Undifferentiated Pleomorphic Sarcoma of Soft Tissue with Multinucleated Giant Cells with Osteogenic Phenotypes: A Mimicker of Malignant Giant Cell Tumor of Soft Tissue

: This study aimed to summarize the clinicopathological findings and assess the immunophenotypes for undifferen tiated pleomorphic sarcoma of soft tissue with multinucleated giant cells (UPS-ST-MGCs). We retrospectively identified five cases of UPS-ST-MGCs between 2010 and 2020, and evaluate histological and immunohistochemical findings using osteogenic markers, which were receptor activator of nuclear factor-kappa B ligand (RANKL), runt-related transcription factor 2 (RUNX2), and special AT-rich sequence-binding protein 2 (SATB2). Cases were divided into two types, based on the distribution of multinucleated giant cells (MGCs), as diffusely (MGCs diffuse type) or focally scattering (MGCs focal type). One out of five cases was classified as MGCs diffuse type and comprised relatively monotonous proliferation of atyp ical spindle cells widely expressing RANKL, RUNX2, and SATB2. This case showed aggressive clinicopathological features, such as a rapidly growing tumor with a high maximum standardized uptake value, high Ki-67 labeling index, and early postoperative recurrence, which can be called malignant giant cell tumor (GCT-ST). Conversely, the other four cases of the MGCs focal type were focally positive for RANKL, and negative for RUNX2 and STAB2, which appeared to be consistent with conventional features of undifferentiated pleomorphic sarcoma of soft tissue. Our results indicate that malignant GCT-ST can be included in UPS-ST-MGCs. Therefore, it is important to note its aggressive malignant characteristics and osteogenic differentiation. Osteogenic immunohistochemical examinations should be considered for UPS-ST-MGCs to con firm an accurate diagnosis and provide appropriate treatment.