World Health Organization Classification Research Articles

Expanding the Imaging Spectrum of Polymorphous Low-Grade Neuroepithelial Tumor of the Young in Children.

Polymorphous low-grade neuroepithelial tumors of the young (PLNTY) are rare brain tumors first described in 2017 and recently included in the 2021 5th World Health Organization Classification of Tumors of the Central Nervous System. They typically affect children and young adults. Few pediatric cases have been reported in the literature. The most common imaging features described, include location within the temporal lobe, involvement of the cortical/subcortical region, coarse calcifications, and well-defined margins with solid and cystic morphology, with slight-or-no enhancement. However, there is limited information on imaging features in children. We present the imaging spectrum of neuroimaging features in a series of pediatric patients with a histologically and molecularly proved PLNTY diagnosis. Coarse calcifications are uncommon in children compared with the adult literature, and they may develop with time. The transmantle-like sign can be observed, and adjacent cortical dysplasia may be seen. Seizure recurrence may occur despite gross total resection of the tumor.

Advances towards genome-based acute myeloid leukemia classification: A comparative analysis of WHO-HAEM4R, WHO-HAEM5, and International Consensus Classification.

Two recent guidelines, the 5th edition of the World Health Organization Classification of Haematolymphoid Tumours (WHO-HAEM5) and the International Consensus Classification (ICC), were published to refine the diagnostic criteria of acute myeloid leukemia (AML). They both consider genomic features more extensively and expand molecularly defined AML subtypes. In this study, we compared the classifications of 1135 AML cases under both criteria. According to WHO-HAEM5 and ICC, the integration of whole transcriptome sequencing, targeted gene mutation screening, and conventional cytogenetic analysis identified defining genetic abnormalities in 89% and 90% of AML patients, respectively. The classifications displayed discrepancies in 16% of AML cases after being classified using the two guidelines, respectively. Both new criteria significantly reduce the number of cases defined by morphology and differentiation. However, their clinical implementation heavily relies on comprehensive and sophisticated genomic analysis, including genome and transcriptome levels, alongside the assessment of pathogenetic somatic and germline variations. Discrepancies between WHO-HAEM5 and ICC, such as the assignment of RUNX1 mutations, the rationality of designating AML with mutated TP53 as a unique entity, and the scope of rare genetic fusions, along with the priority of concurrent AML-defining genetic abnormalities, are still pending questions requiring further research for more elucidated insights.

Salivary gland secretory carcinoma presenting as a cervical soft tissue mass: a case report

BackgroundSecretory carcinoma (SC) has been described as a distinct salivary gland tumor in the fourth edition of the World Health Organization (WHO) classification of head and neck tumors. SC is generally considered as a slow-growing low-grade malignant tumor, while several cases have been reported with high-grade features, and even metastases in the literature up until now. In this article, a soft tissue SC case is discussed with high-grade microscopic features and neural invasion. A review of the salivary gland SC cases with aggressive behavior is also debated.Case presentationA 65-year-old Caucasian man presented with a left neck mass for the past six months. The imaging studies demonstrated a very large cystic cervical mass (46 × 23 mm) with papillary projections in the anterolateral aspect of the left neck zone Vb. He underwent left radical neck dissection (level I-V) and was followed up for 12 months with the diagnosis of Secretory carcinoma.ConclusionAlthough SC generally has a good outcome, multiple recurrences and unusual metastases may occur, which should be considered by either the pathologists or clinicians.

Recurrent MTOR Mutations in Renal Cell Carcinoma With Fibromyomatous Stroma: A Report of 2 Tumors.

Renal cell carcinoma with fibromyomatous stroma, recognized as a provisional entity in the current 2022 World Health Organization classification of renal neoplasms, is rare. Recent evidence suggests recurrent alterations in the mTOR pathway, supporting its recognition as a distinct entity. Herein, we report 2 renal cell carcinomas with fibromyomatous stroma with MTOR mutations occurring in 62- and 72-year-old women and review the literature to support its recognition as a distinct entity, focusing on the characteristic morphology, immunohistochemical staining patterns as well as genetic alterations.

