Controversies in orthopaedic oncology.

Chondrosarcoma is the second most common surgically treated primary bone sarcoma. Despite a large number of scientific papers in the literature, there is still significant controversy about diagnostics, treatment of the primary tumour, subtypes, and complications. Therefore, consensus on its day-to-day treatment decisions is needed. In January 2024, the Birmingham Orthopaedic Oncology Meeting (BOOM) attempted to gain global consensus from 300 delegates from over 50 countries. The meeting focused on these critical areas and aimed to generate consensus statements based on evidence amalgamation and expert opinion from diverse geographical regions. In parallel, periprosthetic joint infection (PJI) in oncological reconstructions poses unique challenges due to factors such as adjuvant treatments, large exposures, and the complexity of surgery. The meeting debated two-stage revisions, antibiotic prophylaxis, managing acute PJI in patients undergoing chemotherapy, and defining the best strategies for wound management and allograft reconstruction. The objectives of the meeting extended beyond resolving immediate controversies. It sought to foster global collaboration among specialists attending the meeting, and to encourage future research projects to address unsolved dilemmas. By highlighting areas of disagreement and promoting collaborative research endeavours, this initiative aims to enhance treatment standards and potentially improve outcomes for patients globally. This paper sets out some of the controversies and questions that were debated in the meeting.

Modern treatment of unicameral and aneurysmatic bone cysts.

The best treatment of unicameral bone cyst and aneurismatic bone cyst (ABC) is debated in the literature. For simple bone cysts, multiple treatments were proposed from observation only to open curettage. The historical treatment with intraosseous injection of methylprednisolone acetate into the bone cysts nowadays is reduced due to the morbidity of multiple injections and the risk of multiple pathologic fractures until the healing. Different types of treatments for ABC are reported, including surgery, percutaneous treatments, and medical treatments; however, there is currently no consensus on the best approach. The association of curettage, bone graft, and elastic stable intramedullary nail (ESIN) had a success rate of over 85%. Decompressing the cyst wall is more critical for increasing the healing rate than the type of graft used to fill the cavity. In ABC, sclerotherapy offers the advantages of lower invasiveness and morbidity, associated with better functional scores and faster return to full weight-bearing. Moreover, they can be used in challenging locations. Selective arterial embolization is a complex procedure and often requires association with other treatments. Further studies are needed to confirm the effectiveness of denosumab and its side effects on skeletally immature patients. Curettage with adjuvants and autogenous bone grafting still shows promising results and can be used in larger, aggressive defects or superficial lesions. For simple bone cysts, the combination of curettage, bone graft, and ESIN showed the best results. Sclerotherapy for ABC also shows promising results.

Electrochemotherapy in Spine Metastases: A Case Series Focused on Technical Aspects, Surgical Strategies and Results.

Metastases are complications of primary tumors due to prolonged cancer survival and have become an important issue for oncological patients and the most frequent cause of death and disability. Bone metastases occur at a later stage of cancer disease, and the spine is the most frequent site. To date, the aim of the treatment of metastases remains to be the control of disease and provide a satisfactory quality of life. The decision making of treatment is influenced by several factors such as the status of the primary disease, the number of metastases, site involvement, and the performance status of the patients. For this reason, the treatment of metastases is challenging and undergoes constant development. Therefore, alternative techniques with respect to surgery, which is the first option but not always practicable, and radiochemotherapy are attractive. Lately, electrochemotherapy has emerged as an innovative method for treating various primary and metastatic solid tumors, showing promising outcomes in terms of inducing tumor tissue necrosis and alleviating symptoms. This technique uses electric pulses to increase the uptake of chemotherapy by tumor cells. Despite the initial enthusiasm and good results in the treatment of bone tumors, relatively few papers have described its use in spine metastases. Therefore, we conducted a systemic review of this intriguing topic while also reporting our experience in the use of electrochemotherapy for the treatment of spine metastases.

The Evaluation and Management of Lung Metastases in Patients with Giant Cell Tumors of Bone in the Denosumab Era.

