Sarcoma

Sarcomas are a group of uncommon malignant neoplasms occurring in both bone and soft tissue with a wide range of histologic types and prognoses. Keys to treatment and prognosis are age of patient, and location, size, and histologic type of tumor.

  • Diagnosis
  • Background
  • Lab Tests
  • References
  • Related Topics
  • Videos

Indications for Testing

  • Biopsy of tumor suspicious for sarcoma

Laboratory Testing

  • Initial testing – complete blood count (CBC), lactate dehydrogenase (LDH), alkaline phosphatase

Histology

  • Histology of some sarcomas may be similar to that of benign neoplasms, making diagnostic distinction difficult
  • Molecular markers
    • May aid in histologic diagnosis by identification of mutations, amplifications, and translocations
  • FISH, MDM2 – amplification is useful to distinguish well-differentiated liposarcoma from lipomas
    • Important due to difference in risk of recurrence and progression of a well-differentiated liposarcoma from a benign lipoma
  • DDIT3 fusion (formerly CHOP) – found in myxoid/round cell tumors; absent in histologically similar lipoblastomas, which have a benign prognosis

Imaging Studies

  • Plain film x-ray, CT, and MRI to assess tumor location and extent
  • Bone scintigraphy, chest x-ray, and CT scans – for general staging

Prognosis

  • Histologic grade and size – most important prognostic factors in adult tumors
  • Alkaline phosphatase and LDH may be useful in prognosis 

Epidemiology

  • Incidence
    • ~1% of adult malignancies
    • ~15% of pediatric malignancies
  • Age – mean is 50s; varies with type of sarcoma
    • 15% in children <15 years
    • 40% in adults >55 years
  • Sex –  M>F, 1.5:1, in Ewing and osteosarcoma

Classification

  • Tumors are classified by their histology – refer to table in Diagnosis section

Risk Factors

Pathophysiology

  • Mesodermal derivation from musculoskeletal tissues such as connective tissue, lymphatic vessels, smooth and skeletal muscle, fat, 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 pain, tenderness, or mechanical symptoms due to entrapment, pressure, or traction
  • Bony tumors
    • Pain and swelling of the affected area
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.

MDM2 Gene Amplification by FISH 2003016
Method: Fluorescence in situ Hybridization

Limitations 

Results may be compromised if the recommended fixation procedures have not been followed

Test cannot be used to assess dedifferentiation of liposarcomas

DDIT3 (CHOP) (12q13) Gene Rearrangement by FISH 2007223
Method: Fluorescence in situ Hybridization

Limitations 

Results may be compromised if the recommended fixation procedures have not been followed

Cannot be used to assess dedifferentiation of liposarcomas

FOXO1 (FKHR) (13q14) Gene Rearrangement by FISH 2001497
Method: Fluorescence in situ Hybridization

Limitations 

Results may be compromised if the recommended fixation procedures have not been followed

This test will not identify the specific translocation partner

EWSR1 (22q12) Gene Rearrangement by FISH 2007225
Method: Fluorescence in situ Hybridization

Limitations 

Results may be compromised if the recommended fixation procedures have not been followed

Does not identify specific translocation partner

SS18 (SYT) (18q11) Gene Rearrangement by FISH 2007222
Method: Fluorescence in situ Hybridization

Limitations 

Testing using tissue fixed in alcohol-based or nonformalin fixatives has not been validated using this method

SS18 fusion partners are not detected

Chromosome FISH, Interphase 2002298
Method: Fluorescence in situ Hybridization

Chromosome Analysis, Solid Tumor 2002296
Method: Giemsa Band

Anaplastic Lymphoma Kinase 1 (ALK-1) by Immunohistochemistry 2003439
Method: Immunohistochemistry

CD21 (Dendritic Cell) by Immunohistochemistry 2003535
Method: Immunohistochemistry

