World Health Organization Classification Research Articles

Clinical analysis of 1,038 cases of odontogenic jawbone cysts.

This study aims to analyse the clinical characteristics of different types of odontogenic jawbone cysts (OJCs) and to provide a theoretical basis for prevention and clinical treatment. Data from 1,038 patients with OJCs were collected, and relevant information, such as sex, age, clinical symptoms and signs, imaging data, number of lesions, lesion location, pathological diagnosis, clinical treatment and prognosis, was statistically analysed. According to the World Health Organization (WHO) classification of OJCs in 2022, the highest incidence rate was observed for radicular cysts (RCs), accounting for 58.96% of the total number of cases, followed by dentigerous cysts (DCs), accounting for approximately 23.22% of cases. lateral periodontal cysts (LPCs) and calcifying odontogenic cysts (COCs) comprised the lowest number of cases. The age distribution of patients was between 4 and 89 years, and the high incidence age group was youth and middle age, accounting for 66.67% of the total number of cases. The male-to-female ratio of patients was 1.51:1, and there was a statistically significant difference between the sexes(p < 0.05).In terms of the site of incidence, odontogenic keratocysts (OKCs) were prevalent in the mandibular molar region. In addition, mandibular ramus, inflammatory collateral cysts (ICCs) and dentigerous cysts (DCs) were more common in the mandibular third molar, and radicular cysts (RCs) and calcifying odontogenic cysts (COCs) were prevalent in the maxillary anterior region. On imaging, 955 (92.0%) lesions were solitary, and 83 (8.0%) were multiple. The treatment included four types of surgery, including simple curettage, marsupialization, marsupialization followed by secondary curettage, and partial resection of the jaw, and a total of 921 patients were followed up, with a recurrence rate of 2.82%. OJCs are more common in males than in females, and a statistically significant difference is observed in the most prevalent types of cysts occurring at different ages and in various regions of the jawbone (p < 0.05). Early diagnosis should be made with the help of X-rays, age, location, and clinical symptoms. In addition, appropriate treatment methods should be selected, and long-term follow-up observation is needed.

Evaluation of the GATIS score for predicting prognosis in rectal neuroendocrine neoplasms

The GATIS score, developed by Zeng et al , represents a significant advancement in predicting the prognosis of patients with rectal neuroendocrine neoplasms (R-NENs). This study, which included 1408 patients from 17 major medical centres in China over 12 years, introduces a novel prognostic model based on the tumour grade, T stage, tumour size, age, and the prognostic nutritional index. Compared with traditional methods such as the World Health Organization classification and TNM staging systems, the GATIS score has superior predictive power for overall survival and progression-free survival. With a C-index of 0.915 in the training set and 0.812 in the external validation set, the GATIS score’s robustness and reliability are evident. The study’s use of a large, multi-centre cohort and rigorous validation processes underscore its significance. The GATIS score offers clinicians a powerful tool to accurately predict patient outcomes, guide treatment decisions, and improve follow-up strategies. This development represents a crucial step forwards in the management of R-NENs, addressing the complexity and variability of these tumours and setting a new benchmark for future research and clinical practice.

BCOR-ITD Rearranged Sarcoma in the Mandible of a 5-Year-Old Child: A Case Report Highlighting Diagnostic Distinction From Odontogenic Fibromyxoma.

The 5th edition of the World Health Organization (WHO) classification of soft tissue and bone has recognized three distinct groups among Ewing-like sarcomas, namely, CIC-rearranged sarcoma, sarcomas with BCOR genetic alterations, and round cell sarcomas with EWSR1:: non-ETS fusions. Sarcomas with BCOR genetic alterations are a distinct clinicopathological group of high-grade tumors, representing 5% of small round cell tumors. BCOR-ITD rearranged tumors commonly manifest as spindle cell sarcomas and many of them display low cellularity with monomorphous cell morphology and myxoid background resembling benign fibroblastic tumors. We present an intriguing case report of a 5-year-old boy diagnosed with a moderately cellular mandibular spindle cell tumor exhibiting BCOR-ITD rearrangement which was initially misdiagnosed as an odontogenic fibromyxoma. This case report illustrates the histological and immunophenotypic findings of BCOR-ITD rearranged sarcoma, requiring a comprehensive immunohistochemical panel and additional molecular tests for accurate diagnosis.

