Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
Medical College of Wisconsin, Milwaukee, WI, USA.
Mod Pathol. 2018 Dec;31(12):1801-1806. doi: 10.1038/s41379-018-0097-4. Epub 2018 Jul 4.
Poorly differentiated non-keratinizing squamous cell carcinoma of the thymus, also known as lymphoepithelioma-like carcinoma, is a rare primary malignant neoplasm of thymic origin. The mainstay of treatment for these tumors is surgical and they tend to respond poorly to chemotherapy. The checkpoint programmed cell death ligand-1 protein (PD-L1) bound to its receptor (PD-1) has been demonstrated to be an important therapeutic target for many different tumors. Expression of PD-L1/PD-1 in lymphoepithelioma-like carcinoma of the thymus may indicate that these tumors are potential targets for inhibitor therapy. Twenty-one cases of lymphoepithelioma-like carcinoma of the thymus were collected and reviewed. Tissue microarrays were created using triplicate 2 mm cores for each case. PD-L1/PD-1 staining pattern (neoplastic cells versus tumor infiltrating lymphocytes) was documented for each case. Out of 21 cases, 15 (71.4%) showed various degrees of membranous PD-L1 staining. Of the positive cases, 48% showed high expression of PD-L1 (>50% of tumor cells) and 24% showed low expression (<50%). PD-1 staining showed focal positivity in 12/20 (60%) cases among tumor infiltrating lymphocytes. PD-L1/PD-1 inhibitor therapy has been applied successfully in other solid malignant tumors with high expression of PD-L1/PD-1. The high level of PD-L1 expression in our cases indicates that PD-L1 may play a role in the pathogenesis of these tumors and that PD-L1/PD-1 blockade may be a viable therapeutic option for patients with lymphoepithelioma-like carcinoma of the thymus who have failed other first-line therapies.
胸腺低分化非角化性鳞状细胞癌,又称淋巴上皮样癌,是一种罕见的胸腺原发性恶性肿瘤。这些肿瘤的主要治疗方法是手术,且对化疗的反应较差。已证实细胞程序性死亡配体 1 蛋白(PD-L1)与受体(PD-1)结合是许多不同肿瘤的重要治疗靶点。胸腺癌中的 PD-L1/PD-1 的表达可能表明这些肿瘤是抑制剂治疗的潜在靶点。收集并回顾了 21 例胸腺癌。为每个病例创建了组织微阵列,每个病例使用 3 个 2mm 核心的重复进行。记录了每个病例的 PD-L1/PD-1 染色模式(肿瘤细胞与肿瘤浸润淋巴细胞)。在 21 例中,有 15 例(71.4%)显示出不同程度的膜 PD-L1 染色。在阳性病例中,48%显示 PD-L1 高表达(>50%的肿瘤细胞),24%显示低表达(<50%)。PD-1 染色显示肿瘤浸润淋巴细胞中有 12/20(60%)例存在局灶性阳性。PD-L1/PD-1 抑制剂治疗已成功应用于其他 PD-L1/PD-1 高表达的实体恶性肿瘤。我们的病例中 PD-L1 表达水平较高,这表明 PD-L1 可能在这些肿瘤的发病机制中起作用,并且 PD-L1/PD-1 阻断可能是其他一线治疗失败的胸腺癌患者的一种可行的治疗选择。