B Cells Unhinged: Concurrent PR3+ ANCA-Associated Vasculitis and Diffuse Large B Cell Lymphoma Treated Effectively

Introduction: We present a case of PR3+ ANCA vasculitis diagnosed simultaneously with diffuse large B-cell lymphoma (DLBCL). Both improved after rituximab and chemotherapy. This appears to be the third case of DLBCL-associated ANCA vasculitis described in the literature. The mechanisms of this association and implications for therapy warrant future investigation. Case Description: 71-year-old man with hypermetabolic lung and left tonsillar masses on outpatient PET-CT presented for fatigue, anorexia, and weight loss. Laboratory testing showed an elevated creatinine of 5.87 mg/dL. Serologic workup revealed an elevated proteinase-3 level of 183. CT chest confirmed a spiculated right upper lobe nodule measuring 3.1 cm with architectural distortion. He received three dialysis treatments and was started on pulse dose steroids. He underwent renal and lung biopsy, showing diffuse necrotizing and crescentic pauci-immune glomerulonephritis (Fig. 1), and pulmonary parenchyma effaced by sheets of large, atypical B-lymphocytes compatible with DLBCL. Two months later, after daily prednisone, 4 doses of weekly rituximab, and 2 cycles of Pola-CHP, his creatinine was 1.31 mg/dL. Repeat PET-CT showed complete resolution of the hypermetabolic left tonsillar mass and near complete resolution of the right upper lobe mass. Discussion: While uncommon, malignancy is diagnosed more frequently in patients with ANCA vasculitis, especially granulomatosis with polyangiitis (GPA). The most common cancers diagnosed include bladder cancer, non-melanoma skin cancer, leukemia, and lymphoma. Association with the latter two may relate to overexpression of PR3 in response to granulocyte colony stimulating factor. The overexpression of PR3 may trigger an immune response that harms normal and malignant tissue. Alternatively, PR3-specific B cell clones may proliferate to become lymphoma. Our patient’s improvement with combination therapy may support a common cause.Fig. 1