Not All Leiomyosarcomas Are the Same: How to Best Classify LMS

Leiomyosarcoma arises from smooth muscle and represents one of the most common soft tissue sarcomas. Despite aggressive multimodality care, over half of the patients will ultimately develop metastatic and incurable disease with a median survival of 12-18 months. At present, there is no standard system to classify leiomyosarcoma, which itself is a heterogeneous disease. Classification by tumor location is the most simplistic approach and is most frequently utilized in clinical practice. Tumor location impacts diagnosis (recognition pre-operatively versus at the time of surgery) as well as treatment (ability to completely resect with clear margins with minimal morbidity). While tumor location can impact prognosis, for example, extremity tumors would generally be considered as lower risk than inferior vena cava tumors, leiomyosarcoma can exhibit a heterogeneous behavior irrespective of tumor location. Specifically, some patients have rapidly progressing disease despite aggressive chemotherapy, while others display a more indolent course even in the metastatic setting. The pathogenic drivers of the heterogeneity observed in tumor behavior are not well understood. As we learn more about the molecular composition of leiomyosarcoma, various classification groups have been proposed as discussed here. Ultimately, it is unlikely that one variable will be adequate for tumor classification, and a combination of location and molecular composition will be necessary to develop appropriate risk stratification nomograms and treatment strategies.