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Laryngeal rare tumors include benign and malignant tumors of epithelial, non-epithelial, or mesenchymal origin. Chondrosarcomas are the most common mesenchymal malignant tumors of the larynx. We performed a literature review (Pubmed/Medline; PRISMA 2020) to detect the frequency of published studies from 2021 to April 2024 regarding benign and malignant epithelial, non-epithelial, or mesenchymal rare tumors of the larynx, emphasizing laryngeal chondrosarcoma (LC) cases. Articles including cases discussed before 2021 were excluded and articles without available English translations. We included 154 articles investigating rare tumors of the larynx, the majority of them discussed non-epithelial or mesenchymal entities (75â¯%). Specifically, a high proportion of studies examined benign non-epithelial or mesenchymal tumors (79.5â¯%) or mesenchymal rare malignancies (72â¯%) of the larynx concerning epithelial tumors in the last three years. Sarcomas were discussed in 74â¯% of mesenchymal laryngeal malignancies and more than 50â¯% of rare laryngeal tumor studies, and LC was discussed in â¼50â¯% of laryngeal sarcoma studies. LC studies reported 174 cases, 21â¯% of them of high-grade LC (II), including a new case of LC presented here in the supraglottic (grade II), which showed intense staining for the S100 marker. Our study highlights the awareness of rare laryngeal tumors emphasizing non-epithelial benign tumors and laryngeal sarcomas, including chondrosarcomas, as pathologic entities of the larynx. Although the majority of LC included low-grade neoplasms, a markedness proportion of LC cases was evaluated as high-grade. Future research approaches, including a range of low and high-grade tumors, would reveal prognostic markers or therapeutic targets for LC and other rare laryngeal malignancies of non-epithelial or mesenchymal origin.
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Condrossarcoma , Neoplasias Laríngeas , Humanos , Neoplasias Laríngeas/patologia , Condrossarcoma/patologia , Sarcoma/patologia , Masculino , Pessoa de Meia-Idade , FemininoRESUMO
Glioblastoma multiforme (GBM) is an aggressive primary brain tumor characterized by extensive heterogeneity and vascular proliferation. Hypoxic conditions in the tissue microenvironment are considered a pivotal player leading tumor progression. Specifically, hypoxia is known to activate inducible factors, such as hypoxia-inducible factor 1alpha (HIF-1α), which in turn can stimulate tumor neo-angiogenesis through activation of various downward mediators, such as the vascular endothelial growth factor (VEGF). Here, we aimed to explore the role of HIF-1α/VEGF immunophenotypes alone and in combination with other prognostic markers or clinical and image analysis data, as potential biomarkers of GBM prognosis and treatment efficacy. We performed a systematic review (Medline/Embase, and Pubmed database search was completed by 16th of April 2024 by two independent teams; PRISMA 2020). We evaluated methods of immunoassays, cell viability, or animal or patient survival methods of the retrieved studies to assess unbiased data. We used inclusion criteria, such as the evaluation of GBM prognosis based on HIF-1α/VEGF expression, other biomarkers or clinical and imaging manifestations in GBM related to HIF-1α/VEGF expression, application of immunoassays for protein expression, and evaluation of the effectiveness of GBM therapeutic strategies based on HIF-1α/VEGF expression. We used exclusion criteria, such as data not reporting both HIF-1α and VEGF or prognosis. We included 50 studies investigating in total 1319 GBM human specimens, 18 different cell lines or GBM-derived stem cells, and 6 different animal models, to identify the association of HIF-1α/VEGF immunophenotypes, and with other prognostic factors, clinical and macroscopic data in GBM prognosis and therapeutic approaches. We found that increased HIF-1α/VEGF expression in GBM correlates with oncogenic factors, such as miR-210-3p, Oct4, AKT, COX-2, PDGF-C, PLDO3, M2 polarization, or ALK, leading to unfavorable survival. Reduced HIF-1α/VEGF expression correlates with FIH-1, ADNP, or STAT1 upregulation, as well as with clinical manifestations, like epileptogenicity, and a favorable prognosis of GBM. Based on our data, HIF-1α or VEGF immunophenotypes may be a useful tool to clarify MRI-PET imaging data distinguishing between GBM tumor progression and pseudoprogression. Finally, HIF-1α/VEGF immunophenotypes can reflect GBM treatment efficacy, including combined first-line treatment with histone deacetylase inhibitors, thimerosal, or an active metabolite of irinotecan, as well as STAT3 inhibitors alone, and resulting in a favorable tumor prognosis and patient survival. These data were supported by a combination of variable methods used to evaluate HIF-1α/VEGF immunophenotypes. Data limitations may include the use of less sensitive detection methods in some cases. Overall, our data support HIF-1α/VEGF's role as biomarkers of GBM prognosis and treatment efficacy.
