RESUMO
Myxoid leiomyosarcoma (MLS) is a rare variant of leiomyosarcoma, with most cases occurring in the uterus. A case of MLS arising in the periosteal region of the tibia, mimicking extraskeletal myxoid chondrosarcoma (EMC), is described. The evaluation included histological and cytological comparison with EMC. The patient was a 77-year-old man with a palpable mass at the anterior aspect of the right lower leg. After diagnosis by cytopathology and biopsy examination, a wide resection was performed. The resulting cytological smears were composed primarily of spindle-shaped tumor cells in a myxoid and hemorrhagic background. Histologically, the tumor showed abundant myxoid matrix and tumor cells proliferating in a cord-like to reticular pattern, exhibiting a lace-like arrangement that mimicked EMC. Although immunohistochemical findings suggested leiomyosarcoma, a diagnosis of EMC eventually was excluded by the lack of a split signal when assessed for a rearrangement of NR4A3 by chromogenic in situ hybridization. Despite histological similarity to EMC, characteristic cytological findings of EMC such as epithelioid structures with a cord-like pattern and chondroblast-like lacunar structures were not observed in the smears of this patient's MLS. We propose that cytopathological examination of bone and soft tissue lesions is useful as a diagnostic tool in similar cases. A total diagnostic workup, including clinical, radiographic, cytopathological, histopathological, and molecular findings, is needed to ensure an accurate final diagnosis and to reduce diagnostic error.
Assuntos
Neoplasias Ósseas/patologia , Condrossarcoma/patologia , Leiomiossarcoma/patologia , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/patologia , Tíbia/patologia , Idoso , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Neoplasias Ósseas/química , Neoplasias Ósseas/genética , Neoplasias Ósseas/cirurgia , Condrossarcoma/química , Condrossarcoma/genética , Proteínas de Ligação a DNA/genética , Diagnóstico Diferencial , Rearranjo Gênico , Humanos , Imuno-Histoquímica , Hibridização In Situ , Leiomiossarcoma/química , Leiomiossarcoma/genética , Leiomiossarcoma/cirurgia , Masculino , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/química , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/genética , Valor Preditivo dos Testes , Receptores de Esteroides/genética , Receptores dos Hormônios Tireóideos/genética , Tíbia/química , Tíbia/cirurgiaRESUMO
PURPOSE: To detect the expression level of hsa_circ_0005721 in osteosarcoma specimen and plasma of osteosarcoma patients, and to analyze the clinical significance of hsa_circ_0005721 as a diagnostic marker for osteosarcoma. METHODS: Expression levels of hsa_circ_0005721 in osteosarcoma specimen and osteosarcoma cell lines were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between hsa_circ_0005721 expression difference and overall survival in osteosarcoma was analyzed by Kaplan-Meier method. Expression level of hsa_circ_0005721 was stably downregulated in U-2OS and HOS cells by shRNA transfection. Proliferative potential in osteosarcoma cells regulated by hsa_circ_0005721 was assessed by colony formation and 5-Ethynyl-2'- deoxyuridine (EdU) assay. Differentially expressed hsa_circ_0005721 in the plasma of healthy controls, benign bone tumor patients and osteosarcoma patients was determined by qRT-PCR. The diagnostic capacity of hsa_circ_0005721 in osteosarcoma was examined by receiver operating characteristic (ROC) curves. RESULTS: hsa_circ_0005721 was upregulated in osteosarcoma specimen and osteosarcoma cell lines. High level of hsa_circ_0005721 predicted poor prognosis in osteosarcoma patients. In vitro experiments showed that knockdown of hsa_circ_0005721 suppressed proliferative ability in osteosarcoma cells. Compared with that in healthy controls and benign bone tumor patients, plasma level of hsa_circ_0005721 was higher in osteosarcoma patients. ROC curves demonstrated the diagnostic potential of hsa_circ_0005721 in osteosarcoma. CONCLUSIONS: hsa_circ_0005721 is upregulated in osteosarcoma samples, which acts as an oncogene responsible for aggravating the progression. hsa_circ_0005721 can be a promising diagnostic marker for osteosarcoma.