Grading Melanocytic Dysplasia: Updated Histopathologic Criteria.

Dr. Martin C. Mihm, Jr.'s innovative work on the dysplastic nevus achieved a milestone in his chapter in the World Health Organisation Classification of Skin Tumours (WHO-C). WHO-C presents a dichotomous classification (high-grade versus low-grade dysplastic nevi) and a quantitative metric to assess melanocytic nuclear enlargement. The Duke classification is a related approach that provides mostly quantitative histopathologic criteria for dysplastic nevi and gives due weight to architectural features as well as cytology. This paper proposes and illustrates updated criteria for scoring and grading melanocytic dysplasia, incorporating some of the definitions and categories of WHO-C, while refining the quantitative and architectural elements of the Duke grading system to facilitate more detailed and precise assessment of dysplastic nevi.

Impact of the WHO-5 classification of haematolymphoid tumours on clinical practice

SummaryThe long-awaited 2022 World Health Organization Classification of Haematolymphoid Tumours (WHO-5-HAEM) has finally been published as part of the IARC Blue Book series. This two-volume edition is significantly more comprehensive than its predecessors, reflecting the integration of extensive advancements in genetic and molecular understanding, alongside clinically relevant findings. This brief review will highlight the key changes in the classification of the most common B‑cell lymphoproliferative disorders, specifically follicular lymphomas and large B‑cell lymphomas (LBCL). It will also introduce new entities and summarize the most critical updates within these lymphoma categories.

BIOM-02. A HIGH-GRADE GLIOMA, NOT ELSEWHERE CLASSIFIED IN AN OLDER ADULT WITH DISCORDANT GENETIC AND EPIGENETIC ANALYSES

Abstract World Health Organization (WHO) Classification of Tumors of the Central Nervous System (CNS) uses integrated diagnoses, which incorporates both histologic and molecular features of the neoplasms. With each new iteration, there is refinement and expansion of the diagnostic categories. DNA methylation profiling is a powerful technique to diagnose existing CNS tumors and define new tumor types. However, challenging diagnostic cases that do not conform to the updated WHO classification remain. We present a case of a 72-year-old male with a high grade glioma (HGG) suggestive of high grade astrocytoma with piloid features (HGAP), but it did not “match” to HGAP on DNA methylation profiling, which is essential diagnostic criterion for HGAP. This resulted in an HGG, not elsewhere classified (NEC) diagnosis. This lack of classification posed additional challenges for treatment decision-making.

Evaluation of ploidy and the DNA index by flow cytometry in central nervous system tumors: a review.

Research on central nervous system tumors (CNSTs) has a significant impact on the diagnosis and prognosis of patients. Currently, CNSTs are classified according to the schema proposed by the World Health Organization (WHO), which considers clinical, histopathological, and molecular characteristics, highlighting the importance of tumor biology for accurate diagnosis and optimal treatment approaches. Despite these advances, assessing DNA ploidy-a marker of tumor aggressiveness-remains complex in CNSTs. This review investigates the utility of DNA index (DNAi) and DNA ploidy analysis by flow cytometry in diagnosing CNSTs and prognosing their outcomes. We systematically reviewed studies in the PubMed database from 1990 to the present using the keywords "DNA Index", "Brain", "Flow cytometry", and "Ploidy". We identified 151 studies, 36 of which met our inclusion criteria. We found considerable variation in sample sizes and methodological variation across the studies. Discrepancies between the reported DNAi and ploidy values were observed. Aneuploidy is generally associated with more aggressive tumors, although exceptions exist. Higher DNAi levels correlate with increased malignancy, notably in glioblastomas, astrocytomas, and meningiomas, whereas diploid astrocytomas and oligodendrogliomas are associated with shorter survival rates. DNA ploidy assessment via flow cytometry could predict CNST behavior, yet methodological issues with tissue selection, adequate control samples, and technique variability remain. DNAi and ploidy assessments show promise as prognostic markers in CNSTs. However, the standardization of flow cytometry protocols and alignment with the current WHO classification schema are essential steps to integrate ploidy analysis in routine CNST assessment.

