Evolution of Recurrent Myxofibrosarcoma of the Thoracic Wall at Single-Cell Resolution: A Case Report

Myxofibrosarcoma (MFS) is a common yet understudied type of soft tissue sarcoma. It is characterized by diverse cellular morphology, unusual growth patterns, and a propensity for local tumor recurrences. A 76-year-old patient underwent multiple surgical removals of MFS recurrences of the thoracic cavity and surrounding tissues with the subsequent development of metastases. Single-cell RNA sequencing was used to analyze the earlier (R7) and later (R8) MFS recurrences, with R8 removed less than a year before the detection of metastases in the lungs. The earlier MFS recurrence displays tumor clusters with multiple immunomodulatory markers (DKK1, APP, CD24, GRN) and genes involved in lipid metabolism and cell stress (DDIT3, ABCA1, ABCA10, ATF4, NEU1), combined with an anti-inflammatory TME. The later MFS recurrence shifts to a functionally less diverse phenotype, enriched in fibroblast-typical markers (POSTN, NES, COL1A1/A2), and a pro-inflammatory TME. The proliferative (MKI67, TOP2A, BUB1B) and mRNA splicing and processing (SNRNP70, SRSF2/5/11, RSRP1, LUC7L/7L3, SRRM1/2) tumor clusters are observed in both MFS recurrences, and their signatures match the previous data on primary MFS tumor populations. ScRNA-seq analysis of two subsequent MFS recurrences from one patient show a change from functionally diverse to more uniform ECM remodeling enriched tumor populations, an accompanying shift to the pro-inflammatory TME, and the presence of two common tumor clusters enriched in proliferative and mRNA-processing gene signatures.