Seung-Sook Lee

The journal retracts the article, “Inhibition of EphA2 by Dasatinib Suppresses Radiation-Induced Intestinal Injury”

Background: Human papillomavirus (HPV) independent cervical malignancies (HPV-IDCMs) have recently been classified by the World Health Organization (WHO) 5th edition. These malignancies have historically received limited attention due to their rarity and the potential for evasion of HPV-based screening.Methods: We retrospectively reviewed 5,854 biopsy-confirmed cervical malignancies from 22 institutions over 3 years (July 2020–June 2023). Histologic classification followed the WHO guidelines. HPV independence was confirmed by dual negativity for p16 and HPV; discordant cases (p16-positive/HPV-negative) underwent additional HPV testing using paraffin-embedded tissue. Cytological results were matched sequentially to histological confirmation.Results: The prevalence of HPV-IDCM was 4.4% (257/5,854) overall and was 3.6% (208/5,805 cases) among primary cervical malignancy. Patient age of HPV-IDCM was 29 to 89 years (median, 57.79). Its histologic subtypes included primary adenocarcinoma (n = 116), endometrial adenocarcinoma (n = 35), squamous cell carcinoma (n = 72), metastatic carcinoma (n = 14), carcinoma, not otherwise specified (n = 10), neuroendocrine carcinoma (n = 3), and others (n = 7). Among 155 cytology-histological matched cases, the overall and primary Pap test detection rates were 85.2% (132/155) and 83.2% (104/125), respectively. The interval between cytology and histologic confirmation extended up to 38 months.Conclusions: HPV-IDCMs comprised 3.6% of primary cervical malignancies with a high detection rate via cytology (83.2%). These findings affirm the value of cytological screening, particularly in patients with limited screening history or at risk for HPV-independent lesions, and may guide future screening protocols.

Background: Digital cytopathology (DC) is emerging as a transformative approach in quality assurance programs (QAP), though its comprehensive evaluation remains limited. Since 2020, the Korean Society for Cytopathology has progressively incorporated DC into its national QAP, including digital proficiency testing (PT), sample adequacy testing (SAT), a customizable PT module, and a self-assessment module (SAM), aiming for full digital implementation by 2026. Methods: This 5-year study assessed diagnostic concordance between conventional and digital PT formats and analyzed participant feedback on service quality and digital image usability across PT, SAT, and SAM. Parallel testing was conducted during the transitional phase, and satisfaction was measured through structured surveys. Results: Participation in digital PT increased from 48 institutions in 2020 to 93 in 2024, while digital SAT participation rose from 29 to 71 between 2022 and 2024. In 2023, 56 institutions joined SAM. Diagnostic concordance rates were comparable between digital and conventional PTs (78.6%–84.6% vs. 82.0%–85.1%), including similar category C (major discordance) rates. Satisfaction with digital PT services and image quality exceeded 85%, and over 90% of institutions reported positive feedback on SAT and SAM. Over 80% were satisfied with the customizable PT module. Conclusions: DC is a reliable and effective modality for cytopathology QAP. It demonstrates diagnostic equivalence to conventional methods and high user satisfaction, supporting its broader implementation in national quality assurance frameworks.

