ArticleInnere Medizin (Heidelberg, Germany)2025
[Positron emission tomography-negative hemophagocytic lymphohistiocytosis in two patients with aggressive B-cell lymphoma].
Article in Innere Medizin (Heidelberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
introductionHemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome caused by various diseases, with lymphoma being one of the most important triggers. Positron emission tomography/computed tomography (PET/CT) is considered an important tool in establishing the etiology of HLH. CASE DESCRIPTIONS: We present two cases of HLH caused by diffuse large B‑cell lymphoma (DLBCL) in which 18F-fluorodeoxyglucose (18F-FDG) PET/CT showed no abnormal FDG uptake. Case 1: A 72-year-old man presented with intermittent fever and B symptoms. A comprehensive workup, including PET/CT, were inconclusive. HLH was diagnosed with 6 of 8 HLH criteria, a 99% probability in the H‑score, and a positive Optimized HLH Inflammatory (OHI) index. After performing bone marrow aspiration and skin biopsy, HLH-directed therapy with etoposide and dexamethasone was initiated. The patient died unexpectedly. Postmortem histopathologic examination revealed DLBCL in the bone marrow, and additional infiltration of the peripancreatic adipose tissue, and myocardium, and intravascular manifestations in the liver. Case 2: A 58-year-old woman presented with a history of fever and elevated inflammatory markers. Comprehensive diagnostic workup including PET/CT revealed no abnormal findings. The diagnosis of HLH was made (7 of 8 HLH criteria, H‑score > 99%, positive OHI index). Bone marrow and liver aspiration revealed hemophagocytosis without evidence of lymphoma. A biopsy of macroscopically normal skin finally revealed intravascular DLBCL. Treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) and high-dose methotrexate resulted in complete remission.
conclusionHLH is a rare complication of DLBCL. PET/CT may show no evidence of underlying lymphoma. Extensive biopsies, including macroscopically unremarkable structures, may lead to the diagnosis of lymphoma. Persistent fever should be a reason to investigate possible HLH. Once the diagnosis of HLH is established, a rapid work-up with early bone marrow aspiration, skin biopsy and possibly other structures is key for diagnosis.
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