2 - Adjuvant Techniques–Immunohistochemistry, Cytogenetics, and Molecular Genetics

Abstract

Soft tissue and bone tumors encompass a vast array of histologically diverse neoplasms, including many that are morphologically undifferentiated or primitive-appearing. This histologic diversity and morphologic ambiguity accounts for the particularly important role of ancillary diagnostic techniques in soft tissue and bone pathology. Increasingly, these techniques are also used to characterize specific molecular alterations that are amenable to targeted anti-tumor therapies. This chapter provides a practical framework for the efficient incorporation of adjuvant diagnostic tools in soft tissue and bone pathology, relying primarily on careful morphological assessment to guide subsequent immunohistochemical, cytogenetic, and molecular studies. In addition to describing the morphology-driven immunohistochemistry panels broadly aimed at determining tumor cytodifferentiation, this chapter discusses the key immunohistochemical markers of many specific diagnostic entities. The most common techniques for the molecular characterization of formalin-fixed paraffin-embedded specimens are also introduced, alongside a summary of the many molecular abnormalities now known to be recurrently identified in soft tissue and bone tumors, including those for which molecularly targeted therapies are currently available. In parallel, many of the most frequently encountered challenges regarding the use and interpretation of these ancillary studies are shared. The result is an integrated approach that aims to empower the practicing pathologist with an understanding of ancillary techniques required to efficiently arrive at an accurate classification of soft tissue and bone tumors.