Pathology updates and diagnostic approaches to haemophagocytic lymphohistiocytosis

Haemophagocytic lymphohistiocytosis (HLH) is a complex, often under-recognised hyperinflammatory immune dysregulation syndrome arising in a diverse range of clinical scenarios and conditions. The accurate and timely diagnosis of HLH is crucial for patient survival, and usually requires a high level of clinical suspicion. The histological corollary to clinical HLH-haemophagocytosis-is neither necessary nor sufficient for the diagnosis of HLH, as it may be seen in a variety of reactive conditions and may be absent in true HLH. Nevertheless, the finding of haemophagocytosis in specific clinical situations should prompt consideration of HLH and further testing to exclude the condition. Although haemophagocytosis is traditionally described in bone marrow, identification of it in other tissues, including lymphoid, splenic, liver or neural tissue, can contribute importantly to the overall recognition of HLH. In this review we discuss the underlying pathophysiology and aetiologies of HLH, and the morphological aspects of haemophagocytosis and its associated histological findings in different tissues, and give a brief overview of diagnostic criteria and clinical evaluation.