Hoshida Yoshihiko, Tomita Yasuhiko, Zhiming Dong, Yamauchi Amane, Nakatsuka Shin-Ichi, Kurasono Yoshiko, Arima Yasuhiro, Tsudo Mitsuru, Shintaku Masayuki, Aozasa Katsuyuki
Department of Pathology, Osaka University Medical School, Suita, Osaka, Japan.
Int J Cancer. 2004 Jan 20;108(3):443-9. doi: 10.1002/ijc.11582.
Lymphoproliferative disorders (LPD) occasionally develop in individuals with immune deficiencies such as immunosuppressive conditions and autoimmune diseases (AID). In our study, the clinicopathologic features and virus status were analyzed in 53 cases with LPD developing in rheumatoid arthritis (RA) and other AID. AID in only 4 of 53 patients had been treated with some sort of immunosuppressive therapy, including methotrexate. Median age at the diagnosis of LPD in AID was 60 years old with marked female predominance (M/F = 0.4). The median interval between the onset of AID and LPD development was 45 months, and longer in RA patients than in other AID (p < 0.01). The primary site of lymphoma was nodal in 21 cases and extra-nodal in 24, with clinical Stage I in 17, II in 5, III in 13, and IV in 13. Immunohistochemistry showed that 39 cases were B cell type, 10 were T cell type and 4 were Hodgkin lymphoma (HL). Then majority of B cell cases were diffuse large B cell lymphomas, and 2 were diffuse polymorphic type. EBER-1 in situ hybridization for Epstein-Barr virus (EBV) showed positive signals in tumor cells in 16 of 53 (30.2%) cases. The EBV-positive rate in T cell LPD (70%) was much higher than that in B cell LPD (12.8%) (p < 0.01). All 4 cases of HL were EBV-positive. Immunohistochemistry showed a latency II pattern of EBV infection (LMP-1(+) and EBNA-2(-)). Five-year overall survival rate was 33%. Multivariate analysis showed that only type of AID was an independent factor for survival of patients, i.e., LPD in RA showed the most favorable prognosis. In conclusion, LPD in AID generally shared common features with sporadic LPD except for a much higher EBV-positive rate in T cell LPD.
淋巴增殖性疾病（LPD）偶尔会在免疫缺陷个体中发生，如免疫抑制状态和自身免疫性疾病（AID）。在我们的研究中，分析了53例类风湿关节炎（RA）和其他AID患者发生LPD的临床病理特征和病毒状态。53例患者中只有4例的AID接受过某种免疫抑制治疗，包括甲氨蝶呤。AID患者诊断LPD时的中位年龄为60岁，女性占明显优势（男/女 = 0.4）。AID发病至LPD发生的中位间隔时间为45个月，RA患者的间隔时间长于其他AID患者（p < 0.01）。淋巴瘤的原发部位21例为淋巴结，24例为结外，临床分期I期17例，II期5例，III期13例，IV期13例。免疫组织化学显示39例为B细胞型，10例为T细胞型，4例为霍奇金淋巴瘤（HL）。大多数B细胞病例为弥漫性大B细胞淋巴瘤，2例为弥漫多形型。针对爱泼斯坦-巴尔病毒（EBV）的EBER-1原位杂交显示，53例中有16例（30.2%）肿瘤细胞呈阳性信号。T细胞LPD的EBV阳性率（70%）远高于B细胞LPD（12.8%）（p < 0.01）。所有4例HL均为EBV阳性。免疫组织化学显示EBV感染呈潜伏II型模式（LMP-1(+)和EBNA-2(-)）。5年总生存率为33%。多因素分析显示，只有AID类型是患者生存的独立因素，即RA患者的LPD预后最佳。总之，AID患者的LPD与散发性LPD一般具有共同特征，但T细胞LPD的EBV阳性率要高得多。