CD34, QBEnd/10 by Immunohistochemistry 2003556
Method: Immunohistochemistry

CD56 (NCAM) by Immunohistochemistry 2003589
Method: Immunohistochemistry

Ewing Sarcoma (O13) by Immunohistochemistry 2004055
Method: Immunohistochemistry

CD117 (c-Kit) by Immunohistochemistry 2003806
Method: Immunohistochemistry

CDK4 by Immunohistochemistry 2005534
Method: Immunohistochemistry

Desmin by Immunohistochemistry 2003863
Method: Immunohistochemistry

DOG1 by Immunohistochemistry 2010168
Method: Immunohistochemistry

Epithelial Membrane Antigen (EMA) by Immunohistochemistry 2003872
Method: Immunohistochemistry

Friend Leukemia Integration-1 (Fli-1) by Immunohistochemistry (Temporary Referral as of 10/09/17) 2003887
Method: Immunohistochemistry

INI1 (BAF47) by Immunohistochemistry 2003448
Method: Immunohistochemistry

MDM2 by Immunohistochemistry 2005848
Method: Immunohistochemistry

Muscle-Specific Actin (MSA) by Immunohistochemistry 2004011
Method: Immunohistochemistry

Myogenin (Myf4) by Immunohistochemistry 2004017
Method: Immunohistochemistry

Myoglobin by Immunohistochemistry 2004031
Method: Immunohistochemistry

Myosin by Immunohistochemistry 2004034
Method: Immunohistochemistry

Smooth Muscle Actin (SMA) by Immunohistochemistry 2004130
Method: Immunohistochemistry

STAT6 by Immunohistochemistry 2013251
Method: Immunohistochemistry

TFE3 by Immunohistochemistry 2010688
Method: Immunohistochemistry

Vimentin by Immunohistochemistry 2004181
Method: Immunohistochemistry

Wilms Tumor (WT-1), N-terminus by Immunohistochemistry 2004184
Method: Immunohistochemistry

Guidelines

ESMO/European Sarcoma Network Working Group. Bone sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014; 25 Suppl 3: iii113-23. PubMed

NCCN Clinical Practice Guidelines in Oncology, Bone Cancer. National Comprehensive Cancer Network. Fort Washington, PA [Accessed: Apr 2017]

NCCN Clinical Practice Guidelines in Oncology, Soft Tissue Sarcomas, Version 2.2017. National Comprehensive Cancer Network. Fort Washington, PA [Accessed: Jun 2017]

Protocol for the Examination of Specimens from Patients with Tumors of Soft Tissue. Based on AJCC/UICC TNM, 7th ed. Protocol web posting date: Oct 2013. College of American Pathologists (CAP). Northfield, IL [Revised: Oct 2013; Accessed: Apr 2017]

General References

Bovée JV, Hogendoorn PC. Molecular pathology of sarcomas: concepts and clinical implications. Virchows Arch. 2010; 456(2): 193-9. PubMed

Ceyssens S, Stroobants S. Sarcoma. Methods Mol Biol. 2011; 727: 191-203. PubMed

Cheah AL, Billings SD. The role of molecular testing in the diagnosis of cutaneous soft tissue tumors. Semin Cutan Med Surg. 2012; 31(4): 221-33. PubMed

Choi EK, Gardner JM, Lucas DR, McHugh JB, Patel RM. Ewing sarcoma. Semin Diagn Pathol. 2014; 31(1): 39-47. PubMed

Demicco EG. Sarcoma diagnosis in the age of molecular pathology. Adv Anat Pathol. 2013; 20(4): 264-74. PubMed

Fritchie KJ, Goldblum JR, Tubbs RR, Sun Y, Carver P, Billings SD, Rubin BP. The expanded histologic spectrum of myxoid liposarcoma with an emphasis on newly described patterns: implications for diagnosis on small biopsy specimens. Am J Clin Pathol. 2012; 137(2): 229-39. PubMed

Guillou L, Aurias A. Soft tissue sarcomas with complex genomic profiles. Virchows Arch. 2010; 456(2): 201-17. PubMed

