RESUMO
BACKGROUND: Challenging emerging entities with distinctive molecular signatures may benefit from algorithms for diagnostic work-up. METHODS: Fusion sarcomas (2020-2021, during pandemic) were diagnosed by clinicoradiology, morphology, phenotype, and next-generation sequencing (NGS). RESULTS: Six fusion sarcomas in two males and four females involved the chest-wall, neck, or extremities; ages ranged 2-73, median 18â¯years. Sizes ranged 5.3-25.0, median 9.1â¯cm. These include high grade 1) TPR-NTRK1 of proximal femur with a larger rounded soft tissue mass, previously considered osteosarcoma yet without convincing tumor matrix. A pathologic fracture necessitated emergency hemipelvectomy (NED) and 2) novel KANK1-NTRK2 sarcoma of bone and soft tissue with spindled pleomorphic to epithelioid features (AWD metastases). 3) Novel ERC1-ALK unaligned fusion, a low grade infiltrative deep soft tissue hand sarcoma with prominent-vascularity, myopericytoid/lipofibromatosis-like ovoid cells, and collagenized stroma, was successfully treated with ALK-inhibitor (Crizotinib), avoiding amputation. These NTRK and ALK tumors variably express S100 and CD34 and were negative for SOX10. 4) and 5) CIC-DUX4 round cell tumors (rapid metastases/demise), one with COVID superinfection, were previously treated as Ewing sarcoma. These demonstrated mild pleomorphism and necrosis, variable myxoid change and CD99 reactivity, and a distinctive dot-like-Golgi WT1 immunostaining pattern. 6) A chest wall/thoracic round cell sarcoma, focal CD34/ keratins/CK7, revealed nuclear-STAT6, STAT6-NAB2 by NGS, confirming malignant solitary fibrous tumor, intermediate-risk-stratification (AWD metastases). CONCLUSIONS: Recent fusion sarcomas include new KANK1-NTRK2 and ERC1-ALK, the latter successfully treated by targeted-therapy. ALK/NTRK fusion partners TPR and KANK1 suggest unusual high-grade morphology/behavior. Clinicoradiologic, morphologic, and phenotypic algorithms can prompt molecular-targeted immunostains or NGS for final classification and promising inhibitor therapy.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias Femorais/genética , Fusão Gênica , Neoplasias de Cabeça e Pescoço/genética , Sarcoma/genética , Neoplasias de Tecidos Moles/genética , Neoplasias Torácicas/genética , Adolescente , Adulto , Idoso , Algoritmos , Antineoplásicos/uso terapêutico , Criança , Pré-Escolar , Extremidades/patologia , Feminino , Neoplasias Femorais/diagnóstico , Neoplasias Femorais/tratamento farmacológico , Neoplasias Femorais/patologia , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Fenótipo , Prognóstico , Sarcoma/diagnóstico , Sarcoma/tratamento farmacológico , Sarcoma/patologia , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/tratamento farmacológico , Neoplasias de Tecidos Moles/patologia , Neoplasias Torácicas/diagnóstico , Neoplasias Torácicas/tratamento farmacológico , Neoplasias Torácicas/patologia , Parede Torácica/patologia , Adulto JovemRESUMO
BACKGROUND: Ewing-like sarcoma with capicua transcriptional repressor (CIC) rearrangement is a unique class of undifferentiated round cell sarcomas characterized by CIC-double homeobox 4 gene fusion. Despite showing great histologic resemblance to Ewing sarcomas, they have proved to be a distinct pathological entity from the immunohistochemistry and genetic examinations and the response to treatment. We have presented a case of CIC-rearranged Ewing-like sarcoma with cerebral metastasis managed with operative resection and gamma knife radiosurgery. CASE DESCRIPTION: A 56-year-old woman had initially presented with an ulcerating lesion of the right fifth toe. The histological and immunohistochemical analysis revealed features consistent with CIC-rearranged Ewing-like sarcoma, which was confirmed with genetic analysis. Despite aggressive local control and a multidrug chemotherapy regimen, the patient developed multifocal metastases involving the lungs, femur, and cerebrum. The cerebral lesions were managed with surgery and gamma knife radiosurgery, with mixed results. CONCLUSION: CIC-rearranged Ewing-like sarcomas have recently been recognized as a distinct disease entity with a highly aggressive course. Treatment paradigms have yet to be defined to properly manage such an aggressive pathological process.