RESUMEN
Epithelioid osteoblastoma, sometimes equated with aggressive osteoblastoma, is a variant of osteoblastoma that typically demonstrates more worrisome imaging and pathological features compared to conventional osteoblastoma. These more aggressive features can overlap with those seen in osteosarcoma, creating a diagnostic challenge for radiologists and pathologists. Recent identification of FOS and FOSB gene rearrangements in osteoid osteoma and osteoblastoma has allowed for greater diagnostic confidence following biopsy, but careful radiological-pathological correlation remains a key component for guiding appropriate management. Although the imaging features of conventional osteoblastoma have been previously described, there are limited examples in the literature of the imaging appearance of epithelioid osteoblastoma, and none with secondary aneurysmal bone cyst. In this case report, we detail the clinical, imaging, and histological characteristics of a proximal femoral epithelioid osteoblastoma which was pathologically confirmed by FOS and FOSB genetic testing. The initial imaging impression favored a malignancy, but when the biopsy results were correlated in a multidisciplinary fashion with the imaging, epithelioid osteoblastoma became the leading diagnosis which was subsequently genetically confirmed. This case emphasizes the value of multidisciplinary radiology-pathology correlation in routine practice.
Asunto(s)
Quistes Óseos Aneurismáticos , Neoplasias Óseas , Osteoblastoma , Osteoma Osteoide , Quistes Óseos Aneurismáticos/diagnóstico por imagen , Quistes Óseos Aneurismáticos/genética , Quistes Óseos Aneurismáticos/cirugía , Neoplasias Óseas/complicaciones , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/genética , Reordenamiento Génico , Humanos , Osteoblastoma/diagnóstico por imagen , Osteoblastoma/genética , Osteoblastoma/cirugía , Osteoma Osteoide/complicaciones , Osteoma Osteoide/diagnóstico por imagen , Osteoma Osteoide/genéticaRESUMEN
Bone tumours are difficult to diagnose and treat, as they are rare and over 60 different subtypes are recognised. The emergence of next-generation sequencing has partly elucidated the molecular mechanisms behind these tumours, including the group of bone forming tumours (osteoma, osteoid osteoma, osteoblastoma and osteosarcoma). Increased knowledge on the molecular mechanism could help to identify novel diagnostic markers and/or treatment options. Osteoid osteoma and osteoblastoma are bone forming tumours without malignant potential that have overlapping morphology. They were recently shown to carry FOS and-to a lesser extent-FOSB rearrangements suggesting that these tumours are closely related. The presence of these rearrangements could help discriminate these entities from other lesions with woven bone deposition. Osteosarcoma is a malignant bone forming tumour for which different histological subtypes are recognised. High-grade osteosarcoma is the prototype of a complex karyotype tumour, and extensive research exploring its molecular background has identified phenomena like chromothripsis and kataegis and some recurrent alterations. Due to lack of specificity, this has not led to a valuable novel diagnostic marker so far. Nevertheless, these studies have also pointed towards potential targetable drivers of which the therapeutic merit remains to be further explored.
Asunto(s)
Neoplasias Óseas/patología , Osteoblastoma/patología , Osteoma Osteoide/patología , Osteosarcoma/patología , Neoplasias Óseas/genética , Reordenamiento Génico , Genes p53 , Predisposición Genética a la Enfermedad , Humanos , Osteoblastoma/genética , Osteoma/genética , Osteoma/patología , Osteoma Osteoide/genética , Proteína de Retinoblastoma/genéticaRESUMEN
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.
