经典霍奇金淋巴瘤的复发中有相当比例是克隆无关的第二原发淋巴瘤。
A significant proportion of classic Hodgkin lymphoma recurrences represents clonally unrelated second primary lymphoma.
发表日期：2023 Aug 08
作者：
Diede Ag van Bladel, Wendy B C Stevens, Leonie I Kroeze, Ruben Al de Groen, Fleur A de Groot, Jessica Lm van der Last-Kempkes, Madeleine R Berendsen, Jos Rijntjes, Jeroen A C W Luijks, Irina Bonzheim, Ellen van der Spek, Wouter J Plattel, Johannes Pruijt, Susan Dpwm de Jonge-Peeters, Gerjo A Velders, Chantal Lensen, Esther R van Bladel, Birgit Federmann, Brigiet Hoevenaars, Agata Pastorczak, Jutte van der Werff Ten Bosch, Joost S P Vermaat, Peet Nooijen, Konnie M Hebeda, Falko Fend, Arjan Diepstra, J Han Jm van Krieken, Patricia J T A Groenen, Michiel van den Brand, Blanca Scheijen
来源：
Blood Advances
摘要：
尽管传统霍奇金淋巴瘤（cHL）的治愈率很高，但仍会发生复发。复发的cHL是第二原发淋巴瘤还是模仿cHL的潜在T细胞淋巴瘤（TCL）尚未得到充分研究。为了分析cHL复发的特性，对60名患者的cHL诊断和复发标本进行了深入的免疫球蛋白（IG）和T细胞受体（TR）重排的克隆性检测，并辅以淋巴瘤相关基因定点突变分析。通过下一代测序（NGS）检测到120个标本中69个（58%）存在克隆性IG重排。共有34例能够确定克隆关系，其中24例（71%）患者确诊为克隆相关的复发cHL。通过IG-NGS克隆性评估发现，34例中有10例（29%）复发cHL存在克隆性不相关的情况，并通过在配对的cHL样本中检测到主要互斥的基因突变来进行确认。在复发时间超过2年的病例中，约有60%的cHL患者能够确定克隆关系，显示为第二原发cHL。在125个标本中，检测到14个（11%）有克隆性TR基因重排，同时检测到7个样本有TCL相关基因的突变。回顾性病理学评估与分子学结果相结合，发现年龄超过50岁的5名患者存在潜在的TCL。该研究显示，基于NGS的IG/TR克隆性测试和基因突变分析揭示了一些cHL复发，特别是在2年后复发的情况，有时代表新的原发cHL或模仿cHL的TCL。鉴于治疗的重要后果，对cHL复发的分子测试对于后续针对特定淋巴瘤表现的适当治疗策略至关重要。Copyright © 2023 American Society of Hematology.
Despite high cure rates in classic Hodgkin lymphoma (cHL), relapses are observed. Whether relapsed cHL represents second primary lymphoma or an underlying T-cell lymphoma (TCL) mimicking cHL is under-investigated. To analyze the nature of cHL recurrences, in-depth clonality testing of immunoglobulin (IG) and T-cell receptor (TR) rearrangements was performed in paired cHL diagnosis and recurrences of 60 patients, supported by targeted mutation analysis of lymphoma-associated genes. Clonal IG rearrangements were detected by next-generation sequencing (NGS) in 69/120 (58%) diagnosis and recurrence samples. The clonal relationship could be established in 34 cases, identifying clonally related relapsed cHL in 24/34 patients (71%). Clonally unrelated cHL was observed in 10/34 patients (29%) as determined by IG-NGS clonality assessment, and confirmed by the identification of predominantly mutually exclusive gene mutations in the paired cHL samples. In recurrences of >2 years, ~60% of cHL patients for which the clonal relationship could be established showed a second primary cHL. Clonal TR gene rearrangements were identified in 14/125 samples (11%), and TCL-associated gene mutations were detected in 7/14 samples. Retrospective pathology review with integration of the molecular findings were consistent with an underlying TCL in 5 patients aged >50 years. This study shows that cHL recurrences, especially after 2 years, sometimes represent a new primary cHL or TCL mimicking cHL, as uncovered by NGS-based IG/TR clonality testing and gene mutation analysis. Given the significant therapeutic consequences, molecular testing of a presumed relapse in cHL is crucial for subsequent appropriate treatment strategies adapted to the specific lymphoma presentation.Copyright © 2023 American Society of Hematology.