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/terapia , Neoplasias Pulmonares/terapia , Metastasectomia , Radiocirurgia , Sarcoma/terapia , Neoplasias de Tecidos Moles/cirurgia , Dedos do Pé/cirurgia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/secundário , Feminino , Neoplasias Femorais/diagnóstico por imagem , Neoplasias Femorais/genética , Neoplasias Femorais/secundário , Neoplasias Femorais/terapia , Rearranjo Gênico , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundário , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Proteínas Repressoras/genética , Sarcoma/diagnóstico por imagem , Sarcoma/genética , Sarcoma/secundário , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/patologia , Cirurgia Torácica Vídeoassistida , Tomografia Computadorizada por Raios XRESUMO
CASE: We report the case of a 78-year-old woman with undifferentiated pleomorphic sarcoma (UPS) of the proximal femur arising in a previous site of fibrous dysplasia (i.e., a liposclerosing myxofibrous tumor) that had been treated 4 years earlier with curetted surgery. GNAS mutation was detected in both the previous benign lesion and the UPS. CONCLUSION: Genetic analysis is useful in demonstrating the origin of the tumor especially in fibrous dysplasia with severe degeneration that have undergone malignant transformation.
Assuntos
Cromograninas/genética , Neoplasias Femorais/patologia , Fêmur/patologia , Displasia Fibrosa Poliostótica/complicações , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Sarcoma/patologia , Idoso , Feminino , Neoplasias Femorais/diagnóstico por imagem , Neoplasias Femorais/genética , Fêmur/diagnóstico por imagem , Fêmur/cirurgia , Displasia Fibrosa Poliostótica/genética , Displasia Fibrosa Poliostótica/cirurgia , Humanos , Imageamento por Ressonância Magnética , Complicações Pós-Operatórias/genética , Sarcoma/diagnóstico por imagem , Sarcoma/genética , Tomografia Computadorizada por Raios XRESUMO
Mazabraud's syndrome is a rare disorder characterised by the association of fibrous dysplasia with intramuscular myxomas. We present a 36-year-old woman with right anterior knee pain and a buttock mass. Imaging showed aggressive bone destruction within an area of fibrous dysplasia in the right femur and a mass with myxoid signal characteristics in the right adductor region. Biopsy of the femur revealed both fibrous dysplasia and a high-grade spindle cell sarcoma. Biopsy of the adductor mass confirmed a soft-tissue myxoma. Molecular genetic analysis revealed an identical R201H substitution in the GNAS1 gene in the sarcoma, the myxoma, and also the conventional fibrous dysplasia.
Assuntos
Cromograninas/genética , Neoplasias Femorais/diagnóstico por imagem , Neoplasias Femorais/genética , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Mixoma/diagnóstico por imagem , Mixoma/genética , Sarcoma/diagnóstico por imagem , Sarcoma/genética , Neoplasias de Tecidos Moles/diagnóstico por imagem , Neoplasias de Tecidos Moles/genética , Adulto , Biópsia , Nádegas/diagnóstico por imagem , Nádegas/patologia , Nádegas/cirurgia , Diagnóstico Diferencial , Feminino , Neoplasias Femorais/patologia , Neoplasias Femorais/cirurgia , Fêmur , Humanos , Imageamento por Ressonância Magnética , Mixoma/patologia , Mixoma/cirurgia , Gradação de Tumores , Mutação Puntual , Sarcoma/patologia , Sarcoma/cirurgia , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/cirurgia , Síndrome , Tomografia Computadorizada por Raios XRESUMO
