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We aimed to evaluate the utility of simple, cost-effective, and non-invasive strategies alternative to BIPSS and peripheral CRH stimulation in differential diagnosis of ACTH-dependent CS. First, we performed ROC analysis to evaluate the performance of various tests for differential diagnosis of ACTH-dependent CS in our cohort (CD, n=76 and EAS, n=23) and derived their optimal cut-offs. Subsequently, combining various demographic (gender), clinical (hypokalemia), biochemical (plasma ACTH, HDDST, peripheral CRH stimulation) and imaging (MRI pituitary) parameters, we derived non-invasive models with 100% PPV for CD. Patients with pituitary macroadenoma (n=14) were excluded from the analysis involving non-invasive models. Relative percent ACTH (AUC: 0.933) and cortisol (AUC: 0.975) increase on peripheral CRH stimulation demonstrated excellent accuracy in discriminating CD from EAS. Best cut-offs for CD were plasma ACTH<97.3 pg/ml, HDDST≥57% cortisol suppression, CRH stimulation≥77% ACTH increase and≥11% cortisol increase. We derived six models that provided 100% PPV for CD and precluded the need for BIPPS in 35/85 (41.2%) patients with ACTH-dependent CS and no macroadenoma (in whom BIPSS would have otherwise been recommended). The first three models included basic parameters and avoided both peripheral CRH stimulation and BIPSS in 19 (22.4%) patients, while the next three models included peripheral CRH stimulation and avoided BIPSS in another 16 (18.8%) patients. Using simple and non-invasive alternative strategies, BIPSS can be avoided in 41% and peripheral CRH stimulation in 22% of patients with ACTH-dependent CS and no macroadenoma; such patients can be directly referred for a pituitary surgery.
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Adamantinomatous craniopharyngioma is a grade 1 tumor that arises in a sellar/suprasellar location. Despite being a grade 1 tumor, there is high recurrence and endocrinal insufficiency. Malignancy arising in craniopharyngioma is extremely rare, has a dismal prognosis, and is currently not included as a separate entity in the World Health Organization Classification of Central Nervous System 5th edition. Here we describe a case of adamantinomatous craniopharyngioma and its malignant counterpart. The malignant part had unique histomorphology and basaloid cells with pseudoglandular architecture and a myxoid background. It bore a striking resemblance to adenoid cystic carcinoma. Both the benign and malignant counterparts were beta-catenin and SOX-2 positive, providing proof of the malignant part arising from the benign part. Tumors like squamous cell carcinoma and odontogenic ghost cell carcinoma have been described in cranipharyngioma. This case study is the first to describe this unique morphology of adenoid cystic carcinoma-like features. The possibility of adenoid cystic carcinoma was excluded by immunohistochemistry.
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Craniofaringioma , Neoplasias Hipofisárias , Humanos , Craniofaringioma/patologia , Neoplasias Hipofisárias/patologia , Masculino , Carcinoma Adenoide Cístico/patologia , Adulto , FemininoRESUMO
Astroblastoma is an uncommon circumscribed glial tumor mostly involving the cerebral hemisphere. The characteristic molecular alteration is meningioma (disrupted in balanced translocation) 1 (MN1) rearrangement. No definite World Health Organization grade has been assigned as both low- and high-grade tumors are known to occur. Tumors in the spine are extremely rare; to date only three cases have been reported in the literature. A vigilant microscopy and ancillary testing aid in diagnosis when the tumors present in unusual locations, as in our case. The prompt differentiation of this tumor from its mimickers is a mandate as modalities of management are different and not clearly established.
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Neoplasias Neuroepiteliomatosas , Humanos , Neoplasias Neuroepiteliomatosas/patologia , Neoplasias Neuroepiteliomatosas/genética , Neoplasias Neuroepiteliomatosas/diagnóstico por imagem , Pré-Escolar , Proteínas Supressoras de Tumor/genética , Neoplasias da Medula Espinal/patologia , Neoplasias da Medula Espinal/genética , Neoplasias da Medula Espinal/diagnóstico por imagem , Masculino , Feminino , TransativadoresRESUMO
BACKGROUND: Pilocytic astrocytoma (PAs) represents a significant portion of childhood primary brain tumors, with distinct histological and radiological features. The prevalence of KIAA1549::BRAF fusion in PAs has been well-established, this study aims to assess the prevalence of KIAA1549::BRAF fusions and explore their associations with tumor characteristics, radiological findings, and patient outcomes in PAs. METHODS: Histologically confirmed cases of PAs from a 5-year period were included in the study. Demographic, histopathological, and radiological data were collected, and immunohistochemistry was performed to characterize tumor markers. FISH and qRT-PCR assays were employed to detect KIAA1549::BRAF fusions. Statistical analyses were conducted to examine associations between fusion status and various other parameters. RESULTS: Histological analysis revealed no significant differences in tumor features based on fusion status. However, younger age groups showed higher fusion prevalence. Radiologically, fusion-positive cases were distributed across different tumor subtypes SE, CWE and NCWE. Survival analysis did not demonstrate a significant impact of fusion status on overall survival, however most cases with recurrence and death harboured KIAA1549::BRAF fusion. Of 200 PAs, KIAA1549::BRAF fusions were detected in 64 % and 74 % of cases via qRT-PCR and FISH, respectively. Concordance between the two platforms was substantial (86 %). CONCLUSION: KIAA1549::BRAF fusions are prevalent in PAs and can be reliably detected using both FISH and qRT-PCR assays. Cost considerations suggest qRT-PCR as a more economical option for fusion detection in routine clinical practice.
