A 77-year-old man was admitted to the Affiliated Hospital of Nantong University in November 2018 with a >1-month history of repeated fever, with night sweats and weight loss. Laboratory results showed thrombocytopenia and liver function reports showed increased lactate dehydrogenase and decreased albumin levels. A hepatitis B surface antigen test was positive, serum IgG levels were low, peripheral blood EBV-DNA was 2885 viral copies/mL (reference range, 0-1000 viral copies/mL), VCA IgG antibodies showed 170 U/mL (reference range, 0-20 U/mL) and EBNA IgG antibodies were 119U/mL (reference range, 0-5 U/mL). Lymphocyte subset analyses showed decreased lymphocyte, total T lymphocyte, helper T cell, and cytotoxic T cell counts. No obvious abnormality was detected by bone marrow puncture. Positron emission tomography (PET)/computed tomography (CT) showed increased 18F-fluorodeoxyglucose (FDG) uptake in multiple masses, including extensive lymphadenopathy in the neck, chest, abdomen, pelvic cavity, and inguinal region, with evident splenomegaly and nodular lesions, some of which showed slightly higher FDG standardized uptake values (SUVmax; approximately 10, short diameter <2 cm). In addition, an intestinal mass (measuring 5.8x4.5x3.7 cm) revealed a notably higher FDG SUVmax of 20.5. Core needle aspiration cytology of the left axillary nodule performed the unnormal lymph node architecture with a infiltrate of atypical lymphoid proliferation, predominantly composed of medium-sized T cells with a clear cytoplasm, occasional eosinophils, immunoblasts, and proliferation of high endothelial venules. Immunohistochemistry showed these neoplastic T cells were positive for CD3, PD-1, CD10, Bcl-6, CD4, CD8, CD5, CD21 (expansion of the follicular dendritic cell meshwork +), Ki67 (30%+), and negativity for CD56, CD20, CXCL13, and Epstein-Barr-encoded RNA (EBER), with partial loss of CD7. T cell receptor gene rearrangement was positive but no clonal IgH gene rearrangement was detected (Figure 1). The patient was diagnosed with AITL, with a prognostic index for T-cell lymphoma (PIT) score of 3. Before treatment, he suddenly developed severe abdominal pain, and abdominal CT showed gastrointestinal perforation. He therefore underwent emergency surgery, and pathological examination showed an ulcerative mass on the ileum. Immunohistochemical staining revealed that the diffuse infiltration of these abnormal medium-to-large-sized lymphocytes with prominent nucleoli was predominantly positive for Bcl-6, MUM1, CD20, CD21, CD10, EBER (>200/high-power field), and Ki67 (80%+), but negative for CD3, PD-1, CD8, CD4, CD5, CD7, and CXCL13 (Figure 2). He was subsequently diagnosed with EBV-positive DLBCL (stage IV, group B). The International Prognostic Index (IPI) was 4, indicating high risk. The patient had a history of tuberculosis for 40 years and had undergone a left upper lobe resection 7 months prior with postoperative pathology of the lung tissue suggesting carcinoma in situ. Considering his complex illness and inferior performance status, the patient was administered six cycles of R2-miniCHOP (lenalidomide 25 mg by oral administration on days 1-10, rituximab 600 mg on day 0, cyclophosphamide 600 mg on day 1, doxorubicin liposome 20 mg on day 1, vinorelbine 30 mg on day 1, and prednisone 30 mg on days 1-5), with no serious adverse events during treatment. His symptoms subsequently improved, with weight gain. PET/CT scan demonstrated decreased FDG uptake in many parts of the body compared with before treatment (Figure 3). The patient was then treated with lenalidomide (10 mg/day on days 1-21, every 28 days) as maintenance therapy and remained in sustained remission for more than 20 months.