Technological advances in high-throughput next-generation sequencing (NGS) along with advances in computational processes have brought about the dawn of the genomic medicine era. NGS has enabled molecular characterization of malignancies, and facilitated the development and approval of gene- and immune-targeted therapies, both of which impact the mutanome. Clinical implementation of this technology, approval of novel targeted agents, and establishment of molecular tumor boards has enabled precision oncology to become a reality.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Femorais/tratamento farmacológico , Oncologia/métodos , Osteossarcoma/tratamento farmacológico , Equipe de Assistência ao Paciente , Medicina de Precisão/métodos , Adulto , Antineoplásicos/efeitos adversos , Tomada de Decisão Clínica , Mineração de Dados , Bases de Dados Genéticas , Medicina Baseada em Evidências/métodos , Feminino , Neoplasias Femorais/diagnóstico por imagem , Neoplasias Femorais/genética , Neoplasias Femorais/patologia , Predisposição Genética para Doença , Humanos , Comunicação Interdisciplinar , Modelos Teóricos , Terapia de Alvo Molecular , Osteossarcoma/diagnóstico por imagem , Osteossarcoma/genética , Osteossarcoma/secundário , Segurança do Paciente , Fenótipo , Medição de Risco , Pesquisa Translacional Biomédica/métodosRESUMO
Although prognosis in patients with localized osteosarcoma has been dramatically improved by the introduction of multiple chemotherapy agents known as combination chemotherapy, there is growing concern about the development of secondary malignant neoplasms. We report the case of a 13-year-old girl in whom the diagnosis of Ewing sarcoma of bone localized on the shaft of left femur was made 2 years after successful treatment without radiotherapy for osteosarcoma of right proximal femur. EWS-FLI1 fusion gene was detected by reverse transcriptase-polymerase chain reaction. To our knowledge, this is the first case with Ewing sarcoma of the bone as a secondary malignant neoplasm developed in osteosarcoma survivor. We collected 15 cases, included this case, with secondary Ewing sarcoma family of tumor by utilizing the PubMed search and might consider the causes of this secondary cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Femorais/tratamento farmacológico , Neoplasias Femorais/genética , Segunda Neoplasia Primária/genética , Proteínas de Fusão Oncogênica/genética , Osteossarcoma/tratamento farmacológico , Proteína Proto-Oncogênica c-fli-1/genética , Proteína EWS de Ligação a RNA/genética , Sarcoma de Ewing/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Criança , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Terapia Combinada , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Doxorrubicina/análogos & derivados , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Neoplasias Femorais/cirurgia , Humanos , Ifosfamida/administração & dosagem , Ifosfamida/efeitos adversos , Salvamento de Membro , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Segunda Neoplasia Primária/tratamento farmacológico , Segunda Neoplasia Primária/cirurgia , Osteossarcoma/cirurgia , Indução de Remissão , Sarcoma de Ewing/tratamento farmacológico , Sarcoma de Ewing/cirurgia , Vincristina/administração & dosagemRESUMO
Malignant transformation of fibrous dysplasia (FD) is exceedingly rare, occurring in less than 1% of all FD cases, and has been described in both monostotic and polyostotic forms of this entity. We report a case of a large proximal femur mass arising in a 45-year-old man. The biopsy revealed a high-grade pleomorphic malignancy that focally expressed multiple keratins. Based on the presence of keratin immunoreactivity, the morphologic differential diagnosis included metastatic sarcomatoid carcinoma. However, review of the clinical information revealed a history of polyostotic FD, and imaging findings were compatible with malignant transformation of FD. The resected neoplasm was biphasic and composed of areas of conventional FD admixed with a high-grade pleomorphic malignancy. Activating GNAS mutations were identified in both components. To the best of our knowledge, this is the first description of keratin expression in malignant transformation of FD.
