World Health Organization Classification Research Articles

Update on Pathologic Conditions, Imaging Findings, Prevention, and Management of Human Papillomavirus-related Neoplasms.

Human papillomavirus (HPV) is the most common sexually transmitted infection that proliferates in the squamous epithelium and is the most common source of viral-related neoplasms. Low-risk subtypes (HPV-6 and -11) cause respiratory papillomas (laryngeal, tracheal, and bronchial) and condyloma acuminata of the penis, anus, and perineal region (anogenital warts). High-risk subtypes (HPV-16, -18, -31, and -33) are responsible for oropharyngeal squamous cell carcinoma (SCC) that involves the tongue base, tonsils, posterior pharyngeal wall, and larynx and malignancies of the anogenital region (cancers of the cervix, vagina, vulva, penis, and anal canal). Recent studies have increasingly shown a favorable treatment response and substantial differences in the overall prognosis associated with HPV-associated oropharyngeal cancers. Given this fact, oropharyngeal, cervical, and penile SCCs are classified as HPV-associated and HPV-independent cancers in the current World Health Organization classification. Imaging is essential in the early detection, diagnosis, and staging of HPV-associated cancers. Imaging also helps assess treatment response and postoperative complications and is used for long-term surveillance. HPV-associated oropharyngeal SCCs have well-defined borders and solid and cystic nodal metastases at imaging. Updated screening and vaccination guidelines are currently available that have great potential to decrease the overall disease burden and help control this worldwide public health concern. Novel therapeutic strategies, such as immunotherapies, are being explored, and imaging biomarkers that can predict treatment response and prognosis are being investigated; radiologists play a pivotal role in these efforts. ©RSNA, 2024 Supplemental material is available for this article.

Spread Through Air Spaces: Interresponder Agreement and Comparison Between Pulmonary and General Pathologists

Spread through air spaces (STAS), an important prognostic indicator included in the 2015 World Health Organization classification, is defined as micropapillary, solid, and/or single tumor cell clusters beyond the edge of the main mass and distinct from processing artifacts. This study aimed to assess the interresponder agreement on current STAS criteria vs artifacts, identify discrepancies, and compare responses between pulmonary and general pathologists. A multiple-choice online questionnaire illustrating multiple criteria for STAS vs artifacts was available internationally for 6 days to Pulmonary Pathology Society members, thoracic pathology course attendees, and International Association for the Study of Lung Cancer pathology committee members. Additional 4 questions gathered demographic and practice setting information. One hundred thirty-six unique responses were analyzed. The majority were from North America and Europe (42.6% and 30.2%), practicing pulmonary pathology (70.6%) in academia (64.7%), and with >20 years of experience (31.6%). Excluding trainees, the greatest overall agreement was in defining solid and micropapillary tumor clusters of STAS located ≥3 alveolar spaces from the main tumor edge (91.5%) and recognizing strips of ciliated cells as artifacts (97.7%). Lesser agreement on STAS was evident when tumor cell clusters were immediately adjacent to the tumor edge, a single tumor cell cluster was present at the tissue edge, tumor cell clusters were jagged edged, or tumor cell clusters were admixed with ciliated cell strips (artifacts). There was no significant difference in agreements on STAS for multiple criteria between pulmonary and general pathologists. Significant interresponder agreement on STAS vs artifacts was achieved only for a few criteria. To improve the reproducibility of STAS vs artifacts, areas of lesser agreement require further clarification.

Pesticide knowledge and attitude among the potato growing farmers of Bangladesh and determinant factors.

The study aimed to assess the extent of pesticide use among potato-growing farmers in Bangladesh and its relationship with their knowledge, attitude, and socio-demographic characteristics. Data were collected from 553 farmers using a semi-structured questionnaire through multistage random sampling. Bivariate analysis was conducted to examine the relationship between the frequency of pesticide use and various socio-demographic factors. Results showed that out of 321 different pesticide brands reported, 50.5% were registered, while 47.7% were unregistered and 1.9% were banned. Among the registered pesticides, 5.6% were highly hazardous, 24.8% were moderately hazardous, and 6.2% were slightly hazardous as per World Health Organization category. A high percentage (96%) of farmers reported using pesticides in their fields, with 16.6% applying pesticides more than five times in a cropping season. Data revealed that majority of the farmers were aware of the negative effect of pesticides on health and environment. Most farmers used hand towels (77.9%) and ordinary shirts (70.0%) to cover their bodies to avoid pesticide exposure. Inappropriate disposal of empty pesticide containers was also observed. Negative binomial regression analysis revealed significant positive associations between the frequency of pesticide application and potato productivity, rate of fertilizer application, area of land owned by farmers, and their knowledge about the negative effects of pesticides on human health. The study suggests adopting integrated pest management practices, developing pest-resistant potato varieties, ensuring safe handling practices and disposal as well as stringent enforcement of laws to mitigate pesticide externalities and hence ensure sustainability in agriculture.

