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De novo germline pathogenic variants (gPV) of the BReast CAncer 1 (BRCA1) gene are very rare. Only a few have been described up to date, usually in patients with a history of ovarian or breast cancer. Here, we report the first case of an incidental de novo BRCA1 germline pathogenic variant which was identified within the framework of the Plan France Médecine Génomique (PFMG) 2025 French national tumor sequencing program. The proband was a 29-year-old man diagnosed with metastatic osteosarcoma. Tumor whole exome sequencing identified a BRCA1 c.3756_3759del p.(Ser1253Argfs*10) pathogenic variant without loss-of-heterozygosity. A low genomic instability score and the absence of single base substitution signatures of homologous recombination deficiency suggested that the BRCA1 variant was not driver in the osteosarcoma tumorigenesis. Germline whole genome sequencing asserted the germline nature of this variant, with a 36% allele frequency, suggesting a mosaicism caused by a post-zygotic mutational event. The proband's family (parents and siblings) were not carriers of this variant confirming the de novo occurrence. Tumor sequencing programs like the French PFMG 2025 have been implemented worldwide and may help identify new gPV, including de novo variants.
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Chondroblastoma is a rare benign cartilaginous tumor mostly confined to the epiphyses and apophyses. Cases outside the epiphyseal region are exceedingly rare. Extramedullary chondroblastomas are exceptional; to our knowledge, only two cases qualified as "periosteal chondroblastoma" have been described in the literature. We report two cases of metaphyseal periosteal chondroblastoma both located on the inferior surface of the femoral neck. Both cases were paucicellular with an unusual dense sclerotic reaction. The diagnosis of chondroblastoma was supported by the expression of histone 3.3, K36M mutant in tumor cells.
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Neoplasias Óseas , Condroblastoma , Humanos , Condroblastoma/patología , Cuello Femoral/patología , Neoplasias Óseas/patología , Epífisis/patología , HistonasRESUMEN
Background-The purpose of this study was to investigate the bone resorption, as well as the vascular and immune microenvironment, of jaw osteosarcomas (JO) and to correlate these features with patient clinical outcomes. Methods-We studied 50 JO biopsy samples by immunohistochemical analysis of tissue microarrays (TMAs). We investigated the bone remodeling markers RANK/RANKL/OPG, the endothelial glycoprotein CD146, and biomarkers of the immune environment (CD163 and CD68 of macrophages, CD4+ and CD8+ of tumor-infiltrating lymphocytes (TILs), and an immune checkpoint PD-1/PD-L1). The biomarkers were analyzed for their influence on progression (recurrence and metastasis), overall survival (OS), and disease-free survival (DFS). Results-A strong and significant correlation has been found between CD163 staining and lower OS and DFS. The level of CD4+ and CD8+ staining was low and non-significantly associated with survival outcomes. High levels of RANK and RANKL were found in the tumor samples and correlated with lower DFS. Conclusion-Our findings suggest that CD163+ TAMs represent markers of poor prognosis in JO. Targeting TAMs could represent a valuable therapeutic strategy in JO.
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This review provides an overview of histopathology, clinical presentation, molecular pathways, and potential new systemic treatments of high-grade chondrosarcomas (CS), including grade 2−3 conventional, dedifferentiated, and mesenchymal CS. The diagnosis of CS combines radiological and histological data in conjunction with patient clinical presentations. Conventional CS is the most frequent subtype of CS (85%) and represents about 25% of primary bone tumors in adults; they can be categorized according to their bone location into central, peripheral, and periosteal chondrosarcomas. Central and peripheral CS differ at the molecular level with either IDH1/2 mutations or EXT1/2 mutations, respectively. CDKN2A/B deletions are also frequent in conventional CS, as well as COL2A1 mutations. Dedifferentiated CS develops when low-grade conventional CS transforms into a high-grade sarcoma and most frequently exhibits features of osteosarcoma, fibrosarcoma, or undifferentiated pleomorphic sarcoma. Their molecular characteristics are similar to conventional CS. Mesenchymal CS is a totally different pathological entity exhibiting recurrent translocations. Their clinical presentation and management are different too. The standard treatment of CSs is wide en-bloc resection. CS are relatively radiotherapy resistant; therefore, doses >60 Gy are needed in an attempt to achieve local control in unresectable tumors. Chemotherapy is possibly effective in mesenchymal chondrosarcoma and is of uncertain value in dedifferentiated chondrosarcoma. Due to resistance to standard anticancer agents, the prognosis is poor in patients with metastatic or unresectable chondrosarcomas. Recently, the refined characterization of the molecular profile, as well as the development of new treatments, allow new therapeutic options for these rare tumors. The efficiency of IDH1 inhibitors in other malignancies suggests that these inhibitors will be part of IDH1/2 mutated conventional CS management soon. Other treatment approaches, such as PIK3-AKT-mTOR inhibitors, cell cycle inhibitors, and epigenetic or immune modulators based on improving our understanding of CS molecular biology, are emerging.
