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ABSTRACT: Although CD20×CD3 bispecific antibodies are effective against systemic B-cell lymphomas, their efficacy in central nervous system (CNS) lymphoma is unknown. Here, we report the CD20×CD3 bispecific glofitamab penetrates the blood-brain barrier, stimulates immune-cell infiltration of CNS tumors, and induces clinical responses in patients with secondary CNS.
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Anticuerpos Biespecíficos , Neoplasias del Sistema Nervioso Central , Humanos , Neoplasias del Sistema Nervioso Central/inmunología , Neoplasias del Sistema Nervioso Central/patología , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Anticuerpos Biespecíficos/uso terapéutico , Barrera Hematoencefálica/patología , Antígenos CD20/inmunología , Complejo CD3/inmunología , Femenino , Masculino , Linfoma de Células B/inmunología , Linfoma de Células B/patología , Linfoma de Células B/tratamiento farmacológico , Linfoma/inmunología , Linfoma/patología , Linfoma/tratamiento farmacológico , Persona de Mediana EdadRESUMEN
The convergence of digital pathology and artificial intelligence could assist histopathology image analysis by providing tools for rapid, automated morphological analysis. This systematic review explores the use of artificial intelligence for histopathological image analysis of digitised central nervous system (CNS) tumour slides. Comprehensive searches were conducted across EMBASE, Medline and the Cochrane Library up to June 2023 using relevant keywords. Sixty-eight suitable studies were identified and qualitatively analysed. The risk of bias was evaluated using the Prediction model Risk of Bias Assessment Tool (PROBAST) criteria. All the studies were retrospective and preclinical. Gliomas were the most frequently analysed tumour type. The majority of studies used convolutional neural networks or support vector machines, and the most common goal of the model was for tumour classification and/or grading from haematoxylin and eosin-stained slides. The majority of studies were conducted when legacy World Health Organisation (WHO) classifications were in place, which at the time relied predominantly on histological (morphological) features but have since been superseded by molecular advances. Overall, there was a high risk of bias in all studies analysed. Persistent issues included inadequate transparency in reporting the number of patients and/or images within the model development and testing cohorts, absence of external validation, and insufficient recognition of batch effects in multi-institutional datasets. Based on these findings, we outline practical recommendations for future work including a framework for clinical implementation, in particular, better informing the artificial intelligence community of the needs of the neuropathologist.
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Inteligencia Artificial , Neoplasias del Sistema Nervioso Central , Humanos , Neoplasias del Sistema Nervioso Central/patología , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
PURPOSE: To develop and validate a pathomics signature for predicting the outcomes of Primary Central Nervous System Lymphoma (PCNSL). METHODS: In this study, 132 whole-slide images (WSIs) of 114 patients with PCNSL were enrolled. Quantitative features of hematoxylin and eosin (H&E) stained slides were extracted using CellProfiler. A pathomics signature was established and validated. Cox regression analysis, receiver operating characteristic (ROC) curves, Calibration, decision curve analysis (DCA), and net reclassification improvement (NRI) were performed to assess the significance and performance. RESULTS: In total, 802 features were extracted using a fully automated pipeline. Six machine-learning classifiers demonstrated high accuracy in distinguishing malignant neoplasms. The pathomics signature remained a significant factor of overall survival (OS) and progression-free survival (PFS) in the training cohort (OS: HR 7.423, p < 0.001; PFS: HR 2.143, p = 0.022) and independent validation cohort (OS: HR 4.204, p = 0.017; PFS: HR 3.243, p = 0.005). A significantly lower response rate to initial treatment was found in high Path-score group (19/35, 54.29%) as compared to patients in the low Path-score group (16/70, 22.86%; p < 0.001). The DCA and NRI analyses confirmed that the nomogram showed incremental performance compared with existing models. The ROC curve demonstrated a relatively sensitive and specific profile for the nomogram (1-, 2-, and 3-year AUC = 0.862, 0.932, and 0.927, respectively). CONCLUSION: As a novel, non-invasive, and convenient approach, the newly developed pathomics signature is a powerful predictor of OS and PFS in PCNSL and might be a potential predictive indicator for therapeutic response.
