Chen Ying-Ren, Yu Shan-Chi, Wang Ren-Ching, Lee Chih-Ling, Song Hsiang-Lin, Medeiros L Jeffrey, Yue Chung-Tai, Chang Kung-Chao
Department of Pathology, National Cheng Kung University Hospital, Dou-Liou Branch, College of Medicine, National Cheng Kung University, Yunlin.
Department of Pathology, National Taiwan University Hospital, College of Medicine, National Taiwan University.
Am J Surg Pathol. 2023 Mar 1;47(3):387-396. doi: 10.1097/PAS.0000000000002007. Epub 2022 Dec 13.
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.
伴有免疫球蛋白（Ig）G4⁺浆细胞增多的淋巴结病可能是一种非特异性表现，或是免疫球蛋白G4相关疾病（IgG4-RD）的一种表现形式。目前尚不清楚IgG4-RD累及淋巴结是否具有特征性病理特征，或者IgG4-RD淋巴结病是否可在无IgG4-RD其他表现的情况下发生。在本研究中，我们评估了55例伴有IgG4⁺浆细胞增多的淋巴结活检标本（44例男性和11例女性，平均年龄55岁），这些标本具有6种已详细描述的病理模式中的1种。我们还将这些发现与IgG4血清水平进行了关联，并对这些患者进行了7至108个月（平均34.9个月）的随访，以观察结外IgG4-RD的发生情况。我们进一步比较了出现IgG4-RD其他表现的患者（RD⁺，n = 20，36%）与未出现其他表现的患者（RD⁻，n = 35，64%）的淋巴结病情况。我们发现两组之间仅有微小的显著差异包，括接受治疗的频率（RD⁺，90% 对RD⁻，60%，P = 0.021）和较高的血清C反应蛋白水平（>8 mg/L，RD⁺，53% 对RD⁻，13%，P = 0.007）。其他差异要么处于临界状态，要么不显著，包括平均年龄（RD⁺，59.8岁对RD⁻，51.9岁），P = 0.097）、男女比例（RD⁺，16:4对RD⁻，28:7，P = 1）、全身症状（RD⁺，25% 对RD⁻，9%，P = 0.096）、多个肿大淋巴结（RD⁺，45% 对RD⁻，26%，P = 0.143）、对治疗的良好反应（RD⁺，94% 对RD⁻，94%，P = 1）；较高的血清IgG4水平（>280 mg/dL，RD⁺，75% 对RD⁻，51%，P = 0.086）、贫血（RD⁺，45% 对RD⁻，43%，P = 0.877）、白细胞减少症（RD⁺，0% 对RD⁻，3%，P = 0.446）、血小板减少症（RD⁺，10% 对RD⁻，6%，P = 0.556）、抗核抗体阳性（RD⁺，24% 对RD⁻，29%，P = 0.688）、血清乳酸脱氢酶水平升高（>225 U/L，RD⁺，0% 对RD⁻，20%，P = 0.064）、血清IgE水平升高（>100 IU/mL，RD⁺，75% 对RD⁻，92%，P = 0.238）和高球蛋白血症（RD⁺，90% 对RD⁻，86%，P = 0.754）。在形态学模式（P = 0.466）、IgG4⁺细胞位置（P = 0.104）、嗜酸性粒细胞计数（RD⁺，10.3±11.3对RD⁻，13.4±17.5，P = 0.496）、爱泼斯坦-巴尔病毒阳性（RD⁺，35% 对RD⁻，60%，P = 0.074）以及爱泼斯坦-巴尔病毒阳性细胞位置（P = 0.351）方面也没有差异。我们的研究结果表明，严格定义的伴有或不伴有IgG4-RD其他表现的IgG4-RD淋巴结病之间差异极小。这些结果还提示存在IgG4-RD淋巴结病作为IgG4-RD的唯一表现形式。
