WHO Classification Of Tumors Research Articles

Abstract 2158: Emerging epidemiological cancer trends among West African adults in Zaria, Nigeria (1972 to 2022)

Abstract Cancer incidence and mortality rates in Africa are increasing, with sub-Saharan Africa reporting 2.7-fold higher fatality than global averages. The incidence of cancer in Africa in 2020 was about 1.1 million new cases, with 711,000 deaths, indicating a mortality-to-incidence ratio (MIR) of 0.64. These cancer challenges in Africa necessitate a concerted approach towards effective cancer control and management. Here, we present an extensive report of emerging epidemiological cancer trends among West African adults seen between 1972-2022 in Zaria, Nigeria. We used the Zaria cancer registry of the Ahmadu Bello University Teaching Hospital (ABUTH) Zaria, Nigeria to obtain information on histologically diagnosed cancers from January 1st, 1972 to December 31, 2022. Records in the Zaria registry are indexed into a register paper-based and 2008 and transferred by CanReg4 software on the computer. We used WHO classification of tumors (WHO Blue Book) 5th edition to classify all the abstracted cancers for the purpose of this study. Time-trend analyses were performed by utilizing linear regression models. In the analysis of the Zaria cancer registry, 12,114 adults (42.2% male, 57.8% female) were diagnosed with histologically confirmed cancer between 1972 - 2022. The most common diagnosis among male cancer patients was prostate cancer, comprising a quarter of all cases. The median age of diagnosis for prostate cancer was 65 years, with an interquartile range (IQR) of 60 and 70. Among female cancer patients, the most common diagnoses were cervical cancer and breast cancer, together comprising 68.2% of all cases. Median age at diagnosis were 45 (IQR, 40-56) and 42 (IQR, 35-50), respectively. In time-trend analyses, the total number of new cancer cases diagnosed at ABUTH from 1972 to 2022 increased over time (p<0.001). In the analyses of individual cancers, those in which the number of new cases increased over time were neoplasms of the bones and joints, breast, cervix, prostate, colorectum and stomach, head and neck (p<0.001); esophagus (p=0.006); eye and orbit and soft tissue (p=0.002); and ovary (p=0.005). Cancers in which the number of new cases decreased over time were Hodgkin lymphoma, Non-Hodgkin lymphoma, melanoma of the skin, and non-melanoma cancer of the skin (p<0.001). The number of new adult cancer diagnoses recorded in the Zaria cancer registry have increased over time from 1972 to 2022. Prostate cancer accounted for a quarter of all cancer cases among males, whereas cervical cancer and breast cancer accounted for nearly 70% of all cases among females. Westernization with associated change in dietary habits, physical inactivity, obesity and reproductive behaviors and changes in the population size and life expectancy may be attributable factors to change in cancer in Zaria. Better understanding of these factors will inform cancer prevention and control strategies. Citation Format: Faruk Mohammed, David J. Lee, Katy Graef, Abdulmumini Hassan Rafindadi, Sani Ibrahim, Sirajo Mohammed Aminu, Ahmed Adamu, Adamu Abdullahi, Aishatu Maude Suleiman, Abdullahi Mohammed, John Idoko, Abdulkadir Lawal Rafindadi, Danladi Amodu Ameh, Bello Ahmad Kumo, Ahmad Bello, Abdullahi Jubril Randawa, Oguntayo Olanrewaju Adekunle, Usman Mohammed Aminu, Muhammad Manko, Olasinde Tajudeen Tajudeen, Lazarus M. Yusufu, Mohammed Dauda Maigatari, Lawal Khalid, Dahiru Ismail, Aliyu Ahmed Babadoko, Ahmed Tijjani Lawal, Abdullahi Alfa Mohammed, Yahaya Ukwenya, Ahmed Mai, Maitama Yusuf Hussaini, Anisah Yahaya, Caitlin Bishop, Jennifer Dent, Timothy R. Rebbeck, Yawale Iliyasu. Emerging epidemiological cancer trends among West African adults in Zaria, Nigeria (1972 to 2022) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2158.

What's new in thyroid pathology 2024: updates from the new WHO classification and Bethesda system.

In line with the release of the 5th edition WHO Classification of Tumors of Endocrine Organs (2022) and the 3rd edition of the Bethesda System for Reporting Thyroid Cytopathology (2023), the field of thyroid pathology and cytopathology has witnessed key transformations. This digest brings to the fore the refined terminologies, newly introduced categories, and contentious methodological considerations pivotal to the updated classification.

Pediatric CNS tumors and 2021 WHO classification: what do oncologists need from pathologists?