PATH-05. CLINICAL, PATHOLOGICAL AND MOLECULAR DISEASE CHARACTERISTICS OF DIFFUSE HEMISPHERIC GLIOMA, H3 G34-MUTANT

Abstract BACKGROUND Diffuse hemispheric glioma, histone 3 (H3) G34-mutant, is a pediatric-type diffuse high-grade glioma newly defined in the World Health Organization (WHO) classification of central nervous system tumors 2021. Here we sought to define the prognostic roles of clinical, neuroimaging, pathological, and molecular features of these tumors. METHODS We retrospectively assembled a cohort of 114 patients with diffuse hemispheric glioma, H3 G34-mutant and profiled the imaging presentation and the molecular landscape of their tumors. RESULTS Compared with glioblastoma, H3 G34-mutant tumors exhibited less avid contrast enhancement, less necrosis and less edema on MRI. Comprehensive analyses of mutational and DNA copy number profiles revealed recurrent mutations in TP53 and ATRX, homozygous deletions of CDKN2A/B, and amplifications of PDGFRA, EGFR, CCND2, and MYCN. MGMT promoter methylation was detected in 79 tumors (75%); 11 tumors (13%) showed DNA copy number profiles suggestive of circumscribed deletions on 10q26.3 involving the MGMT locus. Median survival was 21.5 months (95% CI 15.3-27.7) and eight patients (7.0%) survived for ≥ five years. Female sex, gross total resection, and MGMT promoter methylation were positive prognostic factors on univariate analysis. Among radiological, pathological and molecular features, absence of pial invasion, and presence of microvascular proliferation and CDK6 amplification were positive prognostic factors on univariate analyses. CONCLUSION This study refines the clinical and molecular landscape of H3 G34-mutant diffuse hemispheric gliomas. Dedicated trials for this novel tumor type are urgently needed.

SURG-02. ANAPLASTIC PLEOMORPHIC XANTHOASTROCYTOMA WITH LEPTOMENINGEAL DISSEMINATION PRESENTING WITH CRANIAL NEUROPATHY IN AN ADULT PATIENT: ILLUSTRATIVE CASE AND REVIEW OF THE LITERATURE

Abstract INTRODUCTION Anaplastic pleomorphic xanthoastrocytomas (APXA) are very rare, grade III malignant astrocytic glial neoplasms first described as a distinct entity in the 2016 World Health Organization (WHO) Classification of Tumors of the Central Nervous System (CNS). They are generally seen in pediatric and young adult patients as supratentorial lesions with both solid and cystic components and have a high propensity for recurrence despite local treatment. APXAs occasionally demonstrate leptomeningeal dissemination (LMD) but extremely seldom at the time of diagnosis. They are typically treated via surgical resection with adjuvant chemoradiation, although there is no standard of care for adjuvant therapy. Case Presentation: The authors describe the case of a 37-year-old male with a history of seizures since age 11 who presented with four months of worsening headache, increasingly frequent seizures, and diplopia with right cranial nerve III palsy. Imaging at the time of diagnosis of his seizure disorder as a child demonstrated a small left temporal lesion, which remained stable on imaging for over 20 years and was never biopsied, however MRI at current presentation showed significant interval enlargement with intralesional hemorrhage and leptomeningeal enhancement involving the left temporal and parietal lobes, left internal auditory canal, and right oculomotor nerve. He underwent surgical resection with gross total resection achieved and pathology revealed WHO Grade III pleomorphic xanthoastrocytoma with ATG7::RAF1 fusion, 9p21 deletion, and TERT promoter mutation on next generation sequencing. This was followed by adjuvant whole brain radiation with boost and treatment with MEK inhibitor cobimetinib. His postoperative course was remarkable for intermittent speech difficulty and improving right third nerve palsy. CONCLUSION We describe the unusual presentation of an already exceedingly rare primary CNS tumor, namely APXA in an adult patient with LMD and cranial neuropathy at the time of diagnosis, and detail tailored adjuvant therapy based on genomic profiling.

