Acta Ortop Bras aob Acta Ortopédica Brasileira Acta Ortop. Bras. 1413-7852 1809-4406 Sociedade Brasileira de Ortopedia e Traumatologia, Brazil Resumo Objetivo: Avaliar o perfil do paciente com diagnóstico de tumor de células gigantes atendidos no Hospital Ophir Loyola. Método: Estudo analítico em forma de coorte retrospectiva, realizado por revisão dos prontuários e exames de imagem dos pacientes atendidos no hospital no período de 1 de janeiro de 2020 a 31 de dezembro de 2021. Resultado: Foram avaliados 19 pacientes, com tempo médio de 10,5 meses entre a suspeita diagnóstica e a primeira consulta com a equipe da Oncologia Ortopédica. Conclusão: Dos pacientes estudados, 73% apresentavam-se em estágio avançado, necessitando tratamento cirúrgico agressivo com ressecção ampla e substituição por endoprótese. Nível de Evidência II; Estudo Prognóstico de Caráter Retrospectivo. INTRODUCTION Giant cell tumors (GCT) are rare, accounting for less than 10% of benign primary bone tumors. They have a higher prevalence after skeletal maturity, although they can also be found in patients with open growth plates. It is considered one of the most controversial and least predictable tumors in its behavior.1,2 They preferably affect long bones, although they have been reported in the spine, pelvis, patella, and sacrum. They are differentially diagnosed from aneurysmal bone cyst, chondroblastoma, and simple bone cyst.3 The main clinical symptoms are pain and swelling. Diagnoses can be suspected through a pathological fracture as the initial presentation. Imaging tests such as X-rays, often show the triad: epiphyseal, eccentric, and lytic lesions. The bone cortex may show thinning or local destruction. The transition zone is not well defined, but in less aggressive cases, there is sclerotic reaction. Invasion and destruction of the cortex with invasion of soft tissues are commonly observed. Sometimes there is no joint involvement due to the barrier formed by the subchondral bone.4,5 The interval between the first symptom and the definitive diagnosis is termed as “delay time”. The period between the initial symptoms and the initial treatment can be divided into two main categories: patient delay, which is defined as the time between the initial symptoms and the first medical consultation, and professional delay, primarily caused by the physician, defined as the time between the first consultation and the initial treatment. The addition of these two delays is called the overall symptom interval.6 Diagnosis is made through biopsy, and treatment is surgical, which may involve intralesional resection with curettage, adjuvants and/or cavity filling with bone cement, auto or allograft; in more advanced cases, wide resection with endoprosthesis replacement or even amputation may be performed.2,7 Since the morbidity of these patients is directly related to the time between diagnosis and treatment, it is important to understand the patient entry profile into the service and the outcomes of their treatment. Furthermore, there are no similar studies in the Amazon region. To address the issues, this study aims to evaluate the profile of patients diagnosed with GCT treated at Hospital Ophir Loyola in the Years 2020 and 2021, demonstrating the time between diagnostic suspicion and the first consultation with the Orthopedic Oncology team, the characteristics of the lesion at the initial consultation and the proposed treatment. METHODOLOGY This is an analytical study, in the form of a retrospective cohort, which will be conducted through the analysis of medical records and imaging studies of patients seen in the outpatient clinic from January 1, 2020, to December 31, 2021, at a quaternary hospital. The study includes 19 patients diagnosed with GCT treated at the Orthopedic Oncology outpatient clinic from January 1, 2020, to December 31, 2021. The medical records of patients seen in the years 2022 and 2023 were not analyzed due to data unavailability at the service until the study was completed. Patients with suspected diagnosis but who did not undergo biopsy were excluded from the study. The research was conducted through medical record review and analysis of imaging studies. The studied variables were divided into demographic and clinical. Demographic variables include age, sex, and place of origin. Clinical