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Astrocitoma , Biomarcadores Tumorais , Neoplasias Encefálicas , Proteínas de Fusão Oncogênica , Proteínas Proto-Oncogênicas B-raf , Humanos , Feminino , Masculino , Criança , Astrocitoma/genética , Astrocitoma/patologia , Pré-Escolar , Proteínas de Fusão Oncogênica/genética , Proteínas Proto-Oncogênicas B-raf/genética , Adolescente , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Lactente , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Imuno-Histoquímica/métodos , Hibridização in Situ Fluorescente/métodos , Adulto JovemRESUMO
A 19-year-old female presented with left flank discomfort and swelling. Imaging revealed a large mass arising from the left kidney, and radical nephrectomy confirmed the diagnosis of alveolar soft part sarcoma (ASPS) based on histopathological and ultrastructural examination. Postoperatively, positron emission tomography-computerized tomography showed lung metastasis and renal bed recurrence. Sunitinib was initiated for metastatic ASPS. This case underscores challenges in diagnosing and managing ASPS, highlighting the role of tyrosine kinase inhibitors. Multidisciplinary care and vigilant follow-up are crucial for rare tumors such as ASPS.
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BACKGROUND: Osteosarcoma is a type of bone cancer that predominantly affects young individuals, including children and adolescents. The disease progresses through heterogeneous genetic alterations, and patients often develop pulmonary metastases even after the primary tumors have been surgically removed. Ubiquitin-specific peptidases (USPs) regulate several critical cellular processes, such as cell cycle progression, transcriptional activation, and signal transduction. Various studies have revealed the significance of USP37 in the regulation of replication stress and oncogenesis. METHODS: In this study, the Cancer Genome Atlas (TCGA) database was analyzed to investigate USP37 expression. RNA sequencing was utilized to assess the impact of USP37 overexpression and depletion on gene expression in osteosarcoma cells. Various molecular assays, including colony formation, immunofluorescence, immunoprecipitation, and DNA replication restart, were employed to examine the physical interaction between USP37 and PCNA, as well as its physiological effects in osteosarcoma cells. Additionally, molecular docking studies were conducted to gain insight into the nature of the interaction between USP37 and PCNA. Furthermore, immunohistochemistry was performed on archived tissue blocks from osteosarcoma patients to establish a correlation between USP37 and PCNA expression. RESULTS: Analysis of the TCGA database revealed that increased expression of USP37 was linked to decreased progression-free survival (PFS) in osteosarcoma patients. Next-generation sequencing analysis of osteosarcoma cells demonstrated that overexpression or knockdown of USP37 led to the expression of different sets of genes. USP37 overexpression provided a survival advantage, while its depletion heightened sensitivity to replication stress in osteosarcoma cells. USP37 was found to physically interact with PCNA, and molecular docking studies indicated that the interaction occurs through unique residues. In response to genotoxic stress, cells that overexpressed USP37 resolved DNA damage foci more quickly than control cells or cells in which USP37 was depleted. The expression of USP37 varied in archived osteosarcoma tissues, with intermediate expression seen in 52% of cases in the cohort examined. CONCLUSION: The results of this investigation propose that USP37 plays a vital role in promoting replication stress tolerance in osteosarcoma cells. The interaction between USP37 and PCNA is involved in the regulation of replication stress, and disrupting it could potentially trigger synthetic lethality in osteosarcoma. This study has expanded our knowledge of the mechanism through which USP37 regulates replication stress, and its potential as a therapeutic target in osteosarcoma merits additional exploration.
