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Composite hemangioendothelioma is a rare, locally aggressive, and rarely metastasizing vascular neoplasm which affects both children and adults. Recently, a number of gene fusions including YAP1::MAML2, PTBP1::MAML2, and EPC1::PHC2 have been detected in a small subset of cases with or without neuroendocrine expression. Herein, we present four additional cases with novel in-frame fusions. The cohort comprises two females and two males with a wide age range at diagnosis (24-80 years). Two tumors were deep involving the right brachial plexus and mediastinum, while the remaining were superficial (right plantar foot and abdominal wall). The size ranged from 1.5 to 4.8 cm in greatest dimension. Morphologically, all tumors had an admixture of at least two architectural patterns including retiform hemangioendothelioma, hemangioma, epithelioid hemangioendothelioma, or angiosarcoma. The tumors were positive for endothelial markers CD31 (3/3), ERG (4/4), and D2-40 (1/4, focal), while SMA was expressed in 2/3 highlighting the surrounding pericytes. Synaptophysin showed immunoreactivity in 2/3 cases. One patient had a local recurrence after 40 months, while two patients had no evidence of disease 4 months post-resection. Targeted RNA sequencing detected novel in-frame fusions in each of the cases: HSPG2::FGFR1, YAP1::FOXR1, ACTB::MAML2, and ARID1B::MAML2. The two cases with neuroendocrine expression occurred as superficial lesions and harbored YAP1::FOXR1 and ARID1B::MAML2 fusions. Our study expands on the molecular spectrum of this enigmatic tumor, further enhancing our current understanding of the disease.
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Hemangioendotelioma Epitelioide , Hemangioendotelioma , Hemangioma , Adulto , Masculino , Criança , Feminino , Humanos , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Hemangioendotelioma/patologia , Hemangioendotelioma Epitelioide/genética , Sequência de Bases , Diagnóstico Diferencial , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas , Proteína de Ligação a Regiões Ricas em PolipirimidinasRESUMO
GLI1(12q13.3) amplification is identified in a subset of mesenchymal neoplasms with a distinct nested round cell/epithelioid phenotype. MDM2 and CDK4 genes are situated along the oncogenic 12q13-15 segment, amplification of which defines well-differentiated liposarcoma (WDLPS)/dedifferentiated liposarcoma (DDLPS). The 12q amplicon can occasionally include GLI1, a gene in close proximity to CDK4. We hereby describe the first cohort of GLI1/MDM2/CDK4 coamplified WD/DDLPS. The departmental database was queried retrospectively for all cases of WD/DDLPS having undergone next-generation (MSK-IMPACT) sequencing with confirmed MDM2, CDK4, and GLI1 coamplification. Clinicopathologic data was obtained from a review of the medical chart and available histologic material. Four hundred eighty-six WD/DDLPS cases underwent DNA sequencing, 92 (19%) of which harbored amplification of the GLI1 locus in addition to that of MDM2 and CDK4. These included primary tumors (n = 60), local recurrences (n = 29), and metastases (n = 3). Primary tumors were most frequently retroperitoneal (47/60, 78%), mediastinal (4/60, 7%), and paratesticular (3/60, 5%). Average age was 63 years, with a male:female ratio of 3:2. The cohort was comprised of DDLPS (86/92 [93%], 6 of which were WDLPS with early dedifferentiation) and WDLPS without any longitudinal evidence of dedifferentiation (6/92, 7%). One-fifth (13/86, 17%) of DDLPS cases showed no evidence of a well-differentiated component in any of the primary, recurrent, or metastatic specimens. Dedifferentiated areas mostly showed high-grade undifferentiated pleomorphic sarcoma-like (26/86,30%) and high-grade myxofibrosarcoma-like (13/86,16%) morphologies. A disproportionately increased incidence of meningothelial whorls with/without osseous metaplasia was observed as the predominant pattern in 16/86 (19%) cases, and GLI1-altered morphology as described was identified in a total of 10/86 (12%) tumors. JUN (1p32.1), also implicated in the pathogenesis of WD/DDLPS, was coamplified with all 3 of MDM2, CDK4, and GLI1 in 7/91 (8%) cases. Additional loci along chromosomal arms 1p and 6q, including TNFAIP3, LATS1, and ESR1, were also amplified in a subset of cases. In this large-scale cohort of GLI1 coamplified WD/DDLPS, we elucidate uniquely recurrent features including meningothelial whorl-like and GLI-altered morphology in dedifferentiated areas. Assessment of tumor location (retroperitoneal or mediastinal), identification of a well-differentiated liposarcoma component, and coamplification of other spatially discrete genomic segments (1p and 6q) might aid in distinction from tumors with true driver GLI1 alterations.