The fifth edition of the WHO Classification of Tumors of the Central Nervous System (CNS), published in 2021, established new approaches to both CNS tumor nomenclature and grading, emphasizing the importance of integrated diagnoses and layered reports. This edition increased the role of molecular diagnostics in CNS tumor classification while still relying on other established approaches such as histology and immunohistochemistry. Moreover, it introduced new tumor types and subtypes based on novel diagnostic technologies such as DNA methylome profiling. Over the past decade, molecular techniques identified numerous key genetic alterations in CSN tumors, with important implications regarding the understanding of pathogenesis but also for prognosis and the development and application of effective molecularly targeted therapies. This review summarizes the major changes in the 2021 fifth edition classification of pediatric CNS tumors, highlighting for each entity the molecular alterations and other information that are relevant for diagnostic, prognostic, or therapeutic purposes and that patients' and oncologists' need from a pathology report.

Circulating serum miR-362-3p and miR-6721-5p as potential biomarkers for classification patients with adult-type diffuse glioma.

According to the fifth edition of the WHO Classification of Tumours of the Central Nervous System (CNS) published in 2021, grade 4 gliomas classification includes IDH-mutant astrocytomas and wild-type IDH glioblastomas. Unfortunately, despite precision oncology development, the prognosis for patients with grade 4 glioma remains poor, indicating an urgent need for better diagnostic and therapeutic strategies. Circulating miRNAs besides being important regulators of cancer development could serve as promising diagnostic biomarkers for patients with grade 4 glioma. Here, we propose a two-miRNA miR-362-3p and miR-6721-5p screening signature for serum for non-invasive classification of identified glioma cases into the highest-grade 4 and lower-grade gliomas. A total of 102 samples were included in this study, comprising 78 grade 4 glioma cases and 24 grade 2-3 glioma subjects. Using the NanoString platform, seven miRNAs were identified as differentially expressed (DE), which was subsequently confirmed via RT-qPCR analysis. Next, numerous combinations of DE miRNAs were employed to develop classification models. The dual panel of miR-362-3p and miR-6721-5p displayed the highest diagnostic value to differentiate grade 4 patients and lower grade cases with an AUC of 0.867. Additionally, this signature also had a high AUC = 0.854 in the verification cohorts by RT-qPCR and an AUC = 0.842 using external data from the GEO public database. The functional annotation analyses of predicted DE miRNA target genes showed their primary involvement in the STAT3 and HIF-1 signalling pathways and the signalling pathway of pluripotency of stem cells and glioblastoma-related pathways. For additional exploration of miRNA expression patterns correlated with glioma, we performed the Weighted Gene-Co Expression Network Analysis (WGCNA). We showed that the modules most associated with glioma grade contained as many as six DE miRNAs. In conclusion, this study presents the first evidence of serum miRNA expression profiling in adult-type diffuse glioma using a classification based on the WHO 2021 guidelines. We expect that the discovered dual miR-362-3p and miR-6721-5p signatures have the potential to be utilised for grading gliomas in clinical applications.

Thrombotic Complications, Disease Progression, and Survivals in BCR::ABL1-Negative Myeloproliferative Neoplasms: A 12-Year Retrospective Study at a Single Center in Thailand

Objective: To assess the incidence of thrombotic events among patients with BCR::ABL1-negative myeloproliferative neoplasm (MPN) within a single center in Thailand. Materials and Methods: Conducted as a retrospective cohort study between 2008 and 2019, the present research focused on patients diagnosed with BCR::ABL1-negative MPN. Diagnoses were reviewed and reclassified based on the WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues (2017). Data collected encompassed demographic details, comorbidities, investigation results, treatments, and outcomes. The primary focus was on thrombosis rates in arterial and venous sites. Secondary outcomes included the incidence of major bleeding, thrombosisfree survival (TFS), and overall survival (OS). Results: One hundred seventy-five patients participated in the present study and comprised of 46 patients (26.3%) with polycythemia vera (PV), 123 (70.3%) patients with essential thrombocythemia (ET), and six patients (3.4%) with primary myelofibrosis (PMF). Most patients were over 60 years old. The rate of overall thrombosis rate was 28.0%, with 43.5% in PV and 23.6% in ET. Common sites of thrombotic events included the cerebral artery at 16.6%, coronary artery at 6.3%, peripheral artery at 4.0% and venous thromboembolism at 3.4%. The overall bleeding event rate was 13.7%, with 70.8% classified as major bleeding. The all-cause mortality rate within the present cohort was 30.9%. TFS and OS stood 72.0% and 69.1%, respectively. Conclusion: Thrombosis emerged as a significant complication in patients with BCR::ABL1-negative MPN, affecting 28.0% of individuals in the present cohort. Arterial thromboses, particularly ischemic stroke and cardiovascular events, were the predominant occurrences. Keywords: Myeloproliferative neoplasm; Polycythemia vera; Essential thrombocythemia; Thrombosis; Bleeding

