Identification of the novel HLA-DPB1*1591:01 allele by next-generation sequencing.

The novel HLA-DPB1*1591:01 allele was detected during the HLA typing for kidney transplantation.

Age-Related Differences in Neutralizing Antibody Responses against SARS-CoV-2 Delta and Omicron Variants in 151 SARS-CoV-2-Naïve Metropolitan Residents Boosted with BNT162b2.

BACKGROUND: Although age negatively correlates with vaccine-induced immune responses, whether the vaccine-induced neutralizing effect against variants of concern (VOCs) substantially differs across age remains relatively poorly explored. In addition, the utility of commercial binding assays developed with the wild-type SARS-CoV-2 for predicting the neutralizing effect against VOCs should be revalidated. METHODS: We analyzed 151 triple-vaccinated SARS-CoV-2-naïve individuals boosted with BNT162b2 (Pfizer-BioNTech). The study population was divided into young adults (age < 30), middle-aged adults (30 ≤ age < 60), and older adults (age ≥ 60). The plaque reduction neutralization test (PRNT) titers against Delta (B.1.617.2) and Omicron (B.1.1.529) variants were compared across age. Antibody titers measured with commercial binding assays were compared with PRNT titers. RESULTS: Age-related decline in neutralizing titers was observed for both Delta and Omicron variants. Neutralizing titers for Omicron were lower than those against Delta in all ages. The multiple linear regression model demonstrated that duration from third dose to sample collection and vaccine types were also significant factors affecting vaccine-induced immunity along with age. The correlation between commercial binding assays and PRNT was acceptable for all age groups with the Delta variant, but relatively poor for middle-aged and older adults with the Omicron variant due to low titers. CONCLUSIONS: This study provides insights into the age-related dynamics of vaccine-induced immunity against SARS-CoV-2 VOCs, corroborating the need for age-specific vaccination strategies in the endemic era where new variants continue to evolve. Moreover, commercial binding assays should be used cautiously when estimating neutralizing titers against VOCs, particularly Omicron.

Identification of the novel HLA-DQA1*01:138 allele by next-generation sequencing.

HLA-DQA1*01:138 is identical to HLA-DQA1*01:03 except for a single nucleotide substitution in exon 3.

Differences in the Clinical and Molecular Profiles of Subungual Melanoma and Acral Melanoma in Asian Patients.

Subungual melanoma (SUM) is a rare type of malignant melanoma that arises beneath the nails. SUM is categorized as a type of acral melanoma (AM), which occurs on the hands and feet. SUM is an aggressive type of cutaneous melanoma that is most common among Asian patients. Recent studies reveal that SUM and AM might have different molecular characteristics. Treatment of melanoma relies on analysis of both clinical and molecular data. Therefore, the clinical and molecular characteristics of SUM need to be established, especially during metastasis. To define the mutation profiles of SUM and compare them with those of AM, we performed next-generation sequencing of primary and metastatic tumors of SUM and AM patients. Subungual location was a better independent prognostic factor than acral location for better overall survival (p = 0.001). Patients with SUM most commonly had the triple wild-type (75%) driven by GNAQ (58%) and KIT (25%) mutations, whereas patients with AM had BRAF (28.6%) and RAF (14.3%) molecular types of mutations. Single-nucleotide variations (SNVs) were more common in SUM than in AM, whereas copy number alterations (CNAs) were more common metastatic lesions of AM. Metastatic tumors in patients with SUM and AM showed increases in CNAs (43% and 80%, respectively), but not in SNVs. The number of CNAs increased during metastasis. When compared with AM, SUM has distinct clinical and molecular characteristics.

Effect of Two Cystatin C Reagents and Four Equations on Glomerular Filtration Rate Estimations After Standardization.

