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.Primary Cutaneous CD30+ Lymphoproliferative Disorders in South Korea: A Nationwide, Multi-Center, Retrospective, Clinical, and Prognostic Study
Woo Jin LEE ; Sook Jung YUN ; Joon Min JUNG ; Joo Yeon KO ; Kwang Ho KIM ; Dong Hyun KIM ; Myung Hwa KIM ; You Chan KIM ; Jung Eun KIM ; Chan-Ho NA ; Je-Ho MUN ; Jong Bin PARK ; Ji-Hye PARK ; Hai-Jin PARK ; Dong Hoon SHIN ; Jeonghyun SHIN ; Sang Ho OH ; Seok-Kweon YUN ; Dongyoun LEE ; Seok-Jong LEE ; Seung Ho LEE ; Young Bok LEE ; Soyun CHO ; Sooyeon CHOI ; Jae Eun CHOI ; Mi Woo LEE ; On behalf of The Korean Society of Dermatopathology
Annals of Dermatology 2025;37(2):75-85
Background:
Primary cutaneous CD30+ lymphoproliferative disorders (pcCD30-LPDs) are a diseases with various clinical and prognostic characteristics.
Objective:
Increasing our knowledge of the clinical characteristics of pcCD30-LPDs and identifying potential prognostic variables in an Asian population.
Methods:
Clinicopathological features and survival data of pcCD30-LPD cases obtained from 22 hospitals in South Korea were examined.
Results:
A total of 413 cases of pcCD30-LPDs (lymphomatoid papulosis [LYP], n=237; primary cutaneous anaplastic large cell lymphoma [C-ALCL], n=176) were included. Ninety percent of LYP patients and roughly 50% of C-ALCL patients presented with multiple skin lesions. Both LYP and C-ALCL affected the lower limbs most frequently. Multiplicity and advanced T stage of LYP lesions were associated with a chronic course longer than 6 months. Clinical morphology with patch lesions and elevated serum lactate dehydrogenase were significantly associated with LPDs during follow-up in LYP patients. Extracutaneous involvement of C-ALCL occurred in 13.2% of patients. Lesions larger than 5 cm and increased serum lactate dehydrogenase were associated with a poor prognosis in C-ALCL. The survival of patients with C-ALCL was unaffected by the anatomical locations of skin lesions or other pathological factors.
Conclusion
The multiplicity or size of skin lesions was associated with a chronic course of LYP and survival among patients with C-ALCL.
7.2023 Consensus Korean Diagnostic Criteria for Atopic Dermatitis
Ji Hyun LEE ; Sul Hee LEE ; Youin BAE ; Young Bok LEE ; Yong Hyun JANG ; Jiyoung AHN ; Joo Yeon KO ; Hyun-Chang KO ; Hye One KIM ; Chan Ho NA ; Young-Joon SEO ; Min Kyung SHIN ; Yu Ri WOO ; Bark Lyn LEW ; Dong Hun LEE ; Sang Eun LEE ; Jiehyun JEON ; Sun Young CHOI ; Tae Young HAN ; Yang Won LEE ; Sang Wook SON ; Young Lip PARK
Annals of Dermatology 2025;37(1):12-21
Background:
In 2006, the Korean Atopic Dermatitis Association (KADA) working group released the diagnostic criteria for Korean atopic dermatitis (AD). Recently, more simplified, and practical AD diagnostic criteria have been proposed. Objective: Based on updated criteria and experience, we studied to develop and share a consensus on diagnostic criteria for AD in Koreans.
Materials and Methods:
For the diagnostic criteria, a questionnaire was constructed by searching the English-language literature in MEDLINE and the Cochrane Database of Systematic Reviews. A modified Delphi method composed of 3 rounds of email questionnaires was adopted for the consensus process. Fifty-four KADA council members participated in the 3 rounds of votes and expert consensus recommendations were established.
Results:
Diagnostic criteria for AD include pruritus, eczema with age-specific pattern, and chronic or relapsing history. Diagnostic aids for AD encompass xerosis, immunoglobulin E reactivity, hand–foot eczema, periorbital changes, periauricular changes, perioral changes, nipple eczema, perifollicular accentuation, and personal or family history of atopy.
Conclusion
This study streamlined and updated the diagnostic criteria for AD in Korea, making them more practicable for use in real-world clinical field.