DETERMINANTS MODELING OF UNDERNUTRITION IN TODDLERS IN ACEH PROVINCE: A PLS-SEM APPROACH

This study examines the escalating prevalence of underweight and wasting in Indonesia from 2019 to 2022. The prevalence of underweight has increased from 16.35% in 2019 to 17.1% in 2022 while wasting has increased from 7.4% to 7.7% during the same period. Aceh province faces a pressing issue of toddler malnutrition, ranking second with the highest prevalence of underweight (24.8%) and fourth highest in wasting prevalence (11.3%). According to the World Health Organization's malnutrition indicators classification, Aceh experiences notably high levels of underweight and very high levels of wasting. Employing Partial Least Squares Structural Equation Modeling (PLS-SEM) with data sourced from SSGI, publications from the Ministry of Health and BPS-Statistics Indonesia, and Aceh Provincial Food Agency, this research aims to model undernutritioned toddlers in Aceh Province. Findings reveal that undernutrition is directly affected by health access and food intake, with socioeconomic factors exerting an indirect effect. Notably, food intake emerges as the primary determinant of undernutrition.

SNO-EANO-EURACAN consensus on management of pineal parenchymal tumors.

Pineal parenchymal tumors are rare neoplasms for which evidence-based treatment recommendations are lacking. These tumors vary in biology, clinical characteristics, and prognosis, requiring treatment that ranges from surgical resection alone to intensive multimodal antineoplastic therapy. Recently, international collaborative studies have shed light on the genomic landscape of these tumors, leading to refinement in molecular-based disease classification in the 5th edition of the World Health Organization (WHO) classification of tumors of the central nervous system. In this review, we summarize the literature on diagnostic and therapeutic approaches, and suggest pragmatic recommendations for the clinical management of patients presenting with intrinsic pineal region masses including parenchymal tumors (pineocytoma, pineal parenchymal tumor of intermediate differentiation, and pineoblastoma), pineal cyst, and papillary tumors of the pineal region.

Glioma Type Prediction with Dynamic Contrast-Enhanced MR Imaging and Diffusion Kurtosis Imaging-A Standardized Multicenter Study.

The aim was to explore the performance of dynamic contrast-enhanced (DCE) MRI and diffusion kurtosis imaging (DKI) in differentiating the molecular subtypes of adult-type gliomas. A multicenter MRI study with standardized imaging protocols, including DCE-MRI and DKI data of 81 patients with WHO grade 2-4 gliomas, was performed at six centers. The DCE-MRI and DKI parameter values were quantitatively evaluated in ROIs in tumor tissue and contralateral normal-appearing white matter. Binary logistic regression analyses were performed to differentiate between high-grade (HGG) vs. low-grade gliomas (LGG), IDH1/2 wildtype vs. mutated gliomas, and high-grade astrocytic tumors vs. high-grade oligodendrogliomas. Receiver operating characteristic (ROC) curves were generated for each parameter and for the regression models to determine the area under the curve (AUC), sensitivity, and specificity. Significant differences between tumor groups were found in the DCE-MRI and DKI parameters. A combination of DCE-MRI and DKI parameters revealed the best prediction of HGG vs. LGG (AUC = 0.954 (0.900-1.000)), IDH1/2 wildtype vs. mutated gliomas (AUC = 0.802 (0.702-0.903)), and astrocytomas/glioblastomas vs. oligodendrogliomas (AUC = 0.806 (0.700-0.912)) with the lowest Akaike information criterion. The combination of DCE-MRI and DKI seems helpful in predicting glioma types according to the 2021 World Health Organization's (WHO) classification.

