Journal of Pathology and Translational Medicine

Case Study

Diagnostic challenge in Burkitt lymphoma of the mandible initially misdiagnosed as osteomyelitis: a case report: Jiwon Do, Jin-Young Choi; J Pathol Transl Med. 2025;59(6):460-466. Published online November 14, 2025; DOI: https://doi.org/10.4132/jptm.2025.09.18

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Abstract PDF: Burkitt lymphoma (BL) is a highly aggressive B-cell neoplasm that rarely involves the mandible in elderly without apparent immunodeficiency. We report a case of a 72-year-old male who presented with persistent mandibular pain following extraction of tooth #46. Initial imaging findings were consistent with incipient osteomyelitis, and the patient was treated with antibiotics. Despite treatment, pain persisted, and follow-up imaging revealed swelling and diffusion restriction in the lateral pterygoid muscle without evidence of a distinct mass. Biopsy revealed BL confirmed by immunohistochemistry: CD10+, BCL6+, c-MYC+, Ki-67 >95%, and negative for BCL2, MUM-1, and Epstein-Barr virus. Although c-MYC immunopositivity was demonstrated, fluorescence in situ hybridization for MYC rearrangement could not be performed due to limited tissue, representing a diagnostic limitation. Notably, the patient had no trismus despite deep muscle involvement, but complained of facial paresthesia and showed remote swelling in the scapular area during hospitalization. Systemic staging with imaging, cerebrospinal fluid cytology, and imaging revealed disseminated nodal and extranodal involvement including the central nervous system, corresponding to stage IV disease by Lugano classification. This case highlights the diagnostic challenge of distinguishing lymphoma from osteomyelitis and underscores the importance of considering malignancy in cases of refractory mandibular inflammation with atypical features.

Original Articles

Diagnostic value of cytology in detecting human papillomavirus–independent cervical malignancies: a nation-wide study in Korea: Hye-Ra Jung, Junyoung Shin, Chong Woo Yoo, Eun Na Kim, Cheol Lee, Kyeongmin Kim, Ho-chang Lee, Yonghee Lee, Ji Hye Kim, Soo Jin Jung, Yumin Chung, Joo Yeon Kim, Hye Eun Park, Tae Hoen Kim, Wonae Lee, Min-Sun Cho, Ran Hong, Yoon Jung Choi, Younghee Choi, Young Sub Lee, Sang-Ryung Lee, Myunghee Kang, Young Jin Seo, Seung-Sook Lee, Yoon-Jung Hwang, Hyun-Jung Kim; J Pathol Transl Med. 2025;59(6):444-452. Published online November 11, 2025; DOI: https://doi.org/10.4132/jptm.2025.10.21

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Abstract PDF: 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.

Modified plasma-thrombin method using patient-derived plasma for cell block preparation in endobronchial ultrasound–guided transbronchial fine-needle aspiration: Xizhe Zhang, Chunli Tang, Yingying Gu, Zeyun Lin, Shiqi Tang, Anzi Tan, Mengshi Li, Zhucheng Chen, Yuying Chen, Shi-yue Li, Juhong Jiang; J Pathol Transl Med. 2025;59(6):434-443. Published online November 11, 2025; DOI: https://doi.org/10.4132/jptm.2025.08.20

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Abstract PDF: Background
The plasma-thrombin method, which uses expired blood bank plasma as an ancillary component, has been widely used in cell block (CB) preparation. However, the application of expired blood bank plasma raises concerns about nucleic acid contamination. This study investigated the feasibility of using patient-derived plasma as a substitute for blood bank plasma in the modified plasma-thrombin (MPT) method for CB preparation in endobronchial ultrasound–guided transbronchial needle aspiration (EBUS-TBNA) samples. Methods: A prospective study was conducted to compare the adequacy of CB preparation between a previously used self-clotting (SC) method and the MPT method. The EBUS-TBNA specimens from each targeted lesion were divided into paired samples: one processed using the SC method and the other using the MPT method, substituting the blood bank plasma with patient-derived plasma. Results: A total of 82 paired EBUS-TBNA samples from 59 patients were analyzed. The diagnostic yield of the SC method and the MPT method was 86.6% and 97.6%, respectively. Among patients diagnosed with non–small cell lung cancer, the adequacy rate for molecular testing was 79.2% with the SC method and 91.7% with the MPT method. Conclusions: The MPT method significantly improved the cellular yield of EBUS-TBNA–derived CBs. Using patient-derived fresh plasma rather than expired blood bank plasma avoids a known contamination risk. The additional step modestly prolongs the procedure and introduces minimal risks by vein puncture. This approach is generally considered cost-effective.

E-cadherin expression and tumor-stroma ratio as prognostic biomarkers of peritoneal recurrence in advanced gastric cancer: a digital image analysis-based stratification study: Somang Lee, Binnari Kim; J Pathol Transl Med. 2025;59(6):408-420. Published online November 6, 2025; DOI: https://doi.org/10.4132/jptm.2025.08.27

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Abstract PDF: Background
Gastric cancer remains a significant global health burden, with a high peritoneal recurrence rates after curative surgery. E-cadherin and the tumor-stroma ratio (TSR) have been proposed as prognostic indicators, but their combined prognostic utility remains unclear. Methods: This retrospective study included 130 patients with T3/T4a gastric cancer who underwent curative gastrectomy at Ulsan University Hospital between 2014 and 2019. Immunohistochemistry for E-cadherin and Vimentin was performed. Digital image analysis using QuPath’s object classifier quantified E-cadherin expression and TSR. Results: Low E-cadherin expression was associated with diffuse-type histology and advanced T stage. Low TSR was linked to younger age, female sex, and XELOX treatment. In Kaplan-Meier analysis, low TSR showed a non-significant trend toward higher peritoneal recurrence (p = .054), while low E-cadherin expression was significantly associated with increased peritoneal recurrence (p = .002). Combined biomarker analysis also revealed a significant difference in recurrence-free survival (RFS) among the four groups (p = .005); patients with both high TSR and high E-cadherin expression experienced the most favorable RFS. In multivariable analysis, E-cadherin expression remained the only independent predictor of peritoneal recurrence (high vs. low; hazard ratio, 0.348; 95% confidence interval, 0.149 to 0.816; p = .015). Conclusions: E-cadherin and TSR reflect distinct tumor biology such as epithelial integrity and stromal composition, and their combined evaluation improves prognostic stratification. Digital image analysis enhances reproducibility and objectivity, supporting their integration into clinical workflows.

