Pathology updates and diagnostic approaches to hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a complex, often under-recognized 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 histologic corollary to clinical HLH - hemophagocytosis - 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 hemophagocytosis in specific clinical situations should prompt consideration of HLH and further testing to exclude the condition. While traditionally described in bone marrow, identification of hemophagocytosis in other tissues, including lymphoid, splenic, liver, or neural tissue, can be an important asset to the overall recognition of HLH. In this review we discuss the underlying pathophysiology and etiologies of HLH, morphologic aspects of hemophagocytosis and its associated histologic findings in different tissues, and give a brief overview of diagnostic criteria and clinical evaluation.