Hypothermia in preterm infants admitted to low-resource neonatal units in northern Nigeria: an observational study of occurrence and risk factors

BackgroundHypothermia is an important cause of morbidity and mortality among preterm and low-birth-weight neonates. In resource-constrained settings, limited referral infrastructure and technologies for temperature control potentiate preterm hypothermia. While there is some documentation on point-of-admission hypothermia from single center studies, there are limited multicenter studies on the occurrence of hypothermia among preterm infants in resource-limited-settings. Therefore, we conducted a multicenter study to determine the prevalence and risk factors for hypothermia at the time of admission and during the first 72 h after admission in northern Nigeria.MethodWe carried out a prospective cohort study on preterm infants admitted to four referral hospitals in northern Nigerian between August 2020 and July 2021. We documented temperature measurements at admission and the lowest and highest temperatures in the first 72 h after admission. We also collected individual baby-level data on sociodemographic and perinatal history data. We used the World Health Organization classification of hypothermia to classify the babies’ temperatures into mild, moderate, and severe hypothermia. Poisson regression analysis was used to identify risk factors for moderate-severe hypothermia.ResultsOf the 933 preterm infants enrolled, 682 (72.9%) had hypothermia at admission although the prevalence of hypothermia varied across the four hospitals. During the first 24 h after admission, 7 out of every 10 babies developed hypothermia. By 72 h after admission, between 10 and 40% of preterm infants across the 4 hospitals had at least one episode of moderate hypothermia. Gestational age (OR = 0.86; CI = 0.82–0.91), birth weight (OR = 8.11; CI = 2.87–22.91), presence of a skilled birth attendant at delivery (OR = 0.53; CI = 0.29–0.95), place of delivery (OR = 1.94 CI = 1.13–3.33) and resuscitation at birth (OR = 1.79; CI = 1.27–2.53) were significant risk factors associated with hypothermia.ConclusionThe prevalence of admission hypothermia in preterm infants is high and hypothermia is associated with low-birth-weight, place of delivery and presence of skilled birth attendant. The prevalence of hypothermia while in care is also high and this has important implications for patient safety and quality of patient care. Referral services for preterm infants need to be developed while hospitals need to be better equipped to maintain the temperatures of admitted small and sick newborns.

Reclassification of Myelodysplastic Neoplasms According to the 2022 World Health Organization Classification and the 2022 International Consensus Classification Using Open-Source Data: Focus on SF3B1- and TP53-mutated Myelodysplastic Neoplasms.

In 2022, the WHO and International Consensus Classification (ICC) published diagnostic criteria for myelodysplastic neoplasms (MDSs). We examined the influence of the revised diagnostic criteria on classifying MDSs in a large population. We retrieved an open-source pre-existing dataset from cBioPortal and included 2,454 patients with MDS in this study. Patients were reclassified based on the new diagnostic 2022 WHO and ICC criteria. Survival analysis was performed using Cox regression to validate the new criteria and to assess risk factors. Based on the 2022 WHO criteria, 1.4% of patients were reclassified as having AML. The 2022 WHO criteria provide a superior prognostic/diagnostic model to the 2017 WHO criteria (Akaike information criterion, 14,152 vs. 14,516; concordance index, 0.705 vs. 0.681). For classifying MDS with low blast counts and SF3B1 mutation, a variant allele frequency cut-off of 5% (2022 WHO criteria) and the absence of RUNX1 co-mutation (2022 ICC criteria) are diagnostically relevant. For classifying MDSs with mutated TP53, a blast count cut-off of 10% (2022 ICC criteria) and multi-hit TP53 (2022 WHO criteria) are independent risk factors in cases with ≥10% blasts. Our findings support the refinements of the new WHO criteria. We recommend the complementary use of the new WHO and ICC criteria in classifying SF3B1- and TP53-mutated MDSs for better survival prediction.

Histopathological Spectrum of Gliomas and Its Immunohistochemical Correlation in a Tertiary Care Setup.