Spectrum of thyroiditis types: clinical, cytomorphological, and radiological findings: Anam Singh, Indrajeet Kundu; J Pathol Transl Med. 2025;59(6):421-433. Published online November 6, 2025; DOI: https://doi.org/10.4132/jptm.2025.08.13

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Abstract PDF: Background
Thyroiditis encompasses a range of inflammatory conditions affecting the thyroid gland. Lymphocytic thyroiditis (LT) is a common form of thyroiditis, with acute suppuration of the thyroid, while tuberculous thyroiditis is relatively rare. Fine-needle aspiration cytology (FNAC) remains a safe and cost-effective tool for diagnosing thyroid-related diseases, especially when paired with ultrasound (US) and clinical examination. Methods: This is a cross-sectional study including 21 cases. The cases were reported as thyroiditis on US and FNAC, and the findings were correlated with patient clinical history, symptoms during presentation, and serological profiles. Results: The cases of thyroiditis encompassed the more common forms, LT and subacute granulomatous thyroiditis (SAT), as well as relatively rare forms like tuberculous thyroiditis and thyroid abscess. Cases of follicular neoplasms (FN) arising in the context of LT also are included in this study. The case of tuberculous thyroiditis presented as a bulky thyroid gland that appeared heterogeneous on US with extensive necrosis on FNAC. The cases of thyroid abscess and SAT presented with painful neck swellings, with granulomas in the latter cases. US features of LT showed an array of appearances ranging from pseudonodular to an atrophic thyroid gland. All cases of FN showed a lymphocytic background. Conclusions: Thyroiditis is a commonly encountered condition that needs to be sub-categorized accurately into acute, subacute, and chronic types for appropriate clinical management, as they can sometimes show overlapping features. Though rare, acute suppurative and tuberculous thyroiditis are often encountered and warrant immediate care and treatment.

Case Study

Primary thyroid diffuse large B-cell lymphoma: fine needle aspiration and histological correlation: Woo Sung Moon, Yong Tae Hong, Ae Ri Ahn; J Pathol Transl Med. 2025;59(6):467-471. Published online November 3, 2025; DOI: https://doi.org/10.4132/jptm.2025.08.28

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Abstract PDF: Primary thyroid lymphoma (PTL) is a rare type of cancer that arises within the thyroid gland, representing about 2%–8% of all thyroid malignancies. Fine-needle aspiration cytology is commonly used as the first-line diagnostic approach for thyroid nodules and can assist in identifying PTL when suggestive features are present. Herein, we report the case of a 59-year-old female patient who presented with a rapidly enlarging anterior neck mass over 20 days. Clinically, the case was challenging to distinguish from anaplastic thyroid carcinoma because of the sudden enlargement of the neck mass. However, pathological examination confirmed the diagnosis of primary thyroid diffuse large B-cell lymphoma. Fine-needle aspiration cytology proved valuable in avoiding unnecessary surgical resection and guiding appropriate treatment. Additionally, we provide a brief review of the clinical and cytopathological features of primary thyroid lymphomas.

Review Article

Breast schwannoma: review of entity and differential diagnosis: Sandra Ixchel Sanchez, Ashley Cimino-Mathews; J Pathol Transl Med. 2025;59(6):353-360. Published online November 3, 2025; DOI: https://doi.org/10.4132/jptm.2025.08.12

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Abstract PDF: Schwannomas are benign peripheral nerve sheath tumors composed of Schwann cells, which uncommonly involve the breast. Most breast schwannomas are clinically present as a superficial palpable breast mass but may also be detected on screening mammography. Excision is the preferred treatment if symptomatic, and these are not known to recur. Histomorphology is similar to other anatomic sites: bland spindle cells with wavy nuclei, nuclear palisading (Verocay bodies), variably hypercellular (Antoni A) and hypocellular (Antoni B) areas, myxoid stroma, hyalinized vessels and variable cystic degeneration. Classic immunohistochemistry is diffuse and strong labeling for S100 and Sox10. Notable diagnostic pitfalls specific to the breast include myofibroblastoma, particularly the palisaded variant, and fascicular pseudoangiomatous stromal hyperplasia.

Case Study

Clinicopathological characteristics of digestive system angioleiomyomas: case report and literature review: Georgios Kalliopitsas, Christos Topalidis, Constantine Halkias, Theodora Gkeka, Konstantinos Sapalidis, Triantafyllia Koletsa; J Pathol Transl Med. 2025;59(6):453-459. Published online October 28, 2025; DOI: https://doi.org/10.4132/jptm.2025.08.04

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Abstract PDF: Angioleiomyomas are benign soft tissue tumors originating from the vascular wall. Although angioleiomyomas mainly occur in extremities, followed by head, neck, and trunk, they can also be found throughout the digestive system and especially in the oral cavity. Herein, the fourth case of a rectal angioleiomyoma in the English literature is reported and the clinicopathological features of digestive system angioleiomyomas were investigated. In contrast to their soft tissue counterparts, digestive system angioleiomyomas mainly affect males at a slightly younger age. Angioleiomyomas are mainly asymptomatic and only rarely elicit pain. Clinicians consider angioleiomyomas infrequently and instead include more common soft tissue or epithelial tumors in their differential diagnosis. To prevent angiomyolipoma misdiagnosis, pathologists should exercise caution when examining an angioleiomyoma composed of adipose tissue, smooth muscle, and blood vessels. Pathologists, radiologists, and surgeons should be aware that angioleiomyomas can occur in the digestive system.

Newsletter

What’s new in hematopathology 2025: myeloid neoplasms in the WHO 5th edition and ICC: Barina Aqil; J Pathol Transl Med. 2025;59(6):472-475. Published online October 22, 2025; DOI: https://doi.org/10.4132/jptm.2025.09.24

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Abstract PDF: The previous edition of the World Health Organization (WHO) classification of hematolymphoid neoplasms was published in 2008 and later revised in 2017. A new 5th edition of the WHO classification of hematolymphoid neoplasms was released in 2022. Additionally, the Clinical Advisory Committee developed the International Consensus Classification (ICC) of hematolymphoid tumors, which differs from the WHO classification in several key defining features as outlined below.

Original Articles

Adenomatoid odontogenic tumor: clinicopathological analysis of 34 cases from Karachi, Pakistan: Summaya Zafar, Sehar Sulaiman, Madeeha Nisar, Poonum Khan, Nasir Ud Din; J Pathol Transl Med. 2025;59(6):390-397. Published online October 16, 2025; DOI: https://doi.org/10.4132/jptm.2025.07.11

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Abstract PDF: Background
Adenomatoid odontogenic tumor (AOT) is a benign slow-growing neoplasm of odontogenic epithelial origin that is relatively uncommon. Only a few studies have described its histological features. Hence, we aimed to describe the clinicopathological features of AOT in a cohort of patients. Methods: AOT cases diagnosed between 2009 and 2024 were searched electronically. Glass slides were retrieved from archives and were reviewed by two pathologists to record the associated morphological features. Other data including patient demographics and tumor site were collected by reviewing histopathology reports. Results: The age of patients ranged from 9 to 44 years (mean, 17.7 years), and most were female (55.9%). The maxilla (44.1%) was the most common tumor site. Histologically, a predominantly solid growth pattern (n = 34) accompanied by ducts with a cuboidal/columnar epithelial lining (n = 31), eosinophilic secretions (n = 31), calcifications (n = 31), lattice work pattern (n = 30), and cystic areas (n = 20) were observed. Less frequent features included calcifying epithelial odontogenic tumor (CEOT)–like areas (n = 13), osteodentin (n = 6), association with impacted tooth (n = 3), mucin in tubules (n = 7), fibrocollagenous stroma (n = 6), mucin in ducts (n = 3) and ossifying fibroma-like areas (n = 6). The association of ducts with a cuboidal/columnar epithelial lining, lattice work pattern, calcifications, and eosinophilic secretions with gingival tumors was statistically significant (p ≤ .05). Additionally, tooth tumors were significantly associated with CEOT-like areas (p = .03). Conclusions: Our study confirms the trends in the clinicopathological features of AOT in previous case reports. Our results suggest that AOTs usually exhibit a predominantly solid pattern with duct-like spaces. Only a few cases with CEOT-like and ossifying fibroma-like areas were observed, similar to infrequent cases reported in the past.

