Clinicopathologic Considerations: How Can We Fine Tune Our Approach to Sarcoma?

Bone and soft tissue sarcomas are an uncommon and sundry group of solid tumors traditionally categorized together according to their presumed mesenchymal differentiation. They are histologically, behaviorally, and genetically diverse, and their pathogenesis is poorly understood. Moreover, treatment options are limited, with surgical resection continuing to provide the only possibility of cure in many cases. However, there has been tremendous progress in the last decade in understanding the behavior and molecular pathogenesis of sarcoma, which may ultimately lead to more effective therapy and prognostication for these rare malignancies. In this article, we address the histologic and molecular classification of sarcomas, with emphasis on the increasing role of molecular diagnostics in both classification and prognostication. In addition, we review recent advances in the understanding of critical cell signaling pathways involved in this group of malignancies, and how this knowledge relates to the potential role of newer targeted therapies in sarcoma treatment. The role and rationale for grading and staging of sarcomas is discussed, as well as more recent advances in the development of prognostic nomograms, based on clinical and histopathologic findings. Finally, we conclude with a discussion of the importance of multidisciplinary care, with integration of histologic, molecular, radiographic, and clinical data in the management of sarcoma.