Assuntos
Biomarcadores Tumorais/análise , Neoplasias Ósseas/sangue , Neoplasias Ósseas/química , Osteossarcoma/sangue , Osteossarcoma/química , RNA Circular/análise , Biomarcadores Tumorais/genética , Neoplasias Ósseas/diagnóstico , Humanos , Osteossarcoma/diagnóstico , RNA Circular/genética , Células Tumorais CultivadasRESUMO
Environmentally, bisphenol A (BPA) is a well-known pollutant caused human health risk, including osteosarcoma (OS). OS, a deadly bone neoplasia, may occur in children and adults. However, the anti-OS pharmacotherapy prescribes limitedly in clinical practice. Interestingly, previous experimental evidences indicate calycosin-exerting potential anti-OS actions. Thus, in this report, we aimed to further characterize and detail the therapeutic targets and molecular mechanisms of calycosin-anti-BPA-related OS by using network pharmacology and molecular docking analyses. In results, the bioinformatics data disclosed all mapped, core targets, biological functions, molecular pathways of calycosin to treat BPA-related OS. The computational analysis using molecular docking indicated that potential binding ability of core targets in calycosin to treat BPA-related OS was identified. Moreover, detailed biological functions and optimal pathways of calycosin-anti-BPA-related OS were revealed, as shown in integrated network maps. Taken together, these network pharmacology and structural biology findings illustrate the core biotargets, pharmacological functions and pathways of calycosin-anti-BPA-related OS. Potentially, these core targets identified by molecular docking may attribute to the potential clinical application of calycosin against BPA-related OS.[Formula: see text].
Assuntos
Antineoplásicos , Neoplasias Ósseas/metabolismo , Isoflavonas , Osteossarcoma/metabolismo , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Compostos Benzidrílicos , Neoplasias Ósseas/química , Biologia Computacional , Regulação Neoplásica da Expressão Gênica , Humanos , Isoflavonas/química , Isoflavonas/metabolismo , Isoflavonas/farmacologia , Simulação de Acoplamento Molecular , Osteossarcoma/química , FenóisRESUMO
Cementoblastomas are rare odontogenic tumors developing in close proximity to the roots of teeth. Due to their striking morphologic resemblance to osteoblastomas of the peripheral skeleton, we set out to determine whether cementoblastomas harbor the same FOS rearrangements with overexpression of c-FOS as has recently been described for osteoblastomas. In total, 16 cementoblastomas were analyzed for FOS expression by immunohistochemistry and for FOS rearrangements by fluorescence in situ hybridization (FISH). We observed strong and diffuse staining of c-FOS in 71% of cementoblastomas and identified a FOS rearrangement in all cases (n=3) applicable for FISH. In the remaining cases, FISH failed due to decalcification. Cementoblastomas harbor similar FOS rearrangements and show overexpression of c-FOS like osteoblastomas, suggesting that both entities might represent parts of the spectrum of the same disease.
Assuntos
Biomarcadores Tumorais , Neoplasias Ósseas , Cemento Dentário , Rearranjo Gênico , Tumores Odontogênicos , Osteoblastoma , Proteínas Proto-Oncogênicas c-fos , Raiz Dentária , Adolescente , Adulto , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Neoplasias Ósseas/química , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Criança , Cemento Dentário/química , Cemento Dentário/patologia , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Países Baixos , Tumores Odontogênicos/química , Tumores Odontogênicos/genética , Tumores Odontogênicos/patologia , Osteoblastoma/química , Osteoblastoma/genética , Osteoblastoma/patologia , Proteínas Proto-Oncogênicas c-fos/análise , Proteínas Proto-Oncogênicas c-fos/genética , Suíça , Raiz Dentária/química , Raiz Dentária/patologia , Adulto JovemRESUMO
The aim of this study is to assess the usefulness of beta-catenin immunohistochemical expression in the differential diagnosis of osteoid-producing primary tumors of bone. Seventy cases of osteoid-producing tumors of bone (24 conventional osteosarcomas, 18 osteoblastomas, 13 osteoblastoma-like osteosarcomas, 10 chondroblastomas, and 5 chondroblastoma-like osteosarcomas) diagnosed at Istituto Ortopedico Rizzoli were reviewed and evaluated for the intensity, extension, and subcellular distribution of immunohistochemical expression of beta-catenin. A majority of cases (73%, 51 cases) exhibited cytoplasmic and/or membranous positivity in varied degrees of intensity and proportion of positive cells, in the absence of nuclear staining. Fifteen cases (21%) were completely negative, including two osteoblastomas, five chondroblastomas, three conventional osteosarcomas, four osteoblastoma-like osteosarcomas, and one chondroblastoma-like osteosarcoma. A minority of cases (6%) including three osteoblastoma-like osteosarcomas and one osteoblastoma showed focal nuclear beta-catenin positivity with or without concomitant cytoplasmic staining. In the current series, beta-catenin showed not to be useful in the differential diagnosis of osteoid-producing primary bone tumors.
