New CNS tumor classification: The importance in pediatric neurosurgical practice.

Background: The management of the central nervous system (CNS) tumors in the pediatric population is crucial in neurosurgical practice. The World Health Organization (WHO) has evolved its classification of CNS tumors from the 19th century to the 5th edition, published in 2021, incorporating molecular advancements. This transition from morphology to molecular characterization is ongoing. Methods: This manuscript analyzes the modifications introduced in the 5th edition of WHO's CNS tumor classification, particularly focusing on pediatric tumor families. The paper integrates clinical, morphological, and molecular information, aiming to guide pediatric neurosurgeons in their daily practice and interdisciplinary discussions. Results: The 5th edition of the WHO classification introduces a hybrid taxonomy that incorporates both molecular and histological components. The terminology shifts from "entity" to "type" and "subtype," aiming to standardize terminology. Tumor grading experiences changes, integrating molecular biomarkers for prognosis. The concept of integrated layered diagnosis is emphasized, where molecular and histological information is combined systematically. Conclusion: The 5th edition of the WHO CNS classification signifies a paradigm shift toward molecular characterization. The incorporation of molecular advances, the layered diagnostic approach, and the inclusion of clinical, morphological, and molecular information aim to provide comprehensive insights into pediatric CNS tumors. This classification offers valuable guidance for pediatric neurosurgeons, aiding in precise diagnosis and treatment planning for these complex neoplasms.

Validation and comparison of 5th edition World Health Organization classification (WHO 2022) and International Consensus Classification proposals for MDS-SFB31.

The criteria of myelodysplastic syndromes (MDS) with mutated SFB31 (MDS-SFB31) proposed by the 5th edition of the WHO classification (WHO 2022) and the International Consensus Classification (ICC) need validation. We analysed 125 consecutive MDS cases with SFB31 mutation or ring sideroblasts (RS) ≥15% without excess blasts. We found that SFB31-negative MDS with RS had significantly different clinical features and worse prognosis. According to WHO 2022, the detection of ≥15% RS may substitute for SF3B1 mutation and our analyses support this proposal for similar prognosis of two groups after excluding high-risk genetic features referred by WHO 2022. Patients with variant allele frequency (VAF) <10% SFB31 tend to have briefer survival, supporting the VAF 10% threshold of ICC. Patients with multilineage dysplasia (MLD) had significantly shorter OS than those with single lineage dysplasia. MLD is still a powerful morphological marker of worse outcome in WHO 2022 and ICC-defined MDS-SF3B1.

Imaging of supratentorial intraventricular masses in children:a pictorial review- part 1.

PURPOSE: This article is the first in a two-part series designed to provide a comprehensive overview of the range of supratentorial intraventricular masses observed in children. Our primary objective is to discuss the diverse types of intraventricular masses that originate not only from cells within the choroid plexus but also from other sources. METHODS: In this article, we review relevant epidemiological data, the current genetics/molecular classification as outlined in the fifth edition of the World Health Organization's Classification of tumours of the Central Nervous System and noteworthy imaging findings. We conduct an exhaustive analysis of primary choroid plexus tumours as well as other conditions such as choroid plexus hyperplasia, choroid plexus cyst, choroid plexus xanthogranuloma, atypical teratoid rhabdoid tumour, meningioma, arteriovenous malformation and metastasis. RESULTS: We comprehensively evaluated each supratentorial intraventricular mass, providing an in-depth analysis of their unique clinical and histological characteristics. The fifth edition of the World Health Organization Classification of Tumours of the Central Nervous System introduces major modifications. These important changes could potentially have a profound impact on the management strategies and subsequent outcomes of these tumours. CONCLUSION: Intraventricular masses in children can arise from various sources. Surgical intervention is key for certain supratentorial intraventricular masses in paediatric patients, with preoperative neuroimaging essential to decide the best treatment approach, surgical or otherwise, as some cases may not require surgery.

The fifth edition of the WHO classification of mature B-cell neoplasms: open questions for research.

