1.Multicenter evaluation of the PASS score as a negative predictive tool and the impact of inter-observer variability in pheochromocytoma and paraganglioma risk stratification
Sungyeon JUNG ; Hye-Ri SHIN ; Su-Jin SHIN ; Hee Young NA ; Soon-Won HONG ; So Yeon PARK ; Chan Kwon JUNG ; Kyeong Cheon JUNG ; Young Lyun OH ; Jae-Kyung WON
Journal of Pathology and Translational Medicine 2026;60(2):202-213
The Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) is widely used for risk stratification in pheochromocytoma and paraganglioma (PPGL), but its clinical utility is limited by inter-observer variability of its parameters and inconsistent predictive performance. Methods: We conducted a multicenter retrospective study of 1,518 patients with PPGL from five tertiary referral centers in Korea. Prognostic utility of PASS system was assessed using logistic regression, Kaplan-Meier analysis, and receiver operating characteristic (ROC) curve analysis. Inter-observer variability was inferred by comparing area under the ROC curve (AUCs) across institutions. Simplified PASS systems were developed based on multivariable analysis of key histopathological parameters. Results: The PASS system was a significant predictor of adverse events and recurrence-free survival. Although the PASS system demonstrated only modest discriminative ability (AUC, 0.673), it showed a high negative predictive value (NPV, 0.885), supporting its usefulness as a screening tool for benign behavior. However, there was significant inter-institutional variability in PASS performance (AUC; range, 0.513 to 0.727; p < .05). The 3-factor Simple PASS, which incorporates necrosis, spindling, and mitotic figures, exhibited less inter-observer variation. The 4-factor Simple PASS, which adds vascular invasion to the 3-factor model, also showed reduced inter-observer variability and improved AUC and NPV compared to the original PASS system. Conclusions: In this multicenter cohort, the PASS system demonstrated high NPV and screening potential, but significant inter-observer variability remains a challenge. Simplification of the PASS system and enhanced pathologist training may improve reproducibility and clinical utility in PPGL risk stratification.
2.Radiological Approach to Splenomegaly: Etiologies, Pathophysiologies, and Diagnostic Strategies
Na Yeon HAN ; Yong PARK ; Min Ju KIM
Korean Journal of Radiology 2026;27(2):122-136
The spleen is frequently referred to as the “silent and forgotten” organ of the abdomen by clinicians and radiologists, primarily because of the secondary nature of most splenic pathologies and their relative rarity compared with hepatic diseases.Nevertheless, the term splenomegaly frequently appears in radiological reports. Although it is often reported in the context of a known underlying cause, it is also commonly used as a purely descriptive term without reference to the underlying etiology.Although splenomegaly may occasionally be idiopathic, it commonly represents an underlying pathological condition.Therefore, radiologists are instrumental in accurately identifying splenomegaly, evaluating plausible differential diagnoses, and guiding appropriate clinical management and workups. Given the wide spectrum of etiologies and overlapping imaging features, a systematic approach is essential to enhance the diagnostic accuracy and clinical relevance. Here, we present a comprehensive literature review of splenomegaly from a radiological perspective, with causes categorized according to pathophysiological mechanisms.
3.IARC Group 1 Pharmaceuticals and Associated Cancer Risks: A Nationwide Population-Based Cohort Study in Korea
Woojin LIM ; Na Rae LEE ; Ho Gyun SHIN ; Su-Yeon YU ; Sue K. PARK
Cancer Research and Treatment 2026;58(2):376-392
Purpose:
The aim of this study is to summarize cancer risk among patients with clinical indications of immunosuppressive and antineoplastic drugs in Korea, which are pharmaceuticals defined as group 1 by International Agency for Research on Cancer.
Materials and Methods:
We conducted a nationwide population-based retrospective cohort study using the Korean National Health Insurance Service claims data from 2002 to 2018. Patients with clinical indications for group 1 pharmaceuticals from 2002 to 2017 were selected as baseline population, and followed up until 2018. Cox proportional hazards regression model was used to analyze the risk of cancer and dose-response relationship between group 1 pharmaceuticals and cancer.
