High-grade Pleomorphic Sarcoma Associated with Metallosis in a Patient with Total Hip Arthroplasty.

Although the relationship between hip arthroplasty and the development of sarcoma was first described in the literature about forty years ago, this association is extremely rare. In the present case report, we describe the association between orthopedic implants and soft tissue sarcoma in a 79-year-old man who underwent primary total hip arthroplasty (THA) for coxarthrosis 24 years ago. In the present case report, we describe the clinical evolution and the radiographic and histopathological findings of the lesion. In the intraoperative period of the second revision surgery, loosening of the acetabular and femoral components in association with extensive areas of necrosis and metallosis was evidenced. We performed debridement of the hip and right thigh region and removed the implants. Due to the extent of the lesion and to necrosis, it was not possible to perform a new joint reconstruction. The histopathological diagnosis of high-grade undifferentiated pleomorphic sarcoma associated with extensive areas of metallosis was confirmed in tissue adjacent to the implant. The patient developed pulmonary metastases and died 6 months after the diagnosis. Despite the rarity of this association, sarcomas should be considered in the differential diagnosis of aseptic loosening, especially in the presence of metallosis in the peri-implant tissue. To our knowledge, the 24-year latency period between primary THA and the establishment of a sarcoma diagnosis is one of the longest reported to date.

RESECTION OF ANKLE TUMOR LESION AND RECONSTRUCTION WITH THE USE OF ALLOGRAFT.

Reconstruction of the distal third of the tibia due to resection of a malignant tumor has some hindering factors, such as a thin subcutaneous layer, neurovascular bundles that cross compartments, prolonged operative duration, specific orthopedic material, and a trained multidisciplinary team. Allografting with material from tissue banks is part of this orthopaedic arsenal. OBJECTIVE: To describe the protocol used at Instituto Nacional de Traumatologia e Ortopedia Jamil Haddad. METHODS: Series of six cases subjected to resection with oncologic margins, allograft reconstruction, and use of a retrograde ankle nail as limb-salvage surgery. Three of the six patients were women, the lesions were on average 9.3 cm long, and the average operative duration was 3.25 hours. RESULTS: The main short-term complication (≤ 30 days) was peroneal nerve palsy, while the main long-term complication (> 30 days) was surgical site infection (two cases). Consolidation of the two foci occurred in three patients, and two patients developed asymptomatic pseudoarthrosis of the proximal focus with consolidation of the distal focus. CONCLUSION: Despite the complications, the proposed surgery gives patients the chance to preserve their limb in the face of immediate radical surgery. Level of Evidence IV, Case Series.

A reconstrução do terço distal da tíbia devido à ressecção de tumor maligno apresenta alguns fatores que dificultam sua realização, como camada subcutânea delgada, feixes neurovasculares que transpassam os compartimentos, tempo cirúrgico prolongado, material ortopédico específico e equipe multidisciplinar treinada. O aloenxerto de banco de tecido faz parte deste arsenal ortopédico. Objetivo: Descrever o protocolo realizado no Instituto Nacional de Traumatologia e Ortopedia Jamil Haddad. Métodos: Série de seis casos submetidos à ressecção com margens oncológicas, reconstrução com aloenxerto e uso de haste retrógrada de tornozelo como cirurgia preservadora do membro. Três dos seis pacientes eram do sexo feminino, as lesões tinham em média 9,3 cm de comprimento e o tempo cirúrgico médio foi de 3,25 horas. Resultados: A principal complicação de curto prazo (≤ 30 dias) foi a paralisia do nervo fibular, enquanto a principal complicação de longo prazo (> 30 dias) foi a infecção do sítio cirúrgico (dois casos). A consolidação dos dois focos ocorreu em três pacientes, e dois pacientes evoluíram para pseudoartrose assintomática do foco proximal com consolidação do foco distal. Conclusão: Apesar das complicações, a cirurgia proposta permite ao paciente a chance de preservar seu membro diante de uma cirurgia radical imediata. Nível de Evidência IV, Série de Casos.

Osteosarcoma, chondrosarcoma and Ewing sarcoma: Clinical aspects, biomarker discovery and liquid biopsy.

Bone sarcomas, although rare, are associated with significant morbidity and mortality. The most frequent primary bone cancers include osteosarcoma, chondrosarcoma and Ewing sarcoma. The treatment approaches are heterogeneous and mainly chosen based on precise tumour staging. Unfortunately, clinical outcome has not changed significantly in over 30 years and tumour grade is still the best prognosticator of metastatic disease and survival. An option to improve this scenario is to identify molecular biomarkers in the early stage of the disease, or even before the disease onset. Blood-based liquid biopsies are a promising, non-invasive way to achieve this goal and there are an increasing number of studies which investigate their potential application in bone cancer diagnosis, prognosis and personalised therapy. This review summarises the interplay between clinical and molecular aspects of the three main bone sarcomas, alongside biomarker discovery and promising applications of liquid biopsy in each tumour context.

