Giant cell tumor of bone: a multicenter epidemiological study in brazil / Tumor de células gigantes ósseas: estudo epidemiológico multicêntrico no brasil

ABSTRACT Introduction: Giant cell tumor of bone (GCTB) mainly affects young adults' long bone epiphyses, threatening bone strength and joint function. Surgery is the primary treatment, although post-surgery recurrence is significant. This study analyzes patient profiles, treatments, and outcomes for GCTB in Brazil. Methods: We retrospectively assessed local recurrence, metastasis, and treatment approaches in 643 GCTB patients across 16 Brazilian centers (1989-2021), considering regional differences. Results: 5.1% (n=33) developed pulmonary metastases, 14.3% (n=92) had pathological fractures, and the local recurrence rate was 18.2% (n=114). Higher rates of pulmonary metastases (12.1%) and advanced tumors (Campanacci III, 88.9%) were noted in lower-income North and Northeast regions. The North also had more pathological fractures (33.3%), extensive resections (61.1%), and amputations (27.8%). These regions faced longer surgical delays (36-39 days) than the South and Southeast (27-33 days). Conclusions: Our findings corroborate international data, underscoring regional disparities in Brazil that may lead to worse outcomes in disadvantaged areas. This highlights the need for improved orthopedic oncology care in Brazil's economically and structurally challenged regions. Level of Evidence III; Retrospective Cohort.

RESUMO Introdução: O tumor de células gigantes do osso (TCG) atinge principalmente epífises de ossos longos em adultos jovens, impactando a resistência óssea e a funcionalidade articular. O tratamento principal é cirúrgico, mas há significativa recorrência pós-operatória. Este estudo analisa o perfil de pacientes e tumores de TCG no Brasil, abordagens de tratamento e resultados. Métodos: Avaliamos retrospectivamente taxas de recorrência, metástase e tratamentos em 643 pacientes tratados em 16 centros brasileiros de 1989 a 2021, considerando a distribuição geopolítica. Resultados: 5,1% desenvolveram metástases pulmonares e 14,3% tiveram fraturas patológicas. A recorrência local foi de 18,2%. Regiões economicamente menos favorecidas, como Norte e Nordeste, mostraram maiores incidências de metástases pulmonares (12,1%) e tumores avançados (Campanacci III, 88,9%). O Norte teve alta ocorrência de fraturas patológicas (33,3%), cirurgias extensas (61,1%) e amputações (27,8%). Nessas regiões, o tempo pré-cirúrgico foi mais longo (médias de 36 e 39 dias) comparado ao Sul e Sudeste (27 e 33 dias, respectivamente). Conclusões: Os resultados refletem disparidades regionais no Brasil, sugerindo que condições socioeconômicas influenciam os desfechos clínicos. Estes achados são importantes para melhorar o cuidado oncológico ortopédico em regiões desfavorecidas do país. Nível de Evidência III; Coorte Retrospectiva.

Argon Beam Coagulation as an Adjuvant for Extended Curettage for Giant Cell Tumors of the Bone: A Study of 50 Cases / Coagulação por plasma de argônio como adjuvante à curetagem estendida em tumores de células gigantes do osso: Um estudo de 50 casos

Abstract Objective Extended curettage with adjuvants of giant cell tumors of bone is associated with a lower rate of recurrence of the tumor while preserving the adjacent joint. The present study was conducted to estimate the recurrence rate and functional outcome after using argon beam as an adjuvant for extended curettage. Methods We selected 50 patients with giant cell tumors, meeting all the inclusion criteria, who underwent extended curettage using high speed burr and argon beam photocoagulation between July 2016 to January 2019. On their follow-up visit, they were assessed for any complaints of pain and signs like tenderness, locally raised temperature, and decreased range of motion of the adjacent joint. Radiologically, the patients were assessed for any increased lucency around the cement mantle and uptake of the subarticular graft. Musculoskeletal Tumor Society Score (MSTS) was administered to the patients, and range of motion of the adjacent joint was compared with the contralateral joint. Results Recurrence was found in 4 patients, that is, an 8% recurrence rate. Twenty-six out of 28 patients with a tumor in the lower limb had a grade-5 weight bearing status 6 months from the surgery, and their range of motion was comparable to contralateral healthy joint with an average MSTS score of 27 (18-30). Conclusion Extended curettage of giant cell tumors using argon beam coagulation is associated with low recurrence rates of the tumor and is an effective modality in the treatment of these tumors besides having a functional outcome comparable to the healthy limb.

Resumo Objetivo A curetagem estendida com adjuvantes de tumores de células gigantes do osso está associada a uma menor taxa de recidiva da neoplasia e à preservação da articulação adjacente. Este estudo foi feito para estimar a taxa de recidiva e o resultado funcional após o uso de plasma de argônio como adjuvante à curetagem estendida. Métodos Cinquenta pacientes com tumores de células gigantes que atendiam a todos os critérios de inclusão foram selecionados para o estudo e submetidos à curetagem estendida com broca de alta velocidade e fotocoagulação com plasma de argônio entre julho de 2016 e janeiro de 2019. À consulta de acompanhamento, os pacientes foram avaliados quanto a quaisquer queixas de dor e sinais como sensibilidade, aumento local da temperatura e diminuição da amplitude de movimento da articulação adjacente. Radiologicamente, os pacientes foram avaliados quanto à presença de qualquer aumento de radiotransparência ao redor do manto de cimento e incorporação do enxerto subarticular. O questionário Musculoskeletal Tumor Society Score (MSTS) foi administrado aos pacientes e a amplitude de movimentação da articulação adjacente foi comparada à articulação contralateral. Resultados Quatro pacientes apresentaram recidiva, o que corresponde a uma taxa de 8%. Seis meses após a cirurgia, 26 de 28 pacientes com tumor no membro inferior tinham capacidade de sustentação de peso de grau 5 e amplitude de movimento comparável à articulação saudável contralateral, com pontuação MSTS média de 27 (intervalo de 18 a 30). Conclusão A curetagem estendida de tumores de células gigantes com coagulação por plasma de argônio está associada a baixas taxas de recidiva da neoplasia; é uma modalidade eficaz no tratamento desses tumores e o resultado funcional é comparável ao do membro saudável.