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Biomarcadores Tumorais , Neoplasias Encefálicas , Glioblastoma , Subunidade alfa do Fator 1 Induzível por Hipóxia , Fator A de Crescimento do Endotélio Vascular , Glioblastoma/patologia , Glioblastoma/metabolismo , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo , Prognóstico , Biomarcadores Tumorais/metabolismo , Animais , Microambiente TumoralRESUMO
Low-grade gliomas present a formidable challenge in neuro-oncology because of the challenges imposed by the blood-brain barrier, predilection for the young adult population, and propensity for recurrence. In the past two decades, the systematic examination of genomic alterations in adults and children with primary brain tumors has uncovered profound new insights into the pathogenesis of these tumors, resulting in more accurate tumor classification and prognostication. It also identified several common recurrent genomic alterations that now define specific brain tumor subtypes and have provided a new opportunity for molecularly targeted therapeutic intervention. Adult-type diffuse low-grade gliomas are frequently associated with mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2), resulting in production of 2-hydroxyglutarate, an oncometabolite important for tumorigenesis. Recent studies of IDH inhibitors have yielded promising results in patients at early stages of disease with prolonged progression-free survival (PFS) and delayed time to radiation and chemotherapy. Pediatric-type gliomas have high rates of alterations in BRAF, including BRAF V600E point mutations or BRAF-KIAA1549 rearrangements. BRAF inhibitors, often combined with MEK inhibitors, have resulted in radiographic response and improved PFS in these patients. This article reviews emerging approaches to the treatment of low-grade gliomas, including a discussion of targeted therapies and how they integrate with the current treatment modalities of surgical resection, chemotherapy, and radiation.
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Neoplasias Encefálicas , Glioma , Isocitrato Desidrogenase , Gradação de Tumores , Humanos , Glioma/genética , Glioma/terapia , Glioma/tratamento farmacológico , Glioma/patologia , Isocitrato Desidrogenase/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/tratamento farmacológico , Gerenciamento Clínico , Mutação , Terapia de Alvo MolecularRESUMO
Individuals with neurofibromatosis type 1 (NF-1), an autosomal dominant neurogenetic and tumor predisposition syndrome, are susceptible to developing low-grade glioma (LGG) and, less commonly, high-grade glioma (HGG). These gliomas exhibit loss of the neurofibromin gene (NF1), and 10-15% of sporadic HGG have somatic NF1 alterations. Loss of NF1 leads to hyperactive RAS signaling, creating opportunity given the established efficacy of MEK inhibitors (MEKi) in plexiform neurofibromas and some individuals with LGG. We observed that NF1-deficient glioblastoma neurospheres were sensitive to the combination of a MEKi (mirdametinib) with irradiation, as evidenced by synergistic inhibition of cell growth, colony formation, and increased cell death. In contrast, NF1-intact neurospheres were not sensitive to the combination, despite complete ERK pathway inhibition. No neurosphere lines exhibited enhanced sensitivity to temozolomide combined with mirdametinib. Mirdametinib decreased transcription of homologous recombination genes and RAD51 foci, associated with DNA damage repair, in sensitive models. Heterotopic xenograft models displayed synergistic growth inhibition to mirdametinib combined with irradiation in NF1-deficient glioma xenografts, but not those with intact NF1. In sensitive models, benefits were observed at least three weeks beyond the completion of treatment, including sustained phosphor-ERK inhibition on immunoblot and decreased Ki-67 expression. These observations demonstrate synergistic activity between mirdametinib and irradiation in NF1-deficient glioma models and may have clinical implications for patients with gliomas that harbor germline or somatic NF1 alterations.