Clinicopathological implications of miR-3127 in melanoma: Truong Phan-Xuan Nguyen, Minh-Khang Le, Chau M. Bui, Vuong Gia Huy; J Pathol Transl Med. 2025;59(6):371-381. Published online October 16, 2025; DOI: https://doi.org/10.4132/jptm.2025.07.08

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Abstract PDF Supplementary Material: Background
Cutaneous melanoma is the most lethal of all skin cancers. Recent studies suggested that miR-3127 is dysregulated in multiple tumor types and has important roles in tumorigenesis and cancer progression, giving it potential as a prognostic biomarker. The aim of this study was to use bioinformatic analysis to assess miR-3127 expression and correlate expression patterns with disease course in patients with cutaneous melanoma. Methods: miRNA, mRNA sequencing, DNA methylation data, and clinical information of cutaneous melanoma cases were downloaded from the Human Cancer Atlas – Skin Cutaneous Melanoma (TCGA-SKCM). miR-3127 expression was classified into miR-3127–low and miR-3127–high clusters using maximally selected rank statistics. Results: Clustering analysis showed that high expression of miR-3127 (≥20.3 reads per million) was associated with worse progression-free (p < .001) and overall (p = .011) survival compared to low miR-3127 expression. More than five thousand differentially expressed genes between the two miR-3127 sample groups encoded cell differentiation markers, cytokines, growth factors, translocated cancer genes, and oncogenes. Pathway analysis revealed that miR-3127–high samples related to activity of proliferation, DNA repair, and ultraviolet response. Conclusions: The expression level of miR-3127 could act as a prognostic indicator for patients with melanoma.

Attitudes toward artificial intelligence in pathology: a survey-based study of pathologists in northern India: Manupriya Sharma, Kavita Kumari, Navpreet Navpreet, Sushma Bharti, Rajneesh Kumari; J Pathol Transl Med. 2025;59(6):382-389. Published online October 2, 2025; DOI: https://doi.org/10.4132/jptm.2025.07.10

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Abstract PDF Supplementary Material: Background
Artificial intelligence (AI) is transforming pathology by enhancing diagnostic accuracy, efficiency, and workflow standardization. Despite its growing presence, AI adoption remains limited, particularly in resource-constrained settings like India. This study assessed the knowledge, awareness, and perceptions of AI among pathologists in Northern India. Methods: A cross-sectional survey was conducted among 138 practicing pathologists in Northern India between April and June 2024. A structured online questionnaire was used to collect data on demographics, AI awareness, self-reported knowledge, sources of AI education, technological proficiency, and interest in AI-related training programs. Data analysis included descriptive statistics and chi-square tests, with p < .05 considered statistically significant. Results: AI awareness was high (88.4%), with significant sex differences (93.5% in females vs. 78.3% in males, p = .008). However, formal AI training was limited (6.5%), and only 16.7% had used AI as a diagnostic tool. Academic pathologists were more likely to engage with AI literature than their non-academic counterparts (p = .003). Interest in AI workshops was strong (92.8%). Access to whole slide imaging (WSI) correlated with higher AI knowledge (p = .008), as did self-reported technological proficiency (p = .001). Conclusions: Despite high AI awareness among pathologists, significant gaps remain in training, infrastructure, and practical application. Expanding access to digital pathology tools like WSI and improving digital literacy could facilitate AI adoption. Structured educational programs and greater investment in digital infrastructure are crucial for integrating AI into pathology practice.

National quality assurance program using digital cytopathology: a 5-year digital transformation experience by the Korean Society for Cytopathology: Yosep Chong, Hyeong Ju Kwon, Soon Auck Hong, Sung Soon Kim, Bo-Sung Kim, Younghee Choi, Yoon Jung Choi, Jung-Soo Pyo, Ji Yun Jeong, Soo Jin Jung, Hoon Kyu Oh, Seung-Sook Lee; J Pathol Transl Med. 2025;59(5):320-333. Published online September 15, 2025; DOI: https://doi.org/10.4132/jptm.2025.06.27

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Abstract PDF: 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.

Frozen section histopathology and preanalytical factors affecting nucleic acid integrity in biobanked fresh-frozen human cancer tissues: Soungeun Kim, Jaewon Kang, Boyeon Kim, Yoonjin Kwak, Hye Seung Lee; J Pathol Transl Med. 2025;59(6):398-407. Published online September 12, 2025; DOI: https://doi.org/10.4132/jptm.2025.07.22

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Abstract PDF Supplementary Material: Background
In this study, we evaluated the effects of storage duration and ischemic time on nucleic acid quality of fresh-frozen tissue (FFT) from colon adenocarcinoma (COAD), hepatocellular carcinoma (HCC), and renal cell carcinoma (RCC) collected at the Cancer Tissue Bank of Seoul National University Hospital. Methods: A total of 102 FFT samples were analyzed to compare DNA integrity number (DIN) and RNA integrity number (RIN) according to storage duration and ischemic time. Additionally, the effects of histopathologic features—such as tumor cell proportion, inflammatory cell infiltration, and stromal fibrosis—on nucleic acid quality were evaluated. Results: DIN and RIN remained stable overall even though the storage duration increased, with no statistically significant differences observed. In particular, there was almost no decrease in RNA quality in HCC and RCC samples, but in COAD samples, RIN tended to decrease slightly as the storage duration increased. No significant difference was confirmed between ischemic time and nucleic acid quality, but in COAD tissue, RNA quality variability tended to increase as the ischemic time increased. Furthermore, RIN increased as the tumor cell proportion increased, whereas inflammatory cell infiltration and extracellular mucin pool were identified as independent negative predictors of RIN. Conclusions: This study confirmed that nucleic acid integrity can be maintained even during long-term storage of FFT and demonstrated that histologic features are closely related to RNA quality. This study would contribute to the establishment of quality assessment and management standards for biobank FFT samples.