Results:
Azathioprine use increased the risk of skin and hematologic cancer (hazard ratio [HR], 4.63; 95% confidence interval [CI], 2.91 to 7.39 and HR, 3.15; 95% CI, 2.41 to 4.13). Cyclosporine use increased the risk of skin and hematologic cancer (HR, 2.30; 95% CI, 1.79 to 2.95 and HR, 2.96; 95% CI, 2.59 to 3.40). Cyclophosphamide use increased the risk of bladder and hematologic cancer (HR, 2.69; 95% CI, 1.92 to 3.78 and HR, 3.83; 95% CI, 3.20 to 4.59). Chlorambucil use increased the risk of hematologic cancer (HR, 3.51; 95% CI, 2.53 to 4.87) and melphalan use increased the risk of hematologic cancer (HR, 16.31; 95% CI, 13.41 to 19.85). Methoxsalen use increased the risk of skin cancer (HR, 2.32; 95% CI, 1.36 to 3.95).
Conclusion
Group 1 pharmaceuticals were associated with increased risk of cancer. The results are expected to help establish alternative clinical strategies and policies for patients with clinical indications of group 1 pharmaceuticals, by continuous risk analysis and discussions on the surveillance systems.
4.Clinical Application of Pharmacogenomics in Stroke Management: Current Evidence and Future Directions
Keon-Joo LEE ; Minkyung KANG ; Eung Joon LEE ; Jaeseong OH ; Na-Young HAN ; Jeong-Yoon LEE ; Joo-Yeon LEE ; Soo Ji LEE ; Stéphanie DEBETTE ; Guillaume PARÉ ; Daniel WOO ; Andrew ELDEIRY ; Young Seo KIM ; Jinkwon KIM ; Jong-Moo PARK ; Juneyoung LEE ; Joohon SUNG ; Jay Chol CHOI ; Hee-Joon BAE
Journal of Stroke 2026;28(1):58-75
Pharmacogenomic variations may significantly influence responses to commonly prescribed stroke medications. Despite accumulating evidence, genetic testing has not yet been widely integrated into stroke care. This review summarizes current evidence and provides practical guidance for clinical implementation. Pharmacogenomic studies and clinical guidelines related to antiplatelet agents, anticoagulants, and statins were reviewed, with particular emphasis on East Asian populations. Substantial evidence supports genotype-guided use of clopidogrel (CYP2C19), warfarin (CYP2C9, VKORC1, CYP4F2), and statins (SLCO1B1, ABCG2). For aspirin, PTGS1/2 and PEAR1 variants have been investigated; however, current data remain insufficient for clinical application. Regarding direct oral anticoagulants (DOACs), candidate genes such as ABCB1 and CES1 demonstrate pharmacokinetic associations, though robust clinical outcome data are lacking. Distinct allele frequencies in East Asians—such as higher prevalence of CYP2C19 and ABCG2 variants—underscore the need for population-specific strategies. Beyond single-gene approaches, polygenic risk scores, pharmacogenomic panels, and integration with multi-omics data and artificial intelligence represent promising directions for personalized therapy. Pharmacogenomic testing can enhance stroke pharmacotherapy, particularly in populations with high frequencies of actionable variants. Broader implementation requires rapid testing platforms, clinician education, tailored clinical guidelines, and real-world validation of aspirin, DOACs, and multi-gene approaches. Future research should expand population-specific studies and integrate pharmacogenomics within the broader framework of precision medicine to ensure equitable clinical benefit.