The fifth edition of the World Health Organization Classification of Haematolymphoid Tumours (WHO-HAEM5) is the product of an evidence-based evolution of the revised fourth edition with wide multidisciplinary consultation. Nonetheless, while every classification incorporates scientific advances and aims to improve upon the prior version, medical knowledge remains incomplete and individual neoplasms may not be easily subclassified in a given scheme. Thus, optimal classification requires ongoing study, and there are certain aspects of some entities and subtypes that require further refinements. In this review, we highlight a selection of these challenging areas to prompt more research investigations. These include (1) a 'placeholder term' of splenic B-cell lymphoma/leukaemia with prominent nucleoli (SBLPN) to accommodate many of the splenic lymphomas previously classified as hairy cell leukaemia variant and B-prolymphocytic leukaemia, a clear new start to define their pathobiology; (2) how best to classify BCL2 rearrangement negative follicular lymphoma including those with BCL6 rearrangement, integrating the emerging new knowledge on various germinal centre B-cell subsets; (3) what is the spectrum of non-IG gene partners of MYC translocation in diffuse large B-cell lymphoma/high-grade B-cell lymphoma and how they impact MYC expression and clinical outcome; how best to investigate this in a routine clinical setting; and (4) how best to define high-grade B-cell lymphoma not otherwise specified and high-grade B-cell lymphoma with 11q aberrations to distinguish them from their mimics and characterise their molecular pathogenetic mechanism. Addressing these questions would provide more robust evidence to better define these entities/subtypes, improve their diagnosis and/or prognostic stratification, leading to better patient care. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Imaging of supratentorial intraventricular masses in children: a pictorial review-part 2.

PURPOSE: This article is the second in a two-part series aimed at exploring the spectrum of supratentorial intraventricular masses in children. In particular, this part delves into masses originating from cells of the ventricular lining, those within the septum pellucidum, and brain parenchyma cells extending into the ventricles. The aim of this series is to offer a comprehensive understanding of these supratentorial intraventricular masses, encompassing their primary clinical findings and histological definitions. METHODS: We conducted a review and analysis of relevant epidemiological data, the current genetics/molecular classifications as per the fifth edition of the World Health Organization (WHO) Classification of Tumors of the Central Nervous System (WHO CNS5), and imaging findings. Each supratentorial intraventricular mass was individually evaluated, with a detailed discussion on its clinical and histological features. RESULTS: This article covers a range of supratentorial intraventricular masses observed in children. These include colloid cysts, subependymal giant cell astrocytomas, ependymomas, gangliogliomas, myxoid glioneuronal tumors, central neurocytomas, high-grade gliomas, pilocytic astrocytomas, cavernous malformations, and other embryonal tumors. Each mass type is characterized both clinically and histologically, offering an in-depth review of their individual imaging characteristics. CONCLUSION: The WHO CNS5 introduces notable changes, emphasizing the vital importance of molecular diagnostics in classifying pediatric central nervous system tumors. These foundational shifts have significant potential to impact management strategies and, as a result, the outcomes of intraventricular masses in children.

[Chronic neutrophilic leukemia/chronic eosinophilic leukemia].

Chronic neutrophilic leukemia (CNL) is a clonal disorder that is characterized by increasing mature neutrophils. Colony stimulating factor 3 receptor (CSF3R) T618I mutation was frequently identified in patients with CNL and is defined as a molecular marker of the disease. Ruxolitinib, a JAK2 inhibitor, provided a promising therapeutic effect in a phase II study. In particular, ruxolitinib was more efficient for patients with CSF3R mutation. Allogeneic stem cell transplantation (Allo-SCT) may be a curative treatment for CNL. On the other hand, further studies are needed to define the optimal method of transplantation, source of donor, conditioning therapy, and timing of transplantation. Chronic eosinophilic leukemia (CEL) is a clonal disorder that is characterized by increasing eosinophils. In the World Health Organization Classification 5th edition, diagnostic criteria for CEL are renewed. Because the new criteria will be more specific for CEL than criteria in the older edition, "not otherwise specified (NOS) " is removed from the name of the disease. Anti-CD52 antibody, alemtuzumab, or anti-IL-5 antibody, mepolizumab, are promising drugs to control symptoms that are associated with hypereosinophilic syndrome. Allo-SCT is anticipated as a curative treatment for CEL, but the evidence of Allo-SCT for CEL is still limited. Further study is required to define the treatment strategy.

