Abstract
Reactive and clonal proliferations of histiocytes (macrophages/dendritic cells) represent a broad spectrum of disorders, which can affect virtually any organ of the body. The clinical spectrum ranges from benign, localized and self-limiting manifestations to severe multi-system disease. Hemophagocytic lymphohistiocytosis (HLH) is a frequently life-threatening, systemic hyperinflammatory process triggered by massive cytokine release by activated, reactive macrophages. Familial and secondary forms of HLH are discerned. Histiocytoses are clonal inflammatory myeloid disorders characterized by proliferations of mature histiocytes/macrophages and dendritic cells with recurrent kinase-activating mutations which result in constitutive activation of the ERK signaling pathway. Although traditionally subclassified according to the phenotype of the lesional cells, the clonal cells can show significant plasticity, and the occurrence of mixed histiocytoses is increasingly recognized. This is in part due to their derivation from a myeloid progenitor cell and explains the frequent association with clonal hematopoiesis or overt myeloid neoplasms in adults. At the joint Workshop of the Chinese Society of Hematopathology, the European Association for Haematopathology and the Society for Hematopathology on histiocytic/dendritic cell proliferations, neoplasms, and their mimics in Hefei, China, April 2024, in sessions 1 and 2 a total of 8 cases of HLH, 9 cases of reactive histiocytic proliferations and 40 cases of histiocytoses were submitted and reviewed by the panel. The latter included cases of LCH, indeterminate cell histiocytosis, Erdheim Chester disease, juvenile xanthogranuloma, Rosai Dorfman disease, multicentric reticulohistiocytosis, ALK-positive histiocytosis, and mixed histiocytoses. The present report summarizes important findings and open questions arising from discussing the workshop cases.