BACKGROUND: Odontogenic carcinoma with dentinoid (OCD) is a rare and controversial entity, which has not yet been included in the current World Health Organization classification of odontogenic lesions. Owing to the small number of reported cases, the clinicopathological characteristics, biological behavior, prognosis, and appropriate treatment strategies for OCD remain to be defined. Herein, we present an additional case of OCD with a focus on the differential diagnosis and review of the pertinent literature, in order to enable better recognition by oral clinicians and pathologists and further characterization of this entity.
METHODS: This paper reports a case of OCD in the posterior mandible of a 22-year-old female. Radiography showed a well-defined unilocular radiolucency with radiopaque materials. The intraoperative frozen section pathology gave a non-committed diagnosis of odontogenic neoplasm with uncertain malignant potential. Then a partial mandibulectomy with free iliac crest bone graft and titanium implants was performed. Microscopically, the tumor consisted of sheets, islands, and cords of round to polygonal epithelial cells associated with an abundant dentinoid matrix. Immunohistochemically, the tumor cells were diffusely positive for CK19, p63, and β-catenin (cytoplasmic and nuclear). No rearrangement of the EWSR1 gene was detected. The final diagnosis was OCD. There has been no evidence of recurrence or metastasis for 58 months after surgery. We also provide a literature review of OCD cases, including one case previously reported as ghost cell odontogenic carcinoma from our hospital.
CONCLUSIONS: OCD is a locally aggressive low grade malignancy without apparent metastatic potential. Wide surgical excision with clear margins and long-term period follow-up to identify any possible recurrence or metastases are recommended. Histopathological examination is essential to conclude the diagnosis. Special care must be taken to distinguish OCD from ghost cell odontogenic carcinoma and clear cell odontogenic carcinoma, as misdiagnosis might lead to unnecessary overtreatment. Study of additional cases is required to further characterize the clinicopathological features and clarify the nosologic status and biological behavior of this tumor.

The nomenclature and diagnostic criteria of well-differentiated papillary mesothelial tumour (WDPMT) have been changed in the 2021 World Health Organization (WHO) classification of thoracic tumours, and a new entity, mesothelioma in situ (MIS), introduced. Histologically these two entities may be similar. However, MIS is regarded as a precursor to invasive mesothelioma and requires demonstration of loss of BAP1 and/or MTAP/CDKN2A for diagnosis, whereas performance of these ancillary tests is desirable but not essential for a diagnosis of WDPMT, in which the significance of BAP1 and/or MTAP/CDKN2A loss is not well understood or well defined. Against this backdrop, we undertook an investigation of 21 cases of WDPMT, identified from our case files and diagnosed according to 2021 WHO criteria, to explore the relationship between histology and BAP1 and MTAP/CDKN2A expression with clinical features including asbestos exposure, focality of tumours and clinical outcome. There were 18 women and three men, with ages ranging from 23-77 years (median 62 years), in which six had a history of asbestos exposure, two had no exposure, and in 13 exposure history was unavailable. Of 20 peritoneal tumours and one pleural tumour, 13 were detected incidentally at the time of surgery for unrelated conditions and eight peritoneal tumours were multifocal at the time of diagnosis. BAP1 immunohistochemistry (IHC) was performed in all 21 tumours, with nine tumours showing BAP1 expression loss. MTAP/CDKN2A testing was performed in 14 tumours, comprising MTAP IHC in 12 and CDKN2A fluorescence in situ hybridisation (FISH) in two, with three tumours showing MTAP/CDKN2A expression loss. Two tumours with MTAP/CDKN2A loss also showed BAP1 expression loss. Four patients progressed to invasive mesothelioma, including one male with a pleural tumour and asbestos exposure, and three females with multifocal peritoneal tumours, two with asbestos exposure and one without exposure. BAP1 expression loss was seen in all tumours from the four patients who progressed to invasive mesothelioma, whilst two of these tumours showed retained MTAP IHC and two were not tested. There was one patient with a tumour with MTAP loss and retained BAP1 who died from unrelated causes 5 months after diagnosis. Eight patients received WDPMT-specific treatment in addition to the initial excision. Survival for all patients ranged from 4-218 months, with one patient dying of mesothelioma at 49 months. Based on our results in this series of 21 patients with WDPMT diagnosed according to 2021 WHO criteria, we propose that WDPMT with BAP1 expression loss may best be regarded as papillary MIS and that a history of asbestos exposure and the presence of multifocal tumours in patients diagnosed with WDPMT should prompt ancillary testing with BAP1 IHC. Further we propose that BAP1 IHC should be essential in the diagnosis of WDPMT, with the diagnosis restricted to those tumours which show retained BAP1 expression. However more studies in larger cohorts of patients are needed to explore the relationship between BAP1 expression and MTAP loss in WDPMT, which will help to define this entity and separate it more clearly from MIS and invasive mesothelioma.

