Molecular Pathology of Soft Tissue and Bone Tumors
This chapter presents cytogenetic and molecular pathology of sarcomas, with emphasis on recurrent abnormalities that are characteristic features of individual cancer types. General concepts concerning biology, pathology, diagnostic techniques, and molecular diagnostic applications of cancers are presented in the beginning of the chapter. The second portion presents each of the major sarcoma types, in alphabetical order, with a specific structure: basic pathology, clinical features, molecular genetic pathology, and molecular diagnosis. Most of the tumors presented herein are soft tissue sarcomas, as few recurrent abnormalities have been established to have biologic and diagnostic significance in bone tumors. In contrast to other diseases and cancers presented in this textbook, sarcomas are more commonly associated with cytogenetic changes, as opposed to molecular changes. Nevertheless, a variety of approaches (e.g., classical cytogenetic analysis, fluorescence in situ hybridization, reverse-transcriptase polymerase chain reaction, immunohistochemistry) are presented, with strengths and weaknesses of each for clinical application in each tumor type, as appropriate.
KeywordsEwing Sarcoma Molecular Diagnostics Chromosomal Variant Endometrial Stromal Sarcoma Basic Pathology
- Antonescu CR, Nafa K, Segal NH, Dal Cin P, Ladanyi M. EWS-CREB1: a recurrent variant fusion in clear cell sarcoma association with gastrointestinal location and absence of melanocytic differentiation. Clin Cancer Res. 2006;12:5356–62.Google Scholar
- Antonescu CR, Zhang L, Chang N, Pawel BR, Travis W, Rosenberg AE, et al. Novel EWSR1-POU5F1 fusion in soft tissue myoepithelial tumors. A molecular analysis of 66 cases, including soft tissue, bone and visceral lesions, showing common involvement of EWSR1 gene rearrangement. Genes Chromosomes Cancer. 2010;49:1114–24.PubMedCrossRefGoogle Scholar
- Atlas of Genetics and Cytogenetics in Oncology and Haematology, http://www.infobiogen.fr/services/chromcancer/index.html. Barr FG, Ladanyi M. Sarcomas. In: Leonard DGB, editor. Diagnostic molecular pathology. Philadelphia: Saunders; 2003, p. 53–76.
- Mariño-Enríquez A, Wang WL, Roy A, Lopez-Terrada D, Lazar AJ, Fletcher CD, et al. Epithelioid inflammatory myofibroblastic sarcoma: an aggressive intra-abdominal variant of inflammatory myofibroblastic tumor with nuclear membrane or perinuclear ALK. Am J Surg Pathol. 2011;35:135–44.PubMedCrossRefGoogle Scholar
- O’Leary TJ, Frisman DM. Soft tissue and bones. In: O’Leary TJ, editor. Advanced diagnostic methods in pathology. Saunders: Philadelphia; 2003. p. 421–58.Google Scholar
- Sumegi J, Streblow R, Frayer RW, Dal Cin P, Rosenberg A, Meloni-Ehrig A, et al. Recurrent (2;2) and (2;8) translocations in rhabdomyosarcoma without the canonical PAX-FOXO1 fuse PAX3 to members of the nuclear receptor transcriptional coactivator (NCOA) family. Genes Chromosomes Cancer. 2010;49:224–36.PubMedGoogle Scholar