A snapshot of the landscape of endometrial cancer in Kenya: Implications of recent updates in pathological classification

Background: The incidence of endometrial carcinoma is rising worldwide, partly due to the risingprevalence of obesity. From a diagnostic pathology perspective, it is a heterogeneous disease with avaried range of histomorphological features and is prone to poor interobserver reproducibility. This oftenhas downstream effects on treatment protocols and patient outcomes. The current WHO Classification ofTumors of the Female Genital Tract recommends the incorporation of histology, immunohistochemistry,and molecular testing where possible in the classification of endometrial carcinoma into clinically relevantsubtypes. In Kenya, access to ancillary testing is limited and prohibitively expensive, negatively affectingaccurate tumor classification. In addition, there are limited local data on the various histologic subtypes ofendometrial carcinoma and their respective clinical outcomes.Objectives: To review the classification of endometrial carcinoma as defined by the current WHOClassification contextualized with local clinical, demographic, pathology, and outcome data from twotertiary referral centers in Kenya.Methods: Formalin-fixed paraffin-embedded blocks (FFPE) of 123 cases of endometrial carcinomasbetween 2012 and 2020 were retrieved from the Aga Khan University and Moi Teaching and ReferralHospitals. The clinical history and follow-up data were abstracted. Hematoxylin and eosin sections werereviewed and 11 immunohistochemical markers (MLH1, MSH2, MSH6, PMS2, ER, PR, ARID1A, P16,PTEN, napsin A, and p53) were determined, and analyzed to arrive at a consensus diagnosis.Results: Six endometrial carcinoma subtypes: endometrioid (68 cases, 55%), serous (32 cases, 26%),carcinosarcoma (15 cases, 12%), clear cell (5 cases, 4%), mixed carcinoma (2 cases, 1.5%), anddedifferentiated carcinoma (1 case, <1%) were reported. The median age of presentation was 63 years(range of 34-90 years) and the median body mass index (BMI) was 27.4 kg/m2. Staging data wereavailable in 95 cases, of which 64 (67%) were in the early stage at presentation. Follow-up data wereavailable in 70 patients with a median follow-up time of 18 months. Recurrences were reported in 11cases, 5 of which were of the serous subtype. Of the 26 patients whose status was known at the time ofthe conclusion of the study, 7 died of the disease.Conclusion: To our knowledge, this is the first comprehensive review of the clinical and pathologicalprofiles of various subtypes of endometrial cancer in Kenya with follow-up and outcome data using awide array of immunohistochemical markers for accurate classification as per the WHO classification.

Molecular Determinants of Neurocognitive Deficits in Glioma: Based on 2021 WHO Classification

Cognitive impairment is a common feature among patients with diffuse glioma. The objective of the study is to investigate the relationship between preoperative cognitive function and clinical as well as molecular factors, firstly based on the new 2021 World Health Organization’s updated classification of central nervous system tumors. A total of 110 diffuse glioma patients enrolled underwent preoperative cognitive assessments using the Mini-Mental State Examination and Montreal Cognitive Assessment. Clinical information was collected from medical records, and gene sequencing was performed to analyze the 18 most influenced genes. The differences in cognitive function between patients with and without glioblastoma were compared under both the 2016 and 2021 WHO classification of tumors of the central nervous system to assess their effect of differentiation on cognition. The study found that age, tumor location, and glioblastoma had significant differences in cognitive function. Several genetic alterations were significantly correlated with cognition. Especially, IDH, CIC, and ATRX are positively correlated with several cognitive domains, while most other genes are negatively correlated. For most focused genes, patients with a low number of genetic alterations tended to have better cognitive function. Our study suggested that, in addition to clinical characteristics such as age, histological type, and tumor location, molecular characteristics play a crucial role in cognitive function. Further research into the mechanisms by which tumors affect brain function is expected to enhance the quality of life for glioma patients. This study highlights the importance of considering both clinical and molecular factors in the management of glioma patients to improve cognitive outcomes.

MANEC TUMOR OF RECTUM. A RARE CASE SERIES OF 3 PATIENTS AND A LITERATURE REVIEW.

The term Mixed Adeno-Neuro-Endocrine Carcinoma (MANEC) was introduced in 2010 by the WHO Classification of Tumors of the Digestive System. It refers to a neoplasm with dual epithelial and neuroendocrine differentiation, each component representing at least 30% of the tumor. It is an uncommon tumor accounting for < 3% of all colon and rectum malignancies. We report three cases of this extremely rare MANEC of the rectum. All three cases presented with hematochezia, variable constipation, and abdominal pain. They were diagnosed and staged appropriately with colonoscopy, biopsy with immunohistochemistry, and imaging. They underwent an anterior resection with circular stapled anastomoses. Because of the low incidence of this histotype, we reviewed the clinical presentation, diagnostic characteristics, and treatment of MANEC of the colon and rectum.

