Department of Pathology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, 23561, Taiwan; Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 110, Taiwan.
Department of Clinical Pathology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, 23561, Taiwan.
Hum Pathol. 2024 Aug;150:58-66. doi: 10.1016/j.humpath.2024.07.002. Epub 2024 Jul 4.
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.
DUSP22 重排是在系统性间变大细胞淋巴瘤（S-ALCL）、原发性皮肤间变大细胞淋巴瘤（C-ALCL）和淋巴母细胞性丘疹病（LyP）的一部分中观察到的遗传改变。先前的研究表明，LEF1+/TIA1-免疫表型和 MSC E116K 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 中的 LEF1/TIA1 免疫表型和 MSC 突变状态的了解仍然有限。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 突变情况，以及一组组织学模拟物作为对照组。通过荧光原位杂交在 8 例（6/10 C-ALCL，2/13 LyP）中检测到 DUSP22 重排。我们发现 8 例 DUSP22 重排病例中有 5 例（63%）表达 LEF1（3/6 C-ALCL，2/2 LyP），而在 15 例缺乏 DUSP22 重排的病例中均未发现。此外，我们还发现对照组中的成人 T 细胞白血病/淋巴瘤（ATLL；11 例中的 10 例，91%）中经常表达 LEF1。在所有检测的 DUSP22 重排 C-ALCL/LyP 和 ATLL 病例中，TIA1 表达均为阴性。在 5 例 DUSP22 重排的 C-ALCL 中发现了 MSC E116K 突变。对 DUSP22 重排的 C-ALCL 进行 RNA 测序发现了一种新的 DUSP22::SNHG 融合，同时存在 CD58::WNT2B 融合。总之，与主要关注 S-ALCL 的先前报道相比，我们发现 DUSP22 重排的 C-ALCL/LyP 中 LEF1 表达率较低。此外，我们观察到大多数 ATLL 病例也表达 LEF1，表明 LEF1+/TIA1-免疫表型不能将 DUSP22 重排的 C-ALCL/LyP 与 ATLL 区分开来。
