Department of Pathology, Groupement Hospitalier Est, Hospices Civils de Lyon, UCBL Lyon 1 University, Lyon, France.
SIREDO Oncology Center, Institut Curie, PSL University, Paris, France.
Mod Pathol. 2019 Apr;32(4):546-559. doi: 10.1038/s41379-018-0174-8. Epub 2018 Nov 6.
The prognosis of malignant pediatric adrenocortical tumors is closely related to disease stage, which is used to guide perioperative treatment recommendations. However, current scoring systems are inadequate to distinguish between benign and malignant adrenocortical tumors. Robust microscopic prognostic features that could help determine perioperative therapy are also lacking. The aim of this national study was to review the prognostic value of the Wieneke scoring criteria and Ki67 labeling index in unselected pediatric adrenocortical tumors. Using strict definitions previously defined by expert pathologists, a Wieneke score was re-attributed to each tumor after an independent and centralized review. In addition, Ki67 proliferation index was performed and reviewed for each case. A total of 95 cases were selected; all were treated between 2000 and 2018 and had histopathologic material and sufficient outcome-related information available. Localized disease was found in 88% of patients. Among those with advanced disease, 6% had tumor extension into adjacent organs and 5% had metastases at diagnosis. Median follow-up was 5 years and 3 months. The 5-year PFS was 82%, 95% CI [73%-91%]. Tumor stage significantly correlated with PFS (p < 0.0001). Tumor weight up to 200 g, extra-adrenal extension and initial non-complete surgical resection were statistically associated with worse outcomes. No recurrences nor metastases occurred when the Ki67 index was < 15%. Up to two of the following five factors including tumor necrosis, adrenal capsular invasion, venous invasion, mitotic count > 15/20 high-power fields, and Ki67 index > 15%, significantly correlated with worse outcomes. We propose a pathological scoring system incorporating the Ki67 index as part of a two-step approach after disease staging to guide adjuvant treatment in pediatric adrenocortical tumors, especially after incomplete resection. These results should be validated in an independent cohort.
儿童恶性肾上腺皮质肿瘤的预后与疾病分期密切相关，分期用于指导围手术期治疗建议。然而，目前的评分系统不足以区分良恶性肾上腺皮质肿瘤。也缺乏能够帮助确定围手术期治疗的强有力的微观预后特征。本研究的目的是回顾分析 Wieneke 评分标准和 Ki67 标记指数在未选择的儿童肾上腺皮质肿瘤中的预后价值。使用之前由专家病理学家定义的严格定义，对每个肿瘤进行独立和集中的重新评估，重新归因 Wieneke 评分。此外，对每个病例进行 Ki67 增殖指数检测和评估。共选择了 95 例；所有病例均于 2000 年至 2018 年接受治疗，且具有组织病理学材料和足够的与结局相关的信息。88%的患者存在局限性疾病。在进展期患者中，6%的患者肿瘤侵犯邻近器官，5%的患者在诊断时存在转移。中位随访时间为 5 年 3 个月。5 年 PFS 为 82%，95%CI [73%-91%]。肿瘤分期与 PFS 显著相关（p < 0.0001）。肿瘤重量达 200 g、肾上腺外侵犯和初始不完全手术切除与预后不良统计学相关。Ki67 指数<15%时，无复发或转移。肿瘤坏死、肾上腺被膜侵犯、静脉侵犯、有丝分裂计数>15/20 高倍视野和 Ki67 指数>15%等 5 个因素中的 2 个或 2 个以上与预后不良显著相关。我们提出了一种病理评分系统，将 Ki67 指数纳入疾病分期后的两步法中，以指导儿童肾上腺皮质肿瘤的辅助治疗，特别是在不完全切除后。这些结果应在独立队列中得到验证。