An association between successful engraftment of osteosarcoma patient-derived xenografts and clinicopathological findings.

Although osteosarcoma is a rare disease, with a global incidence rate estimated at 5.0/million/year, it is the most frequent primary bone sarcoma in children and adolescents. In translational research, the patient-derived xenograft (PDX) model is considered an authentic in vivo model for several types of cancer, as tumorgrafts faithfully retain the biological characteristics of the primary tumors. Our goal was to investigate the association between PDX formation and clinical findings of osteosarcoma patients and the ability of the model to preserve in immunocompromized mice the characteristics of the parental tumor. A fresh sample of the patient tumor obtained from a representative biopsy or from surgical resection was implanted into nude mice. When tumor outgrowths reached ~1,500mm³, fresh PDX fragments were re-transplanted into new hosts. Engraftment in mice was obtained after a latency period of 19-225 days (median 92 days) in 40.54% of the implanted samples. We confirmed the histopathological fidelity between the patient tumor and their respective established PDXs, including the expression of biomarkers. PDX take rate was higher in surgical resection samples, in post-chemotherapy surgical samples and in samples from patients with metastatic disease at presentation. In conclusion, we have shown that the osteosarcoma PDX model reliably recapitulates the morphological aspects of the human disease after serial passage in mice. The observation that more aggressive forms of osteosarcoma, including those with metastatic disease at presentation, have a higher efficiency to generate PDXs provides a promising scenario to address several unanswered issues in clinical oncology.

PATIENT-DERIVED XENOGRAFTS AS A PRECLINICAL MODEL FOR BONE SARCOMAS.

OBJECTIVE: The purpose of this study was to reproduce a mouse model of bone sarcomas for use in cancer research. METHODS: A fresh sample of the tumor tissue was implanted subcutaneously into nude mice. When the patient-derived xenograft (PDX) reached a volume of 1500 mm3, it was harvested for re-implantation into additional mice. Histology was used to compare the morphological characteristics of different generations of sarcoma xenografts with the primary tumor. RESULTS: Sixteen sarcoma tissue samples were engrafted into nude mice. Nine patients were diagnosed with osteosarcoma, two with chondrosarcoma, two with malignant peripheral nerve sheath tumor, one with synovial sarcoma, one with pleomorphic sarcoma, and one with Ewing's sarcoma. PDX tumors were generated in 11 of the 16 implanted specimens (69% success rate in P1). Six P1 tumors grew sufficiently for transfer into additional mice, producing the P2 generation, and three P2 tumors established the P3 generation. CONCLUSION: PDX tumors generated from bone sarcomas were successfully established in immunodeficient mice and reproduced the characteristics of the primary tumor with a high degree of fidelity. The preclinical PDX model described herein may represent an important tool for translational oncology research and for evaluating therapeutic strategies for bone sarcomas. Level of Evidence I; Experimental study.

OBJETIVO: O propósito deste estudo foi reproduzir em camundongos um modelo de sarcomas ósseos para uso em pesquisa oncológica. MÉTODO: Amostras frescas de tecido tumoral foram implantadas por via subcutânea em camundongos Nude. Quando o xenoenxerto derivado do paciente (PDX) alcançava 1500 mm3, ele era retirado do animal e reimplantado em outros camundongos. Estudos histológicos foram realizados para comparar as características morfológicas de diferentes gerações de xenoenxertos com o tumor primário. RESULTADOS: Dezesseis amostras de tecido sarcomatoso foram enxertadas em camundongos. Nove pacientes foram diagnosticados com osteossarcoma, dois com condrossarcoma, dois com tumor maligno de bainha de nervo periférico, um com sarcoma sinovial, um com sarcoma pleomórfico e um com sarcoma de Ewing. Foram gerados tumores PDX em 11 das 16 amostras enxertadas (taxa de sucesso de 69% em P1). Destes, seis tumores P1 cresceram o suficiente para serem transferidos para outros camundongos, dando origem à geração P2 e três dos tumores P2 estabeleceram a geração P3. CONCLUSÕES: Os tumores PDX de sarcomas ósseos foram estabelecidos com sucesso em camundongos imunodeficientes e reproduziram com alta precisão as características do tumor primário. O modelo pré-clínico de PDX descrito pode representar uma ferramenta importante para a pesquisa oncológica translacional e para avaliar estratégias terapêuticas para sarcomas ósseos. Nível de Evidência I; Estudo experimental.

