Otsuka Yasuyuki, Nishikori Momoko, Fujimoto Masakazu, Nakao Kensuke, Hishizawa Masakatsu, Haga Hironori, Takaori-Kondo Akifumi
Department of Hematology and Oncology Graduate School of Medicine Kyoto University Kyoto Japan.
Department of Diagnostic Pathology Kyoto University Hospital Kyoto Japan.
EJHaem. 2020 Jun 3;1(1):323-327. doi: 10.1002/jha2.28. eCollection 2020 Jul.
Intraclonal diversity is commonly observed in patients with follicular lymphoma (FL), whereas tumor cells at the onset and relapse usually share early genetic events such as VDJ rearrangement of the immunoglobulin genes and t(14;18) translocation. We report a case of FL with relapse with FL that was clonally different from the tumor cells at onset. A 59-year-old male presented with paraaortic lymph node swelling and thickening of the right renal pelvic and ureteral wall was histologically diagnosed as FL, grade 1. Karyotypic analysis revealed t(14;18)(q32;q21) with +12 and +der(18)t(14;18). Ten years after the initial diagnosis, he suddenly developed systemic lymphadenopathy as a second relapse, and histological examination led to the diagnosis of FL grade 3B with diffuse large B-cell lymphoma. Surprisingly, karyotypic analysis demonstrated the presence of +12 and 3q27 abnormality, which was proved to be a BCL6 translocation by fluorescence in situ hybridization, but the absence of t(14;18)(q32;q21). We compared VDJ rearrangement of the FL cells at onset and relapse and found that they were completely independent of each other. These tumor cells sharetrisomy 12 as a common genetic abnormality, and it is speculated that trisomy 12 may have occurred earlier than BCL2 and BCL6 translocations. These results suggest that there can even be cases of "relapse" of FL with an independent origin of the primary tumor cells. Our observation highlights the importance of re-biopsy of relapsed FL, especially when it occurs after a long remission with different clinical presentation from that at the onset.
在滤泡性淋巴瘤（FL）患者中通常可观察到克隆内多样性，而疾病初发和复发时的肿瘤细胞通常共享早期遗传事件，如免疫球蛋白基因的VDJ重排和t(14;18)易位。我们报告了一例FL复发病例，其复发时的肿瘤克隆与初发时不同。一名59岁男性因腹主动脉旁淋巴结肿大以及右肾盂和输尿管壁增厚就诊，组织学诊断为1级FL。核型分析显示存在t(14;18)(q32;q21)以及+12和+der(18)t(14;18)。初次诊断十年后，他突然出现全身淋巴结病，为第二次复发，组织学检查诊断为3B级FL伴弥漫性大B细胞淋巴瘤。令人惊讶的是，核型分析显示存在+12和3q27异常，荧光原位杂交证实这是一种BCL6易位，但不存在t(14;18)(q32;q21)。我们比较了初发和复发时FL细胞的VDJ重排，发现它们完全相互独立。这些肿瘤细胞共享12号染色体三体作为共同的遗传异常，推测12号染色体三体可能比BCL2和BCL6易位更早发生。这些结果表明，甚至可能存在原发性肿瘤细胞起源独立的FL“复发”病例。我们的观察强调了对复发FL进行再次活检的重要性，尤其是在长期缓解后复发且临床表现与初发时不同的情况下。