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Neoplasias Ósseas , Osteossarcoma , Criança , Humanos , Adolescente , Antígeno Nuclear de Célula em Proliferação , Endopeptidases/genética , Endopeptidases/metabolismo , Simulação de Acoplamento Molecular , Proteases Específicas de Ubiquitina , Osteossarcoma/genética , Neoplasias Ósseas/genéticaRESUMO
BACKGROUND: Spinal atypical teratoid rhabdoid tumor (AT/RT) is an extremely rare tumor and represents less than 2% of all AT/RTs. METHODS: Available medical literature on spinal AT/RT in English was retrieved from PubMed and comprehensively reviewed. Clinical presentation, diagnosis, management, prognosis, and outcome in patients with spinal AT/RT have been elucidated by citing a case of extradural AT/RT of the cervicodorsal spine. RESULTS: The age at presentation is usually less than 3 years. The most common site is the cervicodorsal spine. The most frequent tumor location is intradural extramedullary. A contrast-enhanced magnetic resonance imaging (MRI) of the entire neuraxis is the imaging modality of choice. The incidence of leptomeningeal dissemination is high (15-30%). Histopathological examination shows an admixture of primitive neuroectodermal, mesenchymal, and epithelial elements along with rhabdoid cells. Loss of SMARCB1/INI1 is considered pathognomonic of AT/RT. Maximal safe resection of tumor is the initial management of choice. Thereafter focal radiotherapy for localized tumor or craniospinal irradiation for leptomeningeal dissemination should be considered. Post-operative intensive polychemotherapy including intrathecal and high-dose chemotherapy (with autologous stem cell rescue) is usually considered to optimize survival. Typically, the time to recurrence and overall survival are less than 6 and 12 months, respectively. However, with judicious multimodality management long-term survivors are increasingly being recognized. The illustrative patient was a 18-month-old girl diagnosed with extradural AT/RT of the cervicodorsal spine (C3-D1), who was managed with maximal safe resection of tumor, multiagent chemotherapy (ICE-ifosfamide, carboplatin, etoposide) and focal RT to the tumor bed-50.4 Gy/28 fractions/5.5 weeks. At the last follow-up visit, 30 months after surgery, she had complete clinicoradiological response. CONCLUSION: Multimodal treatment comprising maximal safe resection of tumor, multiagent chemotherapy (ICE), and focal RT can lead to successful outcome in patients with localized spinal AT/RT, under the age of 3 years.
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Neoplasias do Sistema Nervoso Central , Tumor Rabdoide , Teratoma , Feminino , Humanos , Pré-Escolar , Lactente , Teratoma/diagnóstico por imagem , Teratoma/terapia , Tumor Rabdoide/diagnóstico por imagem , Tumor Rabdoide/terapia , Coluna VertebralRESUMO
BACKGROUND: Non-invasive biomarkers for early chemotherapeutic response in Ewing sarcoma family of tumors (ESFT) are useful for optimizing existing treatment protocol. PURPOSE: To assess the role of diffusion-weighted magnetic resonance imaging (MRI) in the early evaluation of chemotherapeutic response in ESFT. MATERIAL AND METHODS: A total of 28 patients (mean age = 17.2 ± 5.6 years) with biopsy proven ESFT were analyzed prospectively. Patients underwent MRI acquisition on a 1.5-T scanner at three time points: before starting neoadjuvant chemotherapy (baseline), after first cycle chemotherapy (early time point), and after completion of chemotherapy (last time point). RECIST 1.1 criteria was used to evaluate the response to chemotherapy and patients were categorized as responders (complete and partial response) and non-responders (stable and progressive disease). Tumor diameter, absolute apparent diffusion coefficient (ADC), and normalized ADC (nADC) values in the tumor were measured. Baseline parameters and relative percentage change of parameters after first cycle chemotherapy were assessed for early detection of chemotherapy response. RESULTS: The responder:non-responder ratio was 21:7. At baseline, ADC ([0.864 ± 0.266 vs. 0.977 ± 0.246]) × 10-3mm2/s; P = 0.205) and nADC ([0.740 ± 0.254 vs. 0.925 ± 0.262] × 10-3mm2/s; P = 0.033) among responders was lower than the non-responders and predicted response to chemotherapy with AUCs of 0.6 and 0.735, respectively. At the early time point, tumor diameter (27% ± 14% vs. 4.6% ± 10%; P = 0.002) showed a higher reduction and ADC (75% ± 44% vs. 52% ± 72%; P = 0.039) and nADC (81% ± 44% vs. 48% ± 67%; P = 0.008) showed a higher increase in mean values among responders than the non-responders and identified chemotherapy response with AUC of 0.890, 0.723, and 0.756, respectively. CONCLUSION: Baseline nADC and its change after the first cycle of chemotherapy can be used as non-invasive surrogate markers of early chemotherapeutic response in patients with ESFT.