Assuntos
Biomarcadores Tumorais/análise , Transformação Celular Neoplásica/química , Transformação Celular Neoplásica/patologia , Neoplasias Femorais/química , Neoplasias Femorais/patologia , Displasia Fibrosa Poliostótica/patologia , Queratinas/análise , Biomarcadores Tumorais/genética , Biópsia , Transformação Celular Neoplásica/genética , Cromograninas/genética , Análise Mutacional de DNA , Neoplasias Femorais/genética , Neoplasias Femorais/cirurgia , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Mutação , OsteotomiaRESUMO
BACKGROUND: Ewing sarcoma is the second most common bone tumor, occurring mainly in children and young adults. It shows a typical primitive, small round cell morphology and a characteristic fusion oncogene involving EWSR1 and members of the ETS family in most of the cases. Neuronal maturation after chemotherapy is a rare phenomenon and we herein describe such an exceptional case. CASE PRESENTATION: An 8-year old boy was diagnosed with a Ewing sarcoma in the left femur. On biopsy the morphology was typical and there was an EWSR1-FLI1 gene fusion. He underwent neo-adjuvant chemotherapy and resection of the tumor. On microscopic evaluation, part of the tumor showed ganglioneuroblastoma-like differentiation with expression of neuronal markers. The continued presence of EWSR1 rearrangement in both the blue round cell component and the ganglioneuroblastoma-like component was shown by FISH analysis. CONCLUSIONS: In conclusion, this case describes the possibility of a Ewing sarcoma to differentiate into a ganglioneuroblastoma-like lesion after neo-adjuvant chemotherapy treatment; the prognostic value of this phenomenon remains questionable.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Proteínas de Ligação a Calmodulina/genética , Neoplasias Femorais/genética , Ganglioneuroblastoma/genética , Proteínas de Fusão Oncogênica/genética , Proteínas de Ligação a RNA/genética , Sarcoma de Ewing/genética , Diferenciação Celular , Quimioterapia Adjuvante , Criança , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Neoplasias Femorais/diagnóstico por imagem , Neoplasias Femorais/tratamento farmacológico , Neoplasias Femorais/cirurgia , Fêmur/patologia , Ganglioneuroblastoma/diagnóstico por imagem , Ganglioneuroblastoma/tratamento farmacológico , Rearranjo Gênico , Humanos , Ifosfamida/administração & dosagem , Masculino , Terapia Neoadjuvante , Prognóstico , Proteína EWS de Ligação a RNA , Sarcoma de Ewing/diagnóstico por imagem , Sarcoma de Ewing/tratamento farmacológico , Sarcoma de Ewing/cirurgia , Resultado do Tratamento , Vincristina/administração & dosagemAssuntos
Neoplasias Ósseas/diagnóstico por imagem , Exostose Múltipla Hereditária/diagnóstico por imagem , Adolescente , Neoplasias Ósseas/genética , Progressão da Doença , Feminino , Neoplasias Femorais/diagnóstico por imagem , Neoplasias Femorais/genética , Humanos , Úmero/diagnóstico por imagem , Masculino , Compostos Radiofarmacêuticos/análise , Medronato de Tecnécio Tc 99m/análise , Imagem Corporal Total , Adulto JovemRESUMO
Epithelial glandular differentiation in dedifferentiated chondrosarcoma has not been described. Our patient was a 64-year-old man with a history of prostate cancer status post-radiation and hormonal therapy. On screening bone scan, he was found to have increased uptake in his right femoral shaft. Biopsy revealed intermediate-grade conventional chondrosarcoma. Subsequent femoral resection was remarkable for an intermediate-grade chondrosarcomatous component juxtaposed to an area composed of anastomosing nests and cords of malignant epithelial cells showing nuclear atypia and increased mitotic activity. A fibroblastic-appearing spindle cell population was intimately associated with the epithelial cells. The epithelial cells labeled with 34bE12, AE1/AE3, EMA, and Vimentin (both spindled and epithelial components) while being negative for prostate-specific antigen, prostate specific acid phosphatase, cytokeratin 20, thyroid transcription factor-1, and CDX2. The patient developed local recurrence 9 months after the initial resection but has had no metastatic disease and consistently undetectable prostate-specific antigen levels. Deep parallel sequencing of the dedifferentiated component showed a nonsynonymous mutation at exon 4 of IDH1 gene at codon R132 leading to a substitution of arginine, with serine confirming glandular differentiation in dedifferentiated chondrosarcoma.
Assuntos
Biomarcadores Tumorais/genética , Desdiferenciação Celular , Condrossarcoma/genética , Condrossarcoma/patologia , Neoplasias Femorais/genética , Neoplasias Femorais/patologia , Isocitrato Desidrogenase/genética , Biópsia , Condrossarcoma/enzimologia , Condrossarcoma/cirurgia , Análise Mutacional de DNA , Éxons , Neoplasias Femorais/enzimologia , Neoplasias Femorais/cirurgia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia , Osteotomia , Fatores de Tempo , Resultado do TratamentoRESUMO
Dedifferentiated chondrosarcoma is a primary bone tumor characterized by the presence of both low-grade cartilaginous and high-grade malignant noncartilaginous components. The high-grade noncartilaginous component is typically a pleomorphic fibroblastic spindle cell sarcoma. Dedifferentiation into a malignant epithelial component is extremely rare. In this report, we present a 74-year-old woman who developed a metastatic squamous cell carcinoma in the right inguinal area 1 year after wide resection of her right proximal femur for a dedifferentiated chondrosarcoma. The dedifferentiated component was composed of poorly differentiated epithelioid cells with foci of squamous cell carcinoma. Mutational analysis was performed, and the isocitrate dehydrogenase 1 R132C mutation was detected in the low-grade chondrosarcoma, dedifferentiated chondrosarcoma as well as the metastatic squamous cell carcinoma. And this mutation was not detected in patient's normal tissue. Our study supports the theory that both the chondrosarcoma cells and dedifferentiated epithelioid tumor cells arose from the same clonal origin.