Assuntos
Biomarcadores Tumorais/análise , Neoplasias Ósseas/química , Condroblastoma/química , Imuno-Histoquímica , Osteoblastoma/química , Osteossarcoma/química , beta Catenina/análise , Adolescente , Adulto , Idoso , Neoplasias Ósseas/patologia , Criança , Pré-Escolar , Condroblastoma/patologia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoblastoma/patologia , Osteossarcoma/patologia , Valor Preditivo dos Testes , Adulto JovemRESUMO
Epithelial-myoepithelial carcinoma (EMC) is a rare, low-grade, malignant salivary neoplasm. Establishing an accurate cytological diagnosis is often challenging owing to its rarity, bland cytologic appearance and variable representation of cell populations in the smears. The diagnostic struggle is more so when the aspiration is from a metastatic site with an unknown primary, as in such cases the list of differential diagnoses expands further. A 58-year-old female presented with a low-back pain from last one month. On examination, she also had a level III, right cervical swelling for the last 20 years. Radiology revealed a lytic lesion in the left acetabulum. She had undergone surgery 35 years ago for a right-sided upper neck swelling, the medical records of which were not available. Fine needle aspiration (FNA) from the cervical swelling was performed. The smears were cellular and showed predominantly dispersed, round to polygonal tumor cells with mild pleomorphism, eccentric nuclei, coarse chromatin, occasional nucleoli and moderate cytoplasm with some showing vacuolations. The cell-block section revealed tumor cells arranged in the form of tubules lined by dual layer of tumor cells without any chondromyxoid stroma. On immunocytochemistry, the luminal cells showed positivity for CK7 (epithelial marker) and the abluminal cells showed positivity for p63 (myoepithelial marker). Based on these features, a final diagnosis of metastatic epithelial-myoepithelial carcinoma was rendered. The present report highlights the characteristic cytomorphological and immunocytochemical features of EMC and reiterates the diagnostic accuracy of FNAC for diagnosis of such challenging cases.
Assuntos
Acetábulo/patologia , Neoplasias Ósseas/secundário , Neoplasias de Cabeça e Pescoço/secundário , Mioepitelioma/secundário , Neoplasias Epiteliais e Glandulares/secundário , Neoplasias Primárias Desconhecidas/patologia , Acetábulo/química , Biomarcadores Tumorais/análise , Biópsia por Agulha Fina , Neoplasias Ósseas/química , Diagnóstico Diferencial , Feminino , Neoplasias de Cabeça e Pescoço/química , Humanos , Pessoa de Meia-Idade , Mioepitelioma/química , Neoplasias Epiteliais e Glandulares/química , Valor Preditivo dos TestesRESUMO
Distant metastasis of retinoblastoma to sites outside the central nervous system is rare; such cases may present years following primary treatment. Diagnosis may be difficult given the rarity of such events and considerable histologic mimics. We describe the clinicopathologic features of 6 cases of metastatic retinoblastoma to distant bone and soft tissue sites from 2 large academic centers. Patients were 3 female and 3 male children; median age was 9.5 years (range: 5 to 15 y) with a mean interval from primary disease diagnosis of 8.0 years (range: 0.75 to 14 y). Metastasis to bones of the lower extremities was most common, occurring in 4 of 6 cases. Tumors showed typical histologic features of retinoblastoma, with sheets of primitive round cells with minimal cytoplasm and indistinct nucleoli; however, characteristic Flexner-Wintersteiner rosettes were absent. A subset of cases demonstrated an alveolar growth pattern, and 2 cases showed higher grade cytology with nuclear anaplasia and prominent nucleoli. Immunohistochemistry for CRX and RB1 showed uniform positivity and loss of expression, respectively. Metastatic retinoblastoma outside the central nervous system may present following long disease-free intervals. Immunohistochemistry for CRX is helpful to confirm this challenging diagnosis.
