A 52-year-old female presented with recurrent fever for more than 1 month, with a highest temperature of 38.8 C and chills. The patient experienced numbness in her left mandible and slight pain in her left teeth. The blood routine examination was normal, C-reactive protein (CRP) was 7.33 mg/L, erythrocyte sedimentation rate (ESR) was 42 mm/h, rheumatoid factor was 5.7 IU/ml, anti-o was 89 IU/ml, anti-nuclear antibody, alpha work, Epstein Barr virus, cytomegalovirus DNA, tumor biomarkers were negative. The head (including the mandible region), chest, and abdomen CT showed no active lesions, and echocardiography showed no abnormality. Prior to hospitalization, the patient had a full-body positron emission tomography (PET) scan performed, which revealed an elevated glucose metabolism in the left alveolar branch of the mandible (standardized uptake value (SUV) max = 5.87) (Figure 1). In addition, multiple small nodules were seen in both lungs and exudative changes in the lower lobes of both lungs and splenomegaly were observed. These findings were also confirmed by chest, abdomen, and pelvis enhanced CT. As a result, microbial infection was primarily suspected. Following 4 weeks of antibacterial and antiviral treatment, the patient still had recurrent fever, which was accompanied by perspiration. The blood routine showed the red blood cell count was 3.10*1012/L, hemoglobin was 86 g/L, neutrophil was 1.77*109/L, lymphocyte was 0.71*109/L, CRP was 16.6 mg/L.
Urine routine examination showed that urine occult blood was weakly positive. Stool routine, blood transfusion routine, blood culture, urine culture, humoral immunity, Widal test, Ana antibody spectrum, antineutrophil cytoplasmic antibody, G test, and EBV-DNA were negative. GM test (0.59) and T-spot.TB test were positive. The biochemical examination showed normal liver and kidney function, albumin 26.7 g/L, ESR 46 mm/h, coagulation function showed D-Dimer was 0.73 mg/L, and prothrombin time was 15.30 s. Tumor biomarker test showed ferritin was 363.36 ng/ml, and serum immunofixation electrophoresis was negative. Ultrasound examination showed no obvious abnormalities of superficial lymph nodes, esophagus, and heart. However, abdominal ultrasound showed substantial echo at the lower pole of spleen, and accessory spleen was considered.
The patient was first administered with ticarcillin and moxifloxacin. Nine days after treatment, the fever was still present that peaked at 38.6 C. The blood routine and biochemical examination showed no apparent changes. The serum protein electrophoresis and free light chain quantitative were negative. The antibiotics were then escalated to linezolid combined with sulperazon and tinidazole. Three days later, the patient's symptoms did not improve, and thus antibiotics were withdrawn.
Due to little effect of antibiotic treatment, the patient's peripheral blood was collected for mNGS. No pathogen was detected, suggesting a likelihood of non-infectious disease. Meanwhile, the chromosomal copy number analysis showed significant alterations (both duplications and deletions) in chromosomes 1, 5, 6, 11, and 14, which indicated the presence of malignant tumor DNA (Figure 2). The same CNV analysis was repeated using buccal swab that showed no abnormalities, suggesting the CNVs were not due to inherited diseases.
The patient underwent bone marrow biopsy. The morphological examination showed that the percentage of erythroid cells was slightly higher, and iron staining showed that iron utilization was impaired. Hemophagocytes were sporadically seen in the bone marrow. A biopsy of the left mandible was taken, and the immunohistochemical results showed cells positive for CD20, CD79a, Bcl-2, CD5 and c-myc, and Ki-67 value-added index was 90% (Figure 3). In addition, CD10, kappa, lambda, CD138, CD38, CD3, Desmin, MyoD1, Myogenin, CD99, CK, Syn, EMA, CyclinD1, Bcl-6, MUM1, CD30 and Sox11 were negative. The pathological findings suggested that the tumor was malignant B-cell lymphoma (diffuse large B-cell type). The patient was diagnosed with DLBCL and transferred to the Hematology department for immunochemotherapy [rituximab 600 mg d1, cyclophosphamide 1.1 g d2, doxorubicin 40 mg d2, vindesine 4 mg d2, and prednisone 15 mg d1-5 (R-CHOP)]. Five cycles of R-CHOP were administered and another full-body PET-CT was performed, which showed a decline of glucose metabolism in the left mandible region (Supplementary Figure 1). Adjuvant radiation therapy was initiated following the conclusion of chemotherapy and a total of 15 sessions were performed, after which the patient was discharged. During the most recent follow up visit, the patient had no fever, no cough, no abdominal pain, normal diet, and sleep.