variables include the date of diagnostic suspicion, the date of the first consultation with the Orthopedic Oncology team, the date of diagnosis, the anatomical location of the tumor, the tumor stage, the presence of pulmonary metastasis, the presence of recurrence, date of pathological fracture (if applicable), type of surgery, type of cavity filling (if applicable), adjuvants used (if applicable), and the use and indication of denosumab. First, the medical records of patients seen in the outpatient clinic with ICD-10 D16 were selected to screen for patients diagnosed with GCT. Then, date contained in the medical records and Imaging studies database were collected. A questionnaire was filled out for standardization purposes. A descriptive analysis of the sample characterization was conducted, with frequencies, percentages, mean, standard deviation, median, interquartile range (p25%-p75%), presented in tables and/or graphs. Continuous quantitative variables, such as age (years) and duration of suspicion (months), were first subjected to the Shapiro-Wilk test to analyze their normal distribution. For comparative analysis between the stage and recurrence groups, the Mann-Whitney test was Applied for continuous variables. The Fisher’s Exact Test was used for comparative analysis between categorical variables. All statistical analyses were performed using SPSS 20.0 software respecting a significance level of 5% (p≤0.05). This research was approved by the Institutional Ethics Committee through the Plataforma Brazil, with identification number CAEE 7509023.6.0000.5550 (amendment no. 6.585.557). The administration of questionnaires and retrospective medical record collection were preceded by a Data Use Agreement to ensure the reliability of the collected information, and a request for Waiver of Informed Consent was submitted. RESULTS The initial database included 137 patients. After reviewing the medical records, patients diagnosed with GCT through biopsy were selected. Thus, the final database consisted of 19 patients treated at the Orthopedic Oncology outpatient clinic in the years 2020 and 2021. The majority of patients were male (57.89%); with mean age of 37.32 (±13.47) years; residents of other regions of the state of Pará (47.37%), outside the Metropolitan region of Belém; with a mean patient delay time of 10.47 (±13.08) months; predominantly with lesions located in the distal femur region (47.37%), at Campanacci stage 3 (73.68%); without a history of pathological fracture (84.21%); undergoing mostly marginal/wide surgical type (73.68%) and without a history of recurrence (84.21%), as detailed in Table 1. Table 1 Analysis of the demographic and clinical profile of patients diagnosed with giant cell tumor treated at a quaternary hospital in Northern Brazil, in the years 2020 and 2021. Variable Frequency (n. 19) Percentage (%) CI95% Sex Male 11 57.89 36.8 - 78.9 Female 8 42.11 21.1 - 63.2 Age (years) Mean ( sd) 37.32 ( 13.47) 31.0 - 43.8 Median (p25-75%) 39.00 (24.00 - 45.50) 24.0 - 44.0 Age range < 30 years 6 31.58 10.5 - 52.6 ≥ 30 years 13 68.42 47.4 - 89.5 Location Metropolitan region of Belém 6 31.58 10.5 - 52.6 Other regions of Pará 9 47.37 26.3 - 68.4 Other state 4 21.05 5.3 - 42.1 Patient delay (months) Mean ( sd) 10.47 ( 13.08) 6.1 - 17.1 Median (p25-75%) 7.00 (4.00 - 12.00) 4.0 - 12.0 Patient delay ≥ 12 months Yes 6 31.58 10.5 - 52.6 No 13 68.42 47.4 - 89.5 Anatomic location Proximal femur 1 5.26 0.0 - 15.8 Distal femur 9 47.37 21.2 - 68.4 Proximal tibia 6 31.58 10.5 - 52.6 Calcaneus 1 5.26 0.0 - 15.8 Hand bones 2 10.53 0.0 - 26.3 Campanacci Stage 1 2 10.53 0.0 - 26.3 Stage 2 3 15.79 0.0 - 31.6 Stage 3 14 73.68 52.5 - 89.5 Pathological fracture Yes 3 15.79 0.0 - 36.8 No 16 84.21 63.2 - 100.0 Surgery type Wide resection 14 73.68 52.5 - 89.5 Marginal/Intralesional 3 15.79 0.0 - 31.6 Not performed 2 10.53 0.0 - 26.3 Recurrence Yes 3 15.79 0.0 - 36.8 No 16 84.21 63.2 - 100.0 Denosumab use Yes 5 26.32 10.5 - 47.4 No 14 73.68 52.5 - 89.5 Pulmonary metastasis Yes 0 0.00 0.0 - 0.0 No 19 100.00 100.0 - 100.0 Sd: Standard deviation. P: Percentile. CI: confidence interval. The most employed treatment among patients in this study was surgery with wide resection and replacement with unconventional endoprosthesis. Only 2 patients did not undergo treatment at the hospital due to loss