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A meta-analysis was designed and conducted to estimate the effect of tumoral microvessel density (MVD) on the survival of patients with osteosarcoma. There was no difference between high and low MVD regarding the overall (OS) and disease-free (DFS) survival. Low MVD tumors displayed a lower DFS at the third year of follow-up. Although primary metastases did not affect the mean MVD measurements, tumors with a good chemotherapy response had a higher MVD value. Although no significant differences between tumoral MVD, OS and DFS were found, good adjuvant therapy responders had a significant higher vascularization pattern.
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Neoplasias Ósseas , Densidade Microvascular , Osteossarcoma , Humanos , Osteossarcoma/patologia , Osteossarcoma/irrigação sanguínea , Osteossarcoma/tratamento farmacológico , Neoplasias Ósseas/patologia , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/irrigação sanguínea , Neoplasias Ósseas/tratamento farmacológico , Neovascularização Patológica/patologia , Intervalo Livre de Doença , Microvasos/patologia , PrognósticoRESUMO
The purpose of this systematic review is to summarize all existing evidence, regarding the immunohistochemical expression of REV-7 in different human cancer pathology specimens. Moreover, the association of REV-7 expression with disease severity (clinical course), patients' survival, prognosis, and response to various treatments, such as chemotherapy and irradiation, was investigated. Three databases (PubMed, Scopus, and Cochrane) were systematically screened, from inception to September 2, 2023, as suggested by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Only studies using immunohistochemical staining for REV-7 in paraffin-embedded cancer tissues were included. Nine studies met the inclusion criteria and were included in the final qualitative synthesis. All nine studies were retrospective and non-comparative ones. Selected studies reported immunohistochemical expression of REV-7 in different types of cancer, including testicular cancer, ovarian cancer, esophagus squamous cell carcinoma, prostate cancer, colorectal cancer, diffuse large B-cell lymphoma, breast cancer, lung cancer, and skin cancer. High REV-7 expression was associated with faster disease progression, resistance to available treatment options, and worse prognosis in the majority of included studies. These results indicate that immunohistochemical staining of REV-7 protein could potentially be used as a predictive tissue marker in certain cases. Promising results, arising from REV-7 inactivation experiments, render REV-7 targeting a potential therapeutic strategy for future cancer management, especially in the cases of chemoresistant or radioresistant disease.
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Emphysema is prevalent in various respiratory diseases like Chronic Obstructive Pulmonary Disease (COPD) and cystic fibrosis. Colistin and vasoconstrictive drugs are crucial for treating these patients when diagnosed with sepsis in the ICU. This study examines colistin impact in ether-induced emphysematous septic and non-septic animals, focusing on lung pathophysiology and inflammatory responses, including IL-1ß, TNF-α, AMPK, caspase-3, cyclin-D1, and colistin levels in lung tissue. All animals exhibited significant emphysematous changes, accentuated by LPS-induced septic conditions, validating the emphysema model and highlighting the exacerbating effect of sepsis on lung pathology. Colistin, alone or with vasoconstrictive drugs, stimulated immune responses through increased inflammatory cell infiltration and the presence of lymphocytes, indicating potential immunomodulatory effects. Vasoconstriction did not alter the effects of colistin or sepsis but correlated with increased colistin levels in the lungs of septic animals. These observations suggest a potential interplay between vasoconstrictive drugs and colistin distribution/metabolism, leading to enhanced local concentrations of colistin in the lung microenvironment. The findings suggest the need for further investigations to optimize colistin and vasoconstrictive drug delivery in critically ill patients with lung pathologies. Understanding these complexities may guide more effective management of inflammatory responses and lung pathologies in these critical conditions.
