Pathol Int. 2024 Jul 29.
Naohiro Makise,
Jason Lin,
Hajime Kageyama,
Naoki Takeda,
Mariko Oikawa,
Takahiro Sugiyama,
Hidetada Kawana,
Akinobu Araki,
Hideyuki Kinoshita,
Hiroto Kamoda,
Yoko Hagiwara,
Akihiko Yoshida,
Tsukasa Yonemoto,
Masahito Kawazu,
Makiko Itami.
Myxoid liposarcoma (MLPS) is a rare sarcoma, typically arising in deep soft tissues during the fourth to fifth decades of life. Histologically, MLPS is composed of uniform oval cells within a background of myxoid stroma and chicken-wire capillaries. Genetically, MLPS is characterized by the FUS/EWSR1::DDIT3 fusion gene, which generally results from balanced interchromosomal translocation and is detectable via DDIT3 break-apart fluorescence in situ hybridization (FISH). Here, we report an unusual intra-articular MLPS case, negative for DDIT3 break-apart FISH but positive for EWSR1::DDIT3. An 18-year-old female was referred to our hospital complaining of an intra-articular mass in the right knee joint. Histologically, the tumor was mainly composed of mature adipocytes, brown fat-like cells, and lipoblasts. Nanopore sequencing detected DNA rearrangements between EWSR1 and DDIT3 and clustered complex rearrangements involving multiple chromosomes, suggesting chromoplexy. Methylation classification using random forest, t-distributed stochastic neighbor embedding, and unsupervised hierarchical clustering correctly classified the tumor as MLPS. The copy number was almost flat. The TERT promoter C-124T was also detected. This report highlights, for the first time, the potential value of a fast and low-cost nanopore sequencer for diagnosing sarcomas.
Keywords: adaptive sampling; chromoplexy; methylation; myxoid liposarcoma; nanopore