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Neoplasias del Sistema Nervioso Central , Linfoma , Aprendizaje Automático , Humanos , Femenino , Masculino , Neoplasias del Sistema Nervioso Central/patología , Neoplasias del Sistema Nervioso Central/diagnóstico , Neoplasias del Sistema Nervioso Central/mortalidad , Persona de Mediana Edad , Pronóstico , Linfoma/patología , Linfoma/diagnóstico , Linfoma/mortalidad , Anciano , Adulto , Curva ROC , Anciano de 80 o más Años , Tasa de Supervivencia , Adulto Joven , Estudios Retrospectivos , Biomarcadores de Tumor/metabolismoRESUMEN
PURPOSE: Central nervous system (CNS) embryonal tumors are a diverse group of malignant tumors typically affecting pediatric patients that recently have been better defined, and this paper describes evolution of a unique type of embryonal tumor at relapse. METHODS: Two pediatric patients with CNS embryonal tumors with EWSR1-PLAGL1 rearrangements treated at Arkansas Children's Hospital with histopathologic and molecular data are described. RESULTS: These two patients at diagnosis were classified as CNS embryonal tumors with EWSR1-PLAGL1 rearrangements based on histologic appearance and molecular data. At relapse both patient's disease was reclassified as atypical teratoid rhabdoid tumor (ATRT) based on loss of INI-1, presence of SMARCB1 alterations, and methylation profiling results. CONCLUSION: CNS embryonal tumors with EWSR1-PLAGL1 rearrangements acquire or include a population of cells with SMARCB1 alterations that are the component that predominate at relapse, suggesting treatment aimed at this disease component at diagnosis should be considered.
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Neoplasias del Sistema Nervioso Central , Recurrencia Local de Neoplasia , Neoplasias de Células Germinales y Embrionarias , Proteína EWS de Unión a ARN , Proteína SMARCB1 , Femenino , Humanos , Masculino , Neoplasias del Sistema Nervioso Central/genética , Neoplasias del Sistema Nervioso Central/patología , Reordenamiento Génico , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Neoplasias de Células Germinales y Embrionarias/genética , Neoplasias de Células Germinales y Embrionarias/patología , Tumor Rabdoide/genética , Tumor Rabdoide/patología , Proteína EWS de Unión a ARN/genética , Proteína SMARCB1/genética , LactanteRESUMEN
PURPOSE: Immunosuppression is a well-established risk factor for primary central nervous system lymphomas (PCNSLs), which present in this context distinct radiological characteristics. Our aim was to describe the radiological evolution of treated PCNSL in immunocompromised patients and suggest adapted MRI response criteria. METHODS: We conducted a multicenter retrospective study of patients from the French LOC, K-Virogref and CANCERVIH network databases and enrolled adult immunocompromised patients with newly diagnosed PCNSL. RESULTS: We evaluated the baseline, intermediate, end-of-treatment and follow-up MRI data of 31 patients (9 living with HIV, 16 with solid organ transplantation and 6 with an autoimmune disease under chronic immunosuppressive therapy). At baseline, 23/30 (77%) patients had necrotic lesions with ring enhancement and 28% of the lesions were hemorrhagic. At the end of the first-line treatment, 12/28 (43%) patients could not be classified according to the IPCG criteria. Thirteen of 28 (46%) patients still harbored contrast enhancement, and 11/28 (39%) patients had persistent large necrotic lesions with a median diameter of 15 mm. These aspects were not associated with a pejorative outcome and progressively diminished during follow-up. Six patients relapsed; however, we failed to identify any neuroimaging risk factors on the end-of-treatment MRI. CONCLUSION: In immunocompromised patients, PCNSLs often harbor alarming features on end-of-treatment MRI, with persistent contrast-enhanced lesions frequently observed. However, these aspects seemed to be related to the necrotic and hemorrhagic nature of the lesions and were not predictive of a pejorative outcome. Specific response criteria for this population are thereby proposed.