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Sarcoma de Ewing , Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Sarcoma de Ewing/diagnóstico por imagem , Sarcoma de Ewing/tratamento farmacológico , Resultado do Tratamento , Imagem de Difusão por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética , Critérios de Avaliação de Resposta em Tumores Sólidos , Terapia NeoadjuvanteRESUMO
Low-grade dysembryoplastic neuroepithelial tumors (DNTs) are a frequent cause of drug-refractory epilepsy. Molecular mechanisms underlying seizure generation in these tumors are poorly understood. This study was conducted to identify altered genes in nonneoplastic epileptogenic cortical tissues (ECTs) resected from DNT patients during electrocorticography (ECoG)-guided surgery. RNA sequencing (RNAseq) was used to determine the differentially expressed genes (DEGs) in these high-spiking ECTs compared to non-epileptic controls. A total of 477 DEGs (180 upregulated; 297 downregulated) were observed in the ECTs compared to non-epileptic controls. Gene ontology analysis revealed enrichment of genes belonging to the following Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways: (i) glutamatergic synapse; (ii) nitrogen metabolism; (iii) transcriptional misregulation in cancer; and (iv) protein digestion and absorption. The glutamatergic synapse pathway was enriched by DEGs such as GRM4, SLC1A6, GRIN2C, GRM2, GRM5, GRIN3A, and GRIN2B. Enhanced glutamatergic activity was observed in the pyramidal neurons of ECTs, which could be attributed to altered synaptic transmission in these tissues compared to non-epileptic controls. Besides glutamatergic synapse, altered expression of other genes such as GABRB1 (synapse formation), SLIT2 (axonal growth), and PROKR2 (neuron migration) could be linked to epileptogenesis in ECTs. Also, upregulation of GABRA6 gene in ECTs could underlie benzodiazepine resistance in these patients. Neural cell-type-specific gene set enrichment analysis (GSEA) revealed transcriptome of ECTs to be predominantly contributed by microglia and neurons. This study provides first comprehensive gene expression profiling of nonneoplastic ECTs of DNT patients and identifies genes/pathways potentially linked to epileptogenesis.
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Neoplasias Encefálicas , Neoplasias Neuroepiteliomatosas , Criança , Humanos , Benzodiazepinas , Neoplasias Encefálicas/patologia , Perfilação da Expressão Gênica , Neoplasias Neuroepiteliomatosas/genética , Neoplasias Neuroepiteliomatosas/metabolismo , Neoplasias Neuroepiteliomatosas/patologia , Nitrogênio , TranscriptomaRESUMO
BACKGROUND: Early prediction of response to neoadjuvant chemotherapy (NACT) is important to aid personalized treatment in osteosarcoma. Diffusion-weighted Intravoxel Incoherent Motion (IVIM) MRI was used to evaluate the predictive value for response to NACT and survival outcome in osteosarcoma. METHODS: Total fifty-five patients with biopsy-proven osteosarcoma were recruited prospectively, among them 35 patients were further analysed. Patients underwent 3 cycles of NACT (Cisplatin + Doxorubicin) followed by surgery and response adapted adjuvant chemotherapy. Treatment outcomes were histopathological response to NACT (good-response ≥ 50% necrosis and poor-response < 50% necrosis) and survival outcome (event-free survival (EFS) and overall survival (OS)). IVIM MRI was acquired at 1.5T at baseline (t0), after 1-cycle (t1) and after 3-cycles (t2) of NACT. Quantitative IVIM parameters (D, D*, f & D*.f) were estimated using advanced state-of-the-art spatial penalty based IVIM analysis method bi-exponential model with total-variation penalty function (BETV) at 3 time-points and histogram analysis was performed. RESULTS: Good-responders: Poor-responders ratio was 13 (37%):22 (63%). EFS and OS were 31% and 69% with 16.27 and 25.9 months of median duration respectively. For predicting poor-response to NACT, IVIM parameters showed AUC = 0.87, Sensitivity = 86%, Specificity = 77% at t0, and AUC = 0.96, Sensitivity = 86%, Specificity = 100% at t1. Multivariate Cox regression analysis showed smaller tumour volume (HR = 1.002, p = 0.001) higher ADC-25th-percentile (HR = 0.047, p = 0.005) & D-Mean (HR = 0.1, p = 0.023) and lower D*-Mean (HR = 1.052, p = 0.039) were independent predictors of longer EFS (log-rank p-values: 0.054, 0.0034, 0.0017, 0.0019 respectively) and non-metastatic disease (HR = 4.33, p < 10-3), smaller tumour-volume (HR = 1.001, p = 0.042), lower D*-Mean (HR = 1.045, p = 0.056) and higher D*.f-skewness (HR = 0.544, p = 0.048) were independent predictors of longer OS (log-rank p-values: < 10-3, 0.07, < 10-3, 0.019 respectively). CONCLUSION: IVIM parameters obtained with a 1.5T scanner along with novel BETV method and their histogram analysis indicating tumour heterogeneity were informative in characterizing NACT response and survival outcome in osteosarcoma.
