Abstract：
DUSP22 rearrangements are genetic alterations observed in a subset of systemic anaplastic large cell lymphoma (S-ALCL), primary cutaneous anaplastic large cell lymphoma (C-ALCL), and lymphomatoid papulosis (LyP). Previous investigations have shown that the LEF1+/TIA1- immunoprofile and MSC E116K mutations are highly associated with DUSP22 rearrangement in ALCL. However, the existing literature primarily focuses on S-ALCL. Our understanding of the LEF1/TIA1 immunoprofile and MSC mutation status in C-ALCL/LyP is still limited. In this study, we aimed to assess LEF1/TIA1 expression and MSC mutations in a cohort of 23 C-ALCL/LyP cases, along with a control group of histological mimickers. DUSP22 rearrangements were detected by fluorescence in situ hybridization in eight cases (6/10 C-ALCL, 2/13 LyP). We found LEF1 expression in five out of eight (63%) DUSP22-rearranged cases (3/6 C-ALCL, 2/2 LyP), and none of the 15 cases lacking DUSP22 rearrangements. Furthermore, we also found frequent LEF1 expression in adult T-cell leukemia/lymphoma (ATLL; 10 of 11, 91%) within the control group. TIA1 expression was consistently negative in all DUSP22-rearranged C-ALCL/LyP and ATLL cases tested. MCS E116K mutation was identified in one of five DUSP22-rearranged C-ALCL cases. RNA sequencing of a DUSP22-rearranged C-ALCL revealed a novel DUSP22::SNHG fusion coexisting with a CD58::WNT2B fusion. In conclusion, our findings demonstrated a lower rate of LEF1 expression in DUSP22-rearranged C-ALCL/LyP compared to previous reports that predominantly focused on S-ALCL. Moreover, we observed that the majority of ATLL cases also expressed LEF1, suggesting that the LEF1+/TIA1- immunoprofile does not differentiate DUSP22-rearranged C-ALCL/LyP from ATLL.
摘要：
DUSP22重排是在系统性间变性大细胞淋巴瘤（S-ALCL）的一部分中观察到的遗传改变，原发性皮肤间变性大细胞淋巴瘤（C-ALCL），和淋巴瘤样丘疹病（LyP）。先前的研究表明，LEF1/TIA1-免疫谱和MSCE116K突变与ALCL中的DUSP22重排高度相关。然而,现有文献主要集中在S-ALCL上。我们对C-ALCL/LyP中LEF1/TIA1免疫谱和MSC突变状态的理解仍然有限。在这项研究中,我们旨在评估23例C-ALCL/LyP病例的LEF1/TIA1表达和MSC突变，以及组织学模拟者的对照组。用荧光原位杂交法检测DUSP22重排8例(6/10C-ALCL,2/13LyP）。我们发现LEF1在8例(63%)DUSP22重排的病例中表达(3/6C-ALCL,2/2LyP），15例没有DUSP22重排。此外，我们还在对照组中的成人T细胞白血病/淋巴瘤中发现了频繁的LEF1表达(ATLL;11人中的10人,91%).在所有DUSP22重排的C-ALCL/LyP和ATLL病例中，TIA1表达始终为阴性。在5例DUSP22重排的C-ALCL病例之一中发现了MCSE116K突变。DUSP22重排的C-ALCL的RNA测序揭示了与CD58::WNT2B融合物共存的新型DUSP22::SNHG32融合物。总之,我们的研究结果表明,与以前主要关注S-ALCL的报道相比,DUSP22重排的C-ALCL/LyP中LEF1的表达率较低.此外，我们观察到大多数ATLL病例也表达LEF1,提示LEF1+/TIA1-免疫谱不能区分DUSP22重排的C-ALCL/LyP和ATLL.
