Intravascular Large B-cell Lymphoma Diagnosed by Renal Biopsy Presenting with Nephrotic Syndrome

Intravascular large B-cell lymphoma (IVLBCL) is a rare, aggressive subtype of extranodal diffuse large B-cell lymphoma characterized by selective proliferation of neoplastic lymphoid cells within small vessels. Its features are heterogeneous and nonspecific, often including fever of unknown origin (FUO) and organ dysfunction, leading to delayed diagnosis. We report a case of IVLBCL diagnosed by renal biopsy in a patient presenting with nephrotic syndrome and unexplained fever.

Case Presentation：A 72-year-old man was admitted with persistent fever and hypoxemia despite antibiotic therapy. On arrival, temperature was 38.2℃, BP 150/115 mmHg, HR 100 bpm, and SpO₂ 97% on low-flow oxygen. Physical findings included leg edema and left lung crackles. His past history included hypertension, dyslipidemia, and chronic obstructive pulmonary disease, treated with amlodipine, atorvastatin, indacaterol, and silodosin. He had smoked 30 cigarettes/day for 30 years (20–50 ages) but did not drink alcohol. Family history was unremarkable. Laboratory tests showed creatinine 1.4 mg/dL, albumin 1.9 g/dL, and nephrotic-range proteinuria (UPCR 5.6 g/gCr). Blood counts were normal, autoantibodies negative, and soluble IL-2 receptor markedly elevated (5497 U/mL). Imaging revealed pulmonary infiltrates and systemic edema without masses. Renal biopsy demonstrated large atypical lymphoid cells confined to glomerular capillaries. Immunostaining was positive for CD20/CD45, negative for CD3, consistent with B-cell lineage. Bcl-6 and MUM1 were positive, indicating an activated B-cell phenotype, confirming renal-limited IVLBCL. R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) was initiated, followed by high-dose methotrexate for CNS prophylaxis. Fever resolved, oxygen supplementation was discontinued, and edema improved. Renal function normalized, and proteinuria decreased from UPCR 5.6 to 0.9 g/gCr.

Discussion：IVLBCL is exceedingly rare, with an age-adjusted incidence of 0.095 per 1,000,000 person-years. Clinical presentation varies, and organ-specific manifestations often obscure diagnosis. Renal-limited IVLBCL, as seen in this case, is particularly uncommon. In a multicenter series of 73 renal IVLBCL cases, 26% presented with nephrotic-range proteinuria. In renal IVLBCL, tumor cells fill glomerular and peritubular capillaries, leading to endothelial injury, podocyte effacement, and microvascular occlusion, resulting in heavy proteinuria. Rituximab-based chemotherapy such as R-CHOP is standard and has greatly improved survival. Early recognition and treatment are crucial, as delayed diagnosis leads to poor outcomes. In this case, prompt therapy achieved full renal recovery, suggesting reversibility when treated early.

We report a rare case of IVLBCL diagnosed by renal biopsy in a patient with nephrotic syndrome and FUO. This case emphasizes the importance of considering hematologic malignancy in the differential diagnosis of nephrotic syndrome with unexplained fever, even in the absence of hematologic abnormalities. Early renal biopsy allowed timely R-CHOP chemotherapy and resulted in favorable clinical and renal outcomes.