Tumours of the nipple – evidence gaps mapped from the fifth edition of the WHO classification of tumours of the breast: preliminary results

Tumours of the nipple – evidence gaps mapped from the fifth edition of the WHO classification of tumours of the breast: preliminary results

Biphenotypic lung carcinoma with coexpression of TTF-1 and ΔNP63/P40 within most of the same individual cells: a further case confirming poor prognosis and a review of literature.

The WHO Classification of Tumors, Thoracic Tumors, 5th edition, has outlined the use of TTF-1 and ΔNP63/P40 to discriminate between adenocarcinoma and squamous cell carcinoma. In 2015, the first description of a rare non-small cell lung carcinoma featuring co-expression of glandular and squamous differentiation within most of the same individual tumor cells was reported on, with ultrastructural and molecular demonstration of such a biphenotypic differentiation. We herein describe an additional case of this rare tumor entity, which is confirmed to be an aggressive neoplasm despite potential targets of therapy.

Progress in diagnosing and treating thyroid squamous cell carcinoma under the 5th edition of WHO classification.

Squamous cell carcinoma of the thyroid (SCCT) is a rare thyroid gland malignancy, with only a few hundred cases reported in the literature, mostly as case reports or small sample studies. In the previous WHO classification, squamous cell carcinoma of the thyroid was defined as a carcinoma composed entirely of squamous cells without differentiated carcinoma components. It was once included in the WHO tumor classification separately. However, the 2022 WHO classification of squamous cell carcinoma of the thyroid was reclassified as a morphologic subtype of anaplastic thyroid carcinoma (ATC). The squamous cell carcinoma pattern is similar to the other histologic types of ATC, but the phenotype associated has a poorer prognosis. The typical clinical manifestation of this condition is a cervical mass, accompanied by indications and symptoms of compression on adjacent structures such as the esophagus and trachea in advanced stages. Secondary squamous cell carcinoma of the thyroid may occur due to the spread of squamous carcinoma of the larynx or esophagus or distant metastases from other sites. Diagnosis of squamous cell carcinoma of the thyroid includes neck Ultrasound (US), Computed Tomography (CT) or Magnetic Resonance Imaging (MRI), puncture tissue biopsy, and full endoscopy to identify metastatic lesions from the nasopharynx, oropharynx, hypopharynx, larynx, esophagus, or bronchi and to help with the initial staging of the tumor. Current treatment modalities include surgery, radiotherapy, chemotherapy, or a combination. Because of the poor prognosis of patients with this disease, the short survival period, usually less than one year, and the difficulty of preoperative diagnosis, this article reviews the epidemiological features, origin, clinical features, pathological features, and differential diagnosis to improve the diagnosis and treatment of this disease by clinicians.

Development and validation of clinical-radiomics analysis for preoperative prediction of IDH mutation status and WHO grade in diffuse gliomas: a consecutive L-[methyl-11C] methionine cohort study with two PET scanners.

Determination of isocitrate dehydrogenase (IDH) genotype is crucial in the stratification of diagnosis and prognostication in diffuse gliomas. We sought to build and validate radiomics models and clinical features incorporated nomogram for preoperative prediction of IDH mutation status and WHO grade of diffuse gliomas with L-[methyl-11C] methionine ([11C]MET) PET/CT imaging according to the 2016 WHO classification of tumors of the central nervous system. Consecutive 178 preoperative [11C]MET PET/CT images were retrospectively studied for radiomics analysis. One hundred six patients from PET scanner 1 were used as training dataset, and 72 patients from PET scanner 2 were used for validation dataset. [11C]MET PET and integrated CT radiomics features were extracted, respectively; three independent predictive models were built based on PET features, CT features, and combined PET/CT features, respectively. The SelectKBest method, Spearman correlation analysis, Least Absolute Shrinkage and Selection Operator (LASSO) regression, and machine learning algorithms were applied for feature selection and model building. After filtering the satisfactory predictive model, key clinical features were incorporated for the nomogram establishment. The combined [11C]MET PET/CT radiomics model, which consisted of four PET features and eight integrated CT features, was significantly associated with IDH genotype (p < 0.0001 for both training and validation datasets). Nomogram based on the [11C]MET PET/CT radiomics score, patients' age, and dichotomous tumor location status showed satisfactory discrimination capacity, and the AUC was 0.880 (95% CI, 0.726-0.998) in the training dataset and 0.866 (95% CI, 0.777-0.956) in the validation dataset. In IDH stratified WHO grade prediction, the final radiomics model consists of four PET features and two CT features had reasonable and stable differential efficacy of WHO grade II and III patients from grade IV patients in IDH-wildtype patients, and the AUC was 0.820 (95% CI, 0.541-1.000) in the training dataset and 0.766 (95% CI, 0.612-0.921) in the validation dataset. [11C]MET PET radiomics features could benefit non-invasive IDH genotype prediction, and integrated CT radiomics features could enhance the efficacy. Radiomics and clinical features incorporation could establish satisfactory nomogram for clinical application. This non-invasive predictive investigation based on our consecutive cohort from two PET scanners could provide the perspective to observe the differential efficacy and the stability of radiomics-based investigation in untreated diffuse gliomas.