Assuntos
Carcinoma de Células Escamosas/patologia , Condrossarcoma/patologia , Neoplasias Femorais/patologia , Isocitrato Desidrogenase/genética , Mutação , Neoplasias Primárias Múltiplas/patologia , Idoso , Carcinoma de Células Escamosas/genética , Condrossarcoma/genética , Feminino , Neoplasias Femorais/genética , Humanos , Neoplasias Primárias Múltiplas/genéticaAssuntos
Adamantinoma/diagnóstico , Biomarcadores Tumorais/análise , Neoplasias Ósseas/diagnóstico , Carcinoma/diagnóstico , Erros de Diagnóstico , Neoplasias Femorais/diagnóstico , Neoplasias Pulmonares/diagnóstico , Proteínas Nucleares/análise , Proteínas Oncogênicas/análise , Tíbia/patologia , Adamantinoma/química , Adamantinoma/genética , Adamantinoma/patologia , Adolescente , Biomarcadores Tumorais/genética , Biópsia , Neoplasias Ósseas/química , Neoplasias Ósseas/genética , Neoplasias Ósseas/secundário , Neoplasias Ósseas/terapia , Carcinoma/química , Carcinoma/genética , Carcinoma/secundário , Carcinoma/terapia , Progressão da Doença , Evolução Fatal , Feminino , Neoplasias Femorais/química , Neoplasias Femorais/genética , Neoplasias Femorais/secundário , Neoplasias Femorais/terapia , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/química , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Metástase Linfática , Proteínas de Neoplasias , Proteínas Nucleares/genética , Proteínas Oncogênicas/genética , Valor Preditivo dos Testes , Tíbia/química , Tomografia Computadorizada por Raios X , Falha de Tratamento , Imagem Corporal TotalAssuntos
Neoplasias Ósseas/genética , Carcinoma Hepatocelular/genética , Neoplasias Femorais/genética , Mutação em Linhagem Germinativa , Neoplasias Hepáticas/genética , Neoplasias Primárias Múltiplas/genética , Osteossarcoma/genética , Mutação Puntual , Proteína Supressora de Tumor p53/genética , Idade de Início , Criança , Feminino , HumanosRESUMO
Transformed sarcomas rarely arise from bone infarct lesions, although the majority of bone sarcomas are primary in origin. However, the pathogenesis of the condition is unknown. In this report, we describe a malignant fibrous histiocytoma with a p53 gene mutation. A 59-year-old woman complained of having pain in her left knee for three months. Plain radiographs of the distal metaphysis of her left femur revealed an ill-defined lytic lesion, which was consistent with a malignant tumor in the infarct lesion. An open biopsy specimen did not show any evidence of malignancy. Immunohistochemical examination of the biopsy specimen failed to show p53 protein-positive cells. However, a mutation in the p53 gene was detected when polymerase chain reaction/single-strand conformation polymorphism (PCR-SSCP) analysis was performed. A functionally relevant p53 missense mutation in codon 273 of exon 8 [CGT (Arg) -> CAT (His)] was confirmed by direct sequencing. We concluded that this lesion was a malignant bone tumor arising from the bone infarct lesion, and we thus performed a wide resection. The histopathological diagnosis of the resected specimen was that it was a malignant fibrous histiocytoma associated with bone infarction. Immunohistochemistry revealed that the tumor cells were positive for the p53 protein. To our knowledge, our patient is the first patient having a bone infarct-associated sarcoma with a p53 gene mutation. Identification of the p53 mutation helps in diagnosing the malignant transformation of the bone infarct lesion. One pathogenesis of this condition may be a mutation in the p53 gene.