8.Advancing Natural Killer Cell Therapy: Genetic Engineering Strategies for Enhanced Cancer Immunotherapy
Joo Dong PARK ; Ha Eun SHIN ; Yeon Su AN ; Hye Jung JANG ; Juwon PARK ; Se-Na KIM ; Chun Gwon PARK ; Wooram PARK
Annals of Laboratory Medicine 2025;45(2):146-159
Natural killer (NK) cells are pivotal innate immune system components that exhibit spontaneous cytolytic activity against abnormal cells, such as infected and tumor cells. NK cells have shown significant promise in adoptive cell therapy because of their favorable safety profiles and minimal toxicity in clinical settings. Despite their advantages, the therapeutic application of unmodified NK cells faces challenges, including limited in vivo persistence, particularly in the immunosuppressive tumor microenvironment. Recent advances in genetic engineering have enhanced the therapeutic potential of NK cells by addressing these limitations and improving their therapeutic efficacy. In this review, we have described various methodologies for the genetic modification of NK cells, including viral vectors, electroporation, and nanoparticle-based approaches. The ongoing research on nanomaterialbased approaches highlights their potential to overcome current limitations in NK cell therapy, paving the way for advanced cancer therapy and improved clinical outcomes. In this review, we also emphasize the potential of engineered NK cells in cancer immunotherapy and other clinical applications, highlighting the expanding scope of NK cell-based treatments and the critical role of innovative genetic engineering techniques.
9.Clinical Implications of Circulating Tumor DNA in Multiple Myeloma and Its Precursor Diseases
Sung-Soo PARK ; Na Yung KIM ; Ji-Young LIM ; Jung Yeon LEE ; Sujin YUN ; Yeun-Jun CHUNG ; Seung-Hyun JUNG ; Chang-Ki MIN
Annals of Laboratory Medicine 2025;45(3):279-290
Background:
Genetic alterations play a pivotal role in multiple myeloma (MM) development and therapeutic resistance. Traditionally, the genetic profiling of MM requires invasive bone marrow (BM) procedures; however, these procedures are associated with patient discomfort and cannot fully capture the spatial and temporal heterogeneity of the disease.Therefore, we investigated the clinical implications of liquid biopsy using targeted deep sequencing.
Methods:
We analyzed the genetic profiles of circulating tumor DNA (ctDNA) by targeted deep sequencing from 102 patients, including those with monoclonal gammopathy of undetermined significance (MGUS, N = 7), smoldering MM (N = 6), and symptomatic MM (N = 89).
Results:
The number of ctDNA mutations increased with disease progression from MGUS to MM, with averages of 1.0 mutations in MGUS, 1.8 mutations in smoldering MM, and 1.9 mutations in MM, respectively. Shared mutations between BM and ctDNA were more prevalent in MM (68.9%) than in MGUS (25.0%). RAS/RAF and TP53 mutations were significantly enriched in MM ctDNA. Specific mutations were associated with clinical features in patients with MM: hypercalcemia and TET2 (P = 0.006), renal insufficiency and NRAS (P = 0.012), paramedullary myeloma and TP53(P = 0.02), and extramedullary myeloma and NRAS (P = 0.007). TET2 mutations significantly affected 2-yr progression-free survival (hazard ratio = 7.11, P = 0.003). Serial ctDNA profiling accurately predicted treatment response in patients with MM.
Conclusions
Our findings highlight the potential of liquid biopsy for understanding MM progression and prognosis utilizing a minimally invasive approach, paving the way for its integration into personalized treatment strategies and real-time disease monitoring.
10.Clinical evaluation and management of endometriosis: 2024 guideline for Korean patients from the Korean Society of Endometriosis
Hyun Joo LEE ; Sang-Hee YOON ; Jae Hoon LEE ; Youn-Jee CHUNG ; So Yun PARK ; Sung Woo KIM ; Yeon Hee HONG ; Sung Eun KIM ; Youjin KIM ; Sungwook CHUN ; Yong Jin NA
Obstetrics & Gynecology Science 2025;68(1):43-58
Endometriosis, a prevalent but debilitating condition affecting women, poses significant challenges in diagnosis and management. The current 2024 guideline, developed by the Korean Society of Endometriosis (KSE), builds upon the 2018 KSE guideline. This guideline aims to provide customized recommendations tailored to Korea’s unique clinical aspects and medical environment, and addresses key areas such as diagnosis, medical and surgical management, considerations for special populations, and its complex relationship with cancer.

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