Discussion

GCTs are classified according to their site of origin, namely bone, soft tissue, synovium or tendon sheath. Those that arise from tendons and synovium are classified into two forms: localised (nodular tenosynovitis) mainly involves the digits and diffuse [pigmented villonodular synovitis (PVNS)] involving large joints such as knee, hip, ankle and elbow. ^{Reference Gouin and Noailles1,Reference Heijden, Gibbons and Dijkstra2} The latter is rare with incidence of 2 cases per million per year. It is a benign proliferative tumour that develops in the synovium with high risk of recurrence. ^{Reference Somerhausen and Fletcher3} The aetiology and pathogenesis of PVNS are unknown, but it may be due to chronic inflammation. ^{Reference Oehler, Hans and Fassbender4} There is no difference between genders with younger patients seem predominantly affected. The most common complaint is intermittent joint pain. ^{Reference Myers, Masi and Feigenbaum5}

There is no standard guideline or consensus on surgical procedure or postoperative therapy. The treatment is extrapolated from previous case series. A multimodality approach including MRI, evaluation of the knee and complete synovectomy, either as a single or a staged procedure with postoperative therapy results in a lower recurrence rate and fewer complications. MRI features of PVNS include different extent of synovial proliferation, joint effusion and erosion of bone, and in particular the deposit of hemosiderin within the synovial masses. ^{Reference Cheng, You, Liu, Zhao and Qu6}

PVNS of the knee is associated with a higher recurrence rate than PVNS at other joints ^{Reference Schwartz, Unni and Pritchard7} due to the anatomical limitation of the lesion; radical resection of diffuse PVNS is very difficult. Arthroscopic synovectomy is an appropriate treatment for knee PVNS. Extended synovectomy is recommended for diffuse PVNS. ^{Reference Ponti, Sansone and Malchere8} This technique requires technical expertise, and complete excision is rarely achieved even by experienced arthroscopic surgeons.

The risk factors for recurrence include diffuse form of the disease, incomplete resection, location of the lesions, the experience and skills of the surgeon, and adjuvant therapy after surgery. ^{Reference Fang and Zhang9}

Postoperative RT has been used to achieve better local control in patients with primary or recurrent PVNS. ^{Reference O’Sullivan, Cummings and Catton10} It should also be considered for patients receiving a radical synovectomy to treat inaccessible or hidden disease sites. ^{Reference Blanco, Leon and Guthrie11} A large number of reports have confirmed that adjuvant postoperative external beam RT can further reduce the recurrence rate. De Carvalho et al reported that 8 patients with diffuse PVNS of the knee who had synovectomy with subsequent local external beam RT had a recurrence rate of 12.5% at 8.6 years of follow-up. ^{Reference de Carvalho, Soares, Goncalves, Temponi and Melo Silva12} Griffin et al treated 49 patients with a mean follow-up of 94 months, with no recurrence of the disease in 94% of the patients and had better joint function in 41 patients. ^{Reference Griffin, Ferguson and Catton13} A German review analysed data where RT was applied in 39 cases (95.1%) with excellent or good functional outcome noted in 34 cases (82.9%). The use of RT was not associated with early or late toxicity larger than Radiation Therapy Oncology Group toxicity grade II. Total doses in the range of 30–36 Gy are recommended. ^{Reference Heyd, Seegenschmiedt and Micke14}

There have been no studies on radiation dose-response relationships to date. At Asan Medical Center, patients have been given the conventional dose (32–34 Gy) or a lower dose (20 Gy) as postoperative treatment for diffuse PVNS of the knee, depending on the treating physicians who favoured different pathogenesis theories—neoplasia or chronic inflammation. ^{Reference Park, Young and Jong15}

Horoschak et al recommended that using 34 to 36 Gy radiation dose can achieve a better local control rate. ^{Reference Horoschak, Tran and Bachireddy16} A retrospective study compared the clinical outcomes of patients who were treated with conventional or low-dose RT. It analysed the data of 23 patients who underwent Synovectomy followed by 4-MV or 6-MV external beam RT with a median dose of 20 (12–34) Gy in 10 fractions. At a median follow-up of 9 (0.8–12) years, 4 patients had recurrent disease, with a median disease-free interval of 5 years. Low-dose (20 Gy) RT appears to be as effective as moderate-dose treatment (around 35 Gy). ^{Reference Park, Kim and Kim17}

The recent development and investigation of systemic therapies targeting the colony-stimulating factor one (CSF1) pathway represent an important advancement in the treatment of GCT. These therapies may play a major role in the treatment of advanced, recurrent and recalcitrant diseases for which surgery carries more morbidity than expected benefit. The efficacy of four different tyrosine kinase inhibitors of the CSF1 receptor has recently been tested. This includes nilotinib, imatinib, emactuzumab and pexidartininb. ^{Reference Tap, Wainberg and Anthony18}