Abstract：
The study was designed to review the demographic, clinical, and pathologic characteristics of follicular helper T cells (TFH)-derived nodal PTCL in India including angioimmunoblastic T-cell lymphoma (AITL), peripheral T-cell lymphoma (PTCL) with follicular helper T cell phenotype (P-TFH), and follicular T-cell lymphoma with additional immunohistochemistry (IHC) and RHOAG17V mutational analysis, as well as their impact on survival. This retrospective study included 88 cases of PTCL that were reclassified using IHC for TFH markers (PD1, ICOS, BCL6, and CD10) and dendritic-meshwork markers (CD21, CD23). Cases of TFH cell origin were evaluated for RHOAG17V mutation using Sanger sequencing and amplification-refractory mutation system-polymerase chain reaction (PCR) (validated using cloning and quantitative PCR) with detailed clinicopathologic correlation. Extensive re-evaluation with added IHC panel resulted in a total of 19 cases being reclassified, and the final subtypes were AITL (37 cases, 42%), PTCL-not otherwise specified (44, 50%), P-TFH (6, 7%), and follicular T-cell lymphoma (1, 1%). The presence of at least 2 TFH markers (>20% immunopositivity) determined the TFH origin. AITL patients tended to be male and showed increased presence of B-symptoms and hepatosplenomegaly. Histomorphology revealed that 92% of AITL cases had pattern 3 involvement. Sanger sequencing with conventional PCR did not yield any mutation, while RHOAG17V was detected by amplification-refractory mutation system-PCR in AITL (51%, P =0.027) and P-TFH (17%), which was validated with cloning followed by sequencing. Cases of RHOAG17V-mutant AITL had a worse Eastern Cooperative Oncology Group performance status initially but fared better in terms of overall outcome ( P =0.029). Although not specific for AITL, RHOAG17V mutation shows an association with diagnosis and requires sensitive methods for detection due to low-tumor burden. The mutant status of AITL could have prognostic implications and translational relevance.
摘要：
这项研究旨在审查人口统计学，临床,以及印度滤泡辅助性T细胞（TFH）衍生的淋巴结PTCL的病理学特征，包括血管免疫母细胞性T细胞淋巴瘤（AITL），外周T细胞淋巴瘤（PTCL）与滤泡辅助性T细胞表型（P-TFH），和滤泡性T细胞淋巴瘤进行额外的免疫组织化学（IHC）和RHOAG17V突变分析，以及它们对生存的影响。这项回顾性研究包括88例PTCL，使用IHC对TFH标记进行重新分类（PD1，ICOS，BCL6和CD10）和树突网状标记（CD21，CD23）。使用Sanger测序和扩增-难治性突变系统-聚合酶链反应（PCR）（使用克隆和定量PCR验证）评估了TFH细胞来源的病例的RHOAG17V突变，并具有详细的临床病理相关性。通过添加IHC小组进行广泛的重新评估，总共有19例被重新分类，最后的亚型是AITL(37例，42%），PTCL-未另作规定(44,50%),P-TFH（6，7%），滤泡性T细胞淋巴瘤（1%）。至少2种TFH标志物(>20%免疫阳性)的存在确定了TFH起源。AITL患者倾向于男性，并且表现出B症状和肝脾肿大的增加。组织形态学显示，92％的AITL病例涉及模式3。传统PCR的Sanger测序没有产生任何突变，而在AITL中通过扩增-难治性突变系统-PCR检测到RHOAG17V(51%，P=0.027)和P-TFH(17%)，通过克隆然后测序进行验证。RHOAG17V突变型AITL的病例最初东部合作肿瘤学组的表现较差，但总体预后较好（P=0.029）。虽然不是针对AITL的，RHOAG17V突变显示与诊断相关，并且由于肿瘤负荷低，需要灵敏的检测方法。AITL的突变状态可能具有预后意义和翻译相关性。