NIMG-08. IMAGING FINDINGS AND PROGNOSTIC FACTORS IN DIFFUSE HEMISPHERIC GLIOMA, H3 G34-MUTANT

Abstract INTRODUCTION Diffuse hemispheric glioma, H3 G34-mutant (DHGs), are a newly categorized tumor in pediatric-type diffuse high-grade gliomas in the 2021 World Health Organization classification, with a poor prognosis. DHGs has been reported to occur in less than 1% of all gliomas, but prognostic factors have not been fully investigated in previous studies due to small sample sizes. In this study, we investigated the relationship between clinical factors, including imaging findings, and prognosis in patients with DHGs. METHODS We searched Medline through the PubMed database using two search terms: “G34” and “glioma”, between 1 April 2012 and 1 July 2023. We retrieved articles that described imaging findings and overall survival (OS), and added one DHG case from our institution. We defined midline invasion (MI) as invasion to the contralateral cerebrum, brainstem, corpus callosum, thalamus, and basal ganglia on magnetic resonance imaging. The primary outcome was 12-month survival, estimated using Kaplan–Meier curves and logistic regression. RESULTS A total of 96 patients were included in this study. The median age was 22 years, and the proportion of male patients was 48.4%. Lesions were most frequently located in the frontal lobe (52.6%). MI was positive in 39.6% of all patients. The median OS of all cases was 14.4 months. Univariate logistic regression analysis with 12-month OS as the outcome showed that the MI-positive group had a significantly higher mortality than that in the MI-negative group, and the gross total resection achieved group had a significantly lower mortality than that in the group that underwent biopsy alone. Multivariate logistic regression analysis revealed that MI was an independent prognostic factor in DHGs. CONCLUSIONS Similar to glioblastomas, DHGs have a poor prognosis if they invade deep structures or the contralateral cerebrum; however, safe and maximal tumor resection may prolong survival.

PATH-19. DIAGNOSTIC UTILITY OF MOLECULAR PROFILING IN ADULT DIFFUSE GLIOMA

Abstract INTRODUCTION With the publication of World Health Organization Classification of the Central Nervous System Tumors (WHO CNS5), molecular profiling has become essential for the diagnosis of CNS tumors. To test for the diagnostic molecular alterations, we developed a targeted DNA sequencing panel (Nakashima et al. 2024) to analyze 113 genes, chromosomal abnormalities, and MGMT promoter methylation. This study aimed to evaluate our diagnostic approach using the targeted sequencing panel. PATIENTS AND METHODS We included 72 cases of diffuse adult gliomas diagnosed at our institute between June 2023 and May 2024. We analyzed the tumor diagnoses based on the pathological and immunohistochemical findings as well as the targeted sequencing panel findings. RESULTS The tumor diagnoses were as follows: glioblastoma, IDH-wildtype: 32 cases, astrocytoma, IDH-mutant: 17 cases, oligodendroglioma, IDH-mutant and 1p/19q-codeleted: 15 cases, others: 8 cases. Among 32 cases of IDH1/2 mutations, 28 cases (87.5%) with IDH1 R132H mutation were diagnosed by immunohistochemistry using anti-IDH1 R132H antibody, whereas 4 (12.5%) (3 with IDH2 mutation, and 1 with IDH1 R132S) were diagnosed by the targeted sequencing panel. Of the 32 glioblastoma cases, 6 (18.8%) did not show necrosis or microvascular proliferation and were diagnosed based on either TERT promoter mutation, EGFR amplification, or chromosome 7/chromosome 10 abnormalities. Moreover, 24 out of 26 resected cases (92.3%) were diagnosed morphologically, whereas 4 of 6 biopsy cases (66.7%) were diagnosed molecularly (p=0.0056). Among the 17 cases of astrocytoma, IDH-mutant, 2 (11.8%) showed homozygous deletion of CDKN2A/B. There were 4 cases (5.6%) out of 72 that did not satisfy the diagnostic criteria for glioblastoma, astrocytoma, oligodendroglioma. CONCLUSION Approximately 95% of cases were diagnosed based on WHO CNS5 criteria with molecular profiling. We also demonstrate molecular profiling is useful in glioblastoma diagnostics, especially in biopsy cases where morphological diagnostic evidence is not recognized.

