned. Oncology (Williston Park). 2007;21(6):731-2, 735.

Reid R. Update on sarcomas of bone and soft tissue. Scott Med J. 2007;52(2):31-35.

Swallow CJ, Catton CN. Local management of adult soft tissue sarcomas. Semin Oncol. 2007;34(3):256-269.

References from the ARUP Institute for Clinical and Experimental Pathology Research®

Joyner DE, Wade ML, Szabo A, Bastar J, Coffin CM, Albritton KH, Bernard PS, Randall RL. Discriminate gene lists derived from cDNA microarray profiles of limited samples permit distinguishing mesenchymal neoplasia ex vivo. J Cancer Res Clin Oncol. 2005;131(3):137-146.

Liu K, Tripp S, Layfield LJ. Heterotopic ossification: review of histologic findings and tissue distribution in a 10-year experience. Pathol Res Pract. 2007;203(9):633-640.

Medical Reviewers

Lamb, Allen N., Ph.D. Medical Director, Cytogenetics, ARUP Laboratories; Associate Professor, Department of Pathology, University of Utah

Layfield, Lester , M.D. Fine-Needle Aspiration Services and Molecular Diagnostics at ARUP Laboratories; Professor and Division Head, Anatomic Pathology, University of Utah

Perkins, Sherrie L. , M.D., Ph.D. Medical Director, Hematopathology at ARUP Laboratories; Professor, Anatomic Pathology, University of Utah

South, Sarah T. , Ph.D. Medical Director, Cytogenetics at ARUP Laboratories; Assistant Medical Director, CGH Microarray Laboratory, and Assistant Professor, Department of Pediatrics, University of Utah

Comprehensive Review: March 2008
Last Update: September 2008