Department of Respiratory Medicine, NTT East Sapporo Hospital, Hokkaido, Japan.
Department of Pathology, School of Medicine, Sapporo Medical University, Hokkaido, Japan
Anticancer Res. 2021 Jul;41(7):3699-3706. doi: 10.21873/anticanres.15161.
BACKGROUND/AIM: Immune checkpoint inhibitors (ICIs), including nivolumab and pembrolizumab, have recently been shown to have clinical benefits in patients with advanced non-small cell lung cancer (NSCLC). The novel tumour responses to these agents are changing the management of patients with cancer. Pseudo-progression of disease (pseudo-PD), that is, an initial flare followed by shrinkage of the tumour, has been described as a distinctive response to ICIs. However, pseudo-PD manifest initial progression and is difficult to segregate with hyper progressive disease (HPD). We, therefore, analysed a case with pseudo-PD histologically.
A 68-year-old Japanese man with stage IV non-small cell lung carcinoma (NSCLC) was treated by anti-PD-1 antibody (pembrolizumab). Four weeks later after second time treatment with pembrolizumab, the patient showed severe melena followed by Trousseau syndrome and died at day 174 after first treatment by pembrolizumab, suggesting HPD clinically. Primary lesion and metastatic lesions were analysed histologically.
Histological analysis revealed that NSCLC cells expressed PD-L1, and CD8+ tumor-infiltrated lymphocytes (TILs) were observed. CD8+ TILs showed higher rates of PD-1 indicating that lesions were of the inflamed type and the case was pseudo-PD. Furthermore, it was found that cancer cells expressed MUC1.
The clinical appearance of the case was aggressive after treatment by pembrolizumab, and the case seemed to be HPD; however, histological analysis revealed that the case was likely pseudo-PD. Therefore, careful histological evaluation is important when investigating the clinical response to an ICI and mucin expression might be a predictive marker for Trousseau syndrome.
背景/目的：免疫检查点抑制剂（ICIs），包括纳武利尤单抗和帕博利珠单抗，最近已被证明对晚期非小细胞肺癌（NSCLC）患者具有临床益处。这些药物引起的新型肿瘤反应正在改变癌症患者的治疗方法。疾病假性进展（pseudo-PD），即初始 flares 后肿瘤缩小，已被描述为 ICI 独特的反应。然而，pseudo-PD 表现为初始进展，与超进展性疾病（HPD）难以区分。因此，我们对一例具有 pseudo-PD 的病例进行了组织学分析。
一名 68 岁的日本男性患有 IV 期非小细胞肺癌（NSCLC），接受了抗 PD-1 抗体（pembrolizumab）治疗。第二次使用 pembrolizumab 治疗四周后，患者出现严重黑便，随后出现 Trousseau 综合征，在第一次 pembrolizumab 治疗后第 174 天死亡，临床上提示 HPD。对原发性病变和转移性病变进行了组织学分析。
组织学分析显示 NSCLC 细胞表达 PD-L1，并观察到 CD8+肿瘤浸润淋巴细胞（TILs）。CD8+TILs 显示更高的 PD-1 表达率，表明病变为炎症型，本例为 pseudo-PD。此外，发现癌细胞表达 MUC1。
pembrolizumab 治疗后，该病例的临床表现具有侵袭性，似乎为 HPD；然而，组织学分析显示该病例可能为 pseudo-PD。因此，在研究 ICI 的临床反应时，仔细的组织学评估很重要，黏蛋白表达可能是 Trousseau 综合征的预测标志物。
