Occult Diffuse Neoplasm in the Lungs: Intravascular Large B-Cell Lymphoma

BackgroundIntrathoracic involvement with lymphomas is common and manifests lymphadenopathy as well as a wide spectrum of imaging abnormalities in the lungs. Intravascular large B-cell lymphoma (IVLBCL) is a rare extranodal subtype of large B-cell lymphoma that typically involves small blood vessels and is difficult to detect.MethodsUsing a computer-assisted search, we identified patients with histopathologically proven IVLBCL in the lungs at Mayo Clinic from 2001 through 2018. Medical records, imaging studies, and pathologic specimens were reviewed.ResultsA total of 5 patients were diagnosed with a median age at diagnosis of 68 years (range, 44-73); 4 patients were male. The diagnosis of IVLBCL was achieved by surgical lung biopsy in 3 and at autopsy in 2. At presentation, all 5 patients had dyspnea and systemic symptoms including fever, fatigue, night sweats, and/or weight loss. Chest radiography and computed tomography (CT) failed to demonstrate the diffuse infiltrative process; positron emission tomography (PET) scan performed in 2 patients did not show fluorodeoxyglucose (FDG) uptake in the lungs. Pulmonary function tests obtained in 3 patients showed reduced diffusing capacity in all; transthoracic echocardiography yielded evidence of pulmonary hypertension in 2 of 4 patients. All 3 patients diagnosed antemortem underwent chemotherapy with 1 patient remaining alive at 4 years after diagnosis.ConclusionsIVLBCL is difficult to diagnose given variable and nonspecific clinical presentations. Microvascular disease processes such as IVLBCL should be kept in mind in cases of undiagnosed progressive dyspnea accompanied by systemic symptoms even when imaging studies are unrevealing.     

Systemic Lupus Erythematosus and Related Diseases

NZB (H-2^d) mice are well known for the production of IgM autoantibodies to ssDNA. However, an FI cross between NZB and either NZW or SWR mice is required to produce IgG nephritogenic antibodies to dsDNA and glomerulonephritis. The contribution of parental class II loci in the hybrid mice is clearly important to the development of anti-dsDNA antibodies, In contrast, NZB mice congenic with the la^bm12 mutation develop IgG autoantibodies to dsDNA despite being homozygous for Ia. As a part of our effort to examine the mechanisms of disease development in NZB.H-2^bm12 mice, we have generated a panel of monoclonal antibodies against nucleic acids. A subgroup of these antibodies exhibited strong electrostatic interaction with nucleic acids as evidenced by inhibition of their binding by a moderate increase in ionic strength. Interestingly, the effect of salt was either all or none; e.g., antibodies were either markedly inhibited or virtually unaffected. The importance of this ionic interaction was highlighted by analysis of DNA binding of antibodies from serum and nephritic kidneys of NZB.H-2^bm12 mice. Antibodies specific for ssDNA, which are common in NZB mice and not associated with nephritic lupus, are largely unaffected by salt. However, serum and kidney eluted IgG antibodies specific for dsDNA were markedly inhibited by salt. We postulate that B cell clones whose antibodies exhibit electrostatic interaction with DNA are preferentially expanded during the course of lupus in NZB.H-2^bm12 mice and that such antibodies contribute significantly to glomerulonephritis.