BACKGROUND AND OBJECTIVE Drug-induced myopathy is among the most common causes of muscle disease. An association has recently been described between programmed death-1 (PD-1)/PD-1 ligand (PD-L1) inhibitors and immune-related adverse events (irAE) affecting the muscle. Here, we report the clinical and pathological findings of nine unrelated patients with PD-1 and PD-L1 inhibitors-associated myopathy. METHODS We retrospectively analyzed 317 muscle biopsies performed for diagnostic purposes from January 2017 to June 2019. Patients were attended in two tertiary centers and muscle biopsies were performed and analyzed by two myology experts. Muscle biopsies were frozen in cooled isopenthane, cryostat sectioned and stained. Immunohistochemistry studies were also performed as a routine procedure in our lab. RESULTS We identified 9 patients receiving anti-PD-1 or PD-L1 inhibitors consulting for either muscle weakness, asthenia, myasthenic-like syndrome or other muscle related-symptoms, along with biopsy-proven inflammatory myopathy. One had concomitant myocarditis. In most of the cases muscle biopsy showed a marked phenomenon of necrosis, macrophagy and muscle regeneration with perivascular inflammatory infiltrates with a large component of macrophagic cells. A tendency to perifascicular atrophy was also noticed. The expression of MHC class I antigens predominated in the perifascicular zones. Raised muscle enzymes were detected in 7 patients. CONCLUSION A characteristic clinic-pathological pattern, including a myasthenia gravis-like syndrome plus myositis was found in patients receiving PD-1 and PD-1 L inhibitors. A large component of macrophages resembling granulomas seems to be the pathological hallmark of the syndrome. Further information is required to understand the wide spectrum of immune-related adverse events involving the muscle during or after treatment with anti-PD-1 inhibitors, but the pathological picture seems to be characteristic.

中文翻译：

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新兴的PD-1和PD-1L抑制剂与肌病相关，具有典型的组织病理学特征。

背景和目的药物引起的肌病是肌肉疾病的最常见原因。最近已经描述了程序性死亡1（PD-1）/ PD-1配体（PD-L1）抑制剂与影响肌肉的免疫相关不良事件（irAE）之间的关联。在这里，我们报告9名与PD-1和PD-L1抑制剂相关的肌病的无关患者的临床和病理学发现。方法我们回顾性分析了2017年1月至2019年6月进行的317例肌肉活检，以进行诊断。在两个大专院校就诊的患者均由两名肌病专家进行了肌肉活检和分析。将肌肉活检样品在冷却的异戊烷中冷冻，将低温恒温器切片并染色。免疫组织化学研究也在我们的实验室中作为常规程序进行。结果我们确定了9位接受抗PD-1或PD-L1抑制剂治疗的患者，这些患者针对肌肉无力，虚弱，肌无力综合征或其他肌肉相关症状，以及经活检证实的炎症性肌病进行咨询。一个伴有心肌炎。在大多数情况下，肌肉活检显示出明显的坏死现象，巨噬细胞和肌肉再生，伴有大量巨噬细胞成分的血管周围炎性浸润。还发现了束周围萎缩的趋势。MHC I类抗原的表达主要在束周围区域。在7例患者中检测到肌肉酶升高。结论在接受PD-1和PD-1 L抑制剂的患者中发现了特征性的临床病理模式，包括重症肌无力样综合征和肌炎。巨噬细胞类似肉芽肿的很大一部分似乎是该综合征的病理标志。需要进一步的信息来了解在使用抗PD-1抑制剂治疗期间或之后涉及肌肉的与免疫相关的各种不良事件，但病理学特征似乎是特征性的。