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BACKGROUND: Gastrointestinal stromal tumors (GISTs) are considered the most common mesenchymal tumors of the gastrointestinal tract. Microvessel density (MVD) constitutes a direct method of vascularity quantification and has been associated with survival rates in multiple malignancies. AIM: To appraise the effect of MVD on the survival of patients with GIST. METHODS: This study adhered to Systematic reviews and Meta-Analyses guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. Electronic scholar databases and grey literature repositories were systematically screened. The Fixed Effects or Random Effects models were used according to the Cochran Q test. RESULTS: In total, 6 eligible studies were identified. The pooled hazard ratio (HR) for disease free survival (DFS) was 8.52 (95%CI: 1.69-42.84, P = 0.009). The odds ratios of disease-free survival between high and low MVD groups at 12 and 60 mo did not reach statistical significance. Significant superiority of the low MVD group in terms of DFS was documented at 36 and 120 mo (OR: 8.46, P < 0.0001 and OR: 22.71, P = 0.0003, respectively) as well as at metastases rate (OR: 0.11, P = 0.0003). CONCLUSION: MVD significantly correlates with the HR of DFS and overall survival rates at 36 and 120 mo. Further prospective studies of higher methodological quality are required.
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Cytokinesis relies on membrane trafficking pathways regulated by Rabs and guanine nucleotide exchange factors (GEFs). During cytokinesis, the intercellular cytokinetic bridge (ICB) connecting daughter cells undergoes abscission, which requires actin depolymerization. Rab35 recruits MICAL1 to oxidize and depolymerize actin filaments. We show that DENND2B, a protein linked to cancer and congenital disorders, functions as a Rab35 GEF, recruiting and activating Rab35 at the ICB. DENND2B's N-terminal region also interacts with an active form of Rab35, suggesting that DENND2B is both a Rab35 GEF and effector. Knockdown of DENND2B delays abscission, leading to multinucleated cells and filamentous actin (F-actin) accumulation at the ICB, impairing recruitment of ESCRT-III at the abscission site. Additionally, F-actin accumulation triggers the formation of a chromatin bridge, activating the NoCut/abscission checkpoint, and DENND2B knockdown activates Aurora B kinase, a hallmark of checkpoint activation. Thus, our study identifies DENND2B as a crucial player in cytokinetic abscission.
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Actinas , Citocinese , Proteínas de Ligação a DNA , Proteínas rab de Ligação ao GTP , Humanos , Citoesqueleto de Actina/metabolismo , Actinas/metabolismo , Citocinese/fisiologia , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Células HeLa , Proteínas dos Microfilamentos/metabolismo , Oxigenases de Função Mista/metabolismo , Tetraploidia , Proteínas rab de Ligação ao GTP/metabolismo , Proteínas de Ligação a DNA/metabolismoRESUMO
Alzheimer's disease (AD) is an irreversible neurodegenerative disorder characterized by amyloid plaques, neurofibrillary tangles, and cerebral amyloid angiopathy (CAA). CAA is a condition manifesting as amyloid deposits in the cerebral vasculature, eventually leading to microhemorrhage. Here, we have treated the CRND8 mouse model with the C5a agonist (EP67) in order to observe the effects on cerebral amyloidosis, CAA, and hyperphosphorylated tau. EP67 attaches to the C5a receptor on phagocytes and stimulates the engulfment and digestion of fibrillar and prefibrillar amyloid while exhibiting minimal inflammation. Older CRND8 mice and their respective controls were treated with EP67 for a prolonged period of time. Following treatment, the CRND8 mice displayed improved spatial memory, while both amyloid deposition and tau hyperphosphorylation were found to be diminished.