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Neoplasias del Sistema Nervioso Central , Huésped Inmunocomprometido , Linfoma , Imagen por Resonancia Magnética , Humanos , Masculino , Femenino , Persona de Mediana Edad , Neoplasias del Sistema Nervioso Central/inmunología , Neoplasias del Sistema Nervioso Central/patología , Neoplasias del Sistema Nervioso Central/diagnóstico por imagen , Estudios Retrospectivos , Huésped Inmunocomprometido/inmunología , Anciano , Adulto , Linfoma/diagnóstico por imagen , Linfoma/patología , Linfoma/inmunología , Estudios de SeguimientoRESUMEN
PURPOSE: Von Hippel-Lindau (VHL) disease is an autosomal-dominantly inherited tumor predisposition syndrome. One of the most common tumors are central nervous system (CNS) hemangioblastomas. Recommendations on the initiation and continuation of the screening and surveillance program for CNS tumors in pediatric VHL patients are based on small case series and thus low evidence level. To derive more robust screening recommendations, we report on the largest monocentric pediatric cohort of VHL patients. METHODS: We performed a retrospective analysis on a pediatric cohort of 99 VHL patients consulted at our VHL center from 1992 to 2023. Clinical, surgical, genetic, and imaging data were collected and statistically analyzed. RESULTS: 42 patients (50% male) developed CNS hemangioblastomas, of whom 18 patients (56% male) underwent hemangioblastoma surgery (mean age at first surgery: 14.9 ± 1.9 years; range 10.2-17). The first asymptomatic patient was operated on at the age of 13.2 years due to tumor progress. Truncating VHL mutation carriers had a significantly higher manifestation rate (HR = 3.7, 95% CI: 1.9-7.4, p < 0.0001) and surgery rate (HR = 3.3, 95% CI: 1.2-8.9, p = 0.02) compared with missense mutation carriers. CONCLUSION: We recommend starting MRI imaging at the age of 12 years with examination intervals every (1-) 2 years depending on CNS involvement. Special attention should be paid to patients with truncating variants. Affected families should be educated regularly on potential tumor-associated symptoms to enable timely MRI imaging and eventually intervention, as CNS hemangioblastoma may develop before screening begins. GERMAN CLINICAL TRIALS REGISTER REGISTRATION NUMBER: DRKS00029553, date of registration 08/16/2022, retrospectively registered.
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Hemangioblastoma , Enfermedad de von Hippel-Lindau , Humanos , Enfermedad de von Hippel-Lindau/genética , Enfermedad de von Hippel-Lindau/complicaciones , Hemangioblastoma/cirugía , Hemangioblastoma/genética , Hemangioblastoma/patología , Masculino , Femenino , Adolescente , Niño , Estudios Retrospectivos , Neoplasias Cerebelosas/genética , Neoplasias Cerebelosas/cirugía , Neoplasias Cerebelosas/patología , Neoplasias del Sistema Nervioso Central/genética , Neoplasias del Sistema Nervioso Central/diagnóstico , Neoplasias del Sistema Nervioso Central/cirugía , Neoplasias del Sistema Nervioso Central/patología , Estudios de Seguimiento , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/genéticaRESUMEN
BACKGROUND: The contribution of tumor type, multimodal treatment, and other patient-related factors upon long-term cognitive sequelae in infant brain tumor survivors remains undefined. We add our retrospective analysis of neuropsychological and quality of survival (QoS) outcome data of survivors of atypical teratoid/rhabdoid tumors (ATRT) and extracranial malignant rhabdoid tumors of the soft tissues (eMRT) and kidneys (RTK) treated within the same framework. Neuropsychological data from children with ATRT were compared to data from children with non-irradiated low-grade glioma (LGG). PATIENTS AND METHODS: Following surgery, patients (0-36 months at diagnosis) had received radio-chemotherapy (up to 54 Gy; ATRT: n = 13; eMRT/RTK: n = 7), chemotherapy only (LGG: n = 4; eMRT/RTK: n = 1) or had been observed (LGG: n = 11). Neuropsychological evaluation employing comparable tests was performed at median 6.8 years (ATRT), 6.6 years (eMRT/RTK), and 5.2 years (LGG) post diagnosis. RESULTS: We detected sequelae in various domains for all tumor types. Group comparison showed impairments, specifically in fluid intelligence (p = .041; d = 1.11) and visual processing (p = .001; d = 2.09) in ATRT patients when compared to LGG patients. Results for psychomotor speed and attention abilities were significantly below the norm for both groups (p < .001-.019; d = 0.79-1.90). Diagnosis predicted impairments of cognitive outcome, while sex- and age-related variables did not. QoS outcome for all rhabdoid patients displayed impairments mainly in social (p = .008; d = 0.74) and school functioning (p = .048; d = 0.67), as well as lower overall scores in psychosocial functioning (p = .023; d = 0.78) and quality of life (p = .006; d = 0.79) compared to healthy controls. CONCLUSION: Survivors of infant ATRT experience various late effects in cognition and QoS following multimodal treatment, while infant LGG patients without radiotherapy demonstrated comparable impairments in psychomotor and attention abilities. Early onset and multimodal treatment of rhabdoid tumors require close monitoring of neuropsychological and QoS sequelae.