Background: Serum cystatin C (cysC), which is less affected by sex, race, and muscle mass than creatinine, is a useful biomarker of the estimated glomerular filtration rate (eGFR). The standardization of cysC measurements remains controversial, although a certified reference material (ERM-DA471/IFCC) is available. Moreover, the effect of combinations of cysC reagents and equations for eGFR is unclear. Methods: We conducted a simulation analysis of cysC measured using two reagents standardized against ERM-DA471/IFCC-Gentian cystatin C immunoassay (Gentiancys; GentianAS, Moss, Norway) and Roche Tina-quant Cystatin C Gen.2 (Rochecys; Roche, Mannheim, Germany)-on a Cobas c702 system (Roche) and eGFR generated by eight combinations of four equations: 2012 cystatin C-based Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPIcys); the Caucasian, Asian, pediatric, and adult equation (CAPAeq); full age spectrum equation (FASeq); and 2023 cystatin C-based European Kidney Function Consortium equation (EKFCcys). Results: A total of 148 participants (mean age, 60.5±14.5 years; 43% female) were enrolled. The mean cysC was 1.72±1.44 mg/L for Gentiancys and 1.71±1.35 mg/L for Rochecys. Regression analysis showed concordance between the reagents within 0.85-4.40 mg/L when using ±7.61% total allowable error. Lin's concordance correlation coefficient of eGFR, by combining the measuring system and equation, varied from 0.73 to 1.00. Conclusions: The equivalence of cysC values at low concentrations (<0.85 mg/L) between the two reagents was unsatisfactory. Results obtained with different measurement systems could lead to larger differences in eGFR varying with the combination.

Multi-Scale Hybrid Vision Transformer for Learning Gastric Histology: AI-Based Decision Support System for Gastric Cancer Treatment.

Gastric endoscopic screening is an effective way to decide appropriate gastric cancer treatment at an early stage, reducing gastric cancer-associated mortality rate. Although artificial intelligence has brought a great promise to assist pathologist to screen digitalized endoscopic biopsies, existing artificial intelligence systems are limited to be utilized in planning gastric cancer treatment. We propose a practical artificial intelligence-based decision support system that enables five subclassifications of gastric cancer pathology, which can be directly matched to general gastric cancer treatment guidance. The proposed framework is designed to efficiently differentiate multi-classes of gastric cancer through multiscale self-attention mechanism using 2-stage hybrid vision transformer networks, by mimicking the way how human pathologists understand histology. The proposed system demonstrates its reliable diagnostic performance by achieving class-average sensitivity of above 0.85 for multicentric cohort tests. Moreover, the proposed system demonstrates its great generalization capability on gastrointestinal track organ cancer by achieving the best class-average sensitivity among contemporary networks. Furthermore, in the observational study, artificial intelligence-assisted pathologists show significantly improved diagnostic sensitivity within saved screening time compared to human pathologists. Our results demonstrate that the proposed artificial intelligence system has a great potential for providing presumptive pathologic opinion and supporting decision of appropriate gastric cancer treatment in practical clinical settings.

Targeting the Sequences of Circulating Tumor DNA of Cholangiocarcinomas and Its Applications and Limitations in Clinical Practice.

Cholangiocarcinoma is a malignant epithelial tumor arising from bile ducts that is frequently fatal. Diagnosis is difficult due to tumor location in the biliary tract. Earlier diagnosis requires less invasive methods of identifying effective biomarkers for cholangiocarcinoma. The present study investigated the genomic profiles of cell-free DNA (cfDNA) and DNA from corresponding primary cholangiocarcinomas using a targeted sequencing panel. Somatic mutations in primary tumor DNA and circulating tumor DNA (ctDNA) were compared and clinical applications of ctDNA validated in patients with cholangiocarcinoma. A comparison of primary tumor DNA and ctDNA identified somatic mutations in patients with early cholangiocarcinomas that showed clinical feasibility for early screening. The predictive value of single-nucleotide variants (SNVs) of preoperative plasma cfDNA positive for somatic mutations of the primary tumor was 42%. The sensitivity and specificity of postoperative plasma SNVs in detecting clinical recurrence were 44% and 45%, respectively. Targetable fibroblast growth factor receptor 2 (FGFR2) and Kirsten rat sarcoma virus (KRAS) mutations were detected in 5% of ctDNA samples from patients with cholangiocarcinoma. These findings showed that genomic profiling of cfDNA was useful in clinical evaluation, although ctDNA had limited ability to detect mutations in cholangiocarcinoma patients. Serial monitoring of ctDNA is important clinically and in assessing real-time molecular aberrations in cholangiocarcinoma patients.

