To investigate the clinical manifestations and diagnosis of Epstein-Barr virus (EBV)-associated pulmonary lymphomatoid granulomatosis (PLG) complicated with hemophagocytic syndrome (HPS).

We retrospectively analyzed the clinical features, laboratory findings, and treatment course of a patient with EBV-associated PLG and HPS, along with a literature review.

A 66-year-old female presented with fever, cough, and cutaneous nodular ecchymosis. The comprehensive examination revealed multiple nodules in both lungs, mediastinal lymphadenopathy, and splenomegaly; blood routine test: white blood cell count 2.15×10⁹/L, hemoglobin 77 g/L, platelet count 67×10⁹/L; C-reactive protein (CRP) 24.98 mg/L, erythrocyte sedimentation rate 35mm/1 h, ferritin>2 000.00μg/L, interleukin-2 receptor 7 500.00 U/ml, Epstein-Barr virus quantification positive, hepatitis B surface antigen, hepatitis B e antibody, and hepatitis B core antibody positive; bronchoalveolar lavage fluid next-generation sequencing(NGS) indicated Epstein-Barr virus positivity; bone marrow aspiration showed decreased platelet count and a bone marrow picture. Lung tissue biopsy immunohistochemistry (IHC) shows CD20(+ ) and Ki-67(+ ). Special stains: PAS (-) and PASM (-). In situ hybridization: EBER (+ ). The final pathological diagnosis suggests lymphomatoid granulomatosis cannot be excluded. The final diagnosis included HPS, PLG, EBV infection, chronic hepatitis B, and pulmonary infection. Initial treatment with anti-infectives, anti-inflammatory agents, and antivirals led to symptomatic improvement. However, the patient experienced recurrent pulmonary infections post-discharge. Ten months after onset, she was readmitted for fever and cough, and repeat lung biopsy confirmed B-cell lymphoma, prompting referral to hematology.

This report describes a rare case of EBV-associated PLG progressing to B-cell lymphoma with concurrent HPS. The findings aim to enhance clinicians′awareness of this disease entity.