Case Study

Cytological characteristics of Müllerian adenosarcoma of the uterine corpus: a case report and literature review: Junko Kuramoto, Chihiro Matsubara, Yasuko Sasamoto, Hitomi Tsukada, Shigemichi Hirose; J Pathol Transl Med. 2025;59(5):340-347. Published online September 11, 2025; DOI: https://doi.org/10.4132/jptm.2025.08.11

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Abstract PDF: Müllerian adenosarcoma of the uterus is a rare morphological variant of uterine sarcoma. Müllerian adenosarcoma has been described histologically, though it is rare in the cytological literature. This report describes the cytological findings of a case of adenosarcoma arising from the endometrium. The patient was a Japanese woman in her 40s. Endometrial cytological and histological findings were observed for 5 years, from the appearance of a polypoid lesion until adenosarcoma was suspected, and then hysterectomy was performed. Based on these longitudinal cytological and histological observations, it was possible to identify the cytological characteristics of adenosarcoma: decrease in the glandular-to-stromal ratio; increase in stromal cell density; and progression of stromal cell atypia. This case stresses the importance and usefulness of endometrial cytology in the identification of the sarcomatous component in adenosarcoma.

Original Article

A single-institution demographic study of pathologically proven kidney disease in South Korea over the last 33 years: Hyejin Noh, Jiyeon Kim, Yeong Jin Choi; J Pathol Transl Med. 2025;59(5):306-319. Published online September 10, 2025; DOI: https://doi.org/10.4132/jptm.2025.06.18

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Abstract PDF Supplementary Material: Background
To date, epidemiological studies on the entire spectrum of kidney disease based on pathology have been rarely reported. Methods: A retrospective study was conducted on patients diagnosed with kidney disease at Seoul St. Mary's Hospital between 1991 and 2023. Results: Among 7,803 patients with native kidney disease, glomerular disease (70.3%) was the most common, followed by tubulointerstitial (15.1%) and vascular disease (8.8%). In kidney biopsy, glomerular disease (77.8%) showed the highest frequency, particularly in those under 20s (95.6%) (p = .013). Primary glomerulonephritis (GN) (72.8%) was the predominant glomerular disease, with IgA nephropathy (IgAN) (47.3%) being the most common one. Tubulointerstitial and vascular diseases increased with age, showing the highest prevalence in those over 60 years (p = .008 and p = .032, respectively). Glomerular disease was diagnosed at a younger age (39.7 ± 16.7 years) than tubulointerstitial (49.1 ± 16.2) and vascular (48.1 ± 15.3) diseases (p < .001). When glomerular diseases were classified morphologically, proliferative GN (57.9%) was the most common, followed by non-proliferative (39.6%) and sclerosing (1.6%). When classified by etiology, primary GN accounted for the most (72.8%), followed by secondary (19.3%) and hereditary GN (5.7%). In nephrectomy, tubulointerstitial disease (64.6%) was the most common. Those with a tubulointerstitial disease had a higher mean age than those with a glomerular disease (p < .001). In cases where nephrectomy was performed for glomerular diseases, IgAN (34.1%) was the most common diagnosis. Conclusions: Kidney disease has been increasing in South Korea for 33 years. Glomerular disease was the most common across all age groups, tubulointerstitial and vascular diseases increased over 60 years.

Letter to the Editor

Variation in mitotic counting and risk classification practices for gastrointestinal stromal tumors: a survey of pathologists in South Korea: In Hye Song, Soomin Ahn, Jeong-Hyeon Jo, Young Soo Park; J Pathol Transl Med. 2025;59(5):348-352. Published online September 8, 2025; DOI: https://doi.org/10.4132/jptm.2025.08.14

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Original Article

Characterization of undifferentiated carcinoma of the salivary gland: clinicopathological and immunohistochemical analyses in comparison with lymphoepithelial carcinoma: Sangjoon Choi, Gyuheon Choi, Hee Jin Lee, Joon Seon Song, Yoon Se Lee, Seung-Ho Choi, Kyung-Ja Cho; J Pathol Transl Med. 2025;59(6):361-370. Published online September 8, 2025; DOI: https://doi.org/10.4132/jptm.2025.07.07

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Abstract PDF: Background
This study aimed to reclassify a subset of poorly differentiated salivary gland carcinoma that do not conform to any entities of the current World Health Organization (WHO) classification into the category of undifferentiated carcinoma (UDC) because they lack specific histologic differentiation or immunophenotype. Methods: Cases of salivary gland carcinomas from Asan Medical Center (2002–2020) that did not fit any existing WHO classification criteria and were diagnosed as poorly differentiated carcinoma, high-grade carcinoma, or UDC, were retrospectively reviewed. Immunohistochemical (IHC) staining for p40, neuroendocrine markers, androgen receptor (AR), and gross cystic disease fluid protein 15 (GCDFP-15) and Epstein-Barr virus (EBV) in situ hybridization (ISH) were performed. Clinical data were collected from the electronic medical records. Results: Six salivary gland carcinomas did not align with any specific entities and lacked distinct differentiation. Two of six cases displayed lymphoepithelial carcinoma (LEC)-like morphology but were negative or showed negligible immunoreactivity for p40 and EBV ISH, distinguishing them from LEC of the salivary gland. Two cases showed strong AR positivity, suggesting a potential overlap with salivary duct carcinoma (SDC) but lacked classic SDC morphologies and GCDFP-15 expression. No cases expressed neuroendocrine markers. Conclusions: This study proposes reclassifying these poorly differentiated or high-grade salivary gland carcinomas as UDC based on their indeterminate differentiation and IHC profiles. This may lead to a clearer diagnostic category and enhance our understanding of these high-grade tumors.

Case Study

Composite chronic lymphocytic leukemia and mantle cell lymphoma involving the bone marrow: a case report and literature review: Roksolana Demianets, Susan O’Brien, Khosrow Mahdavi, Chenchen Niu, Sumayya Aslam, Truc Tran, Ying Zhang, Ashley Gamayo, Xiaohui Zhao, Sherif A. Rezk; J Pathol Transl Med. 2025;59(5):334-339. Published online September 8, 2025; DOI: https://doi.org/10.4132/jptm.2025.07.02

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Abstract PDF: Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a clinically indolent lymphoproliferative disorder characterized by accumulation of mature B-cell lymphocytes. Given the common CD5 co-expression, mantle cell lymphoma (MCL) is one of the most important entities in the differential diagnosis. MCL and CLL/SLL might exhibit overlapping morphologic and immunohistochemical features, making diagnosis particularly difficult in cases of composite lymphomas. Here, we present a unique case of composite lymphoma in an 86-year-old male, along with a literature review on the immunophenotypic variability of both MCL and CLL, which should always be confirmed with additional ancillary cytogenetic and molecular studies.