The usefulness of chemical-shift magnetic resonance imaging for the evaluation of osteoid osteoma.

OBJECTIVE: The purpose of this study was to determine whether chemical-shift magnetic resonance imaging (MRI) could be useful in the diagnosis of osteoid osteoma when clinical and radiological tumor features are inconclusive. MATERIALS AND METHODS: This retrospective study included 17 patients who underwent chemical-shift MRI for the evaluation of osteoid osteoma. For all patients, two musculoskeletal radiologists independently recorded signal intensities on in-phase and out-of-phase images in the nidus of the tumor, in abnormal-intensity bone marrow surrounding the lesion, and in normal-appearing bone marrow. For each region, relative signal intensity ratios were calculated by dividing out-of-phase by in-phase values. Relative ratios > 1 were considered indicative of neoplastic lesions. Statistical analysis was carried out to analyze the sample. Inter-observer and intra-observer agreement for each imaging method were assessed using intraclass correlation coefficients according to the Fleiss method and a value > 0.65 was considered to indicate substantial agreement. RESULTS: The mean relative signal intensity ratios were 1.2 (range, 0.9-1.4) for the nidus and 0.35 (range, 0.11-0.66) for the surrounding tissue; these values differed significantly from the relative signal-intensity ratios for normal-appearing bone marrow (p < 0.05). CONCLUSION: Chemical-shift MRI is useful for the diagnosis and evaluation of osteoid osteoma.

PERCUTANEOUS TREATMENT OF ANEURYSMAL BONE CYST WITH CALCITONIN AND METHYLPREDNISOLONE.

OBJECTIVE: To introduce the intralesional calcitonin and methylprednisolone percutaneous injection method, which results in the promotion of primary aneurysmal bone cyst (ABC) healing. METHODS: A retrospective cohort study involving 76 patients diagnosed with ABC was performed between 2005 and 2014. Patients treated with calcitonin and methylprednisolone injection and who underwent more than 2 years of follow-up were considered eligible for the study (n=47). The Enneking staging and Capanna classification systems were used during the initial evaluation. Treatment response was assessed by Rastogi radiographic grading based on the degree of healing. X2 and Wilcoxon signed-rank tests and odds ratio calculations were used in the statistical analysis with a 5% significance level. RESULTS: The proximal tibia extremity was the most commonly affected site (17.0%). Thirty-three (70.3%) ABC cases were staged as B3 and 28 (59.7%) were classified as type II. The average number of injections performed was 2.8 per patient, with an average reduction of the initial lytic area of 83.7% (p-value=0.00001). Satisfactory results for 91.4% (n=43; p-value=0.00001) were obtained and 5 recurrences occurred. No side effects were observed. CONCLUSION: Intralesional calcitonin and methylprednisolone percutaneous injection is a minimally invasive, effective, and safe method for promoting primary ABC healing. Level of evidence IV, Type of study: case series.

OBJETIVO: Apresentar o método de injeção intralesional percutânea de calcitonina e metilprednisolona para promover a ossificação do cisto ósseo aneurismático (COA). MÉTODOS: Foi realizado um estudo retrospectivo de coorte envolvendo 76 pacientes com diagnóstico de COA entre 2005 e 2014. Os pacientes tratados com injeção de calcitonina e metilprednisolona e acompanhados durante mais de dois anos foram considerados elegíveis para o estudo (n = 47). Foram utilizados o sistema de estadiamento de Enneking e a classificação de Capanna durante a avaliação inicial. A resposta ao tratamento foi avaliada pela classificação radiográfica Rastogi, com base no grau de cicatrização. Os testes X2, Wilcoxon e o cálculo da razão de chances foram utilizados na análise estatística com nível de significância de 5%. RESULTADOS: A extremidade proximal da tíbia foi o local mais frequente (17,0%). Trinta e três (70,3%) COA eram B3 e 28 (59,7%) do tipo II. O número médio de injeções aplicadas foi de 2,8 por paciente, com redução média da área lítica inicial de 83,7% (p = 0,00001). Resultados satisfatórios para 91,4% (n = 43; p = 0,00001) dos pacientes e houve cinco recidivas. Nenhum efeito colateral foi observado. CONCLUSÃO: A injeção intralesional percutânea de calcitonina e metilprednisolona é um método minimamente invasivo, eficaz e seguro para promover a ossificação do COA. Nível de evidência IV, Tipo de estudo: série de casos.