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Quinase 4 Dependente de Ciclina , Amplificação de Genes , Lipossarcoma , Proteína GLI1 em Dedos de Zinco , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores Tumorais/genética , Quinase 4 Dependente de Ciclina/genética , Lipossarcoma/genética , Lipossarcoma/patologia , Proteínas Proto-Oncogênicas c-mdm2/genética , Estudos Retrospectivos , Proteína GLI1 em Dedos de Zinco/genéticaRESUMO
Osteosarcoma is the most common primary bone cancer, whose standard treatment includes pre-operative chemotherapy followed by resection. Chemotherapy response is used for prognosis and management of patients. Necrosis is routinely assessed after chemotherapy from histology slides on resection specimens, where necrosis ratio is defined as the ratio of necrotic tumor/overall tumor. Patients with necrosis ratio ≥90% are known to have a better outcome. Manual microscopic review of necrosis ratio from multiple glass slides is semiquantitative and can have intraobserver and interobserver variability. In this study, an objective and reproducible deep learning-based approach was proposed to estimate necrosis ratio with outcome prediction from scanned hematoxylin and eosin whole slide images (WSIs). To conduct the study, 103 osteosarcoma cases with 3134 WSIs were collected. Deep Multi-Magnification Network was trained to segment multiple tissue subtypes, including viable tumor and necrotic tumor at a pixel level and to calculate case-level necrosis ratio from multiple WSIs. Necrosis ratio estimated by the segmentation model highly correlates with necrosis ratio from pathology reports manually assessed by experts. Furthermore, patients were successfully stratified to predict overall survival with P = 2.4 × 10-6 and progression-free survival with P = 0.016. This study indicates that deep learning can support pathologists as an objective tool to analyze osteosarcoma from histology for assessing treatment response and predicting patient outcome.
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Neoplasias Ósseas , Aprendizado Profundo , Osteossarcoma , Humanos , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Prognóstico , Necrose/patologia , Osteossarcoma/tratamento farmacológico , Osteossarcoma/patologiaRESUMO
AIMS: Chondromyxoid fibroma (CMF) is a rare, benign bone tumour which arises primarily in young adults and is occasionally diagnostically challenging. Glutamate metabotropic receptor 1 (GRM1) gene encodes a metabotropic glutamate receptor and was recently shown to be up-regulated in chondromyxoid fibroma through gene fusion and promoter swapping. The aim of this study was to interrogate cases of CMF for the presence of GRM1 gene rearrangements, gene fusions and GRM1 protein overexpression. METHODS AND RESULTS: Selected cases were subjected to testing by fluorescent in-situ hybridisation (FISH) with a GRM1 break-apart probe, a targeted RNA sequencing method and immunohistochemical study with an antibody to GRM1 protein. Two cases were subjected to whole transcriptomic sequencing. In 13 of 13 cases, GRM1 protein overexpression was detected by immunohistochemistry using the GRM1 antibody. Of the 12 cases successfully tested by FISH, nine of 12 showed GRM1 rearrangements by break-apart probe assay. Targeted RNA sequencing analysis did not detect gene fusions in any of the eight cases tested, but there was an increase in GRM1 mRNA expression in all eight cases. Two cases subjected to whole transcriptomic sequencing (WTS) showed elevated GRM1 expression and no gene fusions. CONCLUSION: GRM1 gene rearrangements can be detected using FISH break-apart probes in approximately 75% of cases, and immunohistochemical detection of GRM1 protein over-expression is a sensitive diagnostic method. The gene fusion was not detected by targeted RNA sequencing, due most probably to the complexity of fusion mechanism, and is not yet a reliable method for confirming a diagnosis of CMF in the clinical setting.
