Morphologic and genetic features of sarcomas : improving diagnosis and exploring biomarkers

Sammanfattning: Sarcomas are malignant tumors of soft tissue and bone origin. They are a family of rare but diverse neoplasms which pose clinical challenges due to their heterogeneous properties. In order to increase our understanding of sarcoma biology, we are continuously reviewing clinical cohorts regarding morphological presentation and underlying genetic changes. This thesis focuses on translational research from improving diagnostics to exploring biomarkers in select sarcoma subtypes. In Paper I we investigated fine needle aspirations of synovial sarcomas (SS) in order to identify common characteristics. Samples from SS displayed similar features such as abundant oval, round or spindle-shaped cells with pericapillary formation and pink background stroma. All tumors also harbored the pathognomonic fusion gene SYT-SSX, which can be detected by sequencing and is recommended to verify a diagnosis of SS. In Paper II we investigated FNAs of clear cell chondrosarcomas (CCCS) in order to identify common characteristics. Samples from CCCS displayed similar features such as abundant clear cells with round nucleus and prominent nuclei, which separated it from its most common differential diagnosis chondroblastoma, a benign tumor. Due to the rarity of CCCS we also conducted a literature review and found that CCCS was more common in patients >25 and chondroblastoma more common in patients <25 years of age. There is however a significant overlap and a clear cutoff age cannot be established. In Paper III we investigated the role of TERT promoter mutation in chondrosarcomas (CS). We found that TERT promoter mutation (C228T) was common in CS and was significantly correlated with higher tumor grade, increased risk of metastasis and tumor-related death, as well as a more aggressive course of disease. We also found that CS undergo branching evolution, as patients can have a wild-type primary tumor and a mutated metastasis or vice versa. As TERT promoter mutation status is easily detected by sequencing it can be useful as a prognostic biomarker. In Paper IV we investigated the expression of PD-L1 in three common sarcoma types: liposarcoma (LS), undifferentiated pleomorphic sarcoma (UPS), and CS. We found that PD-L1 expression was most common in UPS, rare in LS and very rare in CS, but it did not correlate to metastasis or death from disease in any sarcoma subtype.

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