Resection of ankle tumor lesion and reconstruction with the use of allograft / Ressecção de lesão tumoral do tornozelo e reconstrução com uso de aloenxerto

RESUMO A reconstrução do terço distal da tíbia devido à ressecção de tumor maligno apresenta alguns fatores que dificultam sua realização, como camada subcutânea delgada, feixes neurovasculares que transpassam os compartimentos, tempo cirúrgico prolongado, material ortopédico específico e equipe multidisciplinar treinada. O aloenxerto de banco de tecido faz parte deste arsenal ortopédico. Objetivo: Descrever o protocolo realizado no Instituto Nacional de Traumatologia e Ortopedia Jamil Haddad. Métodos: Série de seis casos submetidos à ressecção com margens oncológicas, reconstrução com aloenxerto e uso de haste retrógrada de tornozelo como cirurgia preservadora do membro. Três dos seis pacientes eram do sexo feminino, as lesões tinham em média 9,3 cm de comprimento e o tempo cirúrgico médio foi de 3,25 horas. Resultados: A principal complicação de curto prazo (≤ 30 dias) foi a paralisia do nervo fibular, enquanto a principal complicação de longo prazo (> 30 dias) foi a infecção do sítio cirúrgico (dois casos). A consolidação dos dois focos ocorreu em três pacientes, e dois pacientes evoluíram para pseudoartrose assintomática do foco proximal com consolidação do foco distal. Conclusão: Apesar das complicações, a cirurgia proposta permite ao paciente a chance de preservar seu membro diante de uma cirurgia radical imediata. Nível de Evidência IV, Série de Casos.

ABSTRACT Reconstruction of the distal third of the tibia due to resection of a malignant tumor has some hindering factors, such as a thin subcutaneous layer, neurovascular bundles that cross compartments, prolonged operative duration, specific orthopedic material, and a trained multidisciplinary team. Allografting with material from tissue banks is part of this orthopaedic arsenal. Objective: To describe the protocol used at Instituto Nacional de Traumatologia e Ortopedia Jamil Haddad. Methods: Series of six cases subjected to resection with oncologic margins, allograft reconstruction, and use of a retrograde ankle nail as limb-salvage surgery. Three of the six patients were women, the lesions were on average 9.3 cm long, and the average operative duration was 3.25 hours. Results: The main short-term complication (≤ 30 days) was peroneal nerve palsy, while the main long-term complication (> 30 days) was surgical site infection (two cases). Consolidation of the two foci occurred in three patients, and two patients developed asymptomatic pseudoarthrosis of the proximal focus with consolidation of the distal focus. Conclusion: Despite the complications, the proposed surgery gives patients the chance to preserve their limb in the face of immediate radical surgery. Level of Evidence IV, Case Series.

Patient-derived osteosarcoma cells are resistant to methotrexate.

Osteosarcoma is the most common primary bone tumor in children and young adults. The median survival of osteosarcoma patients has not significantly improved since 1990, despite administration of different classes of chemotherapy agents, such as methotrexate, cisplatin and doxorubicin. Cancer stem cells (CSCs) are responsible for the resistance of osteosarcoma to chemotherapy and OCT4, SOX2 and SSEA4 have been used to identify CSCs in osteosarcoma. Here, we used low-passage patient-derived osteosarcoma cells and osteosarcoma cells directly isolated from patients before and after chemotherapy treatments to evaluate the effects of chemotherapy on stem cell markers expression. We demonstrate that primary osteosarcoma cells are resistant to methotrexate treatment and sensitive to cisplatin and doxorubicin in vitro. We also verified that cisplatin and doxorubicin reduce the expression of SOX2 and OCT4 in primary osteosarcoma cells whereas methotrexate does not alter SOX2 and OCT4 expression, however it increases SSEA4 expression in primary osteosarcoma cells. Finally, we found that, although the combination treatment cisplatin plus doxorubicin inhibited the in vivo growth of osteosarcoma cells in NOD-SCID gamma mice subcutaneously injected with SaOs2, the combination treatment cisplatin plus doxorubicin plus methotrexate did not inhibit the in vivo growth of these cells. These observations may provide an explanation for the poor response of osteosarcomas to chemotherapy and point to the need of reevaluating the therapeutic strategies for human osteosarcomas.

Liposclerosing myxofibrous tumor: A series of 9 cases and review of the literature.

