Case Report: A diagnostic pitfall of diffuse large B-cell lymphoma with hemophagocytic lymphohistiocytosis and atypical tongue pain: the critical role of PET/CT-guided repeat bone marrow biopsy

Background: Diffuse large B-cell lymphoma (DLBCL) associated hemophagocytic lymphohistiocytosis (HLH) represents a rare but life-threatening clinical entity characterized by diagnostic complexity and high mortality. Early manifestations are often nonspecific, and initial bone marrow examination may be falsely negative due to patchy infiltration, leading to delayed recognition of the underlying malignancy. Case presentation: We report a 68-year-old woman who presented with prolonged fever and atypical tongue pain, initially suspected to be caused by pulmonary infection. Despite broad-spectrum antimicrobial therapy, fever persisted and progressive cytopenias, hyperferritinemia, hypofibrinogenemia, and elevated soluble interleukin-2 receptor levels fulfilled the HLH-2004 diagnostic criteria. Although corticosteroid therapy achieved transient clinical improvement, the initial bone marrow biopsy revealed no malignancy. Following relapse of fever after steroid withdrawal, positron emission tomography-computed tomography (PET/CT) demonstrated diffuse hypermetabolic activity in the spleen and bone marrow. PET/CT-guided repeat bone marrow biopsy subsequently confirmed non-germinal center B-cell-type DLBCL with marrow involvement. The patient achieved clinical remission after initiation of immunochemotherapy. Conclusion: This case highlights HLH as a major diagnostic blind spot in occult B-cell lymphoma and underscores the limitations of single-site bone marrow biopsy. Persistent atypical extranodal symptoms such as tongue pain, together with steroid-responsive HLH, should prompt early functional imaging. PET/CT-guided repeat tissue sampling plays a pivotal role in establishing timely diagnosis and guiding therapeutic decisions in critically ill patients.