Original Articles

Evaluation of potential prognostic significance of JUNB in human prostate cancer: a bioinformatic and histopathological study: Noha R. Noufal, Einas M. Yousef, Mohamed Taha; J Pathol Transl Med. 2025;59(5):291-305. Published online September 8, 2025; DOI: https://doi.org/10.4132/jptm.2025.06.06

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Abstract PDF Supplementary Material: Background
Prostate cancer is one of the most common malignancies in males worldwide. Serum prostate-specific antigen is a frequently employed biomarker in the diagnosis and risk stratification of prostate cancer; however, it is known for its low predictive accuracy for disease progression. New prognostic biomarkers are needed to distinguish aggressive prostate cancer from low-risk disease. This study aimed to identify and validate potential prognostic biomarkers of prostate cancer. Methods: Two prostate cancer datasets from the Gene Expression Omnibus were analyzed to identify differentially expressed genes between benign prostatic hyperplasia (BPH) and prostatic carcinoma. Immunohistochemistry was used to evaluate the JUNB proto-oncogene, a subunit of the AP-1 transcription factor (JUNB), in 70 prostate cancer patients and 10 BPH samples. Results: Our findings showed that JUNB was significantly enriched in prostate cancer-related pathways and biological processes. JUNB expression was considerably higher in prostatic adenocarcinoma patients than in BPH patients. Regarding JUNB expression in prostate cancer cases, lower levels of JUNB expression were associated with higher grades of prostatic adenocarcinoma. Lower JUNB expression was associated with a higher risk of prostatic adenocarcinoma progression and shorter overall survival. Conclusions: These results suggest that JUNB is a promising prognostic biomarker and a potential tumor suppressor in prostate cancer.

Unraveling the crucial role of CCL3 in nasopharyngeal carcinoma: bioinformatics and immunohistochemical insights: Xiaopeng Guo, Zhen Sun, Ya Liang, Aoshuang Chang, Junjun Ling, Houyu Zhao, Xianlu Zhuo; J Pathol Transl Med. 2025;59(5):281-290. Published online September 8, 2025; DOI: https://doi.org/10.4132/jptm.2025.05.23

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Abstract PDF: Background
C-C motif chemokine ligand 3 (CCL3) is a crucial chemokine that plays a fundamental role in the immune microenvironment and is closely linked to the development of various cancers. Despite its importance, there is limited research regarding the expression and function of CCL3 in nasopharyngeal carcinoma (NPC). Therefore, this study seeks to examine the expression of CCL3 and assess its clinical significance in NPC using bioinformatics analysis and experiments. Methods: The bioinformatics approach was employed to assess the expression and function of CCL3 in NPC. Subsequently, protein expression of CCL3 was detected in an NPC cohort using immunohistochemistry based on a tissue microarray. The relationship between CCL3 expression and clinical features was then investigated. Results: A total of 20 CCL3-related genes and 14 possible target genes were identified through bioinformatics analysis, many of which play crucial roles in pathways such as chemokine signaling pathway and transcriptional misregulation in cancer signaling pathways. CCL3 was found to be associated with drug resistance and various immune cell infiltrations. In NPC, CCL3 expression was significantly higher than normal controls, and high expression of CCL3 correlated with cervical lymph node metastasis, tumor recurrence, advanced clinical stage, and poor prognosis. Conclusions: CCL3 may be a key gene in the initiation and progression of NPC. It has the potential to serve as both a diagnostic biomarker and a therapeutic target for NPC.

Review Article

Central nervous system tumors with BCOR internal tandem duplications: a systematic review of clinical, radiological, and pathological features in 69 cases: Ji Young Lee, Sung Sun Kim, Hee Jo Baek, Tae-Young Jung, Kyung-Sub Moon, Jae-Hyuk Lee, Kyung-Hwa Lee; J Pathol Transl Med. 2025;59(5):273-280. Published online September 1, 2025; DOI: https://doi.org/10.4132/jptm.2025.07.23

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Abstract PDF Supplementary Material: Central nervous system tumors with BCL6 corepressor (BCOR) internal tandem duplications (ITDs) constitute a rare, recently characterized pediatric neoplasm with distinct molecular and histopathological features. To date, 69 cases have been documented in the literature, including our institutional case. These neoplasms predominantly occur in young children, with the cerebellum representing the most frequent anatomical location. Radiologically, these tumors present as large, well-circumscribed masses frequently demonstrating necrosis, hemorrhage, and heterogeneous enhancement. Histologically, they are characterized by a monomorphic cellular population featuring ependymoma-like perivascular pseudorosettes, myxoid stroma, and elevated mitotic activity. Immunohistochemically, these tumors exhibit sparse glial fibrillary acidic protein expression while consistently demonstrating positive staining for vimentin and CD56. The defining molecular hallmark is a heterozygous ITD within exon 15 of the BCOR gene, with insertions ranging from 9 to 42 amino acids in length. BCOR immunohistochemistry reveals nuclear positivity in 97.9% of examined cases, although this finding is not pathognomonic for BCOR ITDs. This comprehensive review synthesizes data from all published cases of this novel tumor entity, providing a detailed analysis of clinical presentation, neuroimaging findings, histopathological features with differential diagnostic considerations, therapeutic approaches, and prognostic outcomes.

Newsletter

What’s new in medical renal pathology 2025: Updates on podocytopathy and immunofluorescence staining in medical kidney: Astrid Weins, Ibrahim Batal, Paola Romagnani, Geetika Singh, Rahul Raj, Nicole Andeen, Jonathan Zuckerman, Martina Uzzo, Mariam Priya Alexander, Anjali Satoskar; J Pathol Transl Med. 2025;59(4):269-272. Published online July 10, 2025; DOI: https://doi.org/10.4132/jptm.2025.06.19

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Abstract PDF: Diffuse podocytopathy, including minimal change disease and primary focal segmental glomerulosclerosis, is a common cause of nephrotic syndrome in adults and children. It is increasingly recognized to be autoimmune-mediated associated with anti-nephrin and other emerging anti-slit diaphragm antibodies, and can recur in the kidney allograft. Immunofluorescence is routinely used in evaluation of kidney biopsies, and updates include those on fibrillar diseases, monoclonal staining, lupus-like staining, and use of antibody KM55 in IgA-dominant glomerulonephritis.

Original Articles

Pancreatic cancer in liquid-based cytology: cytological features and cell block utility from 254 fine-needle aspiration samples: Jaeyong Min, Wookjin Oh, Baek-hui Kim; J Pathol Transl Med. 2025;59(4):249-261. Published online July 3, 2025; DOI: https://doi.org/10.4132/jptm.2025.05.27

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Abstract PDF Supplementary Material: Background
Despite the increasing use of liquid-based cytology (LBC) for pancreatic cancer diagnosis, relatively few studies have directly examined such research. This study analyzed the cytopathological features of pancreatic cancer in LBC and demonstrated the utility of cell blocks in diagnosing pancreatic lesions. Methods: A retrospective review identified LBC from 254 pancreatic fine-needle aspirations (FNAs) (221 patients). FNAs were categorized into five subgroups based on cytopathological, clinical, and histopathological findings. Two pathologists evaluated cytological features in LBC samples, cell blocks, and tissue slides. Comparative analysis assessed differences between groups. Results: Compared to benign lesions, LBC of pancreatic cancer more frequently showed a necrotic background, intermediate to high cellularity, mixed architecture, nuclear/cytoplasmic ratio >0.8, anisonucleosis >4:1, irregular and thick nuclear membranes, multinucleated tumor cells, hyperchromatic nuclei, coarse to clumped chromatin, and a prominent single nucleolus. In cases of conventional pancreatic ductal adenocarcinoma, the palliative treatment subgroup showed a higher incidence of necrotic background than the resection subgroup. In the cell block analysis, tumor cells not identified in LBC slides were detected in 16 FNAs. Additionally, 13 FNAs contributed to differential diagnosis: ancillary tests aided diagnosis in 12 FNAs, while histopathological evaluation of the cell block slide alone was helpful in one case. Conclusions: The cytological features of pancreatic cancer in LBC are similar to those observed in conventional smears, with a necrotic background suggesting advanced (unresectable) disease. The cell block methodology minimizes tumor cell loss and facilitates differential diagnosis by enabling ancillary testing.