BACKGROUND: Liposclerosing myxofibrous primary bone tumor is a rare benign bone lesion that was characterized by complex mixture of various histological elements. METHODS: We have studied the radiological, clinical and pathological features of nine patients with this disorder. Pain and limping were the main symptoms. RESULTS: Radiographic images typically showed a geographic lytic lesion with thick sclerotic margin, reflecting a pattern of slow growth. Histological sections revealed a polymorphic neoplasia characterized by predominant proliferation of stellate and fusiform cells aimed the myxoid matrix. CONCLUSIONS: These features suggest that the lesion may represent a variant of fibrous dysplasia with a high risk of malignant transformation.

Epidemiological study on giant cell tumor recurrence at the Brazilian National Institute of Traumatology and Orthopedics.

OBJECTIVE: Giant cell tumors are benign bone neoplasms that are relatively rare in adults and their biological behavior is still unpredictable. The incidence of local recurrence has presented variation between 0% and 65% in studies conducted worldwide, but few data are available on this complication in the Brazilian population. METHODS: Information on 155 patients with confirmed histological diagnoses of giant cell tumor who were treated in our institution's orthopedic oncology service between January 2000 and July 2014 was gathered. Demographic characteristics were evaluated and compared between patients who presented local recurrence during the clinical follow-up. RESULTS: Local recurrence was observed in 26 patients (16.7%), of whom 22 were female (84.6%). The most common site of local recurrence was the distal femur (38.4%). Eleven patients presented early recurrence, while 15 cases were diagnosed after 15 months, representing 42.3% and 57.7%, respectively. Metastases were identified in five patients (3.2%). CONCLUSION: Tumor-related factors did not show any increased incidence of local recurrence of giant cell tumors. Surgical treatment with an intralesional margin is a valid option for treating local recurrences and does not show any difference in disease-free survival in relation to other types of procedures. Clinical treatment is reserved for cases of unresectable tumors or when surgical treatment is impossible.

OBJETIVOS: O tumor de células gigantes (TCG) é uma neoplasia óssea benigna relativamente rara em adultos, porém seu comportamento biológico ainda é imprevisível. A incidência de recidiva local apresenta variação entre 0­65% em estudos internacionais, porém há poucos dados referentes a essa complicação em nossa população. MÉTODOS: Foram coletadas informações sobre 155 pacientes com diagnóstico histológico confirmado de TCG, acompanhados no serviço de oncologia ortopédica da nossa instituição, de janeiro de 2000 a julho de 2014. As características demográficas foram avaliadas e comparadas entre os pacientes que apresentaram recidiva local durante o seguimento clínico. RESULTADOS: Houve recidiva local em 26 pacientes (16,7%), dos quais 22 eram do sexo feminino (84,6%). A localização mais comum de recidiva local foi o fêmur distal (38,4%). Onze pacientes apresentaram recidiva precoce, enquanto 15 casos foram diagnosticados após 15 meses, o que representa, respectivamente, 42,3% e 57,7%. Metástases foram identificadas em cinco pacientes (3,2%). CONCLUSÃO: Os fatores relacionados ao tumor não evidenciaram aumento da incidência de recidiva local de tumor de células gigantes. O tratamento cirúrgico com margem intralesional é uma opção válida no tratamento de recidivas locais e não apresenta diferença de sobrevida livre de doença entre outros tipos de procedimentos. Tratamento clínico é reservado em casos de tumores irressecáveis ou impossibilidade de tratamento cirúrgico.

Parosteal aneurysmal bone cyst.

The incidence of aneurysmal bone cysts is 0.14 cases per 100,000 individuals. Parosteal aneurysmal bone cysts are the least prevalent subtype and represent 7% of all aneurysmal bone cysts. We present the case of a 38-year-old male patient with pain and bulging in his right arm for eight months. He had previously been diagnosed as presenting giant-cell tumor, but his slides were reviewed and his condition was then diagnosed as parosteal aneurysmal bone cyst. The patient was treated with corticosteroid and calcitonin infiltration into the lesion and evolved with clinical and radiological improvement within the first five weeks after the operation.

O cisto ósseo aneurismático tem uma incidência de 0,14 a cada 100 mil indivíduos. O subtipo parosteal é o menos prevalente, representa 7% de todos. Apresentamos um paciente masculino, 38 anos, com dor e abaulamento em braço direito havia oito meses. Diagnosticado previamente como tumor de células gigantes, teve sua lâmina revisada e então foi feito o diagnóstico de cisto ósseo aneurismático parosteal. O paciente foi tratado com infiltração intralesional de corticosteroide e calcitonina e evoluiu com melhoria clínica e radiológica já nas primeiras cinco semanas pós-operatórias.