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Nanomedicines loaded in macrophages (MAs) can actively target tumors without dominantly relying on the enhanced permeability and retention (EPR) effect, making them effective for treating EPR-deficient malignancies. Herein, copper-crosslinked carbon dot clusters (CDCs) are synthesized with both photodynamic and chemodynamic functions to manipulate MAs, aiming to direct the MA-mediated tumor targeting. First, green fluorescent CDs (g-CDs) are prepared by a one-step hydrothermal method. Subsequently, the g-CDs are complexed with divalent copper ions to form copper-crosslinked CDCs (g-CDCs/Cu), which are incubated with MAs for their manipulation. Experimental results revealed that the prepared g-CDCs/Cu displayed good aqueous dispersibility and fluorescent emission properties. The nanoassemblies can be activated to deplete the overexpressed glutathione (GSH) and generate reactive oxygen species (ROS) in the presence of laser irradiation through the combined Cu-mediated chemodynamic therapy and CD-mediated photodynamic therapy. Furthermore, the ROS produced in MAs enabled polarization of MAs to antitumor M1 phenotype, suggesting the future potential use to reverse the immunosuppressive tumor microenvironment. These results obtained from the current study suggest a significant potential to develop g-CDCs/Cu for GSH depletion, ROS generation, and MA M1 polarization as a theransotic agent to tackle cancer.
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Bone consists of separate inner endosteal and outer periosteal compartments, each with distinct contributions to bone physiology and each maintaining separate pools of cells owing to physical separation by the bone cortex. The skeletal stem cell that gives rise to endosteal osteoblasts has been extensively studied; however, the identity of periosteal stem cells remains unclear1-5. Here we identify a periosteal stem cell (PSC) that is present in the long bones and calvarium of mice, displays clonal multipotency and self-renewal, and sits at the apex of a differentiation hierarchy. Single-cell and bulk transcriptional profiling show that PSCs display transcriptional signatures that are distinct from those of other skeletal stem cells and mature mesenchymal cells. Whereas other skeletal stem cells form bone via an initial cartilage template using the endochondral pathway4, PSCs form bone via a direct intramembranous route, providing a cellular basis for the divergence between intramembranous versus endochondral developmental pathways. However, there is plasticity in this division, as PSCs acquire endochondral bone formation capacity in response to injury. Genetic blockade of the ability of PSCs to give rise to bone-forming osteoblasts results in selective impairments in cortical bone architecture and defects in fracture healing. A cell analogous to mouse PSCs is present in the human periosteum, raising the possibility that PSCs are attractive targets for drug and cellular therapy for skeletal disorders. The identification of PSCs provides evidence that bone contains multiple pools of stem cells, each with distinct physiologic functions.
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Desenvolvimento Ósseo , Osso e Ossos/citologia , Periósteo/citologia , Células-Tronco/citologia , Animais , Catepsina K/metabolismo , Diferenciação Celular , Feminino , Fêmur/citologia , Consolidação da Fratura , Regulação da Expressão Gênica , Humanos , Masculino , Células-Tronco Mesenquimais/citologia , Camundongos , Osteoblastos/citologia , Crânio/citologiaRESUMO
Digital pathology workflows can improve pathology operations by allowing reliable and fast retrieval of digital images, digitally reviewing pathology slides, enabling remote work and telepathology, use of computer-aided tools, and sharing of digital images for research and educational purposes. The need for quality systems is a prerequisite for successful clinical-grade digital pathology adoption and patient safety. In this article, we describe the development of a structured digital pathology laboratory quality management system (QMS) for clinical digital pathology operations at Memorial Sloan Kettering Cancer Center (MSK). This digital pathology-specific QMS development stemmed from the gaps that were identified when MSK integrated digital pathology into its clinical practice. The digital scan team in conjunction with the Department of Pathology and Laboratory Medicine quality team developed a QMS tailored to the scanning operation to support departmental and institutional needs. As a first step, systemic mapping of the digital pathology operations identified the prescan, scan, and postscan processes; instrumentation; and staffing involved in the digital pathology operation. Next, gaps identified in quality control and quality assurance measures led to the development of standard operating procedures and training material for the different roles and workflows in the process. All digital pathology-related documents were subject to regulatory review and approval by departmental leadership. The quality essentials were developed into an extensive Digital Pathology Quality Essentials framework to specifically address the needs of the growing clinical use of digital pathology technologies. Using the unique digital experience gained at MSK, we present our recommendations for QMS for large-scale digital pathology operations in clinical settings.