Giant cell tumor of bone (GCTB) is characterized by uncertain biological behavior due to its local aggressiveness and metastasizing potential. In this study, we conducted a meta-analysis of the contemporary literature to evaluate all management strategies for GCTB metastases. A combination of the terms "lung metastases", "giant cell tumor", "bone", "treatment", and "oncologic outcomes" returned 133 patients meeting our inclusion criteria: 64 males and 69 females, with a median age of 28 years (7-63), at the onset of primary GCTB. Lung metastases typically occur at a mean interval of 26 months (range: 0-143 months) after treatment of the primary site, commonly presenting as multiple and bilateral lesions. Various treatment approaches, including surgery, chemotherapy, radiotherapy, and drug administration, were employed, while 35 patients underwent routine monitoring only. Upon a mean follow-up of about 7 years (range: 1-32 years), 90% of patients were found to be alive, while 10% had died. Death occurred in 25% of patients who had chemotherapy, whereas 96% of those not treated or treated with Denosumab alone were alive at a mean follow-up of 6 years (range: 1-19 years). Given the typically favorable prognosis of lung metastases in patients with GCTB, additional interventions beyond a histological diagnosis confirmation may not be needed. Denosumab, by reducing the progression of the disease, can play a pivotal role in averting or delaying lung failure.

Ortho-oncoplastic surgery in foot and ankle: A narrative overview on reconstruction of soft-tissue defects after oncologic resections.

INTRODUCTION: Malignant tumors of the foot are rare, and treatment strategies are challenging considering the complex anatomy of this area. In recent years, dramatic advances in technology and collaborations between different specialties (such as orthopedic, oncology, radiology, plastic, and vascular surgery) significantly changed the approach to complex malignant tumors without resorting to limb removal. The combination of the strengths of both orthopedic surgery and plastic surgery constitutes the modern definition of "orthoplasty." The aim of this review article is to provide treatment strategies that are available for reconstruction of foot and ankle in limb-salvage surgery after tumor resection, with a specific focus on microsurgical techniques in plastic surgery. METHODS: We conducted a comprehensive search for relevant papers across PubMed, Scopus, Embase, and Web of Science. We included patient-based studies reporting on procedures for soft-tissue reconstruction with small and large soft tissue defects. Indications, pros and cons, and technique tips are discussed for each type of reconstructive technique. RESULTS: The search was done using literature of the past 30 years (from 1990 to date), resulting in about 725 articles describing over 2000 cases. Cutaneous flaps included lateral supramalleolar flap, medial plantar flap, reverse sural neurocutaneous island flap, medial leg flap, and lateral leg flap. Free flaps included anterolateral thigh flap, radial forearm flap, latissimus dorsi flap, gracilis muscle flap, lateral arm flap, and rectus abdominis flap. CONCLUSIONS: The orthoplastic approach in musculoskeletal oncology is a collaborative model of orthopedic and plastic surgeons working together, resulting in a higher rate of successful limb salvage in patients at risk for amputation. Protocols, biologic substitutes, and surgical techniques are largely improved in the last decades increasing the possibility of functional reconstruction. Microsurgical strategies represent the new frontiers in these demanding reconstructions.

When Is a Two-Stage Surgical Procedure Indicated in the Treatment of Pseudotumors of the Hip? A Retrospective Study of 21 Cases and a Review of the Literature.

(1) Background: A pseudotumor of the hip is a sterile, non-neoplastic soft tissue mass associated with total hip arthroplasties. Pseudotumors may mimic soft tissue tumors or infections, and thus a differential diagnosis is crucial, and biopsy is recommended. The purpose of this study was to compare the complications and functional results between one-stage and two-stage procedures. (2) Methods: We retrospectively analyzed 21 patients surgically treated at our institution with "pseudotumors" associated with hip prosthesis (8 male, 13 female with a mean age of 69 years). One-stage revision was performed in 10 cases and two-stage reversion in 10, with excision only in 1 case. Complications were classified as major and minor and functional results assessed using the Harris Hip Score (HHS). (3) Results: Five patients (24%) reported major complications. The survival rate for all complications was 75%. The overall survival rate was 95% at 5 years. The mean HHS ranged from 35 pre-op to 75 post-op, highlighting improved functional results in all cases. We recorded no differences in complications or functional outcomes between the one- and two-stage procedures. (4) Conclusions: In our experience, the two-stage surgical approach is preferable in cases with major bone defects and larger pseudotumor sizes. The use of custom-made 3D-printed prostheses is increasing and is a further reason to prefer two-stage revision.

Primary vascular tumors of bone: A comprehensive literature review on classification, diagnosis and treatment.