The usefulness of chemical-shift magnetic resonance imaging for the evaluation of osteoid osteoma / O uso da sequência T1 em fase e fora de fase da ressonância magnética para a avaliação do osteoma osteoide

Abstract Objective: The purpose of this study was to determine whether chemical-shift magnetic resonance imaging (MRI) could be useful in the diagnosis of osteoid osteoma when clinical and radiological tumor features are inconclusive. Materials and Methods: This retrospective study included 17 patients who underwent chemical-shift MRI for the evaluation of osteoid osteoma. For all patients, two musculoskeletal radiologists independently recorded signal intensities on in-phase and out-of-phase images in the nidus of the tumor, in abnormal-intensity bone marrow surrounding the lesion, and in normal-appearing bone marrow. For each region, relative signal intensity ratios were calculated by dividing out-of-phase by in-phase values. Relative ratios > 1 were considered indicative of neoplastic lesions. Statistical analysis was carried out to analyze the sample. Inter-observer and intra-observer agreement for each imaging method were assessed using intraclass correlation coefficients according to the Fleiss method and a value > 0.65 was considered to indicate substantial agreement. Results: The mean relative signal intensity ratios were 1.2 (range, 0.9-1.4) for the nidus and 0.35 (range, 0.11-0.66) for the surrounding tissue; these values differed significantly from the relative signal-intensity ratios for normal-appearing bone marrow (p < 0.05). Conclusion: Chemical-shift MRI is useful for the diagnosis and evaluation of osteoid osteoma.

Resumo Objetivo: O objetivo deste estudo foi determinar se a sequência T1 em fase e fora de fase da ressonância magnética (RM) poderia ser útil no diagnóstico de osteoma osteoide em situações nas quais características clínicas e radiológicas são indefinidas. Materiais e Métodos: Este estudo retrospectivo incluiu 17 pacientes submetidos a RM para avaliação do osteoma osteoide. Em todos os pacientes, dois radiologistas musculoesqueléticos registraram, independentemente, as intensidades de sinal em imagens em fase e fora de fase no nidus do tumor, na medula óssea de intensidade anormal ao redor da lesão e na medula óssea de aspecto normal. Para cada região, as relações de intensidade de sinal relativas foram calculadas dividindo os valores na sequência fora de fase pelos valores em fase. Razões relativas > 1 foram consideradas indicativas de lesões neoplásicas. A análise estatística foi realizada para analisar a amostra. A concordância interobservador e intraobservador para cada método de imagem foi avaliada por meio dos coeficientes de correlação intraclasse, segundo o método de Fleiss, e considerou-se um valor > 0,65 para indicar concordância substancial. Resultados: As razões de intensidade de sinal relativa média foram 1,2 (variação: 0,9-1,4) para o nidus e 0,35 (variação: 0,11-0,66) para o tecido circundante. Estes valores diferiram significativamente das relações de sinal-intensidade relativa da medula óssea com aspecto normal (p < 0,05). Conclusão: A sequência em fase e fora de fase da RM mostrou-se útil para o diagnóstico e avaliação do osteoma osteoide.

Percutaneous treatment of aneurysmal bone cyst with calcitonin and methylprednisolone / Tratamento percutâneo de cisto ósseo aneurismático com calcitonina e metilprednisolona

ABSTRACT Objective: To introduce the intralesional calcitonin and methylprednisolone percutaneous injection method, which results in the promotion of primary aneurysmal bone cyst (ABC) healing. Methods: A retrospective cohort study involving 76 patients diagnosed with ABC was performed between 2005 and 2014. Patients treated with calcitonin and methylprednisolone injection and who underwent more than 2 years of follow-up were considered eligible for the study (n=47). The Enneking staging and Capanna classification systems were used during the initial evaluation. Treatment response was assessed by Rastogi radiographic grading based on the degree of healing. X2 and Wilcoxon signed-rank tests and odds ratio calculations were used in the statistical analysis with a 5% significance level. Results: The proximal tibia extremity was the most commonly affected site (17.0%). Thirty-three (70.3%) ABC cases were staged as B3 and 28 (59.7%) were classified as type II. The average number of injections performed was 2.8 per patient, with an average reduction of the initial lytic area of 83.7% (p-value=0.00001). Satisfactory results for 91.4% (n=43; p-value=0.00001) were obtained and 5 recurrences occurred. No side effects were observed. Conclusion: Intralesional calcitonin and methylprednisolone percutaneous injection is a minimally invasive, effective, and safe method for promoting primary ABC healing. Level of evidence IV, Type of study: case series.

