A 77-year-old woman admitted to a hospital in Chengdu with eight months of recurrent fever met the 2019 EULAR and ACR classification criteria for systemic lupus erythematosus with a score of 13, and was treated for it. Her inflammatory markers never moved on full-dose steroids, flow cytometry found a small monoclonal B-cell population, and splenectomy returned non-germinal-center diffuse large B-cell lymphoma. She died of sudden cardiac arrest six days after the operation.
- Report: He, Zeng, Zeng, Zhao and Wang, General Hospital of Western Theater Command, Chengdu, published in Frontiers in Medicine on August 3, 2026.
- Serology: antinuclear antibody 1:320 in a cytoplasmic granular centromere pattern, positive anti-centromere antibody, lupus anticoagulant ratio 1.24, positive direct Coombs test.
- Missing: anti-Sm and anti-dsDNA antibodies were absent and complements were normal, none of which the classification criteria require.
- Clonal burden: aberrant monoclonal B cells at 0.46% of nucleated cells in bone marrow and 0.79% in peripheral blood.
- Imaging: PET-CT showed mild splenomegaly at about 5.3 cm maximum thickness with diffuse uptake, SUVmax 17.9, and no systemic lymphadenopathy.
- Final diagnosis: primary splenic DLBCL, non-GCB subtype, stage IV, IPI 4 and CNS-IPI 4, high risk.
Eight months of fever before anyone reached the spleen
She arrived on November 11, 2024, after three hospitalizations elsewhere for fevers that had answered antibiotics each time. In the month before this admission the fevers came back at up to 41 degrees Celsius, mostly in the afternoon and evening, with roughly 6 kg of weight loss, anorexia and exertional dyspnea, and physical examination on admission was unremarkable. Her history included more than a decade of hypertension and coronary artery disease found on CT angiography six months earlier, with mild aortic regurgitation on echocardiography.
The admission workup produced hemoglobin of 96 g/L, lymphocytes at 0.63 x 10^9/L, ferritin 581.6 ng/mL, high-sensitivity CRP 133.9 mg/L, interleukin-6 at 62.67 pg/mL and TNF-alpha at 26.17 pg/mL. Abdominal ultrasound showed a spleen of about 4.3 cm thickness with homogeneous echotexture and no focal lesion. Four blood cultures, three sputum cultures and a blood metagenomic sequencing assay all came back negative. On glucocorticoids at 1 mg per kg per day her temperature normalized, and hemoglobin and platelets kept falling while the inflammatory markers stayed up.
The 0.79% that changed the workup
Flow cytometry of bone marrow and peripheral blood found monoclonal B cells with an identical aberrant phenotype in both compartments, 0.46% of nucleated cells in marrow and 0.79% in blood. A population under 1% is easy to dismiss, and here it carried the diagnosis. Peripheral blood detection was no less accurate than the marrow, required no biopsy, and can be repeated, which the authors argue makes it the more practical test in a patient with poor performance status or a platelet count of 42 x 10^9/L. PET-CT then found diffuse splenic hypermetabolism with no mass and no nodes, the rare pattern: splenic nodules are reported in 97% of primary splenic DLBCL, and their absence here is a plausible reason nobody looked at the spleen sooner.
Hemophagocytic lymphohistiocytosis was excluded on the numbers: four HLH-2004 criteria were met, but marrow showed no hemophagocytosis, NK activity, soluble interleukin-2 receptor, triglycerides and fibrinogen were all normal, and repeated HScore calculations came to 96 points. Having excluded infection and solid tumor, the authors write that "the application of Occam's Razor supports a diagnosis of DLBCL mimicking systemic lupus erythematosus."
Red pulp, CD20 and a Ki-67 of 80%
Laparoscopic splenectomy was done on hospital day 20 after multidisciplinary discussion, chosen over ultrasound-guided biopsy because a needle risked a nondiagnostic result and bleeding at that platelet count, and because removing the spleen was potentially therapeutic. Pathology on postoperative day 3 showed neoplastic cells diffusely infiltrating the splenic red pulp, medium to large with vesicular nuclei resembling centroblasts. The panel was positive for CD20, PAX-5, MUM-1, Bcl-2 at 40%, Bcl-6 at 40% and C-Myc at 20%, with a Ki-67 index of 80%, and negative for CD10, CD3, CD4, CD8, CD21, CD23, CD35, MPO and P53, placing it in the non-germinal-center group.
She developed atrial fibrillation and heart failure in the intensive care unit, was extubated on day 5, and arrested and died the day after transfer to hematology. The bedside monitor recorded ventricular standstill. The family declined an autopsy, and the authors say so directly, writing that the absence of pathological confirmation means their reconstruction of the arrest "remains speculative and reliant on clinical evidence alone."
Why This Matters to the APO|APE Reader
An ANA of 1:320, a positive Coombs test and a lupus anticoagulant ratio of 1.24 did not make lymphoma less likely in this woman. The authors cite series putting antinuclear antibody positivity at 30.9% of non-Hodgkin lymphoma cases, a quarter of those at titers of 1:320 or higher, and one 39-patient study of treatment-naive patients in which 77% were ANA positive and 86.6% had a lupus anticoagulant. A rheumatology referral carrying fever, cytopenias and that serology is therefore a hematopathology question until proven otherwise, and the trigger for asking it here was not the antibody panel but a steroid course that fixed the temperature and left the CRP alone.