Jain S, Xu R, Prieto VG, Lee P. Molecular classification of soft tissue sarcomas and its clinical applications. Int J Clin Exp Pathol. 2010; 3(4): 416-28. PubMed

Loeb DM, Thornton K, Shokek O. Pediatric soft tissue sarcomas. Surg Clin North Am. 2008; 88(3): 615-27, vii. PubMed

Merchant MS, Mackall CL. Current approach to pediatric soft tissue sarcomas. Oncologist. 2009; 14(11): 1139-53. PubMed

Ordóñez JL, Osuna D, García-Domínguez DJ, Amaral AT, Otero-Motta AP, Mackintosh C, Sevillano MV, Barbado MV, Hernández T, de Alava E. The clinical relevance of molecular genetics in soft tissue sarcomas. Adv Anat Pathol. 2010; 17(3): 162-81. PubMed

Osuna D, de Alava E. Molecular pathology of sarcomas. Rev Recent Clin Trials. 2009; 4(1): 12-26. PubMed

Puls F, Niblett AJ, Mangham C. Molecular pathology of bone tumours: diagnostic implications. Histopathology. 2014; 64(4): 461-76. PubMed

Szuhai K, Cleton-Jansen A, Hogendoorn PC, Bovée JV. Molecular pathology and its diagnostic use in bone tumors. Cancer Genet. 2012; 205(5): 193-204. PubMed

Weaver J, Downs-Kelly E, Goldblum JR, Turner S, Kulkarni S, Tubbs RR, Rubin BP, Skacel M. Fluorescence in situ hybridization for MDM2 gene amplification as a diagnostic tool in lipomatous neoplasms. Mod Pathol. 2008; 21(8): 943-9. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Collins BT, Janney CG, Ong M, Cortese C. Fine needle aspiration biopsy of monophasic spindle synovial sarcoma of lung with fluorescence in situ hybridization identification of t(x;18) translocation: a case report. Acta Cytol. 2009; 53(1): 105-8. PubMed

Hall BJ, Grossmann AH, Webber NP, Ward RA, Tripp SR, Rosenthal HG, Florell SR, Randall L, Cockerell CJ, Layfield LJ, Liu T. Atypical intradermal smooth muscle neoplasms (formerly cutaneous leiomyosarcomas): case series, immunohistochemical profile and review of the literature. Appl Immunohistochem Mol Morphol. 2013; 21(2): 132-8. PubMed

Joyner DE, Wade ML, Szabo A, Bastar J, Coffin CM, Albritton KH, Bernard PS, Randall L. 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): 137-46. PubMed

Kikuchi K, Taniguchi E, Chen HH, Svalina MN, Abraham J, Huang ET, Nishijo K, Davis S, Louden C, Zarzabal LA, Recht O, Bajwa A, Berlow N, Suelves M, Perkins SL, Meltzer PS, Mansoor A, Michalek JE, Chen Y, Rubin BP, Keller C. Rb1 loss modifies but does not initiate alveolar rhabdomyosarcoma. Skelet Muscle. 2013; 3(1): 27. 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): 633-40. PubMed

Swensen JJ, Keyser J, Coffin CM, Biegel JA, Viskochil DH, Williams MS. Familial occurrence of schwannomas and malignant rhabdoid tumour associated with a duplication in SMARCB1. J Med Genet. 2009; 46(1): 68-72. PubMed

Wallander ML, Tripp S, Layfield LJ. MDM2 amplification in malignant peripheral nerve sheath tumors correlates with p53 protein expression. Arch Pathol Lab Med. 2012; 136(1): 95-9. PubMed

Willmore-Payne C, Holden J, Turner KC, Proia A, Layfield LJ. Translocations and amplifications of chromosome 12 in liposarcoma demonstrated by the LSI CHOP breakapart rearrangement probe. Arch Pathol Lab Med. 2008; 132(6): 952-7. PubMed

Medical Reviewers

Content Reviewed: 
May 2017

Last Update: October 2017