to follow-up; for one male patient with GCT in the calcaneus, intralesional resection with cavity filing was requested, and for one female patient with GCT in the distal third of the femur, wide resection and replacement with unconventional endoprosthesis were requested, both patients did not attend for hospitalization. Three patients experienced tumor recurrence after primary treatment. Two patients experienced recurrence about 2 years after surgery with wide resection and replacement with unconventional endoprosthesis, and they were managed with denosumab prescription. The third patient was diagnosed with tumor recurrence 6 months after surgical treatment, also with wide resection and unconventional endoprosthesis, denosumab was prescribed without significant improvement, progressing to transfemoral limb amputation. Although not planned criteria, during the research, complications were noted in 4 patients undergoing surgical treatment. One patient initially treated with intralesional resection and osteosynthesis required endoprosthesis replacement due to significant worsening of knee osteoarthritis after initial surgical treatment. Two patients required surgery revision due to dislocation or loosening of components. And one patient progressed to transfemoral limb amputation due to surgical site infection. None of the patients in this study were diagnosed with pulmonary metastasis. When comparing demographic and clinical differences between the Campanacci stages groups, it was observed that patients in Stage 3 differed significantly (p-value: 0.002) from Stages 1 and 2 regarding the type of surgery performed. While in stages 1 and 2, the most used surgery type was intralesional or marginal (60%), in the stage 3, wide surgery stood out (92.9%). The other variables did not differ significantly, as detailed in Table 2. Table 2 Comparative analysis of the demographic and clinical profile of patients diagnosed with GCT in Stages 1/2 and Stage 3 treated at a quaternary hospital in Northern Brazil, in the years 2020 and 2021. Variable Stage 1 e 2 (n. 5) Stage 3 (n. 14) p-value Sex Male 1(20.0%) 10(71.4%) 0.071a Female 4(80.0%) 4(28.6%) Age(years) Mean( sd) 38.6( 9.6) 36.8( 14.9) 0.830b Median(p25-75%) 39.0(39.0-43.0) 36.5(24.0-47.0) Agerange <30years 1(20.0%) 5(35.7%) 0.480a >30years 4(80.0%) 9(64.9%) Location MetropolitanregionofBelém 1(20.0%) 5(35.7%) 0.814a OtherregionsofPará 3(60.0%) 6(42.9%) Otherstate 1(20.0%) 3(21.4%) Patientdelay Mean( sd) 14.0( 25.7) 9.2( 5.2) 0.070b Median(p25-75%) 3.0(2.0-4.0) 7.5(6.0-12.0) Patientdelay≥12months Yes 1(20.0%) 5(35.7%) 0.631a No 4(80.0%) 9(64.3%) Anatomiclocation Proximalfemur 0(0.0%) 1(7.1%) 0.164a Distalfemur 3(60.0%) 6(42.9%) Proximaltibia 0(0.0%) 6(42.9%) Calcaneus 1(20.0%) 0(0.0%) Handbones 1(20.0%) 1(7.1%) Pathologicalfracture Yes 0(0.0%) 3(21.4%) 0.530a No 5(100.0%) 11(78.6%) Surgerytype Wideresection 1(20.0%) 13(92.9%) 0.002a* Marginal/Intralesional 3(60.0%) 0(0.0%) Notperformed 1(20.0%) 1(7.1%) Recurrence Yes 0(0.0%) 3(21.4%) 0.530a No 5(100.0%) 11(78.6%) Denosumabuse Yes 0(0.0%) 5(35.7%) 0.257a No 5(100.0%) 9(64.3%) Pulmonarymetastasis Yes 0(0.0%) 0(0.0%) 1.000a No 5(100.0%) 14(100.0%) Sd: Standard deviation. P: percentile a: Fisher’s exact test. B: Mann-Whitney test. *. p-value < 0.05. DISCUSSION To better understand the profile of patients diagnosed with GCT seen at our service, we noted that the average time between diagnostic suspicion and consultation with the Orthopedic Oncology team was 10.5 months, with the tumor being in an advanced stage, necessitating extensive surgical treatment. Among all patients seen in the service during the study period, those diagnosed with GCT presented a prevalence of approximately 14%. This is above the average described in the literature, but it is important to consider that the initial sample does not solely account for bone tumors.8,9 Despite epidemiological studies showing a slight predominance among females, most of our patients were male.8,9,10 The average range of most patients, the primary site of the tumor, and the presence of pathological fractures in our study are consistent with epidemiological studies. At diagnosis, most patients were between 20 and 39 years old, a finding similar to the literature.11,12 The most common primary sites were the distal third of the femur and the