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Neoplasias Óseas , Condrosarcoma , Osteosarcoma , Adulto , Humanos , Condrosarcoma/diagnóstico , Condrosarcoma/genética , Condrosarcoma/terapia , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/genética , Radiografía , Osteosarcoma/patología , BiologíaRESUMEN
Artificial intelligence (AI) is increasingly being studied in musculoskeletal oncology imaging. AI has been applied to both primary and secondary bone tumors and assessed for various predictive tasks that include detection, segmentation, classification, and prognosis. Still, in the field of clinical research, further efforts are needed to improve AI reproducibility and reach an acceptable level of evidence in musculoskeletal oncology. This review describes the basic principles of the most common AI techniques, including machine learning, deep learning and radiomics. Then, recent developments and current results of AI in the field of musculoskeletal oncology are presented. Finally, limitations and future perspectives of AI in this field are discussed.
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Inteligencia Artificial , Aprendizaje Automático , Humanos , Reproducibilidad de los Resultados , Oncología Médica , PronósticoRESUMEN
OBJECTIVES: Synovial sarcomas (SS) of the extremities are rare soft tissue sarcomas that are more common in young adults. We deciphered the imaging phenotype of SS with the aim to determine if imaging could provide an incremental value to currently known prognostic factors (PF)-age and histological grade-to predict long-term overall survival (OS). METHODS: This retrospective multicenter study included consecutive pediatric and adult patients with synovial sarcomas of the extremities from December 2002 to August 2020. Inclusion criteria were (i) a follow-up greater than 5 years and (ii) available pre-therapeutic MRI. A subset analysis included MRI and CT-scan. Clinical, pathological, and imaging variables were collected in all patients. The primary endpoint was to evaluate the association of these variables with OS using univariate and multivariate Cox regressions. RESULTS: Out of 428 patients screened for eligibility, 98 patients (mean age: 37.1 ± 15.2 years) were included (MRI: n = 98/98, CT scan: n = 34/98; 35%). The median OS was 75.25 months (IQR = 55.50-109.12) and thirty-six patients (n = 36/98;37%) died during follow-up. The recurrence rate was 12.2% (n =12/98). SS lesions were mostly grade 2 (57/98; 58%). On MRI, SS had a mean long-axis diameter of 67.5 ± 38.3 mm. On CT scan, 44% (15/34) were calcified. Grade (hazard ratio [HR] = 2.71; 95%CI = 1.30-5.66; p = 0.008), size of the lesions evaluated on MRI (HR = 1.02; 95% CI = 1.01-1.03; p < 0.001), and calcifications on CT scan (HR = 0.10; 95% CI = 0.02-0.50; p = 0.005) were independent PF of OS. CONCLUSIONS: This study demonstrated that imaging biomarkers can be used to predict long-term outcome in patients with SS. Strikingly, the presence of calcifications on CT scan is associated with favorable outcome and provides an incremental value over existing PF such as age, grade, and size. KEY POINTS: ⢠Beyond its diagnostic value, MRI is a pre-operative prognostic tool in synovial sarcomas of the extremities since the size of the lesion is an important prognostic factor. ⢠Calcifications on CT scans are independently and significantly associated with prolonged overall survival.