Primary vascular tumors of bone are a heterogeneous group of neoplasms, ranging from benign hemangiomas to frankly malignant epithelioid hemangioendotheliomas and angiosarcomas. Over the years, their classification has been a matter of discussion, due to morphologic similarities and uncertainty regarding biologic behavior. Over the past decade, with the development of next-generation sequencing, there has been a significant improvement in the molecular characterization of these lesions. The integration of their morphologic, immunohistochemical and molecular features has led to a better stratification, with important prognostic and therapeutic implications. Nevertheless, primary vascular bone tumors still represent a challenge for medical oncologists. Given their rarity and heterogeneity, in the last few years, there has been no significant progress in medical treatment options, so further research is needed. Here we present a review of the current knowledge regarding primary vascular tumors of the bone, correlating clinicopathologic features with tumor behavior and therapeutic approaches.

Are IDH1 R132 Mutations Associated With Poor Prognosis in Patients With Chondrosarcoma of the Bone?

BACKGROUND: Because chondrosarcomas vary widely in their behavior, and because anticipating their behavior based on histology alone can be challenging, genetic markers represent an appealing area of inquiry that may help us refine our prognostic approaches. Isocitrate dehydrogenase (IDH) mutations are involved in the pathogenesis of a variety of neoplasms, and recently, IDH1/2 mutations have been found in the tissue of benign cartilage tumors as well as in conventional chondrosarcomas and highly aggressive dedifferentiated chondrosarcomas. However, their association with patient survival is still controversial. QUESTIONS/PURPOSES: (1) What proportion of patients with chondrosarcomas carry IDH mutations, and which IDH mutations can be found? (2) Are any specific IDH mutations associated with poorer overall survival, metastasis-free survival, or local recurrence-free survival? METHODS: Between April 2017 and December 2022, we treated 74 patients for atypical cartilaginous tumors or chondrosarcomas in a musculoskeletal tumor referral center. Patients were considered potentially eligible for the present study if the histologic diagnosis was confirmed by two expert soft tissue and bone pathologists following the current WHO classification, complete preoperative imaging and follow-up data were available, surgical excision was performed by sarcoma orthopaedic surgeons directed by a team leader, and the minimum follow-up was 2 years after surgical treatment unless the patient died. Data including sex, age, diagnosis, grade, type of operation, local recurrence, metastasis, and oncologic follow-up were recorded. Forty-one patients (55%) were eligible for the study. For each patient, DNA was extracted and quantified from paraffin-embedded sections of tumor tissue, and the mutational status of IDH1 (codons 105 and 132) and IDH2 (codons 140 and 172) genes was assessed. Of those, 56% (23 of 41) of patients had adequate DNA for analysis of IDH mutations: 10 male and 13 female patients, with a median age of 59 years (range 15 to 98 years). There were 22 conventional chondrosarcomas (8 atypical cartilaginous tumors, 11 Grade 2, and 3 Grade 3) and 1 dedifferentiated chondrosarcoma. Stage was IA in 3 patients, IB in 5, IIA in 1, IIB in 13, and III in 1, according to the Musculoskeletal Tumor Society classification. At a median follow-up of 3.5 years (range 4 months to 5.6 years), 14 patients were disease-free, 2 were alive with disease, and 7 died (3 within 2 years from surgery). Eight patients had metastases, and 7 developed local recurrence. We determined the proportion of patients who carried IDH mutations, and compared patients with and without those mutations in terms of overall survival, metastasis-free survival, and local recurrence-free survival using Kaplan-Meier curves. RESULTS: Six patients showed wild-type IDH genes, and 17 had IDH mutations (12 had IDH1 R132, 3 had IDH1 G105, and 2 had IDH2 R172). Overall survival at 2 years using the Kaplan-Meier estimator was lower in patients with an IDH mutation than in those with the wild-type gene (75% [95% confidence interval 50% to 99%] versus 100% [95% CI 100% to 100%]; p = 0.002). Two-year metastasis-free survival was also lower in patients with an IDH mutation than in those with the wild-type gene (33% [95% CI 7% to 60%] versus 100% [95% CI 100% to 100%]; p = 0.001), as was 2-year local recurrence-free survival (70% [95% CI 42% to 98%] versus 100% [95% CI 100% to 100%]; p = 0.02). CONCLUSION: We found that IDH1 R132 mutations were negatively associated with the prognosis of patients with bone chondrosarcomas. Nevertheless, more extensive studies (such as multicenter international studies) are needed and advisable to confirm our observations in this preliminary small series. Moreover, evaluating mutational status in fresh samples instead of in paraffin-embedded sections could help to increase the number of patients with adequate DNA for analysis. If our findings will be confirmed, the evaluation of IDH mutational status in biopsy samples or resection specimens could be considered when stratifying patients, highlighting those who may benefit from more aggressive treatment (such as adjuvant chemotherapy) or closer follow-up. LEVEL OF EVIDENCE: Level III, prognostic study.