Rapid intraoperative multi-molecular diagnosis of glioma with ultrasound radio frequency signals and deep learning

Molecular diagnosis is crucial for biomarker-assisted glioma resection and management. However, some limitations of current molecular diagnostic techniques prevent their widespread use intraoperatively. With the unique advantages of ultrasound, this study developed a rapid intraoperative molecular diagnostic method based on ultrasound radio-frequency signals. We built a brain tumor ultrasound bank with 169 cases enrolled since July 2020, of which 43483 RF signal patches from 67 cases with a pathological diagnosis of glioma were a retrospective cohort for model training and validation. IDH1 and TERT promoter (TERTp) mutations and 1p/19q co-deletion were detected by next-generation sequencing. We designed a spatial-temporal integration model (STIM) to diagnose the three molecular biomarkers, thus establishing a rapid intraoperative molecular diagnostic system for glioma, and further analysed its consistency with the fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5). We tested STIM in 16-case prospective cohorts, which contained a total of 10384 RF signal patches. Two other RF-based classical models were used for comparison. Further, we included 20 cases additional prospective data for robustness test (ClinicalTrials.govNCT05656053). In the retrospective cohort, STIM achieved a mean accuracy and AUC of 0.9190 and 0.9650 (95% CI, 0.94-0.99) respectively for the three molecular biomarkers, with a total time of 3s and a 96% match to WHO CNS5. In the prospective cohort, the diagnostic accuracy of STIM is 0.85±0.04 (mean±SD) for IDH1, 0.84±0.05 for TERTp, and 0.88±0.04 for 1p/19q. The AUC is 0.89±0.02 (95% CI, 0.84-0.94) for IDH1, 0.80±0.04 (95% CI, 0.71-0.89) for TERTp, and 0.85±0.06 (95% CI, 0.73-0.98) for 1p/19q. Compared to the second best available method based on RF signal, the diagnostic accuracy of STIM is improved by 16.70% and the AUC is improved by 19.23% on average. STIM is a rapid, cost-effective, and easy-to-manipulate AI method to perform real-time intraoperative molecular diagnosis. In the future, it may help neurosurgeons designate personalized surgical plans and predict survival outcomes. A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

Acute Non-Lymphoblastic Leukemias Presenting with Gingival Hyperplasia: Diagnosis and Management Updates