Assuntos
Biomarcadores Tumorais/análise , Neoplasias Ósseas/química , Proteínas de Homeodomínio/análise , Imuno-Histoquímica , Neoplasias da Retina/química , Retinoblastoma/química , Neoplasias de Tecidos Moles/química , Transativadores/análise , Adolescente , Neoplasias Ósseas/secundário , Boston , California , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Neoplasias da Retina/patologia , Retinoblastoma/secundário , Proteínas de Ligação a Retinoblastoma/análise , Neoplasias de Tecidos Moles/secundário , Ubiquitina-Proteína Ligases/análiseRESUMO
Cellular adaptation to a hypoxic microenvironment is essential for tumour progression and is largely mediated by HIF-1α and hypoxia-regulated factors, including CXCR4, VEGF-A and GLUT-1. In human osteosarcoma, hypoxia is associated with resistance to chemotherapy as well as with metastasis and poor survival, whereas little is known about its role in canine osteosarcoma (cOSA). This study aimed primarily to evaluate the prognostic value of several known hypoxic markers in cOSA. Immunohistochemical analysis for HIF-1α, CXCR4, VEGF-A and GLUT-1 was performed on 56 appendicular OSA samples; correlations with clinicopathological features and outcome was investigated. The second aim was to investigate the in vitro regulation of markers under chemically induced hypoxia (CoCl2). Two primary canine osteosarcoma cell lines were selected, and Western blotting, immunofluorescence and qRT-PCR were used to study protein and gene expression. Dogs with high-grade OSA (35.7%) were more susceptible to the development of metastases (P = 0.047) and showed high HIF-1α protein expression (P = 0.007). Moreover, HIF-1α overexpression (56%) was correlated with a shorter disease-free interval (DFI; P = 0.01), indicating that it is a reliable negative prognostic marker. The in vitro experiments identified an accumulation of HIF-1α in cOSA cells after chemically induced hypoxia, leading to a significant increase in GLUT-1 transcript (P = 0.02). HIF-1α might be a promising prognostic marker, highlighting opportunities for the use of therapeutic strategies targeting the hypoxic microenvironment in cOSA. These results reinforce the role of the dog as a comparative animal model since similar hypoxic mechanisms are reported in human osteosarcoma.
Assuntos
Neoplasias Ósseas/veterinária , Hipóxia Celular/fisiologia , Doenças do Cão/fisiopatologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/fisiologia , Osteossarcoma/veterinária , Animais , Biomarcadores Tumorais/análise , Neoplasias Ósseas/química , Neoplasias Ósseas/fisiopatologia , Linhagem Celular Tumoral , Doenças do Cão/patologia , Cães , Feminino , Regulação Neoplásica da Expressão Gênica , Transportador de Glucose Tipo 1/análise , Subunidade alfa do Fator 1 Induzível por Hipóxia/análise , Imuno-Histoquímica/veterinária , Masculino , Metástase Neoplásica/fisiopatologia , Osteossarcoma/química , Osteossarcoma/fisiopatologia , Prognóstico , Receptores CXCR4/análise , Fator A de Crescimento do Endotélio Vascular/análiseRESUMO
Recent molecular discoveries have refined vascular bone tumor classification. To investigate the clinical relevance of these refinements, we reviewed all cases of primary vascular bone tumors treated at our Institute. On the basis of morphology, cases were assessed immunohistochemically and molecularly. A total of 427 cases of primary vascular tumor of bone with available follow-up and histologic material were retrieved and reclassified according to the most recent diagnostic criteria as follows: 289 hemangiomas, 38 epithelioid hemangiomas, 21 epithelioid hemangioendotheliomas, 2 retiform hemangioendotheliomas, 1 intraosseous papillary intralymphatic angioendothelioma, 24 pseudomyogenic hemangioendotheliomas, and 52 angiosarcomas (of these, 45 were epithelioid angiosarcomas and 7 spindle cell secondary angiosarcoma). Both epithelioid and classic hemangiomas behave as benign tumors with excellent prognosis. The distinction between cellular and conventional type of epithelioid hemangioma was not associated with a different clinical course. Conversely, epithelioid hemangioendothelioma exhibited a more aggressive clinical behavior than hemangioma, with higher rates of multifocality and distant spread. Immunohistochemical positivity for CAMTA1 or TFE3 did not have a prognostic implication. In epithelioid hemangioendothelioma, the presence of morphologic malignant features was associated with reduced disease-free (P=0.064) and overall survival (P=0.055). Pseudomyogenic hemangioendothelioma featured local aggressiveness in 5/24 patients exhibiting a clinical behavior closer to epithelioid hemangioma than epithelioid hemangioendothelioma. Last, 32/45 patients with epithelioid angiosarcoma died of disease with a median survival time of 10 months from diagnosis. In conclusion, the integration of morphologic, immunohistochemical, and molecular features allows a better stratification of primary vascular tumors of bone with significant prognostic and therapeutic implications.