Tumor de células gigantes malignizado: a propósito de un caso

Introducción: La rodilla es la región anatómica donde asientan la mayor cantidad de tumores benignos y malignos que afectan el esqueleto humano, entre ellos se encuentra el tumor de células gigantes. Objetivo: Conocer un paciente con un tumor de células gigantes que sufrió transformación maligna. Caso clínico: Paciente, masculino de 28 años de edad, blanco sin antecedentes mórbidos de salud, que acudió a la consulta externa de la especialidad de Ortopedia y Traumatología por presentar desde hace dos años una tumoración dolorosa a nivel de la rodilla que en los últimos dos meses ha aumentado de tamaño. Se realizaron exámenes imagenológicos mediante radiografía simple, tomografía axial computarizada e imagen de resonancia magnética, además de toma de biopsia incisional para confirmar el diagnóstico. Al analizar los resultados de los exámenes anteriores el equipo multidisciplinario decidió la amputación de la extremidad. Conclusiones: El tumor de células gigantes es una enfermedad que se presenta con mayor frecuencia desde la tercera a quinta décadas de la vida, sus complicaciones principales son la recidiva, las metástasis pulmonares y la transformación maligna. Por lo general, los enfermos con esta última complicación necesitan de procedimientos como la amputación de la extremidad.

Introduction: The knee is the anatomical region where the largest number of benign and malignant tumors that affect the human skeleton settle, among them is the giant cell tumor. Objective: To present a patient with a giant cell tumor that underwent malignant transformation. Clinical case: A 28-year-old white male with no morbid health history, who attended the Orthopedics and Traumatology outpatient clinic for presenting a tumor accompanied by pain at the level of the right knee. It appeared two years ago, but has increased in size rapidly in the last two months. Imaging tests were performed using plain radiography, computed tomography, and magnetic resonance imaging, as well as incisional biopsy to confirm the diagnosis. After analyzing the results of the previous examinations, the multidisciplinary team decided to amputate the limb. Conclusions: The giant cell tumor is an entity that occurs most frequently from the third to fifth decades of life; its main complications are recurrence, lung metastases and malignant transformation. In general, patients with this last complication need procedures such as amputation of the limb.

Mid-term efficacy of surface knee prosthesis combined with bionic block in joint reconstruction after resection of giant cell tumor in proximal tibia / 中华骨科杂志

A total of 6 patients were treated with surface knee joint prosthesis combined with 3D-printed customized bionic tibial block for reconstruction of bone defect after giant cell tumor (GCT) in proximal tibia (1 male and 5 females, aged 50, 40, 68, 53, 35, 42, respectively). 3 patients with primary and 3 patients with recurrence of GCT. After resection of the tumor, the bone defect was filled with 3D-printed block combined with surface knee prosthesis, the surrounding ligaments were reconstructed with microporous structure and artificial mesh. All cases were followed up for 60, 90, 60, 60, 75, and 50 months, respectively. During the follow-up, there was no local recurrence, no radiolucent lines around prosthesis, and no signs of loosening. The clinical scores of the American Knee Society Score (KSS) were 87, 92, 85, 90, 95 and 78. The functional scores were 70, 100, 70, 100, 100 and 80 respectively. Musculoskeletal Tumor Society Score (MSTS) were 27, 28, 26, 26, 26, 27, respectively. Surface knee prosthesis combined with bionic block can effectively fill the bone defect after resection of GCT in proximal tibia, achieve anatomical and functional reconstruction of knee joint.

Anti-Histone H3.3 G34W antibody is a sensitive and highly specific immunohistochemistry marker for the diagnosis of Giant cell tumor of bone. A validation based on analysis of 198 cases from a single centre in India

Context: The diagnosis of giant cell tumor of bone (GCTB) is difficult in small biopsies with unusual age of presentation, location, and extensive secondary changes. Most of the GCTBs harbor H3F3A G34W mutations with a subset of cases showing alternate G34V, G34R, and G34L mutations. Objectives: To analyze the expression of anti-histone H3.3G34W antibody in different cellular components of GCTB across different locations and presentations (including the unusual ones) and validate the utility of this antibody in the diagnosis of GCTB and differentiate it from the other osteoclast-like giant-cell-rich lesions. Design: Immunohistochemistry was performed using anti-histone H3.3G34W antibody in the diagnosed cases of GCTB (136 cases of GCTB from 133 patients, including two malignant GCTBs) and other giant cell-containing lesions (62 cases). The presence of unequivocal crisp nuclear staining was considered positive. Results: Immunohistochemistry revealed unequivocal nuclear positivity in the mononuclear cells in 87.3% of the cases of GCTB. Of these, most showed diffuse expression with moderate to strong intensity staining. The positive staining was restricted to the nuclei of mononuclear cells with the nuclei of osteoclastic giant cells being distinctly negative. In addition to conventional GCTBs, two cases each of multicentric and malignant GCTB showed positive staining. The other giant-cell containing lesions were distinctly negative. The present study showed a sensitivity of 87.3% with specificity and positive predictive value of 100%. Conclusion: The anti-histone G34W antibody is a highly sensitive and specific marker for the diagnosis of GCTB and differentiating it from its mimics. The positive staining is restricted to the mononuclear cell component of GCTB with sparing the osteoclastic giant cells further reiterating the fact that the mononuclear stromal cells are the true neoplastic component of GCTB.