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Neoplasias , Patologia Clínica , Telepatologia , Humanos , Laboratórios , Neoplasias/diagnóstico , Neoplasias/cirurgia , Patologia Clínica/métodos , Telepatologia/métodos , Gestão da Qualidade TotalRESUMO
The distinction between undifferentiated melanoma (UM) or dedifferentiated melanoma (DM) from undifferentiated or unclassifiable sarcoma can be difficult and requires the careful correlation of clinical, pathologic, and genomic findings. In this study, we examined the utility of mutational signatures to identify patients with UM/DM with particular attention as to whether this distinction matters for treatment because the survival of patients with metastatic melanoma has dramatically improved with immunologic therapy, whereas durable responses are less frequent in sarcomas. We identified 19 cases of UM/DM that were initially reported as unclassified or undifferentiated malignant neoplasm or sarcoma and submitted for targeted next-generation sequencing analysis. These cases were confirmed as UM/DM by harboring melanoma driver mutations, UV signature, and high tumor mutation burden. One case of DM showed melanoma in situ. Meanwhile, 18 cases represented metastatic UM/DM. Eleven patients had a prior history of melanoma. Thirteen of 19 (68%) of the tumors were immunohistochemically completely negative for 4 melanocytic markers (S100, SOX10, HMB45, and MELAN-A). All cases harbored a dominant UV signature. Frequent driver mutations involved BRAF (26%), NRAS (32%), and NF1 (42%). In contrast, the control cohort of undifferentiated pleomorphic sarcomas (UPS) of deep soft tissue exhibited a dominant aging signature in 46.6% (7/15) without evidence of UV signature. The median tumor mutation burden for DM/UM vs UPS was 31.5 vs 7.0 mutations/Mb (P < .001). A favorable response to immune checkpoint inhibitor therapy was observed in 66.6% (12/18) of patients with UM/DM. Eight patients exhibited a complete response and were alive with no evidence of disease at the last follow-up (median 45.5 months). Our findings support the usefulness of the UV signature in discriminating DM/UM vs UPS. Furthermore, we present evidence suggesting that patients with DM/UM and UV signatures can benefit from immune checkpoint inhibitor therapy.
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Histiocitoma Fibroso Maligno , Melanoma , Segunda Neoplasia Primária , Sarcoma , Neoplasias de Tecidos Moles , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Melanoma/genética , Melanoma/terapia , Melanoma/patologia , Sarcoma/genética , Sarcoma/terapia , Sarcoma/patologia , Biomarcadores Tumorais/genética , Imunoterapia , Mutação , Melanoma Maligno CutâneoRESUMO
AIMS: Soft-tissue tumours are rare and both accurate diagnosis and proper treatment represent a global challenge. Current treatment guidelines also recommend review by specialised pathologists. Here we report on international consensus-based datasets for the pathology reporting of biopsy and resection specimens of soft-tissue sarcomas. The datasets were produced under the auspices of the International Collaboration on Cancer Reporting (ICCR), a global alliance of international pathology and cancer organisations. METHODS AND RESULTS: According to the ICCR's guidelines for dataset development, an international expert panel consisting of pathologists, a surgical oncologist, and a medical oncologist produced a set of core and noncore data items for biopsy and resection specimens based on a critical review and discussion of current evidence. All professionals involved were subspecialised soft-tissue sarcoma experts and affiliated with tertiary referral centres. Commentary was provided for each data item to explain the rationale for selecting it as a core or noncore element, its clinical relevance, and to highlight potential areas of disagreement or lack of evidence, in which case a consensus position was formulated. Following international public consultation, the documents were finalised and ratified, and the datasets, which included a synoptic reporting guide, were published on the ICCR website. CONCLUSION: These first international datasets for soft-tissue sarcomas are aimed to promote high-quality, standardised pathology reporting. Their adoption will improve consistency of reporting, facilitate multidisciplinary communication, and enhance comparability of data, all of which will help to improve patient's management.