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Neoplasias Encefálicas , Neoplasias del Sistema Nervioso Central , Glioma , Neoplasias Neuroepiteliales , Tumor Rabdoide , Teratoma , Niño , Lactante , Humanos , Tumor Rabdoide/complicaciones , Tumor Rabdoide/terapia , Estudios Retrospectivos , Calidad de Vida , Teratoma/complicaciones , Teratoma/terapia , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/terapia , Neoplasias del Sistema Nervioso Central/patología , Progresión de la Enfermedad , Percepción Visual , Cognición , SobrevivientesRESUMEN
The addition of rituximab to standard regimens for primary mediastinal large B-cell lymphoma (PMBCL) has significantly improved overall survival. However, the optimal management of isolated central nervous system (CNS) relapse and role of CNS prophylaxis remains undefined. We present cases of two adolescents with PMBCL who developed isolated CNS relapses. While isolated CNS relapse may be managed with high-dose chemotherapy and autologous stem cell transplant with or without CNS radiotherapy, review of these cases and the literature highlight the need for further work to define risk factors for CNS relapse, and identify patients who may benefit from CNS prophylaxis.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias del Sistema Nervioso Central , Linfoma de Células B Grandes Difuso , Neoplasias del Mediastino , Rituximab , Humanos , Neoplasias del Mediastino/patología , Neoplasias del Mediastino/terapia , Neoplasias del Mediastino/tratamiento farmacológico , Adolescente , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células B Grandes Difuso/terapia , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Sistema Nervioso Central/terapia , Neoplasias del Sistema Nervioso Central/patología , Masculino , Rituximab/administración & dosificación , Rituximab/uso terapéutico , Vincristina/administración & dosificación , Etopósido/administración & dosificación , Etopósido/uso terapéutico , Doxorrubicina/administración & dosificación , Ciclofosfamida/administración & dosificación , Femenino , Prednisona/administración & dosificación , Prednisona/uso terapéutico , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapiaRESUMEN
BACKGROUND: Diagnosis of primary diffuse large B-cell lymphoma of the central nervous system (PCNSL) is challenging and often delayed. MRI imaging, CSF cytology and flow cytometry have a low sensitivity and even brain biopsies can be misleading. We report three cases of PCNSL with various clinical presentation and radiological findings where the diagnosis was suggested by novel CSF biomarkers and subsequently confirmed by brain biopsy or autopsy. CASE PRESENTATIONS: The first case is a 79-year-old man with severe neurocognitive dysfunction and static ataxia evolving over 5 months. Brain MRI revealed a nodular ventriculitis. An open brain biopsy was inconclusive. The second case is a 60-year-old woman with progressive sensory symptoms in all four limbs, evolving over 1 year. Brain and spinal MRI revealed asymmetric T2 hyperintensities of the corpus callosum, corona radiata and corticospinal tracts. The third case is a 72-year-old man recently diagnosed with primary vitreoretinal lymphoma of the right eye. A follow-up brain MRI performed 4 months after symptom onset revealed a T2 hyperintense fronto-sagittal lesion, with gadolinium uptake and perilesional edema. In all three cases, CSF flow cytometry and cytology were negative. Mutation analysis on the CSF (either by digital PCR or by next generation sequencing) identified the MYD88 L265P hotspot mutation in all three cases. A B-cell clonality study, performed in case 1 and 2, identified a monoclonal rearrangement of the immunoglobulin light chain lambda (IGL) and kappa (IGK) gene. CSF CXCL-13 and IL-10 levels were high in all three cases, and IL-10/IL-6 ratio was high in two. Diagnosis of PCNSL was later confirmed by autopsy in case 1, and by brain biopsy in case 2 and 3. CONCLUSIONS: Taken together, 5 CSF biomarkers (IL-10, IL-10/IL-6 ratio, CXCL13, MYD88 mutation and monoclonal IG gene rearrangements) were strongly indicative of a PCNSL. Using innovative CSF biomarkers can be sensitive and complementary to traditional CSF analysis and brain biopsy in the diagnosis of PCNSL, potentially allowing for earlier diagnosis and treatment.