Assuntos
Biomarcadores Tumorais , Neoplasias Ósseas/classificação , Células Epitelioides , Neoplasias de Tecido Vascular/classificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Biópsia , Neoplasias Ósseas/química , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Diferenciação Celular , Criança , Pré-Escolar , Intervalo Livre de Doença , Células Epitelioides/química , Células Epitelioides/patologia , Feminino , Fusão Gênica , Rearranjo Gênico , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Itália , Masculino , Pessoa de Meia-Idade , Neoplasias de Tecido Vascular/química , Neoplasias de Tecido Vascular/genética , Neoplasias de Tecido Vascular/patologia , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Adulto JovemRESUMO
Biological reconstruction of allografts and recycled autografts have been widely implemented in high-grade osteogenic sarcoma. For treating tumor-bearing autografts, extracorporeal irradiation (ECIR) and liquid nitrogen (LN) freezing techniques are being used worldwide as a gold standard treatment procedure. Both the methods aim to eradicate the tumor cells from the local recurrence and restore the limb function. Therefore, it is essential and crucial to find, and compare the alterations at molecular and physiological levels of the treated and untreated OGS recycled autografts to obtain valuable clinical information for better clinical practice. Thus, we aimed to investigate the significantly expressed altered proteins from ECIR-and cryotherapy/freezing- treated OGS (n = 12) were compared to untreated OGS (n = 12) samples using LC-ESI-MS/MS analysis, and the selected proteins from this protein panel were verified using immunoblot analysis. From our comparative proteomic analysis identified a total of 131 differentially expressed proteins (DEPs) from OGS. Among these, 91 proteins were up-regulated (2.5 to 3.5-folds), and 40 proteins were down-regulated (0.2 to 0.5 folds) (p < 0.01 and 0.05). The functional enrichment analysis revealed that the identified DEPs have belonged to more than 10 different protein categories include cytoskeletal, extracellular matrix, immune, enzyme modulators, and cell signaling molecules. Among these, we have confirmed two potential candidates' expressions levels such as Fibronectin and Protein S100 A4 using western blot analysis. Our proteomic study revealed that LN-freezing and ECIR treatments are effectively eradicating tumor cells, and reducing the higher expressions of DEPs at molecular levels which may help in restoring the limb functions of OGS autografts effectively. To the best of our knowledge, this is the first proteomic study that compared proteomic profiles among freezing, ECIR treated with untreated OGS in recycled autografts. Moreover, the verified proteins could be used as prognostic or diagnostic markers that reveal valuable scientific information which may open various therapeutic avenues in clinical practice to improve patient outcomes.
Assuntos
Neoplasias Ósseas/diagnóstico , Crioterapia , Osteossarcoma/diagnóstico , Proteoma/análise , Adulto , Idoso , Biomarcadores Tumorais/análise , Western Blotting , Neoplasias Ósseas/química , Neoplasias Ósseas/terapia , Terapia Combinada , Crioterapia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/análise , Osteossarcoma/química , Osteossarcoma/terapia , Adulto JovemRESUMO
There is a growing interest in immunotherapy in childhood cancers. Osteosarcoma is a compelling potential target as there are few targeted options available for this aggressive cancer. We provide a description of the landscape of programmed cell death-1 (PD-1), programmed cell death-ligand 1 (PD-L1) and relevant immune markers in serial samples from 15 osteosarcoma patients. PD-1 and PD-L1 expression was present in biopsy samples (47% and 53%, respectively), absent in resections, and present in metastases (40% and 47%). Both decalcified and nondecalcified specimens demonstrated expression of PD-1 and PD-L1. The results suggest that biopsy or metastatic specimens maybe most valuable in assessing expression of PD-1 and PD-L1.
Assuntos
Antígeno B7-H1/análise , Neoplasias Ósseas/química , Osteossarcoma/química , Receptor de Morte Celular Programada 1/análise , Adolescente , Biópsia , Neoplasias Ósseas/patologia , Criança , Feminino , Humanos , Masculino , Metastasectomia , Necrose , Osteossarcoma/patologia , Osteossarcoma/secundário , Linfócitos T/patologia , Adulto JovemAssuntos
Neoplasias Ósseas/secundário , Neoplasias Cardíacas/patologia , Neoplasias Pulmonares/secundário , Artéria Pulmonar/patologia , Sarcoma/secundário , Esterno/patologia , Valva Tricúspide/patologia , Biomarcadores Tumorais/análise , Neoplasias Ósseas/química , Neoplasias Ósseas/terapia , Quimioterapia Adjuvante , Progressão da Doença , Evolução Fatal , Neoplasias Cardíacas/química , Neoplasias Cardíacas/terapia , Implante de Prótese de Valva Cardíaca , Humanos , Neoplasias Pulmonares/química , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Cuidados Paliativos , Artéria Pulmonar/química , Artéria Pulmonar/cirurgia , Sarcoma/química , Sarcoma/terapia , Esterno/química , Esterno/cirurgia , Fatores de Tempo , Resultado do Tratamento , Valva Tricúspide/química , Valva Tricúspide/cirurgiaRESUMO
We describe the case of a Ewing sarcoma with prominent myxoid stroma of the temporal bone in a 26-year-old female. Histologically, the tumor exhibited a fascicular growth pattern of round to spindled cells with a minimal amount of pale eosinophilic to clear cytoplasm and oval or spindled nuclei with finely dispersed chromatin and small nucleoli. Myxoid changes were prominent (>50%), with reticular or pseudoacinar growth of the loosely cohesive cells. The tumor showed strong expression of CD99, FLI1, and CD56 and was positive for the EWSR1-FLI1 fusion transcript. The diagnosis of Ewing sarcoma with myxoid stroma (myxoid variant) is particularly problematic owing to the large number of potential mimics. The tumor extends the morphologic spectrum of Ewing sarcoma beyond the previously described histological variants, and broadens the differential diagnosis. For any round/spindle cell sarcoma, prominent myxoid stroma and CD99 immunoreactivity should prompt consideration for molecular studies that include analysis of both EWSR1 and FLI1.