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Patologia Clínica , Sarcoma , Neoplasias de Tecidos Moles , Humanos , BiópsiaRESUMO
Improved understanding of tumor biology through molecular alteration and genetic advances has resulted in a number of major changes in the 2020 World Health Organization's (WHO) classification of bone tumors. These changes include the reclassification of the existing tumors and the introduction of several new entities. A new chapter on undifferentiated small round cell sarcomas of bone and soft tissue was added to classify Ewing sarcoma and the family of Ewing-like sarcomas, which share similar histologies but different molecular and clinical behaviors. Knowledge of the current classification of bone tumors is essential to ensure the appropriate recognition of the inherent biological potential of individual osseous lesions for optimal treatment, follow-up, and overall outcome. This article reviews the major changes to the 2020 WHO's classification of primary bone tumors and the pertinent imaging of selected tumors to highlight these changes.
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Neoplasias Ósseas , Sarcoma de Ewing , Sarcoma , Neoplasias de Tecidos Moles , Humanos , Neoplasias Ósseas/patologia , Sarcoma de Ewing/diagnóstico por imagem , Sarcoma de Ewing/patologia , Sarcoma/patologia , Organização Mundial da Saúde , Neoplasias de Tecidos Moles/patologia , Biomarcadores Tumorais , RadiologistasRESUMO
OBJECTIVE: To evaluate MR features and clinical course of malignant melanotic nerve sheath tumor (MMNST), previously known as melanotic schwannoma and considered indolent and rarely metastasizing. MATERIALS AND METHODS: This IRB-approved retrospective study searched 31 patients (20 male: 11 female, mean age 48; range 15-76) with histologically confirmed MMNST in a single tertiary cancer center over 22 years. Pre-treatment MR was available in 12 patients and evaluated by two radiologists in consensus regarding lesion location, size, morphology, signal characteristics, contrast enhancement, local invasion, and presence of classic signs of peripheral nerve sheath tumors. Clinical outcomes, including local recurrence, metastasis, and survival, were examined in 12 patients for whom follow-up was available. RESULTS: The spine was the most frequent site (13/31) among all identified cases. In 12 cases with MR, lesions were well-circumscribed in 11/12 cases, with a mean size of 4.5 cm (2.3-13.0 cm). Ten of 12 cases showed T1 hyperintensity. In 5/9 spinal MRI, tumor involved multiple levels. All lesions showed contrast enhancement, and local bone invasion in > 50%. A dumb-bell shape was common to all spinal lesions. Classical signs of nerve sheath tumors were uncommon. Among 12 patients with a mean follow-up of 4.8 years (range 1.3-10.2 years), six were disease-free, while two had recurrence or metastases, and four had died of metastases. CONCLUSION: MMNST usually presents as a T1 hyperintense enhancing dumb-bell shaped mass in the spine. Multi-level involvement and bone invasion are common. MMNST is clinically aggressive with high rates of metastases and death.