Desmoid Tumors in the Active Surveillance Era: Evaluation of Treatment Options and Pain Relief in a Single-Center Retrospective Analysis.

In patients with desmoid tumors (DTs), active surveillance has been increasingly preferred over surgery, while treatment (including pharmacological therapy, radiotherapy, and/or surgery) is performed in cases with confirmed disease progression. This study aimed to evaluate event-free survival and pain management according to different treatment strategies. We evaluated event-free survival, including recurrence after initial surgical treatment or changes in the therapeutic management after initial non-surgical treatment and pain management according to different treatment strategies. All patients referred for DT in 2001-2021 at our institutions were stratified into four groups: those treated surgically prior to 2012 (SGPre12) or after 2012 (SGPost12), those treated pharmacologically (MG), and those under active surveillance (ASG). An event was defined as recurrence after initial surgical treatment or a change in therapeutic management. Overall, 123 patients were included in the study: 28 in SGPre12, 41 in SGPost12, 38 in MG, and 16 in ASG. Pharmacological treatment resolved painful symptoms in 16/27 (60%) patients (p = 0.0001). The median follow-up duration was 40 months (IQR 23-74). Event-free survival at 1, 3, and 5 years was: 85%, 70%, and 62% in SGPre12; 76%, 58%, and 49% in SGPost12; 49%, 31%, and 31% in MG; and 45%, 45%, and 45% in ASG. Our findings support the role of active surveillance as initial management, as demonstrated by the fact that about half the patients did not experience any progression, while surgery can be reserved as a first-line approach for selected patients. In terms of pain relief, medical therapy led to symptom resolution in more than half the cases.

Management of metastatic bone disease of the pelvis: current concepts.

PURPOSE: Metastatic disease of the pelvis is frequently associated with severe pain and impaired ambulatory function. Depending on the patient's characteristics, primary tumor, and metastatic pelvic disease, the treatment choice may be varied. This study aims to report on the current management options of metastatic pelvic disease. METHODS: We comprehensively researched multiple databases and evaluated essential studies about current concepts of managing a metastatic bone disease of the pelvis, focusing on specific indications as well as on the result of treatment. RESULTS: Pelvic metastases not in the periacetabular region can be managed with modification of weight-bearing, analgesics, bisphosphonates, chemotherapy and/or radiotherapy. Minimally invasive approaches include radiofrequency ablation, cryoablation, embolization, percutaneous osteoplasty, and percutaneous screw placement. Pathological or impending periacetabular fracture, excessive periacetabular bone defect, radioresistant tumor, and persistent debilitating pain despite non-surgical treatment and/or minimally invasive procedures can be managed with different surgical techniques. Overall, treatment can be divided into nonoperative, minimally invasive, and operative based on specific indications, the expectations of the patient and the lesion. CONCLUSION: Different treatment modalities exist to manage metastatic pelvic bone disease. Decision-making for the most appropriate treatment should be made with a multidisciplinary approach based on a case-by-case basis.

An Institutional Standardised Protocol for the Treatment of Acute Displaced Midshaft Clavicle Fractures (ADMCFs): Conservative or Surgical Management for Active Patients?

BACKGROUND AND OBJECTIVES: The treatment of acute displaced midshaft clavicle fractures (ADMCFs) is still under debate. The aim of this study was to verify the effectiveness of our institutional protocol by comparing the clinical and radiographic outcomes of two groups of patients with ADMCFs treated operatively and non-operatively. MATERIALS AND METHODS: active patients with a traumatic, isolated non-pathological ADMCF with at least 1-year clinical and radiographic follow up were included. Surgical treatment was performed in the cases where the residual displacement was higher than 140% after the application of a figure-of-eight bandage (F8-B). All other cases were treated conservatively with a F8-B. A total of 134 patients were enrolled and divided into two groups: surgical and conservative groups, with 59 and 75 patients, respectively. Radiological and clinical parameters were evaluated. RESULTS: Good clinical (Constant-Murley Score, the Quick Disability of the Arm, Shoulder and Hand score, and VAS satisfaction) and radiographic outcomes (initial and residual shortening, initial and residual displacement) were obtained for ADMCFs in both groups. Multivariate analysis showed that patients treated conservatively had better clinical outcomes compared to surgically treated patients (p < 0.001). Return to sports was longer in those treated with surgery. Initial shortening was found to impact clinical outcomes as well as initial displacement. None of the patients showed signs of non-union in both groups. CONCLUSIONS: Very good mid-term clinical results can be obtained in adult patients with ADMCFs, conservatively or operatively managed, by applying our institutional treatment protocol based on objective radiographic parameters evaluated in the ER.