Evaluation of the Kaira COVID-19/Flu/RSV Detection Kit for detection of SARS-CoV-2, influenza A/B, and respiratory syncytial virus: A comparative study with the PowerChek SARS-CoV-2, influenza A&B, RSV Multiplex Real-time PCR Kit.

BACKGROUND: Co-circulation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory viruses, such as influenza and respiratory syncytial virus (RSV), can be a severe threat to public health. The accurate detection and differentiation of these viruses are essential for clinical laboratories. Herein, we comparatively evaluated the performance of the Kaira COVID-19/Flu/RSV Detection Kit (Kaira; Optolane, Seongnam, Korea) for detection of SARS-CoV-2, influenza A and B, and RSV in nasopharyngeal swab (NPS) specimens with that of the PowerChek SARS-CoV-2, Influenza A&B, RSV Multiplex Real-time PCR Kit (PowerChek; Kogene Biotech, Seoul, Korea). METHODS: A total of 250 archived NPS specimens collected for routine clinical testing were tested in parallel by the Kaira and PowerChek assays. RNA standards were serially diluted and tested by the Kaira assay to calculate the limit of detection (LOD). RESULTS: The positive and negative percent agreements between the Kaira and PowerChek assays were as follows: 100% (49/49) and 100% (201/201) for SARS-CoV-2; 100% (50/50) and 99.0% (198/200) for influenza A; 100% (50/50) and 100% (200/200) for influenza B; and 100% (51/51) and 100% (199/199) for RSV, respectively. The LODs of the Kaira assay for SARS-CoV-2, influenza A and B, and RSV were 106.1, 717.1, 287.3, and 442.9 copies/mL, respectively. CONCLUSIONS: The Kaira assay showed comparable performance to the PowerChek assay for detection of SARS-CoV-2, influenza A and B, and RSV in NPS specimens, indicating that the Kaira assay could be a useful diagnostic tool when these viruses are co-circulating.

Patterns of Extrathoracic Metastasis in Lung Cancer Patients.

Metastasis is a major cause of death in lung cancer patients. Therefore, a deeper understanding of the metastatic mechanisms is important for developing better management strategies for lung cancer patients. This study evaluated the patterns of extrathoracic metastases in lung cancer. We retrieved data for 25,103 lung cancer patients from an institutional database and then evaluated the impacts of clinicopathologic factors on metastasis patterns. We found that 36.5% of patients had extrathoracic metastasis. Younger patients had a significantly higher extrathoracic metastasis rate in most histologic subtypes. Metastases to the bone (58.3%), central nervous system (CNS) (44.3%), liver (26.6%) and adrenal gland (18.3%) accounted for 85.5% of all extrathoracic metastases. Patients with nonmucinous adenocarcinoma had significantly higher bone metastasis rate. Patients with small cell carcinoma and large cell neuroendocrine carcinoma (LCNEC) had significantly higher liver metastasis rates. Further, patients with LCNEC also had a significantly lower bone metastasis rate, and patients with squamous cell carcinoma had a significantly lower CNS metastasis rate. Patients with multiple cancers had similar patterns of metastasis compared to patients with only lung cancer. In conclusion, different histologic subtypes of lung cancer have different metastatic patterns. Our study might help clinicians decide on follow-up strategies.