Brain Tumor Imaging in Adolescents and Young Adults: 2021 WHO Updates for Molecular-based Tumor Types.

Published in 2021, the fifth edition of the World Health Organization (WHO) classification of tumors of the central nervous system (CNS) introduced new molecular criteria for tumor types that commonly occur in either pediatric or adult age groups. Adolescents and young adults (AYAs) are at the intersection of adult and pediatric care, and both pediatric-type and adult-type CNS tumors occur at that age. Mortality rates for AYAs with CNS tumors have increased by 0.6% per year for males and 1% per year for females from 2007 to 2016. To best serve patients, it is crucial that both pediatric and adult radiologists who interpret neuroimages are familiar with the various pediatric- and adult-type brain tumors and their typical imaging morphologic characteristics. Gliomas account for approximately 80% of all malignant CNS tumors in the AYA age group, with the most common types observed being diffuse astrocytic and glioneuronal tumors. Ependymomas and medulloblastomas also occur in the AYA population but are seen less frequently. Importantly, biologic behavior and progression of distinct molecular subgroups of brain tumors differ across ages. This review discusses newly added or revised gliomas in the fifth edition of the CNS WHO classification, as well as other CNS tumor types common in the AYA population.

Biomarker characterization in endometrial cancer in Europe: first survey data analysis from 69 pathological academic and hospital labs.

Endometrial carcinoma (EC) is the commonest gynecological cancer affecting women in Western populations. To predict patient risk, the 2020 edition of the World Health Organization (WHO) Classification of Tumors of the Female Genital Tract stressed the importance of integrated histo-molecular classification of the disease. This survey analysis poses attention on the most frequently used immunohistochemical and molecular markers adopted in daily categorization of ECs in European laboratories. We analyzed data collected through questionnaires administered to 40 Italian, 20 Spanish, 3 Swiss and 6 United Kingdom (UK) laboratories. We collected information regarding daily practice in EC evaluation, specifically concerning mismatch repair status (MMR) and microsatellite instability (MSI). Summary and descriptive statistical analyses were carried out to evaluate the current practice of each laboratory. The results show that MMR status is mainly evaluated by using immunohistochemistry (IHC) on most EC samples. The most frequent approach for the analysis of MMR status is IHC of four proteins (PMS2, MSH6, MSH2, MLH1). MSI analysis by molecular methods is uncommon but useful as a supplemental tool in specific conditions. MLH1 promoter hypermethylation and BRAF V600 mutations analysis are performed in case of negative expression of MLH1/PMS2. Other markers (mainly p53 followed by POLE and PTEN) are investigated in particular in Spain and Switzerland in a consistent number of cases. Guidelines consultation and standardization of laboratory procedures are efficient means for EC prognostic risk stratification and improving the quality of care.

Myelodysplastic syndromes del(5q): Pathogenesis and its therapeutic implications.

Myelodysplastic syndromes (MDS) encompass a heterogeneous set of acquired bone marrow neoplastic disorders characterized by ineffective hematopoiesis within one or more bone marrow lineages. Nearly half of MDS patients carry cytogenetic alterations, with del(5q) being the most prevalent. Since its first description, del(5q) was consistently correlated with a typical clinical phenotype marked by anemia, thrombocytosis, and a low risk of evolving into acute leukemia. Presently, the World Health Organization (WHO) classification of myeloid neoplasms recognizes a specific subtype of MDS known as "myelodysplastic neoplasm with low blast and isolated del(5q)" identified by the sole presence of 5q deletion or in combination with one other abnormality excluding -7/del(7q). Several studies have sought to unravel the biological processes triggered by del(5q) in the development of MDS, revealing the involvement of various genes localized in specific regions of chromosome 5 referred to as common deleted regions (CDR). This intricate biological landscape makes the MDS cells with del(5q) exceptionally sensitive to lenalidomide. Several studies have confirmed the efficacy of lenalidomide in this context. Regrettably, the response to lenalidomide is not conclusive, prompting ongoing research into biological mechanisms that drive patients toward leukemia and strategies to circumvent lenalidomide resistance and disease progression.