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Sarcoma Sinovial , Sarcoma , Humanos , Pronóstico , Sarcoma Sinovial/diagnóstico por imagen , Sarcoma/patología , Extremidades/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Estudios RetrospectivosRESUMEN
BACKGROUND: Separating benign from malignant soft-tissue masses often requires a biopsy. The objective of this study was to assess whether shear-wave elastography (SWE) helped to separate benign from malignant soft-tissue masses. METHODS: In 2015-2016, we prospectively included patients with soft-tissue masses deemed by our multidisciplinary sarcoma board to require a diagnostic biopsy. All patients underwent ultrasonography (US) followed by SWE to measure elasticity. We compared benign and malignant tumors, overall and after separating tumors with vs. without a fatty component. The biopsy findings, and surgical-specimen histology when available, served as the reference standard. RESULTS: We included 136 patients, 99 with non-fatty and 37 with fatty soft-tissue masses. Mean elasticity and tumor-to-fat elasticity ratio (T/F) values were significantly lower for the benign than the malignant soft-tissue masses in the overall cohort (30.9 vs. 50.0 kilopascals (kPa), P = 0.03; and 2.55 vs. 4.30, P = 0.046) and in the non-fatty subgroup (37.8 ± 31.9 vs. 58.9 ± 39.1 kPa, P = 0.049 and 2.89 ± 5.25 vs. 5.07 ± 5.41, P = 0.046). Data for fatty tumors were non relevant due to lack of conclusive results. By receiver operating characteristics curve analysis, a T/F cutoff of 3.5 had 46% sensitivity and 84% specificity for separating benign and malignant soft-tissue masses. CONCLUSIONS: SWE had good specificity and poor sensitivity for separating benign from malignant soft-tissue masses.
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Neoplasias de la Mama , Diagnóstico por Imagen de Elasticidad , Neoplasias de los Tejidos Blandos , Femenino , Humanos , Diagnóstico por Imagen de Elasticidad/métodos , Ultrasonografía Mamaria/métodos , Sensibilidad y Especificidad , Neoplasias de los Tejidos Blandos/diagnóstico por imagen , Ultrasonografía , Diagnóstico Diferencial , Reproducibilidad de los ResultadosRESUMEN
The International Society for the Study of Vascular Anomalies (ISSVA) has defined four vascular lesions in the central nervous system (CNS): arteriovenous malformations, cavernous angiomas (also known as cerebral cavernous malformations), venous malformations, and telangiectasias. From a retrospective central radiological and histopathological review of 202 CNS vascular lesions, we identified three cases of unclassified vascular lesions. Interestingly, they shared the same radiological and histopathological features evoking the cavernous subtype of angioleiomyomas described in the soft tissue. We grouped them together with four additional similar cases from our clinicopathological network and performed combined molecular analyses. In addition, cases were compared with a cohort of 5 soft tissue angioleiomyomas. Three out 6 CNS lesions presented the same p.Gly41Cys GJA4 mutation recently reported in hepatic hemangiomas and cutaneous venous malformations and found in 4/5 soft tissue angioleiomyomas of our cohort with available data. Most DNA methylation profiles were not classifiable using the CNS brain tumor (version 12.5), and sarcoma (version 12.2) classifiers. However, using unsupervised t-SNE analysis and hierarchical clustering analysis, 5 of the 6 lesions grouped together and formed a distinct epigenetic group, separated from the clusters of soft tissue angioleiomyomas, other vascular tumors, inflammatory myofibroblastic tumors and meningiomas. Our extensive literature review identified several cases similar to these lesions, with a wide variety of denominations. Based on radiological and histomolecular findings, we suggest the new terminology of "dural angioleiomyomas" (DALM) to designate these lesions characterized by a distinct DNA methylation pattern and frequent GJA4 mutations.