5.Early-Onset Dementia Risk Escalates with Diabetes Duration: Insights from a Nationwide Cohort Study
Ji-Hong PARK ; Sun-Joon MOON ; Da Yeon LEE ; Ji-Hee KO ; Han Na JANG ; Hye-Mi KWON ; Se-Eun PARK ; Kyung-Do HAN ; Eun-Jung RHEE ; Won-Young LEE
Endocrinology and Metabolism 2026;41(2):235-244
Background:
The prevalence of diabetes mellitus and early-onset dementia (EOD), defined as dementia diagnosed at an age <65 years, is increasing worldwide, with significant socioeconomic implications. We investigated the association between diabetes, prediabetes, and EOD, focusing on the influence of diabetes duration on EOD risk.
Methods:
Using the Korean National Health Insurance Service database, we analyzed data from 1,979,509 patients aged 40–60 years who underwent health checkups in 2009. Patients were categorized into five groups: normal, impaired fasting glucose (IFG), newly diagnosed diabetes, diabetes duration <5 years, and diabetes duration ≥5 years. Cox proportional hazard models were used to estimate the adjusted hazard ratios (aHRs) for EOD after adjusting for demographic and clinical covariates.
Results:
During the observation period (mean 7.75 years), 8,921 patients with EOD were identified. The diabetes group demonstrated a significantly higher incidence of EOD compared to the normal group (aHR, 1.334; 95% confidence interval [CI], 1.226 to 1.451). EOD risk increased with longer diabetes duration, with the highest risk observed in patients with diabetes ≥5 years (aHR, 1.543; 95% CI, 1.368 to 1.741). No significant difference was observed between the IFG and normal groups (aHR, 0.989; 95% CI, 0.938 to 1.043). Additionally, the hypertension group exhibited a significantly higher incidence of EOD compared to the non-hypertension group (aHR, 1.364; 95% CI, 1.291 to 1.442).
Conclusion
Diabetes is independently associated with increased risk of EOD, and this risk increases with longer diabetes duration. This association remained significant regardless of the presence and duration of hypertension.
6.Comparison of tissue-based and plasma-based testing for EGFR mutation in non–small cell lung cancer patients
Yoon Kyung KANG ; Dong Hoon SHIN ; Joon Young PARK ; Chung Su HWANG ; Hyun Jung LEE ; Jung Hee LEE ; Jee Yeon KIM ; JooYoung NA
Journal of Pathology and Translational Medicine 2025;59(1):60-67
Background:
Epidermal growth factor receptor (EGFR) gene mutation testing is crucial for the administration of tyrosine kinase inhibitors to treat non–small cell lung cancer. In addition to traditional tissue-based tests, liquid biopsies using plasma are increasingly utilized, particularly for detecting T790M mutations. This study compared tissue- and plasma-based EGFR testing methods.
Methods:
A total of 248 patients were tested for EGFR mutations using tissue and plasma samples from 2018 to 2023 at Pusan National University Yangsan Hospital. Tissue tests were performed using PANAmutyper, and plasma tests were performed using the Cobas EGFR Mutation Test v2.
Results:
All 248 patients underwent tissue-based EGFR testing, and 245 (98.8%) showed positive results. Of the 408 plasma tests, 237 (58.1%) were positive. For the T790M mutation, tissue biopsies were performed 87 times in 69 patients, and 30 positive cases (38.6%) were detected. Plasma testing for the T790M mutation was conducted 333 times in 207 patients, yielding 62 positive results (18.6%). Of these, 57 (27.5%) were confirmed to have the mutation via plasma testing. Combined tissue and plasma tests for the T790M mutation were positive in nine patients (13.4%), while 17 (25.4%) were positive in tissue only and 12 (17.9%) in plasma only. This mutation was not detected in 28 patients (43.3%).
Conclusions
Although the tissue- and plasma-based tests showed a sensitivity of 37.3% and 32.8%, respectively, combined testing increased the detection rate to 56.7%. Thus, neither test demonstrated superiority, rather, they were complementary.