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Neoplasias Ósseas , Osteossarcoma , Humanos , Terapia Neoadjuvante , Imageamento por Ressonância Magnética/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Osteossarcoma/diagnóstico por imagem , Osteossarcoma/tratamento farmacológico , Osteossarcoma/patologia , Necrose , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/tratamento farmacológicoRESUMO
ABSTRACT: Primary cutaneous anaplastic large-cell lymphoma (C-ALCL) is a cutaneous CD30-positive lymphoproliferative disorder. The patients usually present with single or multiple cutaneous nodules or papules and about 10% cases present with extracutaneous manifestations, which are predominantly in the form of regional lymph nodal involvement. Visceral involvement especially pulmonary or hepatic involvement in C-ALCL is only rarely described in the scientific literature. Approximately 20%-42% cases show spontaneous regression, about 50% cases may recur; however, C-ALCL generally carries a good prognosis. We present a rare case of primary C-ALCL in a 66-year-old man with regional lymph nodal and hepatic involvement. Differential diagnostic entities are discussed in this report with the review of the literature.
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Linfoma Anaplásico de Células Grandes , Linfoma Anaplásico Cutâneo Primário de Células Grandes , Transtornos Linfoproliferativos , Dermatopatias , Neoplasias Cutâneas , Idoso , Humanos , Linfoma Anaplásico de Células Grandes/diagnóstico , Linfoma Anaplásico de Células Grandes/patologia , Linfoma Anaplásico Cutâneo Primário de Células Grandes/diagnóstico , Linfoma Anaplásico Cutâneo Primário de Células Grandes/patologia , Transtornos Linfoproliferativos/patologia , Masculino , Recidiva Local de Neoplasia , Receptores Proteína Tirosina Quinases , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologiaRESUMO
PURPOSE: VEGF and HIF-1α are important regulators of angiogenesis, overexpressed in various tumors. Lacrimal gland Adenoid cystic carcinoma (ACC) is a malignant tumor whose angiogenic properties remain unexplored. This study was designed to evaluate the expression of HIF-1α and VEGF in lacrimal gland ACC. METHODS: VEGF and HIF-1α immunoexpression was undertaken in 30 lacrimal gland ACC cases. mRNA expression of VEGF and HIF-1α was analysed in 17 cases by quantitative real time PCR. The results obtained were correlated with clinicopathological features and survival of the patients to determine the prognostic significance. RESULTS: Immunoexpression of HIF-1α and VEGF was seen in 36.6% and 46.6% ACC cases. HIF-1α expression showed significant association with advanced T-stage (P = 0.001) and VEGF with intracranial extension (P = 0.014) and solid histological pattern (P = 0.045). HIF-1α mRNA expression was seen in 29.4% cases and showed significant association with perineural invasion (P = 0.027). Recurrence occurred in 60%, distant metastasis in 20% and death in 20% cases. Survival analysis revealed that patients with HIF-1α, VEGF immunoexpression, solid histological pattern, perineural invasion, bone erosion, intracranial extension, metastasis, advanced T-stage, and exenteration had poor survival. On multivariate analysis VEGF immunoexpression (hazard ratio, 16.785; 95% confidence interval, 1.872-150.495; P = 0.012) was the most significant poor prognostic factor. CONCLUSIONS: This study demonstrates that VEGF is a potential predictor for poor clinical outcome in lacrimal gland Adenoid cystic carcinoma.
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Biomarcadores Tumorais/metabolismo , Carcinoma Adenoide Cístico/metabolismo , Neoplasias Oculares/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Doenças do Aparelho Lacrimal/metabolismo , Aparelho Lacrimal/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adolescente , Adulto , Idoso , Carcinoma Adenoide Cístico/diagnóstico , Carcinoma Adenoide Cístico/mortalidade , Neoplasias Oculares/diagnóstico , Neoplasias Oculares/mortalidade , Feminino , Seguimentos , Humanos , Doenças do Aparelho Lacrimal/diagnóstico , Doenças do Aparelho Lacrimal/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Adulto JovemRESUMO
Aim of the study: Activating Transforming factor 3 (ATF3) is a stress induced gene and closely associated with neuro-inflammation while Transforming growth Factor Beta (TGFß) signalling is also reported to be involved in neuro-inflammation and hyper-excitability associated with drug resistant epilepsy. Animal model studies indicate the involvement of ATF3 and TGFß receptors to promote epileptogenesis. Human studies also show that TGFß signalling is activated in MTLE-HS. However, lack of studies on ATF3 and TGFßRI expression in MTLE-HS patients exists. We hypothesize that ATF3 and TGFßRI might be expressed in hippocampi of patients with MTLE-HS and playing role in epileptogenesis.Materials & methods: Protein expression of ATF3 and TGFßRI was performed by western blotting. Localisation of ATF3 was performed by immunohistochemistry and immunoflorescence.Results: Protein expression of ATF3 and TGFßRI was significantly up-regulated in hippocampi of patients as compared to controls. Also ATF3 IR was significantly expressed in hippocampi of patients and ATF3 was expressed predominantly in cytoplasm as compared to nucleus. No correlation was found between ATF3 expression and epilepsy duration and seizure frequency.Conclusions: ATF3 and TGFßRI are both important players in neuro-inflammation and might potentiate epileptogenesis in these patients.
