NKX3.1 immunohistochemistry and methylome profiling in mesenchymal chondrosarcoma: additional diagnostic value for a well-defined disease?

Mesenchymal chondrosarcoma (MCS) is a rare and highly aggressive tumour of soft tissue and bone that is defined by an underlying and highly specific fusion transcript involving HEY1 and NCOA2. Histologically, the tumours show a biphasic appearance consisting of an undifferentiated blue and round cell component as well as islands of highly differentiated cartilage. Particularly in core needle biopsies, the chondromatous component can be missed and the non-specific morphology and immunophenotype of the round cell component can cause diagnostic challenges. We applied NKX3.1 immunohistochemistry which was recently reported as a highly specific marker as well as methylome and copy number profiling to a set of 45 well characterised MCS cases to evaluate their potential diagnostic value. Methylome profiling revealed a highly distinct cluster for MCS. Notably, the findings were reproducible also when analysing the round cell and cartilaginous component separately. Furthermore, four outliers were identified by methylome profiling for which the diagnosis had to be revised. NKX3.1 immunohistochemistry showed positivity in 36% of tumours, the majority of which was rather focal and weak. Taken together, NKX3.1 expression showed a low sensitivity but a high specificity in our analysis. Methylome profiling on the other hand represents a sensitive, specific and reliable tool to support the diagnosis of MCS, particularly if only the round cell component is obtained in a biopsy and the diagnosis is not suspected. Furthermore, it can aid in confirming the diagnosis in case RNA sequencing for the HEY1::NCOA2 fusion transcript is not available.

Discontinuation of dual antiplatelet therapy and bleeding in intensive care in patients undergoing urgent coronary artery bypass grafting: a retrospective analysis.

OBJECTIVES: Our goal was to evaluate the impact of the discontinuation times of dual antiplatelet therapy with clopidogrel, prasugrel or ticagrelor on postoperative bleeding rates and the use of blood products in patients undergoing isolated urgent coronary artery bypass grafting (CABG). METHODS: We retrospectively analysed 334 patients with acute coronary syndrome undergoing urgent CABG at the University Hospital Basel. A total of 262 patients continued to take dual antiplatelet therapy during the surgery (72 received clopidogrel; 68, prasugrel; and 122, ticagrelor). They were stratified by the discontinuation time of dual antiplatelet therapy (<24 h, 24-48 h, 48-72 h and >72 h). Seventy-two patients taking acetylsalicylic acid (ASA) as monotherapy served as a comparison group. RESULTS: Median postsurgical bleeding rates were significantly higher with ticagrelor if it was discontinued <24 h [1220 ml, interquartile range (IQR) 978-1520 ml; P < 0.001], 24-48 h (1200 ml, IQR 800-1550 ml; P < 0.001) and 48-72 h (1100 ml, IQR 845-1245 ml; P = 0.036) but not if discontinued >72 h (700 ml, IQR 520-825 ml; P = 0.22) and with prasugrel if discontinued <24 h (1320 ml, IQR 900-1950 ml; P < 0.001) but not if discontinued 24-48 h (1050 ml, IQR 638-1438 ml; P = 0.089) or >72 h (750 ml, IQR 488-1040; P = 0.63) compared to ASA monotherapy (800 ml, IQR 593-1043 ml). The postsurgical use of blood products compared to ASA monotherapy (0, IQR 0-2 units) was significantly higher with ticagrelor and prasugrel if discontinued <24 h (2.5 units, IQR 0-6; P < 0.001 and 2 units, IQR 1-6; P < 0.001, respectively). CONCLUSIONS: Discontinuation of ticagrelor and prasugrel for more than 72 h before urgent CABG was not associated with higher bleeding rates compared to treatment with ASA monotherapy. In contrast, discontinuation for less than 24 h was associated with higher use of blood products. For ticagrelor, this study supports evidence and recent guidelines proposing a shorter discontinuation time of 3 days and raises the question of whether the same could be true for prasugrel.