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Angiomioma , Conexinas , Hemangioma , Angiomioma/genética , Conexinas/genética , Metilación de ADN , Hemangioma/genética , Humanos , Mutación , Estudios Retrospectivos , Proteína alfa-4 de Unión ComunicanteRESUMEN
Breast carcinomas (BC) with osteoclast-like giant cells (OGC) are rare. Despite their distinct stromal features, their molecular characteristics remain unknown. Here, we report comprehensive clinico-pathological and molecular findings for 27 patients diagnosed with BC-OGC at Institut Curie between 2000 and 2021. Seventeen (63%) cases were invasive carcinomas of no special type (IC NST) with OGC (OGC-IC NST), four (15%) were mixed or multifocal cases with and without OGC (OGC-Mixed), and six (22%) were metaplastic carcinomas with OGC (OGC-MC). All OGC-IC NST and OGC-Mixed cases were ER+ HER2- tumors (most being luminal A based on transcriptomic subtyping, when available), while all OGC-MC were triple-negative. The median age at diagnosis was 46, 45 and 62 years for OGC-IC NST, OGC-Mixed and OGC-MC, respectively. Three patients developed distant metastases (one OGC-IC NST, two OGC-Mixed), one of whom died of metastatic disease (OGC-Mixed), and one other patient died of locally advanced disease (OGC-MC). Histopathological evaluation comparing 13 OGC-IC NST and 19 control IC NST without OGC confirmed that OGC-IC NST showed significantly higher density of vessels (by CD34 immunohistochemistry (IHC)), iron deposits (Perls stain), and CD68 and CD163-positive cell infiltrates. Genomic findings for nine OGC-IC NST and four OGC-MC were consistent with the underlying histologic subtype, including activating alterations of the PI3K/AKT/mTOR pathway in 7/13 cases. Using RNA-seq data, differential gene expression analysis between OGC-IC NST (n = 7) and control IC NST without OGC (n = 7) revealed significant overexpression of TNFSF11 (RANK-L), TNFRSF11A (RANK), CSF1 (M-CSF), CSF1R, and genes encoding osteoclastic enzymes (MMP9, ACP5, CTSK, CTSB) in OGC-IC NST, while OPG (osteoprotegerin) was underexpressed. We also confirmed for the first time RANK-L expression in BC with OGC by IHC (seen in 15 out of 16 cases, and only in 2 of 16 controls without OGC). These findings could offer a rationale for further investigating RANK-L as a therapeutic target in BC with OGC.
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Neoplasias de la Mama , Carcinoma , Ligando RANK , Femenino , Humanos , Neoplasias de la Mama/patología , Carcinoma/patología , Células Gigantes/patología , Hierro , Factor Estimulante de Colonias de Macrófagos , Metaloproteinasa 9 de la Matriz , Osteoclastos/patología , Osteoprotegerina , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Serina-Treonina Quinasas TOR , Ligando RANK/genéticaRESUMEN
Giant cell tumors of bone (GCTs) are rare mesenchymal tumors classified as intermediate in the WHO 2020 classification, i.e. neither completely benign nor definitely malignant, due to recurrence (frequent) and pulmonary metastases (rare). They involve the end of long bones as well as the axial bones of mature skeletons. They are made of mononuclear stromal tumor cells of (pre-) osteoblastic phenotype, mononuclear cells of the monocyte-macrophage lineage and osteoclast-like multinuclear giant cells responsible for tumor osteolysis. In 95% of cases, the stromal cells have a specific mutation in the H3F3A gene which encodes histone H3.3. The mutated H3.3 G34W protein (90% of cases) can be easily detected by immunohistochemistry, even on small samples. Many tumors or bone pseudotumors contain osteoclast-like giant cells, cells of the bone microenvironment, and should not be confused with GCT: mainly brown tumor of hyperparathyroidism, aneurysmal bone cyst, chondroblastoma, non-ossifying fibroma and central giant cell granuloma.
