Good prognosis of adult hemophagocytic lymphohistiocytosis associated with the germline HAVCR2 mutation

•Hepatitis A virus-cellular receptor 2 (HAVCR2) mutation can be detected in hemophagocytic lymphohistiocytosis (HLH), which is associated with good prognosis.•Detection of HAVCR2 mutation should be done, especially in idiopathic HLH.•HAVCR2 mutation–associated HLH may respond well to immunosuppressive agents. Hemophagocytic lymphohistiocytosis (HLH) in adults may be idiopathic or secondary to various conditions. Recent studies identified germline hepatitis A virus-cellular receptor 2 (HAVCR2) mutations in subcutaneous panniculitis-like T-cell lymphoma (SPTCL) with HLH. The roles of this mutation in HLH, especially in idiopathic group, have never been explored. Of the 65 HLH cases, we detected germline HAVCR2Y82C mutations in nine (13.8%) cases (five SPTCL and four idiopathic HLH). Other causes of HLH were hematologic malignancies excluding SPTCL (32.3%), idiopathic HLH without HAVCR2 mutation (29.2%), infections (15.3%), and autoimmune diseases (9.2%). Germline HAVCR2 mutation was significantly associated with less anemia and better survival. This defines a distinct subgroup of HLH.