Background/Objectives: Myeloid neoplasms are the most common secondary blood cancer in B-cell non-Hodgkin lymphoma (BNHL) patients treated with cytotoxic therapies. We aimed to characterize the genetic and clinicopathologic features of myeloid neoplasms arising after B-cell non-Hodgkin lymphoma (MN-BNHL) by comparing their features with myeloid neoplasms developing after solid cancer (MN-SC). Methods: We retrospectively analyzed the clinicopathologic and genetic data of myeloid neoplasm patients diagnosed between 2008 and 2023, categorized as MN-BNHL or MN-SC. Further NGS analysis was performed on available bone marrow samples with missing genetic data. The genetic profiles of myeloid neoplasms between BNHL and solid cancer groups were compared. Results: Sixteen patients developed MN-BNHL. Among the 11 MN-BNHL patients undergoing NGS, all harbored tier 1 mutations. PPM1D mutations (PPM1Dms) were most frequent (73%), followed by DNMT3A (46%) and TP53 (36%). PPM1Dms were significantly more prevalent than in MN-SC (n = 21), where TP53 mutations were most common (64%) (p < 0.001). PPM1Dms often co-occurred with DNMT3A. They were associated with prior radioimmunotherapy (relative risk (RR): 3.3 and RR 3.57). MN-BNHL patients with PPM1Dms exhibited improved survival compared to those without (p = 0.0376), but this benefit was negated by the presence of TP53 mutations (p = 0.0049). Conclusions: PPM1Dms are a prominent genetic feature in MN-BNHL, suggesting a distinct role in its development compared to MN-SC. Further investigation is needed to elucidate the precise contribution of PPM1D and its interaction with other mutations in BNHL-related myeloid neoplasm development and prognosis.

Since the late 1990s, online e-learning has offered unparalleled convenience and affordability, becoming increasingly popular among pathologists. Traditional learning theories have been successfully applied to web/mobile-based learning systems, with mobile technologies even enhancing conventional offline education. In cytopathology, hands-on microscope training has traditionally been paramount, complemented by real-case presentations and lectures. However, the coronavirus disease 2019 (COVID-19) pandemic disrupted regular academic activities, making online e-learning platforms essential. We designed a web/mobile-based learning platform to enhance continued medical education in cytopathology at various levels, particularly during the era of COVID-19 and beyond. Since 2021, we have integrated curriculum materials, virtual education files, and whole-slide images (WSIs) of cytopathology, submitted from over 200 institutions across Korea, with the support of numerous instructors. We develop a new e-learning platform named “CytoAcademy” composed of a basic session for each organ and level across the range of morphologic findings; on-demand lectures to enhance cytopathologic knowledge; WSI archives that allow users to explore various histologically confirmed cases; and a self-assessment test to help organize diagnostic knowledge acquired through the web/mobile-friendly learning system. The platform provides not just an opportunity to achieve a correct diagnosis, but also a learning experience based on problem-solving point. Members interact, identify their deficiencies, and focus on specific educational materials. In this manner, all participants can actively engage in creating and maintaining knowledge and foster a proactive approach to learning.

Background: Fine needle aspiration cytology (FNAC) is a valuable tool for evaluating lymphadenopathy. The purpose of this study was to assess the reliability and effectiveness of FNAC in the diagnosis of lymphadenopathy. Methods: Cytological characteristics were evaluated in 432 patients who underwent lymph node FNAC and follow-up biopsy at the Korea Cancer Center Hospital from January 2015 to December 2019. Results: Fifteen (3.5%) of the four hundred and thirty-two patients were diagnosed as inadequate by FNAC, with five (33.3%) of these diagnosed as metastatic carcinoma on histological examination. Of the 432 patients, 155 (35.9%) were diagnosed as benign by FNAC, with seven (4.5%) of these diagnosed histologically as metastatic carcinoma. A review of the FNAC slides, however, showed no evidence of cancer cells, suggesting that the negative results may have been due to FNAC sampling errors. An additional five samples regarded as benign on FNAC were diagnosed as non-Hodgkin lymphoma (NHL) by histological examination. Of the 432 patients, 223 (51.6%) were cytologically diagnosed as malignant, with 20 (9.0%) of these diagnosed as tissue insufficient for diagnosis (TIFD) or benign on histological examination. A review of the FNAC slides of these 20 patients, however, showed that 17 (85.0%) were positive for malignant cells. The sensitivity, specificity, positive predictive value (PPV), negative predictive values (NPV), and accuracy of FNAC were 97.8%, 97.5%, 98.7%, 96.0%, and 97.7%, respectively. Conclusions: Preoperative FNAC was safe, practical, and effective in the early diagnosis of lymphadenopathy. This method, however, had limitations in some diagnoses, suggesting that additional attempts may be required according to the clinical situation.