A Comparison of the Fifth World Health Organization and the International Consensus Classifications of Mature T-Cell Lymphomas.

Peripheral T-cell lymphomas (PTCLs) are a rare subset of non-Hodgkin lymphomas that often carry significant difficulty in diagnosis and classification because of their rarity and biological complexity. Previous editions of the World Health Organization (WHO) classifications of hemopoietic neoplasms in 2001, 2008, and 2017 aimed to standardize hemopoietic neoplasm diagnosis in general. Since then, crucial clinico-pathological, immunophenotypic, and recent molecular discoveries have been made in the field of lymphomas, contributing to refining diagnostic criteria of several diseases, upgrading entities previously defined as provisional, and identifying new entities. In 2022, two different models were proposed to classify hematolymphoid neoplasms: the 5th edition of the WHO classification (WHO-HAEM5) and the International Consensus Classification (ICC). Of note, a common nosography is mandatory to ensure progress in health science and ensure the basis for a real precision medicine. In this article, the authors summarized the main differences with the previous fourth WHO edition and reviewed the main discrepancies between the two newest classifications, as far as PTCLs are concerned.

"A tumour registry initiative".

Background: Published literature on epidemiological profile of paediatric brain tumours in India is limited. Aim: To present a retrospective analysis of the histological spectrum of 158 paediatric age group central nervous system tumours operated in a single tertiary care hospital in Coastal South India between January 2015 and December 2021. Material and methods: Retrospective analysis of the data regarding frequencies of various primary brain tumours among 158 paediatric patients (<18 years of age). The tumours were categorised according to the revised 4th edition of World Health Organization (WHO) classification of tumours of the Central Nervous system. Results: Paediatric CNS constituted 8.5% of total intracranial tumours (158/1860) operated in the study period. The mean age of the patients was 10.2 years and a definite male predominance was noted (1.54:1) Astrocytomas, glioneuronal tumours, and neuronal tumours constituted the majority (72/158; 45.6%) followed by embryonal tumours (31/158; 19.6%) and craniopharyngiomas(24/158; 15.4%).Of the glial neoplasms majority were pilocytic and other astrocytic tumours(41.6%), followed by mixed neuroglial tumours (19.4%), diffuse high grade astrocytomas (Grade III/IV) (11.1%), diffuse low -grade astrocytomas (Grade II) (9.7%) and ependymomas (13.8%). Our series also included six meningiomas (3.8%), five germ cell tumours (3.16%), four nerve sheath tumours (2.53%), two choroid plexus tumours (1.26%), two pineal parenchymal tumours (1.26%) and one metastasis from a soft tissue sarcoma from the thigh. Supratentorial tumours (58.2%) were more common than posterior fossa (34.6%) and spinal tumours (7.6%) and visual pathway gliomas accounted for 5.6% of all our tumours. Conclusions: Paediatric central nervous system tumours are more common in boys and in the second decade of life. Astrocytomas are the most common paediatric brain tumours followed by medulloblastomas and craniopharyngiomas. Pediatric tumours affect the supratentorial compartment more often than the infratentorial compartment. The profile of paediatric brain tumours in our series is similar to that reported from other Indian centres as well as most western literature.

Proceedings of the North American Society of Head and Neck Pathology Companion Meeting, New Orleans, LA, March 12, 2023: Oral Cavity Dysplasia: Why Does Histologic Grading Continue to be Contentious?

