Challenging diagnosis of haemophagocytic lymphohistiocytosis secondary to T-cell/histiocyte-rich large B-cell lymphoma

Haemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening disorder of uncontrolled immune activation by macrophages, cytotoxic T cells and natural killer (NK) cells, marked by severe inflammation. It is often categorised as primary (genetic) or secondary (acquired). Here, a case of a young male with a history of stage IA seminoma in remission, who presented with persistent fevers, night sweats, weight loss and fatigue, is reported. He met ≥5 of 8 HLH-2004 criteria. Initial workup for secondary HLH, including infectious, autoimmune and malignancy, was negative. Bone marrow, sacral bone and splenic biopsies showed lymphohistiocytic infiltrates without malignancy. Genetic testing was unrevealing. With no identified aetiology and declining clinical status, the HLH-94 protocol was initiated. He improved initially, but fevers recurred, suggestive of HLH progression. A repeat positron emission tomography-CT (PET-CT) showed new hepatic hypermetabolic activity, leading to a biopsy diagnosing T-cell/histiocyte-rich large B-cell lymphoma. This case highlights the challenges in identifying the aetiologies of secondary HLH, particularly searching for an occult malignancy and ensuring prompt treatment is initiated.