A Distinctive Case of Hemophagocytic Lymphohistiocytosis in Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (CLL) is an indolent malignancy characterized by the accumulation of dysfunctional B-cell lymphocytes. Complications such as hemophagocytic lymphohistiocytosis (HLH) can arise, particularly during disease progression. HLH has been increasingly reported as a complication of CLL, often triggered by factors such as superimposed infections, chemotherapy, Richter transformation, or disease progression. This case explores HLH as an initial presentation of undiagnosed CLL without any identifiable trigger. We present the case of a 65-year-old woman who presented with a high-grade fever, sore throat, and pancytopenia. Despite broad-spectrum antibiotic treatment, her condition deteriorated. Investigations revealed elevated ferritin levels, low natural killer cell activity, and other findings consistent with HLH. Flow cytometry and bone marrow biopsy ultimately confirmed the diagnosis of CLL. HLH is characterized by the hyperactivation of immune cells and is known to be triggered by a variety of factors, including infections and malignancies. In this case, the absence of identifiable triggers raises important questions about the underlying pathophysiology linking HLH with CLL. While previous reports have highlighted HLH as a complication of CLL, typically secondary to infection or treatment, this case is particularly noteworthy due to the unexplained onset of HLH in the absence of such triggers. This case underscores the need for heightened awareness of HLH as a potential manifestation of underlying malignancy, especially in non-septic patients presenting with unexplained fever and pancytopenia. In addition, the simultaneous presentation of normal pressure hydrocephalus emphasizes the complex interplay of inflammatory processes in CLL. Further research is needed to explore the relationship between inflammation and the pathogenesis of CLL.