Head and neck squamous cell carcinoma (HNSCC) is the world's 6th most common malignancy. Oral cavity SCC (OCSCC) represents approximately one third of the HNSCC cases diagnosed annually in the United States. Despite therapeutic advances, OCSCC is frequently lethal, with a modest 5-year survival. Because OCSCC is often preceded by premalignant lesions, it is an ideal disease for screening initiatives. The conventional visual and tactile exam (CVTE), coupled with a tissue biopsy, remains the gold standard. However, CVTE alone cannot reliably differentiate between reactive/inflammatory and dysplastic lesions. Further, the histologic diagnosis of dysplasia is subjective in nature and a highly imperfect predictor of malignant transformation. This prognostic uncertainty creates a significant clinical management dilemma-watchful waiting with increased patient psychological and economic burdens versus unnecessary aggressive treatment. As such, the development and validation of novel diagnostic platforms such as Artificial Intelligence (AI) and prognostic molecular biomarkers may help address these critical unmet clinical needs.

Proceedings of the North American Society of Head and Neck Pathology Companion Meeting, New Orleans, LA, March 12, 2023: Classification of Salivary Gland Tumors: Remaining Controversial Issues?

The salivary gland section in the 5th edition of the World Health Organization Classification of Head and Neck Tumours includes a description of several new entities. In addition, numerous tumor variants were described and new concepts proposed, most of which have been based on recent molecular discoveries. However, there are still some controversial issues that remain to be resolved, and some of them are discussed in this review.

Classification of Chondrosarcoma: From Characteristic to Challenging Imaging Findings.

Chondrosarcomas can be classified into various forms according to the presence or absence of a precursor lesion, location, and histological subtype. The new 2020 World Health Organization (WHO) Classification of Tumors of Soft Tissue and Bone classifies chondrogenic bone tumors as benign, intermediate (locally aggressive), or malignant, and separates atypical cartilaginous tumors (ACTs) and chondrosarcoma grade 1 (CS1) as intermediate and malignant tumors. respectively. Furthermore, the classification categorizes chondrosarcomas (including ACT) into eight subtypes: central conventional (grade 1 vs. 2-3), secondary peripheral (grade 1 vs. 2-3), periosteal, dedifferentiated, mesenchymal, and clear cell chondrosarcoma. Most chondrosarcomas are the low-grade, primary central conventional type. The rarer subtypes include clear cell, mesenchymal, and dedifferentiated chondrosarcomas. Comprehensive analysis of the characteristic imaging findings can help differentiate various forms of chondrosarcomas. However, distinguishing low-grade chondrosarcomas from enchondromas or high-grade chondrosarcomas is radiologically and histopathologically challenging, even for experienced radiologists and pathologists.

Clinicopathological characteristics of mixed neuroendocrine-non-neuroendocrine neoplasms in gastrointestinal tract.

BACKGROUND: In 2019, the World Health Organization (WHO) classification system updated the definition of mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs), previously known as mixed adenoneuroendocrine carcinomas (MANECs). The clinicopathological characteristics of this new definition remains to be clarified. METHODS: We analyzed the clinical data of 43 patients diagnosed with MiNENs in Wuhan Union Hospital from 2011 to 2020 according to the definition of MiNENs proposed in 2019. RESULTS: Among the 43 patients with MiNENs, the top two most common sites were stomach and colon, and 69.8% were males. Nearly half (21/43) of the patients were diagnosed at TNM stage III, and about 53.5% (23/43) of patients were the neuroendocrine neoplasm dominant type. Among the non-neuroendocrine tumor components of 43 MiNENs patients, adenocarcinoma accounted for 95.3% (41/43) and squamous cell carcinoma accounted for 4.7% (2/43)；95.3% (41/43) of the neuroendocrine neoplasm components were neuroendocrine carcinoma (NEC) and 4.7% (2/43) were neuroendocrine tumor (NET). Approximately 60.5% (26/43) neuroendocrine components had a Ki-67 index ≥ 55%. In addition, we further compared the prognosis of different subtypes of the MiNENs based on the neuroendocrine neoplasm component and non-neuroendocrine neoplasm component, and the results showed that there was no significant difference in survival between different subtypes of MiNENs (P > 0.05). CONCLUSIONS: MiNENs can exhibit diverse clinicopathological characteristics, and there is no significant difference in prognosis among MiNENs subtypes, indicating that the definition of MiNENs can well summarize the prognosis of this type of tumor.

