APLAR GRAND ROUND CASE Refractory knee giant cell tumor of the synovial membrane treated with intra-articular injection of Infliximab: a case series and review of the literature Emanuela PRAINO, 1 Giovanni LAPADULA, 1 Crescenzio SCIOSCIA, 1 Giuseppe INGRAVALLO, 2 Michele COVELLI, 1 Giuseppe LOPALCO 1 and Florenzo IANNONE 1 1 Rheumatology Unit, Medical School, University of Bari, and 2 Pathology Unit, Medical School, University of Bari, Bari, Italy Abstract Giant cell tumor (GCT) of the synovial membrane, also known as pigmented villonodular synovitis, causes a pro- gressive, relapsing and destructive arthropathy affecting one or more synovial joints. Systemic therapy can be com- bined to intra-articular treatments, including surgical synoviectomy, especially when monoarticular. Despite that, the synovial membrane commonly grows again with clinical relapse. Here, we report three case of patients diag- nosed with GCT of the knee who had an early relapse of the disease even after surgical synoviectomy. All of them underwent intra-articular therapy with infliximab and subsequent synoviectomy to eradicate residual tissue. A complete remission of CGT was achieved without relapse occurring during the follow-up. These preliminary data need to be confirmed by further clinical trials; however, intra-articular therapy with infliximab might be deemed a potential option to treat CGT of a single joint. Key words: blocking-TNFa, giant cell tumor, intra-articular injection of infliximab, knee, pigmented villonodular synovitis. INTRODUCTION Giant cell tumour (GCT) of the synovial membrane and pigmented villonodular synovitis (PVNS) have been proposed to be unified because they have identical histological and genetic features 1 and more recently the term GCT or PVNS is indifferently used to indicate the same disease. 2,3 GCT (PVNS) has the following patho- gnomonic histological features: moderate synovial-like cell proliferation together with a variable number of multinucleated giant cells scattered within an inflam- matory infiltrate, siderophages, and xanthomatous cells. 4 The pathogenesis of GCT is still controversial. In 1852 Chassaignac 5 defined it as ‘cancer of the tendon sheath’, but a century later Jaffe et al. 6 described it as an inflammatory reparative lesion of the synovial tissue caused by joint trauma. Current data strongly suggest that GCT is sustained by a proliferation of neoplastic- like synoviocytes. The hypothesis considering GCT as a benign tumor originating from the synovial cells 7,8 is based on the findings of aneuploid DNA, cytogenetic abnormalities, the tendency to spontaneous growth and relapse, and the abnormalities of the cell cycle with over-expression of protein Ki-67 (as in severe forms of dysplasia), protein Bc12 and humanin peptide. 9,10 Cases of isolated GCT have definite clinical signs and histological features of malignant tumors, and lymph node metastases have been rarely reported. 11 On the other hand, some studies have provided evi- dence that chronic inflammation plays a key role in the pathogenesis, given that some pro-inflammatory cyto- kines and metalloproteinases are over-expressed in GCT. 12 Tumor necrosis factor-a (TNF-a) plays a direct role in increasing synovial proliferation, leading to the Correspondence: Associate Professor Florenzo Iannone, D.I.M.- Rheumatology Unit, Policlinico, Piazza G.Cesare 11, 70124 Bari, Italy. Email: florenzo.iannone@uniba.it © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd International Journal of Rheumatic Diseases 2015; 18: 908–912