Extranodal Histiocytic Sarcoma

Histiocytic sarcoma (HS) is an extremely rare hematopoietic neoplasm derived from the monocytic/histiocytic/dendritic cell lineage. While sporadic cases of primary soft-tissue HS have been reported, its clinicopathological and molecular features remain incompletely characterized. This study investigates the clinicopathological features of two cases of soft-tissue HS and reviews the relevant literature. Microscopically, the tumor cells exhibited a diffuse growth pattern, with morphologic features varying from spindle-shaped sarcomatoid to epithelioid subtypes. Occasional bizarre cells were observed. Immunohistochemically, the tumor cells were positive for CD68, Lysozyme, S100, CD4, and CD163, but negative for a comprehensive panel of markers, including those for myeloid, Langerhans, follicular dendritic, lymphoid (T, B, NK), epithelial, vascular endothelial, and melanocytic lineages. Next-generation sequencing (NGS) revealed distinct mutational profiles: Case 1 harbored mutations in BRAF V600E, BRAF V600E, CDKN2A, and CIITA, while Case 2 exhibited mutations in CREBBP, INPP4B, RB1, PTEN, KMT2D, MSH2, and TP53, which may contribute to tumorigenesis and progression. Despite therapeutic efforts, both patients died within 6 and 9 months of follow-up, respectively. In conclusion, HS is a diagnostically challenging malignancy due to its rarity and morphological overlap with other soft tissue tumors. Immunohistochemical markers (CD68, Lysozyme, S100, CD4, CD163) are essential for diagnosis. Currently, no standard treatment exists. This study characterizes the molecular profiles of two extranodal HS cases, contributing to the understanding of their clinicopathological and genetic features.