Cytopathologic features of human papillomavirus-independent, gastric-type endocervical adenocarcinoma.

BACKGROUND: Gastric-type endocervical adenocarcinoma (GEA) is unrelated to human papillomavirus (HPV) infection and is clinically aggressive compared with HPV-associated usual-type endocervical adenocarcinoma (UEA). The cytological diagnosis falls short of a definitive diagnosis of GEA and is often categorized as atypical glandular cells (AGCs). To improve cytologic recognition, cytological findings of HPV-independent GEA were analyzed and the results compared with HPV-associated UEA. METHODS: Cervical Papanicolaou (Pap) smears from eight patients with a histopathologic diagnosis of GEA and 12 control cases of UEA were reviewed. All slides were conventionally prepared and/or liquid-based prepared (ThinPrep) and stained following the Pap method. A mucinous background, architectural, nuclear, and cytoplasmic features were analyzed and compared with UEA. RESULTS: Preoperative cytologic diagnoses of the eight GEA cases were AGCs, favor neoplastic in three cases, adenocarcinoma in situ in one case, and adenocarcinoma in four cases. Cytologically, monolayered honeycomb-like sheets (p = .002) of atypical endocervical cells with vacuolar granular cytoplasm (p = .001) were extensive in GEA, and three-dimensional clusters (p = .010) were extensive in UEA. Although the differences were not statistically significant, background mucin (p = .058), vesicular nuclei (p = .057), and golden-brown intracytoplasmic mucin (p = .089) were also discriminatory findings for GEA versus UEA. CONCLUSIONS: Although GEA is difficult to diagnose on cytologic screening, GEA can be recognized based on cytologic features of monolayered honeycomb sheets of atypical endocervical cells with abundant vacuolar cytoplasm and some golden-brown intracytoplasmic mucin. UEA cases are characterized by three-dimensional clusters.

Assessing Resection Margin Status in Breast-conserving Surgery Specimens: Comparison Among Gross Evaluation, Frozen Section Analysis, and Permanent Section Diagnosis in 725 Patients With Breast Cancer.

BACKGROUND/AIM: An accurate evaluation of resection margin (RM) is critical in breast-conserving surgery (BCS) as negative RM status is critical for successful local control. We compared gross and microscopic methods for RM evaluation and analyzed their concordances. PATIENTS AND METHODS: Gross evaluation (GE), frozen section analysis (FSA), and permanent section diagnosis (PSD) were compared for specimens from 725 breast cancer patients. RESULTS: The RM was grossly involved in 74 cases (10.2%). The sensitivity and specificity of GE were 22.9% and 96.1%, respectively. FSA revealed positive RM in 290 cases (40.0%), with high sensitivity (86.7%) and specificity (83.1%). With PSD, 240 cases (33.1%) showed RM involvement. Discordant results between gross and microscopic methods were observed in 104 cases (14.3%). CONCLUSION: Our observations of the low sensitivity of GE, high discordance rate between gross and microscopic methods, and high sensitivity and specificity of FSA support the necessity of intraoperative FSA for assessing RM status during BCS.

Cosuppression of NF-κB and AICDA Overcomes Acquired EGFR-TKI Resistance in Non-Small Cell Lung Cancer.