proximal third of the tibia, at 47% and 31%, respectively. The knee is the most common primary site in the body, with the distal third of the femur being the main site, followed by the proximal third of the tibia. When it affects, the distal third of the radius, the third most common site described in the literature, it usually exhibits more evident aggressive characteristics. Involvement of the sacrum is rare.8,9 Our service recorded the bones of the hand as the third most common site. The fact that 10% of tumors were in the hand differs from the epidemiology found in the literature. In 2021, a study demonstrated the low prevalence of giant cell tumors in the phalanges. In a study involving 2.400 patients, there were fewer than 50 cases, while another study showed only 1 case among 327 patients.13 Pathological fractures occurred in 3 patients, corresponding to 15% of the group. Most patients experience progressive pain, initially manifesting during activities but progressing to rest pain. It is not usually disabling, except in cases associated with pathological fractures which are evident in the initial examination of 10 to 30% of patients.14 The average diagnosis delay time is considered high, which directly influences the increased likehood of diagnosis tumors at advanced stages.15 The average patient delay time of 10.5 months may reflect the size of the state of Pará, the difficulties faced by the Public Health Service in identifying the need for specialized care early on and may also indicate difficulties in accessing health services for the more deprived population in remote areas. Additionally, there were patients from the state of Maranhão receiving treatment, showing that the complexity of health problems extends nationally (Figure 1 2). Figure 1 Political map of the state of Pará. Source: Brazilian Institute of Geography and Statistics (IBGE), 2024. Figure 2 Political map of the state of Maranhão. Source: IBGE, 2024. Currently, in our service the increase in the Orthopedic Oncologist team in 2023, there is no longer a surgical procedure waiting list, as was the reality in the period of 2020 and 2021. There is now a window of only a few weeks between the indication for surgical treatment and the procedure. However, the main difficulty lies in the stage at which patients arrive for the initial consultation. Over 70% of patients presented at Campanacci stage 3, highlighting the diagnostic delay we face in the state and the direct relationship between Campanacci Stage 3 and the average time of 10.5 months for diagnosis.15,16 Due to this, the primary surgical treatment employed in these patients was wide resection with replacement with unconventional endoprosthesis, differing from much of the national and worldwide literature, which shows that most diagnosed patients are in Campanacci stage 2 and are managed with intralesional resection and cavity grafting.17 Even with aggressive treatment, there was still a case requiring amputation due to recurrence, highlighting the importance of early diagnosis as a major modulator in the prognosis of these patients. Studies over the last decade have already demonstrated the relationship between early diagnosis and the severity of the lesion, as well as the temporal relationship between symptom onset and tumor severity. Early diagnoses reduce morbidity related to both diagnosis and surgical treatment, in addition to bringing benefits to the public health system.15 Recurrences are defined on symptomatic evidence or changes in imaging studies. They are considered from three months after treatment, but can be detected within the first two years.8 The rate of local recurrence can be influenced by diagnostic delay and the surgical technique employed. Campanacci 1 and 2 are treated with curettage and adjuvants. Isolated intralesional surgeries have a recurrence risk of 50%, decreasing to 30% with the use of local adjuvants. Campanacci 3 is generally treated with radical excision due to the high risk of recurrence, often requiring joint reconstruction with endoprosthesis. The risk of recurrence after this therapeutic modality is around 0-12%. The recurrence rate in our study was 15% with the need for denosumab treatment or limb amputation.8,10,18 In our service, denosumab treatment was used before surgical approach in 2 patients. In another 3, was used after the diagnosis the tumor recurrence. The medication is a biological agent that prevents bone cell destruction by interrupting osteoclast maturation, as it prevents RANK activation by binding to RANK-L. It is indicated for use in cases where it is not possible to completely excise the tumor, which would increase the risk of recurrence, and in cases where surgery is contraindicated. 