A Multicenter Study on Hepatocellular Adenomas in Korea: Clinicopathological and Imaging Features With an Emphasis on β-Catenin Mutated Subtype.

The clinicopathologic and imaging features of hepatocellular adenomas (HCAs) in Asian population remain unclear. We aimed to analyse clinicopathologic and imaging features of HCAs in Korea and propose an imaging-based method to differentiate β-catenin mutated HCA (βHCA) from other subtypes. This retrospective multicenter study included pathologically confirmed HCAs from three tertiary institutions in Korea between 2010 and 2023. HCA subtypes were determined according to the current World Health Organization classification using immunohistochemical staining. Two abdominal radiologists reviewed computed tomography and magnetic resonance imaging scans. The clinical characteristics and imaging features of HCA subtypes were compared. A scoring system for βHCA was developed and validated using development (January 2010-April 2021) and validation (May 2021-March 2023) cohorts. 121 patients (47 men; mean age, 39.0 years ±13.5) with 138 HCAs were included. HCAs displayed characteristic clinicopathologic features, including a high proportion of male (38.8%) and obese patients (35.5%), with the inflammatory subtype being the most common (38.4%) and a low percentage of patients using oral contraceptive (5.0%). Each HCA subtype demonstrated distinct clinical and imaging features. The scoring system incorporating tumour heterogeneity and iso to high hepatobiliary phase signal intensity on MRI for differentiating βHCA exhibited high performance in both the development (AUC 0.92, 95% CI: 0.87-0.97) and the validation cohort (AUC 0.91, 95% CI: 0.77-1.00). This comprehensive analysis of clinicopathologic and imaging features of HCAs in Korea contributes to the characterisation of HCAs across different geographical regions. The imaging-based scoring system effectively differentiates βHCA.

A clinicopathological and molecular series of five TFEB-altered renal cell carcinoma (RCC) cases: highlighting an aggressive subset of TFEB-rearranged RCC concomitant with TFEB amplification/gene copy number gains.

The classification of TFEB-altered renal cell carcinoma (RCC) has been revised to include TFEB-rearranged RCC and TFEB-amplified RCC in the 2022 World Health Organization (WHO) Classification of Tumors of the Urinary System. Given the wide spectrum of TFEB-altered RCC in terms of morphology and clinical behavior, an accurate diagnosis is challenging yet crucial, particularly in aggressive cases. Moreover, the concurrence of TFEB gene rearrangement and amplification/gene copy number (GCN) gains was also observed, but there was limited knowledge of these cases. We presented three TFEB-rearranged RCC cases, one TFEB-amplified RCC case, and one case of concomitant TFEB-rearranged and -amplified RCC, comparing the similarities and differences among these three subgroups. Furthermore, we summarized the clinicopathological and molecular features of TFEB-rearranged RCC concomitant with TFEB amplification/GCN gains from the literature and the present study. TFEB-altered RCCs exhibit significant heterogeneity in morphology and clinical behavior while displaying similar immunohistochemical profiles, including positive staining for Melan-A, PAX8, and CD117, and negative staining for CK7. A typical biphasic "rosette-like" morphology has been observed in a proportion of TFEB-rearranged RCC concomitant with TFEB amplification/GCN gains, which has been noted in TFEB-rearranged RCC, but not in cases with only TFEB amplification. Notably, TFEB-rearranged RCCs concomitant with TFEB amplification/GCN gains tend to be aggressive, in contrast to the often indolent nature of TFEB-rearranged cases, irrespective of the extent of TFEB gene copy increase. Therefore, a TFEB FISH assay is essential for unclassified RCC cases that exhibit melanocytic marker expression, and fluorescent signals should be counted and interpreted acurrately.

