Pathology updates and diagnostic approaches to haemophagocytic lymphohistiocytosis

Abstract

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.

A Malignant Mimicker: Features of Kikuchi-Fujimoto Disease in the Pediatric Population

“…While hemophagocytosis has been reported in cases of KFD, it is also associated with infections, autoimmune diseases, and malignant entities including lymphoma. 4,6,38 Additionally, while only a few of the KFD lymph nodes in our series had flow cytometry performed, the findings included increased T: B cell ratios and decreased CD4:CD8 ratios compared to published normal ratios. 21,22 Though these findings are notable, they are non-specific as increased T:B cell ratios can be seen in T-cell lymphomas, Hodgkin lymphomas, some B-cell lymphomas, and reactive conditions.…”

A case of hemophagocytic lymphohistiocytosis after BNT162b2 COVID-19 (Comirnaty®) vaccination

“…As patients with HLH are frequently critically ill, achieving an accurate and rapid diagnosis is optimal for the best patient outcomes. [14] In the present case, the patient's age should be considered. The "normal" ratio of CD4:CD8 cells becomes much higher in older age groups, due to a significant decrease in CD8 T cells.…”

“…As patients with HLH are frequently critically ill, achieving an accurate and rapid diagnosis is optimal for the best patient outcomes. [ 14 ]…”

Neonatal familial hemophagocytic lymphohistiocytosis diagnosed with ultrarapid whole‐genome sequencing

“…Clinical and laboratory criteria include fever, organomegaly, cytopenias, hypertriglyceridemia, hemophagocytosis, hyperferritinemia, low/absent NK-cell activity, elevated soluble CD25/IL-2 receptor, and/or elevated aspartate aminotransferase. 4,5 Alternatively, gene testing consistent with an inherited cause of HLH (e.g., perforin variant) is diagnostic for fHLH. [4][5][6] Standard targeted gene testing, whole-exome and wholegenome sequencing commonly take weeks to result, precluding timely diagnosis in patients where a diagnosis is urgent.…”