Comparison of Forced Expiratory Flow (FEF) 25-75% between Post-COVID-19 Patients with Different Severity at Universitas Gadjah Mada Academic Hospital

Introduction: Shortness of breath is the most distressing long COVID-19 symptom associated with the decline of small airway function, as shown by a decrease in forced expiratory flow (FEF) 25-75% value in the spirometry test. This study aimed to compare FEF 25-75% values as a predictor of small airway disease between mild-moderate and severe-critical long COVID-19 patients. Methods: This study used a prospective cohort design that included 24 post-hospitalized COVID-19 patients who came to the long COVID-19 clinic at Universitas Gadjah Mada Academic Hospital (UGM AH), Yogyakarta. The subjects were divided into mild-moderate and severe-critical groups based on the World Health Organization (WHO) classification. The subjects were tested for spirometry three months after the onset of COVID-19 symptoms. The comparison of both severity groups used the percent prediction of FEF 25-75% spirometry results. The value was interpreted as abnormal if the predicted FEF 25-75% value was below 65%. Results: There were three (25%) and two (16.67%) subjects with FEF 25-75% predicted below normal values in the mild-moderate and severe-critical groups consecutively, which showed a decline in small airway function. This study showed no statistically significant differences (p-value = 0.882) between the means of FEF 25-75% predicted values of the two groups. Conclusion: A small proportion of post-COVID-19 syndrome patients had small airway disease, and there were no statistical differences in small airway function between the groups.

A real-world analysis of clinical outcomes in AML with myelodysplasia-related changes: a comparison of ICC and WHO-HAEM5 criteria

AbstractThe proposed fifth edition of the World Health Organization classification of hematolymphoid tumors (WHO-HAEM5) and International Consensus Classification (ICC) provide different definitions of acute myeloid leukemia with myelodysplasia-related genetics (AML-MR). We conducted a retrospective study which included a cohort of 432 patients, with 354 patients fulfilling WHO-HAEM5 criteria for WHO-AML-MR or 276 patients fulfilling ICC criteria for ICC-AML-MR by gene mutation or cytogenetics (ICC-AML-MR-M/CG). The clinicopathological features were largely similar, irrespective of the classification used, except for higher rates of complex karyotype, monosomy 17, TP53 mutations, and fewer RUNX1 mutations in the WHO-AML-MR group. TP53 mutations were associated with distinct clinicopathological features and dismal outcomes (hazard ratio [HR], 2.98; P < .001). ICC-AML-MR-M/CG group had superior outcome compared with the WHO-AML-MR group (HR, 0.80, P = .032), largely in part due to defining TP53 mutated AML as a standalone entity. In the intensively-treated group, WHO-AML-MR had significantly worse outcomes than AML by differentiation (HR, 1.97; P = .024). Based on ICC criteria, ICC-AML-MR-M/CG had more inferior outcomes compared to AML not otherwise specified (HR, 2.11; P = .048 and HR, 2.55; P = .028; respectively). Furthermore, changing the order of genetic abnormalities defining AML-MR (ie, by gene mutations or cytogenetics) did not significantly affect clinical outcomes. ICC-AML-MR-M/CG showed similar outcomes regardless of the order of assignment. We propose to harmonize the 2 classifications by excluding TP53 mutations from WHO-HAEM5 defined AML-MR group and combining AML-MR defined by gene mutations and cytogenetics to form a unified group.

Concordance Between Biopsy and Resection Diagnoses of Uterine Cervical Adenocarcinoma According to the Updated World Health Organization 2020 Classification: A Multi-Institutional Study Elucidating Real-World Practice in Japan.