OBJECTIVE: To determine the prevalence of tuberous sclerosis complex (TSC) in the paediatric Saudi population and to characterise the range of clinical symptoms, neurocutaneous findings, neuroimaging results, and complications of the disease.
METHODS: A total of 61 genetically confirmed TSC patients from the National Guard Health Affairs (NGHA) in Saudi Arabia were the subject of this retrospective descriptive analysis. The data were presented using descriptive measures.
RESULTS: The mean age at diagnosis was found to be 4.9 years. Subependymal nodules (86.9%), numerous cortical tubers and/or radial migration lines (63.9%), and hypomelanotic macules (63.9%) were the 3 most common significant criteria. The vast majority (86.9%) of those diagnosed had epilepsy, of which 50% were considered medically intractable. Nearly half of our subjects underwent genetic testing, which revealed that TSC2 predominated over TSC1. Symptoms of Tuberous Sclerosis Complex-Associated Neuropsychiatric Disorders (TAND) were present in 66.7% of TSC1 patients and 73.9% of TSC2 patients.
CONCLUSIONS: The findings of this study demonstrate that the clinical spectrum of TSC among Saudi children is consistent with the body of existing literature. The TSC2 was more prevalent than TSC1. The most frequent signs were cutaneous and neurological. Monitoring TSC patients regularly is crucial to identify any issues as soon as possible.

BACKGROUND: Methylation analysis has become a powerful diagnostic tool in modern neurooncology. This technique is valuable to diagnose new brain tumor types.
OBJECTIVE: To describe the MRI and histological pattern of neuroepithelial tumor with PLAGL1 gene fusion.
METHODS: We present a 6-year-old patient with small right frontal intraaxial tumor causing drug resistant epilepsy. Despite indolent preoperative clinical course and MRI features suggesting glioneuronal tumor, histological evaluation revealed characteristics of high-grade glioma, ependymoma and neuroblastoma.
RESULTS: Methylation analysis of tumor DNA confirmed a new type of a recently discovered neoplasm - neuroepithelial tumor with PLAGL1 fusion (NET PLAGL1). PCR confirmed fusion of PLAGL1 and EWSR1 genes. No seizures were observed throughout the follow-up period. There was no tumor relapse a year after surgery.
CONCLUSIONS: Methylation analysis in neurooncology is essential for unclear tumor morphology or divergence between histological and clinical data. In our case, this technique confirmed benign nature of tumor, and we preferred follow-up without unnecessary adjuvant treatment.
Определение метиляционного профиля генома опухоли становится значимым способом диагностики новообразований центральной нервной системы. На основании этой методики также возможно выявлять новые классы опухолей головного мозга.
UNASSIGNED: Описать результаты магнитно-резонансной томографии (МРТ) и гистологическую картину нейроэпителиальной опухоли со слиянием гена PLAGL1.
UNASSIGNED: Представлено клиническое наблюдение ребенка 6 лет с внутримозговой опухолью лобной доли и фармакорезистентной эпилепсией. По рентгенологическим характеристикам, до операции предполагалась доброкачественная глионейрональная опухоль, однако гистология соответствовала новообразованию, имевшему черты злокачественной глиомы, эпендимомы и нейробластомы.
UNASSIGNED: Проведен метиляционный анализ ткани опухоли, показавший, что она относится к недавно описанному новому классу — «нейроэпителиальная опухоль со слиянием гена PLAGL1». Тест полимеразной цепной реакции подтвердил слияние генов PLAGL1 и EWSR1. После операции отмечено прекращение приступов, спустя 1 год на МРТ рецидива опухоли не определялось.
UNASSIGNED: Метиляционный анализ в нейроонкологии играет решающую роль в случаях неоднозначной морфологии опухоли, расхождения ее гистологической и клинико-рентгенологической картины. В приведенном клиническом примере стало возможным доказать доброкачественный характер опухоли и выбрать выжидательную тактику, избежав адъювантного лечения у ребенка.