Impact of the International Consensus Classification of myelodysplastic syndromes.

The impact of the 2022 International Consensus Classification (ICC) of myelodysplastic syndromes (MDS) needs study. We analysed data from 989 MDS subjects classified using the 2016 World Health Organization (WHO) criteria to determine the impact of the new proposal. Our analyses suggested the ICC criteria of MDS-SF3B1 identifies a more homogenous disease entity than the WHO 2016 criteria of myelodysplastic syndromes with ring sideroblasts (MDS-RS). MDS, not otherwise specified with single lineage dysplasia (MDS, NOS-SLD) patients had a better prognosis than MDS, NOS with multilineage dysplasia (MDS, NOS-MLD) patients. MDS with mutated TP53 and MDS/acute myeloid leukaemia with mutated TP53 patients had the briefest survivals. These data support the ICC of MDS, which allows more accurate diagnoses and risk stratification.

Utility of non-contrast-enhanced magnetic resonance imaging in predicting preoperative clinical stage and prognosis in patients with thymic epithelial tumor.

PURPOSE: The purpose of this study was to find useful imaging features on non-contrast-enhanced magnetic resonance imaging (MRI) that can divide patients with thymic epithelial tumor (TET) into clinical stage I-II and III-IV groups under assumption that contrast media are contraindicated. MATERIALS AND METHODS: This retrospective study included 106 patients (median age, 60 years; range, 27-82 years; 62 women) with surgically resected TET who underwent MRI between August 1986 and July 2015. All cases were classified according to the 2015 WHO classification and staged using the eighth edition of the TNM system. Two radiologists independently evaluated 14 categories of MRI findings; the findings in patients with stage I-II were compared with those of patients with stage III-IV using a logistic regression model. Disease-specific survival associated with significant findings was calculated using the Kaplan-Meier method. RESULTS: Univariate analysis showed that stage III-IV patients were more likely to have tumors with an irregular contour, heterogeneity on T1WI, low-signal intensity on T2WI, irregular border with lung, findings of great vessel invasion (GVI) (hereafter, GVI sign), pericardial thickening/nodule, and lymphadenopathy (all, P < 0.01). On multivariable analysis, only two findings, irregular border between tumor and lung (odds ratio [OR], 272.8; 95% CI 26.6-2794.1; P < 0.001) and positive GVI sign (OR, 49.3; 95% CI 4.5-539.8; P = 0.001) remained statistically significant. Patients with one or both features had significantly worse survival (log-rank test, P < 0.001). CONCLUSION: For patients with TET who are unable to receive contrast for preoperative staging, the two image findings of an irregular border between tumor and lung and the positive GVI sign on non-contrast-enhanced MRI could be helpful in determining stage III-IV disease which is associated with a worse survival.

Molecular targets for the treatment of AML in the forthcoming 5th World Health Organization Classification of Haematolymphoid Tumours.

INTRODUCTION: Acute myeloid leukemia (AML) is a genetically heterogeneous disease for which the treatment armamentarium has been historically restricted to chemotherapy. However, genomic and epigenomic alterations that contribute to AML initiation, maintenance, and relapse have disclosed new insights to the 5th update in WHO Classification of Haematolymphoid Tumours. AREAS COVERED: After four decades of intensive chemotherapy as a 'one-size-fits-all' concept, several targeted agents have been approved for the treatment of AML. Several compounds, directed against regulators of apoptotic, epigenetic, or micro-environmental pathways, and immune-system modulators, are currently in development and investigation in clinical trials. We review advances in target-based therapy for AML focusing on their mechanism of action, examining the intracellular events and pathways, and the results from published clinical trials. EXPERT OPINION: To improve patient clinical outcomes, find new biomarkers for therapeutic response, and pinpoint patients who might benefit from novel targeted medicines, next-generation sequencing is being used to evaluate AML-associated mutations. In fact, the new 5th edition of WHO classification has reaffirmed the importance of genetically defined entities that have a prognostic impact, but not all have a specific treatment available. New class of target drugs are in clinical development and could be beneficial to improve the therapeutic armamentarium available.

