Department of Pathology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Plastic, Reconstructive, and Hand Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands.
Blood. 2020 Dec 17;136(25):2927-2932. doi: 10.1182/blood.2020005372.
Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a very rare type of T-cell lymphoma that is uniquely caused by a single environmental stimulus. Here, we present a comprehensive genetic analysis of a relatively large series of BIA-ALCL (n = 29), for which genome-wide chromosomal copy number aberrations (CNAs) and mutational profiles for a subset (n = 7) were determined. For comparison, CNAs for anaplastic lymphoma kinase (ALK)- nodal anaplastic large cell lymphomas (ALCLs; n = 24) were obtained. CNAs were detected in 94% of BIA-ALCLs, with losses at chromosome 20q13.13 in 66% of the samples. Loss of 20q13.13 is characteristic of BIA-ALCL compared with other classes of ALCL, such as primary cutaneous ALCL and systemic type ALK+ and ALK- ALCL. Mutational patterns confirm that the interleukin-6-JAK1-STAT3 pathway is deregulated. Although this is commonly observed across various types of T-cell lymphomas, the extent of deregulation is significantly higher in BIA-ALCL, as indicated by phosphorylated STAT3 immunohistochemistry. The characteristic loss of chromosome 20 in BIA-ALCL provides further justification to recognize BIA-ALCL as a separate disease entity. Moreover, CNA analysis may serve as a parameter for future diagnostic assays for women with breast implants to distinguish seroma caused by BIA-ALCL from other causes of seroma accumulation, such as infection or trauma.
乳房植入物相关间变性大细胞淋巴瘤(BIA-ALCL)是一种非常罕见的 T 细胞淋巴瘤,仅由单一环境刺激引起。在这里,我们对相对较大系列的 BIA-ALCL(n = 29)进行了全面的遗传分析,其中一部分(n = 7)确定了全基因组染色体拷贝数异常(CNAs)和突变谱。为了进行比较,还获得了间变性淋巴瘤激酶(ALK)-结外间变性大细胞淋巴瘤(ALCL;n = 24)的 CNAs。在 94%的 BIA-ALCL 中检测到 CNAs,66%的样本中存在 20q13.13 染色体的缺失。与其他类型的 ALCL 相比,如原发性皮肤 ALCL 和系统性 ALK+和 ALK-ALCL,20q13.13 的缺失是 BIA-ALCL 的特征。突变模式证实白细胞介素-6-JAK1-STAT3 途径被失调。尽管这在各种类型的 T 细胞淋巴瘤中都很常见,但 BIA-ALCL 的失调程度要高得多,这可以通过磷酸化 STAT3 免疫组化来表明。BIA-ALCL 中染色体 20 的特征缺失进一步证明了将 BIA-ALCL 视为一种独立的疾病实体的合理性。此外,CNA 分析可以作为未来用于乳房植入物女性的诊断检测的参数,以区分 BIA-ALCL 引起的血清肿与其他血清肿积聚的原因,如感染或创伤。