Endocervical adenocarcinoma is divided into human papillomavirus (HPV)-associated (HPVA) and HPV-independent (HPVI) in the 5h edition of the World Health Organization (WHO) tumor classification launched in 2020. However, the validity of the morphological criteria used for biopsy specimens in real-world practice remains undetermined. To validate the utility of the 5th edition of the WHO classification for biopsy samples, focusing on its diagnostic criteria with the aid of ancillary studies. We retrieved 217 cases of endocervical adenocarcinoma from 6 institutions, in which glass slides of both biopsy and resection specimens were available for review. Concordance between the biopsy and resection specimen diagnoses was evaluated. For discordant diagnoses, an algorithmic approach with ancillary studies proposed by the international group was applied to confirm their utility to improve the accuracy of biopsy diagnosis. The biopsy diagnosis matched the resection specimen diagnosis in 197 cases (concordance rate, 91%; κ = 0.75). The concordance rate was significantly higher for HPVA than HPVI (95% versus 81%, P = .001). There were no significant differences in the proportions of HPVA and HPVI or the accuracy of biopsy diagnosis between the participating institutions. All 19 discordant cases with unstained glass slides available were accurately recategorized as HPVA or HPVI using HPV in situ hybridization; p16 immunohistochemistry was positive in 3 of 9 cases of gastric-type HPVI that were negative by in situ hybridization. The 5th edition of the WHO criteria for biopsy diagnosis of endocervical adenocarcinoma distinguishes HPVA from HPVI well when ancillary studies are adequately applied.

Eosinophilic Solid and Cystic Renal Cell Carcinoma: Morphologic and Immunohistochemical Study of 18 Cases and Review of the Literature.

Eosinophilic solid and cystic renal cell carcinoma is now defined in the 5th edition of the 2022 World Health Organization classification of urogenital tumors. To perform morphologic, immunohistochemical, and preliminary genetic studies about this new entity in China for the purpose of understanding it better. The study includes 18 patients from a regional tertiary oncology center in northern China (Tianjin, China). We investigated the clinical and immunohistochemical features of these cases. The mean age of patients was 49.6 years and the male to female ratio was 11:7. Macroscopically, 1 case had the classic cystic and solid appearance whereas the others appeared purely solid. Microscopically, all 18 tumors shared similar solid and focal macrocystic or microcystic growth pattern, and the cells were characterized by voluminous and eosinophilic cytoplasm, along with coarse amphophilic stippling. Immunohistochemically, most of the tumors had a predominant cytokeratin (CK) 20-positive feature, ranging from focal cytoplasmic staining to diffuse membranous accentuation. Initially, we separated these cases into different immunohistochemical phenotypes. Group 1 (7 of 18; 38.5%) was characterized by positive phospho-4EBP1 and phospho-S6, which can imply hyperactive mechanistic target of rapamycin complex 1 (mTORC1) signaling. Group 2 (4 of 18; 23%) was negative for NF2, probably implying a germline mutation of NF2. Group 3 (7 of 18; 38.5%) consisted of the remaining cases. One case had metastatic spread and exhibited an aggressive clinical course, and we detected cyclin-dependent kinase inhibitor 2A (CDKN2A) mutation in this case; other patients were alive and without disease progression. Our research proposes that eosinophilic solid and cystic renal cell carcinoma exhibits prototypical pathologic features with CK20 positivity and has aggressive potential.

Eye Health Seeking Behavior and Its Associated Factors among Adult Population in Mangu LGA, Plateau State, Nigeria

Purpose: This study was aimed to explore the eye health-seeking behaviors and its associated factors among adult population of Mangu Local Government Area (LGA) of Plateau State, Nigeria in order to promote individual determination for attaining better eye health-seeking behaviors. Methods: This study was a population-based descriptive cross-sectional survey of 802 adult population aged 18 years and above was conducted in Mangu L.G.A, Plateau State, Nigeria using a multi-stage cluster random sampling design. Sociodemographic and eye health-seeking behavior data were collected using self-administered questionnaires. Vision status was defined using World Health Organization categories of visual impairment based on presenting Visual Acuity (VA). Data collected were analyzed using IBM SPSS version 20.0. All p-values reported were two tailed and significance was defined as P&lt;0.05. Results: Although a total of 960 respondents were enumerated for the study, 802 (83.5%) adults participated. There were more female 525 (65.5%) than males 277 (34.5%). The majority 585 (72.9%) of respondents who had eye problems sought care for the eye problem. One hundred and fifty-seven (36.0%) and 153 (35.1%) sought care at the General hospital and at the community health centre respectively. While 38 (8.7%) and 29 (6.7%) sought care from ophthalmologists and Optometrists respectively. Cost of services (34.4%), language barrier (13.0%), decides not to seek care (10.1%) and transportation (9.1%) were the major reasons for not seeking eye care. Conclusion: Although the majority of the respondents sought care for their eye problems, quite a large number of them sought care from non-eye care professionals. Cost of services, language barrier, transportation and services not available in the area were the major factors associated with eye health-seeking behaviour. Reduction in cost of services and health insurance coverage will mitigate these barriers substantially.