RESUMO Objetivo: Apresentar o método de injeção intralesional percutânea de calcitonina e metilprednisolona para promover a ossificação do cisto ósseo aneurismático (COA). Métodos: Foi realizado um estudo retrospectivo de coorte envolvendo 76 pacientes com diagnóstico de COA entre 2005 e 2014. Os pacientes tratados com injeção de calcitonina e metilprednisolona e acompanhados durante mais de dois anos foram considerados elegíveis para o estudo (n = 47). Foram utilizados o sistema de estadiamento de Enneking e a classificação de Capanna durante a avaliação inicial. A resposta ao tratamento foi avaliada pela classificação radiográfica Rastogi, com base no grau de cicatrização. Os testes X2, Wilcoxon e o cálculo da razão de chances foram utilizados na análise estatística com nível de significância de 5%. Resultados: A extremidade proximal da tíbia foi o local mais frequente (17,0%). Trinta e três (70,3%) COA eram B3 e 28 (59,7%) do tipo II. O número médio de injeções aplicadas foi de 2,8 por paciente, com redução média da área lítica inicial de 83,7% (p = 0,00001). Resultados satisfatórios para 91,4% (n = 43; p = 0,00001) dos pacientes e houve cinco recidivas. Nenhum efeito colateral foi observado. Conclusão: A injeção intralesional percutânea de calcitonina e metilprednisolona é um método minimamente invasivo, eficaz e seguro para promover a ossificação do COA. Nível de evidência IV, Tipo de estudo: série de casos.

Patient-derived xenografts as a preclinical model for bone sarcomas / Xenoenxertos derivados de pacientes como modelo pré-clínico de sarcomas ósseos

ABSTRACT Objective: The purpose of this study was to reproduce a mouse model of bone sarcomas for use in cancer research. Methods: A fresh sample of the tumor tissue was implanted subcutaneously into nude mice. When the patient-derived xenograft (PDX) reached a volume of 1500 mm3, it was harvested for re-implantation into additional mice. Histology was used to compare the morphological characteristics of different generations of sarcoma xenografts with the primary tumor. Results: Sixteen sarcoma tissue samples were engrafted into nude mice. Nine patients were diagnosed with osteosarcoma, two with chondrosarcoma, two with malignant peripheral nerve sheath tumor, one with synovial sarcoma, one with pleomorphic sarcoma, and one with Ewing's sarcoma. PDX tumors were generated in 11 of the 16 implanted specimens (69% success rate in P1). Six P1 tumors grew sufficiently for transfer into additional mice, producing the P2 generation, and three P2 tumors established the P3 generation. Conclusion: PDX tumors generated from bone sarcomas were successfully established in immunodeficient mice and reproduced the characteristics of the primary tumor with a high degree of fidelity. The preclinical PDX model described herein may represent an important tool for translational oncology research and for evaluating therapeutic strategies for bone sarcomas. Level of Evidence I; Experimental study.

RESUMO Objetivo: O propósito deste estudo foi reproduzir em camundongos um modelo de sarcomas ósseos para uso em pesquisa oncológica. Método: Amostras frescas de tecido tumoral foram implantadas por via subcutânea em camundongos Nude. Quando o xenoenxerto derivado do paciente (PDX) alcançava 1500 mm3, ele era retirado do animal e reimplantado em outros camundongos. Estudos histológicos foram realizados para comparar as características morfológicas de diferentes gerações de xenoenxertos com o tumor primário. Resultados: Dezesseis amostras de tecido sarcomatoso foram enxertadas em camundongos. Nove pacientes foram diagnosticados com osteossarcoma, dois com condrossarcoma, dois com tumor maligno de bainha de nervo periférico, um com sarcoma sinovial, um com sarcoma pleomórfico e um com sarcoma de Ewing. Foram gerados tumores PDX em 11 das 16 amostras enxertadas (taxa de sucesso de 69% em P1). Destes, seis tumores P1 cresceram o suficiente para serem transferidos para outros camundongos, dando origem à geração P2 e três dos tumores P2 estabeleceram a geração P3. Conclusões: Os tumores PDX de sarcomas ósseos foram estabelecidos com sucesso em camundongos imunodeficientes e reproduziram com alta precisão as características do tumor primário. O modelo pré-clínico de PDX descrito pode representar uma ferramenta importante para a pesquisa oncológica translacional e para avaliar estratégias terapêuticas para sarcomas ósseos. Nível de Evidência I; Estudo experimental.

