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Objective: To investigate the clinical, imaging, histological, and molecular features and the differential diagnosis of radiation-associated sarcomas of bone and soft tissue. Methods: Forty-six cases of radiation-associated sarcomas of the bone and soft tissue in Beijing Jishuitan Hospital from January 2010 to January 2022 were retrospectively analyzed; and the imaging, histological features and immunophenotype were examined. Results: There were 33 females and 13 males, aged from 18 to 74 years, with a mean of 52 years. The most common site of radiation-associated sarcomas were the limbs and spine (15 cases), followed by the chest (9 cases). The primary diseases included epithelial tumors (15 breast cancer, 6 cervical cancer, and 5 bowel cancer), hematolymphoid tumors, bone and soft tissue tumors and infectious lesions. The latent period of radiation-associated sarcomas ranged from 2-22 years, with an average of 11.6 years. Histopathologically, the morphology was divergent from the primary tumor. The most common malignant tumor type was undifferentiated sarcoma (22 cases), followed by osteosarcoma (16 cases). The immunophenotype of radiation-related sarcoma was almost the same as the corresponding soft tissue sarcoma. Conclusions: Radiation-induced sarcoma has a wide range of primary tumor types and its imaging, morphology and immunohistochemical features are similar to those of the primary sarcoma of bone and soft tissue. Clinical correlation is often recommended for the differential diagnosis.
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Neoplasias Óseas , Osteosarcoma , Sarcoma , Neoplasias de los Tejidos Blandos , Masculino , Femenino , Humanos , Estudios Retrospectivos , Sarcoma/patología , Osteosarcoma/diagnóstico por imagen , Neoplasias de los Tejidos Blandos/patología , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/patologíaAsunto(s)
Melanoma , Sarcoma de Células Claras , Neoplasias Cutáneas , Neoplasias de los Tejidos Blandos , Humanos , Sarcoma de Células Claras/diagnóstico , Sarcoma de Células Claras/patología , Melanoma/diagnóstico , Melanoma/patología , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patología , Errores Diagnósticos , Melanoma Cutáneo MalignoRESUMEN
Objective: To investigate the distribution and characteristics of gene mutations in osteosarcoma, and to analyze the frequency and types of detectable mutations, and to identify potential targets for individualized treatment of osteosarcoma. Methods: The fresh tissue or paraffin-embedded tissue samples of 64 cases of osteosarcoma that were surgically resected or biopsied and then subject to next generation sequencing, were collected from Beijing Jishuitan Hospital, China from November 2018 to December 2021. The tumor DNA was extracted to detect the somatic and germline mutations using targeted sequencing technology. Results: Among the 64 patients, 41 were males and 23 were females. The patient age ranged from 6 to 65 years with a median age of 17 years, including 36 children (under 18 years old) and 28 adults. There were 52 cases of conventional osteosarcoma, 3 cases of telangiectatic osteosarcoma, 7 cases of secondary osteosarcoma, and 2 cases of parosteosarcoma. The detection rate of gene mutations was overall 84.4% (54/64). There were 324 variations in 180 mutated genes, including 125 genes with copy number variations, 109 single nucleotide variants, 83 insertions or deletions, and 7 gene fusions. The most common mutated genes were TP53, VEGFA, CCND3, ATRX, MYC, RB1, PTEN, GLI1, CDK4 and PTPRD. Among them, TP53 had the highest mutation rate (21/64, 32.8%), single nucleotide variant was the main mutation type (14/23, 60.9%), and 2 cases carried the TP53 germline mutation. VEGFA and CCND3 showed copy number amplification simultaneously in 7 cases. Conclusions: The high-frequency mutation of TP53 suggests that it plays an important role in the pathogenesis and development of osteosarcoma. VEGFA, CCND3 and ATRX are mutated genes in osteosarcoma and worthy of further studies. Combination of pathologic diagnosis and next generation sequencing with clinical practice can guide individualized treatment for patients with refractory, recurrent and metastatic osteosarcoma.