Background: Leukemias represent a heterogeneous group of hematological malignancies, which are characterized by the disordered proliferation of neoplastic hematopoietic cells, with the diffuse bone marrow involvement. Most frequent oral findings in leukemias are cyanotic or erythematous gingival hyperplasia with or without necrosis, petechiae, ecchymoses, mucosal ulcers and hemorrhage. Gingival hyperplasia is reported as a consistent symptom, which forwards patients for a dentistry consultation, that may lead to an early diagnosis of acute leukemias. The recognition of gingival enlargement as an initial oral manifestation of leukemic involvement assumes major practical significance, especially for the early diagnosis of non-lymphoblastic leukemias. Objectives: The aims of researches were the evaluation of diagnosis and management of hyperplastic gingivitis in acute leukemias. Material and Methods: The patients' follow-up and treatment were realized at the comprehensive cancer center. Our observational, analytical and descriptive study enrolled 8 patients with acute leukemias, who were treated at the Institute of Oncology from Moldova between 2012-2023. The diagnosis was asserted by the bone marrow aspiration with cytochemical reactions, tissue biopsy, buccal swab, or fine needle aspiration cytology. The immunophenotyping was performed in selected cases. The types of acute leukemias were assessed and distinguished according to the 2017 Revision of WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues. This prospective study was related to the hospitalized and outpatient care. Results: Hyperplastic gingivitis developed in cases with myelomonocytic and monocytic acute leukemias. The leukemia patients were admitted to the Institute of Oncology with a history of fatigue, fever, bone pain, gingival bleeding and enlargement detected by dentistry and family doctors from the consulting centers. ECOG-WHO performance score was 2-3. The intra-oral examination revealed generalized gingival hyperplasia. There were the amounts of plaque and calculus, which did not justify the enlargement degree. The gingiva was spongy and painless on palpation, with solitary sectors of necrosis and mucosal bleeding. Multiple soft and tender lymph nodes ranging from 0.8-1.5 cm in diameter were palpable bilaterally in the cervical and axillary regions. Splenomegaly of various degree was revealed by ultrasound scan in all patients. Complete blood count values ranged between: Hb 66-104 g/l, RBC 2.3-3.7 x 10 12/l, WBC 11.3-47.2 x 10 9/l, PLT 17.0-115.0 x 10 9/l, blast cells 17-65%. The bone marrow aspiration detected hypercellularity, myeloid and monocytic blast cells (31.0-58.0%), as well as monocytes (9.0-14.0%). The studied cases were not suggestive of presence of FLT3 mutations. Hyperplastic gingivitis regressed in 5 (62.5%) cases after the achievement of complete (4 patients) and partial (1 patient) hematological responses under the first-line combined chemotherapy with conventional doses of cytarabine, anthracyclines and etoposide (2 patients). Local treatment included daily administration of oral steroids, antiseptic and hemostatic drugs. The narrative review of the recent references revealed that 37-53% of patients with monocytic and myelomonocytic leukemias were reported to develop gingival hyperplasia. Conclusions: Hyperplastic gingivitis emerges in acute leukemias mostly due to the gingival infiltration with neoplastic blast cells. Gingival hyperplasia may regress under the combined chemotherapy and local treatment in patients with complete or partial hematological responses. Early diagnosis and treatment, thus, can increase the leukemia patients' prospects for complete hematological and local responses.

NIMG-08. ANALYSIS OF11C-METHIONINE PET UPTAKE AND PROGNOSIS IN LOWER GRADE GLIOMAS

Abstract PURPOSE The 2021 WHO Classification of Tumors of the Central Nervous System incorporates molecular alterations into the classification system, with the goal of creating more homogenous disease categories with greater prognostic value. This study aimed to assess the correlation between 11C-methionine uptake, molecular features and prognosis in newly diagnosed lower-grade gliomas (LGGs). METHODS 93 newly diagnosed LGG patients (Grade 2: 39 patients, Grade 3: 54 patients) who underwent surgery at Tokyo Medical and Dental University Hospital from 2000 to 2020 and imaged preoperatively using 11C-methionine PET were retrospectively included in this study. These patients were re-classified according to the 2021 WHO classification. The tumor-to-normal ratio (T/N) of 11C-methionine uptake was calculated by dividing the mean standardized uptake value (SUV) for the tumor by the mean SUV of the normal brain. RESULTS 44 out of 93 gliomas were IDH wild-type tumors and re-classified as glioblastoma or pediatric-type gliomas according to the 2021 WHO classification and therefore excluded from the analysis. Remaining 49 LGGs were re-classified in two types- Oligodendrogliomas, IDH-mutant and 1p/19q- codeleted (n=25), and Astrocytomas, IDH-mutant (n=24)- following the indications provided by the 2021 WHO classification. The median T/N ratio in Oligodendrogliomas, IDH-mutant and 1p/19q- codeleted were 1.83 in grade 2 and 2.83 in grade 3, which were significantly higher than those in Astrocytoma, IDH-mutant (grade2: 1.38, grade3:1.62). Kaplan–Meier survival analysis revealed that Oligodendroglioma, IDH-mutant and 1p/19q- codeleted had significantly better outcomes regardless of WHO grade. CONCLUSION The results indicated that LGG categories reclassified with molecular classification correlate with the T/N ratio of methionine uptake and the prognosis.

NCOG-05. TREATMENT STRATEGY AND SURVIVAL ANALYSIS OF PATIENTS WITH PRIMARY ADULT-TYPE DIFFUSE GLIOMA IN THE MOLECULAR ERA: A PROSPECTIVE COHORT STUDY FROM THE CGGA NETWORK