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BACKGROUND AND PURPOSE: In presurgical evaluation for epilepsy surgery, information is sourced from various imaging modalities to accurately localize the epileptogenic zone. Magnetoencephalography (MEG) is a newer noninvasive technique for localization. However, there is limited literature to evaluate if MEG provides additional advantage over the conventional imaging modalities in clinical decision making. The objective of this study was to assess the diagnostic added value of MEG in decision making before epilepsy surgery. METHOD: This was a prospective observational study. Patients underwent 3 h of recording in a MEG scanner, and the resulting localizations were compared with other complimentary investigations. Added value of MEG (considered separately from high-density electroencephalography) was defined as the frequency of cases in which (i) the information provided by magnetic source imaging (MSI) avoided implantation of intracranial electrodes and the patient was directly cleared for surgery, and (ii) MSI indicated additional substrates for implantation of intracranial electrodes. Postoperative seizure freedom was used as the diagnostic reference by which to measure the localizing accuracy of MSI. RESULTS: A total of 102 patients underwent epilepsy surgery. MEG provided nonredundant information, which contributed to deciding the course of surgery in 33% of the patients, and prevented intracranial recordings in 19%. A total of 76% of the patients underwent surgical resection in sublobes concordant with MSI localization, and the diagnostic odds ratio for good (Engel I) outcome in these patients was 2.3 (95% confidence interval 0.68, 7.86; p = 0.183) after long-term follow-up of 36 months. CONCLUSION: Magnetic source imaging yields additional useful information which can significantly alter as well as improve the surgical strategy for persons with epilepsy.
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Epilepsia , Eletroencefalografia , Epilepsia/diagnóstico por imagem , Epilepsia/cirurgia , Humanos , Fenômenos Magnéticos , Imageamento por Ressonância Magnética , Magnetoencefalografia , Estudos ProspectivosRESUMO
PURPOSE: H3K27M mutant diffuse midline gliomas (DMGs) are considered grade IV irrespective of histological features and have dismal prognosis. We evaluated clinico-pathologic, radiological, and molecular characteristics of DMGs across all ages. METHODS: One twenty-six DMGs were identified over 10 years. Immunohistochemistry was done for H3K27M, ATRX, IDH1, and p53, and Sanger sequencing performed for IDH1 and H3K27M mutation. Patient demographics and clinico-radiologic characteristics were reviewed and survival analysis performed. RESULTS: DMGs comprised 5.3% of all gliomas with 49.2% H3K27M mutant and 50.8% wild types. Majority (75.68%) of pediatric and 38.20% of adults were H3K27M mutant (p = 0.0001). Amongst H3K27M mutants, brainstem (46.43%) was the commonest location in pediatric and thalamus (61.76%) in adults. H3K27M mutation was mutually exclusive with IDH mutation in 93.55%, while p53, ATRX mutation were seen in 56.4% and 30.6% cases respectively. Software-based immunohistochemistry evaluation (H-scoring) showed 99.2% concordance with sequencing for H3K27M mutation. Radiologically, no significant difference in contrast enhancement was seen between mutant and wild types (p = 0.05). The difference in overall survival (OS) was not significant in mutant versus wild types, with age or location. Tumor resection independently and on correlation with H3K27M did not influence OS (p = 0.51 and p = 0.47). Adjuvant therapy impacted survival significantly in adults (p = 0.0009), however, not in pediatric cases (p = 0.06). CONCLUSIONS: The study highlights the differences in frequency and location of pediatric and adult DMGs. IHC (H-scoring) for H3K27M mutation is an excellent surrogate for sequencing. Prognosis remains dismal irrespective of age, location, and H3K27M status. Potential therapeutic targets need to be explored.