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Neoplasias Óseas , Osteosarcoma , Adulto , Masculino , Niño , Femenino , Humanos , Adolescente , Adulto Joven , Persona de Mediana Edad , Anciano , Variaciones en el Número de Copia de ADN , Osteosarcoma/genética , Osteosarcoma/patología , Mutación , ADN de Neoplasias , Secuenciación de Nucleótidos de Alto Rendimiento , Neoplasias Óseas/genética , Neoplasias Óseas/patología , NucleótidosRESUMEN
Objective: To investigate the clinicopathological features, diagnosis and differential diagnosis of pediatric myofibroma/myofibromatosis of the soft tissue and bone. Methods: All cases of pediatric myoï¬broma/myoï¬bromatosis of the soft tissue and bone diagnosed between January 2011 and December 2018 were retrieved from the surgical pathology records in the Department of Pathology, Beijing Jishuitan Hospital, Beijing, China. Clinical and radiological data were collected. H&E and immunohistochemistry were used to examine histological and immunophenotypic features and to make the diagnosis and differential diagnosis. The relevant literature was also reviewed. Results: Twenty-eight cases of pediatric myofibroma/myofibromatosis of the soft tissue and bone were respectively collected. The patients' ages ranged from 2 months to 14 years, with a mean age of 7 years. There were 7 females and 21 males. There were 12 cases located in soft tissue, including the finger (n=9), upper arm (n=1) and foot (n=2). There were 14 cases located in the bone of limb, including the femur (n=8), tibia (n=4), clavicle (n=2), fibula (n=2) and radius (n=1). There were 2 cases of myofibromatosis involving multiple bones. Radiology showed lytic lesions in the bone. The proliferation of spindle-shaped myofibroblasts arranged in fascicles with indistinct eosinophilic cytoplasm and bland nuclei, with no pleomorphism and cytological atypia. The characteristic histologic structure was the biphasic nodular growth pattern with cellular and paucicellular regions. The tumors might arrange in a hemangiopericytoma-like pattern. The stroma varied between dense fibrosis and myxoid changes. The reactive new bone formation and inflammatory cell infiltration also existed. Immunohistochemical study showed that the SMA was positive. The surgical resections were performed. One of the patients had tumor recurrence as a result of 11-month follow-up. Conclusions: The pediatric myoï¬broma/myoï¬bromatosis of the soft tissue and bone is a very rare benign tumor and has a good prognosis. It has a characteristic morphology and its differential diagnosis from other spindle cell tumors could be made with the immunohistochemical analysis.
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Leiomioma , Miofibroma , Miofibromatosis , Niño , Femenino , Humanos , Lactante , Masculino , Huesos/patología , Diagnóstico Diferencial , Miofibroma/diagnóstico , Miofibromatosis/diagnóstico , Preescolar , AdolescenteRESUMEN
Objective: To investigate the correlation between the joint function and the histologic grading after total knee arthroplasty, to aid in the early diagnosis and prognostication of arthrofibrosis. Methods: A total of 29 patients including 22 females and 7 males were enrolled retrospectively from October 2015 to October 2020. These patients had a mean age of 63 years (range 41 to 79 years) and underwent total knee revision in Jishuitan Hospital due to joint contraction or loss of range of motion. Histologic assessment was carried out by utilizing immunohistochemistry (IHC) and the Masson staining to evaluate the fibrosis and inflammation of the samples. Results: By light microscopy, early stage arthrofibrosis showed massive proliferation of myofibroblasts and fibroblasts with SMA expression by IHC. In late stage arthrofibrosis, hyaline degeneration occured with extensive hyperplasia of fibrosis-related tissue. The arthrofibrosis samples appeared blue with Masson staining. Lymphocytes showed perivascular distribution. The arthrofibrosis tissue was mostly grade 3 (26 samples) in histologic assessment, moderate grade (25 samples) in ALVAL score, and grade 1 (23 samples) in lymphocyte grading. Fibrosis grading showed an overwhelming correlation with range of motion (ROM) of the joint. The ALVAL score was highly correlated with the WOMAC score. There was also a direct correlation between inflammatory cell infiltration and pain. The fibrosis grading joint with ALVAL score showed a good predictive value of joint function after joint replacement surgery. Conclusions: The histologic assessment score is closely correlated to the joint function with predictive values for the prognosis after joint replacement surgery.