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Neoplasias de Bainha Neural , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias de Bainha Neural/diagnóstico por imagem , Neoplasias de Bainha Neural/patologia , Imageamento por Ressonância Magnética/métodos , Coluna Vertebral/patologia , Progressão da DoençaRESUMO
Giant cell tumor of bone (GCTB) is a locally aggressive tumor that shows predilection for the metaphysis/epiphysis of long bones, with an incidence of 4-5% of primary bone tumors. GCTB shows two main populations of cells: mononuclear cells and non-neoplastic multi-nucleated giant cells, with or without fibrous background. On the other hand, giant-cell-poor GCTB are rare with only few reports in the literature. These cases offer a diagnostic challenge, given the absence of giant cells and such cases have consistently been shown to harbor the H3F3A gene mutation by sequencing. The H3.3 G34W mutation-specific monoclonal antibody has shown high specificity in the diagnosis of GCTB. Two cases of giant-cell-poor GCTB are presented in this study, in which giant cells were absent or sparse and the diagnosis of GCTB was confirmed by the expression of H3.3 G34W monoclonal antibody in the mononuclear cells by immunohistochemistry. Whether this represents a histologic variant of GCTB or partial involution of GCTB is not yet fully understood; however, an immune response, infectious/inflammatory reaction, and/or anti-tumor cytokine production have been purported to be factors inciting disease regression in GCTB.
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Neoplasias Ósseas , Tumor de Células Gigantes do Osso , Humanos , Histonas/genética , Tumor de Células Gigantes do Osso/diagnóstico por imagem , Tumor de Células Gigantes do Osso/genética , Anticorpos Monoclonais , Imuno-Histoquímica , Neoplasias Ósseas/diagnósticoRESUMO
Chordomas are rare, low-grade malignant tumors often found in the sacrococcygeal region and prone to local recurrence. We report an atypical presentation of a 40-year-old patient with a symptomatic midline retrococcygeal lesion that was presumptively treated as a pilonidal cyst due to its clinical and imaging features. After surgical pathology rendered the diagnosis of chordoma, the patient required salvage surgery in the form of partial sacrectomy with soft tissue flap coverage. In addition to the unusually predominant retrococcygeal location, surgical pathology identified an intervertebral disc origin rather than the typical osseous origin. To our knowledge, this presentation of chordoma with coccygeal intervertebral origin and a large subcutaneous mass at imaging has rarely been reported in the literature. We describe this case to raise awareness of atypical presentations of sacrococcygeal chordoma that may lead to erroneous presumptive diagnosis and treatment.
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Photochromic inks have been an attractive authentication strategy to improve the anti-counterfeiting efficiency of commercial products. However, recent reports have shown significant disadvantages with photochromic inks, including poor durability and high cost. In this context, we developed novel photochromic nanofibres for advanced anti-counterfeiting applications. Lanthanide-doped strontium aluminate (LdSA) nanoparticles (NPs) were prepared and immobilized into electrospun cellulose acetate nanofibres (CANF). Authentication materials immobilized with inorganic photochromic agents can warranty durability and photostability. Therefore, the ultraviolet-stimulated photochromism of LdSA-encapsulated cellulose acetate nanofibres (LdSA@CANF) demonstrated high reversibility and photostability. A broad range of cellulose acetate nanofibres with unique emission characteristics was developed when applying different ratios of LdSA NPs. LdSA@CANF appeared colourless under visible daylight, whereas a green emission was monitored under ultraviolet-light illumination. The shape and chemical content of the photochromic fibrous films were examined using various analytical techniques. The mechanical characteristics of LdSA@CANF-coated paper were investigated. The emission wavelength was detected at 514 nm to designate green colour, whereas the excitation wavelength was detected at 369 nm to indicate transparency. The prepared cellulose acetate nanofibrous film can be described as an efficient strategy for the anti-counterfeiting of commercialized items.