Asunto(s)
Biomarcadores de Tumor/análisis , Neoplasias Óseas/química , Osteoblastoma/química , Osteoma Osteoide/química , Proteínas Proto-Oncogénicas c-fos/análisis , Adolescente , Adulto , Biomarcadores de Tumor/genética , Neoplasias Óseas/genética , Neoplasias Óseas/patología , Niño , Preescolar , Diagnóstico Diferencial , Inglaterra , Femenino , Reordenamiento Génico , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Osteoblastoma/genética , Osteoblastoma/patología , Osteoma Osteoide/genética , Osteoma Osteoide/patología , Valor Predictivo de las Pruebas , Proteínas Proto-Oncogénicas c-fos/genética , Suiza , Adulto JovenRESUMEN
Neurofibromatosis type 1 (NF1, OMIM 162200), caused by NF1 gene mutations, exhibits multi-system abnormalities, including skeletal deformities in humans. Osteocytes play critical roles in controlling bone modeling and remodeling. However, the role of neurofibromin, the protein product of the NF1 gene, in osteocytes is largely unknown. This study investigated the role of neurofibromin in osteocytes by disrupting Nf1 under the Dmp1-promoter. The conditional knockout (Nf1 cKO) mice displayed serum profile of a metabolic bone disorder with an osteomalacia-like bone phenotype. Serum FGF23 levels were 4 times increased in cKO mice compared with age-matched controls. In addition, calcium-phosphorus metabolism was significantly altered (calcium reduced; phosphorus reduced; parathyroid hormone [PTH] increased; 1,25(OH)2 D decreased). Bone histomorphometry showed dramatically increased osteoid parameters, including osteoid volume, surface, and thickness. Dynamic bone histomorphometry revealed reduced bone formation rate and mineral apposition rate in the cKO mice. TRAP staining showed a reduced osteoclast number. Micro-CT demonstrated thinner and porous cortical bones in the cKO mice, in which osteocyte dendrites were disorganized as assessed by electron microscopy. Interestingly, the cKO mice exhibited spontaneous fractures in long bones, as found in NF1 patients. Mechanical testing of femora revealed significantly reduced maximum force and stiffness. Immunohistochemistry showed significantly increased FGF23 protein in the cKO bones. Moreover, primary osteocytes from cKO femora showed about eightfold increase in FGF23 mRNA levels compared with control cells. The upregulation of FGF23 was specifically and significantly inhibited by PI3K inhibitor Ly294002, indicating upregulation of FGF23 through PI3K in Nf1-deficient osteocytes. Taken together, these results indicate that Nf1 deficiency in osteocytes dramatically increases FGF23 production and causes a mineralization defect (ie, hyperosteoidosis) via the alteration of calcium-phosphorus metabolism. This study demonstrates critical roles of neurofibromin in osteocytes for osteoid mineralization. © 2017 American Society for Bone and Mineral Research.
Asunto(s)
Neoplasias Óseas , Factores de Crecimiento de Fibroblastos/metabolismo , Neurofibromina 1/deficiencia , Osteocitos , Osteoma Osteoide , Osteomalacia , Animales , Neoplasias Óseas/genética , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Factor-23 de Crecimiento de Fibroblastos , Factores de Crecimiento de Fibroblastos/genética , Humanos , Ratones , Ratones Noqueados , Neurofibromatosis 1/genética , Neurofibromatosis 1/metabolismo , Neurofibromatosis 1/patología , Osteocitos/metabolismo , Osteocitos/patología , Osteoma Osteoide/genética , Osteoma Osteoide/metabolismo , Osteoma Osteoide/patología , Osteomalacia/genética , Osteomalacia/metabolismo , Osteomalacia/patologíaRESUMEN
OBJECTIVE: To assess 5-year treatment responses and TGFB1 gene abnormalities in five patients with ribbing disease. METHODS: PCR analysis and bidirectional sequencing of TGFß1 exons 1 through 7 were performed in all five patients. RESULTS: The five patients, four women and one man with a mean age of 34 years at symptom onset, shared the following features: severe diaphyseal pain predominating in the lower limbs with diaphyseal hyperostosis; increased radionuclide uptake at sites of pain and, in some cases at other cortical sites; asymmetric or asynchronous lesions; long symptom duration (5-18 years) despite a variety of treatments; and a delay of several years (2-15) between symptom onset and the diagnosis. Of our five patients, two had a heterozygous missense mutation in exon 2 of TGFß1 (c.466C>T, p.Arg156Cys, previously described in Camurati-Engelmann syndrome) and three had commonly found TGFß1 polymorphisms. Intravenous bisphosphonate therapy was used in all five patients but induced substantial improvements in a single patient. Of the three patients given bolus methylprednisolone therapy, two experienced a lasting response; the exception was one of the two women with a TGFß1 mutation. CONCLUSION: Considerable heterogeneity in the clinical presentations, genetic abnormalities, and treatment responses contribute to the diagnostic challenges raised by ribbing disease. Detailed genetic studies are needed.