Abstract IMPORTANCE The fifth edition of the WHO Classification of Tumors of the Central Nervous System (CNS) marks the entry of the diagnosis and treatment of diffuse glioma into the molecular era. The clinical implications of this landmark change in primary adult-type diffuse glioma need to be revealed. OBJECTIVE To reveal the clinical prognostic factors of adult diffuse glioma under the WHO CNS 5 classification. DESIGN, SETTING, AND PARTICIPANTS In this clinical-based prospective observational registration study, 3,308 glioma patients from 3 major neurosurgical centers were enrolled between Mar. 2005 to Jun. 2021. After excluding patients who did not meet the inclusion criteria, 1,099 primary adult-type diffuse glioma patients were eligible for inclusion in this study. Student t-test, Chi-squared test, and ANOVA were used for differential analysis. Kaplan-Meier curve and univariate and multivariate Cox regression analyses were used for survival analysis. MAIN OUTCOMES AND MEASURES Totally, 1,099 patients diagnosed with primary adult-type diffuse glioma were included in this study. The male-to-female ratio is about 1.4-1.5 to 1. The mean age at diagnosis for astrocytoma, IDH-mutant, oligodendroglioma, IDH-mutant and 1p/19q-codeleted and glioblastoma, IDH-wildtype were 39.0, 40.0, and 53.0 years, respectively. In astrocytoma, preoperative epilepsy, WHO grade, MGMT promoter methylation status, the extent of resection, and postoperative comprehensive treatment were independently associated with overall survival. For oligodendroglioma, gender, WHO grade, and extent of resection were associated with overall survival. As for glioblastoma patients, gender, age at diagnosis, preoperative KPS, preoperative epilepsy, the extent of resection, and postoperative comprehensive treatment were prognostically correlated. CONCLUSIONS AND RELEVANCE Patients in distinct molecular subtypes showed different epidemiological features and were associated with different clinical prognostic factors.

NIMG-27. GLIOBLASTOMA IN THE MAKING? ADVANCED IMAGING TELLS "MOLECULAR GLIOBLASTOMA" APART FROM ASTROCYTOMA

Abstract The fifth WHO classification of tumors of the CNS allows the diagnosis of glioblastoma using specific molecular markers, even if the classical histological criteria (necrosis and neoangiogenesis) are not fulfilled. Since such cases also tend to lack blood-brain barrier disruption and necrosis on conventional imaging, these can be mistaken for low-grade astrocytomas. We investigated the potential of advanced imaging to capture tumor biology and thus reliably distinguish between those entities already preoperatively. Multimodal preoperative 3T-MRI scans were collected from 147 glioblastoma, 4 astrocytomas grade 4, 7 “Molecular glioblastoma” (molGBM) grade 4, 9 astrocytomas grade 2, and 12 astrocytomas grade 3. From AI-based multi-compartimental tumor segmentations, advanced imaging metrics from perfusion- and diffusion-imaging were automatically extracted. Two-sample t-test and one-way ANOVA analysis was performed to test for significant differences between apparent diffusion coefficient (ADC) and relative cerebral blood volume (rCBV). Interestingly, rCBV (signifying neoangiogenesis) was significantly higher in molGBM as opposed to astrocytomas for the 5th percentile as well as for mean and median values (p &amp;lt; 0.05). ADC values were consequently lower (indicating higher cellularity) in molGBM than in astrocytomas grade 2 and 3 in the 95th percentile (p &amp;lt; 0.05). Although no molGBM showed contrast-enhancement initially, one untreated case showed a flaccid barrier disruption at 30d follow-up. Interestingly, the molecular imaging at the earlier timepoint showed significantly higher CBV values in the non-enhancing tumor than common glioblastoma and astrocytoma grade 4 (p = 0.013, ANOVA), which indicates highly active tumor portions. Perhaps it is precisely these areas that are on the verge of barrier disruption. Our results support the hypothesis that molGBM are truly early glioblastomas. Better understanding the molecular mechanisms involved in the transition to “classical” glioblastoma promises to provide important insight into tumor biology and potential therapeutic targets.

Urinary tract cytology showing variant morphology and divergent differentiation.

Urothelial carcinoma represents a diverse group of tumours with distinct histologic subtypes, each exhibiting unique cytomorphologic features, architectural growth patterns, and/or well-developed aberrant differentiation. In fact, there are more than 13 subtypes of urothelial carcinoma recognized in the 2022 WHO classification of tumours in the urinary tract. The identification of these subtypes is crucial for an accurate diagnosis of urothelial carcinoma, and many have important clinical implications. Variant/divergent features may coexist with conventional high-grade urothelial carcinoma (HGUC) or present with 100% variant morphology. In urinary tract cytology (UTC), urothelial carcinoma can display divergent differentiation, such as squamous, glandular, or small cell carcinoma differentiation. The use of cell block preparations and immunohistochemistry with available residual urine can enhance diagnostic accuracy. On the other hand, identifying urothelial carcinoma variants, including nested, micropapillary, and plasmacytoid subtypes, poses significant challenges in UTC. Many cases of these variants are only detected retrospectively after variant histology has been established from resection specimens. Moreover, some variants exhibit features inconsistent with the diagnostic criteria for HGUC according to the Paris System for Reporting Urinary Tract Cytology. Nevertheless, the rarity of pure variant morphology and the occurrence of some false negatives for these variant cases are essential to maintain the specificity of UTC overall. This review covers the histology, cytomorphology, and important clinical aspects observed in urothelial carcinoma exhibiting divergent differentiation and various urothelial carcinoma variants detected in UTC.