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Poly(vinyl chloride) (PVC) was reinforced with electrospun glass nanofibres (EGN) to develop photochromic and afterglow materials such as smart windows and anti-counterfeiting prints. A colourless electrospun glass nanofibres@poly(vinyl chloride) (EGN@PVC) sheet was prepared by physical integration of lanthanide-doped aluminate nanoparticles (LANP). The low concentrations of LANP in the photochromic and photoluminescent EGN@PVC hybrids displayed fluorescence emission with instant reversibility. EGN@PVC with the highest phosphor concentrations showed persistent phosphorescence emission with slow reversibility. Based on the results of the Commission Internationale de l'éclairage Laboratory and luminescence spectroscopy, the translucent EGN@PVC samples became green in the presence of ultraviolet illumination and greenish-yellow in the absence of light. According to scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analyses, the morphological study of EGN and LANP showed diameters of 75-95 and 11-19 nm, respectively. The morphology of the EGN@PVC substrates was studied using SEM, X-ray fluorescence, and energy-dispersive X-ray spectroscopy. The mechanical characteristics of PVC were enhanced by reinforcement with EGN as a roughening agent. When comparing the scratching resistance of LANP-free substrate to photoluminescent EGN@PVC substrates, it was observed that the latter was much superior. The photoluminescence spectra were reported to have an emission peak at 519 nm when excited at 365 nm. These findings demonstrated that the luminous transparent EGN@PVC composites had improved superhydrophobic and UV-blocking characteristics.
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Nanofibras , Cloreto de Vinil , Polímeros , Raios Ultravioleta , LuminescênciaRESUMO
The field of anatomic pathology has been evolving in the last few decades and the advancements have been largely fostered by innovative technology. Immunohistochemistry enabled a paradigm shift in discovery and diagnostic evaluation, followed by booming genomic advancements which allowed for submicroscopic pathologic characterization, and now the field of digital pathology coupled with machine learning and big data acquisition is paving the way to revolutionize the pathology medical domain. Whole slide imaging (WSI) is a disruptive technology where glass slides are digitized to produce on-screen whole slide images. Specifically, in the past decade, there have been significant advances in digital pathology systems that have allowed this technology to promote integration into clinical practice. Whole slide images (WSI), or digital slides, can be viewed and navigated comparable to glass slides on a microscope, as digital files. Whole slide imaging has increased in adoption among pathologists, pathology departments, and scientists for clinical, educational, and research initiatives. Integration of digital pathology systems requires a coordinated effort with numerous stakeholders, not only within the pathology department, but across the entire enterprise. Each pathology department has distinct needs, use cases and blueprints, however the framework components and variables for successful clinical integration can be generalized across any organization seeking to undergo a digital transformation at any scale. This article will review those components and considerations for integrating digital pathology systems into clinical practice.
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Microscopia , Patologia Clínica , Humanos , Microscopia/métodos , Patologistas , Patologia Clínica/métodosRESUMO
In the field of pathology, micro-computed tomography (micro-CT) has become an attractive imaging modality because it enables full analysis of the three-dimensional characteristics of a tissue sample or organ in a noninvasive manner. However, because of the complexity of the three-dimensional information, understanding would be improved by development of analytical methods and software such as those implemented for clinical CT. As the accurate identification of tissue components is critical for this purpose, we have developed a deep neural network (DNN) to analyze whole-tissue images (WTIs) and whole-block images (WBIs) of neoplastic cancer tissue using micro-CT. The aim of this study was to segment vessels from WTIs and WBIs in a volumetric segmentation method using DNN. To accelerate the segmentation process while retaining accuracy, a convolutional block in DNN was improved by introducing a residual inception block. Three colorectal tissue samples were collected and one WTI and 70 WBIs were acquired by a micro-CT scanner. The implemented segmentation method was then tested on the WTI and WBIs. As a proof-of-concept study, our method successfully segmented the vessels on all WTI and WBIs of the colorectal tissue sample. In addition, despite the large size of the images for analysis, all segmentation processes were completed in 10 minutes.
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Imageamento Tridimensional/métodos , Redes Neurais de Computação , Inclusão em Parafina/métodos , Software , Microtomografia por Raio-X/métodos , Humanos , Estudo de Prova de ConceitoRESUMO
Epithelioid hemangioma is a rare, histologically benign but locally aggressive primary vascular neoplasm that can rarely arise in bone. Mainstay treatment is surgical resection or curettage with bone grafting. We report a novel multidisciplinary, joint-sparing treatment approach for an epithelioid hemangioma of bone arising in the acetabulum causing severe thinning of the subchondral bone plate. After 4 sessions of transarterial bland particle and ethanol embolization, the resultant increased ossification of the tumor allowed preservation of the articular surface during surgical resection. Imaging follow-up 14 months after surgical resection showed no evidence of recurrence and continued ossification of the portions of the lesion treated only with embolization.
