Tetzlaff Michael T, Jazaeri Amir A, Torres-Cabala Carlos A, Korivi Brinda R, Landon Genie A, Nagarajan Priyadharsini, Choksi Adrienne, Chen Leon, Uemura Marc, Aung Phyu P, Diab Adi, Sharma Padmanee, Davies Michael A, Amaria Rodabe, Prieto Victor G, Curry Jonathan L
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Department of Translational and Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
J Cutan Pathol. 2017 Dec;44(12):1080-1086. doi: 10.1111/cup.13044. Epub 2017 Oct 13.
Immunotherapies targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death 1 (PD-1) receptor and its ligand (PD-L1) have showed substantial therapeutic benefit in patients with clinically advanced solid malignancies. However, autoimmune toxicities are common and often significant adverse events with these agents. While rash and pruritus remain the most common cutaneous complications in treated patients, novel dermatologic toxicities related to immune checkpoint blockade continue to emerge as the number of patients exposed to immunotherapy increases. Here, we describe 2 patients treated with combination immunotherapy with ipilimumab and nivolumab who developed painful subcutaneous nodules. Although the findings were clinically concerning for disease recurrence, histopathologic examination of biopsies from the lesions revealed a subcutaneous mixed septal and lobular erythema nodosum-like panniculitis. Notably, neither patient received immunosuppressive therapy for these lesions, which subsequently remained stable, and both patients' cancer remained controlled. These cases show that the dermatologic toxicity profile of immune checkpoint blockade is diverse and continues to expand, and illustrates that recognition of such toxicities is critical to optimal patient management.
针对细胞毒性T淋巴细胞相关抗原4（CTLA-4）、程序性细胞死亡蛋白1（PD-1）受体及其配体（PD-L1）的免疫疗法已在临床晚期实体恶性肿瘤患者中显示出显著的治疗益处。然而，自身免疫毒性很常见，并且这些药物往往会引发严重的不良事件。虽然皮疹和瘙痒仍然是接受治疗患者中最常见的皮肤并发症，但随着接受免疫治疗的患者数量增加，与免疫检查点阻断相关的新型皮肤毒性不断出现。在此，我们描述了2例接受伊匹单抗和纳武单抗联合免疫治疗的患者，他们出现了疼痛性皮下结节。尽管这些发现临床上令人担忧疾病复发，但对病变活检组织的组织病理学检查显示为皮下混合性间隔性和小叶性结节性红斑样脂膜炎。值得注意的是，两名患者均未针对这些病变接受免疫抑制治疗，病变随后保持稳定，且两名患者的癌症均得到控制。这些病例表明，免疫检查点阻断的皮肤毒性谱是多样的且不断扩展，并且说明认识到此类毒性对于优化患者管理至关重要。