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Neoplasias Óseas , Condroblastoma , Tumor Óseo de Células Gigantes , Neoplasias Óseas/patología , Tumor Óseo de Células Gigantes/genética , Tumor Óseo de Células Gigantes/patología , Histonas/genética , Histonas/metabolismo , Humanos , Inmunohistoquímica , Microambiente TumoralRESUMEN
BACKGROUND: The management of local sarcoma recurrence about the knee (at the distal femur or proximal tibia) is challenging. The objective of this study was to describe the locations of local sarcoma recurrences about knee megaprostheses, the treatments used for each type of recurrence, and the outcomes according to the treatment used. HYPOTHESIS: The strategy for treating a local sarcoma recurrence about the knee must be based on the topography of tumour involvement. MATERIALS AND METHODS: We included 13 patients who had local sarcoma recurrence about a knee megaprosthesis and were followed up for at least 2 years. The diagnosis was osteosarcoma in 10 patients and chondrosarcoma in 3 patients. The distal femur was involved in 11 patients and the proximal tibia in 2 patients. We classified the patients into two groups based on whether the tumour involved important structures or was at a distance within the soft tissues. RESULTS: The recurrence was a nodule at a distance of important structures in 8 (57%) patients, in whom the mean time to recurrence was 15 months (range, 2-34 months). The remaining 5 (38.5%) patients had involvement of important structures in the popliteal fossa and a mean time to recurrence of 42 months (range, 16-80 months). Surgery was performed in 10 patients; the other 3 patients received palliative care due to rapid metastatic dissemination. Of the 6 patients who had surgery for a recurrence at a distance from important structures, 5 (83.3%) underwent isolated tumour resection with the goal of salvaging the limb and 1 (16.7%) underwent transfemoral amputation. Transfemoral amputation was performed in all 3 patients who had surgery for popliteal recurrences. Lung metastases were detected in 10 (77%) patients, 2 at the time of initial sarcoma diagnosis and 8 at the time of the local recurrence. At last follow-up, 5 patients were alive, including 2 (33.3%) of the 6 patients with recurrences at a distance from important structures and all 3 patients with popliteal recurrences. Of the 5 survivors at last follow-up, 2 had metastases. CONCLUSION: In patients with local recurrence of knee sarcoma, three presentations can be distinguished. When the local recurrence coincides with distant recurrence, failure to control the disease is likely and the local treatment should be designed as a component of palliative care. When no metastases are detected but the local recurrence is in contact with important structures, amputation is advisable at present given the complexity of limb-salvage surgery and high risk of further local recurrence. Finally, when no metastases are detected and the local recurrence is at a distance from important structures, limb-salvage surgery deserves consideration. LEVEL OF EVIDENCE: IV, retrospective observational study.
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Neoplasias Óseas , Osteosarcoma , Sarcoma , Neoplasias de los Tejidos Blandos , Neoplasias Óseas/cirugía , Humanos , Recuperación del Miembro , Osteosarcoma/cirugía , Recurrencia , Estudios Retrospectivos , Sarcoma/cirugía , Neoplasias de los Tejidos Blandos/patología , Neoplasias de los Tejidos Blandos/cirugía , Resultado del TratamientoRESUMEN
The Sphingosine kinase-1/Sphingosine 1-Phosphate (SphK1/S1P) signaling pathway is overexpressed in various cancers, and is instrumental for the adaptation to hypoxia in a number of solid tumor models, but no data are available in osteosarcoma. Here we report that SphK1 and the S1P1 receptor are involved in HIF-1α accumulation in hypoxic osteosarcoma cells. FTY720 (Fingolimod), which targets SphK1 and S1P1, prevented HIF-1α accumulation, and also inhibited cell proliferation in both normoxia and hypoxia unlike conventional chemotherapy. In human biopsies, a significant increase of SphK1 activity was observed in cancer compared with normal bones. In all sets of TMA samples (130 cases of osteosarcoma), immunohistochemical analysis showed the hypoxic marker GLUT-1, SphK1 and S1P1 were expressed in tumors. SphK1 correlated with the GLUT-1 suggesting that SphK1 is overexpressed and correlates with intratumoral hypoxia. No correlation was found between GLUT-1 or SphK1 and response to chemotherapy, but a statistical difference was found with increased S1P1 expression in patients with poor response in long bone osteosarcomas. Importantly, multivariate analyses showed that GLUT-1 was associated with an increased risk of death in flat bone, whereas SphK1 and S1P1 were associated with an increased risk of death in long bones.
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Bone tissue can be involved by primitive or metastatic tumors and requires a specific processing both at the department of pathology and during multidisciplinary meetings. The development of fine-needle percutaneous biopsies and of molecular techniques in bone tumor pathology requires a specific management. Moreover, decalcification of samples is crucial but can be deleterious if not controlled or not appropriate. The aim of this review is to provide recommendations for management and decalcification of bone tumor samples.