AMACR is a highly sensitive and specific immunohistochemical marker for diagnosing prostate cancer on biopsy: a systematic review and meta-analysis: Johannes Cansius Prihadi, Stevan Kristian Lionardi, Nicolas Daniel Widjanarko, Steven Alvianto, Fransiskus Xaverius Rinaldi, Archie Fontana Iskandar; J Pathol Transl Med. 2025;59(4):235-248. Published online July 3, 2025; DOI: https://doi.org/10.4132/jptm.2025.04.16

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Abstract PDF Supplementary Material: Background
Alpha-methylacyl-CoA racemase (AMACR) is the preferred biomarker for distinguishing malignant from benign glands in prostate biopsies, showing high sensitivity and specificity for prostate cancer. A meta-analysis of immunohistochemistry (IHC) for AMACR is essential to further assess its diagnostic accuracy across diverse sample sources. Methods: A systematic search of databases including MEDLINE, ScienceDirect, ProQuest, Google Scholar, and the Cochrane Library was performed, focusing on studies of AMACR to diagnose prostate cancer, particularly in biopsy samples analyzed through IHC over the last 20 years. Quality of studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool, followed by a meta-analysis of regions and subgroups to calculate summary estimates of diagnostic test accuracy. Results: In the final analysis, 37 studies, with a pooled size of 5,898 samples, were included from the examination of 94 full-text papers. Among them, 27 studies with similar sample sources and testing methodologies underwent meta-analysis, yielding a combined sensitivity estimate of 0.90 (95% confidence interval [CI], 0.86 to 0.93) and specificity of 0.91 (95% CI, 0.83 to 0.95), both with significant heterogeneity (p < .01). The region beneath the hierarchical summary receiver operating characteristic curve was 0.95 (95% CI, 0.93 to 0.97), positive likelihood ratio was 9.6 (95% CI, 5.3 to 17.4), negative likelihood ratio was 0.11 (95% CI, 0.08 to 0.15), and diagnostic odds ratio was 88 (95% CI, 42 to 181). Conclusions: Our meta-analysis findings substantiate AMACR as a highly accurate tool for diagnosing prostate cancer, specifically in biopsy samples, via immunohistochemical staining. Further studies involving diverse samples are needed to enhance our understanding of the AMACR diagnostic accuracy in a range of clinical settings.

The Automatable Activity–Based Approach to Complexity Unit Scoring as a task-specific model approach to monetizing outcomes of pathology artificial intelligence solutions: Stavros Pantelakos, Martha Nifora, Georgios Agrogiannis; J Pathol Transl Med. 2025;59(4):225-234. Published online July 3, 2025; DOI: https://doi.org/10.4132/jptm.2025.04.15

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Abstract PDF: Background
Cost-containment policies are increasingly affecting decision-making in healthcare. In this context, the need for monetization of digital health interventions has been recently emphasized. Previous studies have attempted to extrapolate cost containment in conjunction with the implementation of digital pathology solutions mostly on the basis of operational cost savings or diagnostic error reduction. However, no study has attempted to link a wider spectrum of potential diagnostic tasks performed by artificial intelligence algorithms to financial figures.
Methods
Herein, we employ a workload measurement tool for the purpose of monetizing particular outcomes associated with the implementation of a pathology artificial intelligence solution. A hundred and thirty-two prostate core biopsy samples were encoded for workload using the Automatable Activity–Based Approach to Complexity Unit Scoring. Subsequently, avoided workload, full-time equivalent gains, and corresponding cost savings were calculated assuming full clinical deployment of a well-developed prostate cancer screening tool.
Results
For a fixed percentage of negative cores and a steady yearly workload of prostate core biopsies, the estimated total avoided workload amounted to 4,291 complexity units per year, with an average avoidance of 16.25 complexity units per ascension number. The calculated full-time equivalent gains were 0.12, whereas projected cost savings were as high as €2,402.34 per year or €0.55 per complexity unit, which in turn would yield an average of €8.93 per ascension number.
Conclusions
The Automatable Activity–Based Approach to Complexity Unit Scoring appears to be a suitable economic evaluation tool for assessing the possible implementation of task-specific artificial intelligence solutions in a given histopathology laboratory or group of laboratories, considering it is a task-specific workload measurement tool per design.

Review Articles

Recent topics on thyroid cytopathology: reporting systems and ancillary studies: Mitsuyoshi Hirokawa, Ayana Suzuki; J Pathol Transl Med. 2025;59(4):214-224. Published online June 30, 2025; DOI: https://doi.org/10.4132/jptm.2025.04.18

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Abstract PDF: As fine-needle aspiration techniques and diagnostic methodologies for thyroid nodules have continued to evolve and reporting systems have been updated accordingly, we need to be up to date with the latest information to achieve accurate diagnoses. However, the diagnostic approaches and therapeutic strategies for thyroid nodules vary across laboratories and institutions. Several differences exist between Western and Eastern practices regarding thyroid fine-needle aspiration. This review describes the reporting systems for thyroid cytopathology and ancillary studies. Updated reporting systems enhance the accuracy, consistency, and clarity of cytology reporting, leading to improved patient outcomes and management strategies. Although a single global reporting system is optimal, reporting systems tailored to each country is acceptable. In such cases, compatibility must be ensured to facilitate data sharing. Ancillary methods include liquid-based cytology, immunocytochemistry, biochemical measurements, flow cytometry, molecular testing, and artificial intelligence, all of which improve diagnostic accuracy. These methods continue to evolve, and cytopathologists should actively adopt the latest methods and information to achieve more accurate diagnoses. We believe this review will be useful to practitioners of routine thyroid cytology.

