Challenges in identifying biomarkers for Smooth muscle tumors of uncertain malignant potential (STUMP)

Benign uterine leiomyoma (U.LMA) and malignant uterine leiomyosarcoma (U.LMS), which are both uterine mesenchymal tumors, are distinguished by the number of cells with mitotic activity. However, uterine mesenchymal tumors contain tumor cells with various cell morphologies; therefore, making a diagnosis, including differentiation between benign tumors and malignant tumors, is difficult. For example, uterine smooth muscle tumors of uncertain malignant potential (STUMPs) are a group of uterine mesenchymal tumors for which performing a differential diagnosis is challenging. A standardized classification system for uterine mesenchymal tumors has not yet been established. Furthermore, definitive preoperative imaging techniques or hematological examinations for the potential inclusion of STUMP in the differential diagnosis have not been defined. Several clinical studies showed that there is no correlation between biomarker expression and mitotic rate or tumor recurrence. The current immunohistochemical biomarkers cannot effectively help determine the malignant potential of STUMPs in patients who wish to become pregnant in the future. The establishment of gene expression profiles or detection of pathogenic variants by employing next-generation molecular techniques can aid in disease prediction, diagnosis, treatment, and prognosis. Here, we describe the problems in diagnosing uterine mesenchymal tumors along with the results of the latest clinical studies.