Topic Name

A	B	C	D	E	F	G	H	I
J	K	L	M	N	O	P	Q	R
S	T	U	V	W	X	Y	Z	#

Disease Categories > Oncologic Disease

Font

Sarcomas

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

Diagnosis

Requires biopsy with histologic diagnosis
- Histology may be similar between tumors and sometimes makes differentiation difficult
- Histology diagnosis may be aided by identification of mutations and translocations
  - SYT-SSX; t(18;X) – specific for synovial sarcomas
  - CHOP gene rearrangement by FISH – specific for myxoid and round cell liposarcomas
  - EWSR1-FLI1; t(11;22) (q24;q12) – 90% of Ewing’s family of small, round cell tumors, including Ewing’s sarcoma, peripheral primitive neuroectodermal tumor, Askin’s tumor, and esthesioneuroblastoma
    - EWSR1-ERG; t(21;22)(q12;q12) and EWSR1-ETV1; t(7;22)(p22;q12) and EWSR1-E1AF; t(17;22)(q12;q12) – variants EWSR1 translocation found in 5% of Ewing’s tumor family
  - PAX3-FKHR; t(2;13) (q35;q14) – alveolar rhabdomyosarcoma
  - PAX7-FKHR; t(1;13)(p36;q14) – alveolar rhabdomyosarcoma
  - EWSR1-ATF1; t(12;22)(q13;q12) – clear cell sarcoma/malignant melanoma of soft parts
  - EWSR1-WT1; t(11;22)(p13;q12) – desmoplastic small round cell tumor
  - EWSR1-CHN; t(9;22)(q22;q12) – myxoid chondrosarcoma
  - ASPL-TFE3 – alveolar soft part sarcoma
- Histologic grade and size – most important prognostic factors in adult tumors

Click here for table of Common Cytogenetic Changes in Sarcomas

Indications for Ordering

Tests generally appear in the order most useful for common clinical situations
Click on number for test-specific information in the ARUP Laboratory Test Directory

Test Name and Number	Recommended Use	Limitations
Chromosome Analysis, FISH-Interphase 0092615 Method: Fluorescence in situ Hybridization	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	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
Chromosome Analysis, Solid Tumor 0097778 Method: Giemsa-Band Analysis	Detect recurrent chromosome abnormalities in tumor biopsy consistent with the diagnosis of a sarcoma	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)
CHOP Gene Rearrangement by FISH 0049378 Method: Fluorescence in situ Hybridization	Diagnosis of liposarcoma in paraffin-embedded tissue
Ewing Sarcoma by RT-PCR 0051220 Method: Reverse Transcription Polymerase Chain Reaction/Fluorescence Monitoring	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
EWSR1 Break Apart Rearrangement by FISH 0049335 Method: Fluorescence in situ Hybridization	Differential diagnosis of small cell neoplasms in paraffin-embedded tissue Diagnose members of the Ewing family of neoplasms
SYT-SSX t(X;18) Translocations by RT-PCR 0040114 Method: Reverse Transcription Polymerase Chain Reaction/Fluorescence Monitoring	Diagnose synovial sarcoma
Immunohistochemistry Stain Offering arup005 Method: Immunohistochemistry	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

Cited References

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

General References

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

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

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

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

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

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

References from the ARUP Institute for Clinical and Experimental Pathology®

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. (Link to PubMed)

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. (Link to PubMed)

Reviewed by

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: March 2008