Secondary rhabdoid tumors (RTs) with atypical teratoid/rhabdoid tumor-like features rarely arise from, or coexist with, pleomorphic xanthoastrocytomas (PXAs), and their clinicopathological and molecular characteristics remain poorly understood. We report a 17-year-old girl with a temporal lobe mass that, upon gross total resection, pathologically contained both RT and PXA components. Immunohistochemistry revealed loss of INI1 expression restricted to the RT component, while the PXA area retained INI1. Next-generation sequencing identified a shared BRAF::TRIM24 fusion and homozygous deletion of CDKN2A/2B in both components, indicating a shared clonal origin. Additionally, a germline ATM frameshift mutation (c.5288_5289insGA) was identified in both tumor components, making the first such report in central nervous system tumors. SMARCB1 loss was confined to the RT component, further supporting the hypotheses of clonal evolution and secondary transformation. Despite gross total resection, craniospinal irradiation, and chemotherapy, the patient developed rapid leptomeningeal dissemination and died 5 months after surgery. This case provides clinicopathological and molecular evidence for clonal evolution and secondary transformation of PXA into an RT. The presence of germline ATM mutation may have therapeutic and biological relevance. Further studies are required to clarify the pathogenesis and optimal management of these rare and aggressive tumors.

This study aimed to determine the prevalence of human epidermal growth factor receptor 2 (HER2)–ultralow breast cancer among cases initially classified as HER2 immunohistochemistry (IHC) 0 and assess interobserver variability in interpreting low-level HER2 expression. Methods: In this multicenter retrospective study, all invasive breast cancer cases diagnosed between January and December 2022 across 10 Korean institutions were retrieved. Institutional pathologists reexamined HER2 IHC slides originally reported as IHC 0 according to the 2018 American Society of Clinical Oncology/College of American Pathologists guidelines and reclassified them as HER2-null (0), HER2-ultralow (0+), or HER2-low (1+). Slides from 10% of HER2-null and HER2-ultralow cases were digitized for central review and independently assessed by two pathologists, with discrepancies resolved by consensus. Results: Among 8,026 cases, 2,836 cases (35.5%) were initially reported as IHC 0. Upon re-review, 1,673 (59.0%), 1,139 (40.2%), and 24 (0.8%) cases were reclassified as HER2-null, HER2-ultralow, and HER2-low, respectively. The prevalence of HER2-ultralow breast cancer varied considerably across institutions (23.7%–78.1%). Central review of 268 digitized cases showed concordance in 193 cases (72.0%). Among the 75 discordant cases, 54 tumors (72.0%) were upgraded from HER2-null to HER2-ultralow, and 18 (24.0%) tumors were upgraded from HER2-ultralow to HER2-low. Furthermore, two tumors (2.7%) were downgraded from HER2-ultralow to HER2-null. Conclusions: Approximately 40% of cases initially categorized as IHC 0 were reclassified as HER2-ultralow. The substantial inter-institutional variability observed in interpreting low-level HER2 expression highlights the need for standardized training and quality assurance to ensure accurate identification of patients eligible for HER2-targeted antibody–drug conjugates.

In forensic medicine, age estimation commonly involves assessing age-related changes in teeth and skeletal structures. Vertebral morphological alterations, such as osteophyte formation, serve as age indicators. Recent studies using deep-learning techniques, such as neural networks, for age estimation from radiographic images have been conducted, reporting significantly higher accuracy than previous studies. This study aimed to estimate age using neural network-based deep-learning techniques applied to computed tomography (CT) cross-sectional images of the spine and evaluate its feasibility. Postmortem CT scans of 214 cadavers with varying decomposition levels were used. Coronal and sagittal cross-sectional images penetrating the center of each vertebral body were extracted for the 11th and 12th thoracic vertebrae and the first to fifth lumbar vertebrae. Using these images, along with the chronological ages of deceased individuals, an age estimation model was developed through regression analysis in PyTorch, employing a convolutional neural networks architecture with five-fold cross-validation. The model achieved a mean absolute error of 5.385 years, root mean squared error of 7.029 years, and coefficient of determination of 0.793. Although the sample size was relatively small, the results suggested the potential applicability of vertebral imagingbased age estimation in the Korean population. Further research using a larger dataset may improve the accuracy and reliability of the model.

α-Melanocyte-stimulating hormone (α-MSH) is a key physiological inducer of melanogenesis and melanocyte activation. Reactive oxygen species (ROS) function as secondary messengers in intracellular signaling pathways that regulate α-MSH-mediated melanogenesis. However, the mechanism by which α-MSH induces ROS generation in melanocytes remains incompletely understood. Here, we investigated the sources and regulatory mechanisms of α-MSH-induced ROS in murine B16F10 and human MNT-1 melanoma cells. Confocal microscopy revealed that α-MSH predominantly stimulated cytosolic rather than mitochondrial ROS generation. Western blot analysis showed that α-MSH upregulated the expression of NADPH oxidases NOX1 and NOX4 at early time points, key enzymes involved in cytosolic ROS production. Pharmacological inhibition of NOX1/4 significantly reduced α-MSH-induced ROS levels and melanin content, accompanied by decreased phosphorylation of MITF, a melanogenic transcription factor. These findings indicate that α-MSH is a key physiological inducer of melanogenesis and melanocyte-related signaling in melanoma cells. Our study highlights NOX4, together with NOX1, as potential targets for anti-pigmentation strategies.