Introduction Central nervous system (CNS) tumors pose significant diagnostic challenges due to their varied morphological and differentiating characteristics. Modern advancements in immunohistochemistry (IHC) and molecular pathology have greatly enhanced prognostication, screening, and therapeutic management. Gliomas, a type of tumor originating from glial cells in the CNS, can develop from astrocytes, oligodendrocytes, or ependymal cells. According to the 2021 update, the classification of diffuse gliomas is primarily based on the presence or absence of isocitrate dehydrogenase (IDH1/2) mutations. IDH-wildtype gliomas (glioblastomas) have a significantly poorer prognosis compared to IDH-mutant gliomas (astrocytomas and oligodendrogliomas). Gliomas are highly infiltrative and resistant to treatment, making them largely incurable regardless of their grade and prognosis. Objective This study aimed to determine the histopathological diversity of gliomas and its correlation with protein expressions of IDH, ATRX gene (α-thalassemia/mental retardation syndrome X-linked), Ki-67, and p53 mutations (tumor suppressor gene-53), according to the 2021 World Health Organization (WHO) Classification of CNS Tumors, Fifth Edition. Methods This descriptive cross-sectional study was carried out in the Department of Pathology at a tertiary care center, focusing on various types of gliomas received over a two-year period. A total of 54 specimens of gliomas received from the Department of Neurosurgery were subjected to histopathological examination. Sections were stained using hematoxylin and eosin (H&E), and IHC was performed using four markers (IDH, ATRX, p53, Ki-67) in each case. Results were analyzed according to the 2021 WHO Classification of CNS Tumors, Fifth Edition. Results The majority of individuals were between the age group of 40 and 60 years, showing a male predominance (65%). The most common site was the frontal lobe. Glioblastoma constituted the largest proportion (46.2%) of the total cases, followed by astrocytoma (20.3%), oligodendroglioma (18.5%), pilocytic astrocytoma (7.4%), and ependymoma (7.4%). All 11 cases of astrocytoma exhibited IDH mutation and ATRX loss, with p53 positive in the majority of cases. Strong nuclear p53 immunohistochemical positivity in >10% of tumor nuclei correlates with TP53 mutations. Among 25 cases of glioblastoma, IDH was negative, ATRX was retained in all cases, and 11 cases were positive for p53 mutation. For oligodendroglioma, out of 10 cases, IDH mutation was positive, and ATRX was retained in all cases. p53 mutation was not seen in any case. All cases of pilocytic astrocytoma were negative for IDH and p53 mutations, with ATRX retained in all cases. In all cases of ependymoma, IDH and p53 mutations were negative, and ATRX was retained in all cases. Glioblastomas exhibited the highest Ki-67 expression. Conclusion The 2021 WHO Classification of CNS Tumors, Fifth Edition, was updated, building on previously established concepts and continuing to evolve. The final diagnosis of gliomas relies on a comprehensive combination of clinical evaluation, neuroimaging, pathological examination, and molecular analysis. Nonetheless, histopathological examination, along with IHC, remains the cornerstone of diagnosis.

Soft tissue tumor imaging in adults: whole-body staging in sarcoma, non-malignant entities requiring special algorithms, pitfalls and special imaging aspects. Guidelines 2024 from the European Society of Musculoskeletal Radiology (ESSR).

The revised European Society of Musculoskeletal Radiology (ESSR) consensus guidelines on soft tissue tumor imaging represent an update of 2015 after technical advancements, further insights into specific entities, and revised World Health Organization (2020) and AJCC (2017) classifications. This second of three papers covers algorithms once histology is confirmed: (1) standardized whole-body staging, (2) special algorithms for non-malignant entities, and (3) multiplicity, genetic tumor syndromes, and pitfalls. A validated Delphi method based on peer-reviewed literature was used to derive consensus among a panel of 46 specialized musculoskeletal radiologists from 12 European countries. Statements that had undergone interdisciplinary revision were scored online by the level of agreement (0 to 10) during two iterative rounds, that could result in 'group consensus', 'group agreement', or 'lack of agreement'. The three sections contain 24 statements with comments. Group consensus was reached in 95.8% and group agreement in 4.2%. For whole-body staging, pulmonary MDCT should be performed in all high-grade sarcomas. Whole-body MRI is preferred for staging bone metastasis, with [18F]FDG-PET/CT as an alternative modality in PET-avid tumors. Patients with alveolar soft part sarcoma, clear cell sarcoma, and angiosarcoma should be screened for brain metastases. Special algorithms are recommended for entities such as rhabdomyosarcoma, extraskeletal Ewing sarcoma, myxoid liposarcoma, and neurofibromatosis type 1 associated malignant peripheral nerve sheath tumors. Satisfaction of search should be avoided in potential multiplicity. Standardized whole-body staging includes pulmonary MDCT in all high-grade sarcomas; entity-dependent modifications and specific algorithms are recommended for sarcomas and non-malignant soft tissue tumors. These updated ESSR soft tissue tumor imaging guidelines aim to provide support in decision-making, helping to avoid common pitfalls, by providing general and entity-specific algorithms, techniques, and reporting recommendations for whole-body staging in sarcoma and non-malignant soft tissue tumors. An early, accurate, diagnosis is crucial for the prognosis of patients with soft tissue tumors. These updated guidelines provide best practice expert consensus for standardized imaging algorithms, techniques, and reporting. Standardization can improve the comparability examinations and provide databases for large data analysis.

EWSR1::ATF1 fusions characterize a group of extra-abdominal epithelioid and round cell mesenchymal neoplasms, phenotypically overlapping with sclerosing epithelioid fibrosarcomas, and intra-abdominal FET::CREB fusion neoplasms.