Assuntos
Neoplasias Femorais/genética , Neoplasias Femorais/patologia , Histiocitoma Fibroso Maligno/genética , Histiocitoma Fibroso Maligno/patologia , Mutação de Sentido Incorreto/genética , Proteína Supressora de Tumor p53/genética , Feminino , Neoplasias Femorais/irrigação sanguínea , Neoplasias Femorais/diagnóstico por imagem , Histiocitoma Fibroso Maligno/diagnóstico por imagem , Humanos , Imuno-Histoquímica , Infarto/patologia , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Radiografia , Análise de Sequência de DNARESUMO
BACKGROUND: Molecular and cellular events that resulted in leukemia development are well characterized but initial engraftment and proliferation of leukemic cells in bone marrow and early modifications of the bone marrow microenvironment induced by engrafted leukemic cells remain to be clarified. DESIGN AND METHODS: After retro-orbital injection of 1,000 leukemic cells expressing Mixed Lineage Leukemia-Eleven Nineteen Leukemia fusion protein in non-conditioned syngenic mice, kinetics of leukemic burden and alterations of femoral hematopoietic populations were followed using an in vivo confocal imaging system and flow cytometry. RESULTS: Three days after injection, 5% of leukemic cells were found in femurs. Little proliferation of engrafted leukemic cells could then be detected for more than two weeks while the number of femoral leukemic cells remained stable. Twenty days after injection, leukemic cells preferentially proliferated in femoral diaphysis where they formed clusters on the surface of blood vessels and bone. B220(+) lymphoid cells were found near these leukemic cell clusters and this association is correlated with a decreased number of femoral B220(+)IgM(+) cells. Increasing the number of injected leukemic cells or conditioning recipient mice with γ-irradiation resulted in leukemic cell development in diaphysis and knee. Competition experiments indicate that proliferation but not engraftment is a rate-limiting factor of leukemic cells spreading in diaphysis. Finally, 30 days after injection leukemia developed. CONCLUSIONS: After retro-orbital injection of 1,000 leukemic cells expressing Mixed Lineage Leukemia-Eleven Nineteen Leukemia into syngenic mice, leukemic cell burden preferentially initiates in femoral diaphysis and is preceded by changes of femoral B-lymphoid populations.
Assuntos
Linfócitos B/metabolismo , Proteínas de Ligação a DNA/metabolismo , Neoplasias Femorais/metabolismo , Fêmur/metabolismo , Leucemia Aguda Bifenotípica/metabolismo , Proteína de Leucina Linfoide-Mieloide/metabolismo , Proteínas de Fusão Oncogênica/metabolismo , Fatores de Transcrição/metabolismo , Animais , Linfócitos B/patologia , Proteínas de Ligação a DNA/genética , Diáfises/metabolismo , Diáfises/patologia , Neoplasias Femorais/genética , Neoplasias Femorais/patologia , Fêmur/patologia , Histona-Lisina N-Metiltransferase , Leucemia Aguda Bifenotípica/genética , Leucemia Aguda Bifenotípica/patologia , Camundongos , Proteína de Leucina Linfoide-Mieloide/genética , Proteínas de Fusão Oncogênica/genética , Fatores de Transcrição/genética , Carga Tumoral/genéticaRESUMO
Ollier disease and Maffucci syndrome are rare, nonhereditary skeletal disorders characterized by the presence of multiple enchondromas with (Maffucci) or without (Ollier) co-existing multiple hemangiomas of soft tissue. Enchondromas can progress toward central chondrosarcomas. PTH1R mutations are found in a small subset of Ollier patients. The genetic deficit in Maffucci syndrome is unknown. Here, we report the first genome-wide analysis using Affymetrix SNP 6.0 array on Maffucci enchondromas (n = 4) and chondrosarcomas (n = 2) from four cases. Results were compared to a previously studied cohort of Ollier patients (n = 37). We found no loss of heterozygosity (LOH) or common copy number alterations shared by all enchondromas, with the exception of some copy number variations. As expected, chondrosarcomas were found to have multiple genomic imbalances. This is similar to conventional solitary and Ollier-related enchondromas and chondrosarcomas and supports the multistep genetic progression model. Expression profiling using Illumina BeadArray-v3 chip revealed that cartilaginous tumors in Maffucci patients are more similar to such tumors in Ollier patients than to sporadic cartilage tumors. Point mutations in a single gene or other copy number neutral genomic changes might play a role in enchondromagenesis.