Purpose: The triggering receptor expressed on myeloid cells 2 (TREM2) creates an immunosuppressive environment, but the effects of anticancer treatment on TREM2 and the tumor microenvironment (TME) are not well established. This study investigates the impact of chemotherapy on TREM2-expressing macrophages within the lung adenocarcinoma TME. Materials and Methods: Using single-cell RNA sequencing datasets of paired normal-appearing lung tissue (NL) and tumor (Tu), human and mouse lung cancer tissue, and THP-1 cells, we observed the effects of anticancer drugs on them. Results: Myeloid cells (MY) were the second-most abundant non-epithelial component in the Tu, though less prevalent than in NL. Specific MY subclusters abundant in Tu showed overexpression of TREM2. In lung cancer-induced Kras-G12D mice, M2 proportion increased in Tu compared to NL; cisplatin increased TREM2+ M2 proportion in Tu. TREM2+ cells in Tu showed interactions with cell clusters showing characteristics of interstitial macrophage such as mo-lineage, mono-Mc, and CD163/LGMN cells via FN:CD44 and MIF:CD74+CXCR4, suggesting that they influence the recruitment of those cells to Tu and TME reshape. In M0-state THP-1 cells, cisplatin and osimertinib treatments induced polarization towards M1 and M2 states and increased TREM2 expression. Cisplatin promoted uptake of phosphatidylserine-coated latex beads by M0 cells, whereas osimertinib reduced uptake by polarized macrophages. These findings suggest anticancer treatments impact the lung immune microenvironment by altering the TREM2+ cells. Conclusion Given TREM2’s central inhibitory role in the tumor immune environment, effects of chemotherapeutic agents should be considered in developing TREM2-targeting therapies.

Purpose: Malignant hepatocellular neoplasm, not otherwise specified (HCN-NOS) is a provisional diagnostic entity, characterised by intermediate or a combination of hepatoblastoma and pediatric hepatocellular carcinoma (p-HCC) features. We compared the characteristics of HCN-NOS with hepatoblastoma and p-HCC. Materials and Methods: The records of 148 pediatric patients diagnosed with hepatocellular malignancy after resection were retrieved from the institutional database. Clinical parameters and histopathology slides were reviewed to re-establish each patient’s diagnosis. Molecular analyses were conducted in 37 patients. Results: Patients were profiled as 21 (14.2%) with HCN-NOS, 109 (73.6%) with hepatoblastoma, and 18 (12.2%) with p-HCC. The median age was 8.6 years in HCN-NOS, 1.2 years in hepatoblastoma, and 7.9 years in p-HCC. Background liver disease was frequently observed in p-HCC (11/18, 61%) but infrequent in HCN-NOS (4/21, 19%) and hepatoblastoma (4/109, 3.7%). HCN-NOS presented with a more advanced PRETEXT stage (p=0.012), metastasis (p < 0.001), and lymphovascular invasion (p < 0.001) than hepatoblastoma and p-HCC. Patients with HCN-NOS received longer cycles of preoperative chemotherapy; however, they reported a lower decrease in serum alpha-fetoprotein and tumor size than hepatoblastoma (p=0.043, p=0.004, and p=0.044, respectively). HCN-NOS was an independent poor prognostic factor for event-free survival (hazard ratio, 4.968; 95% confidence interval, 2.004 to 12.32; p < 0.001). Conclusion The possibility of HCN-NOS should be considered in pediatric patients with liver cancer, especially those ≥ 5 years old with no background liver disease. Because HCN-NOS exhibits poor chemoresponsiveness and unfavourable postoperative prognosis, liver transplantation should be strongly considered.

Purpose: The aim of this study is to compare the detection ability of quality of life (QoL) changes and responsiveness of the KOrean QUality of life in Stomach cancer patients Study group (KOQUSS)-40 and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ). Materials and Methods: A multicenter prospective observational study was conducted to evaluate QoL changes after various gastrectomies between January 2021 and April 2022. Participants were instructed to complete the KOQUSS-40 and EORTC QLQ-C30/STO22 preoperatively and at 1, 3, 6, and 12 months postoperatively. QoL changes over time and QoL responsiveness were assessed for each questionnaire. Results: Data from 491 patients who underwent curative gastrectomy for gastric cancer at 22 institutions were analyzed. The summary scores of the KOQUSS-40 and EORTC QLQ-STO22 showed significant differences between the total and proximal gastrectomy groups (p=0.044 and p=0.038, respectively), but no difference was observed for the EORTC QLQ-C30. Dysphagia on the KOQUSS-40 was significantly different between the total and proximal gastrectomy groups (p=0.031); however, dysphagia on the EORTC QLQ-STO22 did not differ. The responsiveness of the KOQUSS-40 was similar to that of the EORTC QLQ in patients who experienced ≥ 10% body weight loss, but approximately 10% less in patients receiving adjuvant chemotherapy than the EORTC QLQ. Conclusion KOQUSS-40 has several advantages over EORTC QLQ-C30/STO22 when comparing QoL between the total and proximal gastrectomy groups. The findings provide information for researchers investigating the QoL of patients who have undergone curative gastrectomy for gastric cancer.