With the increasing use of next generation sequencing in soft tissue pathology, particularly in neoplasms not fitting any World Health Organization (WHO) category, the spectrum of EWSR1 fusion-associated soft tissue neoplasms has been expanding significantly. Although recurrent EWSR1::ATF1 fusions were initially limited to a triad of mesenchymal neoplasms including clear cell sarcoma of soft tissue, angiomatoid fibrous histiocytoma and malignant gastrointestinal neuroectodermal tumor (MGNET), this family has been expanding. We herein describe 4 unclassified extra-abdominal soft tissue (n = 3) and bone (n = 1) neoplasms displaying epithelioid and round cell morphology and carrying an EWSR1::ATF1 fusion. Affected were 3 males and 1 female aged 20-56years. All primary tumors were extra-abdominal and deep-seated (chest wall, mediastinum, deltoid, and parapharyngeal soft tissue). Their size ranged 4.4-7.5cm (median, 6.2). One patient presented with constitutional symptoms. Surgery with (2) or without (1) neo/adjuvant therapy was the treatment. At last follow-up (8-21months), 2 patients developed progressive disease (1 recurrence; 1 distant metastasis). The immunophenotype of these tumors is potentially misleading with variable expression of EMA (2 of 3), pankeratin (2 of 4), synaptophysin (2 of 3), MUC4 (1 of 3), and ALK (1 of 3). All tumors were negative for S100 and SOX10. These observations point to the existence of heretofore under-recognized group of epithelioid and round cell neoplasms of soft tissue and bone, driven by EWSR1::ATF1 fusions, but distinct from established EWSR1::ATF1-associated soft tissue entities. Their overall morphology and immunophenotype recapitulate that of the emerging EWSR1/FUS::CREB fusion associated intra-abdominal epithelioid/round cell neoplasms. Our cases point to a potentially aggressive clinical behavior. Recognizing this tumor type is mandatory to delineate any inherent biological and/or therapeutic distinctness from other, better-known sarcomas in the differential diagnosis including sclerosing epithelioid fibrosarcoma.

Mapping the cited evidence of ductal carcinoma in situ from the 5th edition of the World Health Organisation classification of tumours of the breast.

Ductal carcinoma in situ (DCIS) is recognised by the World Health Organisation (WHO) Classification of Tumours (WCT) as a non-invasive neoplastic epithelial proliferation confined to the mammary ducts and lobules. This report categorises the references cited in the DCIS chapter of the 5th edition of the WCT (Breast Tumours) according to prevailing evidence levels for evidence-based medicine and the Hierarchy of Evidence for Tumour Pathology (HETP), identifying potential gaps that can inform subsequent editions of the WCT for this tumour. We included all citations from the DCIS chapter of the WCT (Breast Tumours, 5th edition). Each citation was appraised according to its study design and evidence level. We developed our map of cited evidence, which is a graphical matrix of tumour type (column) and tumour descriptors (rows). Spheres were used to represent the evidence, with size and colour corresponding to their number and evidence level respectively. Thirty-six publications were retrieved. The cited literature in the DCIS chapter comprised mainly case series and were regarded as low-level. We found an unequal distribution of citations among tumour descriptors. 'Pathogenesis' and 'prognosis and prediction' contained the most references, while 'clinical features', 'aetiology' and 'diagnostic molecular pathology' had only a single citation each. 'Prognosis and prediction' had the greatest proportion of moderate- and high-levels of evidence. Our findings align with the disposition for observational studies inherent in the field of pathology. Our map is a springboard for future efforts in mapping all available evidence on DCIS, potentially augmenting the editorial process and future editions of WCTs.

Clear Cell Papillary Renal Cell Carcinoma: Case Series with Review of the Literature

Abstract Clear cell papillary renal cell carcinoma (CCPRCC) was included as a separate entity in the World Health Organisation classification of renal tumours in 2016. Immuno-histopathological and genetic characteristics are much known, but still, clinical features and long-term follow-up require more consolidated data. We report three cases of CCPRCC, detected in different clinical settings. The first case was co-incidentally diagnosed on routine imaging, in a follow-up case of open cystolithotripsy. The second case presented with haematuria under evaluation; and the third case presented with mild thrombocytopenia without anaemia or a positive Coombs test. All the cases revealed characteristic histopathological examination and immunohistochemistry. None of the patients showed tumour recurrence/metastases on follow-up. The study holds importance as it presents CCPRCC cases in different clinical scenarios, describes a rarely reported case of thrombocytopenia without associated anaemia/positive Coombs test, and emphasises the need to consider CCPRCC in relevant clinico-radiological settings and immuno-histopathological features, due to its indolent nature and consequently better prognosis.