Tumor de células gigantes / Giant Cell Tumor

Introducción: El tumor de células gigantes continúa siendo uno de los tumores óseos con muchas controversias en su diagnóstico y manejo, por ortopédicos, radiólogos y patólogos. Objetivo: Enriquecer el diagnóstico de esta enfermedad desde el aporte de las técnicas de imagen. Presentación de caso: Paciente masculino de 33 años de edad, remitido a la consulta de Ortopedia por presentar un aumento de volumen en la rodilla de meses de evolución, que empeoró progresivamente hasta llegar a la impotencia funcional. Al examen físico se constata un marcado aumento del volumen por lo que se indican estudios de imagen. Conclusiones: El diagnóstico temprano ayuda a mejorar el estilo de vida de estos pacientes. El tratamiento quirúrgico es el más indicado en tumores de células gigantes, ya que logra buenos resultados tanto en el tratamiento del tumor primario como de las recidivas (AU)

Introduction: The giant cell tumor continues to be one of the bone tumors with many controversies in diagnosis and management, by orthopedists, radiologists and pathologists. Objective: To enrich the diagnosis of this disease from the contribution of imaging techniques. Casereport: We report the case of a 33-year-old male patient, referred to the Orthopedics consultation for presenting an increase in volume in his knee, with months of evolution, which progressively worsened until functional impotence. Physical examination showed a marked increase in volume, so imaging studies are indicated. Conclusions: Early diagnosis helps to improve the lifestyle of these patients. Surgical treatment is the most indicated in giant cell tumors, since it achieves good results both in the treatment of the primary tumor and recurrences(AU)

Tratamiento reconstructivo de bajo costo tras resección de tumor de células gigantes de radio distal / Low-cost reconstructive treatment after resection of distal radius giant cell tumor

Resumen: Introducción: El tumor de células gigantes (TCG) es un tumor óseo intramedular benigno que surge con frecuencia en los extremos de los huesos largos. Después del fémur distal y la tibia proximal, el radio distal es el tercer sitio más afectado con tumores, particularmente agresivos. Nuestro objetivo es la presentación del caso clínico de una paciente con diagnóstico de TCG de radio distal clasificada en grado III de Campanacci que recibió un tratamiento ajustado a sus posibilidades económicas. Reporte de caso: Paciente femenino de 47 años, sin solvencia económica y sin ningún servicio médico. El tratamiento incluyó resección en bloque, reconstrucción con autoinjerto de peroné distal y artrodesis radiocarpiana con placa de compresión bloqueada. Dieciocho meses después, la paciente presentaba una buena fuerza de prensión (80% respecto al lado sano) y tenía una función motora fina en la mano. La muñeca presentó estabilidad con pronación de 85o, supinación de 80o, flexión-extensión de 0o y una puntuación de 6.7 en el cuestionario de evaluación de resultados funcionales DASH. Su evolución radiológica a cinco años después de su cirugía continuó sin datos de recidiva local y afectación pulmonar. Conclusión: El resultado en esta paciente, junto con los datos publicados, indican que la técnica de resección tumoral en bloque, más el autoinjerto de peroné distal y la artrodesis con placa de compresión bloqueada proporcionan un resultado óptimo de funcionalidad para el tumor radial distal grado III a bajo costo.

Abstract: Introduction: Giant cell tumor (GCT) is a benign intramedullary bone tumor that frequently arises at the ends of long bones. After the distal femur and proximal tibia, the distal radius is the third most affected site with particularly aggressive tumors. Our objective is the presentation of the clinical case of a patient diagnosed with distal radius GCT classified in grade III of Campanacci who received a treatment adjusted to her economic possibilities. Case report: A 47-year-old female, without economic solvency and with some medical service. Treatment included block resection, reconstruction with distal fibula autograft, and radiocarpal fusion with blocked compression plate. Eighteen months later, the patient had good grip strength (80% on the healthy side) and had fine motor function in the hand. The wrist presented stability with pronation of 85o, supination of 80o, flexion-extension of 0o and a score of 6.7 in the DASH functional outcomes assessment questionnaire. His radiological evaluation five years after his surgery continued with no evidence of local recurrence and pulmonary involvement. Conclusion: The result in this patient, together with the published data, indicate that the block tumor resection technique, plus distal fibula autograft and arthrodesis with blocked compression plate provide an optimal result of functionality for the grade III distal radial tumor at low cost.

Tumor de células gigantes en el extremo distal del radio / Giant Cell Tumor Of The Distal Radius

Introducción: El tumor de células gigantes de hueso es uno de los tumores menos frecuentes y su comportamiento local es agresivo. Objetivo: Presentar un caso afectado por un tumor de células gigantes tratado con resección en bloque y artrodesis de la articulación de la muñeca. Presentación del caso: Paciente masculino de 29 años de edad, con antecedentes relativos de salud, que presentaba desde hacía 5 meses aumento de volumen e impotencia funcional al realizar flexo extensión activa de la muñeca izquierda, con empeoramiento progresivo. Se diagnosticó tumor óseo de células gigantes con marcada actividad proliferativa estromal en el extremo distal del radio, se realizó resección en bloque y artrodesis del extremo distal del radio con márgenes oncológicos y transferencia del flexor radial corto al extensor común y del palmar menor al extensor y abductor del pulgar. Conclusiones: La resección en bloque y artrodesis es una de las opciones a tener en cuenta en la cirugía reconstructiva de la extremidad superior con un resultado satisfactorio(AU)

Introduction: Giant cell tumor of bone is one of the least frequent tumors and the local behavior is aggressive. Objective: To report a case with giant cell tumor treated with en bloc resection and arthrodesis of the wrist joint. Case report: A relative healthy 29-year-old male patient had had increased volume and functional impotence when performing active flexor extension of the left wrist for 5 months, with progressive worsening. A giant cell bone tumor with marked stromal proliferative activity was diagnosed in the distal end of the radius. En bloc resection and arthrodesis of the distal end of the radius were performed with oncological margins and the transfer of the flexor radialis brevis to the common extensor and the palmaris minor to the extensor and abductor pollicis. Conclusions: En bloc resection and arthrodesis is one of the options to consider in reconstructive surgery of the upper extremity with a satisfactory result(AU)

Índice de recurrencia de tumor de células gigantes con curetaje y cementación / Recurrence rate of giant-cell tumor treated by curettage and cementation