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Neoplasias Óseas , Neoplasias Óseas/secundario , Neoplasias Óseas/terapia , Huesos , Técnica de Descalcificación/métodos , Humanos , InmunohistoquímicaRESUMEN
Erdheim-Chester disease (EC) is a rare disease that is included in Group L in the 2016 revised classification of Langheransian histiocytoses. This disease may be clinically asymptomatic or manifest as a multi-systemic and life-threatening condition. All organs can be affected but typically there is bone involvement, retroperitoneal fibrosis, pituitary involvement, involvement of large vessels, lung, pleura or central nervous system. We are reporting a 70-year-old patient who, as of 2014, had a pelvic mass with retroperitoneal fibrosis and large vessel vasculitis without a definite diagnosis. Histological and molecular examination of the surgical specimen of the pelvic mass with the discovery of the BRAF V600E mutation provided new elements for the definitive diagnosis of Erdheim-Chester disease. We will describe the clinical, histological and molecular features to be known in EC disease.
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Enfermedad de Erdheim-Chester , Fibrosis Retroperitoneal , Anciano , Sistema Nervioso Central/patología , Enfermedad de Erdheim-Chester/diagnóstico , Enfermedad de Erdheim-Chester/genética , Enfermedad de Erdheim-Chester/patología , Humanos , Enfermedades Raras/patología , Fibrosis Retroperitoneal/patologíaRESUMEN
The benefit of chemotherapy (CT) in rare bone sarcomas is not documented in prospective studies. Our retrospective study from the French sarcoma network for bone tumors ResOs was performed in adult patients (pts) from 1976 to 2014, with histologically verified diagnosis of leiomyosarcomas (LMS), undifferentiated pleomorphic sarcoma (UPS) or radiation-associated sarcomas of bone. The median follow-up was 4.7 years (95% CI: 3.7-6.5). Clinical features, treatment modalities and outcomes were recorded and analyzed from 145 pts (median age 53 years [range 20-87]). Site of disease was extremities (66%) or axial skeleton (34%), 111 (77%) presented with localized and potentially resectable disease. The most common histological subtypes were UPS (58%) and LMS (33%); 58% were high-grade tumors. Surgery was performed in 127 pts. In the 111 localized pts, 28 pts (25%) underwent upfront surgery or exclusive radiotherapy (RT; >50 Gy) without CT, whereas 83 pts (75%) received either neoadjuvant (n = 26) or adjuvant CT (n = 13) or both (n = 44). Neoadjuvant and adjuvant CT was mostly doxorubicin-based (95%/86%) and cisplatin-based (67%/63%). R0 resection was achieved in 59 pts, and a good histological response in 15 patients (25%). Adjuvant RT was performed in 24 (22%) pts. For the whole cohort (n = 145), the 5-year overall survival (OS) rate was 53% [42; 62]. In univariate analysis, age ≤ 60 was associated with a longer disease-free survival (DFS) (P = .0436). Neoadjuvant and adjuvant CT tended to be associated with better DFS (P = .056) with no significant impact on OS in this retrospective series.
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Neoplasias Óseas/terapia , Sarcoma/terapia , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/mortalidad , Quimioterapia Adyuvante , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Pronóstico , Estudios Retrospectivos , Sarcoma/mortalidad , Adulto JovenRESUMEN
FET:CREB fusions have been described in a variety of tumors from various phenotypes. Recently, these fusion transcripts were reported in intracranial tumors, variably named intracranial mesenchymal myxoid tumors or angiomatoid fibrous histiocytomas. Controversy remains concerning the terminology for these tumors. Here, we report 11 cases of central nervous system mesenchymal tumors with proven FET:CREB fusion. Most DNA methylation profiles were not classifiable using the Heidelberg Brain Tumor or Sarcoma Classifier (v11b4/v12.2). However, by using unsupervised t-SNE and hierarchical clustering analyses, six of the cases constituted a distinct cluster. The remaining four tumors showed no obvious relation to any of the other referenced classes but were close to the clusters of extra-CNS angiomatoid fibrous histiocytomas (n = 1), clear cell sarcomas (n = 1), or solitary fibrous tumors (n = 2). Our findings confirm that intracranial FET:CREB-fused tumors do not represent a single molecular tumor entity, although most samples clustered close to each other, indicating the existence of a distinct epigenetic group that could potentially be partially masked by the low number of cases included. Further analyses are needed to characterize intracranial FET:CREB fused-defined tumors in more detail.