Surrogate immunohistochemistry markers in adult gliomas – Experience in a tertiary care hospital

Objectives: The recent World Health Organization classification has recommended the usage of surrogate immunohistochemical markers for molecular classification of gliomas. However, only a few studies have attempted to study the expression of the entire panel of markers. The current study was undertaken to study the association of recognized surrogate immunohistochemical markers (isocitrate dehydrogenase 1 [IDH-1], alpha-thalassemia mental retardation X-linked [ATRX] and p53) in different histological lineages and grades of adult gliomas. Materials and Methods: This study was conducted on 118 cases of adult gliomas diagnosed on histopathology over a 2-year duration in a tertiary care hospital. The expression of surrogate immunohistochemistry markers (IDH-1, ATRX, and p53) in these cases was studied. Statistical analysis: Descriptive statistical analysis with the Statistical Package for the Social Science system version 17.0. Results: The frequency of IDH-1 positivity was significantly higher in oligodendrogliomas (OG: 76.5%; oligoastrocytoma: 100%) versus astrocytoma (AS) (grades 2 and 3: 48.1%). It was also significantly higher in diffuse gliomas (grades 2 and 3) versus glioblastomas (64% vs. 16.9%). Among IDH-mutant diffuse gliomas, ATRX loss was significantly higher in AS versus OGs (84.6% vs. 7.7%). P53 overexpression correlated significantly with histological subtype (AS 2,3: 55.6% vs. OG: 5.9%). Conclusions: The surrogate immunohistochemical panel of IDH-1, ATRX, and p53 showed significant association with distinct histopathological subtypes and is helpful in molecular stratification. Cut-offs of ≥ 10% nuclear positivity for p53 and 50% loss of nuclear ATRX expression showed a good correlation.

Rare atypical type a thymoma: a case report and literature review

BackgroundAn atypical type A thymoma variant was recently added to the World Health Organization classification of type A thymoma in 2015. This novel form of type A thymoma presents with hypercellularity, increased mitotic activity, and necrosis. In particular, necrosis seems to be related to postoperative recurrence and metastasis, but the clinical significance of these changes still needs to be studied.Case presentationA 76-year-old man underwent thoracoscopic surgery for tumour resection due to an anterior mediastinal mass. Pathological examination revealed that the tumour invaded the surrounding thymic tissue. Cells were arranged in nest-like and whirl-like patterns, accompanied by prominent comedo-like necrosis, increased cell density, mild atypia, and a mitotic count of 4–6 per 10 high-power fields. Immunohistochemistry revealed positive expression of cytokeratin 19 and P63 in the tumour cells. Lymphocytes in the background were positive for CD3 and CD5, did not express terminal deoxynucleotide transferase, CD20, or CD117, and had an MIB-1 labelling index(LI) value of 15%. On the basis of these findings, the tumour was finally diagnosed as an atypical type A thymoma variant.ConclusionsWe report a case of atypical type A thymoma and review the literature to enhance our understanding of and provide accumulated pathological data on this rare disease.

Ependymal Tumors: Overview of the Recent World Health Organization Histopathologic and Genetic Updates with an Imaging Characteristic.