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Articulación de la Rodilla , Humanos , Adulto , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Articulación de la Rodilla/cirugía , FibrosisRESUMEN
Objective: To investigate the subtypes of H3F3A DNA mutation in H3.3 immunohistochemistry (IHC) negative giant cell tumors of bone (GCTB). Methods: IHC expression of G34W mutated protein was evaluated in 181 cases GCTB. In H3.3 IHC negative cases, Sanger DNA sequencing analysis was used to detect the subtypes H3F3A mutations. Results: Overall, 164 (90.61%) cases of GCTB showed nuclear expression of H3.3, and 17 cases were negative. These 17 H3.3 negative cases were subjected to Sanger DNA sequencing analysis; results showed that eight presented rare mutation subtypes occurring at glycine 34 to leucine (G34L, 3/181, 1.66%), glycine 34 to valine (G34V, 3/181, 1.66%) and glycine 34 to arginine (G34R, 2/181, 1.10%), and the other nine cases were wild type (glycine 34, 9/181, 4.97%). Sanger DNA sequencing analysis confirmed the absence of G34W mutation in the H3.3 negative cases. Combining IHC and DNA sequencing analysis increased the detection rate of H3F3A mutation in the GCTB to 95.03%. Conclusions: H3.3 IHC could detect H3F3A G34W mutation in GCTB, but not for other rare mutation and wild types loci.
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Neoplasias Óseas , Tumor Óseo de Células Gigantes , Neoplasias Óseas/genética , Tumor Óseo de Células Gigantes/diagnóstico , Tumor Óseo de Células Gigantes/genética , Histonas/genética , Humanos , Inmunohistoquímica , Mutación , Análisis de Secuencia de ADNAsunto(s)
Neoplasias Óseas , Condroblastoma , Biomarcadores , Condroblastoma/diagnóstico , Condroblastoma/genética , Histonas/genética , Humanos , MutaciónAsunto(s)
Conservadores de la Densidad Ósea , Neoplasias Óseas , Tumor Óseo de Células Gigantes , Conservadores de la Densidad Ósea/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Huesos , Denosumab/uso terapéutico , Tumor Óseo de Células Gigantes/tratamiento farmacológico , Tumor Óseo de Células Gigantes/genética , HumanosAsunto(s)
Conservadores de la Densidad Ósea , Neoplasias Óseas , Tumor Óseo de Células Gigantes , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/genética , Denosumab/efectos adversos , Tumor Óseo de Células Gigantes/tratamiento farmacológico , Tumor Óseo de Células Gigantes/genética , Histonas/genética , Humanos , MutaciónRESUMEN
Objective: To investigate the clinicopathological characteristics, histogenesis, immunophenotypes and molecular genetic features of primary intraosseous Rosai-Dorfman disease (RDD) for improving diagnostic accuracy and differential diagnosis. Methods: This retrospective study included 14 RDD cases diagnosed from January 2009 to January 2019 at Beijing Jishuitan Hospital, China. The immunohistochemical staining for S-100, cyclin D1, CD1a and CD207 expression was analyzed. The BRAF V600E and KRAS mutation analyses were performed using the Scorpions amplification refractory mutation system (ARMS) fluorescence quantitative PCR. Results: There were 6 female and 8 male patients, aged from 2 to 64 years (mean 31.4 years). All of the 14 cases occurred in the bone without lymph node disease, while one patient developed additional lesions within vertebra and nasal cavity. Radiographically, the lesions were lytic with sclerotic margins. Histologically, the lesions percolated through the medullary cavity in an infiltrative fashion and alternating hyper- and hypo-cellular regions of histiocytic clusters (seen as alternating dark and light zones at low magnification). Large histiocytes also showed emperipolesis. Some cases had areas of fibrosis and dense lymphoplasmacytic infiltrates. There were vasculitis and an increased number of plasma cells in the cases involving multiple sites. One case showed concurrence of RDD and Langerhans cell histiocytosis(LCH) with inconspicuous increase of Langerhans histiocytes. Immunohistochemical staining showed that the large histiocytes were positive for S-100, CD68 and CD163 in all cases. The nuclear immunoreactivity for cyclin D1 was observed in 13 of the 14 cases. S-100, CD1a and CD207 were positive in the case with concurrence of RDD and LCH. ARMS-PCR results showed that BRAF V600E mutation was observed in the cases with concurrence of RDD and LCH, while there were no KRAS mutations (7/7). Follow-up information was available for 12 patients and ranged from 9 to 49 months. Three of the 12 patients experienced recurrences after the first surgery. Conclusions: Primary intraosseous RDD is rare, and its concurrence with LCH is a very rare phenomenon. Its clinical symptoms, imaging, and pathological manifestations need to be distinguished from other bone lesions. The molecular detection of BRAF V600E and the nuclear expression of cyclin D1 mutations can be used for the diagnosis and differential diagnosis of RDD.