Artificial Intelligence Imaging for Predicting High-risk Molecular Markers of Gliomas.

Gliomas, the most prevalent primary malignant tumors of the central nervous system, present significant challenges in diagnosis and prognosis. The fifth edition of the World Health Organization Classification of Tumors of the Central Nervous System (WHO CNS5) published in 2021, has emphasized the role of high-risk molecular markers in gliomas. These markers are crucial for enhancing glioma grading and influencing survival and prognosis. Noninvasive prediction of these high-risk molecular markers is vital. Genetic testing after biopsy, the current standard for determining molecular type, is invasive and time-consuming. Magnetic resonance imaging (MRI) offers anon-invasive alternative, providing structural and functional insights into gliomas. Advanced MRI methods can potentially reflect the pathological characteristics associated with glioma molecular markers; however, they struggle to fully represent gliomas' high heterogeneity. Artificial intelligence (AI) imaging, capable of processing vast medical image datasets, can extract critical molecular information. AI imaging thus emerges as anoninvasive and efficient method for identifying high-risk molecular markers in gliomas, arecent focus of research. This review presents acomprehensive analysis of AI imaging's role in predicting glioma high-risk molecular markers, highlighting challenges and future directions.

Pathogenic and likely pathogenic germline variation in patients with myeloid malignancies and their unrelated HLA-matched hematopoietic stem cell donors

Aims: The revised 2022 World Health Organization classification recognizes myeloid neoplasms with associated germline predisposition as a defined subcategory, underscoring the clinical significance of likely pathogenic (LPV) and pathogenic (PV) germline variation in these diseases. To better understand the role of LPV/PV in blood or marrow transplants (BMT), a curative therapy for myeloid neoplasms, we measure their frequency and association with mortality in two cohorts of donor-recipient pairs. Methods: LPV/PV frequencies in 665 cancer-related genes were measured using exomechip genotyping data in 1990 acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients and their unrelated donors, registered with the Center for International Blood and Marrow Transplant Research. Cox proportional hazard models were used to test variant association with recipient mortality one-year post-transplant. Results: Thirteen autosomal dominant (AD) LPV/PV in eight genes were found in 2.8% of patients and 2.2% of donors; those linked to autosomal recessive conditions appeared in 11.1% of patients and 11% of donors. The most common AD LPV/PV mutations in recipients were found in DDX41 (n = 18). For donors, the most frequent AD PVs occurred in CHEK2 (n = 21) and Fanconi Anemia (FA) genes (n = 7). DDX41 and CHEK2 variation did not correlate with patient survival, but patients with donors with an LPV/PVs in an FA gene had lower survival (HR = 2.38, 95%CI: 1.06-5.31, P = 0.035) than patients whose donors did not have an FA LPV/PV. Conclusion: We identified LPVs/PVs in cancer genes in donors and recipients and are the first to show an association of donor FA PVs with mortality after BMT.

Impact of Adding Distal Forearm Bone Mineral Density Measurement to Axial Bone Mineral Density Measurement for the Diagnosis of Osteoporosis: Prevalence and Risk Factors for Diagnostic Discordance