Multiple sclerosis: a practical review for pathologists: Rachel A. Multz, Pouya Jamshidi, Jared T. Ahrendsen; J Pathol Transl Med. 2025;59(4):203-213. Published online June 27, 2025; DOI: https://doi.org/10.4132/jptm.2025.05.20

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Abstract PDF

Multiple sclerosis (MS) is an immune-mediated demyelinating disorder of the central nervous system. It is a chronic disorder resulting in neurologic dysfunction that is disseminated both in time (multiple discrete episodes) and space (involving multiple sites). Histologically, MS is characterized by localized loss of myelin with relative preservation of axons. This review will discuss the epidemiology, clinical, laboratory, radiologic, and pathologic features of multiple sclerosis, as well as briefly touch on the differential diagnosis, treatment, and prognosis of the disease, especially as they relate to the pathologic interpretation of tissue specimens.

Citations

Citations to this article as recorded by

White Matter in Crisis: Oligodendrocytes and the Pathophysiology of Multiple Sclerosis
Mario García-Domínguez
Cells.2025; 14(18): 1408. CrossRef
Tumefactive demyelinating lesions: a case report and literature review
Raneem Jaki, Zyad Al-Frejat, Ziad Bitar
BMC Neurology.2025;[Epub] CrossRef

Case Studies

Acquired aberrant partial CD3 expression in recurrent Epstein-Barr virus–negative solitary plasmacytoma of tonsil: Chenchen Niu, Dong Ren, Truc Tran, Ashley Gamayo, Sherif Rezk, Xiaohui Zhao; J Pathol Transl Med. 2025;59(4):262-268. Published online May 15, 2025; DOI: https://doi.org/10.4132/jptm.2025.04.17

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Abstract PDF: The aberrant expression of specific T-cell maker CD3 in B-cell neoplasms can be a potential diagnostic pitfall leading to a misclassification of cell lineage. Here, we report a case of recurrent solitary plasmacytoma with new aberrant expression of CD3. The neoplastic plasma cells of the recurrent tumor were kappa restricted, positive for CD138, MUM1, negative for CD20, cyclin D1, and Epstein-Barr virus. CD79a was positive in majority of the tumor cells, except for a small focus which was strongly positive for CD3, but negative for other T-cell markers (CD2, CD5, CD7, CD4, and CD8) and CD56. The neoplastic plasma cells of the original tumor were negative for CD3. To the best of our knowledge, only one case of recurrent plasmacytoma with aberrant expression of CD3 has been published, which revealed disease progression in the recurrence. However, we did not observe morphologic evidence of disease progression in our case.

Cytological features of atypical adenomatous hyperplasia and adenocarcinoma in situ of the lung: a case report: Misa Takahashi, Seiya Homma, Chisato Setoguchi, Yoko Umezawa, Atsuhiko Sakamoto; J Pathol Transl Med. 2025;59(3):195-200. Published online May 9, 2025; DOI: https://doi.org/10.4132/jptm.2025.04.09

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Abstract PDF: Atypical adenomatous hyperplasia (AAH) and adenocarcinoma in situ (AIS) are generally treated as different lesions, depending on the differences in lesion size and histological findings. However, these differences are not absolute; thus, AAH and AIS are often difficult to distinguish. Moreover, whether AAH and AIS can be regarded as different lesions remains unknown because cytological specimens, especially those of AAH, are rare. In this study, we examined these uncommon cytological specimens and compared the cytological findings between AAH and AIS. We observed many common cytological features with no obvious differences between AAH and AIS. These findings suggest that these two distinct lesions can be grouped into a single category. Therefore, we propose creating a new cytological category.

Original Articles

Primary Merkel cell carcinoma of the salivary gland: a clinicopathologic study of four cases with a review of literature: Gyuheon Choi, Joon Seon Song, Hee Jin Lee, Gi Hwan Kim, Young Ho Jung, Yoon Se Lee, Kyung-Ja Cho; J Pathol Transl Med. 2025;59(3):171-179. Published online April 30, 2025; DOI: https://doi.org/10.4132/jptm.2025.03.25

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Abstract PDF

Background
Primary Merkel cell carcinoma of the salivary gland is currently not listed in the World Health Organization classification. However, cases of Merkel cell type neuroendocrine carcinomas of the salivary gland with perinuclear cytokeratin 20 positivity have been intermittently reported. We here investigated the clinicopathologic features of additional cases.
Methods
Data of four cases of Merkel cell type small cell neuroendocrine carcinoma of the salivary gland were retrieved. To confirm the tumors’ primary nature, clinical records and pathologic materials were reviewed. Optimal immunohistochemical staining was performed to support the diagnosis.
Results
All tumors were located in the parotid gland. Possibilities of metastasis were excluded in all cases through a meticulous clinicopathological review. Tumor histology was consistent with the diagnosis of small cell neuroendocrine carcinoma. Tumors’ immunohistochemical phenotypes were consistent with Merkel cell carcinoma, including Merkel cell polyomavirus large T antigen positivity in two of the four cases.
Conclusions
Merkel cell carcinomas can originate in salivary glands and are partly associated with Merkel cell polyomavirus infection as in cutaneous Merkel cell carcinomas.

Citations

Citations to this article as recorded by

Parotid intranodal metastasis of Merkel cell carcinoma: a rare case report
Tong Gao, Dengshun Wang, Hongwei Yu, Yu’e Wang, Haibin Lu
BMC Oral Health.2025;[Epub] CrossRef

Thoracic aortic calcification as a predictor of coronary artery disease: a systematic review and meta-analysis: Hussein Nafakhi, Alaa Salah Jumaah, Akeel Abed Yasseen; J Pathol Transl Med. 2025;59(3):161-170. Published online April 30, 2025; DOI: https://doi.org/10.4132/jptm.2025.03.05

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Abstract PDF Supplementary Material

Background
The relationship between coronary atherosclerosis (progression, outcome) and calcification in the thoracic aorta (TAC), particularly across its various segments, is complex and often shows conflicting associations in the literature. To address this debated and complex relationship, we aimed to evaluate how TAC and its segments correlate with the presence and severity of coronary artery disease (CAD).
Methods
We reviewed all articles published between January 1990 and September 2024 that examined the link between TAC and CAD and were indexed in PubMed, Scopus, or EMBASE. Using a random-effects model, we calculated pooled proportions, odds ratios, and corresponding 95% confidence intervals (CIs) to evaluate the association between TAC and CAD, with consideration of severity.
Results
The study included 17 studies with 8,187 participants, 2,775 of whom had CAD (1,059 with severe CAD), and 5,412 of whom did not. The pooled odds ratio of TAC in patients with CAD compared to that in those without was 3.874 (95% CI, 2.789 to 5.381). For severe CAD versus mild CAD, the odds ratio was 8.005 (95% CI, 2.611 to 24.542). Calcification of the aortic root (pooled proportion, 51%; 95% CI, 0.282 to 0.733) or descending aorta (pooled proportion, 53.4%; 95% CI, 0.341 to 0.718) had the strongest association with CAD compared to calcification of the arch or ascending aorta.
Conclusions
TAC is significantly associated with both the presence and severity of CAD. Calcification in the descending aorta and aortic root is more strongly linked to CAD than calcification in the arch or ascending aorta.

