Tenosynovial giant cell tumour/pigmented villonodular synovitis: Outcome of 294 patients before the era of kinase inhibitors

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Abstract

Background

Tenosynovial giant cell tumour/pigmented villonodular synovitis (TGCT/PVNS) is a benign neoplasm of synovium and tendon sheath. We conducted a retrospective pooled analysis in three major referral centers.

Methods

Patients treated between 1998 and 2008 were examined. Only patients presenting with primary disease or first relapse were included. 5-year local failure free survival (5-year-LFFS) was analysed.

Results

294 patients were included: 254 with new diagnosis and 40 in 1st local recurrence (171 F/123 M; median age: 36 years; tumour size ⩽2 cm in 27% of patients, >2 to ⩽5 cm in 41%, and >5 cm in 32%). A diffuse pattern was reported in 69%, localised in 31%. No metastases were documented. Local failure (LF) was reported in 28% of patients: 36% in diffuse pattern, 14% in localised (p = 0.002); median time to LF: 16 months.

With a median follow-up of 4.4 years, 5-year-LFFS was 66%, with multiple (up to five) local recurrences in 40% of relapsed patients. Size <2 cm, macroscopically complete resection, female gender and new diagnosis were associated with a better local control. After multivariate analysis, a previous relapse was independently associated with local failure.

Conclusions

This study underlines the propensity of TGCT/PVNS to multiple local recurrences. In absence of clinical factors, biological studies are needed to identify prognostic factors of local failure. After a first local recurrence, surgery does not seem to have a curative potential. In these high risk patients, studies addressing the role of target therapies are needed.

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.

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    Funding: Dr. E. Palmerini work is supported by the Regional High Technology Network, PROMETEO Laboratory at Istituto Ortopedico Rizzoli.

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