Background: Studies have demonstrated the superiority of distal forearm bone mineral density (BMD) measurement over axial BMD measurement for prediction of osteoporotic fractures of distal radius. However, distal forearm BMD measurement is not routinely performed at most centers. Objective: To demonstrate the prevalence of discordance in diagnosis of osteoporosis using axial and distal forearm BMD measurement, and to assess whether age and other potential risk factors can predict major discordance. Materials and Methods: Postmenopausal women aged 45 years or older and men aged 50 years or older who underwent lumbar spine, hip, and distal forearm BMD measurement at Prompt Health Center, Faculty of Associated Medical Sciences, Chiang Mai University, Thailand, between January 2021 and December 2021 were recruited. The T-scores of axial site and distal forearm were categorized based on World Health Organization classification to determine the prevalence of diagnostic discordance. Major discordance was defined as having one osteoporotic and one normal T-score. Factors potentially associated with major discordance were explored using univariate and multivariate logistic regression models. Results: Eight hundred eighty-one participants including 621 women and 260 men with a mean age of 59.2±6.7 years were analyzed. There were 13.2% participants diagnosed with osteoporosis of the axial site, and 16.0% of the one-third (1/3) radius. The rates of major discordance, minor discordance, and concordance between axial and 1/3 radius T-scores were 3.2%, 40.5%, and 56.3%, respectively. Age of 65 years or older was significantly associated with major axial and 1/3 radius T-score discordance, with an adjusted odds ratio of 2.7 and 95% confidence interval 1.24 to 5.87 (p=0.012). Conclusion: Diagnostic discordance is observed for at least one-third of the participants using axial and distal forearm BMD measurement. The age of 65 years or older is a risk factor for major discordance. Keywords: Bone mineral density; Osteoporosis; Spine; Hip; Distal forearm; Discordance

Socio-economic status, functioning and cognition in young versus adult patients newly diagnosed with bipolar disorder and their unaffected relatives; results from a cross-sectional study

BackgroundBipolar disorders (BD) figures on top of the World Health Organization classification of disabling disorders. It is unclear if there are socioeconomic, functioning, and cognition differences in young patients newly diagnosed with BD and whether these are different for young and adult patients newly diagnosed with BD. Understanding these differences is important for tailored treatment and support. MethodsParticipant groups included 401 patients newly diagnosed with BD, 145 of their unaffected first-degree relatives (UR) and 209 healthy control individuals (HC). First, we compared socio-economic status, functioning and cognition between young patients newly diagnosed with BD (150), UR (61) and HC (92) (15–25 years) and adult patients newly diagnosed with BD (251), UR (84) and HC (117) (>25 years), respectively.Second, within patients, we compared functioning and cognition between young and adult patients newly diagnosed with BD. ResultsIn both participant groups, patients newly diagnosed with BD, and to a lesser degree UR, had lower socio-economic status and impaired functioning and cognition compared with HC. Further, young patients newly diagnosed with BD were less functionally impaired, than adults newly diagnosed with BD, whereas cognition did not differ between groups. LimitationsApplied tools for assessments of functioning and cognition are not validated below age 18. ConclusionsOverall, lower socio-economic status and impaired functioning and cognition were found both in young and adult patients newly diagnosed with BD and their UR compared with young and adult HC, respectively. Young patients were less functionally impaired than adults, but cognition was similarly impaired.

Clinicopathological implications of immunohistochemical expression of TBX21, CXCR3, GATA3, CCR4, and TCF1 in nodal follicular helper T-cell lymphoma and peripheral T-cell lymphoma, not otherwise specified.

The classification of nodal peripheral T-cell lymphoma (PTCL) has evolved according to histology, cell-of-origin, and genetic alterations. However, the comprehensive expression pattern of follicular helper T-cell (Tfh) markers, T-cell factor-1 (TCF1), and Th1- and Th2-like molecules in nodal PTCL is unclear. Eighty-two cases of nodal PTCL were classified into 53 angioimmunoblastic T-cell lymphomas (AITLs)/nodal T-follicular helper cell lymphoma (nTFHL)-AI, 18 PTCLs-Tfh/nTFHL-not otherwise specified (NOS), and 11 PTCLs-NOS according to the revised 4th/5th World Health Organization classifications. Immunohistochemistry for TCF1, TBX21, CXCR3, GATA3, and CCR4 was performed. TCF1 was highly expressed in up to 68% of patients with nTFHL but also in 44% of patients with PTCL-NOS (p > .05). CXCR3 expression was higher in AITLs than in non-AITLs (p = .035), whereas GATA3 expression was higher in non-AITL than in AITL (p = .007) and in PTCL-Tfh compared to AITL (p = .010). Of the cases, 70% of AITL, 44% of PTCLTfh/ nTFHL-NOS, and 36% of PTCL-NOS were subclassified as the TBX21 subtype; and 15% of AITL, 38% of PTCL-Tfh/nTFHL-NOS, and 36% of PTCL-NOS were subclassified as the GATA3 subtype. The others were an unclassified subtype. CCR4 expression was associated with poor progression-free survival (PFS) in patients with PTCL-Tfh (p < .001) and nTFHL (p = .023). The GATA3 subtype showed poor overall survival in PTCL-NOS compared to TBX21 (p = .046) and tended to be associated with poor PFS in patients with non-AITL (p = .054). The TBX21 subtype was more prevalent than the GATA3 subtype in AITL. The GATA3 subtype was associated with poor prognosis in patients with non-AITL and PTCL-NOS.