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Neoplasias Encefálicas , Histiocitoma Fibroso Maligno , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Epigénesis Genética , Fusión Génica , Histiocitoma Fibroso Maligno/genética , Humanos , Proteína EWS de Unión a ARN/genéticaRESUMEN
BACKGROUND: Surgical complications are frequent with giant cell tumor of bone; recurrence is the best known and most widely studies; other causes of failure have been less well investigated. We therefore performed a retrospective study to identify and assess the main reasons for surgical revision. HYPOTHESIS: Recurrence is the main cause of surgical revision in giant cell tumor of bone, but other complications, such as mechanical issues or infection, are underestimated. PATIENTS AND METHODS: A single-center retrospective study included 192 patients (included from 2000 to 2016) undergoing first giant cell tumor of bone surgery in a bone tumor reference center. Surgery consisted in curettage for 152 patients (79%) and resection for 40 (21%). The 3 main reconstruction techniques were filling (136 patients; 71%), prosthesis (18 patients; 9%), and fusion (14 patients: 7%). Filling used cement in 9 cases (7%) and bone graft in 127 (93%). Cumulative incidence functions were calculated. RESULTS: There were 171 revision procedures in 92 patients: 43 for mechanical reasons, 30 for infection, 86 for tumor recurrence, 12 for other causes. Cumulative incidence of revision at 10years was 36% (95% CI: 27-44) for recurrence, 26% (95% CI: 17-36) for mechanical causes, and 13% (95% CI: 9-19) for infection, for overall cumulative incidence of revision of 61% (95% CI: 50-69). DISCUSSION: Risk of all-cause surgical revision in giant cell tumor of bone was 61% at 10years, with recurrence accounting for only half of cases. LEVEL OF EVIDENCE: IV.
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Neoplasias Óseas , Tumor Óseo de Células Gigantes , Neoplasias Óseas/cirugía , Legrado/métodos , Tumor Óseo de Células Gigantes/cirugía , Humanos , Recurrencia Local de Neoplasia/cirugía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
People suffering from extreme obesity may be exposed to delayed diagnosis and treatment of cancer. A 37-year-old woman (weight = 245 kg, body mass index (BMI) = 79 kg/m2), presented a sepsis associated with nonspecific abdominal pain for 4 months. After several unsuccessful attempts due to her weight and a large waist circumference, abdominal CT scan was finally successfully performed and showed a large retroperitoneal mass. An ultrasound-guided core needle biopsy was performed and was in favor of a liposarcoma. Surgery was performed to remove the entire tumor of an estimated weight of 98 kg, a giant retroperitoneal dedifferentiated liposarcoma. This case highlights the difficulties to screen, diagnose, and manage cancers encountered in patients suffering from massive obesity.
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Liposarcoma , Neoplasias Retroperitoneales , Adulto , Femenino , Humanos , Liposarcoma/diagnóstico , Liposarcoma/cirugía , Obesidad/complicaciones , Neoplasias Retroperitoneales/diagnóstico , Neoplasias Retroperitoneales/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
Nodular fasciitis, primary aneurysmal bone cyst, myositis ossificans, and their related lesions are benign tumors that share common histological features and a chromosomal rearrangement involving the ubiquitin-specific peptidase 6 (USP6) gene. The identification of an increasing number of new partners implicated in USP6 rearrangements demonstrates a complex tumorogenesis of this tumor spectrum. In this study on a series of 77 tumors (28 nodular fasciitis, 42 aneurysmal bone cysts, and 7 myositis ossificans) from the database of the French Sarcoma Group, we describe 7 new partners of the USP6 gene. For this purpose, rearrangements were first researched by multiplexed RT-qPCRs in the entire population. A targeted RNA sequencing was then used on samples selected according to a high USP6-transcription level expression estimated by RT-qPCR. Thanks to this multistep approach, besides the common USP6 fusions observed, we detected novel USP6 partners: PDLIM7 and MYL12A in nodular fasciitis and TPM4, DDX17, GTF2I, KLF3, and MEF2A in aneurysmal bone cysts. In order to try to bring to light the role played by the recently identified USP6 partners in this lesional spectrum, their functions are discussed. Taking into account that a traumatic participation has long been mentioned in the histogenesis of most of these lesions and because of their morphological resemblance to organizing granulation reparative tissue or callus, a focus is placed on their relationship with tissue remodeling and, to a lesser extent, with bone metabolism.