Assuntos
Neoplasias Ósseas/patologia , Sarcoma de Ewing/patologia , Células Estromais/patologia , Osso Temporal/patologia , Antígeno 12E7/análise , Adulto , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Neoplasias Ósseas/química , Neoplasias Ósseas/genética , Neoplasias Ósseas/terapia , Antígeno CD56/análise , Diagnóstico Diferencial , Feminino , Fusão Gênica , Humanos , Proteínas de Fusão Oncogênica/genética , Valor Preditivo dos Testes , Sarcoma de Ewing/química , Sarcoma de Ewing/genética , Sarcoma de Ewing/terapia , Células Estromais/química , Osso Temporal/químicaRESUMO
Osteoblastoma and osteoid osteoma together are the most frequent benign bone-forming tumor, arbitrarily separated by size. In some instances, it can be difficult to differentiate osteoblastoma from osteosarcoma. Following our recent description of FOS gene rearrangement in these tumors, the aim of this study is to evaluate the value of immunohistochemistry in osteoid osteoma, osteoblastoma, and osteosarcoma for diagnostic purposes. A total of 337 cases were tested with antibodies against c-FOS: 84 osteoblastomas, 33 osteoid osteomas, 215 osteosarcomas, and 5 samples of reactive new bone formation. In all, 83% of osteoblastomas and 73% of osteoid osteoma showed significant expression of c-FOS in the osteoblastic tumor cell component. Of the osteosarcomas, 14% showed c-FOS expression, usually focal, and in areas with severe morphologic atypia which were unequivocally malignant: 4% showed more conspicuous expression, but these were negative for FOS gene rearrangement. We conclude that c-FOS immunoreactivity is present in the vast majority of osteoblastoma/osteoid osteoma, whereas its expression is usually focal or patchy, in no more than 14% of osteosarcoma biopsies. Therefore, any bone-forming tumor cases with worrying histologic features would benefit from fluorescence in situ hybridization analysis for FOS gene rearrangement. Our findings highlight the importance of undertaking a thorough assessment of expression patterns of antibodies in the light of morphologic, clinical, and radiologic features.
Assuntos
Biomarcadores Tumorais/análise , Neoplasias Ósseas/química , Osteoblastoma/química , Osteoma Osteoide/química , Proteínas Proto-Oncogênicas c-fos/análise , Adolescente , Adulto , Biomarcadores Tumorais/genética , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Criança , Pré-Escolar , Diagnóstico Diferencial , Inglaterra , Feminino , Rearranjo Gênico , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Osteoblastoma/genética , Osteoblastoma/patologia , Osteoma Osteoide/genética , Osteoma Osteoide/patologia , Valor Preditivo dos Testes , Proteínas Proto-Oncogênicas c-fos/genética , Suíça , Adulto JovemRESUMO
With the development of minimally invasive endoscopic surgery and image-guided navigation systems, the endoscopic endonasal approach to petrous apex lesions has become more favorable. In this case, a petrous apex cholesterol granuloma was successfully treated with an endoscopic endonasal transpterygoid approach. A navigation system was used, and a contralateral nasoseptal flap and silicone tube stent were applied to maintain the cholesterol granuloma drainage pathway. The authors describe the endoscopic endonasal transpterygoid approach using a pedicled nasoseptal flap for petrous apex cholesterol granuloma and provide an intraoperative video and a literature review.