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Linfoma de Células B Grandes Difuso , Humanos , Masculino , Anciano , Linfoma de Células B Grandes Difuso/líquido cefalorraquídeo , Linfoma de Células B Grandes Difuso/diagnóstico , Persona de Mediana Edad , Femenino , Neoplasias del Sistema Nervioso Central/líquido cefalorraquídeo , Neoplasias del Sistema Nervioso Central/diagnóstico por imagen , Neoplasias del Sistema Nervioso Central/diagnóstico , Neoplasias del Sistema Nervioso Central/patología , Biomarcadores de Tumor/líquido cefalorraquídeo , Encéfalo/patología , Encéfalo/diagnóstico por imagen , Imagen por Resonancia MagnéticaRESUMEN
INTRODUCTION: Cauda equina neuroendocrine tumors (CENETs), previously described as cauda equina paragangliomas (PGLs) are rare and well-vascularized benign entities which can be often misdiagnosed with other intradural tumors more common in this anatomical site, such as ependymomas and neurinomas. We describe three cases of CENETs observed at our institution with particular focus on differential diagnosis and postoperative management. Since the lack of guidelines, we performed a literature review to identify factors that can predict recurrence and influence postoperative decision making. CASE REPORT AND LITERATURE REVIEW: We report on three patients, two of them presenting with a clinical history of lower back pain and sciatica. In all cases magnetic resonance imaging (MRI) of the lumbosacral spine with and without Gd-DTPA revealed an intradural lesion with strong contrast enhancement, first described as atypical ependymoma or schwannoma. A complete tumor resection was achieved in all cases, the histopathological diagnosis classified the tumors as CENETs. In our literature review, a total of 688 articles were screened and 162 patients were included. Patients demographic data, clinical symptoms, resection and recurrence were recorded. DISCUSSION: Differential diagnosis between CENETs and other more common tumors affecting cauda equina region, such as ependymomas or schwannomas (neurinomas), is still very challenging. Due to the lack of specific clinical or radiological characteristics, a correct preoperative diagnosis is almost impossible. With this paper we want to point out that CENETs must be considered in the differential diagnosis, most of all in case of entities with atypical radiological features. According to the literature, tumor recurrence after gross total resection is unlikely, while a long-term follow-up is recommended in case of subtotal resection or local aggressive behavior.
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Cauda Equina , Neoplasias del Sistema Nervioso Central , Ependimoma , Neurilemoma , Tumores Neuroendocrinos , Neoplasias de la Columna Vertebral , Humanos , Cauda Equina/patología , Cauda Equina/cirugía , Diagnóstico Diferencial , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/patología , Recurrencia Local de Neoplasia/diagnóstico , Neoplasias de la Columna Vertebral/cirugía , Neurilemoma/cirugía , Neoplasias del Sistema Nervioso Central/patología , Imagen por Resonancia Magnética , Ependimoma/cirugíaRESUMEN
INTRODUCTION: Primary central nervous system lymphoma (PCNSL) presents a diagnostic enigma due to the inherent absence of lymphoid tissue in the central nervous system (CNS). The hypothesis posits that lymphocytes infiltrating the CNS during inflammatory responses could represent a cellular source for PCNSL, challenging traditional understandings of its etiology. PATIENT CONCERNS: In 2 illustrative cases, patients presented with neurological symptoms initially misdiagnosed as encephalitis and demyelinating disease, respectively. These diagnoses were established based on clinical assessments and initial biopsy findings. DIAGNOSIS: Subsequent biopsies, conducted months after the first signs of disease, confirmed the diagnosis of PCNSL in both patients. Identifying CD20-positive tumor cells was pivotal, indicating a B-cell lymphoma origin. INTERVENTIONS: Treatment strategies included high-dose methotrexate chemotherapy for both patients. In addition, the second patient underwent adjuvant whole-brain radiotherapy after the chemotherapy regimen. OUTCOMES: The therapeutic approach significantly reduced tumor size in both cases, with no evidence of recurrence observed during the follow-up period. This outcome underscores the potential efficacy of the chosen interventions. CONCLUSION: In response to inflammatory lesions, lymphocyte infiltration into the CNS may serve as a pivotal origin for tumor cells in PCNSL. These cases highlight the complexity of diagnosing CNS disorders and suggest that various forms of encephalitis in the early stages could influence the prognosis of lymphoma. This insight into the cellular origins and treatment responses of PCNSL contributes to a broader understanding of its pathophysiology and management.