Epidemiological study on giant cell tumor recurrence at the Brazilian National Institute of Traumatology and Orthopedics / Estudo epidemiológico de recidiva de tumor de células gigantes no Instituto Nacional de Traumatologia e Ortopedia

ABSTRACT OBJECTIVE: Giant cell tumors are benign bone neoplasms that are relatively rare in adults and their biological behavior is still unpredictable. The incidence of local recurrence has presented variation between 0% and 65% in studies conducted worldwide, but few data are available on this complication in the Brazilian population. METHODS: Information on 155 patients with confirmed histological diagnoses of giant cell tumor who were treated in our institution's orthopedic oncology service between January 2000 and July 2014 was gathered. Demographic characteristics were evaluated and compared between patients who presented local recurrence during the clinical follow-up. RESULTS: Local recurrence was observed in 26 patients (16.7%), of whom 22 were female (84.6%). The most common site of local recurrence was the distal femur (38.4%). Eleven patients presented early recurrence, while 15 cases were diagnosed after 15 months, representing 42.3% and 57.7%, respectively. Metastases were identified in five patients (3.2%). CONCLUSION: Tumor-related factors did not show any increased incidence of local recurrence of giant cell tumors. Surgical treatment with an intralesional margin is a valid option for treating local recurrences and does not show any difference in disease-free survival in relation to other types of procedures. Clinical treatment is reserved for cases of unresectable tumors or when surgical treatment is impossible.

RESUMO OBJETIVOS: O tumor de células gigantes (TCG) é uma neoplasia óssea benigna relativamente rara em adultos, porém seu comportamento biológico ainda é imprevisível. A incidência de recidiva local apresenta variação entre 0-65% em estudos internacionais, porém há poucos dados referentes a essa complicação em nossa população. MÉTODOS: Foram coletadas informações sobre 155 pacientes com diagnóstico histológico confirmado de TCG, acompanhados no serviço de oncologia ortopédica da nossa instituição, de janeiro de 2000 a julho de 2014. As características demográficas foram avaliadas e comparadas entre os pacientes que apresentaram recidiva local durante o seguimento clínico. RESULTADOS: Houve recidiva local em 26 pacientes (16,7%), dos quais 22 eram do sexo feminino (84,6%). A localização mais comum de recidiva local foi o fêmur distal (38,4%). Onze pacientes apresentaram recidiva precoce, enquanto 15 casos foram diagnosticados após 15 meses, o que representa, respectivamente, 42,3% e 57,7%. Metástases foram identificadas em cinco pacientes (3,2%). CONCLUSÃO: Os fatores relacionados ao tumor não evidenciaram aumento da incidência de recidiva local de tumor de células gigantes. O tratamento cirúrgico com margem intralesional é uma opção válida no tratamento de recidivas locais e não apresenta diferença de sobrevida livre de doença entre outros tipos de procedimentos. Tratamento clínico é reservado em casos de tumores irressecáveis ou impossibilidade de tratamento cirúrgico.

[Epithelioid sarcoma: clinical behavior, prognostic factors and survival]. / Sarcoma epitelióide: aspectos clínicos, fatores prognósticos e sobrevida.

OBJECTIVE: To relate the clinical characteristics and evaluations of patients with epithelioid sarcomas. METHODS: Careful analysis of 25 epithelioid sarcoma cases registered in Instituto Nacional do Cancer between june 1987 and july 2005. RESULTS: Mean age at diagnosis was 33 years old, ranged from 10 to 70. The primary site of presentation was the upper extremity in twelve patients (48%). The size of the tumor was given in 19 cases, with the mean size of 5 cm, while they ranged from 1.5 to 15 cm. Surgery was made in 17 patients, with eleven amputation. Tumors margins were free in fifteen patients, positive in three and in seven were not studied. Six received any type of chemotherapy and 14 received treatment with radiotherapy with mean dose of 46,5 Gy. Local recurrence occurred in thirteen cases (52%). Nodal spread was diagnosed in nine (36%). Pulmonary metastases were diagnosed in seven patients (28%). Six patients underwent cancer treatment in its entirety at the National Institute of Cancer. At present twelve patients are alive without disease, two have disease and eleven patients have died. CONCLUSION: Epithelioid sarcoma is a rare subset of soft tissue sarcoma with high rate of local recurrence, regional node and distant metastases. Occurs predominantly in young patients, mainly on the superior member extremities. Surgical treatment of epithelioid sarcoma consists of early wide local resection to negative microscopic margins. These patients require carefully follow-up to evaluate local recurrence, nodal metastases, and pulmonary metastases.