The 2021 World Health Organization Classification of Tumors of the Central Nervous System (CNS5), introduced significant changes, impacting tumors ranging from glial to ependymal neoplasms. Ependymal tumors were previously classified and graded based on histopathology, which had limited clinical and prognostic utility. The updated CNS5 classification now divides ependymomas into 10 subgroups based on anatomic location (supratentorial, posterior fossa, and spinal compartment) and genomic markers. Supratentorial tumors are defined by zinc finger translocation associated (ZFTA) (formerly v-rel avian reticuloendotheliosis viral oncogene [RELA]), or yes-associated protein 1 (YAP1) fusion; posterior fossa tumors are classified into groups A (PFA) and B (PFB), spinal ependymomas are defined by MYCN amplification. Subependymomas are present across all these anatomic compartments. The new classification kept an open category of "not elsewhere classified" or "not otherwise specified" if no pathogenic gene fusion is identified or if the molecular diagnosis is not feasible. Although there is significant overlap in the imaging findings of these tumors, a neuroradiologist needs to be familiar with updated CNS5 classification to understand tumor behavior, for example, the higher tendency for tumor recurrence along the dural flap for ZFTA fusion-positive ependymomas. On imaging, supratentorial ZFTA-fused ependymomas are preferentially located in the cerebral cortex, carrying predominant cystic components. YAP1-MAMLD1-fused ependymomas are intra- or periventricular with prominent multinodular solid components and have significantly better prognosis than ZFTA-fused counterparts. PFA ependymomas are aggressive paramedian masses with frequent calcification, seen in young children, originating from the lateral part of the fourth ventricular roof. PFB ependymomas are usually midline, noncalcified solid-cystic masses seen in adolescents and young adults arising from the fourth ventricular floor. PFA has a poorer prognosis, higher recurrence, and higher metastatic rate than PFB. Myxopapillary spinal ependymomas are now considered grade II due to high recurrence rates. Spinal-MYCN ependymomas are aggressive tumors with frequent leptomeningeal spread, relapse, and poor prognosis. Subependymomas are noninvasive, intraventricular, slow-growing benign tumors with an excellent prognosis. Currently, the molecular classification does not enhance the clinicopathologic understanding of subependymoma and myxopapillary categories. However, given the molecular advancements, this will likely change in the future. This review provides an updated molecular classification of ependymoma, discusses the individual imaging characteristics, and briefly outlines the latest targeted molecular therapies.

Characterization of Pediatric Acute Myeloid Leukemia With t(7;12)(q36;p13).

Acute myeloid leukemia (AML) with t(7;12)(q36;p13) is a recurrent translocation in AML in infants or very young children and was recently included in the World Health Organization (WHO) Classification of Hematolymphoid Tumors. AML with t(7;12) is reported to involve MNX1 and ETV6 signaling; however, the mechanism of leukemogenesis is not well understood, and the presence of MNX1::ETV6 fusion transcripts has only been confirmed in approximately 50% of cases. In contrast, high expression of MNX1 has been seen in all investigated cases. In this study, we investigated the clinical as well as biological characteristics of 12 pediatric AML with t(7;12) and performed whole transcriptome (WTS) and whole genome sequencing (WGS) on six of these. There was no significant difference in event-free survival or overall survival of these t(7;12) AML patients compared with other AML in the same age group. Interestingly, WTS identified several fusion transcripts involving ETV6 but not together with MNX1. WGS identified the genomic breakpoints and revealed that a common fusion partner on chromosome 7 was NOM1. Principal component analysis (PCA) of the WTS data showed that all t(7;12) AML cases cluster together, separate from all other pediatric AML subtypes; all cases had high expression of MNX1, MNX1-AS1, and MNX1-AS2. Hence, t(7;12) AML, despite expressing different fusion transcripts and with varying translocation breakpoints, constitutes a phenotypically homogenous subgroup. This underlines that the leukemia-driving event most likely is ectopic expression of MNX1 and that this therefore should be the defining Classifying criteria of this type of AML.

All-in-one bimodal DNA and RNA next-generation sequencing panel for integrative diagnosis of glioma

Previously, we constructed a DNA-based next-generation sequencing (NGS) panel for an integrated diagnosis of gliomas according to the 2021 World Health Organization classification system. The aim of the current study was to evaluate the feasibility of a modified panel to include fusion gene detection via RNA-based analysis. Using this bimodal DNA/RNA panel, we analyzed 210 cases of gliomas and others to identify fusion genes in addition to gene alterations, including TERT promoter (TERTp) mutation and 1p/19q co-deletion, in formalin-fixed paraffin-embedded tissues. Of the 210 patients, fusion genes were detected in tumors of 35 patients. Eighteen of 112 glioblastomas (GBs) harbored fusion genes, including EGFR and FGFR3 fusions. In IDH-mutant astrocytoma, 6 of 30 cases showed fusion genes such as MET and NTRK2 fusions. Eleven molecular GBs and 20 not-elsewhere-classified cases harbored no gene fusions. Other 11 tumors including ependymoma, pilocytic astrocytoma, diffuse hemispheric glioma, infant-type hemispheric glioma, and solitary fibrous tumors exhibited diagnostic fusion genes. Overall, our results suggest that the all-in-one bimodal DNA/RNA panel is reliable for detecting diagnostic gene alterations in accordance with the latest WHO classification. The integrative pathological and molecular strategy could be valuable in confirmation of diagnosis and selection of treatment options for brain tumors.

