Abstract
: Sarcomas are rare mesenchymal malignancies that demonstrate great clinical and biological heterogeneity. A variety of sarcomas develop in the context of well-defined heritable cancer predisposition syndromes, associations that are often overlooked, given the rarity and diversity of sarcomas and the equivalent relative infrequency of cancer genetic syndromes. This review describes in detail selected heritable cancer predisposition syndromes that are known to be associated with sarcomas. Beyond the molecular and clinical features that define each syndrome, disparities in clinical presentation, natural history, and treatment of syndrome-associated compared with otherwise histologically identical sporadic sarcomas will be described. The clinical approach to selected sarcoma subsets with a view to identifying possible associations with these syndromes will then be described. Although the treatment of the majority of sarcomas will not differ significantly between sporadic cases and those associated with predisposition syndromes, knowledge of features such as unique anatomic sites of affliction or excess toxicities with particular cytotoxic therapies can facilitate alterations in therapeutic strategies to maximize efficacy and minimize toxicity. In addition, recognition of cancer genetic predisposition syndrome will allow patients and their relatives to undertake appropriate genetic counseling and testing, as well as screening, surveillance, and interventional measures, as needed. Situating sarcomas within the genetic endowment of particular patients-specifically that which confers a higher risk of malignancy-will enable clinicians to better manage the patient as a whole, complementing the great efforts currently routinely undertaken to genomically characterize somatic tumor changes with a view to achieving the dream of personalized medicine. IMPLICATIONS FOR PRACTICE: Sarcomas are uncommon malignancies that often occur sporadically but can also arise in the setting of a recognized heritable cancer predisposition syndrome. Identification of such associations when present can facilitate refinement and optimization of treatment strategies for the sarcoma so as to minimize toxicity and maximize efficacy. Discerning genetic predisposition can also facilitate institution of genetic counseling, as well as screening or surveillance schema for both the patient and his or her relatives, if required. Vigilance for these syndromes has the potential to significantly enhance the quality and comprehensiveness of sarcoma clinical management.