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Doença de Alzheimer , Angiopatia Amiloide Cerebral , Camundongos , Animais , Receptor da Anafilatoxina C5a , Peptídeos beta-Amiloides/metabolismo , Angiopatia Amiloide Cerebral/tratamento farmacológico , Encéfalo/metabolismo , Doença de Alzheimer/tratamento farmacológico , Cognição , Placa Amiloide , Amiloide/metabolismo , Fosfopiruvato HidrataseRESUMO
OBJECTIVE: Head and neck follicular lymphoma (FL) with marginal zone (MZ) differentiation is a rare high-risk B-cell composite variant that has been reported in nodular but not extranodular sites in the parotid glands. Here we summarize the literature on FL with MZ differentiation in head and neck nodular sites and describe a rare case of extranodular FL with MZ differentiation in the parotid gland. STUDY DESIGN: We examined both the germinal center and MZ components of the parotid and bone-marrow biopsies of a 65-year-old female histologically, immunohistochemically, and molecularly to identify B-cell, germinal center, and follicular dendritic cell markers. RESULTS: The immunohistochemical and molecular analysis provided evidence that the FL and the MZ components derived from the same B-cell clone with a similar BCL2/IGH t(14;18) translocation site. The differentiated cells in the MZ did not express germinal center markers BCL6 and CD10. Both the parotid and bone-marrow proliferative B cells showed BCL6, CD2O, and CD79a positivity. CONCLUSIONS: Head and neck FL with MZ differentiation can develop in both nodular and extranodular sites and is characterized by BCL2 translocation t(14;18). Although the mechanism of MZ differentiation is unclear, the characterization of this rare histopathologic phenomenon might be clinically important.
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Linfoma Folicular , Feminino , Humanos , Idoso , Linfoma Folicular/genética , Linfoma Folicular/química , Linfoma Folicular/patologia , Medula Óssea , Translocação Genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Diferenciação CelularRESUMO
Dysphagia is a common clinical symptom in older people that can be attributed to a wide range of diseases, extending from neoplasm to gastroesophageal reflux diseases such as stroke or achalasia. We are presenting a case of a 78-year-old male with a history of heart failure with preserved ejection fraction and progressive dysphagia, due to a rare case, namely, dysphagia megalatriensis. Even though left ventricular ejection fraction was preserved, the patient improved, when we provided him with optimal medical heart failure with reduced ejection fraction treatment. In our case report, we intend to highlight the benefits of optimized medical therapy in a patient with heart failure with preserved ejection fraction, due to mitral valve regurgitation leading to a hugely dilated left atrium.
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Transtornos de Deglutição , Insuficiência Cardíaca , Disfunção Ventricular Esquerda , Humanos , Masculino , Idoso , Volume Sistólico , Função Ventricular Esquerda , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/etiologia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnósticoRESUMO
CASE: We describe the case of a 53-year-old male patient with a history of acute carpal tunnel syndrome (CTS) provoked by a radio-opaque mass on the palmar side of the wrist. Although the mass disappeared in new radiographs 6 weeks later without any intervention apart from the carpal tunnel release, excisional biopsy was conducted on the residue, revealing tumoral calcinosis. CONCLUSION: Both acute CTS and spontaneous resolution are clinical manifestations of this rare condition on suspicion of which biopsy can be avoided by following a "wait and see" strategy.
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Calcinose , Síndrome do Túnel Carpal , Masculino , Humanos , Pessoa de Meia-Idade , Punho/patologia , Síndrome do Túnel Carpal/diagnóstico por imagem , Síndrome do Túnel Carpal/etiologia , Articulação do Punho/patologia , Radiografia , Calcinose/complicações , Calcinose/diagnóstico por imagem , Calcinose/patologiaRESUMO
BACKGROUND: Microvessel density (MVD) has been proposed as a direct quantification method of tumor neovascularization. However, the current literature regarding the role of MVD in differentiated thyroid carcinoma (DTC) remains inconclusive. AIM: To appraise the effect of tumoral MVD on the survival of patients with DTC. METHODS: This meta-analysis was based on the PRISMA guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. The electronic databases Medline, Web of Science, and Scopus were systematically screened. A fixed-effects or random-effects model was used, according to the Cochran Q test. The data were then extracted and assessed on the basis of the Reference Citation Analysis (https://www.referencecitationanalysis.com/). RESULTS: A total of nine studies were included in the present study. Superiority of low MVD tumors in terms of 10-year disease free survival (OR: 0.21, 95%CI: 0.08-0.53) was recorded. Lowly vascularized thyroid cancers had a lower recurrence rate (OR: 13.66, 95%CI: 3.03-61.48). Moreover, relapsing tumors [weighed mean difference (WMD): 11.92, 95%CI: 6.32-17.52] or malignancies with regional lymph node involvement (WMD: 8.53, 95%CI: 0.04-17.02) presented with higher tumoral MVD values. CONCLUSION: MVD significantly correlates with the survival outcomes of thyroid cancer patients. However, considering several study limitations, further prospective studies of higher methodological and quality level are required.
