Lymph Nodes With Increased IgG4-positive Plasma Cells and Patterns Suspicious for IgG4-related Disease Can Lymph Nodes Be the Only Site of Disease?

Lymphadenopathy with increased immunoglobulin (Ig) G4(+) plasma cells can be a nonspecific finding or a manifestation of immunoglobulin G4-related disease (IgG4-RD). It remains unclear whether there are characteristic pathologic features of IgG4-RD involving lymph nodes, or if IgG4-RD lymphadenopathy can occur without other manifestations of IgG4-RD. In this study, we assessed 55 lymph node biopsy specimens (44 men and 11 women with a mean age of 55 y) with increased IgG4(+) plasma cells that had 1 of the 6 well-described pathologic patterns. We also correlated these findings with IgG4 serum levels and followed these patients for 7 to 108 months (mean, 34.9 mo) for the occurrence of extranodal IgG4-RD. We further compared lymphadenopathy in patients who developed other manifestations of IgG4-RD (RD+, n=20, 36%) versus those who did not (RD-, n=35, 64%). We found that there were only minor significant differences between 2 groups, including frequency of receiving treatment (RD+, 90% vs. RD-, 60%, P=0.021) and higher serum levels of C-reactive protein (>8 mg/L, RD+, 53% vs. RD-, 13%, P=0.007). Other differences were either borderline or not significant, including mean age (RD+, 59.8 y vs. RD-, 51.9 y, P=0.097), male-to-female ratio (RD+, 16:4 vs. RD-, 28:7, P=1), constitutional symptoms (RD+, 25% vs. RD-, 9%, P=0.096), multiple enlarged lymph nodes (RD+, 45% vs. RD-, 26%, P=0.143), good response to therapy (RD+, 94% vs. RD-, 94%, P=1); higher serum IgG4 levels (>280 mg/dL, RD+, 75% vs. RD-, 51%, P=0.086), anemia (RD+, 45% vs. RD-, 43%, P=0.877), leukopenia (RD+, 0% vs. RD-, 3%, P=0.446), thrombocytopenia (RD+, 10% vs. RD-, 6%, P=0.556), positivity for antinuclear antibody (RD+, 24% vs. RD-, 29%, P=0.688), elevated serum levels of lactate dehydrogenase (>225 U/L, RD+, 0% vs. RD-, 20%, P=0.064), elevated serum IgE level (>100 IU/mL, RD+, 75% vs. RD-, 92%, P=0.238), and hypergammaglobulinemia (RD+, 90% vs. RD-, 86%, P=0.754). There were also no differences in morphologic patterns (P=0.466), IgG4(+) cell location (P=0.104), eosinophil counts (RD+, 10.3 +/- 11.3 vs. RD-, 13.4 +/- 17.5, P=0.496), Epstein-Barr virus positivity (RD+, 35% vs. RD-, 60%, P=0.074), and Epstein-Barr virus-positive cell location (P=0.351). Our findings suggest that there are minimal differences between stringently defined IgG4-RD lymphadenopathy with versus without other manifestations of IgG4-RD. These findings also suggest the existence of IgG4-RD lymphadenopathy as the sole presentation of IgG4-RD.