Cutaneous Eruptions in Patients Receiving Immune Checkpoint Blockade: Clinicopathologic Analysis of the Nonlichenoid Histologic Pattern.
Cutaneous Eruptions in Patients Receiving Immune Checkpoint Blockade: Clinicopathologic Analysis of the Nonlichenoid Histologic Pattern.
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DOI：
10.1097/pas.0000000000000900
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发表时间：
2017-10
期刊：
影响因子：
--
通讯作者：
Taube JM
中科院分区：
文献类型：
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作者：
Kaunitz GJ;Loss M;Rizvi H;Ravi S;Cuda JD;Bleich KB;Esandrio J;Sander I;Le DT;Diaz LA Jr;Brahmer JR;Drake CG;Hollmann TJ;Lacouture ME;Hellmann MD;Lipson EJ;Taube JM
皮疹是与抗PD-1/PD-L1治疗相关的最常见免疫相关不良事件（irAE）之一，通常在临床和组织学上表征为苔藓样。非苔藓样模式也可能发生，并可能遇到外科病理学家，鉴于这些药物的临床使用越来越多。本研究的目的是描述接受抗PD-1/PD-L1治疗的各种基础晚期恶性肿瘤患者的非苔藓样皮肤irAE的组织病理学特征。来自两个学术机构的16名患者（17例活检皮疹）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具有丰富的经验。治疗开始后中位10天（范围1天至11.4个月）发生皮疹。组织学检查显示，近一半的标本表现为银屑病样/海绵样或荨麻疹型反应模式。还观察到与Grover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治疗皮肤irAE，19%的患者因皮疹而停止免疫治疗。75%的患者表现出客观的抗肿瘤反应。这里介绍的非苔藓样皮肤irAE的多样性应反映和告知执业外科病理学家所遇到的组织学模式的范围。这种皮疹见于各种潜在肿瘤类型的患者，其中许多人最终表现出对免疫检查点阻断的有利反应。
Cutaneous eruptions are among the most common immune-related adverse events (irAEs) associated with anti-PD-1/PD-L1 therapy, and are often clinically and histologically characterized as lichenoid. Non-lichenoid 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 non-lichenoid cutaneous irAEs from patients receiving anti-PD-1/PD-L1 therapies for a variety of underlying advanced malignancies. Sixteen patients with 17 biopsied eruptions were included from two 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 day to 11.4 months) 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’s 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 non-lichenoid 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.