BACKGROUND: Acquired resistance after EGFR-tyrosine kinase inhibitor (TKI) treatment is the rule rather than the exception. Overcoming resistance to EGFR-TKIs is essential if we are to develop better therapeutic strategies for lung cancer patients. Here, we examine the effector signaling pathways underlying TKI resistance and propose targets to overcome the resistance of lung adenocarcinoma (LAC) to TKI. METHODS: We compared the expression of NF-κB, AICDA, Akt, IL-6, Jak2, and Stat3 by EGFR-TKI-resistant and EGFR-TKI-sensitive LAC cell lines, and by LAC patients treated with EGFR-TKIs; we then evaluated links between expression and treatment responses. We also examined the therapeutic effects of NF-κB and AICDA inhibition in EGFR-TKI-resistant LACs. RESULTS: NF-κB and AICDA were more expressed by EGFR-TKI-resistant LACs than by EGFR-TKI-sensitive LACs. EGFR-TKIs induced a dose-dependent increase in the expression of NF-κB, AICDA, and IL-6. Inhibition of NF-κB suppressed the expression of AICDA, Akt, and IL-6 in EGFR-TKI-resistant and EGFR-TKI-sensitive LACs, whereas knockdown of AICDA suppressed the expression of NF-κB and Akt in both cell types. Treating EGFR-TKI-resistant LACs with an EGFR-TKI, alongside cosuppression of NF-κB and AICDA, had a significant therapeutic effect. CONCLUSION: Treatment with an EGFR-TKI plus cosuppression of NF-κB and AICDA may be a promising strategy to overcome EGFR-TKI resistance in LACs.

Characterization of Poorly Cohesive and Signet Ring Cell Carcinomas and Identification of PTPRM as a Diagnostic Marker.

Background and aims. Signet ring cell (SRC) and poorly cohesive (PC) gastric carcinomas are morphologically similar but exhibit different biological behavior. We compared the clinical and molecular characteristics of SRC and PC carcinomas. Methods. Diffuse-type gastric cancer (GC) cases were classified into SRC carcinomas (>90% of SRCs), PC carcinomas (<10% of SRCs), and combined PC/SRC carcinomas (≤90% but ≥10% of SRCs). The gene expression patterns in SRC and PC carcinomas were examined by transcriptome and protein immunohistochemistry analyses, and diagnostic and prognostic biomarkers were identified. Results. SRC and PC carcinomas showed significantly different clinical behaviors but shared common RNA expression patterns. PC carcinomas showed an increased expression of genes related to cancer progression. Among genes differentially expressed between PC and SRC carcinomas, protein tyrosine phosphatase receptor type M (PTPRM) was overexpressed in PC and related to unfavorable clinical factors. Conclusion. We found that PC and SRC carcinomas had distinct clinical characteristics and should be classified as different carcinoma types. PTPRM was identified as a potential diagnostic and prognostic biomarker for PC carcinomas and could represent a potential therapeutic target.

Mesonephric-like Adenocarcinoma of the Uterine Corpus: Comprehensive Immunohistochemical Analyses Using Markers for Mesonephric, Endometrioid and Serous Tumors.

Mesonephric-like adenocarcinoma (MLA) of the uterine corpus is a rare but distinct malignant tumor of the female genital tract, demonstrating a characteristic morphology and unique immunohistochemical profiles and molecular alterations. We conducted immunohistochemical staining (IHC) to make precise differential diagnoses of uterine MLAs from common histological subtypes of endometrial carcinomas. We collected 25 uterine MLAs and performed IHC for GATA3, TTF1, CD10, ER, PR, p16, p53, and HER2. Seventeen cases (68.0%) showed at least moderate nuclear GATA3 immunoreactivity in ≥25% of tumor cells. Most cases expressed TTF1 (17/21, 81.0%) and CD10 (luminal; 17/21, 81.0%). Heterogeneous TTF1 expression was noted in 12 cases. An inverse pattern of GATA3 and TTF1 staining was observed in eight cases (32.0%). Three cases (12.0%) showed moderate-to-strong ER expression in ≥25% of tumor cells, and two cases (8.0%) showed moderate-to-strong PR expression in ≥5% of tumor cells. These hormone receptor-positive MLAs varied in intensity and proportion of GATA3 staining. None of the 25 cases exhibited either diffuse and strong p16 expression or aberrant p53 expression. Five cases (20.0%) showed equivocal HER2 immunoreactivity (score 2+), but HER2 FISH confirmed that none of them exhibited HER2 gene amplification. In summary, a small subset of uterine MLAs displayed atypical IHC results: focal but strong expression of ER or PR, the complete absence of GATA3 immunoreactivity, the concurrent expression of mesonephric and hormone receptors, and the inverse pattern of GATA3 and TTF1 staining. These unusual immunophenotypes may complicate the differential diagnosis of MLA. Moreover, pathologists should be encouraged to interpret the IHC results cautiously.