7.Evaluation of the physical activity of individuals with spinal cord injury in Korea: a cross-sectional study
Se-Hee PARK ; Na Young LEE ; Jae-Yeon KIM ; Min-Goo LEE
Journal of the Korean Medical Association 2025;68(4):242-252
Purpose:
In Korea, the absence of a modified physical activity (PA) questionnaire specifically tailored for Koreans hinders the accurate assessment of PA among individuals with spinal cord injury (SCI). This study aimed to evaluate PA levels in individuals with SCI using a modified PA questionnaire and to provide insights into their PA patterns in Korea.
Methods:
A self-reported questionnaire was developed by revising and adapting the Korean version of the International Physical Activity Questionnaire (K-IPAQ) during an advisory meeting. Between April and June 2023, 176 individuals with SCI from metropolitan areas in Korea were recruited to assess their weekly PA. PA was quantified in Metabolic Equivalent Task-min/week (MET-min/week) by multiplying the reported PA duration.
Results:
The average PA level among individuals with SCI in Korea was 2,907.2±194.8 MET-min/week. By intensity, high-intensity activities accounted for 2,760.0±280.5 MET-min/week, moderate-intensity activities for 1,148.8±89.0 MET-min/week, and low-intensity activities for 1,869.4±110.3 MET-min/week. Approximately half of the participants met the World Health Organization (WHO) recommendations for PA.
Conclusion
Although Korean individuals with SCI demonstrated higher average PA levels compared to findings from other countries and the WHO recommendations, only about half of the participants met the WHO’s guidelines. These results underscore the need to strengthen efforts to promote PA participation among individuals with SCI.
8.Comparison of tissue-based and plasma-based testing for EGFR mutation in non–small cell lung cancer patients
Yoon Kyung KANG ; Dong Hoon SHIN ; Joon Young PARK ; Chung Su HWANG ; Hyun Jung LEE ; Jung Hee LEE ; Jee Yeon KIM ; JooYoung NA
Journal of Pathology and Translational Medicine 2025;59(1):60-67
Background:
Epidermal growth factor receptor (EGFR) gene mutation testing is crucial for the administration of tyrosine kinase inhibitors to treat non–small cell lung cancer. In addition to traditional tissue-based tests, liquid biopsies using plasma are increasingly utilized, particularly for detecting T790M mutations. This study compared tissue- and plasma-based EGFR testing methods.
Methods:
A total of 248 patients were tested for EGFR mutations using tissue and plasma samples from 2018 to 2023 at Pusan National University Yangsan Hospital. Tissue tests were performed using PANAmutyper, and plasma tests were performed using the Cobas EGFR Mutation Test v2.
Results:
All 248 patients underwent tissue-based EGFR testing, and 245 (98.8%) showed positive results. Of the 408 plasma tests, 237 (58.1%) were positive. For the T790M mutation, tissue biopsies were performed 87 times in 69 patients, and 30 positive cases (38.6%) were detected. Plasma testing for the T790M mutation was conducted 333 times in 207 patients, yielding 62 positive results (18.6%). Of these, 57 (27.5%) were confirmed to have the mutation via plasma testing. Combined tissue and plasma tests for the T790M mutation were positive in nine patients (13.4%), while 17 (25.4%) were positive in tissue only and 12 (17.9%) in plasma only. This mutation was not detected in 28 patients (43.3%).
Conclusions
Although the tissue- and plasma-based tests showed a sensitivity of 37.3% and 32.8%, respectively, combined testing increased the detection rate to 56.7%. Thus, neither test demonstrated superiority, rather, they were complementary.
9.Evaluation of the physical activity of individuals with spinal cord injury in Korea: a cross-sectional study
Se-Hee PARK ; Na Young LEE ; Jae-Yeon KIM ; Min-Goo LEE
Journal of the Korean Medical Association 2025;68(4):242-252
Purpose:
In Korea, the absence of a modified physical activity (PA) questionnaire specifically tailored for Koreans hinders the accurate assessment of PA among individuals with spinal cord injury (SCI). This study aimed to evaluate PA levels in individuals with SCI using a modified PA questionnaire and to provide insights into their PA patterns in Korea.