The new diagnostic criteria for myelodysplasia-related acute myeloid leukemia is useful for predicting clinical outcome: comparison of the 4th and 5th World Health Organization classifications.

Mutations in myelodysplasia-related (MR) genes, rather than morphological features, have been included in the diagnostic criteria of the new 5th World Health Organization (WHO) classification for myelodysplastic syndrome (MDS)-associated acute myeloid leukemia (AML). This study compares the clinical relevance of the new criteria with those of the previous version. In a cohort of 135 patients with newly diagnosed AML, the MDS-related AML patients were classified according to the 5th and 4th edition of the WHO classification (AML, myelodysplasia-related [AML-MR5th] and AML with myelodysplasia-related changes [AML-MRC4th], respectively). The median age of the patients was 70.4 years. MR gene mutations were found in 48 patients (35.6%). Sixty-one patients (46.6%) were diagnosed with AML-MRC4th, while 71 patients (53.0%) were diagnosed with AML-MR5th. Patients with AML-MR5th were significantly older with significantly lower treatment response rate, higher recurrence rate, and shorter relapse-free survival after chemotherapy, whereas AML-MRC4th patients did not show any association with the treatment outcome. Overall, the following prognostic factors for survival were identified: age over 75 years, antecedent MDS or MDS/myeloproliferative neoplasm, chromosome 5 or 7 abnormalities, and KRAS and ZSZR2 mutations. The 5th WHO classification is more useful for predicting the treatment response of patients with AML-MR than the previous version. Among the MR genes, ZSZR2 mutations were found to be independent prognostic factors affecting survival.

Epidermal Growth Factor Receptor Variant III Mutation, an Emerging Molecular Marker in Glioblastoma Multiforme Patients: A Single Institution Study on the Indian Population.

Background Glioblastoma is the most frequent and the most aggressive primary malignant brain tumor in adults. Standard treatment includes surgical removal of the tumor followed by concomitant chemotherapy and radiotherapy. Temozolomide, an oral alkylating agent, is currently the most commonly used chemotherapy. However, the median survival of glioblastoma multiforme (GBM) patients remains very low. Epidermal growth factor receptor variant III (EGFRvIII) is a novel marker for GBM patients of Indian origin as very few studies have been done on this molecular marker in our country. This is the first study utilizing this molecular marker among GBM patients in Rajasthan, India. This was a single institutional study that aimed to estimate the proportion of EGFRvIII mutation in GBM patients of Indian origin. Methodology This was a non-randomized, ambispective, single institutional observational study done on 35 brain tissue biopsies of histopathologically diagnosed and confirmed cases of GBM based on the World Health Organization 2007 Classification received in the pathology department of Dr. Sampurnanand Medical College, Jodhpur from 2015 to 2020 after applying inclusion and exclusion criteria. Molecular study of the EGFRvIII marker was conducted in all cases of GBM in the same institution on the RNA extracted from selected biopsy samples. Statistical analysis was performed using the SPSS version 22.0 software package (IBM Corp., Armonk, NY USA). The correlation between age and gender with EGFR-positive cases was analyzed, and EGFR positivity compared with previous studies. Results The occurrence of the EGFRvIII mutation was found to be 17.4% (6/35 cases). The mean age of presentation of a tumor with this mutation was estimated to be 54.3 years. Males were more commonly found to be affected (66.6%, 4/6 cases). Conclusions Thus, the identification of this mutation would segregate patients who may benefit from newer therapeutic approaches. In the future, personalized treatment may be advised for GBM patients depending on the presence of the EGFRvIII mutation.