3D printing for patient-specific implants in musculoskeletal oncology.

Satisfactory results in terms of functional and oncological outcomes can be obtained in sacral and pelvic malignant bone tumors. Preoperative planning, adequate imaging, and a multidisciplinary approach are needed. 3D-printed prostheses have to fulfill several requirements: (i) mechanical stability, (ii) biocompatibility, (iii) implantability, and (iv) diagnostic compatibility. In this review, we highlight current standards in the use of 3D-printed technology for sacropelvic reconstruction.

Vertebra Plana: A Narrative Clinical and Imaging Overview among Possible Differential Diagnoses.

Vertebra plana is a rare radiologic condition characterized by a uniform loss of height of a vertebral body that represents a diagnostic challenge for surgeons. The purpose of this study was to review all possible differential diagnoses that may present with a vertebra plana (VP) described in the current literature. For that purpose, we performed a narrative literature review in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, analyzing 602 articles. Patient demographics, clinical presentation, imaging characteristics and diagnoses were investigated. VP is not a pathognomonic feature of Langerhans cell histiocytosis, but other oncologic and non-oncologic conditions should be considered. The list of differential diagnoses, based on our literature review, can be recalled with the mnemonic HEIGHT OF HOMO: H-Histiocytosis; E-Ewing's sarcoma; I-Infection; G-Giant cell tumor; H-Hematologic neoplasms; T-Tuberculosis; O-Osteogenesis imperfecta; F-Fracture; H-Hemangioma; O-Osteoblastoma; M-Metastasis; O-Osteomyelitis, chronic.

Malignant Bone and Soft Tissue Lesions of the Foot.

Malignant tumors of the foot are rare pathologies that can involve the skin, soft tissue, or bone. Due to their rarity, they are often misdiagnosed, resulting in inadequate excision and poor outcomes. A correct approach with a careful examination and radiological study, followed by a properly performed biopsy, is thus mandatory to avoid these pitfalls. The present article reviews the most common malignant bone and soft tissue lesions of the foot region, discussing their clinicopathological presentation, imaging features, and current concepts in treatment.

History of the management of talar fractures: from the fall of king Darius to Garibaldi's bullet and from the earliest to current operative strategies.

PURPOSE: This historical review aims to highlight the important roles of the talus in antiquity and to summarise the multiple attempts of managing talar fractures throughout history. METHOD: Archaeological, religious, artistic, literary, historical and scientific accounts were searched for the descriptions of talus fractures in different eras and their treatments to provide a thorough analysis of the evolution of trauma care up to the present. RESULTS: This review shows how the talus has always had an important role in several societies: it was used as a die or considered to have a divinatory function in Mesopotamian civilisations, among Greeks and Romans, in Mongolia and in pre-Columbian Americas. Famous talus fractures are recorded in Herodotus' Histories and in the Acts of the Apostles. We report the earliest injuries described and the first operative managements between 1600 and 1800, including the one that saved Garibaldi's life in 1862, until the modern osteosynthesis by the first screws and nails and the current fixation by plating. CONCLUSION: The blooming of orthopaedic surgery at the end of nineteenth century and the high volume of traumas managed in the World Wars brought a better understanding of fracture patterns and their operative treatment. By the work of Hawkins and his classification, the introduction of the CT scan, a better knowledge of injury modalities and bone vascularisation, these challenging injuries finally land in the contemporary era without mysteries. The subsequently developed surgical procedures, although not guaranteeing success, greatly reduce the risk of necrosis and complication rate, improving patient outcomes.

Functional autonomy and 12-month mortality in older adults with proximal femoral fractures in an orthogeriatric setting: risk factors and gender differences.