Assuntos
Neoplasias Ósseas/cirurgia , Granuloma/cirurgia , Osso Petroso/cirurgia , Neoplasias Ósseas/química , Neoplasias Ósseas/patologia , Colesterol/análise , Drenagem , Endoscopia , Feminino , Granuloma/patologia , Humanos , Pessoa de Meia-Idade , Nariz , Osso Petroso/química , Stents , Retalhos CirúrgicosRESUMO
In metastatic breast cancer (MBC), expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) guides treatment selection. In case of bone-only metastatic disease, ER, PR, and HER2 status assessment may be hampered by decalcification. We aimed to determine the optimal decalcification method, and to study discordance of receptor expression between paired primary breast tumors and optimally decalcified bone metastases. First, decalcification was simulated using acetic acid, hydrochloric/formic acid, and EDTA on 12 primary breast carcinomas. ER, PR, and HER2 immunohistochemistry (IHC) and HER2 in situ hybridization (ISH) were assessed, before and after the 3 decalcification methods. EDTA was considered the optimal method, as it did not affect IHC and as ISH failed in only 1/16 cases. Hydrochloric/formic acid altered ER and PR results, and, with acetic acid and hydrochloric/formic acid, ISH failed in, respectively, 94% and 100%. Second, ER, PR, and HER2 IHC was performed in paired primary tumors and EDTA-decalcified bone metastases obtained from patients with first presentation of MBC. Clinically relevant discordance was defined as changed receptor status with treatment implications. Paired samples of 77 patients, participating in the IMPACT-MBC trial, were evaluable. Hormonal receptor expression change was clinically relevant in 6 patients (7.9%) and HER2 expression change in 1 patient (1.3%). This study shows that EDTA decalcification minimally affects receptor expression results. The incidence of clinically relevant discordance between the primary tumor and bone metastases is low. These findings support that bone biopsies can reliably be used to assess receptor status.
Assuntos
Biomarcadores Tumorais , Neoplasias Ósseas , Neoplasias da Mama , Quelantes de Cálcio/química , Técnica de Descalcificação , Ácido Edético/química , Receptor ErbB-2/genética , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Biópsia , Neoplasias Ósseas/química , Neoplasias Ósseas/genética , Neoplasias Ósseas/secundário , Neoplasias da Mama/química , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Humanos , Imuno-Histoquímica , Hibridização In Situ , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos TestesRESUMO
Our group employs micro- and nano-X-ray fluorescence spectrometry (XRF) for the investigation of bone tissue. The manuscript presents the results of 3 various projects, in which spatial distribution of trace elements in bone samples was studied. The first study investigated the distribution of the elemental constituents of Mg-based implants at various stages of the degradation process in surrounding bone tissue with a focus on magnesium (Mg) and yttrium (Y). The analysis was performed in laboratory of Atominstitut using a special micro-XRF spectrometer for light element detection. The second study is devoted to the spatial distribution of Zn in high-grade sclerosing osteosarcoma mapped by confocal synchrotron radiation induced micro-XRF. Tumor zinc levels were compared with adjacent normal tissue. For discrimination between healthy and diseased bone quantitative backscattered electron imaging was used. The third experiment demonstrates the performance of synchrotron radiation induced nano-XRF with beam size of about 500â¯nm for bone tissue investigation. Special emphasis is set to advantages of micro- and nano-XRF in bone analysis as well as overcoming possible limitations.
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Osso e Ossos/química , Espectrometria por Raios X/métodos , Oligoelementos/análise , Zinco/análise , Animais , Neoplasias Ósseas/química , Humanos , Magnésio/análise , SíncrotronsRESUMO
In recent years, a novel small round cell sarcoma harboring EWSR1-NFATC2 translocation with immunomorphologic overlap with Ewing sarcoma (ES), myoepithelial tumors, and extraskeletal myxoid chondrosarcoma has emerged. There has not been a case series devoted to describing its detailed clinicopathologic and immunohistochemical characteristics. Six sarcomas harboring EWSR1-NFATC2 fusion transcripts by reverse transcription polymerase chain reaction and amplification of the fusion gene by fluorescence in situ hybridization were identified. The patients were 5 adult men and 1 adult woman. Three were primary bone tumors of the radius and 3 were primary soft tissue tumors. Most tumors showed monomorphic round to epithelioid cells in anastomosing cords and abundant myxohyaline to collagenous extracellular matrix. Two tumors had large areas of a solid, matrix-poor histomorphology. All tumors stained for CD99 and NKX2.2; while EMA, dot-like cytokeratin, and focal WT-1 and SMA were present in some tumors. All but 1 tumor showed poor histologic and radiologic responses to neoadjuvant ES-specific chemotherapy. Local or distant recurrences happened in 4 cases. EWSR1-NFATC2 sarcoma is a novel translocation-associated sarcoma. It presents as either a primary bone or soft tissue tumor, usually exhibits distinctive histopathologic features, and has predilection for long bones of adult men. It consistently shows recurrent fusion gene amplification readily detectable by EWSR1 breakapart fluorescence in situ hybridization, which serves as a diagnostic surrogate. It has potential for local and distant recurrence and histologic progression, and is resistant to Ewing sarcoma-specific chemotherapy.
