Paraneoplastic Syndrome of Angiomatoid Fibrous Histiocytoma May Be Caused by EWSR1-CREB1 Fusion-induced Excessive Interleukin-6 Production.

We describe a 7-year-old girl with angiomatoid fibrous histiocytoma (AFH) presenting severe inflammatory symptoms. The cytokine/chemokine profile of serum samples before and after surgery demonstrated that interleukin (IL)-6 had decreased by the greatest percentage. The AFH cells were immunopathologically positive for IL-6 and Tyr705-phosphorylation of signal transducer and activator of transcription 3. The EWSR1-CREB1 fusion gene detected in the tumor leads to continuous activation of CREB1 and IL-6 production, because the promoter region of IL-6 has a CREB binding site. Thus, IL-6 plays pivotal roles in both paraneoplastic syndrome and the oncogenesis of AFH.