18,19 The use of medication does not cure the disease, but has a limb-preserving potential, preventing amputations, hemipelvectomy, neurological disorders, and reducing morbidity associated with surgical treatment.19,20 As mentioned earlier, several factors influence the diagnostic delay of oncology patients. The hospital serves as a reference for the entire state, and the demographic and socioeconomic constraints in the state of Pará are significant and impact the reality of public health. We must also consider the knowledge of generalist physicians and clinical areas regarding bone tumors because often these professionals will provide initial care. Recognizing an aggressive tumor and knowing that referral to a specialized service is necessary directly impact the early treatment of these patients. Our study showed an average time of 10.5 months between diagnostic suspicion and the first consultation with the Orthopedic Oncologist. At the time of diagnosis, 73% of patients presented with Giant Cell Tumor in an advanced stage, Campanacci grade 3, necessitating aggressive surgical treatment with wide resection and endoprosthesis replacement. ACKNOWLEDGMENTS The authors would like to thank Hospital Ophir Loyola and its staff for all the assistance and support provide for the completion of this word. REFERENCES 1 1 Viana EMBO, Batista KT, Carneiro Junior JL. Tumor de células gigantes do sacro inoperável: opções terapêuticas e controle da dor. Rev Bras Ortop. 2019;54(3):347-52. Viana EMBO Batista KT Carneiro JL Junior Tumor de células gigantes do sacro inoperável: opções terapêuticas e controle da dor Rev Bras Ortop 2019 54 3 347 352 2 2 Latorre MR, Albergo JI, Farfalli GL, Roitman PD, Plantalech L, Ayerza MA, et al. Denosumab como tratamiento neoadyuvante del tumor de células gigantes del hueso. Indicaciones, resultados y efectos adversos. Medicina (Buenos Aires). 2021;81(5):767-73. Latorre MR Albergo JI Farfalli GL Roitman PD Plantalech L Ayerza MA Denosumab como tratamiento neoadyuvante del tumor de células gigantes del hueso. Indicaciones, resultados y efectos adversos Medicina (Buenos Aires) 2021 81 5 767 773 3 3 Córdoba CH. Tumor de células gigantes en rótula manejado con patelectomía. Rev Artroscopia. 2022;29(03):124-30. Córdoba CH Tumor de células gigantes en rótula manejado con patelectomía Rev Artroscopia 2022 29 03 124 130 4 4 Alvarez-López A, Valdenbenito-Aceitón V, Soto-Carrasco SR, Fernández-Delgado M. Tumor de células gigantes malignizado: a propósito de un caso. Acta Méd Centro. 2023;17(2):332-9. Alvarez-López A Valdenbenito-Aceitón V Soto-Carrasco SR Fernández-Delgado M Tumor de células gigantes malignizado: a propósito de un caso Acta Méd Centro 2023 17 2 332 339 5 5 Acosta PL, Pérez RP, Torres PR. Tumor de células gigantes del fémur. Rev Cuba Reumatol. 2021;23(1):776-83. Acosta PL Pérez RP Torres PR Tumor de células gigantes del fémur Rev Cuba Reumatol 2021 23 1 776 783 6 6 Schnurr C, Pippan M, Stuetzer H, Delank KS, Michael JWP, Eysel P. Treatment delay of bone tumours, compilation of a sociodemographic risk profile: a retrospective study. BMC Cancer. 2008;8:22. Schnurr C Pippan M Stuetzer H Delank KS Michael JWP Eysel P Treatment delay of bone tumours, compilation of a sociodemographic risk profile: a retrospective study BMC Cancer 2008 8 22 22 7 7 Quiñonez-Flores CM, Arzate-Quintana C, Carrasco-De la Fuente JL, Torres-Castro C. Tratamiento reconstructivo de bajo costo tras resección de tumor de células gigantes de radio distal. Acta Ortop Mex. 2023;36(3):190-4. Quiñonez-Flores CM Arzate-Quintana C Carrasco-De la Fuente JL Torres-Castro C Tratamiento reconstructivo de bajo costo tras resección de tumor de células gigantes de radio distal Acta Ortop Mex 2023 36 3 190 194 8 8 Oliveira Júnior RCL, Pereira MGS, Garcia PBL, Santos PA, Cavalcanti AS, Meohas W. Epidemiological study on giant cell tumor recurrence at the Brazilian National Institute of Traumatology and Orthopedics. Rev Bras Ortop (English Edition). 