Endocervical Adenocarcinoma: Comprehensive Histological Review and Re-classification of 123 Consecutive Cases According to the Updated World Health Organization Classification of Female Genital Tumors.

BACKGROUND/AIM: The updated 2020 World Health Organization (WHO) classification divides endocervical adenocarcinomas (EACs) into human papillomavirus-associated (HPVA) and -independent (HPVI) tumors. The purpose of this study was to review our EAC cases and re-classify them according to the updated WHO classification. PATIENTS AND METHODS: We reviewed the hematoxylin and eosin-stained slides of 123 EACs and reclassified them according to the updated WHO classification. RESULTS: Eighty-one (65.9%) and 42 (34.1%) patients had HPVA and HPVI EACs, respectively. The usual (60/81; 74.1%) and gastric (31/42; 73.8%) types were the most common HPVA and HPVI EACs, respectively. Signet-ring cell (1/123; 0.8%), invasive stratified mucin-producing (10/123; 8.1%), clear-cell (4/123; 3.3%), mesonephric (3/123; 2.4%), and serous (1/123; 0.8%) types were uncommon. Unusual morphologies were seen, including microcystic, elongated, and fragmented patterns of stromal invasion, micropapillary growth patterns, and gastric-type adenocarcinoma in situ. CONCLUSION: We successfully reclassified all the examined cases based on morphology alone. The numbers and relative proportions of EAC histotypes were variable. We found some uncommon histotypes, as well as unusual but clinically important histological features.

New insights in diagnosis and treatment of gastroenteropancreatic neuroendocrine neoplasms.

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare epithelial neoplasms derived from pluripotent endocrine cells along the gastrointestinal tract and pancreas. GEP-NENs are classified into well-differentiated neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas. Despite overlapping morphological features, GEP-NENs vary in molecular biology, epigenetic, clinical behavior, treatment response, and prognosis features and remain an unmet clinical challenge. In this review, we introduce recent updates on the histopathologic classification, including the tumor grading and staging system, molecular genetics, and systemic evaluation of the diagnosis and treatment of GEP-NENs at different anatomic sites, together with some insights into the diagnosis of challenging and unusual cases. We also discuss the application of novel therapeutic approaches for GEP-NENs, including peptide receptor radionuclide therapy, targeted therapy, and immunotherapy with immune checkpoint inhibitors. These findings will help improve patient care with precise diagnosis and individualized treatment of patients with GEP-NENs.

Epidemiological characteristics of central nervous system tumors in children: a 5-year review of 3180 cases from Beijing Tiantan Hospital.

BACKGROUND: To describe the epidemiological characteristics of central nervous system (CNS) tumors in children, based on the neurosurgery department of Beijing Tiantan Hospital. METHODS: From January 2015 to December 2019, 3180 children were histopathologically diagnosed with CNS tumors based on the 2016 World Health Organization (WHO) classification of tumors. Patients were 0 to 15 years old. We analyzed age-related gender preferences, tumor locations, and the histological grades of the tumors. In addition, the epidemiological characteristics of the five most common intracranial tumors were compared to the previous studies. RESULTS: In this study, intracranial and spinal tumors account for 96.4% (3066) and 3.6% (114) of all tumors, with a preponderance of supratentorial tumors (57.9%). Among all pediatric patients, low-grade tumors comprise 67.1% (2 135). The integral gender ratio of males to females is 1.47: 1 and the average age of patients is 7.59 years old. The five most common intracranial tumors are craniopharyngioma (15.4%), medulloblastoma (14.3%), pilocytic astrocytoma (11.8%), diffuse astrocytoma (9.8%), and anaplastic ependymoma (4.8%). CONCLUSIONS: Due to the lack of national data on childhood brain tumors, we used a large nationally representative population sample based on the largest pediatric neurosurgery center in China. We analyzed the data of the past 5 years, reflecting the incidence of CNS tumors in Chinese children to a certain extent, and laying a data foundation for subsequent clinical studies.