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Neoplasias Ósseas , Hemangioma , Neoplasias Vasculares , Acetábulo/diagnóstico por imagem , Acetábulo/patologia , Acetábulo/cirurgia , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/patologia , Neoplasias Ósseas/terapia , Transplante Ósseo , Curetagem/métodos , Hemangioma/diagnóstico por imagem , Hemangioma/terapia , Humanos , Neoplasias Vasculares/patologiaRESUMO
Evolution of poorly differentiated chordoma from conventional chordoma has not been previously reported. We encountered a case of a poorly differentiated chordoma with evidence of whole-genome doubling arising from a SMARCB1-deficient conventional chordoma. The tumor presented as a destructive sacral mass in a 43-year-old man and was comprised of a highly cellular poorly differentiated chordoma with small, morphologically distinct nodules of conventional chordoma accounting for <5% of the total tumor volume. Immunohistochemistry (IHC) revealed both components were strongly reactive for brachyury and lacked normal staining for INI1. Single nucleotide polymorphism (SNP) array analysis identified multiple genomic imbalances in the conventional component, including deletions of 1p, 3p, and 22q (involving SMARCB1) and loss of chromosomes 5 and 15, while the poorly differentiated component exhibited the same aberrations at a more profound level with additional loss of chromosome 4, low level focal deletion of 17p (involving TP53), and tetraploidy. Homozygous deletion of SMARCB1 was present in both components. Fluorescence in situ hybridization (FISH) analysis confirmed the relevant deletions in both components as well as genome doubling in the poorly differentiated tumor. This case suggests that SMARCB1 loss is an early event in rare conventional chordomas that could potentially evolve into poorly differentiated chordoma through additional genomic aberrations such as genome doubling. Further studies with additional patients will be needed to determine if genome doubling is a consistent pathway for evolution of poorly differentiated chordoma.
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Cordoma/genética , Deleção Cromossômica , Proteína SMARCB1/genética , Neoplasias da Coluna Vertebral/genética , Tetraploidia , Adulto , Cordoma/patologia , Proteínas Fetais/genética , Proteínas Fetais/metabolismo , Humanos , Masculino , Proteína SMARCB1/deficiência , Sacro/patologia , Neoplasias da Coluna Vertebral/patologia , Proteínas com Domínio T/genética , Proteínas com Domínio T/metabolismoRESUMO
Extra-axial chordoma is a rare neoplasm of extra-axial skeleton and soft tissue that shares identical histomorphologic and immunophenotypic features with midline chordoma. While genetic changes in conventional chordoma have been well-studied, the genomic alterations of extra-axial chordoma have not been reported. It is well known that conventional chordoma is a tumor with predominantly non-random copy number alterations and low mutational burden. Herein we describe the clinicopathologic and genomic characteristics of six cases of extra-axial chordoma, with genome-wide high-resolution single nucleotide polymorphism array, fluorescence in situ hybridization and targeted next-generation sequencing (NGS) analysis. The patients presented at a mean age of 33 years (range: 21-54) with a female to male ratio of 5:1. Four cases were histologically conventional type, presented with bone lesions and three of them had local recurrence. Two cases were poorly differentiated chordomas, presented with intra-articular soft tissue masses and both developed distant metastases. All cases showed brachyury positivity and the two poorly differentiated chordomas showed in addition loss of INI-1 expression by immunohistochemical analysis. Three of four extra-axial conventional chordomas showed simple genome with loss of chromosome 22 or a heterozygous deletion of SMARCB1. Both poorly differentiated chordomas demonstrated a complex hyperdiploid genomic profile with gain of multiple chromosomes and homozygous deletion of SMARCB1. Our findings show that heterozygous deletion of SMARCB1 or the loss of chromosome 22 is a consistent abnormality in extra-axial chordoma and transformation to poorly differentiated chordoma is characterized by homozygous loss of SMARCB1 associated with genomic complexity and instability such as hyperdiploidy.