Methods:
A self-reported questionnaire was developed by revising and adapting the Korean version of the International Physical Activity Questionnaire (K-IPAQ) during an advisory meeting. Between April and June 2023, 176 individuals with SCI from metropolitan areas in Korea were recruited to assess their weekly PA. PA was quantified in Metabolic Equivalent Task-min/week (MET-min/week) by multiplying the reported PA duration.
Results:
The average PA level among individuals with SCI in Korea was 2,907.2±194.8 MET-min/week. By intensity, high-intensity activities accounted for 2,760.0±280.5 MET-min/week, moderate-intensity activities for 1,148.8±89.0 MET-min/week, and low-intensity activities for 1,869.4±110.3 MET-min/week. Approximately half of the participants met the World Health Organization (WHO) recommendations for PA.
Conclusion
Although Korean individuals with SCI demonstrated higher average PA levels compared to findings from other countries and the WHO recommendations, only about half of the participants met the WHO’s guidelines. These results underscore the need to strengthen efforts to promote PA participation among individuals with SCI.
10.Neutralizing Activity and T-Cell Responses Against Wild Type SARSCoV-2 Virus and Omicron BA.5 Variant After Ancestral SARS-CoV-2 Vaccine Booster Dose in PLWH Receiving ART Based on CD4 T-Cell Count
Na Young HA ; Ah-Ra KIM ; Hyeongseok JEONG ; Shinhye CHEON ; Cho Rong PARK ; Jin Ho CHOE ; Hyo Jung KIM ; Jae Won YOON ; Miryoung KIM ; Mi Yeong AN ; Sukyoung JUNG ; Hyeon Nam DO ; Junewoo LEE ; Yeon-Sook KIM
Journal of Korean Medical Science 2025;40(9):e28-
Background:
We evaluated severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-specific humoral and cellular responses for up to 6 months after the 3rd dose of ancestral coronavirus disease 2019 (COVID-19) vaccination in people living with HIV (PLWH) and healthy controls (HCs) who were not infected with COVID-19.
Methods:
Anti-spike receptor-binding domain IgG (anti-RBD IgG) concentrations using chemiluminescence immunoassay and neutralizing antibodies using focus reduction neutralization test (FRNT) were assessed at 1 week after each dose of vaccination, and 3 and 6 months after the 3rd dose in 62 PLWH and 25 HCs. T-cell responses using intracellular cytokine stain were evaluated at 1 week before, and 1 week and 6 months after the 3rd dose.
Results:
At 1 week after the 3rd dose, adequate anti-RBD IgG (> 300 binding antibody unit /mL) was elicited in all PLWH except for one patient with 36 CD4 T-cell count/mm3 . The geometric mean titers of 50% FRNT against wild type (WT) and omicron BA.5 strains of SARS-CoV-2 in PLWH with CD4 T-cell count ≥ 500 cells/mm3(high CD4 recovery, HCDR) were comparable to HC, but they were significantly decreased in PLWH with CD4 T-cell count < 500/mm3 (low CD4 recovery, LCDR). After adjusting for age, gender, viral suppression, and number of preexisting comorbidities, CD4 T-cell counts < 500/mm3 significantly predicted a poor magnitude of neutralizing antibodies against WT, omicron BA.5, and XBB 1.5 strains among PLWH. Multivariable linear regression adjusting for age and gender revealed that LCDR was associated with reduced neutralizing activity (P = 0.017) and interferon-γ-producing T-cell responses (P = 0.049 for CD T-cell; P = 0.014 for CD8 T-cell) against WT, and strongly associated with more decreased cross-neutralization against omicron BA.5 strains (P < 0.001).
Conclusion
HCDR demonstrated robust humoral and cell-mediated immune responses after a booster dose of ancestral SARS-CoV-2 vaccine, whereas LCDR showed diminished immune responses against WT virus and more impaired cross-neutralization against omicron BA.5 strain.

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