Tenosynovial giant cell tumour/pigmented villonodular synovitis: Outcome of 294 patients before the era of kinase inhibitors
Introduction
The term tenosynovial giant cell tumour (TGCT) refers to a family of proliferative and inflammatory diseases of benign course arising from the synovium of joint, bursae and tendon sheaths. This includes the entity that used to be called pigmented villonodular synovitis (PVNS). The lesion can either present as a single nodule (localised form), or as multiple nodules (diffuse form) along a synovial layer or tendon sheath [1], [2], [3], [4], [5], [6].
Surgery is the mainstay of treatment, but local failure is frequent, with local relapse rates up to 50% [2], [7], [8]. Furthermore, repetitive surgical treatment can lead to substantial morbidity to the joints and quality of life impairment. External-beam radiation therapy [9], isotopic synovectomy [7] and cryosurgery [10] have been proposed, as an adjunct to surgical resection, in order to improve local control.
Historically, there is no effective medical treatment, but new drugs are under investigation. A recent study showed activity of imatinib, a multi-tyrosine kinase inhibitor (TKI), in patients with advanced TGCT/PVNS [11] and clinical trials addressing the activity of MCSF1R inhibitors in PVNS, are being carried out [12], [13], [14], [15]. On this basis, we decided to perform a pooled analysis of the TGCT/PVNS cases observed in three major referral centers for soft tissue tumours, in order to describe clinical presentation, treatment and outcome of TGCT/PVNS, and to identify factors prognostic for local recurrence (LR). This could help identifying high risk patients, candidates for targeted treatments in future clinical trials.
Section snippets
Design
The design of the present study was a systematic tri-institutional retrospective analysis, conducted at the Istituto Ortopedico Rizzoli, Bologna, Italy (IOR), the Fondazione IRCCS Istituto Nazionale Tumori (INT) and Gaetano Pini Hospital (GPI), Milano, Italy and Memorial Sloan Kettering Cancer Center (MSKCC), NY, United States of America (USA).
Patients
The patients in the present study included all cases of biopsy-proven TGCT/PVNS treated with surgery for primary tumour or first local relapse between
Results
A total of 294 consecutive patients with histologic diagnosis of TGCT/PVNS between 1998 and 2008 were identified. Patients were enrolled in the three participating institutions as follows: IOR 149 (51%); INT/GPI 102 (35%); MSKCC 43 (14%). Forty patients (14%) were admitted due to 1st LR after surgical treatment elsewhere, 254 (86%) patients had their first diagnosis at one of the study institutions.
Median age was 36 years (range: 11–89); 171 (58%) patients were female, 123 (42%) were male. The
Discussion
The treatment of choice for TGCT/PVNS is surgery. Marginal excision for localised TGCT/PVNS and total synovectomy for diffuse TGCT/PVNS is generally used [18], [19]. To better understand the outcome after surgical treatment, and to assess prognostic factors for local recurrence in patients with TGCT/PVNS, we carried out this retrospective analysis including data from three referral centers, giving rise to the largest series reported on this rare condition.
The major weakness of this analysis is
Conflict of interest statement
Stacchiotti S. Novartis, Roche: research funding; Plexxikon: advisory.
References (36)
- et al.
Pigmented villonodular synovitis: a retrospective single-center study of 122 cases and review of the literature
Semin Arthritis Rheum
(2011) - et al.
Radiation therapy for treatment of pigmented villonodular synovitis: results of a national patterns of care study
Int J Radiat Oncol Biol Phys
(2010) - et al.
Long-term follow-up of surgically treated localized pigmented villonodular synovitis of the knee
Arthroscopy
(2007) - et al.
Combined partial arthroscopic synovectomy and radiation therapy for diffuse pigmented villonodular synovitis of the knee
Arthroscopy
(2001) - et al.
Outcome following radiation treatment for high-risk pigmented villonodular synovitis
Int J Radiat Oncol Biol Phys
(1995) - et al.
Quality of surgery and neoadjuvant combined therapy in the ISG-GEIS trial on soft tissue sarcomas of limbs and trunk wall
Ann Oncol
(2013) - et al.
Macrophage colony-stimulating factor receptor c-FMS is a novel target of imatinib
Blood
(2005) - Somerhausen N, de S, van de Rijn M. Tenosynovial giant cell tumour, diffuse type. In: Fletcher CDM, Bridge JA,...
- et al.
Pigmented villonodular synovitis of joints
J Surg Oncol
(2011) - et al.
A landscape effect in tenosynovial-giant-cell tumor from activation of CSF1 expression by a translocation in a minority of tumor cells
Proc Natl Acad Sci USA
(2006)
Pathology of the synovium
Am J Clin Pathol
Analysis of 35 cases of localized and diffuse tenosynovial giant cell tumor: a report from the chromosomes and morphology (CHAMP) study group
Genes Chromosomes Cancer
Pigmented villonodular synovitis: a retrospective review of affected large joints
Clin Orthop Relat Res
Open synovectomy with cryosurgical adjuvant for treatment of diffuse pigmented villonodular synovitis of the knee
Bull Hosp Jt Dis
Efficacy of imatinib mesylate for the treatment of locally advanced and/or metastatic tenosynovial giant cell tumor/pigmented villonodular synovitis
Cancer
Cited by (96)
Use of neoadjuvant pexidartinib with limb salvage surgery for diffuse tenosynovial giant cell tumor: A case report
2024, Journal of Orthopaedic ScienceCitation Excerpt :Surgery is the mainstay of treatment but, while curative for localized disease, it is associated with failures above 50% for diffuse cases [2]. Local recurrence of disease has been shown to be a risk factor for subsequent failures of operative treatment, and repeated surgical interventions contribute to overall morbidity, joint stiffness, and impaired quality of life [3,4]. Because of this, multiple adjuvant therapies – including external beam radiotherapy, isotopic synoviorthesis, and cryotherapy – have been utilized attempting to limit local recurrences, but each have limited success and associated risks along with complicating future joint arthroplasty procedures [3,5].
Best clinical management of tenosynovial giant cell tumour (TGCT): A consensus paper from the community of experts
2023, Cancer Treatment ReviewsNew Drug Approvals for Sarcoma in the Last 5 Years
2022, Surgical Oncology Clinics of North AmericaCitation Excerpt :Surgical resection is the standard treatment in first-line but local relapses are frequent. Clinical symptoms involve swelling, pain, and functional impairment that are characteristic of the disease in particular at relapse.58,59 Surgery at relapse is rarely curative with less than 20% of patients free of relapse at 5 years.58
Differential diagnosis of bone- and soft tissue tumours as well as tumour-like lesions of the heel
2022, Fuss und Sprunggelenk
Funding: Dr. E. Palmerini work is supported by the Regional High Technology Network, PROMETEO Laboratory at Istituto Ortopedico Rizzoli.