OBJETIVO Identificar la tasa de recurrencia de tumor de células gigantes (TCG) en pacientes tratados con curetaje y cementación con seguimiento mínimo de tres años. MATERIALES Y METODOS Cohorte retrospectiva y observacional de pacientes con diagnóstico de TCG en estadios 1 y 2 de Enneking tratados con curetaje intralesional y cementación entre 1981 y 2011. Se registraron edad, sexo, región anatómica, y tiempo de recurrencia. Se utilizó estadística descriptiva con medidas de tendencia central y medidas de dispersión (desviación estándar) para variables cuantitativas, y porcentajes para variables cualitativas. RESULTADOS Entre 1981 y 2011, se identificaron 375 casos de TCG, de los cuales 141 (37,6%) fueron tratados con este método. El seguimiento fue de 48 a 240 meses, y la edad, de 27 9 años; 45% de los pacientes eran mujeres, y 55%, varones, con una relación mujer:hombre de 1,2:1. El hueso más afectado fue la tibia (38%), seguida del fémur (32%), del húmero (16%), y del radio (10%). En 88,6%, la resección fue curetaje intralesional, y el resto, marginal. Hubo 15,7% de casos de TCG con fractura, y recidiva en 12,7%. DISCUSIÓN Se ha demostrado que este método de tratamiento reduce el riesgo de recurrencia por los efectos adyuvantes locales de la cementación acrílica. La recurrencia ocurre en los dos primeros años de seguimiento. Sin embargo, hay autores que respaldan que el margen quirúrgico es el único factor que influencia el riesgo de recurrencia local. La extensión extraósea del TCG no es contraindicación para curetaje intralesional y adyuvante con metilmetacrilato. CONCLUSIONES Reportamos tasa una de recurrencia similar a la de la literatura, siendo un recurso factible de reconstrucción de miembros

OBJETIVE To identify the recurrence rate of giant-cell tumor (GCT) in patients treated by curetage and adjuvant therapy with polymethil metacrylate with a minimum followup of 3 years. MATERIALS AND METHODS Observational and retrospective cohort with patients with diagnoses of Enneking stages 1 and 2 GCT treated through intralesional curetage and cementation between 1981 and 2011. Age, gender, anatomic location and relapse period were recorded. The data was analyzed with measures of central tendency and dispersion (standard deviation) for the quantitative variables, percentages for the qualitative variables. RESULTS Between 1981 and 2011 375 cases of GCT were identified, 141 (36.7%) of which were treated by this method. The follow-up ranged from 48 to 240 months, the age was of 27 9 years, 45% of the patients were female, and 55%, male, with a female: male ratio of about 1.2:1. The tibia was the most frequent affected bone (38%), followed by the femur (32%), the humerus (16%), and the radius (10%). The resection thecnique was intralesional curetage in about 88.6% of the cases, and marginal resection in the remaining cases. Pathologic fracture was present in approximately 15.7%, and recurrence occurred in approximately 12.7%. DISCUSSION We demonstrated that this treatment method decreases the risk of recurrence due to the local adjuvant effects of acrylic cementation. Recurrence events occur in the first two years after resection. However, some authors defend that the surgical margin is the only factor that influences the risk of local recurrence. The extraosseus extension of GCT is not a contraindication to perform intralesional curetage or to prescribe the adjuvant treatment with polymethyl metacrylate. CONCLUSIONS We reported a recurrence rate similar to that of the literature, and this is a feasible resource for limb reconstruction

Single-cell transcriptome reveals features of immune environment and mechanisms of immune escape in giant cell tumor of bone / 中华骨科杂志

Objective:This study aims to reveal the special immune infiltrating environment and possible immune escape mechanism of giant cell tumor of bone through single-cell sequencing data.Methods:The fresh samples obtained from 4 patients with primary giant cell tumor of bone from January 2018 to December 2021 were collected, and single-cell transcriptome sequencing was performed on the 10X platform to explore the characteristics and immune environment of giant cell tumor of bone by using t-distributed stochastic neighbor embedding ( t-SNE). The main cell types and signal pathways of immune cell regulation and function in giant cell tumor of bone were observed by cell communication analysis. Results:Cell clustering, the definition of basic cell types, the classification of immune cells, and the mutual regulatory relationship between cell types were analyzed for 35 643 single-cell data from 4 giant cell tumor samples of bone. It was found that giant cell tumor of bone was composed of 9 basic cell types, in which the immune cells were mainly CD8 + T cells (51%) and the non-immune cells were mainly fibroblast like spindle stromal cells (74%). The immune infiltration of giant cell tumor of bone is dominated by cytotoxic CD8 + T cells and lacks exhausted CD8 + T cells. CD4 + T cells are characterized by high expression of immune checkpoint genes CTLA4 and TIGIT. In giant cell tumor of bone, immune cells mainly act on multinucleated osteoclast like giant cells through PARs and CCL signaling pathways, but not stromal cells. Conclusion:This study defined the main cell types of giant cell tumor of bone through single cell sequencing data, and further revealed the composition characteristics of its immune infiltration, and found that the target of its immune cells was mainly multinuclear osteoclast like giant cells, which provided effective information for further understanding the occurrence and development of giant cell tumor of bone.

Long-term use of denosumab in giant cell tumors and vertebral aneurysmal bone cysts / Uso prolongado de denosumab no tumor de células gigantes e cistos ósseos aneurismáticos vertebrais / Uso prolongado de denosumab en tumor de células gigantes y quistes óseos aneurismáticos vertebrales

ABSTRACT Introduction: Denosumab is a human monoclonal antibody that binds to the receptor activator of nuclear factor kB (RANKL), it is used in the treatment of Osteoporosis. The Giant Cell Tumor (GCT) and the Aneurysmal Bone Cyst (ABC) use the same RANKL, and for this reason this drug began to be used for its treatment. There is consensus on the use, dose-time and 12-month duration for Denosumab treatment of GCT. Not so for ABC. In unresectable, disabling or recurrent tumors, its use could be for life. The adverse events of the habitual use of the drug are known, but it is not known if these increase with time. The objective of the present work is to identify the possible adverse events of treatment with Denosumab for more than 12 months. Material and Method: Series of cases with a diagnosis of GCT or ABC in spine, treated with Denosumab for more than 12 months. Adverse events are: arthralgia, fatigue, spinal pain, pain in extremities, headache, hypokalaemia, hypocalcemia, osteonecrosis of the jaw, malignant transformation, pathological fractures. Results: Eight patients, 6 TCG and 2 ABC, with a mean age at diagnosis of 25,6 years; presenting a mean treatment of 4.18 years (range 1.7 - 8.7). Of 6 operated patients, 4 had recurrence (2 to 36 months after surgery). One patient had to suspend treatment due to necrosis of the jaw, another hypocalcemia, both returned to treatment when stabilized. Conclusions: A minor adverse event (hypocalcemia) and a major adverse event (jaw bone necrosis) were observed. Level of Evidence IV; Original.