Asunto(s)
Síndrome de Camurati-Engelmann/tratamiento farmacológico , Síndrome de Camurati-Engelmann/genética , Osteoma Osteoide/tratamiento farmacológico , Osteoma Osteoide/genética , Factor de Crecimiento Transformador beta1/genética , Adulto , Anciano , Síndrome de Camurati-Engelmann/diagnóstico , Difosfonatos/administración & dosificación , Femenino , Glucocorticoides/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Mutación Missense , Osteoma Osteoide/diagnósticoRESUMEN
Benign bone tumors frequently pose a diagnostic challenge for general surgical pathologists. Accurate pathologic diagnosis requires careful clinical and radiological correlation. The most significant recent advances in some benign bone tumors have occurred at the molecular and cytogenetic level. The detection of clonal chromosomal aberrations, various specific molecular genetic events, and the description of the bone cell signaling pathways in the field of osteoimmunology have provided a better understanding of the pathophysiology of certain tumors and an important aid in the diagnostic workup and differential diagnosis of some bone lesions demonstrating overlapping clinical and pathologic features. Future directions include prognostic and therapeutic applications of these findings. Newer less invasive therapeutic techniques and medical management have been developed for the treatment of certain benign bone tumors.
Asunto(s)
Neoplasias Óseas/diagnóstico , Patología Quirúrgica/métodos , Neoplasias Óseas/genética , Neoplasias Óseas/terapia , Huesos/diagnóstico por imagen , Huesos/patología , Condroblastoma/diagnóstico , Condroblastoma/genética , Condroma/diagnóstico , Condroma/genética , Aberraciones Cromosómicas , Femenino , Displasia Fibrosa Ósea/diagnóstico , Displasia Fibrosa Ósea/genética , Tumor Óseo de Células Gigantes/diagnóstico , Tumor Óseo de Células Gigantes/genética , Humanos , Masculino , Notocorda/patología , Osteoblastoma/diagnóstico , Osteoblastoma/genética , Osteocondroma/diagnóstico , Osteocondroma/genética , Osteoma Osteoide/diagnóstico , Osteoma Osteoide/genética , RadiografíaRESUMEN
Recent progress in skeletal molecular biology has led to the clarification of the transcriptional mechanisms of chondroblastic and osteoblastic lineage differentiation. Three master transcription factors-Sox9, Runx2, and Osterix-were shown to play an essential role in determining the skeletal progenitor cells' fate. The present study evaluates the expression of these factors in 4 types of benign bone tumors-chondromyxoid fibroma, chondroblastoma, osteoid osteoma, and osteoblastoma-using immunohistochemistry and tissue microarrays. Osteoid osteoma and osteoblastoma showed strong nuclear expression of Osterix and Runx2. In contrast, only a few chondroblastomas showed positive nuclear expression of Osterix. Strong nuclear expression of Sox9 was detected in all chondroblastomas, whereas nearly half of the osteoblastomas showed focal weak cytoplasmic expression of Sox9.
