Mencel Justin, Gargett Tessa, Karanth Narayan, Pokorny Adrian, Brown Michael P, Charakidis Michail
Department of Medicine, Royal Darwin Hospital, Darwin, Northern Territory, Australia.
Cancer Clinical Trials Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
Asia Pac J Clin Oncol. 2019 Dec;15(6):383-386. doi: 10.1111/ajco.13233. Epub 2019 Aug 1.
Hyperplasia of the thymus is commonly seen in myasthenia gravis and other autoimmune disorders. Thymic size also varies with age, corticosteroid use, infections, and inflammatory disease. Although thymic hyperplasia has been described following chemotherapy, there is no known association of true thymic hyperplasia with immune checkpoint inhibitor therapy. We present two cases of suspected true thymic hyperplasia in patients with stage IV melanoma who were treated with the combination of nivolumab and ipilimumab, which was complicated by immune-related toxicity requiring corticosteroid therapy, and then subsequently also by secondary hypoadrenalism requiring replacement hydrocortisone. In one patient, histological and flurocytometric analyses of an incisional biopsy of the thymus revealed findings consistent with true thymic hyperplasia. In the other case, the stable fluorodeoxyglucose positron emission tomography/Computed tomography (FDG-PET/CT) findings were consistent also with true thymic hyperplasia. These are the first described cases of true thymic hyperplasia following combination immune checkpoint inhibitor therapy for metastatic melanoma. We hypothesize that the true thymic hyperplasia in these cases results from initial lymphocyte depletion caused by intense corticosteroid therapy followed by rebound thymic hyperplasia during the period of relative hypocortisolism, which may have been aggravated by the onset of secondary hypoadrenalism.
胸腺增生常见于重症肌无力和其他自身免疫性疾病。胸腺大小也会因年龄、使用皮质类固醇、感染及炎症性疾病而有所不同。尽管化疗后曾有胸腺增生的描述，但目前尚无已知的真正胸腺增生与免疫检查点抑制剂治疗之间的关联。我们报告了两例IV期黑色素瘤患者疑似真正胸腺增生的病例，这两名患者接受了纳武单抗和伊匹单抗联合治疗，出现了需要皮质类固醇治疗的免疫相关毒性并发症，随后又出现了需要补充氢化可的松的继发性肾上腺皮质功能减退。在一名患者中，胸腺切开活检的组织学和荧光细胞分析结果显示符合真正的胸腺增生。在另一例中，稳定的氟脱氧葡萄糖正电子发射断层扫描/计算机断层扫描（FDG-PET/CT）结果也符合真正的胸腺增生。这些是首次报道的转移性黑色素瘤联合免疫检查点抑制剂治疗后出现真正胸腺增生的病例。我们推测，这些病例中的真正胸腺增生是由于强化皮质类固醇治疗导致初始淋巴细胞耗竭，随后在相对皮质醇缺乏期间出现胸腺增生反弹，而继发性肾上腺皮质功能减退的发生可能加剧了这种情况。