RESUMO Introdução: O denosumab é um anticorpo monoclonal humano que se liga ao receptor ativador do fator nuclear kB (RANKL), sendo utilizado no tratamento da Osteoporose. O Tumor de Células Gigantes (TCG) e o Cisto Ósseo Aneurismático (CAO) utilizam o mesmo RANKL, por isso esse medicamento passou a ser utilizado para seu tratamento. Há consenso sobre o uso, o tempo de dosagem e a duração de 12 meses para o tratamento com Denosumabe de TCG. Não é assim para CAO. Em tumores irressecáveis, incapacitantes ou recorrentes, seu uso pode ser vitalício. Os eventos adversos do uso habitual do medicamento são conhecidos, mas não se sabe se aumentam com o tempo. O objetivo do presente trabalho é identificar os possíveis eventos adversos do tratamento com Denosumabe por mais de 12 meses. Material e Método: Série de casos com diagnóstico de TCG ou CAO na coluna, tratados com Denosumabe por mais de 12 meses. Os eventos adversos são: artralgia, fadiga, dor na coluna, dor nas extremidades, cefaleia, hipocalemia, hipocalcemia, osteonecrose da mandíbula, transformação maligna, fraturas patológicas. Resultados: Oito pacientes, 6 TCG e 2 LRA, com média de idade ao diagnóstico de 25,6 anos; apresentando um tratamento médio de 4,18 anos (variação 1,7 - 8,7). Dos 6 pacientes operados, 4 tiveram recorrência (2 a 36 meses após a cirurgia). Um paciente teve que suspender o tratamento por necrose da mandíbula, outro hipocalcemia, ambos voltaram ao tratamento quando estabilizados. Conclusões: Um evento adverso menor (hipocalcemia) e um evento adverso maior (necrose óssea da mandíbula) foram observados. Nível de Evidência IV; Original.

RESUMEN Introducción: El Denosumab es un anticuerpo humano monoclonal que se une al receptor activador del factor nuclear kB (RANKL), se lo utiliza en el tratamiento de Osteoporosis. El Tumor de Células Gigantes (TCG) y el Quiste Óseo Aneurismático (QOA), utilizan los mismos RANKL, y por ello se comenzó a utilizar esta droga para su tratamiento. Existe consenso en la utilización, dosis-tiempo y 12 meses de duración para el tratamiento con Denosumab del TCG. No así para el QOA. En tumores irresecables, incapacitantes o con recidiva, su uso podría ser de por vida. Se conocen los eventos adversos de la utilización habitual de la droga, pero no se sabe si estas aumentan con relación al tiempo. El objetivo del presente trabajo, es identificar los posibles eventos adversos del tratamiento con Denosumab por más de 12 meses. Material y Método: Serie de casos con diagnóstico de TCG o QOA de columna, tratados con Denosumab por más de 12 meses. Los eventos adversos son: artralgias, fatiga, raquialgia, dolor en extremidades, cefalea, hipopotasemia, hipocalcemia, osteonecrosis de mandíbula, transformación maligna, fractura patológica. Resultados: Ocho pacientes, 6 TCG y 2 QOA, con promedio de edad al diagnóstico de 25,6 años; presentando una media de tratamiento de 4.18 años (rango 1,7 - 8,7). De 6 pacientes operados, 4 presentaron recidiva (2 a 36 meses después de la cirugía). Un paciente se debió suspender el tratamiento al presentar una necrosis de mandíbula, otro hipocalcemia, ambos retornaron al tratamiento al estabilizarse. Conclusiones: Se observa un evento adverso menor (hipocalcemia) y un evento adverso mayor (necrosis ósea de mandíbula). Nivel de Evidencia IV; Original.

Denosumab como tratamiento neoadyuvante del tumor de células gigantes del hueso. Indicaciones, resultados y efectos adversos / Denosumab as a neoadjuvant treatment for giant cell tumor of bone. Indications, results and side effects

Resumen El tumor de células gigantes óseo es una neoplasia de agresividad local intermedia, que raramente metastatiza. En los últimos años el denosumab, anticuerpo monoclonal humano, surgió como una alternativa de tratamiento para esta enfermedad, al bloquear el comportamiento lítico tumoral. El objetivo de este trabajo fue determinar sus indicaciones y efectos adversos, analizando también los resultados oncológicos, y las tasas de recurrencia local en pacientes con diagnóstico de tumor de células gigantes óseo que recibieron denosumab como tratamiento neoadyuvante. Entre 2010 y 2018 se analizaron 80 pacientes con tumor de células gigantes, de los cuales 14 recibieron denosumab como tratamiento neoadyuvante. El seguimiento mínimo fue 12 meses. En 8 pacientes se trató de un tumor primario, mientras que 6 fueron pacientes con recidiva tumoral. En todos los casos se evidenció una mejoría clínica. Trece presentaron cambios radiográficos, y 11 respuesta histológica completa. En 6 de 14 pacientes se evidenció una recurrencia local y en 7 se identificó al menos un efecto adverso relacionado con el denosumab (incluyendo una malignización tumoral). A pesar de ser una herramienta útil para el tratamiento del tumor de células gigantes, el uso de denosumab está asociado a mayor tasa de recurrencias locales y no está exento de efectos adversos.

