Tenosynovial Giant Cell Tumors in Children: A Similar Entity Compared With Adults

Abstract

Background: 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?

Methods: 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.

Results: 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).

Conclusions: 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 of evidence: Level III, therapeutic study.

Fig. 1 A-B

Localized type TGCT: MRI of a 6-year-old boy with TGCT in his left knee. (A) Sagittal T1-weighted image showing a well-circumscribed nodular lesion at the synovial lining of the anterior knee compartment. (B) Sagittal T1-weighted spectral presaturation with inversion recovery (SPIR) image after IV gadolinium administration shows heterogeneous enhancement.

Fig. 2A-B

Diffuse type TGCT: MRI of a 16-year-old boy with TGCT in his left knee. (A) Sagittal T1-weighted turbo spin echo (TSE) image shows extensive intra- and extraarticular villous proliferation of synovium. Posterior is a large Baker’s cyst. (B) Transversal T2-weighted TSE image with heterogeneous low to intermediate signal of the TGCT anterior and posterior (straight arrow). Baker’s cyst is shown posteriorly (curved arrow).

Fig. 3

Skeleton showing TGCT localization in children extracted from a Dutch incidence study, excluding digits [14]. In diffuse TGCT, one patient was classified as “other”; he was treated for TGCT in his vertebral column.

Fig. 4

Local recurrence-free survival curve of localized and diffuse TGCT (Kaplan-Meier), excluding digits. Time zero is the time of the primary surgery. All patients were surgically treated; patients treated with wait-and-see treatment are excluded. In the adult graph, two patients died and were censored at the time of death if recurrence had not occurred.