Xu Bin, Naughton Daisy, Busam Klaus, Pulitzer Melissa
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.
Am J Dermatopathol. 2016 Sep;38(9):672-7. doi: 10.1097/DAD.0000000000000491.
Leukemia cutis (LC) and reactive myeloid infiltrates in the skin may be difficult to distinguish pathologically, sometimes even after an extensive immunohistochemical work-up. This poses a serious clinical dilemma, as the prognosis and treatment of either condition are markedly different. Although most reactive myeloid infiltrates require a simple course of corticosteroids before the symptoms regress, the development of LC may require chemotherapeutic or transplant-variant interventions. Erythroblast transformation specific regulated gene-1 (ERG) is a member of the erythroblast transformation specific family of transcription factors, which are downstream effectors of mitogenic signaling transduction pathways. ERG is a key regulator of cell proliferation, differentiation, angiogenesis, inflammation, and apoptosis and has recently been found to be overexpressed in acute myeloid and lymphoblastic leukemia. In this study, the authors aimed to explore the diagnostic utility of ERG immunohistochemistry in LC by comparing the frequency and expression level of ERG immunostain in 32 skin biopsies, 16 with LC and 16 with reactive leukocytic infiltrates. A significantly higher frequency of ERG positivity was detected in LC (13/16, 81.4%), compared with reactive conditions (0/16). In addition, the expression level of ERG in LC, calculated using H score (mean ± standard error of mean, 188 ± 24), was significantly higher than that in nonneoplastic leukocytic infiltrate (28 ± 8). Our results strongly suggest that ERG expression is potentially an extremely useful marker to distinguish between cases of LC from those of reactive myeloid infiltrates in the skin with a positive predictive value of 100% and negative predictive value of 84.2%.
皮肤白血病(LC)与皮肤中的反应性髓系浸润在病理上可能难以区分,有时即便经过广泛的免疫组织化学检查也是如此。这造成了严重的临床困境,因为这两种情况的预后和治疗明显不同。虽然大多数反应性髓系浸润在症状消退前只需一个简单的皮质类固醇疗程,但LC的发展可能需要化疗或移植相关的干预措施。成红细胞转化特异性调控基因1(ERG)是成红细胞转化特异性转录因子家族的成员,这些转录因子是有丝分裂信号转导途径的下游效应器。ERG是细胞增殖、分化、血管生成、炎症和凋亡的关键调节因子,最近发现其在急性髓系白血病和淋巴细胞白血病中过表达。在本研究中,作者旨在通过比较32例皮肤活检标本(16例为LC,16例为反应性白细胞浸润)中ERG免疫染色的频率和表达水平,探讨ERG免疫组织化学在LC诊断中的应用价值。与反应性情况(0/16)相比,LC中检测到的ERG阳性频率显著更高(13/16,81.4%)。此外,用H评分计算得出的LC中ERG的表达水平(平均值±平均标准误差,188±24)显著高于非肿瘤性白细胞浸润(28±8)。我们的结果强烈表明,ERG表达可能是区分皮肤LC病例与反应性髓系浸润病例的极其有用的标志物,其阳性预测值为100%,阴性预测值为84.2%。