Abstract Giant cell tumor of bone is an intermediate, locally aggressive and rarely metastasiz ing, primary bone neoplasia. In recent years denosumab emerged as a treatment alternative for this pathology. The objective of this work was to analyze its indications as well as the clinical outcomes, side effects and local recurrence rates in patients diagnosed with giant cell tumor of bone, who received denosumab as neoadjuvant treatment. Between 2010 and 2018, 80 patients with giant cell tumor were analyzed, of whom 14 received deno sumab as a neoadjuvant treatment. The minimum follow-up was 12 months. In 8 patients it was a primary tumor, while 6 showed tumor recurrence. In all cases, clinical improvement was evident. Thirteen patients presented radiographic changes, and 11 showed complete histological response. A local recurrence was evidenced in 6 of 14 patients, and at least one adverse effect related to denosumab (including tumor malignancy) was identified in 7. Despite being a useful tool for treating giant cell tumor, the use of denosumab is associated with a higher rate of local recurrences and is not free of adverse effects.

Tumor de células gigantes del fémur / Tumor of giant cells of the femur

El tumor de células gigantes de hueso es un tumor raro de características benignas con un comportamiento agresivo localmente. Predomina en mujeres y por lo general se presenta en la epífisis y metáfisis de los huesos largos. El propósito de este estudio es presentar el caso de un paciente con una lesión tumoral de rodilla y muslo izquierdos de 2 años de evolución y señalar las características diagnósticas de este tumor al mismo tiempo que se revisan los métodos imagenológicos recientes para su confirmación. Se presenta a un paciente masculino de 19 años de edad, que comenzó con dolor, aumento de volumen de la rodilla y muslo izquierdos, acompañado de impotencia funcional. Se reportaron los hallazgos clínicos, radiográficos e histológicos. Debido a la demora entre el inicio de los síntomas y el diagnóstico se practicó el tratamiento quirúrgico del miembro afectado (amputación). Tras 10 meses de observación no se han presentado recidivas o metástasis. Se envió al Servicio de Oncología para valorar e tratamiento con radioterapia. El tumor de células gigantes del hueso es un tumor raro, de buen pronóstico, pero que puede recidivar y causar metástasis cuando se maligniza. Por la posibilidad de transformación en sarcoma requiere estudio y observación periódica. El tiempo para realizar el diagnóstico es fundamental y debe pensarse en este tumor en caso de lesiones líticas de hueso reportadas por imagenología(AU)

The giant cell tumor of bone is a rare benign tumor with a locally aggressive behavior. It predominates in women and usually occurs in the epiphysis and metaphysis of long bones. To present a patient with a tumor lesion left knee and thigh two years of evolution, also noted the diagnostic characteristics of this tumor while recent imaging methods are reviewed for confirmation. 19-year-old male who began with pain, increased volume of the knee and left thigh, accompanied by functional impotensia. clinical, radiological and histological findings were reported. Because of the delay between the onset of symptoms and diagnosis surgical treatment of the affected limb (amputation) was performed. After ten months of observation there have been no recurrences or metastases. The giant cell tumor of bone is a rare tumor with good prognosis but can recur and metastasize when it becomes malignant. The possibility of transformation in sarcoma requires periodic study and observation. The time for diagnosis is essential and should think of this tumor in case of lytic bone lesions reported by imaging(AU)

Tumor de células gigantes de la vaina con infiltración tendinosa / Giant cell tumor of the sheath with tendinous infiltration

Se describe el caso clínico de una paciente de 58 años de edad, quien acudió a la consulta de Ortopedia y Traumatología del Hospital General Docente Dr. Juan Bruno Zayas Alfonso de Santiago de Cuba porque hacía alrededor de 5 años comenzó a notar aumento progresivo de volumen en el dorso de la mano izquierda, cercano a la articulación metacarpofalángica del tercer dedo, que le dificultaba la extensión y resultaba antiestético. Mediante la ecografía se observó una imagen ecogénica, bien delimitada, que infiltraba el espesor del tendón, por lo que se realizó la exéresis del tumor. Se comprobó la infiltración de dicho tendón, el cual se resecó y se sustituyó con autoinjerto del tendón accesorio que envía el tendón del dedo anular. Los resultados de los estudios histológicos informaron que se trataba de un tumor de células gigantes de la vaina con infiltración tendinosa. Se inmovilizó durante 3 semanas y la recuperación funcional se completó a los 45 días.

The case report of a 58 years patient is described. She went to the Orthopedics and Traumatology Service of Dr. Juan Bruno Zayas Alfonso Teaching General Hospital in Santiago de Cuba because she began to notice progressive increase of volume in the back of the left hand around 5 years ago, near the metacarpusphalangic articulation of the third finger that made its extension difficult and was unsightly. By means of the scan, a well defined echogenic image that infiltrated the thickness of the tendon was observed, reason why the exeresis of the tumor was carried out. The infiltration of this tendon was confirmed, which was dried up and substituted with self-graft of the accessory tendon that sends the ring finger tendon. The results of the histologic studies reported that it was a giant cell tumor of the sheath with tendinous infiltration. The hand was immobilized during 3 weeks and the functional recovery was completed at 45 days.

Tumor de células gigantes de la vaina tendinosa / Giant cell tumor of the tendon sheath

Fundamento: el tumor de células gigantes de la vaina tendinosa ocupa el segundo lugar en frecuencia dentro de las neoplasias de la mano. El diagnóstico es clínico y radiológico y se confirma por medios de estudios anatomopatológicos. Objetivo: describir la epidemiología, aspectos clínicos e histológicos del tumor de células gigantes de la vaina tendinosa. Métodos: se realizó un estudio observacional descriptivo para el reporte de seis casos de los archivos del Departamento de Anatomía Patológica de 2016 y 2018, para identificar los casos con diagnóstico tumor de células gigantes de la vaina tendinosa. Resultados: se diagnosticaron un total de seis casos de tumor de células gigantes de la vaina tendinosa, los cuales se correspondieron a igual número de casos para cada sexo, en su mayoría eran pacientes menores de 40 años y en todos los casos el sitio de presentación del tumor fue la mano, con predominio de la región palmar del dedo pulgar. Ninguno de los casos manifestó dolor. En el estudio morfológico microscópico se observaron, los elementos histológicos característicos del tumor de células gigantes de la vaina tendinosa. Conclusiones: los seis pacientes estudiados presentaron la clínica típica del tumor de células gigantes de vaina tendinosa, es decir, refirieron aumento de volumen que se corroboró con el examen físico al palpar una tumoración de tejido subcutáneo, no dolorosa, lisa, blanda y de bordes bien definidos. De igual manera en el estudio histopatológico, se corroboraron los elementos morfológicos característicos, por lo cual se puede establecer que hubo una correlación clínico-patológica del 100 %.

