Fever of unknown origin caused by an intracranial mesenchymal tumor with a EWSR1-CREM fusion presenting associated with IL-6/STAT3 signaling

Abstract BackgroundPediatric neoplastic diseases account for about 10% in fever of unknown origin (FUO), and most neoplastic diseases cases are leukemia, lymphoma, and neuroblastoma. Brain tumors are rarely reported as the cause of FUO, although craniopharyngioma, metastatic brain tumor, and Castleman's disease have been reported. We report a case of intracranial mesenchymal tumor (IMTs) with FET-CREB fusion gene, whose had inflammatory phenotype without neurological signs.Case presentationA 10-year-old girl was admitted with 2 months history of intermittent fever and headache, whereas her past history as well as her family history lacked special events. Sepsis work-up showed no pathological organism and empirical antibiotics therapy was not effective. Bone marrow examination showed a negative result. CSF examination showed elevated protein as well as cell counts and head MRI showed a hyper vascular mass lesion with contrast enhancement in the left cerebellar hemisphere. The patient underwent tumor excision, which made the intermittent fever disappear. Pathological examinations resemble those of classic angiomatoid fibrous histiocytoma (AFH) but the morphologic features are distinct from the AFH myxoid variant, then we performed break-apart fluorescence in situ hybridization (FISH) and confirmed the tumor harbored rare EWSR1-CREM fusion gene (the Ewing sarcoma breakpoint region 1 gene (EWSR1), cAMP response element binding (CREB) family gene). Consequently, we diagnose as IMT with EWSR1-CREM fusion. Elevated serum concentration of IL-6 was normalized after tumor resection, which suggested the fever could be caused by tumor-derived IL-6.ConclusionsThis is the first case of IMT with EWSR1-CREM fusion that showed paraneoplastic symptoms associated with the IL-6/STAT3 signaling pathway. Although brain tumors are rarely diagnosed as a responsible disease for FUO, they should be considered as a cause of unknown fever even in the absence of abnormal neurological findings. (285 words)