Classification of gastric neuroendocrine tumors and associations with survival.

597 Background: The World Health Organization (WHO) classification of gastric body neuroendocrine tumors (GNETs) includes type 1 tumors characterized by hypergastrinemia and arising in a background of atrophic gastritis, type 2 tumors associated with gastrinomas, and type 3 tumors with low serum gastrin level and no background mucosal pathology. However, certain tumors remain unclassified, and the prognostic significance of these tumors is currently unknown. The purpose of this study was to better characterize GNET types and to determine associations with distant metastasis and disease-specific survival (DSS). Methods: Patients diagnosed with GNET (1986-2021) were retrospectively identified and tumors classified as type 1, 2, or 3. Unclassified tumors were reviewed for background gastric mucosal changes associated with chronic proton pump inhibitor (PPI) use. Tumors were categorized as PPI-associated if there were prominent parietal and neuroendocrine cell hyperplasia in the background mucosa, in the absence of a gastrinoma and a positive history of chronic PPI use. WHO grade was determined using mitotic index or Ki-67 proliferative index when available. Characteristics by tumor type, associations with distant metastasis at initial diagnosis, and DSS were determined using standard statistical methods. Results: Of 246 patients, 164 (66.7%) had type 1, 5 (2.0%) had type 2, 52 (21.1%) had type 3, 18 (7.3%) were PPI-associated, and 7 (2.8%) remained unclassified. Multifocal disease was more common for types 1 (56.1%) and 2 (40.0%) than type 3 (13.5%) and PPI-associated tumors (27.8%, P&lt;0.001). Patients with type 3 GNET were also less likely to have WHO grade 1 tumors (26.9%) compared to other GNETs (type 1 37.2%, type 2 40.0%, PPI-associated 50.0%, P&lt;0.001). Additionally, distant metastases at presentation occurred more frequently with type 3 (38.5%) than type 1 (1.2%), type 2 (20.0%), and PPI-associated tumors (11.1%, P&lt;0.001). GNET type (type 1 vs 3, odds ratio [OR] 0.005 [95% confidence interval [CI] 0.001-0.050; PPI-associated vs type 3, OR 0.040 [95% CI 0.004-0.45]), race (non-white vs white, OR 0.17 [95% CI 0.040-0.73]), and WHO grade (2/3 vs 1, OR 10.5 [95% CI 1.93-57.2]) were associated with distant metastasis at presentation. Five-year DSS rates were 100.0% for type 1, 59.7% (95% CI 42.7-73.2%) for type 3, and 90.9% (95% CI 50.8-98.7%) for PPI-associated (log-rank P&lt;0.001). By multivariable analysis, multifocality of primary tumors (hazard ratio [HR] 0.070 [95% CI 0.010-0.46]) and distant metastasis at diagnosis (HR 44.9, 95% CI 6.21-324.8) were independently associated with DSS, while tumor type was not (type 1 vs 3, HR 0.18 [95% CI 0.010-2.44); PPI-associated vs type 3, HR 0.13 [95% CI 0.010-1.33]). Conclusions: PPI-associated tumors may represent a distinct GNET type with intermediate outcomes compared to type 1 and type 3 tumors. However, factors other than tumor type must be considered in determining survival.