Age-adjusted quick Sequential Organ Failure Assessment score for predicting mortality and disease severity in children with infection: a systematic review and meta-analysis.

We assessed the diagnostic accuracy of the age-adjusted quick Sequential Organ Failure Assessment score (qSOFA) for predicting mortality and disease severity in pediatric patients with suspected or confirmed infection. We conducted a systematic search of PubMed, EMBASE, the Cochrane Library, and Web of Science. Eleven studies with a total of 172,569 patients were included in the meta-analysis. The pooled sensitivity, specificity, and diagnostic odds ratio of the age-adjusted qSOFA for predicting mortality and disease severity were 0.69 (95% confidence interval [CI] 0.53-0.81), 0.71 (95% CI 0.36-0.91), and 6.57 (95% CI 4.46-9.67), respectively. The area under the summary receiver-operating characteristic curve was 0.733. The pooled sensitivity and specificity for predicting mortality were 0.73 (95% CI 0.66-0.79) and 0.63 (95% CI 0.21-0.92), respectively. The pooled sensitivity and specificity for predicting disease severity were 0.73 (95% CI 0.21-0.97) and 0.72 (95% CI 0.11-0.98), respectively. The performance of the age-adjusted qSOFA for predicting mortality and disease severity was better in emergency department patients than in intensive care unit patients. The age-adjusted qSOFA has moderate predictive power and can help in rapidly identifying at-risk children, but its utility may be limited by its insufficient sensitivity.

Ovarian Mesonephric-like Adenocarcinoma With Multifocal Microscopic Involvement of the Fimbrial Surface: Potential for Misdiagnosis of Tubal Intraepithelial Metastasis as Serous Tubal Intraepithelial Carcinoma Associated With Ovarian High-grade Serous Carcinoma.

BACKGROUND/AIM: We describe a rare case of ovarian mesonephric-like adenocarcinoma (MLA) involving the fimbria and mimicking serous tubal intraepithelial carcinoma (STIC). CASE REPORT: A 47-year-old woman presented with a 4.4-cm left ovarian mass. Histologically, the ovarian tumor showed papillary and solid architecture, severe nuclear pleomorphism, and increased mitotic activity. Some microscopic foci where the tumor cells spread horizontally along the fimbrial surface epithelium were noted, compatible with STIC. We initially considered the ovarian tumor to be high-grade serous carcinoma accompanied by a fimbrial STIC. However, immunostaining revealed nuclear immunoreactivity for paired box 2 and GATA-binding protein 3, but lacked expression of Wilms tumor 1. A thorough slide review and additional immunostaining revealed architectural diversity, densely eosinophilic intraluminal secretions, and lack of hormone receptor expression, supporting the diagnosis of MLA. CONCLUSION: Microscopic intraepithelial metastases of the MLA to the fimbria mimic STIC. We recommend ancillary tests, such as immunostaining, in patients with ovarian tumors whenever possible, particularly for those with differential diagnosis of MLA and high-grade serous carcinoma.

Mesonephric-like Differentiation of Ovarian Endometrioid and High-grade Serous Carcinomas: Clinicopathological and Molecular Characteristics Distinct from Those of Mesonephric-like Adenocarcinoma.