Giant cell carcinoma of the urinary bladder

We present the clinicopathological features of 23 cases of the giant cell subtype of urothelial carcinoma, a rare subtype of bladder cancer recognized in the current World Health Organization classification of urological tumors. Histologically, the architectural pattern of the tumor varied from infiltrating to the solid expansile pleomorphic tumor with giant, bizarre, anaplastic cells. Typical or atypical mitotic figures were frequently present in all cases. Between 10 and 30% of the tumor had a giant cell component. All cases were associated with conventional high-grade urothelial carcinoma, with areas of squamous cell divergent differentiation and micropapillary carcinoma present in six and two cases, respectively. In one case each had sarcomatoid, nested, small cell, or glandular divergent differentiation. At diagnosis, 35% of patients had advanced disease and 12% had distant metastases. When comparing giant cell urothelial carcinoma with conventional urothelial carcinoma in a matched analysis, differences in overall and cancer-specific survival were observed, particularly in the T1 stage category. Immunohistochemical staining showed a similar profile of urothelial lineage with frequent positive expression of uroplakin II, GATA3, CK20, CK7, and S100P in both giant cell and conventional urothelial carcinomas. High Ki67 proliferation (range, 60–90%; mean, 71%) and nuclear p53 accumulation (mutant profile; range, 50–90%; mean, 64%) were observed. Using the 22C3 assay, the expression of PD-L1 was found to be variable in two cases, and beta-HCG was negative. In conclusion, giant cell carcinoma is a subtype of urothelial carcinoma associated with advanced clinical stage and a trend to lower survival rates.

Cribriform morular thyroid carcinoma: Clinicopathological and molecular basis for both a preventive and therapeutic approach for a rare tumor (Review).

Cribriform morular thyroid carcinoma (CMTC) has been included within the group of thyroid tumors of uncertain histogenesis in the recent World Health Organization classification of endocrine tumors. Most CMTCs occur in young euthyroid women with multiple (and bilateral) thyroid nodules in cases associated with familial adenomatous polyposis (FAP) or as single nodules in sporadic cases. CMTC generally behaves indolently, while aggressiveness and mortality are associated with high‑grade CMTC. This tumor histologically displays a distinctive combination of growth patterns with morular structures. Strong diffuse nuclear and cytoplasmic immunostaining for β‑catenin is the hallmark of CMTC. Tumor cells are also positive for thyroid transcription factor‑1 and for estrogen and progesterone receptors, but negative for thyroglobulin and calcitonin. It is possible that the CMTC phenotype could result from blockage in the terminal/follicular differentiation of follicular cells (or their precursor cells) secondary to the permanent activation of the Wnt/β‑catenin pathway. In CMTC, the activation of the Wnt/β‑catenin pathway is the central pathogenetic event, which in FAP‑associated cases results from germline mutations of the APC regulator of WNT signaling pathway (APC) gene, and in sporadic cases from somatic inactivating mutations in the APC, AXIN1 and CTNNB1 genes. Estrogens appear to play a tumor‑promoting role by stimulating both the PI3K/AKT/mTOR and the RAS/RAF/MAPK signaling pathways. Additional somatic mutations (i.e. RET rearrangements, or KRAS, phosphatidylinositol‑4,5‑bisphosphate 3‑kinase catalytic subunit α, telomerase reverse transcriptase or tumor protein 53 mutations) may further potentiate the development and progression of CMTC. While hemithyroidectomy would be the treatment of choice for sporadic cases without high‑risk data, total thyroidectomy would be indicated in FAP‑associated cases. There is insufficient clinical data to propose therapies targeting the Wnt/β‑catenin pathway, but multikinase or selective inhibitors could be used in a manner analogous to that of conventional thyroid tumors. It is also unknown whether adjuvant antiestrogenic therapy could be useful in the subgroup of women undergoing surgery with high‑risk CMTC, as well as when there is tumor recurrence and/or metastasis.