Predicting the WHO Grading of Pediatric Brain Tumors Based on Their MRI Appearance: A Retrospective Study.

The treatment of central nervous system (CNS) tumors constitutes a significant part of a pediatric neurosurgeon's workload. The classification of such neoplasms spans many entities. These include low- and high-grade lesions, with bothoccurring in the population of patients under 18 years of age. Magnetic resonance imaging serves as the imaging method of choice for neoplastic lesions of the brain. Through its different modalities, such as T1, T2, T1 C+,apparent diffusion coefficient (ADC), diffusion-weighted imaging (DWI), susceptibility-weighted imaging(SWI), fluid-attenuated inversion recovery(FLAIR), etc., it allows the medical team to plan the therapeutic process accordingly while also possibly suggesting the specific tumor subtype prior to obtaining a definitive histological diagnosis. We conducted a retrospective study spanning 32 children treated surgically for brain tumors between July 2021 and January 2023 who had a precise histological diagnosis determined by using the 2021 WHO Classification of Tumors of the Central Nervous System. We divided them into two groups (high-grade and low-grade tumors, i.e., WHO grades 1 and 2, and grades 3 and 4, respectively) and analyzed their demographic data and preoperative MRI results. This was done using the following criteria: sub or supratentorial location of the tumor; lesion is circumscribed or infiltrating; solid, cystic, or mixed solid and cystic character of the tumor; number of compartments in cystic lesions; signal intensity (hypo-, iso-, hyperintensitysequences: T1, T2, T1 C+); presence of restricted diffusion; the largest diameter of the solid component and/or the largest diameter of the largest cyst in the transverse section. Then, we examined the results to find any correlation between the lesions' morphologies and their final assigned degree of malignancy. We found that the only radiological criteria correlating with the final WHO grade of the tumor were an infiltrative pattern of growth (25% of low-grade lesions, 75% of high-grade; p = 0.006) and the presence of a cystic component in the tumor (in 68.75% of low-grade tumors and 43.75% of high-grade tumors; p = 0.041). The only other feature close to attaining statistical significance was diffusion restriction (33.3% of low-grade tumors, 66.7% high-grade; p = 0.055). Older children tended to present with tumors of lower degrees of malignancy, and there was a predominance of female patients (21 female, 11 male).

Multimodel habitats constructed by perfusion and/or diffusion MRI predict isocitrate dehydrogenase mutation status and prognosis in high-grade gliomas

To determine whether tumour vascular and cellular heterogeneity of high-grade glioma (HGG) is predictive of isocitrate dehydrogenase (IDH) mutation status and overall survival (OS) by using tumour habitat-based analysis constructed by perfusion and/or diffusion magnetic resonance imaging (MRI). Seventy-eight HGG patients that met the 2021 World Health Organization WHO Classification of Tumors of the Central Nervous System, 5th edition (WHO CNS5), were enrolled to predict IDH mutation status, of which 32 grade 4 patients with unmethylated O6-methylguanine-DNA methyltransferase (MGMT) promoter were enrolled for prognostic analysis. The deep-learning-based model nnU-Net and K-means clustering algorithm were applied to construct the Traditional Habitat, Vascular Habitat (VH), Cellular Density Habitat (DH), and their Combined Habitat (CH). Quantitative parameters were extracted and compared between IDH-mutant and IDH-wild-type patients, respectively, and the prediction potential was evaluated by receiver operating characteristic (ROC) curve analysis. OS was analysed using Kaplan-Meier survival analysis and the log-rank test. Compared with IDH-mutants, median relative cerebral blood volume (rCBVmedian) values in the whole enhancing tumour (WET), VH1, VH3, CH1-4 habitats were significantly increased in IDH-wild-type HGGs (all p<0.05). Additionally, the accuracy of rCBVmedian values in CH1 outperformed other habitats in identifying IDH mutation status (p<0.001) at a cut-off value of 4.83 with AUC of 0.815. Kaplan-Meier survival analysis highlighted significant differences in OS between the populations dichotomised by the median of rCBVmedian in WET, VH1, CH1-3 habitats (all p<0.05). The habitat imaging technique may improve the accuracy of predicting IDH mutation status and prognosis, and even provide a new direction for subsequent personalised precision treatment.