tetano
Editor, Senior Moderator
Front Immunol
. 2026 Jul 8:17:1879628.
doi: 10.3389/fimmu.2026.1879628. eCollection 2026.
Case Report: Hemophagocytic lymphohistiocytosis after SARS-CoV-2 infection revealing clinically diagnosed stage IVB diffuse large B-cell lymphoma in quiescent adult-onset Still's disease
Ting Long[SUP] #[/SUP][SUP] 1 [/SUP], Juanjuan Song[SUP] #[/SUP][SUP] 2 [/SUP], Sheng-Guang Li[SUP] 1 [/SUP]
Affiliations
Background: Adult hemophagocytic lymphohistiocytosis (HLH) may be triggered by infection, malignancy, or systemic inflammatory disease. Attribution is challenging when recent SARS-CoV-2 infection, quiescent adult-onset Still's disease (AOSD), and an occult B-cell clonal disorder coexist.
Case report: A 71-year-old man with AOSD controlled for 14 years on low-dose methotrexate developed persistent fever and fatigue after mild SARS-CoV-2 infection. He subsequently developed cytopenias, hyperferritinemia, markedly elevated lactate dehydrogenase, diffuse FDG-avid lymphadenopathy, hepatosplenomegaly, elevated soluble interleukin-2 receptor, reduced natural killer-cell activity, and bone marrow hemophagocytosis, fulfilling HLH criteria. Broad pathogen evaluation, including blood and bone marrow metagenomic next-generation sequencing, did not identify an alternative infectious trigger. Bone marrow histopathology did not show definite tumor cells; however, flow cytometry identified monoclonal mature B cells, and peripheral-blood smear high-throughput sequencing detected lymphoma-associated mutations including MYD88, CD79B, IGLL5, PRDM1, DTX1, DUSP2, and BTG1. Multidisciplinary consultation favored probable lymphoma-associated HLH with clinically diagnosed stage IVB diffuse large B-cell lymphoma. HLH-directed therapy followed by rituximab-based lymphoma-directed chemotherapy led to transient clinical improvement, but the patient later died from infectious complications.
Conclusion: Mild SARS-CoV-2 infection may act as a co-trigger or unmasking event rather than the sole cause of HLH. Persistent high lactate dehydrogenase and soluble interleukin-2 receptor, diffuse lymphadenopathy, clonal mature B cells, lymphoma-associated mutations, and negative broad pathogen testing should prompt evaluation for occult lymphoma-associated HLH.
Keywords: SARS-CoV-2; adult-onset Still’s disease; case report; diffuse large B-cell lymphoma; hemophagocytic lymphohistiocytosis.
. 2026 Jul 8:17:1879628.
doi: 10.3389/fimmu.2026.1879628. eCollection 2026.
Case Report: Hemophagocytic lymphohistiocytosis after SARS-CoV-2 infection revealing clinically diagnosed stage IVB diffuse large B-cell lymphoma in quiescent adult-onset Still's disease
Ting Long[SUP] #[/SUP][SUP] 1 [/SUP], Juanjuan Song[SUP] #[/SUP][SUP] 2 [/SUP], Sheng-Guang Li[SUP] 1 [/SUP]
Affiliations
- PMID: 42488632
- PMCID: PMC13388594
- DOI: 10.3389/fimmu.2026.1879628
Background: Adult hemophagocytic lymphohistiocytosis (HLH) may be triggered by infection, malignancy, or systemic inflammatory disease. Attribution is challenging when recent SARS-CoV-2 infection, quiescent adult-onset Still's disease (AOSD), and an occult B-cell clonal disorder coexist.
Case report: A 71-year-old man with AOSD controlled for 14 years on low-dose methotrexate developed persistent fever and fatigue after mild SARS-CoV-2 infection. He subsequently developed cytopenias, hyperferritinemia, markedly elevated lactate dehydrogenase, diffuse FDG-avid lymphadenopathy, hepatosplenomegaly, elevated soluble interleukin-2 receptor, reduced natural killer-cell activity, and bone marrow hemophagocytosis, fulfilling HLH criteria. Broad pathogen evaluation, including blood and bone marrow metagenomic next-generation sequencing, did not identify an alternative infectious trigger. Bone marrow histopathology did not show definite tumor cells; however, flow cytometry identified monoclonal mature B cells, and peripheral-blood smear high-throughput sequencing detected lymphoma-associated mutations including MYD88, CD79B, IGLL5, PRDM1, DTX1, DUSP2, and BTG1. Multidisciplinary consultation favored probable lymphoma-associated HLH with clinically diagnosed stage IVB diffuse large B-cell lymphoma. HLH-directed therapy followed by rituximab-based lymphoma-directed chemotherapy led to transient clinical improvement, but the patient later died from infectious complications.
Conclusion: Mild SARS-CoV-2 infection may act as a co-trigger or unmasking event rather than the sole cause of HLH. Persistent high lactate dehydrogenase and soluble interleukin-2 receptor, diffuse lymphadenopathy, clonal mature B cells, lymphoma-associated mutations, and negative broad pathogen testing should prompt evaluation for occult lymphoma-associated HLH.
Keywords: SARS-CoV-2; adult-onset Still’s disease; case report; diffuse large B-cell lymphoma; hemophagocytic lymphohistiocytosis.