Screening and the analysis of genotypic and phenotypic characterization of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Fujian province, China.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked hereditary disorder in southern China. However, the incidence rate of G6PD deficiency and the frequency of the most common G6PD gene variants vary widely. The purpose of this study was to investigate the prevalence, genotype, and phenotypic features of G6PD deficiency in neonates in Fujian province, southeastern China. This retrospective cohort study enrolled 2,789,002 newborns (1,521,431 males and 1,267,571 females) based on the newborn screening program for G6PD deficiency in Fujian Province between January 2010 and December 2021. Of the 2,789,002 newborns enrolled, 26,437 cases were diagnosed (22,939 males and 3,498 females), and the estimated prevalence of G6PD deficiency in Fujian province was 0.95%. The prevalence was significantly higher among males (1.51%) than in females (0.28%) (p < 0.00001). Among the 3,198 patients with G6PD deficiency, 3,092 cases (2,145 males and 947 females) were detected to have G6PD gene variants. The top six prevalent genotypes identified represented 90.84% (2095/3,198) of the total and included c.1376G > T (44.93%), c.1388G > A (18.42%), c.1024C > T (9.32%), c.95A > G (8.69%), c.392G > T (5.25%), and c.871G > A (4.22%). The frequency of genotypes with c.1388G > A, c.1024C > T, and c.871G > A was higher in males in the Fujian province than in females, while the frequency of genotypes with c.1376G > T was lower. Furthermore, when comparing the enzyme activities of the top six prevalent genotypes, there were significant differences in the enzyme activities among the genotypes of male hemizygotes and female heterozygotes. According to the new classification of G6PD variants proposed by the World Health Organization (WHO), the variants with c.1376G > T, c.95A > G, and c.871G > A were recognized as Class A, while the c.392G > T, c.1388G > A, and c.1024C > T were recognized as Class B. To the best of our knowledge, this study is the first to systematically describe the overview of epidemiological characteristics of newborn G6PD deficiency in Fujian province, China, including the screening rate, incidence rate, and variant spectrum. Additionally, we elucidated the relationship between the distribution of enzyme activity with specific mutations and their WHO classification patterns. Our results could provide strategies for screening, diagnosis, and genetic counseling of G6PD deficiency in this area.

Solitary cutaneous neoplasms: analysing the uncertain behaviour with the aid of histopathology

BACKGROUND: Skin tumours can be classified as either benign or malignant, resulting due to the proliferation of one or more components of the skin. Reportedly, there has been a rise in the prevalence of skin cancer in recent decades, which has led to rely on histological evidence to distinguish between various types of skin cancer. AIM: This study aims to provide a comprehensive description of the occurrence, symptoms, unpredictable nature, and range of histopathological spectrum in different types of skin tumours. METHODS: This prospective research was conducted in the outpatient department of the Department of Dermatology at the Government General Hospital in Anantapur from July 2019 to July 2023. Patients who did not provide informed consent, those with infectious or cystic swellings, or those with multiple lesions were excluded from this study. Histopathological confirmation is obtained from all excisional biopsies of single cutaneous swellings, and tumours are classified based on the criteria established by the World Health Organization (WHO). RESULTS: The study included a total of 123 individual cutaneous tumours, with 98 cases (79.67%) being classified as benign and 25 cases (20.32%) classified as malignant. The age group most affected is adults between the ages of 26 and 44, with a prevalence rate of 31.7%. Following closely behind are middle-aged individuals, with a prevalence rate of 30.08%. The males constitute 46.34% (57 cases) and the females constitutes 53.65% (66 cases). The extremities were the most frequently affected site, accounting for 53 cases (43.08%), followed by the head and neck region (29.26%). Based on the WHO classification of skin tumours, there were 42 cases (34.14%) of subcutaneous tissue tumours and 31 cases (25.20%) of soft tissue tumours. The prevalence of keratinocyte tumours is 26 (21.13%), whereas appendageal tumours account for 16 (13%) of cases. Melanocytic and neural tumours are the least prevalent, each representing 4 (3.25%) of cases. The majority of benign tumours arise from the subcutaneous tissues, whereas malignant tumours grow from keratinocytic differentiation. CONCLUSION: Our study revealed that the majority of tumours displayed ambiguous clinical behaviour, which resulted in erroneous diagnoses. Hence confirmation by histopathology is crucial for accurate diagnosis and prompt management.

Seromucinous tumors of ovary: A case series

Seromucinous neoplasms are new category of ovarian epithelial tumor in the 2014 revised World Health Organization classification. Surface epithelial neoplasms are the most common ovarian tumors. Based on the degree of stratification and the presence or absence of invasion, these epithelial proliferations are further divided into benign, borderline, and malignant categories. Benign tumors are divided into three subtypes: cystadenoma (cystic areas), cystadenofibroma (cystic and fibrous areas), and adenofibroma (predominantly fibrous sections). Serous adenofibromas are rare variant of serous surface epithelial tumors. They affect females between the ages of 15 and 65 and make up 1.7% of all benign ovarian tumors. Serous tumor with a solid, fibrous component is designated as serous cystadenofibroma in which both serous and mucinous components are closely intermixed. Seromucinous adenofibroma is a benign cystic neoplasm composed of glands and cysts lined by an admixture of bland mullerian type epithelium which includes ciliated, endocervical type mucinous, and endometroid. They have a characteristic prominent fibromatous hypocellular stroma which helps differentiate it from the commoner cystadenoma. Seromucinous borderline tumors is 10% -20% of all epithelial ovarian tumors. Develops in younger age, usually bilateral in upto 40%, associated with endometriosis. We discuss about four different cases of seromucinous tumor reported in our institute.

