Jain Ekta, Diaz Jorge A, Goksel Mustafa, Basu Arnab, Magi-Galluzzi Cristina
Department of Pathology, The University of Alabama at Birmingham, Alabama, USA.
Department of Hematology and Oncology, Clearview Cancer Institute, Huntsville, Alabama, USA.
Pathologica. 2025 Jun;117(3):249-257. doi: 10.32074/1591-951X-N998. Epub 2025 Jun 6.
Therapeutic landscape of metastatic renal cell carcinoma (mRCC) has transformed over the last 2 decades, particularly with the advent of immune checkpoint inhibitors (ICI). While ICI offer therapeutic benefits, they can also provoke immune-related adverse events (iRAEs). Vasculitis as a clinical iRAE from ICI is rare in association with RCC treatment.
This study included patients treated at our institution with ICI for mRCC (2019-2024). We collected clinicopathologic data and type and duration of immunotherapy. Histologic sections of tumors were re-reviewed by two pathologists to determine pathologic response and features of ICI-related renal injuries.
We identified 8 patients (median age 61.5 years) of which six (75%) presented with metastases at multiple sites, while two had recurrent oligometastatic disease post-partial nephrectomy. All patients were treated with ICI for a duration ranging from 6 to 20 months; 7 patients received combination therapy (CT) [iplimumab & nivolumab (n = 3), pembrolizumab & lenvatinib (n = 2), nivolumab & carbozantinib (n = 1), pembrolizumab & axitinib (n = 1)], while one received monotherapy (MT) (pembrolizumab). Patients were poor surgical candidates at diagnosis (25% Stage 3, 75% stage 4). Six (75%) patients had clear cell RCC (CCRCC), 2 patients had RCC with papillary and eosinophilic features. Tumor necrosis was noted in 75% of cases. Partial tumor response occurred in 7 (87.5%) patients, with 3 (37.5%) achieving tumor downstaging. One patient showed stable primary disease despite resolution of metastatic burden and none of the patients achieved complete response. Three patients (37.5%) had histopathological confirmed renal iRAEs. Two (25%) patients displayed vascular lymphocytic infiltrates, consistent with medium vessels vasculitis; they received CT for 6 months. One patient, who received CT for 20 months, showed a non-necrotizing granuloma.
This study highlights the potential of ICIs for tumor downstaging and disease control in mRCC, though further investigation is warranted to optimize management of iRAEs and long-term outcomes. ICI-associated renal vasculitis is likely underrecognized and underreported highlighting the need for thorough pathological evaluation of non-neoplastic renal tissue in patients receiving ICI.
在过去20年中，转移性肾细胞癌（mRCC）的治疗格局发生了变化，尤其是随着免疫检查点抑制剂（ICI）的出现。虽然ICI提供了治疗益处，但它们也可能引发免疫相关不良事件（iRAE）。作为ICI临床iRAE的血管炎在RCC治疗中很少见。
本研究纳入了2019年至2024年在我们机构接受ICI治疗mRCC的患者。我们收集了临床病理数据以及免疫治疗的类型和持续时间。两名病理学家对肿瘤组织切片进行重新评估，以确定病理反应和ICI相关肾损伤的特征。
我们确定了8例患者（中位年龄61.5岁），其中6例（75%）出现多处转移，2例在部分肾切除术后出现复发性寡转移疾病。所有患者接受ICI治疗的持续时间为6至20个月；7例患者接受联合治疗（CT）[伊匹木单抗和纳武单抗（n = 3）、帕博利珠单抗和乐伐替尼（n = 2）、纳武单抗和卡博替尼（n = 1）、帕博利珠单抗和阿昔替尼（n = 1）]，1例接受单药治疗（MT）（帕博利珠单抗）。患者在诊断时手术条件较差（25%为3期，75%为4期）。6例（75%）患者为透明细胞肾细胞癌（CCRCC），2例患者的肾细胞癌具有乳头状和嗜酸性特征。75%的病例出现肿瘤坏死。7例（87.5%）患者出现部分肿瘤反应，3例（37.5%）实现肿瘤降期。1例患者尽管转移灶消退但原发疾病稳定，无患者实现完全缓解。3例（37.5%）患者经组织病理学证实存在肾iRAE。2例（25%）患者出现血管淋巴细胞浸润，符合中血管血管炎；他们接受了6个月的CT治疗。1例接受20个月CT治疗的患者出现非坏死性肉芽肿。
本研究强调了ICI在mRCC中使肿瘤降期和控制疾病的潜力，不过仍需进一步研究以优化iRAE的管理和长期结局。ICI相关的肾血管炎可能未得到充分认识和报告，这凸显了对接受ICI治疗的患者的非肿瘤性肾组织进行全面病理评估的必要性。