BACKGROUND: MGMT (O 6 -methylguanine-DNA methyltransferase) promoter methylation is a commonly assessed prognostic marker in glioblastoma (GBM). Epigenetic silencing of the MGMT gene by promoter methylation is associated with greater overall and progression free survival with alkylating agent regimens. To date, there is marked heterogeneity in how MGMT promoter methylation is tested and which CpG sites are interrogated.
METHODS: To further elucidate which MGMT promoter CpG sites are of greatest interest, we performed comprehensive searches in PubMed, Web of Science, and Embase and reviewed 2,925 article abstracts. We followed the GRADE scoring system to assess risk of bias and the quality of the studies we included.
RESULTS: We included articles on adult glioblastoma that examined significant sites or regions within MGMT promoter for the outcomes: overall survival, progression free survival, and/or MGMT expression. We excluded systemic reviews and articles on lower grade glioma. fifteen articles met inclusion criteria with variable overlap in laboratory and statistical methods employed, as well as CpG sites interrogated. Pyrosequencing or BeadChip arrays were the most popular methods utilized, and CpG sites between CpG\'s 70-90 were most frequently investigated. Overall, there was moderate concordance between the CpG sites that the studies reported to be highly predictive of prognosis. Combinations or means of sites between CpG\'s 73-89 were associated with improved OS and PFS. Six studies identified CpG sites associated with prognosis that were closer to the transcription start site: CpG\'s 8, 19, 22, 25, 27, 32,38, and CpG sites 21-37, as well as low methylation level of the enhancer regions.
CONCLUSIONS: The following systematic review details a comprehensive investigation of the current literature and highlights several potential key CpG sites that demonstrate significant association with OS, PFS, and MGMT expression. However, the relationship between extent of MGMT promoter methylation and survival may be non-linear and could be influenced by potential CpG hotspots, the extent of methylation at each CpG site, and MGMT enhancer methylation status. There were several limitations within the studies such as smaller sample sizes, variance between methylation testing methods, and differences in the various statistical methods to test for association to outcome. Further studies of high impact CpG sites in MGMT methylation is warranted.

The transcription factor BCL11B plays an essential role in the development of central nervous system and T cell differentiation by regulating the expression of numerous genes involved in several pathways. Monoallelic defects in the BCL11B gene leading to loss-of-function are associated with a wide spectrum of phenotypes, including neurological disorders with or without immunological features and susceptibility to hematological malignancies. From the genetic point of view, the landscape of BCL11B mutations reported so far does not fully explain the genotype-phenotype correlation. In this review, we sought to compile the phenotypic and genotypic variables associated with previously reported mutations in this gene in order to provide a better understanding of the consequences of deleterious variants. We also highlight the importance of a careful evaluation of the mutation type, its location and the pattern of inheritance of the variants in order to assign the most accurate pathogenicity and actionability of the genetic findings.

BACKGROUND: Williams-Beuren syndrome (WBS) is a rare genetic disorder caused by hemizygous microdeletion of contiguous genes on chromosome 7q11.23. Although the phenotype features extensive heterogeneity in severity and performance, WBS is not considered to be a predisposing factor for cancer development. Currently, hematologic cancers, mainly Burkitt lymphoma, are rarely reported in patients with WBS. Here in, we report a unique case of T-cell acute lymphoblastic leukemia in a male child with WBS.
METHODS: This retrospective study analyzed the clinical data of this case receiving chemotherapy were analyzed. This is a retrospective study.
RESULTS: The patient, who exhibited a typical WBS phenotype and presented with hemorrhagic spots. Chromosomal genome-wide chip analysis (CMA) revealed abnormalities on chromosomes 7 and 9. The fusion gene STIL-TAL1 and mutations in BCL11B, NOTCH1, and USP7 have also been found and all been associated with the occurrence of T-cell leukemia. The patient responded well to the chemotherapy.
CONCLUSIONS: To the best of our knowledge, this is the first reported case of WBS in T-cell acute lymphoblastic leukemia. We want to emphasize that the occurrence of leukemia in this patient might be related to the loss of 7q11.23 and microdeletion of 9p21.3 (including 3 TSGs), but the relationship between WBS and malignancy remains unclear. Further studies are required to clarify the relationship between WBS and malignancy.