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Histiocitosis Sinusal , Adolescente , Adulto , Niño , Preescolar , China , Femenino , Histiocitos , Humanos , Masculino , Persona de Mediana Edad , Proto-Oncogenes Mas , Estudios Retrospectivos , Proteínas S100 , Adulto JovenRESUMEN
Objective: To evaluate the role of histologicalpathology in the diagnosis of periprosthetic joint infection. Methods: A total of 145 cases of joint arthroplasty during October 2017 and October 2018 from Beijing Jishuitan Hospital were collected. There were 23 cases of infection, including knee joint arthroplasty (12 cases) and hip arthroplasty (11 cases). There were 17 females and 6 males. Patients' age ranged from 39 to 76 years (mean 63 years). The infection was diagnosed if there were >5 neutrophils per high power field in at least 5 high power field. The permanent sections were examined twice separately by two pathologists, and the interval time of histologic examination was at least two weeks. Sensitivity (SE), specificity (SP), positive predictivevalue (PPV), and negative predictive value (NPV) were calculated. The consistency evaluation of histologic examination of two pathologists was calculated by Kappa analysis. Results: The neutrophil cells could locate scattered or focally in the synovium tissue of periprosthetic joint infection. Somewhere, the infiltration of vessel and the perivascular distribution could also exist. Opportunity coincidence rate between two pathologists was 91.3% (Kappa=0.817). The results showed that SE was 60.9%, SP was 100.0%, NPV was 93.1%, PPV was 100.0%. Conclusions: The presence of polymorphonuclear cells in histologic examination is correlated with infection. There was high consistency between histologic examination and clinical diagnosis of joint arthroplasty.
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Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Neutrófilos/citología , Infecciones Relacionadas con Prótesis/diagnóstico , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infecciones Relacionadas con Prótesis/patología , Reoperación , Sensibilidad y EspecificidadRESUMEN
Objective: To identify the clinical outcome and prognostic factors of synchronous multicentric osteosarcoma (SMOS). Methods: The clinical data of 2 602 conventional osteosarcoma patients admitted to Beijing Jishuitan Hospital from January 1995 to June 2018 were retrospectively analyzed. Finally, 56 (2.1%) cases were confirmed as SMOS according to clinical and imaging database, medical record and pathological results.All epidemiological data of SMOS cases,initial diagnosis time, tumor site, number of lesions, chemotherapy, surgical treatment, alkline phosphatase (AKP),lactate dehydrogenase (LDH) and oncological results were collected in our institution. The Survival rate, comparison of various parameters, univariate analysis and multivariate Cox regression were performed with statistical software. Results: There were 41 males and 15 females enrolled in this research, the median and mean ages were 15 and 18 years (range, 8-50 years) respectively. All of them were multi-site involved, whereas the initial complaints of sites distribution were 32 cases of femur, 13 cases of tibia, 4 cases of humerus, 3 cases of fibula, 2 cases of spine, 1 case of sternum and 1 case of calcaneus. Forty-four of 56 cases performed adjuvant chemotherapy and 31 of them underwent surgical treatment. The mean follow-up time was 15.4 (range, 1-186) months. Thirty-five cases died of disease at the end of the follow-up. The 5-year survival rate was 10.4%. According to the number of lesions stratification, the 2-year survival rates in patients with low (<5 sites) and high (≥5 sites) tumor load was 33.6% and 0, respectively (χ(2)=6.697, P=0.010). The 2-year survival rate of chemotherapy and non-chemotherapy patients was 20.8% and 0, respectively (χ(2)=6.998, P=0.008), the value of AKP after chemotherapy(median: 272 IU/L) significantly decreased when compared with that at the initial diagnosis (median: 454 U/L) (Z=-3.274, P=0.001).The 2-year survival rate in patients with and without standard chemotherapy was 55.6% and 0, respectively (χ(2)=8.798, P=0.003). The 2-year survival rate was 25.0% in the surgical group and 0 in the non-surgical group, respectively (χ(2)=7.942, P=0.005). Multivariate cox regression analysis with the forward Wald method indicated that standard chemotherapy was the only variable contributor to survival and prognosis of multifocal osteosarcoma. Conclusions: SMOS has low survival rate and poor prognosis. Chemotherapy and surgery can improve the survival rate, standard chemotherapy is an independent prognostic factor.