Infection prevention and control practices in the Pediatrics and Child Health Department of Tikur Anbessa Specialized Hospital, Ethiopia.

Infection prevention and control (IPC) is a set of practices that are designed to minimize the risk of healthcare-associated infections (HAIs) spreading among patients, healthcare workers, and visitors. Implementation of IPC is essential for reducing infection incidences, preventing antibiotic use, and minimizing antimicrobial resistance (AMR). The aim of the study was to assess IPC practices and associated factors in Pediatrics and Child Health at Tikur Anbessa Specialized Hospital. In this study, we used a cross-sectional study design with a simple random sampling method. We determined the sample size using a single population proportion formula with the assumption of a 55% good IPC practice, a 5% accepted margin of error, and a 15% non-response rate and adjusted with the correction formula. The final sample size was 284 healthcare workers. The binary logistic regression model was used for analysis. The World Health Organization (WHO) Infection Prevention and Control Assessment Framework (IPCAF) tool was used to assess IPC core components. A total of 272 healthcare workers participated in the study, with a response rate of 96%. Of the total participants, 65.8% were female and 75.7% were nurses. The overall composite score showed that the prevalence of good IPC practices among healthcare workers was 50.4% (95% CI: 44.3-56.5). The final model revealed that nursing professionals and healthcare workers who received IPC training had AORs of 2.84 (95% CI: 1.34-6.05) and 2.48 (95% CI: 1.36-4.52), respectively. The final average total IPCAF score for the IPC level was 247.5 out of 800 points. The prevalence of good IPC practice was suboptimal. The study participants, who were nursing professionals and healthcare workers who received IPC training, showed a statistically significant association with the IPC practice level. The facility-level IPCAF result showed a "Basic" level of practice based on the WHO categorization. These evidences can inform healthcare workers and decision-makers to identify areas for improvement in IPC practice at all levels. Training of healthcare workers and effective implementation of the eight IPC core components should be strengthened to improve suboptimal practices.

Differentiated high grade thyroid carcinomas: Diagnostic consideration and clinical features

BackgroundDifferentiated high-grade thyroid carcinomas (DHGTCs) are a new diagnostic entity most recently defined in the 2022 World Health Organization's (WHO) Classification of Endocrine and Neuroendocrine Tumors. This new entity has been minimally described in the literature, and additional cases classified as such are missing. Materials and methodsCases of DHGTCs diagnosed at our institution from 2012 to 2022 were identified, and the following were reviewed: cytologic and histologic diagnoses, ancillary testing, immunohistochemical staining, treatments, and patient outcomes. Immunohistochemical staining for Ki67 was performed on selected cases lacking this immunostain. A systematic literature review of the English literature on DHGTCs from 2013 to 2023 was performed using PubMed and Embase. ResultsCase cohort included 32 cases of DHGTCs, with an average age of 52.6 years (range 17–84 years) and a male:female ratio of 1.3:1. All cases underwent fine needle aspiration (FNA) and were categorized by The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) as follows: 14 cases as malignant (43.8 %), 10 as follicular neoplasm (31.3 %), 5 as atypia of undetermined significance (15.6 %), 2 as suspicious for malignancy (6.2 %), and 1 as non-diagnostic (3.1 %). The average tumor size was 5.15 cm, and most were papillary thyroid carcinoma (28, 87.5 %), with classic subtype being the most common. Twenty-one cases revealed tumor necrosis and the mitotic activity in lesions without necrosis averaged to 5.5 mitoses per 2 mm2 (range 0–7). The average Ki67 proliferative index was 5.6 %. Extrathyroidal extension was seen in 17, angioinvasion in 21, lymphatic invasion in 7, and perineural invasion in 1 case. Foci of solid or trabecular growth were identified in five cases. Lymph node metastases at the time of diagnosis were noted in 10 cases and 7 demonstrated distant metastases or locoregional recurrence. To date, 25 patients are alive, and one has died from disease. ConclusionsOur institutional experience demonstrates that DHGTC is a rare, but aggressive thyroid tumor subtype that requires consideration in the setting of a well-differentiated thyroid neoplasm to appropriately assess for possible disease recurrence and determination of patient prognosis.