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Neoplasias del Sistema Nervioso Central , Metotrexato , Humanos , Masculino , Persona de Mediana Edad , Biopsia , Neoplasias del Sistema Nervioso Central/patología , Neoplasias del Sistema Nervioso Central/diagnóstico , Diagnóstico Diferencial , Encefalitis/patología , Encefalitis/diagnóstico , Linfoma de Células B/patología , Linfoma de Células B/diagnóstico , Imagen por Resonancia Magnética , Metotrexato/uso terapéuticoRESUMEN
Central nervous system (CNS) tumors comprise around 20% of childhood malignancies. Germline variants in cancer predisposition genes (CPGs) are found in approximately 10% of pediatric patients with CNS tumors. This study aimed to characterize variants in CPGs in pediatric patients with CNS tumors and correlate these findings with clinically relevant data. Genomic DNA was isolated from the peripheral blood of 51 pediatric patients and further analyzed by the next-generation sequencing approach. Bioinformatic analysis was done using an "in-house" gene list panel, which included 144 genes related to pediatric brain tumors, and the gene list panel Neoplasm (HP:0002664). Our study found that 27% of pediatric patients with CNS tumors have a germline variant in some of the known CPGs, like ALK, APC, CHEK2, ELP1, MLH1, MSH2, NF1, NF2 and TP53. This study represents the first comprehensive evaluation of germline variants in pediatric patients with CNS tumors in the Western Balkans region. Our results indicate the necessity of genomic research to reveal the genetic basis of pediatric CNS tumors, as well as to define targets for the application and development of innovative therapeutics that form the basis of the upcoming era of personalized medicine.
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Neoplasias Encefálicas , Neoplasias del Sistema Nervioso Central , Humanos , Niño , Predisposición Genética a la Enfermedad , Mutación de Línea Germinal , Neoplasias del Sistema Nervioso Central/genética , Neoplasias del Sistema Nervioso Central/patología , Células Germinativas/patologíaAsunto(s)
Neoplasias del Sistema Nervioso Central , Histonas , Proteínas Represoras , Humanos , Neoplasias del Sistema Nervioso Central/metabolismo , Neoplasias del Sistema Nervioso Central/patología , Histonas/metabolismo , Histonas/genética , Proteínas Represoras/genética , Proteínas Represoras/metabolismoAsunto(s)
Neoplasias del Sistema Nervioso Central , Neoplasias de Células Germinales y Embrionarias , Niño , Humanos , Metilación de ADN , Neoplasias del Sistema Nervioso Central/genética , Neoplasias del Sistema Nervioso Central/patología , Neoplasias de Células Germinales y Embrionarias/genética , Sistema Nervioso Central/patologíaRESUMEN
Central nervous system (CNS) metastases represent a small portion of pediatric CNS neoplasms and data surrounding this condition with high morbidity is scarce. Single institutional archival institutional pathology records between 1999 and 2022 were searched for patients over 21 years old and younger with CNS, dura, cranial nerve, CSF, or leptomeningeal metastases; 41 cases were identified. We documented primary tumor types and locations, metastasis locations, types of invasion (direct extension vs distant metastasis), times from imaging or pathologic diagnosis to CNS involvement, and outcomes. Distant metastasis was the most common mechanism of metastasis (n = 32, 78%). Interval times to CNS metastasis varied by both tumor type and primary tumor location. In this cohort, osteosarcoma portended the shortest survival following CNS metastasis. This study highlights the diverse mechanisms and locations of CNS involvement in pediatric CNS metastases and illuminates a need for varied monitoring strategies when considering primary tumor type and anatomic location.
