系统性治疗局限性喉淀粉样变性：病例系列及文献综述

文献信息

中文摘要

背景： 局限性喉淀粉样变性是一种局限于喉部的局部浆细胞介导过程，以细胞外淀粉样物质沉积为特征。传统上手术切除是主要治疗手段；然而，完全切除在解剖上可能困难，且部分患者出现持续或进展性疾病。支持系统性治疗用于局限性疾病的证据仍然有限。方法：我们报告了两例经活检证实为局限性喉淀粉样变性、无全身受累证据的成年女性患者，她们在与耳鼻喉科及头颈外科团队合作下接受了针对浆细胞的免疫化疗。结果：两名患者均表现为进行性加重的发声困难。一例在部分手术切除后症状持续，另一例为多灶性不可切除的声门上病变。鉴于手术选择有限，开始使用达雷妥尤单抗、环磷酰胺、硼替佐米和地塞米松（Dara-CyBorD）治疗。治疗总体耐受良好，仅报告了轻度神经病变和轻度白细胞减少。经过6-14个周期后，两名患者的嗓音质量和功能状态均显著改善，无影像学或临床进展证据。两名患者均无需额外手术干预，且在随访期间均获得了持久的症状控制。结论：这些病例凸显了在手术无法治愈或不可行时，系统性浆细胞靶向治疗在特定局限性喉淀粉样变性患者中的潜在作用。尽管单纯局部切除对许多患者仍可治愈，但在复杂病例中多学科协作至关重要。需要进一步研究以明确患者选择、最佳治疗持续时间以及系统性免疫化疗在这种罕见疾病中的长期结局。

英文摘要

Localized laryngeal amyloidosis is a localized plasma cell-mediated process characterized by extracellular amyloid deposition confined to the larynx. Surgical excision has traditionally been the mainstay of treatment; however, complete resection may be anatomically difficult, and some patients experience persistent or progressive disease. Evidence supporting systemic therapy in localized disease remains limited. We report two adult female patients with biopsy-proven localized laryngeal amyloidosis without evidence of systemic involvement who were treated with plasma cell-directed immunochemotherapy in collaboration with ENT and head and neck surgery teams. Both patients presented with worsening dysphonia. One had persistent symptoms following partial surgical resection, while the other had multifocal unresectable supraglottic disease. Given limited surgical options, treatment with daratumumab, cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) was initiated. Therapy was well tolerated overall, with only mild neuropathy and mild leukopenia reported. After 6-14 cycles, both patients experienced marked improvement in voice quality and functional status, with no radiographic or clinical evidence of progression. Neither patient required additional surgical intervention, and both achieved durable symptom control during follow-up. These cases highlight a potential role for systemic plasma cell-targeted therapy in selected patients with localized laryngeal amyloidosis when surgery is noncurative or not feasible. Although local resection alone remains curative for many patients, multidisciplinary collaboration is essential in complex cases. Further study is needed to clarify patient selection, optimal treatment duration, and long-term outcomes of systemic immunochemotherapy in this rare disorder.