ABSTRACT Background: the giant cell tumor of the tendon sheath occupies the second place in frequency in the neoplasms of the hand. The diagnosis is clinical and radiological, confirmed by anatomic-pathological studies. Objective: to describe the epidemiology, clinical and histological aspects of the giant cell tumor of the tendon sheath. Methods: a descriptive observational study was carried out for the report of six cases from the files of the Department of Pathology from 2016 and 2018, to identify the cases with a diagnosis of giant cell tumor of the tendon sheath. Results: a total of six cases of giant cell tumor of the tendon sheath were diagnosed, corresponding 50% to each sex; the majority were under 40 years old; and in all cases the site of presentation of the tumor was the hand; with a predominance in the palm region of the thumb. None of the cases manifested pain. In the morphological study, the characteristic histological elements of the giant cell tumor of the tendon sheath were observed microscopically. Conclusions: the six patients studied presented the typical symptoms of the Giant cell tumor of the tendon sheath, referring to an increase in volume that was corroborated with the physical examination by palpating a mass of subcutaneous, non-painful, smooth, soft tissue with well-defined borders. In the same way, histopathologically, the characteristic morphological elements were corroborated, for which it can be established that there was a clinical-pathological correlation of 100%.

Radioterapia en tumor de células gigantes tenosinovial (sinovitis villonodular pigmentada) / Radiation therapy in tenosynovial giant cell tumor (pigmented villonodular synovitis)

Presentar nuestra experiencia de 18 años en el tratamiento con radioterapia y evaluar cifras de control tumoral local en pacientes con diagnóstico de tumor de células gigantes tenosinovial difuso sinovitis villonodular pigmentada difusa. 33 pacientes, tratados durante el período 2000-2018. En 19 (57,6 %) se practicó sinovectomía parcial, 10 (30,3 %) fueron tratados con artroplastia y sinovectomía, 4 (12,2 %) con sinovectomía total. 32 pacientes recibieron radioterapia posoperatoria, 1 paciente preoperatoria. Técnica más empleada fue planificación 2D 51,5 % seguida de conformada con planificación 3D (RTC3D) 48,5 %. La dosis total promedio administrada 44 Gy (rango 10,5 - 50). Tiempo promedio de tratamiento radiante 28 días (8-35). Tiempo de seguimiento entre 0,7 - 240,8 meses, mediana 12 meses, promedio 52,1 meses. 26 pacientes (79 %) presentaron mejoría de la sintomatología inicial y 6 (18 %) refirieron estabilidad de los síntomas. La respuesta clínica al tratamiento en relación al tiempo de seguimiento, 12 pacientes (36,4 %) estaban asintomáticos, 10 con un seguimiento mayor a 60 meses; 14 (42,4 %) refieren respuesta clínica satisfactoria, (2 con un seguimiento mayor a 60 meses) 6 pacientes presentaban enfermedad estable, para un control local del 97 %. El 87,9 % presentaron dermatitis grado I, 1 desarrolló dermatitis grado II, 3 no presentaron efectos adversos. La radioterapia es una modalidad de tratamiento muy efectiva como adyuvante a la sinovectomía, observándose altas tasas de control local de la enfermedad con una baja morbilidad(AU)

To report our eighteen-year experience with radiation therapy in the treatment of diffuse tenosinovial giant cell tumor / diffuse pigmented villonodular synovitis and to assess local control of the disease. A review of 33 patients with treated with radiation therapy during the period 2000-2018 was done. 19 (57.6 %) partial synovectomy was performed, 10 (30.3 %) underwent arthroplasty plus synovectomy, 4 (12.2 %) total synovectomy. 32 patients received radiotherapy postoperative and 1 pre-operative. Most common technique employed was conventional (2D) in 51.5 % and 3D conformal (3DCRT) in 48.5 %. The average total dose was 44 Gy (range 10.5-50), with a mean treatment time of 28 days (8-35). Follow-up time ranged from 0.7- 240.8 months, median time and mean time of 12 and 52.1 months respectively After RT 26 (79 %) of the patients obtained improvement of the initial symptoms and 6 (18 %) were stable. 12 patients (36.4 %) were asymptomatic with follow-up time longer than 36 months (10 of 12 had follow-up time >60 months), 14 (42.4 %) had significant clinical improvement (2 of 14 had follow-up time >60 months), and 6 had stable disease, local control of 97 %. Complications were few, acute skin toxicity was grade I in 29 (87.9%) and grade II in 1 patient. There was no significant chronic toxicity. Radiation therapy is an effective adjuvant treatment modality after synovectomy in patients with high local control rates and low morbidity(AU)

Tarsal villonodular tenosynovitis (giant cell tumor of tendon sheath) in a dog / Tenossinovite vilonodular pigmentada (tumor de células gigantes da bainha tendínea) tarsal em um cão

ABSTRACT: A 12-year-old female mixed-breed dog presented with lameness, pain, and an enlarged, non-ulcerated, nodular mass in the region proximal to the tarsal joint of the right pelvic limb. Surgical excision was performed, revealing a 6.5 cm mass adherent to the deep flexor tendon and adjacent tissues. The cut section had cysts filled with blackened clotted material, which exuded reddish serous fluid. Microscopically, the cysts were filled with red blood cells and were either denuded or covered by synoviocytes. In addition, the mass was characterized by marked fibrovascular connective tissue associated with siderophages and multinucleated giant cells. These findings were consistent with those of pigmented villonodular tenosynovitis, a rare condition affecting several animal species and humans.