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Hemophagocytic lymphohistiocytosis (HLH) constitutes a life-threatening inflammatory syndrome. Postmortem histological findings of bone marrow (BM) from COVID-19 patients showed histiocytosis and hemophagocytosis and supported the hypothesis that secondary HLH (sHLH) may be triggered by SARS-CoV-2 infection. However, there are a limited number of sHLH cases in which trephine has been performed in living post-COVID-19 patients. Here we present a recent case and a mini-review of sHLH diagnosed by trephine biopsy in living patients after COVID-19. An 81-year-old man with a past medical history of hypertension, diabetes, ischemic stroke, was referred to the hospital to evaluate leukocytosis, pyuria, and elevation of inflammatory markers four weeks after recovering from COVID-19. Computed tomography of the abdomen did not reveal focal signs of infection or hepatosplenomegaly. The patient received intravenous meropenem and two packed red blood cell units. Leukocytes and C-reactive protein were gradually decreased. A BM biopsy was performed and the patient was discharged on cefixime. BM smear revealed severe anemia, lymphopenia, and dysplastic morphologic findings of erythroblasts, neutrophils, and megakaryocytes. Trephine biopsy revealed hypercellular marrow dyserythropoiesis, plasmacytosis, lymphocytosis, histiocytosis, hemophagocytosis, and the absence of granulomas or carcinoma. Immunohistochemistry documented a mixed population of T lymphocytes (CD3+) and B lymphocytes (CD20+). Strong positivity for CD68 confirmed histiocytosis. CD138 κ, λ staining proved polyclonal plasmacytosis. Perl's staining showed excess hemosiderin deposits. Based on our findings, we document sHLH in trephine BM biopsy of a living post-COVID-19 patient and persistent leukocytosis, underscoring the diagnostic value of trephine biopsy in preventing life-threatening conditions such as COVID-19.
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COVID-19 , Linfo-Histiocitose Hemofagocítica , Idoso de 80 Anos ou mais , Biópsia/efeitos adversos , Medula Óssea/patologia , COVID-19/complicações , Humanos , Leucocitose/complicações , Leucocitose/patologia , Linfo-Histiocitose Hemofagocítica/complicações , Linfo-Histiocitose Hemofagocítica/etiologia , Masculino , SARS-CoV-2RESUMO
Correctly diagnosing a rare childhood cancer such as sarcoma can be critical to assigning the correct treatment regimen. With a finite number of pathologists worldwide specializing in pediatric/young adult sarcoma histopathology, access to expert differential diagnosis early in case assessment is limited for many global regions. The lack of highly-trained sarcoma pathologists is especially pronounced in low to middle-income countries, where pathology expertise may be limited despite a similar rate of sarcoma incidence. To address this issue in part, we developed a deep learning convolutional neural network (CNN)-based differential diagnosis system to act as a pre-pathologist screening tool that quantifies diagnosis likelihood amongst trained soft-tissue sarcoma subtypes based on whole histopathology tissue slides. The CNN model is trained on a cohort of 424 centrally-reviewed histopathology tissue slides of alveolar rhabdomyosarcoma, embryonal rhabdomyosarcoma and clear-cell sarcoma tumors, all initially diagnosed at the originating institution and subsequently validated by central review. This CNN model was able to accurately classify the withheld testing cohort with resulting receiver operating characteristic (ROC) area under curve (AUC) values above 0.889 for all tested sarcoma subtypes. We subsequently used the CNN model to classify an externally-sourced cohort of human alveolar and embryonal rhabdomyosarcoma samples and a cohort of 318 histopathology tissue sections from genetically engineered mouse models of rhabdomyosarcoma. Finally, we investigated the overall robustness of the trained CNN model with respect to histopathological variations such as anaplasia, and classification outcomes on histopathology slides from untrained disease models. Overall positive results from our validation studies coupled with the limited worldwide availability of sarcoma pathology expertise suggests the potential of machine learning to assist local pathologists in quickly narrowing the differential diagnosis of sarcoma subtype in children, adolescents, and young adults.