Immune Deficiency/Dysregulation Associated Lymphoid Proliferations, EBV+ In Persons Living With HIV.

The 5th edition of the World Health Organization Classification of Hematolymphoid Tumors recently defined immune deficiency/dysregulation (IDD)-associated-lymphoid-proliferations in HIV settings, where information is scarce, often gone under or misdiagnosed. To describe the clinical picture, histopathology, and outcomes of IDD-associated-lymphoidproliferations Epstein-Barr virus+ (EBV) in people living with HIV without organ transplantation, antiretroviral therapy (ART) treated. HIV+ patients diagnosed with IDD-associated-lymphoid-proliferations seen at an academic medical center in Mexico from 2016 to 2019 were included. Immunohistochemical studies, in situ hybridization, and polymerase chain reaction analysis for EBV and LMP1 gene deletions were performed and correlated with clinical data. We included 27 patients, all men who have sex with men, median age 36 years (interquartile range [IQR] 22-54). The median baseline CD4+ T cells were 113/mL (IQR 89-243), the CD4+/CD8+ ratio was 0.15 (IQR: 0.09-0.22), and the HIV viral load was 184,280 copies/mL (IQR: 76,000-515,707). Twenty patients (74.07%) had IDD-associated-lymphoid-proliferations hyperplasia plasma cell type EBV+, 3 (11.1%) had hyperplasia mononucleosis-like type (IM-type), 1 patient (3.70%) had florid follicular hyperplasia, 3 (11.1%) IDD-associated-lymphoid-proliferations polymorphic type, and there were 22 cases (81.4%) of synchronic Kaposi Sarcoma. Two patients were diagnosed with Hodgkin lymphoma following a second positron emission tomography-computed tomography scan-guided biopsy. The median follow-up was 228 weeks (IQR 50-269); 6 patients died (22.2%) of causes unrelated to IDD-associated-lymphoid-proliferations related. IDD-associated-lymphoid-proliferations EBV+ occured in severely immunosuppressed HIV+ patients, a high percentage of whom had concomitant Kaposi sarcoma. The prognosis was good in patients treated only with ART.

T2-FLAIR Mismatch Sign Predicts DNA Methylation Subclass and CDKN2A/B Status in IDH-Mutant Astrocytomas.

DNA methylation profiling stratifies isocitrate dehydrogenase (IDH)-mutant astrocytomas into methylation low- and high-grade groups. We investigated the utility of the T2-fluid-attenuated inversion recovery (T2-FLAIR) mismatch sign for predicting DNA methylation grade and cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) homozygous deletion, a molecular biomarker for grade 4 IDH-mutant astrocytomas, according to the 2021 World Health Organization classification. Preoperative MRI scans of IDH-mutant astrocytomas subclassified by DNA methylation profiling (n = 71) were independently evaluated by two radiologists for the T2-FLAIR mismatch sign. The diagnostic utility of T2-FLAIR mismatch in predicting methylation grade, CDKN2A/B status, copy number variation, and survival was analyzed. The T2-FLAIR mismatch sign was present in 21 of 45 (46.7%) methylation low-grade and 1 of 26 (3.9%) methylation high-grade cases (P < 0.001), resulting in 96.2% specificity, 95.5% positive predictive value, and 51.0% negative predictive value for predicting low methylation grade. The T2-FLAIR mismatch sign was also significantly associated with intact CDKN2A/B status (P = 0.028) with 87.5% specificity, 86.4% positive predictive value, and 42.9% negative predictive value. Overall multivariable Cox analysis showed that retained CDKN2A/B status remained significant for progression-free survival (P = 0.01). Multivariable Cox analysis of the histologic grade 3 subset, which was nearly evenly divided by CDKN2A/B status, copy number variation, and methylation grade, showed trends toward significance for DNA methylation grade with overall survival (P = 0.045) and CDKN2A/B status with progression-free survival (P = 0.052). The T2-FLAIR mismatch sign is highly specific for low methylation grade and intact CDKN2A/B in IDH-mutant astrocytomas.