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Neoplasias Encefálicas , Glioma , Adulto , Neoplasias Encefálicas/genética , Criança , Glioma/genética , Histonas/genética , Humanos , Isocitrato Desidrogenase/genética , Mutação , PrognósticoRESUMO
INTRODUCTION: CNS embryonal tumors (CET) other than medulloblastomas (MB) and atypical teratoid/rhabdoid tumors (AT/RTs), previously designated as 'central nervous system primitive neuroectodermal tumors' ('CNS PNETs'), are a heterogenous subset of tumors with poorly defined diagnostic criteria. Other than the subset of embryonal tumor with multilayered rosettes (ETMR) defined by C19MC amplification, most CETs are diagnosed by exclusion of other molecularly defined entities and histological mimics including MB, AT/RTs, and high-grade gliomas, and termed as CET, not otherwise specified (NOS) in the 2016 WHO classification. AIM: To reclassify 'CNS PNETs' as per WHO 2016, and estimate the true proportion of CET, NOS in a tertiary healthcare setting, and to evaluate the diagnostic utility of C19MC amplification, Lin28A and Olig2 expression in the subclassification of CETs. METHODS: Previously diagnosed cases of 'CNS PNETs' (2002-2016) were first evaluated by immunohistochemistry (IHC) for MIC2, RelaA, L1CAM, IDH1R132H, H3K27M, H3G34R, H3G34V, INI1, and BRG1 proteins and by fluorescence in-situ hybridization (FISH) for EWSR1 translocation to exclude histological mimics. The selected CETs (case cohort) and 79 histological mimics (comparison cohort) comprising of MB, AT/RT, pineal parenchymal tumors, Ewing sarcoma, esthesioneuroblastoma, intraocular medulloepithelioma, and H3G34R mutant high-grade glioma were subject to IHC for Olig2 and Lin28A, and FISH for C19MC amplification. RESULTS: Twenty-two cases of 'CNS PNETs' were retrieved, all of which were negative for the first panel of markers and showed retained INI-1/BRG1 expression. Three of them (3/22, 13.6%) showed C19MC amplification (ETMR, C19MC-altered) with ETMR histology, Lin28A positivity, and Olig2 negativity. Among the remaining 19 CETs, one showed medulloepithelioma histology (Medulloepithelioma, NOS) and remaining were non-descript small round cell tumors (CET, NOS), all negative for Lin28A. Olig2 was positive in only 3 CETs (13.6%), all being CET, NOS. All tumors in the comparison cohort were negative for C19MC amplification, Lin28A and Olig2 except for 27% of ATRTs that were Lin28A positive. CONCLUSION: ETMR, C19MC-altered constitute less than 14% of CETs, with majority remaining uncharacterized as CET, NOS. Lin28A is 100% sensitive for the detection of C19MC amplification; however, its specificity is limited by its expression in ATRTs. Olig2 expression is seen only in a small subset of CET, NOS and is of limited diagnostic utility.
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Neoplasias Encefálicas , Neoplasias do Sistema Nervoso Central , Neoplasias Embrionárias de Células Germinativas , Tumores Neuroectodérmicos Primitivos , Glândula Pineal , Neoplasias Encefálicas/genética , Humanos , Neoplasias Embrionárias de Células Germinativas/genética , Tumores Neuroectodérmicos Primitivos/genética , Fator de Transcrição 2 de Oligodendrócitos , Estudos Retrospectivos , Centros de Atenção TerciáriaRESUMO
INTRODUCTION: Spinal atypical teratoid/rhabdoid tumour (AT/RT) is exquisitely rare and constitutes 2% of all AT/RTs. CASE PRESENTATION: A 6-year-old boy presented with low backache for the last 5 months. MRI of the spine showed a 1.5 × 1.5 × 4.7 cm intradural extramedullary mass extending from D10 to D12, causing compression of the conus medullaris. With a preoperative diagnosis of ependymoma, a gross total resection (GTR) of tumour was performed. Post-operative histopathology showed AT/RT. The tumour cells were immunopositive for cytokeratin, epithelial membrane antigen, smooth muscle actin, and p53 and immunonegative for MIC2, desmin, glial fibrillary acidic protein, and INI1. Post-operative neuraxis MRI revealed post-operative changes (D10-D12) with a 9 mm enhancing lesion at L5-S1 junction suggesting drop metastasis. There was no lesion in brain. Cerebrospinal fluid cytology did not show any malignant cell. The metastatic work-up was normal. He received 3 cycles of chemotherapy with ICE regimen (ifosfamide, carboplatin, and etoposide). Subsequently, he received craniospinal irradiation (CSI)-36 Gy/20 fractions/4 weeks followed by focal boost to primary tumour bed and spinal drop metastasis-14.4 Gy/8 fractions/1.5 weeks. Thereafter, he received 3 more cycles of ICE regimen. End-of-treatment MRI spine showed post-op changes (D10-D12) and 38.9% reduction of the L5-S1 lesion suggesting partial response. Six monthly spinal MRI showed serial reduction of the metastatic lesion leading to complete response (CR) 1 year after completion of treatment. On last follow-up (30 months from the initial diagnosis), he was neurologically intact and in CR. CONCLUSION: Multimodality management comprising GTR of tumour, CSI followed by focal boost, and multiagent chemotherapy (ICE) can lead to successful outcome in patients with this rare and aggressive spinal tumour.
