Tsutsumi Y, Tang X, Yamada T
Department of Pathology, Tokai University School of Medicine, Isehara, Japan.
Pathol Int. 1997 Jun;47(6):384-92. doi: 10.1111/j.1440-1827.1997.tb04512.x.
A 27-year-old male suffered from Epstein-Barr virus (EBV)-related liver dysfunction with persistent hypogammaglobulinemia. IgG titers to EBV antigens were significantly high, while other hepatitis markers were negative. Liver biopsy disclosed active intralobular inflammation. Two years later, he manifested persistent fever, leukopenia, effusions and hypoproteinemia, and his general condition worsened progressively. The peripheral blood small lymphocytes predominantly expressed natural killer (NK)-like phenotypes (CD2+, CD7+, CD16+, CD56+). Hepatosplenomegaly and marked elevation of serum lactic dehydrogenase were observed. He died of respiratory failure at the age of 29. At autopsy, the liver (2190 g), spleen (860 g), small bowel and mesenteric lymph nodes showed massive infiltration of large atypical lymphoid cells in close association with hemophagocytic histiocytes. Involvement was mildly noted also in the bone marrow, lungs, gall-bladder and kidneys. The atypical cells belonged to CD30+ activated NK-type cells expressing CD2, cytoplasmic CD3 epsilon, CD7, CD45RO, CD56, HLA-DR and HLA-DQ. T cell receptors (TCR), surface CD3, CD4, CD5 and CD8 were not expressed. Epstein-Barr virus-related small nuclear RNA (EBER1) and Epstein-Barr virus-associated nuclear antigen 1 were detected in the nuclei of a significant number of atypical cells, while EBV-related latent membrane protein-1 was negative. EBER1 was also identified in the nuclei of non-neoplastic small lymphocytes at both biopsy and autopsy. Monoclonal integration of the EBV genome into the lymphoma cells was shown by Southern blot analysis. Clonal rearrangement of TCR was undetectable. Roles of chronic active EBV infection in the development of NK cell-type malignancy resembling malignant histiocytosis are discussed.
一名27岁男性患有与EB病毒（EBV）相关的肝功能障碍，并伴有持续性低丙种球蛋白血症。其针对EBV抗原的IgG滴度显著升高，而其他肝炎标志物均为阴性。肝脏活检显示小叶内有活动性炎症。两年后，他出现持续发热、白细胞减少、积液和低蛋白血症，全身状况逐渐恶化。外周血小淋巴细胞主要表达自然杀伤（NK）样表型（CD2 +、CD7 +、CD16 +、CD56 +）。观察到肝脾肿大和血清乳酸脱氢酶显著升高。他于29岁时死于呼吸衰竭。尸检发现，肝脏（2190克）、脾脏（860克）、小肠和肠系膜淋巴结有大量非典型大淋巴细胞浸润，并与噬血细胞组织细胞密切相关。骨髓、肺、胆囊和肾脏也有轻度受累。这些非典型细胞属于CD30 +活化的NK型细胞，表达CD2、细胞质CD3 ε、CD7、CD45RO、CD56、HLA - DR和HLA - DQ。未表达T细胞受体（TCR）、表面CD3、CD4、CD5和CD8。在大量非典型细胞细胞核中检测到EB病毒相关的小核RNA（EBER1）和EB病毒相关核抗原1，而EB病毒相关的潜伏膜蛋白-1为阴性。在活检和尸检时，非肿瘤性小淋巴细胞细胞核中也发现了EBER1。Southern印迹分析显示EBV基因组单克隆整合到淋巴瘤细胞中。未检测到TCR的克隆重排。本文讨论了慢性活动性EBV感染在类似恶性组织细胞增多症的NK细胞型恶性肿瘤发生中的作用。
