Leiomyosarcoma (LMS) is a rare, aggressive mesenchymal tumor with smooth muscle differentiation. LMS is one of the most common histologic subtypes of soft tissue sarcoma; it most frequently occurs in the extremities, retroperitoneum, or uterus. LMS often demonstrates aggressive tumor biology, with a higher risk of developing distant metastatic disease than most sarcoma histologic types. The prognosis is poor, particularly in patients with uterine disease, and there is a need for the development of more effective therapies. Genetically, LMS is karyotypically complex and characterized by a low tumor mutational burden, with frequent alterations in TP53, RB1, PTEN, and DNA damage response pathways that may contribute to resistance against immune-checkpoint blockade monotherapy. The LMS immune microenvironment is highly infiltrated with tumor-associated macrophages and tumor-infiltrating lymphocytes, which may represent promising biomarkers. This review provides an overview of the clinical and pathologic behavior of both soft tissue and uterine LMS and summarizes the genomic and immune characteristics of these tumors and how they may provide opportunities for the development of biomarker-based immune therapies.

The incidence of melanoma in the United States has been increasing over the past several decades. Prognosis largely depends on disease stage, with 5-year melanoma-specific survival ranging from as high as 99% in patients with stage I disease to less than 10% for some patients with stage IV (distant metastatic) disease. Fortunately, in the last 5–10 years, there have been remarkable treatment advances for patients with high-risk resectable melanoma, including approval of targeted and immune checkpoint blockade therapies. In addition, results of recent clinical trials have confirmed the importance of sentinel lymph node biopsy and continue to refine the approach to regional lymph node basin management. Lastly, the melanoma staging system was revised in the eighth edition AJCC Cancer Staging Manual, which was implemented on January 1, 2018. Here we discuss these changes and the clinicopathological features that confer high risk for locoregional and distant disease relapse and poor survival. Implications regarding the management of melanoma in the metastatic and adjuvant settings are discussed, as are future directions for neoadjuvant therapies.