Hemophagocytic Lymphohistiocytosis As the Initial Presentation of Occult Diffuse Large B-cell Lymphoma: A Diagnostic Challenge.

Hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening hyperinflammatory syndrome characterised by uncontrolled immune activation and cytokine release, resulting in multiorgan dysfunction and high mortality if not recognised and treated promptly. In adults, secondary HLH is frequently triggered by infection, autoimmune disease, or malignancy, with haematological malignancies carrying a particularly poor prognosis. The non-specific nature of its presentation often leads to diagnostic delay, as it can closely mimic sepsis and other inflammatory conditions. We present the case of a 76-year-old man who was admitted with a two-week history of progressive lethargy, exertional dyspnoea, anorexia, and headache after several months of constitutional symptoms. On presentation, he was hypotensive and tachycardic with atrial fibrillation and was initially managed for presumed sepsis with associated haemodynamic compromise. Despite supportive management, his clinical condition and biochemical profile deteriorated, with worsening cytopenias, deranged liver function tests, persistent hyperlactataemia, pyrexia, and escalating inflammatory markers. Further investigation demonstrated marked hyperferritinaemia exceeding 10,000 µg/L, hypertriglyceridaemia, hypofibrinogenaemia, elevated lactate dehydrogenase, and bicytopenia, producing an HScore of 220, which was highly suggestive of secondary HLH. Following multidisciplinary discussion with regional specialists, treatment with high-dose IV methylprednisolone and anakinra was commenced while an urgent search for the underlying trigger continued. Initial imaging failed to identify a clear source of malignancy or infection, and the patient showed only limited improvement with HLH-directed immunomodulatory therapy. Bone marrow biopsy subsequently demonstrated high-grade diffuse large B-cell lymphoma (DLBCL) with marrow involvement, establishing malignancy-associated HLH as the underlying diagnosis. The patient was transferred to a specialist haematology service and commenced on R-mini-CHOP chemotherapy, resulting in rapid clinical recovery and marked improvement in HLH parameters. Subsequent positron emission tomography imaging demonstrated a complete metabolic response after two treatment cycles, with the patient improving from a bedbound state to being independently ambulatory. This case highlights the significant diagnostic challenges associated with adult HLH and emphasises the importance of maintaining a high index of suspicion in patients presenting with unexplained fever, cytopenias, hyperferritinaemia, liver dysfunction, and multiorgan inflammation. It also demonstrates that, while immunosuppressive therapy may provide temporary disease control, successful management of malignancy-associated HLH depends on prompt identification and definitive treatment of the underlying haematological malignancy. Early multidisciplinary collaboration and timely bone marrow examination are critical to improving outcomes in this rapidly progressive and frequently fatal condition.