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Biomarcadores Tumorais/genética , Neoplasias Ósseas/genética , Fusão Gênica , Proteínas de Fusão Oncogênica/genética , Rádio (Anatomia) , Sarcoma/genética , Neoplasias de Tecidos Moles/genética , Adulto , Idoso , Biomarcadores Tumorais/análise , Neoplasias Ósseas/química , Neoplasias Ósseas/patologia , Neoplasias Ósseas/terapia , Colúmbia Britânica , California , Feminino , Amplificação de Genes , Predisposição Genética para Doença , Proteína Homeobox Nkx-2.2 , Proteínas de Homeodomínio , Humanos , Hibridização in Situ Fluorescente , Metástase Linfática , Masculino , Michigan , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Proteínas Nucleares , Fenótipo , Rádio (Anatomia)/química , Rádio (Anatomia)/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sarcoma/química , Sarcoma/secundário , Sarcoma/terapia , Neoplasias de Tecidos Moles/química , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/terapia , Fatores de Transcrição , Resultado do TratamentoRESUMO
INTRODUCTION: Perivascular epithelioid cell (PEC) is a cell type constantly present in a group of tumours including angiomyolipoma (AML), clear-cell «sugar¼ tumour (CCST) of the lung and extrapulmonary sites, lymphangioleiomyomatosis (LAM), and clear-cell tumours of other anatomical sites. It has morphologic distinctive features: epithelioid appearance with a clear to granular cytoplasm, a round to oval, centrally located nucleus and an inconspicuous nucleolus. Immunohistochemically, PEC expresses myogenic and melanocytic markers. Eleven cases of primary bone PEComa presentation have been described since 2002. OBJECTIVE: To report a case of primary bone perivascular epithelioid cell tumour. CASE REPORT: 24 year-old male presented with pain. X-ray revealed an osteolytic lesion at right proximal tibia with soft tissue extension. Evaluation of slides identified a bony perivascular epithelioid cell tumour without immunohistochemical study confirmation. RESULTS: Patient was treated by surgical excision and adjuvant chemotherapy (epirubicin/cysplatin). After two years of follow-up the patient remains disease free. CONCLUSIONS: This is the first-case report in Latin America. Immunohistochemical stains were negative and we believe it may be due to non-described ethnic variations.
Assuntos
Neoplasias Ósseas/patologia , Neoplasias de Células Epitelioides Perivasculares/patologia , Tíbia , Neoplasias Ósseas/química , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/terapia , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Epirubicina/administração & dosagem , Humanos , Masculino , Neoplasias de Células Epitelioides Perivasculares/química , Neoplasias de Células Epitelioides Perivasculares/diagnóstico por imagem , Neoplasias de Células Epitelioides Perivasculares/terapia , Tíbia/diagnóstico por imagem , Tíbia/patologia , Tíbia/cirurgia , Adulto JovemRESUMO
BACKGROUND: Osteosarcoma is a malignant bone tumor with a high potential for lung metastasis, and the prognosis for patients with metastatic disease is very poor. The interaction between fibronectin (FN) and integrin αvß3 in soft-tissue sarcoma promotes cell migration, invasion, and lung metastasis. This study aimed to investigate the prognostic significance of FN and αvß3 in osteosarcoma. METHODS: Immunohistochemistry and western blotting were used to detect the expression of FN and αvß3 in 60 osteosarcoma specimens and in 30 osteochondroma specimens. Furthermore, correlations of FN and αvß3 with the clinicopathological features of osteosarcoma patients were analyzed using the χ2 test and Fisher's exact test. Disease-free survival and overall survival of osteosarcoma patients were assessed using the Kaplan-Meier method and Cox proportional hazards model. The predictive accuracy of the model was determined by the Harrell concordance index. RESULTS: FN (P < 0.05) and αvß3 (P < 0.05) were overexpressed in osteosarcoma specimens compared with osteochondroma specimens. High FN expression was associated with a poor response to chemotherapy (P = 0.001) and poor disease-free (P < 0.001) and overall (P < 0.001) survival. High expression of αvß3 was linked to an advanced surgical stage (P = 0.028), a poor response to chemotherapy (P = 0.002), and both poor disease-free survival (P < 0.001) and overall survival (P < 0.001). FN and αvß3 co-expression were associated with sex (P = 0.011), an advanced surgical stage (P = 0.013), and a poor response to chemotherapy (P = 0.002). Moreover, high expression of both proteins can serve as an independent prognostic value for reduced survival time in osteosarcoma patients. CONCLUSIONS: The results of this study suggest that FN and αvß3 expression is associated with an unfavorable clinical outcome of osteosarcoma, and these molecules may constitute attractive therapeutic targets for osteosarcoma treatment. To improve the survival of osteosarcoma patients, further investigations are required to clarify their prognostic values in a larger population.