Since the description of primary mediastinal large B-cell lymphoma (PMBL) as a distinct entity from diffuse large B-cell lymphomas (DLBCL), numerous studies have made it possible to improve their definition. Despite this, this differential diagnosis can be challenging in daily practice. However, in some centers, PMBL may be treated according to a particular regimen, distinct from those used in DLBCL, emphasizing the importance of accurate identification at diagnosis. This study aimed to describe the histological and molecular characteristics of PMBL to improve the accuracy of their diagnosis. Forty-nine cases of PMBL were retrospectively retrieved. The mean age at diagnosis was 39 years (21–83), with a sex ratio of 0.88. All cases presented a fibrous background with diffuse growth of intermediate to large cells with an eosinophil (26/49, 53%) or retracted cytoplasm (23/49, 47%). “Hodgkin-like” cells were observed in 65% of cases (32/49, 65%). The phenotype was: BCL6+ (47/49, 96%), MUM1+ (40/49, 82%), CD30+ (43/49, 88%), and CD23+ (37/49, 75%). Genomic DNAs were tested by next generation sequencing of 33 cases using a custom design panel. Pathogenic variants were found in all cases. The most frequent mutations were:SOCS1(30/33, 91%),TNFAIP3(18/33, 54.5%),ITPKB(17/33, 51.5%),GNA13(16/33, 48.5%),CD58(12/33, 36.4%),B2M(12/33; 36.4%),STAT6(11/33, 33.3%) as well asARID1A(10/33, 30.3%),XPO1(9/33, 27.3%),CIITA(8/33, 24%), andNFKBIE(8/33, 24%). The present study describes a PMBL cohort on morphological, immunohistochemical, and molecular levels to provide pathologists with daily routine tools. These data also reinforce interest in an integrated histomolecular diagnosis to allow a precision diagnosis as early as possible.
自原发性纵隔大B细胞淋巴瘤（PMBL）被描述为与弥漫性大B细胞淋巴瘤（DLBCL）不同的独立疾病实体以来，大量研究不断深化了对其定义的认识。尽管如此，在日常临床实践中两者的鉴别诊断仍具挑战性。值得注意的是，部分医疗中心对PMBL采用与DLBCL不同的特定治疗方案，这凸显了在诊断阶段进行精准鉴别的重要性。本研究旨在通过描述PMBL的组织学与分子特征，提升其诊断准确性。 研究回顾性收集了49例PMBL病例。诊断时平均年龄为39岁（范围21-83岁），性别比为0.88。所有病例均呈现纤维性背景，可见中等至大体积肿瘤细胞弥漫性生长，其中53%（26/49）病例胞质嗜酸性，47%（23/49）病例胞质收缩。65%（32/49）的病例中观察到“霍奇金样”细胞。免疫表型特征为：BCL6阳性（96%，47/49）、MUM1阳性（82%，40/49）、CD30阳性（88%，43/49）及CD23阳性（75%，37/49）。 通过定制化测序面板对33例样本进行新一代测序检测基因组DNA，所有病例均检出致病性变异。高频突变基因包括：SOCS1（91%，30/33）、TNFAIP3（54.5%，18/33）、ITPKB（51.5%，17/33）、GNA13（48.5%，16/33）、CD58（36.4%，12/33）、B2M（36.4%，12/33）、STAT6（33.3%，11/33），以及ARID1A（30.3%，10/33）、XPO1（27.3%，9/33）、CIITA（24%，8/33）和NFKBIE（24%，8/33）。 本研究从形态学、免疫组化及分子水平系统描述了PMBL队列特征，为病理医师提供了实用的日常诊断工具。这些数据进一步证实了整合组织分子诊断的价值，有助于实现早期精准诊断。
Molecular Characterization of Primary Mediastinal Large B-Cell Lymphomas
肿瘤(癌症)患者之家