Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Department of Dermatology, St Marianna University School of Medicine, Kanagawa, Japan.
Br J Dermatol. 2023 Oct 25;189(5):612-620. doi: 10.1093/bjd/ljad266.
The clinical implications of DUSP22 rearrangement and the association between DUSP22 rearrangement and lymphoid enhancer-binding factor 1 (LEF1) expression pattern in CD30+ cutaneous T-cell lymphomas (CTCLs) are unknown.
This study assessed the incidence of DUSP22 rearrangement and its clinical and immunohistochemical implications in primary cutaneous anaplastic large-cell lymphoma (pcALCL), lymphomatoid papulosis (LyP) and CD30+ mycosis fungoides with large-cell transformation (MF-LCT), focusing especially on the association with the prognosis and LEF1 expression pattern. Prognostic factors of pcALCL were also examined.
We conducted a multicentre retrospective study including patients with pcALCL, LyP and MF-LCT diagnosed between 1 January 2000 and 31 December 2018 in Japan. Baseline data at diagnosis, treatment course, overall survival (OS) and disease-specific survival (DSS) were collected. Immunohistochemical analysis and fluorescence in situ hybridization to detect DUSP22 and TP63 rearrangement were performed using skin samples at diagnosis. We investigated the association between staining pattern and these gene rearrangements. We also assessed the prognostic implications of clinical status, immunohistochemical results and the presence of gene rearrangements.
DUSP22 rearrangement was detected in 50% (11 of 22) of cases of pcALCL, but not in any cases with LyP (0 of 14) or MF-LCT (0 of 11). TP63 rearrangement was not detected in any case. Clinically, patients with pcALCL with DUSP22 rearrangement did not tend to develop ulcers (P = 0.081). There was no significant association between DUSP22 rearrangement status and immunohistochemical results, including LEF1 expression pattern. T3 stage and the presence of lower limb lesions were significantly associated with shorter OS (P = 0.012 and 0.021, respectively, by log-rank test). Similarly, they were significantly correlated with shorter DSS (P = 0.016 and 0.0001, respectively).
DUSP22 rearrangement is relatively specific to pcALCL among CD30+ CTCLs in Japan. Although the LEF1 expression pattern was not related to DUSP22 rearrangement in pcALCL, there was no rearrangement if LEF1 was not expressed. We confirmed that T3 stage and the lower limb involvement were significantly associated with decreased OS and DSS. The presence or absence of lower limb lesions should be included in T-stage subcategorization in the future.
DUSP22 重排的临床意义以及 DUSP22 重排与 CD30+皮肤 T 细胞淋巴瘤（CTCL）中淋巴增强结合因子 1（LEF1）表达模式之间的关系尚不清楚。
本研究评估了 DUSP22 重排在原发性皮肤间变性大细胞淋巴瘤（pcALCL）、淋巴样丘疹病（LyP）和 CD30+蕈样肉芽肿伴大细胞转化（MF-LCT）中的发生率及其临床和免疫组织化学意义，特别是与预后和 LEF1 表达模式的关系。还检查了 pcALCL 的预后因素。
我们进行了一项多中心回顾性研究，纳入了 2000 年 1 月 1 日至 2018 年 12 月 31 日期间在日本诊断为 pcALCL、LyP 和 MF-LCT 的患者。收集了诊断时的基线数据、治疗过程、总生存期（OS）和疾病特异性生存期（DSS）。使用诊断时的皮肤样本进行免疫组织化学分析和荧光原位杂交检测 DUSP22 和 TP63 重排。我们研究了染色模式与这些基因重排之间的关系。我们还评估了临床状态、免疫组织化学结果和基因重排存在的预后意义。
DUSP22 重排在 50%（22 例中的 11 例）pcALCL 病例中检测到，但在任何 LyP（14 例均未检测到）或 MF-LCT（11 例均未检测到）病例中均未检测到。TP63 重排未在任何病例中检测到。临床上，具有 DUSP22 重排的 pcALCL 患者不易发生溃疡（P=0.081）。DUSP22 重排状态与免疫组织化学结果，包括 LEF1 表达模式之间没有显著关联。T3 期和下肢病变的存在与较短的 OS（log-rank 检验 P=0.012 和 0.021）显著相关。同样，它们与较短的 DSS 显著相关（P=0.016 和 0.0001）。
DUSP22 重排在日本的 CD30+ CTCL 中相对特异于 pcALCL。尽管在 pcALCL 中 LEF1 表达模式与 DUSP22 重排无关，但如果 LEF1 不表达，则不存在重排。我们证实 T3 期和下肢受累与 OS 和 DSS 降低显著相关。在未来的 T 分期分类中，应包括下肢病变的存在或不存在。