BACKGROUND: Accurate and non-invasive estimation of MGMT promoter methylation status in glioblastoma (GBM) patients is of paramount clinical importance, as it is a predictive biomarker associated with improved overall survival (OS). In response to the clinical need, recent studies have focused on the development of non-invasive artificial intelligence (AI)-based methods for MGMT estimation. In this systematic review, we not only delve into the technical aspects of these AI-driven MGMT estimation methods but also emphasize their profound clinical implications. Specifically, we explore the potential impact of accurate non-invasive MGMT estimation on GBM patient care and treatment decisions.
METHODS: Employing a PRISMA search strategy, we identified 33 relevant studies from reputable databases, including PubMed, ScienceDirect, Google Scholar, and IEEE Explore. These studies were comprehensively assessed using 21 diverse attributes, encompassing factors such as types of imaging modalities, machine learning (ML) methods, and cohort sizes, with clear rationales for attribute scoring. Subsequently, we ranked these studies and established a cutoff value to categorize them into low-bias and high-bias groups.
RESULTS: By analyzing the \'cumulative plot of mean score\' and the \'frequency plot curve\' of the studies, we determined a cutoff value of 6.00. A higher mean score indicated a lower risk of bias, with studies scoring above the cutoff mark categorized as low-bias (73%), while 27% fell into the high-bias category.
CONCLUSIONS: Our findings underscore the immense potential of AI-based machine learning (ML) and deep learning (DL) methods in non-invasively determining MGMT promoter methylation status. Importantly, the clinical significance of these AI-driven advancements lies in their capacity to transform GBM patient care by providing accurate and timely information for treatment decisions. However, the translation of these technical advancements into clinical practice presents challenges, including the need for large multi-institutional cohorts and the integration of diverse data types. Addressing these challenges will be critical in realizing the full potential of AI in improving the reliability and accessibility of MGMT estimation while lowering the risk of bias in clinical decision-making.

BACKGROUND: Novel biomarkers have been suggested for the diagnosis and prognosis of diabetes mellitus. The biomarker utility of netrin-1 in diabetes as an extracellular protein has been investigated. In this systematic review and meta-analysis, we reviewed the role of netrin-1 as a biomarker in prediabetes, diabetes, and complications of diabetes.
METHODS: PubMed, Embase, Scopus, and Web of Science were systematically searched for studies that measured circulatory and/or urinary netrin-1 levels in diabetes and compared them with non-diabetic patients or evaluated the prognostic role of this marker. Standardized mean difference (SMD) and 95% confidence interval (CI) were calculated using random-effect meta-analysis to compare netrin-1 levels between groups. The impact of mean age, male sex percentage, sample size, mean body mass index, and publication year on the overall heterogeneity was assessed using meta-regression.
RESULTS: Among 413 records from international databases, 19 original studies were included with 2061 cases (1137 diabetics, 196 prediabetics, and 728 healthy controls). Meta-analysis of eight studies measuring netrin-1 in patients with diabetes and comparing it with healthy controls showed no significant difference between the two groups (SMD 0.69, 95% CI -0.78 to 2.16, I2 = 98%, p-value = 0.36). On the other hand, a meta-analysis of netrin-1 levels in patients with prediabetes in comparison with healthy controls revealed that they had lower levels (SMD -0.51, 95% CI -0.81 to -0.21, p-value < 0.01). Diabetic patients with microalbuminuria and macroalbuminuria had significantly higher circulatory netrin-1 levels compared to normoalbuminuric group SMD 1.18, 95% CI 0.83 to 1.53, p-value < 0.01 and SMD 1.67, 95% CI 0.76 to 2.58, p-value < 0.01, respectively). Moreover, no difference in urinary netrin-1 levels was found between micro-, macro-, and normoalbuminuric groups (p-value > 0.05).
CONCLUSIONS: Netrin-1 showed promising results as a biomarker in diabetes prognosis. However, more studies are required to confirm our findings, and higher sample size studies are needed to evaluate the diagnostic utility of this marker.

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