M. J. L. Mastboom, D. Uittenbogaard, M. A. J. v. d. Sande, Orthopaedics Oncology Department, Leiden University Medical Center, Leiden, The Netherlands F. G. M. Verspoor, H.W. B. Schreuder, Orthopaedics Oncology Department, Radboud University Medical Center, Radboud, The Netherlands G. R. Schaap, Orthopaedics Oncology Department, Academic Medical Center Amsterdam, Amsterdam, The Netherlands P. C. Jutte, Orthopaedics Oncology Department, University Medical Center, Groningen, Groningen, The Netherlands.
Clin Orthop Relat Res. 2018 Sep;476(9):1803-1812. doi: 10.1007/s11999.0000000000000102.
Tenosynovial giant cell tumor (TGCT) is a rare, benign, monoarticular entity. Many case-series in adults are described, whereas TGCT is only incidentally reported in children. Therefore, its incidence rate and natural history in children are unknown.
QUESTIONS/PURPOSES: (1) How many cases have been reported of this condition, and what were their characteristics? (2) What is the standardized pediatric incidence rate for TGCT? (3) Is there a clinical difference in TGCT between children and adults? (4) What is the risk of recurrence after open resection in children compared with adults?
Data were derived from three sources: (1) a systematic review on TGCT in children, seeking sources published between 1990 and 2016, included 17 heterogeneous, small case-series; (2) the nationwide TGCT incidence study: the Dutch pediatric incidence rate was extracted from this nationwide study by including patients younger than 18 years of age. This registry-based study, in which eligible patients with TGCT were clinically verified, calculated Dutch incidence rates for localized and diffuse-type TGCT in a 5-year timeframe. Standardized pediatric incidence rates were obtained by using the direct method; (3) from our nationwide bone and soft tissue tumor data registry, a clinical data set was derived. Fifty-seven children with histologically proven TGCT of large joints, diagnosed and treated between 1995 and 2015, in all four tertiary sarcoma centers in The Netherlands, were included. These clinically collected data were compared with a retrospective database of 423 adults with TGCT. Chi-square test and independent t-test were used to compare children and adults for TGCT type, sex, localization, symptoms before diagnosis, first treatment, recurrent disease, followup status, duration of symptoms, and time to followup. The Kaplan-Meier method was used to evaluate recurrence-free survival at 2.5 years.
TGCT is seldom reported because only 76 pediatric patients (39 female), 29 localized, 38 diffuse, and nine unknown type, were identified from our systematic review. The standardized pediatric TGCT incidence rate of large joints was 2.42 and 1.09 per million person-years in localized and diffuse types, respectively. From our clinical data set, symptoms both in children and adults were swelling, pain, and limited ROM with a median time before diagnosis of 12 months (range, 1-72 months). With the numbers available, we did not observe differences in presentation between children and adults in terms of sex, symptoms before diagnosis, first treatment, recurrent disease, followup status, or median time to followup. The 2.5-year recurrence-free TGCT survival rate after open resection was not different with the numbers available between children and adults: 85% (95% confidence interval [CI], 67%-100%) versus 89% (95% CI, 83%-96%) in localized, respectively (p = 0.527) and 53% (95% CI, 35%-79%) versus 56% (95% CI, 49%-64%) in diffuse type, respectively (p = 0.691).
Although the incidence of pediatric TGCT is low, it should be considered in the differential diagnosis in children with chronic monoarticular joint effusions. Recurrent disease after surgical treatment of this orphan disease seems comparable between children and adults. With targeted therapies being developed, future research should define the most effective treatment strategies for this heterogeneous disease.
Level III, therapeutic study.
腱鞘巨细胞瘤（TGCT）是一种罕见的良性、单关节炎实体瘤。许多成人病例系列报告描述了这种疾病，而在儿童中，TGCT 只是偶然报告。因此，其在儿童中的发病率和自然史尚不清楚。
问题/目的：（1）有多少例这种疾病被报告，其特征是什么？（2）TGCT 在儿童中的标准化儿科发病率是多少？（3）儿童和成人之间 TGCT 是否存在临床差异？（4）与成人相比，儿童行开放性切除术后的复发风险如何？
数据来自三个来源：（1）一项关于儿童 TGCT 的系统评价，旨在寻找 1990 年至 2016 年期间发表的来源，其中包括 17 项异质性小病例系列；（2）全国性 TGCT 发病率研究：从这项全国性研究中提取荷兰儿科发病率，纳入年龄小于 18 岁的患者。这项基于注册的研究对患有 TGCT 的符合条件的患者进行了临床验证，在 5 年的时间内计算了局限性和弥漫性 TGCT 的荷兰发病率。通过直接法获得标准化儿科发病率；（3）从我们的全国性骨和软组织肿瘤数据登记处，得出一个临床数据集。纳入了 1995 年至 2015 年间在荷兰四个三级肉瘤中心诊断和治疗的 57 例大关节、组织学证实的 TGCT 患儿，这些患儿均为单侧。这些临床收集的数据与 423 例成人 TGCT 的回顾性数据库进行了比较。使用卡方检验和独立 t 检验比较儿童和成人的 TGCT 类型、性别、部位、诊断前症状、首次治疗、复发病例、随访状态、症状持续时间和随访时间。采用 Kaplan-Meier 方法评估 2.5 年无复发生存率。
由于仅从我们的系统评价中确定了 76 例儿科患者（39 例女性），包括 29 例局限性、38 例弥漫性和 9 例未知类型，因此 TGCT 很少被报告。局限性和弥漫性 TGCT 在大关节中的标准化儿科发病率分别为 2.42 和 1.09/百万人年。从我们的临床数据集来看，儿童和成人的症状均为肿胀、疼痛和活动范围受限，中位诊断前时间为 12 个月（范围 1-72 个月）。根据现有数据，我们没有观察到儿童和成人在性别、诊断前症状、首次治疗、复发病例、随访状态或中位随访时间方面的表现存在差异。开放性切除术后 2.5 年 TGCT 无复发生存率在儿童和成人之间也没有差异：局限性分别为 85%（95%置信区间[CI]，67%-100%）和 89%（95% CI，83%-96%）（p=0.527），弥漫性分别为 53%（95% CI，35%-79%）和 56%（95% CI，49%-64%）（p=0.691）。
尽管儿童 TGCT 的发病率较低，但在儿童慢性单关节炎性关节积液的鉴别诊断中应考虑到这种疾病。这种罕见疾病的手术治疗后复发病例似乎在儿童和成人之间相似。随着靶向治疗的发展，未来的研究应确定这种异质性疾病最有效的治疗策略。
III 级，治疗性研究。