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Neoplasias del Sistema Nervioso Central , Neoplasias Primarias Secundarias , Adulto , Niño , Humanos , Adulto Joven , Sistema Nervioso Central/patología , Neoplasias del Sistema Nervioso Central/patología , Estudios RetrospectivosRESUMEN
Precision in the diagnosis of diverse central nervous system (CNS) tumor types is crucial for optimal treatment. DNA methylation profiles, which capture the methylation status of thousands of individual CpG sites, are state-of-the-art data-driven means to enhance diagnostic accuracy but are also time consuming and not widely available. Here, to address these limitations, we developed Deep lEarning from histoPathoLOgy and methYlation (DEPLOY), a deep learning model that classifies CNS tumors to ten major categories from histopathology. DEPLOY integrates three distinct components: the first classifies CNS tumors directly from slide images ('direct model'), the second initially generates predictions for DNA methylation beta values, which are subsequently used for tumor classification ('indirect model'), and the third classifies tumor types directly from routinely available patient demographics. First, we find that DEPLOY accurately predicts beta values from histopathology images. Second, using a ten-class model trained on an internal dataset of 1,796 patients, we predict the tumor categories in three independent external test datasets including 2,156 patients, achieving an overall accuracy of 95% and balanced accuracy of 91% on samples that are predicted with high confidence. These results showcase the potential future use of DEPLOY to assist pathologists in diagnosing CNS tumors within a clinically relevant short time frame.
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Neoplasias del Sistema Nervioso Central , Metilación de ADN , Aprendizaje Profundo , Humanos , Neoplasias del Sistema Nervioso Central/genética , Neoplasias del Sistema Nervioso Central/patología , Islas de CpG/genética , Femenino , MasculinoRESUMEN
Surgical biopsy is the gold standard for diagnosing central nervous system (CNS) lymphomas. However, reliable liquid biopsy methods for diagnosing CNS lymphomas have quickly developed and have been implicated in clinical decision-making. In the current report, we introduce two patients for whom liquid biopsy was essential for diagnosing CNS lymphomas and discuss the rapidly growing applications of this technology.
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Neoplasias del Sistema Nervioso Central , Anciano , Femenino , Humanos , Masculino , Neoplasias del Sistema Nervioso Central/diagnóstico , Neoplasias del Sistema Nervioso Central/patología , Biopsia Líquida/métodos , Linfoma/diagnóstico , Linfoma/patologíaRESUMEN
OBJECTIVES: Progression of PCNSL remains a challenge with salvage therapies, including the risk of substantial morbidity and mortality. We report patterns of first tumor progression to inform opportunities for improvement. METHODS: This is an institutional retrospective review from 2002 to 2021 of 95 consecutive patients with pathologically confirmed PCNSL, of whom 29 experienced progressive disease. Kaplan-Meier method, log-rank test, and Cox proportional hazard models are used to characterize associations of patient, tumor, and treatment variables with LC, PFS, and patterns of first failure. RESULTS: Most patients were below 65 years old (62%) with KPS >70 (64%) and negative CSF cytology (70%). In 70 patients with MRIs, the median tumor volume was 12.6 mL (range: 0.5 to 67.8 mL). After a median follow-up of 11 months, 1-year PFS was 48% and 1-year LC was 80%. Of the 29 patients with progression, 24% were distant only, 17% were distant and local, and 59% were local only. On MVA, LC was associated with age (HR: 1.08/y, P =0.02), KPS (HR: 0.10, P =0.02), completion of >6 cycles of HD-MTX (HR: 0.10, P <0.01), and use of intrathecal chemotherapy (HR: 0.03, P <0.01). On UVA, local only first failure trended to be increased with >14 mL tumors (OR: 5.06, P =0.08) with 1-year LC 83% (<14 mL) versus 64% (>14mL). There were no significant associations with LC and WBRT ( P =0.37), Rituximab ( P =0.12), or attempted gross total resection ( P =0.72). CONCLUSIONS: Our findings reaffirm the importance of systemic and intrathecal therapies for local control in PCNSL. However, bulky tumors trend to fail locally, warranting further investigation about the role of local therapies or systemic therapy intensification.