Ströbel P, Nanan R, Gattenlöhner S, Müller-Deubert S, Müller-Hermelink H K, Kreth H W, Marx A
Institute of Pathology, University of Würzburg, Germany.
Am J Surg Pathol. 1999 Jul;23(7):829-37. doi: 10.1097/00000478-199907000-00012.
The FAS (CD95/APO-1) receptor and its ligand play an important role in the initiation of apoptosis under many physiologic conditions. Loss of function mutations of the FAS gene have been described in lpr mice and in humans with autoimmune phenomena, recurrent lymphadenopathies, and hepatosplenomegaly. This syndrome is now called autoimmune lymphoproliferative syndrome type I (ALPS I). Recently, patients with similar clinical symptoms due to a functional FAS deficiency without FAS gene mutations have been distinguished. This disease has been termed autoimmune lymphoproliferative syndrome type II (ALPS II) or autoimmune lymphoproliferative disease (ALD). This report is the first description of the lymph node pathology and immunohistochemistry in a patient with ALPS II. After recurrent bacterial infections, a 4-year-old child developed cervical giant lymphadenopathy suggesting lymphoma. Lymph node histology resembled the findings in Epstein Barr virus-associated posttransplant atypical lymphoproliferations. Confluent sheets of immunoblasts, however, showed a monoclonal expression of IgG/lambda and a monoclonal rearrangement of the JH chain. The same clone was also present in the peripheral blood. Although high-grade lymphoma could not be excluded, the patient's parents insisted on the patient's leaving the hospital with only antibiotic treatment. Surprisingly, the giant lymphadenopathy completely resolved within 7 weeks, and the clone was no longer detectable in the peripheral blood. Twelve months later the patient was still free from lymphoma and was doing well. Retrospectively, transient monoclonal B-cell populations could be identified in an archival frozen blood sample taken when the patient was 3 years old. Increased FAS-independent spontaneous apoptosis was a feature of the patient's lymphocytes and could be the molecular basis for self-elimination of B-cell clones. We conclude that the diagnosis of a FAS-FAS-L deficiency should be considered in children with an otherwise unexplained atypical lymphoproliferation and that a diagnosis of lymphoma in patients with functional FAS deficiency should be made with considerable reservation.
FAS（CD95/APO-1）受体及其配体在许多生理条件下的细胞凋亡起始过程中发挥重要作用。FAS基因功能丧失性突变已在lpr小鼠以及患有自身免疫现象、复发性淋巴结病和肝脾肿大的人类中被描述。这种综合征现在被称为I型自身免疫性淋巴增殖综合征（ALPS I）。最近，已鉴别出由于功能性FAS缺陷但无FAS基因突变而出现类似临床症状的患者。这种疾病被称为II型自身免疫性淋巴增殖综合征（ALPS II）或自身免疫性淋巴增殖病（ALD）。本报告首次描述了一名ALPS II患者的淋巴结病理学及免疫组织化学情况。在反复细菌感染后，一名4岁儿童出现颈部巨大淋巴结病，提示淋巴瘤。淋巴结组织学类似于爱泼斯坦-巴尔病毒相关的移植后非典型淋巴增殖的表现。然而，免疫母细胞的融合片显示IgG/λ单克隆表达以及JH链单克隆重排。外周血中也存在相同克隆。尽管不能排除高级别淋巴瘤，但患者父母坚持让患者仅接受抗生素治疗后出院。令人惊讶的是，巨大淋巴结病在7周内完全消退，外周血中不再可检测到该克隆。12个月后，患者仍无淋巴瘤且情况良好。回顾性分析发现，在患者3岁时采集的存档冷冻血样中可识别出短暂的单克隆B细胞群体。FAS非依赖性自发凋亡增加是患者淋巴细胞的一个特征，可能是B细胞克隆自我消除的分子基础。我们得出结论，对于有不明原因非典型淋巴增殖的儿童应考虑FAS - FAS - L缺陷的诊断，对于功能性FAS缺陷患者的淋巴瘤诊断应持相当谨慎的态度。