BACKGROUND: Proximal femur fractures have a negative impact on loss of functional autonomy and mortality. OBJECTIVE: The aim of this retrospective study was to evaluate functional autonomy and mortality in a group of older adults with hip fractures managed in an orthogeriatric setting 12 months after discharge and to determine if gender affected outcome. METHODS: In all participants, we assessed clinical history, functional pre-fracture status using activities of daily living (ADL) and in-hospital details. At 12 months after discharge, we evaluated functional status, place of residence, hospital readmissions and mortality. RESULTS: We studied 361 women and 124 men and we observed a significant reduction in the ADL score at 6 months (1.15 ± 1.58/p < 0.001 in women and 1.45 ± 1.66/p < 0.001 in men). One-year mortality (33.1% in men and 14.7% in women) was associated with pre-fracture ADL score and reduction in ADL at 6 months (HR 0.68/95%, CI 0.48-0.97/p < 0.05 and HR 1.70/95%, CI 1.17-2.48/p < 0.01, respectively) in women, and new hospitalisations at 6 months and polypharmacy in men (HR 1.65/95%, CI 1.07-2.56/p < 0.05 and HR 1.40/95%, CI 1.00-1.96/p = 0.05, respectively) in Cox's regression model. DISCUSSION AND CONCLUSIONS: Our study suggests that functional loss in older adults hospitalised for proximal femur fractures is greatest in the first 6 months after discharge, and this increases the risk of death at 1 year. Cumulative mortality at 12 months is higher in men and appears to be related to polypharmacy and new hospital admissions 6 months after discharge.

New concepts in the surgical treatment of actual and impending pathological fractures in metastatic disease.

INTRODUCTION: Long bone metastases are a disease of high social importance. The goals of surgical treatment are to relieve pain, maintain or restore joint function, and prevent or treat pathological fractures. "Oligometastases" is a disease with a limited number (3-5) of metastatic lesions in the same body district, where an aggressive treatment can be carried out with "curative" intent. This study aimed to evaluate patients with bone metastases surgically treated to determine how surgical treatment can influence prognosis and quality of life, comparing solitary metastasis, oligometastases, and multiple metastases. PATIENTS AND METHODS: This is a retrospective analysis of 130 patients with long bone metastases surgically treated between October 2015 and August 2019: 40 patients had solitary metastasis; 38 had less than three metastases (oligometastases), and 52 had multiple metastases. Surgery was resection and reconstruction with a cemented prosthesis (95) or nailing (35). RESULTS: Overall survival was significantly better in patients with solitary metastasis or oligometastases than in those with multiple metastases (p <0.0001). Patients treated with resection and prosthesis had significantly better survival than those treated with nailing (p <0.0001). Implant complications requiring surgical revision occurred in 20 patients treated with prostheses, while no complications occurred in patients treated with nailing. DISCUSSION: Survival of cancer patients has improved in the last two decades, leading to an increase of diagnosed metastases. Patients with oligometastases have a survival similar to those with a single metastasis. Optimal implants survival curves should stay above the curves of patients survival. CONCLUSIONS: Since there are no differences in survival, patients with oligometastases should be treated as patients with a solitary lesion, with more aggressive surgery (wide resection and reconstruction with prosthesis). Intramedullary nailing is still indicated in metaphyseal or diaphyseal metastases in patients with advanced disease or poor prognosis when the life expectancy does not overcome the expected survival of the nail, avoiding the need for further surgery.

A systematic review of multicentric giant cell tumour with the presentation of three cases at long-term follow-up.

AIMS: We performed a systematic literature review to define features of patients, treatment, and biological behaviour of multicentric giant cell tumour (GCT) of bone. METHODS: The search terms used in combination were "multicentric", "giant cell tumour", and "bone". Exclusion criteria were: reports lacking data, with only an abstract; papers not reporting data on multicentric GCT; and papers on multicentric GCT associated with other diseases. Additionally, we report three patients treated under our care. RESULTS: A total of 52 papers reporting on 104 patients were included in the analysis, with our addition of three patients. Multicentric GCT affected predominantly young people at a mean age of 22 years (10 to 62), manifesting commonly as metachronous tumours. The mean interval between the first and subsequent lesions was seven years (six months to 27 years). Synchronous lesions were observed in one-third of the patients. Surgery was curettage in 63% of cases (163 lesions); resections or amputation were less frequent. Systemic treatments were used in 10% (n = 14) of patients. Local recurrence and distant metastases were common. CONCLUSION: Multicentric GCT is rare, biologically aggressive, and its course is unpredictable. Patients with GCT should be followed indefinitely, and referred promptly if new symptoms, particularly pain, emerge. Denosumab can have an important role in the treatment.Cite this article: Bone Joint J 2022;104-B(12):1352-1361.