Assuntos
Condrossarcoma/genética , Encondromatose/genética , Neoplasias Femorais/genética , Perfilação da Expressão Gênica , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Criança , Análise por Conglomerados , Variações do Número de Cópias de DNA , Feminino , Genes Neoplásicos , Estudo de Associação Genômica Ampla , Humanos , Masculino , Análise de Sequência de DNAAssuntos
Transformação Celular Neoplásica/genética , Cromossomos Humanos Par 11 , Cromossomos Humanos Par 7 , Ciclina D1/genética , Neoplasias Femorais/genética , Amplificação de Genes , Tumor de Células Gigantes do Osso/genética , Proteínas Proto-Oncogênicas c-met/genética , Receptores de Fatores de Crescimento/genética , Adulto , Biópsia , Transplante Ósseo , Curetagem , Feminino , Neoplasias Femorais/patologia , Neoplasias Femorais/cirurgia , Tumor de Células Gigantes do Osso/patologia , Tumor de Células Gigantes do Osso/cirurgia , Humanos , Imuno-Histoquímica , Cariotipagem , Invasividade Neoplásica , Resultado do TratamentoAssuntos
Neoplasias Femorais/genética , Leucemia Mieloide Aguda/genética , Síndrome de Li-Fraumeni/genética , Neoplasias Musculares/genética , Segunda Neoplasia Primária/genética , Osteossarcoma/genética , Rabdomiossarcoma Embrionário/genética , Evolução Fatal , Neoplasias Femorais/diagnóstico , Predisposição Genética para Doença , Humanos , Lactente , Síndrome de Li-Fraumeni/complicações , Síndrome de Li-Fraumeni/diagnóstico , Masculino , Neoplasias Musculares/diagnóstico , Osteossarcoma/diagnóstico , Rabdomiossarcoma Embrionário/diagnóstico , Coxa da Perna/patologiaAssuntos
Antígenos de Diferenciação/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias Femorais/metabolismo , Neoplasias Femorais/patologia , Mastocitose Sistêmica/metabolismo , Mastocitose Sistêmica/patologia , Sarcoma/metabolismo , Sarcoma/patologia , Adulto , Antígenos de Diferenciação/genética , Biomarcadores Tumorais/genética , Diagnóstico Diferencial , Feminino , Neoplasias Femorais/tratamento farmacológico , Neoplasias Femorais/genética , Neoplasias Femorais/secundário , Humanos , Mastocitose Sistêmica/tratamento farmacológico , Mastocitose Sistêmica/genética , Osteólise/tratamento farmacológico , Osteólise/genética , Osteólise/metabolismo , Osteólise/patologia , Sarcoma/tratamento farmacológico , Sarcoma/genética , Sarcoma/secundárioRESUMO
BACKGROUND: A giant cell tumor of bone (GCT) is a histologically benign neoplasma that has an unpredictable pattern of biological aggressiveness. In the present study, we investigated whether there was a correlation between telomere length or the levels of telomerase activity and other clinical features of GCTs, for the possible use of these factors as parameters of aggressiveness or prognosis. METHODS: In 16 surgically resected GCTs specimens, telomere length was assessed by terminal restriction fragments by Southern blot analysis. Telomerase activity was measured by a semiquantitative polymerase chain reaction-based telomeric repeat amplification protocol assay. RESULTS: Telomere length reduction was observed in 69% of the GCT samples. The telomere lengths of tumors were significantly shorter than those of normal tissue (P = .008). The mean telomere length of grade 3 tumors was significantly shorter than those of grade 1 and 2 tumors (P = .038). Telomerase activity was detected in 81% of tumor samples. The level of telomerase activity in tumors with local recurrence was significantly higher than in tumors without local recurrence (P = .011). CONCLUSIONS: These results suggest that telomere length correlates with roentgenographic grade as a result of the frequency of cell division, and high telomerase activity indicates the aggressiveness of GCTs.