Kaunitz Genevieve J, Loss Manisha, Rizvi Hira, Ravi Sowmya, Cuda Jonathan D, Bleich Karen B, Esandrio Jessica, Sander Inbal, Le Dung T, Diaz Luis A, Brahmer Julie R, Drake Charles G, Hollmann Travis J, Lacouture Mario E, Hellmann Matthew D, Lipson Evan J, Taube Janis M
Departments of *Dermatology ‡Pathology §Oncology, Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center ∥The Brady Urologic Institute, Johns Hopkins University School of Medicine, Baltimore, MD Departments of †Medicine, Thoracic Oncology Service ¶Pathology #Dermatology, Memorial Sloan Kettering Cancer Center, New York, NY.
Am J Surg Pathol. 2017 Oct;41(10):1381-1389. doi: 10.1097/PAS.0000000000000900.
Cutaneous eruptions are among the most common immune-related adverse events (irAEs) associated with anti-programmed cell death protein 1/programmed cell death ligand 1 therapy, and are often clinically and histologically characterized as lichenoid. Nonlichenoid patterns may also occur and are likely to be encountered by surgical pathologists, given the increasing clinical use of these agents. The purpose of this study is to describe the histopathologic features of nonlichenoid cutaneous irAEs from patients receiving anti-programmed cell death protein 1/programmed cell death ligand 1 therapies for a variety of underlying advanced malignancies. Sixteen patients with 17 biopsied eruptions were included from 2 academic institutions with extensive experience administering and monitoring responses to immune checkpoint blockade as well as treating the potential side effects. Eruptions occurred a median of 10 days (range, 1 d to 11.4 mo) after treatment initiation. Nearly half of specimens demonstrated either a psoriasiform/spongiotic or an urticarial-type reaction pattern on histologic review. Patterns consistent with Grover disease, bullous pemphigoid, and granulomatous dermatitis were also observed. Nearly two-thirds of patients required systemic corticosteroids for treatment of the cutaneous irAE, and 19% of patients discontinued immunotherapy due to their skin eruptions. 75% of patients showed an objective antitumor response. The diverse array of nonlichenoid cutaneous irAE presented here should reflect and inform the scope of histologic patterns encountered by the practicing surgical pathologist. Such eruptions are seen in patients with a variety of underlying tumor types, many of whom ultimately demonstrate a favorable response to immune checkpoint blockade.
皮肤疹是与抗程序性细胞死亡蛋白1/程序性细胞死亡配体1治疗相关的最常见的免疫相关不良事件（irAE）之一，在临床和组织学上通常表现为苔藓样。非苔藓样模式也可能出现，鉴于这些药物在临床上的使用日益增加，手术病理学家很可能会遇到。本研究的目的是描述接受抗程序性细胞死亡蛋白1/程序性细胞死亡配体1治疗的各种潜在晚期恶性肿瘤患者的非苔藓样皮肤irAE的组织病理学特征。来自2个学术机构的16例患者的17次活检皮疹被纳入研究，这些机构在管理和监测免疫检查点阻断反应以及治疗潜在副作用方面有着丰富的经验。皮疹在治疗开始后的中位时间为10天（范围为1天至11.4个月）出现。在组织学检查中，近一半的标本表现为银屑病样/海绵状或荨麻疹样反应模式。还观察到与格罗弗病、大疱性类天疱疮和肉芽肿性皮炎一致的模式。近三分之二的患者需要全身性皮质类固醇来治疗皮肤irAE，19%的患者因皮肤疹而停止免疫治疗。75%的患者显示出客观的抗肿瘤反应。这里呈现的各种非苔藓样皮肤irAE应反映并告知执业手术病理学家所遇到的组织学模式范围。这些皮疹见于各种潜在肿瘤类型的患者，其中许多患者最终对免疫检查点阻断表现出良好反应。
