Peripheral T-cell Lymphoma With Follicular T-cell Markers
Peripheral T-cell Lymphoma With Follicular T-cell Markers
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DOI：
10.1097/pas.0b013e31817f123e
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发表时间：
2008-12-01
影响因子：
5.6
通讯作者：
Piris, Miguel A.
中科院分区：
文献类型：
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作者：
Maria Rodriguez-Pinilla, Socorro;Atienza, Lidia;Piris, Miguel A.
简介：外周T细胞淋巴瘤（PTCL）在西方国家是少见肿瘤，预后不良。它们可分为间变性大细胞淋巴瘤 (ALCL)、血管免疫母细胞 T 细胞淋巴瘤 (AITL) 或未特指的外周 T 细胞淋巴瘤 (PTCL-U)。最近已证明 AITL 起源于生发中心滤泡辅助 T 细胞 (T-FH)，而其他 PTCL 的正常对应物仍然基本上未知。本研究的目的是确定其他 PTCL 亚群是否也表达 TFH 细胞标记物。 材料和方法：使用一种名为 NAT-105 的新型单克隆抗体，对组织微阵列中 146 个 PTCL 的程序性死亡 1 (PD-1) 表达进行了分析。 PD-1阳性病例不满足AITL的所有标准，在另外12个免疫组化市场的全组织切片中进一步评估，包括TFH细胞标记物CXCL13、CD10和BCL6。还评估了克隆 Ig 和 T 细胞受体重排以及 Epstein-Barr 病毒编码的 RNA 表达。回顾了形态学、临床和随访数据。结果：87 例非 AITL 病例中，25 例 (28.75%) 显示 PD-1 免疫染色。 CXCL13、BCL6 和 CD10 表达分别见于 24/25 (96%)、16/25 (64%) 和 6/25 (24%) 病例。所有病例均表达至少 2 个 T-FH 细胞市场。此外，5 例 4 项标记物均呈阳性。大多数病例（17/25，68%）表现出一些类似 AITL 的特征。在其余的人中，我被认为是早期 AITL，我被诊断为 ALCL 间变性淋巴瘤激酶阴性，其他 6 例 PTCL-U 中的 4 例的形态与淋巴上皮样（伦纳特）淋巴瘤一致。 3 例 AITL 样病例显示 IgH 克隆重排，其中 2 例与 Epstein-Barr 病毒表达相关。我们的系列患者的临床表现与文献中大多数报道的 PTCL 病例没有显着差异：在环磷酰胺、右霉素、长春新碱和基于泼尼松的化疗后中位随访 15 个月后，其中 55% 存活，35% 完全缓解。结论：T-FH 细胞标志物，特别是 PD-1，在未分类为 AITL 的 PTCL 亚群中表达，尽管其中大多数有一些共同点AITL 的形态特征。这表明 AITL 的范围可能比之前想象的更广泛，可能包括淋巴上皮样（伦纳特）淋巴瘤病例。此外，结果表明，PTCLs-U 的一个亚组与 AITL 不同，包括一些称为 ALCL 的病例，也可能源自 T-FH 细胞，尽管它们沿着不同的致病途径发展。
Introduction: Peripheral T-cell lymphomas (PTCLs) in western countries are uncommon tumors with unfavorable prognosis. They may be subclassified as anaplastic large-cell lymphomas (ALCLs), angioimmunoblastic-T-cell lymphomas (AITLs), or unspecified peripheral T-cell lymphomas (PTCLs-U). It has recently been demonstrated that AITLs originate from germinal center follicular helper T cells (T-FH), whereas the normal Counterparts of other PTCLs remain essentially unknown. The aim of this study was to establish whether other PTCL subgroups also express TFH cell markers.Materials and Methods: One hundred forty-six PTCLs were analyzed for programmed death-1 (PD-1) expression in tissue microarrays using a new monoclonal antibody called NAT-105. PD-1-positive cases, which did not fulfill all the criteria for AITL, were further evaluated in whole-tissue sections for another 12 immunohistochemical markets, including the TFH cell markers CXCL13, CD10, and BCL6. Clonal Ig and T-cell receptor rearrangements and Epstein-Barr virus-encoded RNA expression were also evaluated. Morphologic, clinical, and follow-up data were reviewed.Results: Twenty-five Out of 87 non-AITL cases (28.75%) showed PD-1 immunostaining. CXCL13, BCL6, and CD10 expression was found in 24/25 (96%), 16/25 (64%), and 6/25 (24%) cases, respectively. All cases expressed at least 2 T-FH cell markets. Moreover, 5 cases were positive for all 4 markers. Most cases (17/25, 68%) displayed some AITL-like features. Of the remainder, I was considered to be early AITL, I was diagnosed as ALCL-anaplastic lymphoma kinase-negative, and 4 of the other 6 PTCLs-U had morphology consistent with lymphoepithelioid (Lennert's) lymphoma. Three AITL-like cases showed IgH clonal rearrangement, 2 of which were associated with Epstein-Barr virus expression. Our series of patients did not differ significantly in their clinical presentation from most reported PTCL cases in the literature: 55% of them were alive and 35% were in complete remission after a median follow-up of 15 months after cyclophosphamide, dexorubicin, vincristine, and prednisone-based chemotherapy.Conclusions: T-FH cell markers, especially PD-1, were expressed in a subset of PTCLs not classified as AITL, although most of them shared some morphologic features with AITL. This suggests that the spectrum of AITL may be wider than previously thought, possibly including cases of lymphoepithelioid (Lennert's) lymphoma. Additionally, the results suggest that a subgroup of PTCLs-U, distinct from AITL and including some cases denominated as ALCL, may also be derived from T-FH cells, although they develop along a distinct pathogenic pathway.