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Detection of disease‐defining gene fusions in sarcoma has led to refining their classification, as well as to discover several new entities. The advent of anchored multiplex PCR/targeted RNA next‐generation sequencing (AMP/RNA‐seq) has allowed for the development of scalable platforms that can simultaneously examine multiple fusion transcripts without prior knowledge of specific fusion partners.In this study, we assess the utility of a FusionPlex sarcoma panel analysis by AMP/RNA‐seq to detect disease‐defining gene fusions in 16 cases of undifferentiated round cell sarcoma in which prior diagnostic work‐up could not establish a definitive diagnosis. The clinical and pathologic features of these cases were correlated with the molecular findings. Validation of the method using 41 cases with known diagnoses showed analytic sensitivity and specificity of 98% and 100%, respectively. Of the 16 cases of undifferentiated round cell sarcoma, gene fusions were found in 9 (56%). These included three cases with CIC‐DUX4 fusion, two cases with BCOR‐CCNB3, and four single cases with CIC‐NUTM2A, HEY1‐NCOA2, EWSR1‐NFATC2, and NUT‐MGA1 fusions. Overall, despite some degree of morphologic overlap, all fusion‐positive cases had distinct morphologic features, which can be helpful for their histologic classification. We also describe the first adult case of MGA‐NUTM1 fusion sarcoma, as well as cartilaginous differentiation in a BCOR‐CCNB3 fusion sarcoma, which has not been previously reported. Our study demonstrated that FusionPlex sarcoma panel analysis, in the appropriate morphologic context, is a sensitive and precise ancillary method for the detection of disease‐defining gene fusions in undifferentiated round cell sarcomas, aiding in their definitive classification.

BackgroundChondrosarcoma is one of the most common malignant bone tumors in adults. Conventional chondrosarcoma represents around 85% of all chondrosarcomas and is notoriously difficult to treat with chemotherapy.Case presentationWe describe a 67-year-old man with metastatic conventional chondrosarcoma who was treated with nivolumab. Treatment was discontinued after restaging showed increased tumor burden, which later proved to be pseudoprogression. The patient restarted nivolumab and continues to have a near complete response.ConclusionConventional chondrosarcoma may be sensitive to checkpoint inhibitors. Further, this case demonstrates clearly the phenomenon of pseudo-progression in this disease, a factor that must be considered in the design of clinical trials and clinical care. This case supports additional study of immunomodulatory agents in this deadly disease.