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Rabdomiossarcoma Embrionário , Rabdomiossarcoma , Adolescente , Animais , Criança , Humanos , Aprendizado de Máquina , Camundongos , Redes Neurais de Computação , Patologistas , Rabdomiossarcoma/diagnóstico , Rabdomiossarcoma Embrionário/patologia , Adulto JovemRESUMO
BACKGROUND/AIM: Pancreatic cancer (PC) is one of the leading causes of cancer-related death. The purpose of the present study was to establish a patient-derived orthotopic xenograft model (PDOX) for pancreatic ductal adenocarcinoma (PDAC), thus providing a tumor microenvironment resembling that of the human pancreas to identify novel potential biomarkers and treatment regimens. MATERIALS AND METHODS: PDAC tissue samples were received from 35 patients, following informed consent, and three mouse strains were implemented. RESULTS: Successful PDOX engraftment was performed in nonobese diabetic/severe combined immunodeficient (NOD/SCID) and NOD/SCID gamma (NSG) mice. Nonetheless, we found a higher rate of successful engraftment and tumor growth in NSG compared to NOD/SCID mice, possibly owning to the different level of immunosuppression and more specifically of the natural killer cells presence. CONCLUSION: Our suggested PDOX model represents a preclinical cancer research model with a high affinity for the patient's tumor microenvironment, thus enabling the acceleration of PDAC research.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Animais , Carcinoma Ductal Pancreático/patologia , Modelos Animais de Doenças , Xenoenxertos , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Neoplasias Pancreáticas/patologia , Microambiente Tumoral , Neoplasias PancreáticasRESUMO
Prostate cancer is one of the most commonly diagnosed malignancies in men. Most of these tumors are adenocarcinomas. Plasmacytoid is a rare variant of adenocarcinoma described by previous studies in the genitourinary system and is characterized by the plasmacytoid appearance of tumor cells with abundant cytoplasm and abnormally placed hyperchromatic nuclei. However, to the best of our knowledge, plasmacytoid adenocarcinoma has rarely been described in the prostate. This report describes a new case of plasmacytoid adenocarcinoma of the prostate diagnosed by biopsy and summarizes the known literature on plasmacytoid features in the genitourinary system. A 62-year-old male patient presented to the hospital with urinary retention, hematuria, weakness and weight loss. The digital rectal examination revealed an irregular enlargement. Laboratory findings showed elevated levels of prostate specific antigen (PSA; 43.6 ng/ml). Transrectal ultrasound showed invasion of the right seminal vesicle. Prostate tumor core biopsies were collected and sent for diagnosis. Histological examination revealed a high-grade prostatic adenocarcinoma Gleason score of 5+5 (total score 10). The tumor cells had a plasmacytoid appearance with abundant cytoplasm and abnormally placed hyperchromatic nuclei. The immunohistochemical phenotype was characterized by abundant positivity for cytokeratin (CK)AE1/AE3 and PSA. By contrast, tumor cells were negative for p63, CK 34BE12 and GATA binding protein 3 (urothelial markers), synaptophysin (neuroendocrine marker). Tumor cells were also negative for E-cadherin, which is particularly indicative of CDH1 alterations. To the best of our knowledge, this is the first description of a plasmacytoid adenocarcinoma of the prostate diagnosed by biopsy, showing an irregular immunophenotype that may indicate somatic CDH1 alterations. The presentation of a novel rare variant of prostatic carcinoma that differs from other neoplasms of the genitourinary system may contribute to an improved understanding of this uncommonly found histological pattern that may also be mandatory due to the clinical and prognostic implications of this diagnosis.