Asunto(s)
Neoplasias Óseas/genética , Cartílago/crecimiento & desarrollo , Redes Reguladoras de Genes , Neoplasias de Tejido Conjuntivo/genética , Osteogénesis/genética , Factores de Transcripción/genética , Adolescente , Adulto , Anciano , Neoplasias Óseas/patología , Cartílago/patología , Niño , Condroblastoma/genética , Condroblastoma/metabolismo , Condroblastoma/patología , Condroma/genética , Condroma/metabolismo , Condroma/patología , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Femenino , Fibroma/genética , Fibroma/metabolismo , Fibroma/patología , Regulación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de Tejido Conjuntivo/metabolismo , Neoplasias de Tejido Conjuntivo/patología , Osteoblastoma/genética , Osteoblastoma/metabolismo , Osteoblastoma/patología , Osteoma Osteoide/genética , Osteoma Osteoide/metabolismo , Osteoma Osteoide/patología , Factor de Transcripción SOX9/genética , Factor de Transcripción SOX9/metabolismo , Factor de Transcripción Sp7 , Células Madre/metabolismo , Células Madre/patología , Análisis de Matrices Tisulares , Factores de Transcripción/metabolismo , Adulto JovenRESUMEN
Familial occurrence of osteoid osteoma is an exceedingly rare event. This paper describes the second report of this event, where two siblings presented with this lesion in the same location, the proximal left femur. They both presented at 6 years of age, but 3 years apart.
Asunto(s)
Neoplasias Femorales/genética , Osteoma Osteoide/genética , Niño , Neoplasias Femorales/diagnóstico por imagen , Neoplasias Femorales/patología , Cuello Femoral , Humanos , Masculino , Osteoma Osteoide/diagnóstico por imagen , Osteoma Osteoide/patología , Tomografía Computarizada por Rayos XRESUMEN
Cytogenetic analysis was performed in two osteoid osteomas. In both, the modal chromosome number was 46. One of the cases presented a del(22)(q13.1) as the sole clonal chromosome alteration. The other had clonal monosomies of chromosomes 3, 6, 9, 17, 19, and 21, as well as a +del(22)(q13.1) was detected as a non-clonal chromosome alteration. There is only one osteoid osteoma reported so far showing clonal karyotypic alterations. The cytogenetic behavior of osteoid osteomas described here was different from that of the osteoid osteoma of the literature. Numerical alterations of chromosomes 3, 6, 9, 17, 19, 21 and 22 have been described in several neoplasias including bone tumors. The breakpoint of chromosome 22 involves a region where important genes for the regulation of the cell cycle have been mapped.
Asunto(s)
Neoplasias Óseas/genética , Aberraciones Cromosómicas , Cromosomas Humanos Par 22 , Osteoma Osteoide/genética , Niño , Rotura Cromosómica , Femenino , Humanos , Cariotipificación , MasculinoRESUMEN
We cytogenetically investigated six osteoid osteomas, one osteoblastoma and one aggressive osteoblastoma, and observed clonal structural changes in one osteoid osteoma and in the aggressive osteoblastoma. Clonal chromosome changes had not been reported previously in osteoid osteoma, whereas the only reported chromosome change in osteoblastoma was different from the one presented here.
Asunto(s)
Aberraciones Cromosómicas , Osteoblastoma/genética , Osteoma Osteoide/genética , Adolescente , Adulto , Preescolar , Femenino , Humanos , Cariotipificación , Masculino , Osteoblastoma/diagnóstico por imagen , Osteoblastoma/patología , Osteoma Osteoide/diagnóstico por imagen , Osteoma Osteoide/patología , RadiografíaRESUMEN
We report results of the first cytogenetic study of an osteoblastoma. Cells from the tumor were characterized by a three-way unbalanced translocation involving chromosomes 15, 17, and 20. As a consequence of the translocation, most of one chromosome 17 short arm appears to have been lost. This loss suggests the possibility that loss of 17p DNA sequences may be involved in early changes leading to neoplastic proliferation of osteoblasts.
Asunto(s)
Neoplasias Óseas/genética , Deleción Cromosómica , Cromosomas Humanos Par 17 , Osteoma Osteoide/genética , Translocación Genética , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/patología , Niño , Cromosomas Humanos Par 15 , Cromosomas Humanos Par 20 , Humanos , Cariotipificación , Masculino , Osteoma Osteoide/diagnóstico por imagen , Osteoma Osteoide/patología , Tomografía Computarizada por Rayos XRESUMEN
Osteoid osteomas occurred in siblings with a nearly simultaneous onset of symptoms, and with some unusual neoplastic characteristics. The combination of simultaneous occurrence and neoplastic change suggests that a viral or other infectious etiology is possible.