The primary cause of colorectal cancer (CRC) recurrence is increased distant metastasis after radiotherapy, so there is a need for targeted therapeutic approaches to reduce the metastatic-relapse risk. Dysregulation of the cell-surface glycoprotein podocalyxin-like protein (PODXL) plays an important role in promoting cancer-cell motility and is associated with poor prognoses for many malignancy types. We found that CRC cells exposed to radiation demonstrated increased TGFβ and PODXL expressions, resulting in increased migration and invasiveness due to increased extracellular matrix deposition. In addition, both TGFβ and PODXL were highly expressed in tissue samples from radiotherapy-treated CRC patients compared to those from patients without this treatment. However, it is unclear whether TGFβ and PODXL interactions are involved in cancer-progression resistance after radiation exposure in CRC. Here, using CRC cells, we showed that silencing PODXL blocked radiation-induced cell migration and invasiveness. Cell treatment with galunisertib (a TGFβ-pathway inhibitor) also led to reduced viability and migration, suggesting that its clinical use may enhance the cytotoxic effects of radiation and lead to the effective inhibition of CRC progression. Overall, the results demonstrate that downregulation of TGFβ and its-mediated PODXL may provide potential therapeutic targets for patients with radiotherapy-resistant CRC.

Radiation-induced multiorgan dysfunction is thought to result primarily from damage to the endothelial system, leading to a systemic inflammatory response that is mediated by the recruitment of leukocytes. The Eph–ephrin signaling pathway in the vascular system participates in various disease developmental processes, including cancer and inflammation. In this study, we demonstrate that radiation exposure increased intestinal inflammation via endothelial dysfunction, caused by the radiation-induced activation of EphA2, an Eph receptor tyrosine kinase, and its ligand ephrinA1. Barrier dysfunction in endothelial and epithelial cells was aggravated by vascular endothelial–cadherin disruption and leukocyte adhesion in radiation-induced inflammation both in vitro and in vivo. Among all Eph receptors and their ligands, EphA2 and ephrinA1 were required for barrier destabilization and leukocyte adhesion. Knockdown of EphA2 in endothelial cells reduced radiation-induced endothelial dysfunction. Furthermore, pharmacological inhibition of EphA2–ephrinA1 by the tyrosine kinase inhibitor dasatinib attenuated the loss of vascular integrity and leukocyte adhesion in vitro. Mice administered dasatinib exhibited resistance to radiation injury characterized by reduced barrier leakage and decreased leukocyte infiltration into the intestine. Taken together, these data suggest that dasatinib therapy represents a potential approach for the protection of radiation-mediated intestinal damage by targeting the EphA2–ephrinA1 complex.

Background: It is difficult to distinguish parathyroid lesions (PLs) from thyroid lesions using fine needle aspiration cytology (FNAC) because of their proximity and their similar cytomorphological features. Methods: FNAC smears of 46 patients with pathologically proven PLs that were histologically diagnosed as parathyroid adenoma (PA, n = 35), parathyroid hyperplasia (PH, n = 3), atypical parathyroid adenoma (APA, n = 1), and parathyroid carcinoma (PC, n = 7) were retrospectively reviewed and analyzed. Results: Our initial cytological diagnoses indicated correct diagnoses in 31 of 46 PL patients (67%). The 15 erroneous diagnoses were 5 patients with non-specific benign disease (11%), 4 with nodular hyperplasia of the thyroid (9%), 5 with atypical cells (11%), and 1 with a metastatic papillary thyroid carcinoma (2%). Follicular pattern, papillary structures, colloid-like material, and macrophages, which often suggest thyroid lesions, were also present in some PLs. We found that branching capillaries along the papillary structures, stippled nuclear chromatin, and frequent occurrence of naked nuclei were useful for determining a parathyroid origin. Conclusions: It is important to be aware that PLs are frequently mistaken for thyroid lesions based on FNAC. The specific and unique characteristics of PLs identified here may be helpful in diagnosis.