Assuntos
Neoplasias do Sistema Nervoso Central , Ependimoma , Tumor Rabdoide , Teratoma , Criança , Humanos , Masculino , Tumor Rabdoide/diagnóstico por imagem , Tumor Rabdoide/cirurgia , Coluna Vertebral , Teratoma/cirurgiaRESUMO
Atrial myxomas are the most common primary benign cardiac tumors. The embolization of tumor particles is not infrequent, and in nearly half of them, the cerebral arteries are affected, usually leading to embolic ischemic stroke. Formation of intracranial aneurysms, development of parenchymal brain metastasis, and intracerebral hemorrhage due to ruptured aneurysms are rarer. Diagnosis of such lesions in a previously undiagnosed case of myxoma may be challenging for a pathologist. Herein, we present two patients of cardiac myxoma with varied neurological manifestations and their pathological findings.
Assuntos
Neoplasias Encefálicas/secundário , AVC Embólico/etiologia , Neoplasias Cardíacas/complicações , Neoplasias Cardíacas/patologia , Mixoma/complicações , Mixoma/patologia , Adolescente , Feminino , Átrios do Coração/patologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The authors report a case of extremely uncommon malignancy of lacrimal gland epithelial-myoepithelial carcinoma. This carcinoma is more commonly encountered in salivary glands and comprises 1% of all salivary gland tumors. Its occurrence in the orbit is very rare with only 6 cases reported in the literature, most of which arose in a pleomorphic adenoma. Epithelial-myoepithelial carcinoma is primarily a tumor of older adults, with a peak incidence in the sixth and seventh decades of life. The present case is the youngest patient reported to date and had no history of preexisting neoplasm in the lacrimal gland. Histological diagnosis of epithelial-myoepithelial carcinoma is challenging because of the similarity with other lacrimal gland epithelial tumors like malignant adenoid cystic carcinoma and benign pleomorphic adenomas.
Assuntos
Adenoma Pleomorfo , Carcinoma Adenoide Cístico , Carcinoma , Aparelho Lacrimal , Neoplasias das Glândulas Salivares , Adenoma Pleomorfo/diagnóstico , Idoso , Carcinoma Adenoide Cístico/diagnóstico , Humanos , Aparelho Lacrimal/diagnóstico por imagemRESUMO
INTRODUCTION: Molecular classification of medulloblastomas (MB) is prognostically and therapeutically relevant and helps in better risk-stratification. Translation of this subgrouping to routine practice still remains a challenge. The most pathologist accessible techniques for molecular subgrouping include immunohistochemistry (IHC), fluorescent in-situ hybridization (FISH) and NanoString. OBJECTIVES: (1) Molecular subgrouping of MBs by IHC and FISH, and NanoString assay (2) To compare their efficacy and cost for applicability in resource constrained centers. METHODS: Ninety-five cases of MB with adequate tissue were included. Molecular subgrouping was performed by IHC for ß-catenin, GAB1 and YAP1; FISH for MYC amplification, and sequencing for CTNNB1, and by NanoString Assay on the same set of MBs. A subset of cases was subjected to 850k DNA methylation array. RESULTS: IHC + FISH classified MBs into 15.8% WNT, 16.8% SHH, and 67.4% non-WNT/non-SHH subgroups; with MYC amplification identified in 20.3% cases of non-WNT/non-SHH. NanoString successfully classified 91.6% MBs into 25.3% WNT, 17.2% SHH, 23% Group 3 and 34.5% Group 4. However, NanoString assay failure was seen in eight cases, all of which were > 8-years-old formalin-fixed paraffin-embedded tissue blocks. Concordant subgroup assignment was noted in 88.5% cases, while subgroup switching was seen in 11.5% cases. Both methods showed prognostic correlation. Methylation profiling performed on discordant cases revealed 1 out of 4 extra WNT identified by NanoString to be WNT, others aligned with IHC subgroups; extra SHH by NanoString turned out to be SHH by methylation. CONCLUSIONS: Both IHC supplemented by FISH and NanoString are robust methods for molecular subgrouping, albeit with few disadvantages. IHC cannot differentiate between Groups 3 and 4, while NanoString cannot classify older-archived tumors, and is not available at most centres. Thus, both the methods complement each other and can be used in concert for high confidence allotment of molecular subgroups in clinical practice.