Molecular Diagnostics in Bone and Soft Tissue Tumors

Abstract

Molecular diagnostics have greatly advanced our understanding of the pathogenesis of soft tissue and bone neoplasms and have led to the development of numerous useful diagnostic tools. Definitive cytologic diagnosis is now possible for many soft tissue and bone tumors with judicious application of immunohistochemistry and numerous molecular technologies. Immunohistochemistry is primarily used to identify the line of differentiation and protein correlates of underlying molecular alterations and can guide appropriate selection of molecular tests. Currently, the most commonly employed molecular diagnostic approaches are fluorescence in situ hybridization and reverse transcription-polymerase chain reaction. High-throughput molecular techniques (e.g., whole-exome or targeted panel next-generation sequencing) have potential exciting applications for cytology practice, and these platforms can provide useful diagnostic and prognostic information in the diagnosis of soft tissue and bone tumors. While ancillary tests allow for more accurate classification of many soft tissue and bone neoplasms on cytologic material, immunohistochemical and molecular tests always should be interpreted in the context of the clinical, radiologic, and cytomorphologic features, and the cytopathologist must be aware of the pitfalls and limitations of these assays. This chapter reviews the applications of molecular diagnostics, including integration of immunohistochemical markers, in the cytologic diagnosis of soft tissue and bone neoplasms.