RESUMO: Uma cadela de 12 anos, sem raça definida, apresentou claudicação, algia e aumento de volume não ulcerado, de aspecto nodular, na região proximal à articulação do tarso do membro pélvico direito. A excisão cirúrgica foi optada e revelou uma massa de 6,5 cm de diâmetro, aderida ao tendão flexor profundo e aos tecidos adjacentes. Ao corte, exsudava líquido seroso avermelhado e cistos preenchidos por material coagulado enegrecido foram observados. Microscopicamente, a massa apresentava formações císticas frequentemente preenchidas por hemácias, que encontravam-se ora revestidas por sinoviócitos, ora desnudas. Havia ainda acentuada quantidade de tecido fibrovascular associado a siderófagos e células gigantes multinucleadas. Esses achados foram consistentes com tenossinovite vilonodular pigmentada, uma rara condição que afeta diversas espécies de animais e humanos.

The immune microenvironment of giant cell tumor of bone and its role as an indicator to denosumab administration / 中华骨科杂志

Objective:To investigate the alteration of immune microenvironment in giant cell tumor of bone (GCTB) after denosumab treatment from the aspect of immune cellsat single-cell level.Methods:During Nov 2018 and May 2020, fresh tumor excision tissues from GCTB cases were collected and received CyTOF analyses. CyTOF datasets were analyzed and visualized by t-distributed stochastic neighbor embedding (TSNE) method of reduction dimension. The compositions of immune cells in GCTB with or without denosumab treatment were compared. The supernatant of culture medium of ex vivo inoculated primary tumor tissues was harvested to clarify if the culturing supernatant could affect cell growth.Results:A total of 15 primary GCTB cases and three denosumab-treated samples were included in this study and were sent for CyTOF and multicolor FACS assay. GCTB was featured of T-cell and macrophage-like myeloid cell-dominant immune microenvironment. After denosumab treatment, the percentage of T-cells was significantly elevated, while the number of macrophage-like myeloid cells were reduced. Furthermore, the ratio of macrophage-like myeloid cells in total live cells was associated with the treatment period of denosumab. The multinuclear osteoclast like giant cells were characterized by the expression of γδTCR, while most of the intratumoral CD8+ T-cells were activated PD-1+CD69+T-cells. The culturing supernatant of denosumab treatment-free GCTB tissues reinforced cell proliferation in vitro, while this phenomenon was not seen when using denosumab treated tissues.Conclusion:Illustrated the immune cell atlas of GCTB, and preliminarily investigated the potential effects of immune cells on tumor progression in GCTB, providing some theoretical clues for prolonged use of denosumab in unresectable GCTB cases.

Can p63 serve as a biomarker for diagnosing giant cell tumor of bone? A systematic review and meta-analysis

ABSTRACT BACKGROUND: Tumor protein p63 (p63) has been reported to be highly expressed in giant cell tumor of bone (GCTB). Whether p63 can be treated as a diagnostic marker for GCTB remains unclear. OBJECTIVE: We conducted a meta-analysis to evaluate the applicability of p63 in diagnosing GCTB. DESIGN AND SETTING: Systematic review and meta-analysis carried out in a public hospital, Hong Kong, China. METHODS: We searched PubMed, EMBASE and the Cochrane Library from inception to April 30, 2019. Literature in English or Chinese about the differential diagnosis of GCTB using p63 were included. ­Animal experiments, reviews, correspondence, case reports, expert opinions and editorials were excluded. Studies were also excluded if they did not provide sufficient information to construct a 2 × 2 contingency table. We calculated individual and pooled sensitivities and specificities. We used I² as an indicator of heterogeneity. RESULTS: Out of 88 records identified, 8 articles on 788 GCTB patients fulfilled the inclusion criteria and were included in the present analysis. Bivariate analyses yielded a pooled mean sensitivity of 0.87 (95% confidence interval, CI, 0.72-0.95) and specificity of 0.71 (95% CI, 0.56-0.82) for using p63 as a biomarker in diagnosing GCTB. The area under the receiver operating characteristic curve was 0.86 (95% CI, 0.82-0.88). CONCLUSION: p63 is a helpful indicator in diagnosing GCTB due to its high sensitivity and specificity. ­Nonetheless, the results need to be carefully interpreted based on other diagnostic methods such as imaging. SYSTEMATIC REVIEW REGISTRATION: 164115 (PROSPERO registration number)

Comprehensive treatment for multicentric giant cell tumors of the pelvis and spine using apatinib: A case report and literature review

Background: There are no standardized treatments for giant cell tumors of the bone (GCTB) in rare locations such as the spine and pelvis or for those that are inoperable and recurrent, let alone for multicentric GCTB. This study reports a novel case of multicentric GCTB treated with a promising antiangiogenic drug, apatinib, a small-molecule tyrosine kinase inhibitor. The efficacy of apatinib in the treatment of GCTB has not been reported previously. Patients and Methods: A 27-year-old female presented with two giant cell tumors of the spine and sacrum–ilium diagnosed on December 15, 2016. Surgery and selective arterial embolization (SAE) were not reasonable options for this patient, and denosumab was unavailable; therefore, the antiangiogenic drug apatinib and the osteoclast inhibitor zoledronic acid were administered. Apatinib was initially administered at a dose of 850 mg daily, which was decreased to 425 mg daily after 7 months, and then increased again to 635 mg after 11 months. The patient was prescribed a maintenance dose of 500 mg daily after 16 months. The patient reported side effects of Grades I–III nausea, vomiting, and Grades II–III hand–foot syndrome. The patient underwent SAE at 26 months, and at that time, she was switched to denosumab instead of zoledronic acid. Results: The patient showed noticeable symptomatic improvement and visibly reduced tumor size after the first month of treatment. Computed tomography in the 4th month identified a partial response based on the RECIST criteria. The patient has achieved an objective reduction in tumor size at 32 months. Conclusions: Comprehensive treatment including apatinib represents a potential new treatment strategy for inoperable GCTB, with tolerable side effects. However, further clinical trials are now necessary to confirm an effective dose and determine the efficacy and safety of apatinib in the treatment of GCTB