Giant Cell Tumor of Tendon Sheath and Tendinopathy as Early Features of Early Onset Sarcoidosis

Abstract

Giant cell tumor of tendon sheath (GCTTS) is characterized by diffuse proliferation of synovial-like cells and multinucleated giant cells along tendon sheaths. This benign tumor typically presents in the third to fourth decade of life and is exceeding rare in children. Here we describe a case of a 10-years-old girl with a history of soft tissue swelling involving the third digit of left hand, bilateral wrists and ankles. Pathology of the finger mass revealed abundant multinucleated giant cells consistent with GCTTS. Resection of the tendinous masses from the ankles also showed multinucleated giant cells along with chronic bursitis. She began to show features of polyarticular arthritis by age 7. Due to progression of arthritis, whole exome sequencing was performed and found a de novo heterozygous mutation in NOD2 (p. R334Q). This variant is the most common mutation responsible for early onset sarcoidosis (EOS)/Blau syndrome, an autoinflammatory disease characterized by granulomatous inflammation of joints, skin and eyes. The early onset of symptoms and presence of multinucleated giant cells and granuloma in this case are in keeping with a diagnosis of EOS/Blau syndrome. The patient responded well to treatment with methotrexate and etanercept. This case extends the clinical spectrum of EOS/Blau syndrome, which should be considered for GCTTS and other unusual presentations of tendon inflammation in children, even in the absence of the characteristic triad of arthritis, dermatitis and uveitis.

Keywords: Blau syndrome; early onset sarcoidosis; giant cell tumor of tendon sheath; tendinopathy; tumor.

Figure 1

GCTTS presenting in a young child. (A) Presence of a soft tissue mass along the third digit of left hand. (B) Hematoxylin and Eosin (H&E) staining of resected finger mass consistent with a diagnosis of GCTTS. Arrowheads indicate multinucleated giant cells.

Figure 2

Progressive development of tendinopathy and arthritis. (A) Soft tissue swelling along the wrists and ankles. (B) X-ray of hand illustrating bone erosions of left wrist and fifth proximal interphalangeal joint. (C) H&E staining of resected mass from the right ankle. Arrow indicates multinucleated giant cell within a granulomatous structure. (D) MRI of left wrist illustrating erosions of carpal bone.

Figure 3

Identification of a mutation in NOD2. (A) Whole exome sequencing (WES) revealed a de novo mutation of NOD2 in the proband that was not found in the parents. This variant was previously described in EOS/Blau syndrome and is predicted to be pathogenic by multiple mutation analysis algorithms including SIFT, Polyphen2, and CADD. (B) MRI images of the right ankle before treatment and 1 year after initiation of etanercept and methotrexate. Arrows indicate an enhancing mass along the anterior tibialis tendon.