2016;51(4):459-65. Oliveira RCL Júnior Pereira MGS Garcia PBL Santos PA Cavalcanti AS Meohas W Epidemiological study on giant cell tumor recurrence at the Brazilian National Institute of Traumatology and Orthopedics Rev Bras Ortop (English Edition) 2016 51 4 459 465 9 9 Jiang CY, Zhao L, Schuetza SM, Chugh R. Giant Cell Tumor of Bone: effect of longer dosing intervals of denosumab on tumor control and bone-related complications. Oncologist. 2022;27(7):595-9. Jiang CY Zhao L Schuetza SM Chugh R Giant Cell Tumor of Bone: effect of longer dosing intervals of denosumab on tumor control and bone-related complications Oncologist 2022 27 7 595 599 10 10 Aguiar LTA, Vasconcelos JBM, Ribeiro MB. Tratamento de pacientes com diagnóstico de tumor ósseo de células gigantes: Experiência de um hospital filantrópico no Piauí, Brasil. Rev Bras Ortop. 2022;57(5):802-6. Aguiar LTA Vasconcelos JBM Ribeiro MB Tratamento de pacientes com diagnóstico de tumor ósseo de células gigantes: Experiência de um hospital filantrópico no Piauí, Brasil Rev Bras Ortop 2022 57 5 802 806 11 11 Kamal AF, Muhamad A. Outcomes of En bloc resection followed by reconstruction of giant cell tumor around knee and distal radius. A case series. Ann Med Surg (Lond). 2020;49:61-6. Kamal AF Muhamad A Outcomes of En bloc resection followed by reconstruction of giant cell tumor around knee and distal radius. A case series Ann Med Surg (Lond) 2020 49 61 66 12 12 Kumar S, Nandan B, Chauhan R, Dhawan M, Agrawal S, Rivi S. Coagulação por plasma de argônio como adjuvante à curetagem estendida em tumores de células gigantes do osso: um estudo de 50 casos. Rev Bras Ortop. 2022;58(2):211-21. Kumar S Nandan B Chauhan R Dhawan M Agrawal S Rivi S Coagulação por plasma de argônio como adjuvante à curetagem estendida em tumores de células gigantes do osso: um estudo de 50 casos Rev Bras Ortop 2022 58 2 211 221 13 13 Goel A, Gupta A, Bhatia N, Goyal R, Mehndiratta A, Yadav A. Giant Cell Tumor of the Ring Finger Distal Phalanx. J Hand Surg Am. 2021;46(3):249-54. Goel A Gupta A Bhatia N Goyal R Mehndiratta A Yadav A Giant Cell Tumor of the Ring Finger Distal Phalanx J Hand Surg Am 2021 46 3 249 254 14 14 Semino RP, Beltrán RL, Gutiérrez RH. Tumor de células gigantes en el extremo distal del radio / Giant Cell Tumor Of The Distal Radius. Rev Cuba Ortop Traumatol. 2022;36(1):e385. Semino RP Beltrán RL Gutiérrez RH Tumor de células gigantes en el extremo distal del radio / Giant Cell Tumor Of The Distal Radius Rev Cuba Ortop Traumatol 2022 36 1 e385 e385 15 15 Ferraz DFCD, Santos CAT, Costa VHF, Souza AMG, Lima PRG. Tumor de células gigantes: análise sobre importância do diagnóstico precoce e perfil epidemiológico. Rev Bras Ortop. 2016;51(1):58-62. Ferraz DFCD Santos CAT Costa VHF Souza AMG Lima PRG Tumor de células gigantes: análise sobre importância do diagnóstico precoce e perfil epidemiológico Rev Bras Ortop 2016 51 1 58 62 16 16 Becker RG, Galia CR, Pestilho JFCS, Antunes BP, Baptista AM, Guedes A. GIANT CELL TUMOR OF BONE: a multicenter epidemiological study in Brazil. Acta Ortop Bras. 2024;32(1):26-30. Becker RG Galia CR Pestilho JFCS Antunes BP Baptista AM Guedes A GIANT CELL TUMOR OF BONE: a multicenter epidemiological study in Brazil Acta Ortop Bras 2024 32 1 26 30 17 17 Su YP, Chen WM, Chen TH. Giant-cell tumors of bone: an analysis of 87 cases. Int Orthop. 2004;28(4):239-43. Su YP Chen WM Chen TH Giant-cell tumors of bone: an analysis of 87 cases Int Orthop 2004 28 4 239 243 18 18 Mallick AB, Chawla SP. Giant Cell Tumor of Bone: an update. Curr Oncol Rep. 2021;23(5):51. Mallick AB Chawla SP Giant Cell Tumor of Bone: an update Curr Oncol Rep 2021 23 5 51 51 19 19 Montgomery C, Couch C, Emory CL, Nicholas R. Giant Cell Tumor of Bone: Review of Current Literature, Evaluation, and Treatment Options. J Knee Surg. 2018;32(4):331-6. Montgomery C Couch C Emory CL Nicholas R Giant Cell Tumor of Bone: Review of Current Literature, Evaluation, and Treatment Options J Knee Surg 2018 32 4 331 336 20 20 Bazán PL, Falco R, Borri AE, Medina M, Ciccioli NM, Danielle S. The use of denosumab in giant cell tumors in the sacrum. Coluna/Columna. 2020;19(2):151-3. Bazán PL Falco R Borri AE Medina M Ciccioli NM Danielle S The use of denosumab in giant cell tumors in the sacrum Coluna/Columna 2020 19 2 151 153