Early T-cell precursor acute lymphoblastic leukemia: diagnostic pitfalls, genomic alteration, novel therapeutics, and minimal residual disease monitoring

Early precursor T-cell acute lymphoblastic leukemia (ETP-ALL) is a rare type of T-cell ALL (T-ALL) that was initially described in 2009. Since its initial description, it has been formally recognized as a distinct entity, according to the 2016 World Health Organization classification. ETP-ALL is characterized by unique immunophenotypic and genomic profiles. The diagnosis and management of ETP-ALL remain challenging. Poorer outcomes, high incidence of induction failure and relapsed/refractory disease demand novel therapies. This review emphasizes the challenges of initial diagnosis, the molecular mechanisms underlying leukemogenesis, and the available therapeutic options. Additionally, it discusses the importance of induction failure, the prognostic value of detecting minimal residual disease, and the implications of hematopoietic stem cell transplantation, along with emerging novel therapies.

Severity of pulmonary hypertension and pregnancy outcomes: newer insights from the M-PAC registry

Abstract Background Pregnancy outcomes in women with pulmonary hypertension remain suboptimal. Pregnant women with pulmonary hypertension (PH) are placed in the modified WHO category IV, regardless of the severity or etiology of PH. Earlier studies have indicated that pregnancy outcomes may differ based on the etiology, with more favourable outcomes observed with PH related to left to right shunts. However, it is possible that the pregnancy outcomes may vary based on the severity of PH also. Purpose To analyse pregnancy outcomes in women with PH and investigate differences based on disease severity. Methods M-PAC Registry, is a single center prospective study of pregnancies in women with heart diseases, conducted between July 2016 and December 2019 in a low-and middle-income country from South Asia, whose methodology and outcomes have been published(1). The current study analysed pregnancies with PH enrolled in the M-PAC registry. The tricuspid regurgitation velocity obtained during transthoracic echocardiography, was used to estimate right ventricular systolic pressure (RVSP). Based on the estimated RVSP, PH was classified into three groups; mild (36-45 mm of Hg), moderate (46-64 mm of Hg) and severe (≥ 65 mm of Hg). The differences in the maternal and foetal outcomes among the groups were analysed. Results Of the 1029 pregnancies complicated by heart disease enrolled in the M-PAC registry, 352(34.2%)had PH. Among these 352 pregnancies, 186(52.8%) had mild, 73 (20.7%) had moderate and 93 (26.5%) had severe PH. Adverse maternal cardiac events occurred in 77 pregnancies (21.8%), with heart failure in 53(15.1%) and mortality in 10(2.8%). The composite adverse foetal event rate was 38.6%, foetal loss at 9.7%, low birth weight at 28.9%, and preterm labour at 7.1%. The mean (±standard deviation) RVSP was higher in pregnancies with adverse maternal outcome (58.81±16.9 vs 51.16±15.9; P &amp;lt; 0.001) or adverse foetal outcome (58.10±17.3 vs 49.52±14.9; P &amp;lt; 0.001)compared to those without. When comparing the three groups, pregnancies with mild PH exhibited significantly lower rates of adverse maternal and fetal events compared to those with severe and moderate PH (Fig-1 and Table-1). Mild PH was associated with outcomes similar to those without PH in the M-PAC registry. Conclusion The severity of PH significantly correlated with the adverse pregnancy outcomes. Women with mild PH tend to experience pregnancy outcomes comparable to those without PH, suggesting that pregnancy should not be deemed contraindicated in this subgroup. Therefore, re-evaluation of the placement of PH within the modified World Health Organization (mWHO) classification is warranted, considering the severity of PH.Figure 1:Pregnancy Outcomes &amp; PH SeverityTable-1 PH Severity &amp; Pregnacny Outcomes