Purpose: The male predominance in the incidence of gastric cancer (GC) is established; however, sex differences in the prognosis of GC remain controversial. As such, this study analyzed the prognosis of patients with GC based on age and sex. Materials and Methods: Data from 14,739 patients diagnosed with GC at Seoul National University Bundang Hospital between 2003 and 2023 were analyzed. Baseline characteristics, histological types of GC, overall and GC-specific survival rates (age and stage stratification), and associated risk factors were analyzed. Results: Females were significantly younger (p < 0.001) and exhibited more gastric body cancers (p < 0.001) and tumors with diffuse-type or poorly differentiated histology (p < 0.001) than males. Females exhibited an advantage over males in terms of overall survival (p=0.004), but not in GC-specific survival. However, age stratification revealed significant sex differences, that females < 50 years of age exhibited survival disadvantages (p < 0.001); however, this trend was reversed with age, and females > 60 years exhibited survival advantages (p < 0.001) for both overall and GC-specific survival. This may be explained by the lower ratio of diffuse-type GC as females age. Furthermore, in the analysis according to stage, females with stage IV disease exhibited significant survival disadvantages, with significantly younger age and a higher proportion of diffuse-type GC which exhibits aggressive features, resulting in poorer survival than in males. Conclusion Age and stage stratification revealed significant differences in survival between the sexes, which can be helpful for public health strategies.

Purpose: This study compared healthy lifestyle (HLS) practices and awareness regarding the use of chatbots (A-uC) for health management between childhood and adolescent cancer survivors (CACSs) and their parents, with the aim of assessing the feasibility of tailored artificial intelligence (AI) chatbot-based interventions for holistic survivorship care. Methods: A descriptive comparative design was employed involving 80 CACSs and 80 parents (N=160) recruited through the Korean Pediatric Cancer Foundation. HLS practices were assessed using a validated seven-domain instrument encompassing physical activity, nutrition, interpersonal relations, stress management, positive life perspective, health responsibility, and spiritual health. A-uC was evaluated using an extended technology acceptance model-based tool. Responses to the open-ended question addressing unmet HLS practices were analyzed using latent Dirichlet allocation topic modeling. Results: No significant differences were observed between CACSs and parents in overall HLS (CACSs: 3.16±0.80; parents: 3.18±0.36, p=.74). While perceptions across most A-uC domains did not differ significantly, parents demonstrated a significantly higher “intention to use” chatbots for health management than CACSs (p=.03). The mean A-uC scores exceeded 4 (out of 5) in both groups, reflecting positive perceptions of chatbot-based HLS support. Topic modeling identified “exercise,” “healthy diet,” and “regular lifestyle” as common unmet areas. Conclusion CACSs and their parents share largely concordant views on HLS and A-uC, with a strong interest in chatbot interventions. These findings underscore the potential of tailored AI chatbot programs to address unmet lifestyle needs and promote holistic survivorship care.

Background: Asthma remission has recently emerged as an aspirational treatment goal, yet its definition remains inconsistent across studies and expert groups. The absence of a standardized framework hampers its application in clinical practice and research, particularly in Korea where biologics use is rapidly increasing. This study aimed to establish a consensus definition of clinical remission in severe asthma among Korean experts. Methods: A two-round modified Delphi survey, followed by a focused third round, was conducted among 28 board-certified pulmonologists from the Korean Academy of Tuberculosis and Respiratory Diseases (KATRD). The questionnaire consisted of six domains and 27 items. Responses were analyzed using agreement rates, interquartile ranges, and content validity ratios to determine consensus levels. Results: Consensus was reached on defining clinical remission as a composite of no exacerbations, no systemic corticosteroid use, sustained symptom control (Asthma Control Test ≥20 on at least three occasions over 12 months), and stabilization and optimization of pulmonary function while on maintenance treatment. Experts agreed that pulmonary function should be assessed based on clinical judgment rather than absolute thresholds. Complete remission was additionally defined as fulfilling all clinical remission criteria with normalization of type 2 inflammation (blood eosinophils <300/μL and fractional exhaled nitric oxide <25 ppb). Conclusion This Delphi consensus provides a regionally relevant and pragmatic framework for defining remission in severe asthma. These statements may help guide clinical practice, inform guideline development, and support future research on remission as a treatment goal.