Department of Pathology, Section of Dermatopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Translational and Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
J Immunother Cancer. 2018 Feb 12;6(1):14. doi: 10.1186/s40425-018-0323-0.
Immune checkpoint therapy has dramatically changed the landscape of cancer therapy, providing an efficacious and durable therapeutic option for patients with advanced-stage disease. However, dermatologic toxicities are a well-recognized side effect in patients receiving this therapy. A spectrum of immune related adverse events (irAEs) involving the skin can occur and include immunobullous disorders, lichenoid dermatitis, and vitiligo. Granulomatous/sarcoid-like lesions are now being recognized with the current class of checkpoint inhibitors (CPIs) that involve the dermis, the subcutaneous tissue (panniculitis), and lymph nodes.
We report 3 patients who developed granulomatous/sarcoid-like lesions while being treated with immune checkpoint therapy for advanced-stage melanoma, and we provide a comprehensive review of the literature in which similar cases are described. To date, 26 patients (including the 3 from this report) have been described with a median age of 57 years who developed granulomatous/sarcoid-like lesions associated with CPIs (median onset 6 months), of which 77% of patients had melanoma as primary tumor. To manage this adverse side effect, therapy was withheld in 38% of patients and 44% of the patients were treated with systemic steroids and 8% patients with localized therapy (one patient with intralesional triamcinolone). 96% of patients demonstrated either resolution or improvement of granulomatous/sarcoid-like lesions associated with CPIs irrespective of medical intervention. Therapeutic response, stable disease, or remission of primary malignancy was observed in 71% of reported patients who developed granulomatous/sarcoid-like lesions associated with CPIs over a median follow-up of 11.5 months since initiation of treatment.
The development of granulomatous/sarcoid-like lesions associated with CPIs is a recognized manifestation with the current class of immune checkpoint therapy that may clinically and radiographically mimic disease recurrence. Awareness of this type of toxicity is important for appropriate management and possible measurement of therapeutic response in a subset of patients who manifest this type of immune-mediated reaction.
免疫检查点疗法极大地改变了癌症治疗的格局，为晚期疾病患者提供了一种有效且持久的治疗选择。然而，接受这种治疗的患者会出现众所周知的皮肤毒性。在接受当前这一类免疫检查点抑制剂（CPIs）治疗的患者中，会出现涉及皮肤的一系列免疫相关不良反应（irAEs），包括免疫性大疱病、类扁平苔藓样皮炎和白癜风。目前已经认识到真皮、皮下组织（脂膜炎）和淋巴结中存在肉芽肿/类肉瘤样病变。
我们报告了 3 例接受免疫检查点治疗晚期黑色素瘤的患者发生肉芽肿/类肉瘤样病变的情况，并对文献中描述的类似病例进行了全面回顾。迄今为止，已描述了 26 例（包括本报告中的 3 例）患者，中位年龄为 57 岁，这些患者因 CPIs 而发生肉芽肿/类肉瘤样病变（中位发病时间为 6 个月），其中 77%的患者原发肿瘤为黑色素瘤。为了管理这种不良反应，38%的患者暂停了治疗，44%的患者接受了全身皮质类固醇治疗，8%的患者接受了局部治疗（1 例患者接受了皮损内曲安奈德）。无论是否进行了医学干预，96%的患者与 CPIs 相关的肉芽肿/类肉瘤样病变都得到了缓解或改善。在接受 CPIs 治疗的患者中，71%的患者报告了与 CPIs 相关的肉芽肿/类肉瘤样病变，在中位随访 11.5 个月后，观察到原发性恶性肿瘤的治疗反应、疾病稳定或缓解。
与当前这一类免疫检查点疗法相关的肉芽肿/类肉瘤样病变的发生是一种已被认识到的表现，这种病变在临床上和影像学上可能与疾病复发相似。了解这种毒性作用对于适当管理和在表现出这种免疫介导反应的患者亚组中测量治疗反应非常重要。
