滤泡性淋巴瘤（FL）是一种由生发中心B细胞派生的肿瘤，由至少部分滤泡生长模式组成的中心细胞和中心母细胞组成。t(14;18)易位与经常性遗传改变引起的表观遗传失控已被认定为FL的标志。然而，FL在临床、形态和生物学上是异质的。缺乏t(14;18)染色体改变的FL的存在突显了FL复杂的发病机制，并表明存在其他可能诱发滤泡中心B细胞表型肿瘤的病理发生机制。根据其临床表现，缺乏t(14;18)的FL可以分为三个主要类别：淋巴结型表现、非淋巴结型表现以及主要影响儿童和青少年的表现。最近的研究对t(14;18)阴性FL的遗传变异有所启示。在具有淋巴结型表现的t(14;18)阴性FL组中，与CREBBP和/或TNFRSF14的突变经常同时出现的STAT6突变日益被认定为一种特别的分子亚型。具有BCL6重排的FL显示与t(14;18)阳性对应物的临床病理相似性。相反，外淋巴结部位的t(14;18)阴性FL主要以缺乏染色质修饰基因突变的TNFRSF14突变为特征。儿童FL与成人有独特的分子图谱。儿童型滤泡性淋巴瘤（PTFL）以MAP2K1、TNFRSF14和/或IRF8的突变为特征，而具有IRF4重排的大B细胞淋巴瘤已被认定为PTFL不同的实体。最终，对FL生物学和异质性的更好理解应有助于理解临床差异，并有助于指导患者管理和治疗决策。<<版权所有 ©2023美国血液学会。

Follicular lymphoma (FL) is a neoplasm derived from germinal center B cells, composed of centrocytes and centroblasts with at least a focal follicular growth pattern. The t(14;18) translocation together with epigenetic deregulation through recurrent genetic alterations are now recognized as the hallmark of FL. Nevertheless, FL is a heterogeneous disease clinically, morphologically, and biologically. The existence of FL lacking the t(14;18) chromosomal alteration highlights the complex pathogenesis of FL, and indicates that there are alternative pathogenetic mechanisms that can induce a neoplasm with follicular center B-cell phenotype. According to their clinical presentation t(14;18)-negative FL can be divided in three broad groups; nodal presentation, extranodal presentation, and those affecting predominantly children and young adults. Recent studies have shed some light into the genetic alterations of t(14;18)-negative FL. Within the group of t(14;18)-negative FL with nodal presentation, cases with STAT6 mutations are increasingly recognized as a distinctive molecular subgroup, often co-occurring with CREBBP and/or TNFRSF14 mutations. FL with BCL6 rearrangement shows clinicopathological similarities with the t(14;18)-positive counterpart. In contrast, t(14;18)-negative FL in extranodal sites are characterized mainly by TNFRSF14 mutations in the absence of chromatin modifying gene mutations. FL in children have unique molecular landscape when compared to adults. Pediatric-type follicular lymphoma (PTFL) is characterized by MAP2K1, TNFRSF14 and/or IRF8 mutations, whereas large B-cell lymphoma with IRF4 rearrangement is now recognized as a distinct entity different from PTFL. Ultimately, the better understanding of FL biology and heterogeneity should help to understand the clinical differences and help guiding patient management and treatment decisions.Copyright © 2023 American Society of Hematology.