BACKGROUND/AIM: Ovarian endometrioid carcinoma (EC) and high-grade serous carcinoma (HGSC) may exhibit various growth patterns and mimic mesonephric-like adenocarcinoma (MLA). We investigated the clinicopathological and molecular features of ovarian carcinomas with mesonephric-like differentiation (MLD). PATIENTS AND METHODS: We analyzed the electronic medical records and pathology slides of two EC-MLD and three HGSC-MLD patients, and conducted immunostaining and targeted sequencing of their samples. RESULTS: All cases showed architectural diversity, compactly aggregated small tubules and ducts, and eosinophilic intraluminal secretions, indicating the possibility of an ovarian MLA. However, the following histological and immunophenotypical features confirmed the diagnoses of EC-MLD and HGSC-MLD: squamous, tubal, and sertoliform differentiation; serous tubal intraepithelial carcinoma; solid, endometrioid, transitional (SET) feature; solid, transitional, endometrioid, mucinous-like (STEM) feature; diffuse expression of hormone receptors and Wilms tumor 1; mutant p53 immunostaining pattern; and wild-type v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog gene. CONCLUSION: A subset of ovarian ECs and HGSCs can display MLD and mimic an MLA. A thorough histological examination combined with ancillary tests is crucial to differentiate between these ovarian neoplastic entities.

Clinicopathologic and Molecular Characteristics of Gastrointestinal MiNENs.

BACKGROUND: A mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) is a recently defined entity that comprises a neuroendocrine tumor (NEN) component and a non-neuroendocrine tumor (nNEN) component. As MiNEN is a recently defined entity, its molecular nature is not well known. Here, we evaluated the clinicopathologic and molecular characteristics of gastrointestinal (GI) MiNENs. METHODS: We performed a genomic analysis of 31 samples from 12 GI MiNEN cases using next-generation sequencing. We examined the primary NEN and nNEN components, as well as the metastatic NENs and nNENs. The relationships between the clinical tumor features (component, location, and grade) and their molecular characteristics were examined. RESULTS: The 12 MiNENs included in the study were found in the stomach (n=10), distal rectum (n=1), and anus (n=1). Primary MiNENs that had NENs as the major component showed a worse clinical outcome than those that had nNENs as the major component. All distant metastatic tumors originating from MiNENs were NENs. In addition, NENs generally carried 1.5 times more gene mutations and copy number variations than nNENs. The ATRX gene deletion and TP53 gene mutation were the most common variants in both components of GI MiNENs. CONCLUSIONS: We have revealed the detailed clinicopathologic and molecular findings with distinguishable alterations of GI MiNENs. To our knowledge, this is the first study to report the ATRX gene deletion in GI MiNENs. The molecular characteristics of GI MiNENs could provide clues to the pathogenic origin and progression of GI MiNENs.

Mesonephric-like Differentiation of Endometrial Endometrioid Carcinoma: Clinicopathological and Molecular Characteristics Distinct from Those of Uterine Mesonephric-like Adenocarcinoma.

When diagnosing endometrial carcinoma cases, we encountered histological features that strikingly resembled uterine mesonephric-like adenocarcinoma (MLA), but the differential diagnosis remained challenging after performing immunostaining. Considering the aggressive biological behavior and poor prognosis of uterine MLA, we believe that the accurate recognition of mesonephric-like differentiation (MLD) is important in the diagnosis of endometrial carcinoma. We aimed to investigate the clinicopathological and molecular characteristics of such cases and compared them with those of uterine MLAs. Five patients diagnosed with endometrioid carcinoma (EC) with MLD were included in this study. Histological evaluation, immunostaining, and targeted sequencing were performed. All five tumors showed typical morphological features of MLA, including densely aggregated tubular structures, deep basophilia under low-power magnification microscopy, eosinophilic intraluminal secretions, and diverse growth patterns. Immunostaining revealed moderate-to-strong nuclear immunoreactivity for estrogen and progesterone receptors in more than 50% tumor cells. The staining intensities and proportions of PAX2 and GATA3 were variable. None of the tumors harbored KRAS mutations. Considering the prognostic implications, ancillary tests, including immunostaining and targeted sequencing, should be performed to accurately differentiate between endometrial EC-MLD and uterine MLA.