Citations

Citations to this article as recorded by

International Liver Transplantation Society/Liver Intensive Care Group of Europe guidelines for cardiovascular assessment before liver transplantation
Emmanuel Weiss, Gonzalo Crespo, Alexandra Anderson, Gianni Biancofiore, Ryan Chadha, Jacek B. Cywinski, Andrea De Gasperi, James Findlay, Marc Giménez-Milà, Constantine Karvellas, Michael Kaufman, Ashish Malik, Marina Moguilevitch, Sher-Lu Pai, Koen Reynt
American Journal of Transplantation.2025;[Epub] CrossRef

Lessons learned from the first 2 years of experience with thyroid core needle biopsy at an Indonesian national referral hospital: Agnes Stephanie Harahap, Maria Francisca Ham, Retno Asti Werdhani, Erwin Danil Julian, Rafi Ilmansyah, Chloe Indira Arfelita Mangunkusumso, Tri Juli Edi Tarigan; J Pathol Transl Med. 2025;59(3):149-160. Published online April 25, 2025; DOI: https://doi.org/10.4132/jptm.2025.02.19

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Abstract PDF: Background
Core needle biopsy (CNB) improves diagnostic accuracy by providing precise tissue sampling for histopathological evaluation, overcoming the limitation of inconclusive fine-needle aspiration results. This study evaluated the diagnostic performance of CNB in assessing thyroid nodules, with additional analysis of the benefits of BRAF V600E and RAS Q61R immunohistochemical (IHC) markers.
Methods
This retrospective study enrolled patients with thyroid nodules who underwent CNB at Dr. Cipto Mangunkusumo Hospital, Jakarta, from July 2022 to July 2024. CNB diagnoses were classified using the Korean Thyroid Association Criteria. Diagnostic efficacy was evaluated for neoplastic and malignant lesions, both independently and with BRAF V600E and RAS Q61R IHC. The correlation between nodule size and postoperative diagnosis was also analyzed.
Results
A total of 338 thyroid nodule samples was included, and 52.7% were classified as CNB category II. In the 104 samples with postoperative diagnoses, category IV was the most prevalent (39.4%). CNB demonstrated a sensitivity of 74% and a specificity of 100% for neoplastic lesions and 23.8% sensitivity and 100% specificity for malignant lesions. Combining CNB with BRAF V600E and RAS Q1R IHC increased the sensitivity to 77% for neoplastic lesions and 28.8% for malignant lesions. Larger nodules (>3 cm) were significantly associated with neoplastic (p = .005) and malignant lesions (p = .004).
Conclusions
CNB performs well in identifying neoplastic lesions, with or without BRAF V600E and RAS Q61R IHC, but its low sensitivity for malignant lesions warrants caution. While CNB categories V–VI indicate malignancy, the possibility of malignancy in categories I–IV should not be overlooked.

Diagnostic yield of fine needle aspiration with simultaneous core needle biopsy for thyroid nodules: Mohammad Ali Hasannia, Ramin Pourghorban, Hoda Asefi, Amir Aria, Elham Nazar, Hojat Ebrahiminik, Alireza Mohamadian; J Pathol Transl Med. 2025;59(3):180-187. Published online April 16, 2025; DOI: https://doi.org/10.4132/jptm.2025.03.04

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Abstract PDF: Background
Fine needle aspiration (FNA) is a widely utilized technique for assessing thyroid nodules; however, its inherent non-diagnostic rate poses diagnostic challenges. The present study aimed to evaluate and compare the diagnostic efficacy of FNA, core needle biopsy (CNB), and their combined application in the assessment of thyroid nodules.
Methods
A total of 56 nodules from 50 patients was analyzed using both FNA and simultaneous CNB. The ultrasound characteristics were categorized according to the American College of Radiology Thyroid Imaging Reporting and Data Systems classification system. The study compared the sensitivity, specificity, and accuracy of FNA, CNB, and the combination of the two techniques.
Results
The concordance between FNA and CNB was notably high, with a kappa coefficient of 0.837. The sensitivity for detecting thyroid malignancy was found to be 25.0% for FNA, 66.7% for CNB, and 83.3% for the combined FNA/CNB approach, with corresponding specificities of 84.6%, 97.4%, and 97.4%. The accuracy of the FNA/CNB combination was the highest at 94.1%.
Conclusions
The findings of this study indicate that both CNB and the FNA/CNB combination offer greater diagnostic accuracy for thyroid malignancy compared to FNA alone, with no significant complications reported. Integrating CNB with FNA findings may enhance management strategies and treatment outcomes for patients with thyroid nodules.

Case Study

Histopathological characteristics of Epstein-Barr virus (EBV)–associated encephalitis and colitis in chronic active EBV infection: Betty A Kasimo, James J Yahaya, Sun Och Yoon, Se Hoon Kim, Minsun Jung; J Pathol Transl Med. 2025;59(3):188-194. Published online April 16, 2025; DOI: https://doi.org/10.4132/jptm.2025.02.21

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Abstract PDF: Chronic active Epstein-Barr virus (CAEBV) can induce complications in various organs, including the brain and gastrointestinal tract. A 3-year-old boy was referred to the hospital with a history of fever and seizures for 15 days. A diagnosis of encephalitis based on computed tomography (CT) and magnetic resonance imaging findings and clinical correlation was made. Laboratory tests showed positive serology for Epstein-Barr virus (EBV) and negative for Rotavirus antigen and IgG and IgM antibodies for cytomegalovirus, herpes simplex virus, and varicella zoster virus, respectively. Abdominal CT showed diffuse wall thickening with fluid distension of small bowel loops, lower abdomen wall thickening, and a small amount of ascites. The biopsy demonstrated positive Epstein-Barr encoding region in situ hybridization in cells within the crypts and lamina propria. The patient was managed with steroids and hematopoietic stem cell transplantation (HSCT). This case showed histopathological characteristics of concurrent EBV-associated encephalitis and colitis in CAEBV infection. The three-step strategy of immunosuppressive therapy, chemotherapy, and allogeneic HSCT should be always be considered for prevention of disease progression.

Correspondence

Erratum: Diagnostic challenges in the assessment of thyroid neoplasms using nuclear features and vascular and capsular invasion: a multi-center interobserver agreement study: Agnes Stephanie Harahap, Mutiah Mutmainnah, Maria Francisca Ham, Dina Khoirunnisa, Abdillah Hasbi Assadyk, Husni Cangara, Aswiyanti Asri, Diah Prabawati Retnani, Fairuz Quzwain, Hasrayati Agustina, Hermawan Istiadi, Indri Windarti, Krisna Murti, Muhammad Takbir, Ni Made Mahastuti, Nila Kurniasari, Nungki Anggorowati, Pamela Abineno, Yulita Pundewi Setyorini, Kennichi Kakudo; J Pathol Transl Med. 2025;59(3):201-201. Published online March 31, 2025; DOI: https://doi.org/10.4132/jptm.2024.07.25.r; Corrects: J Pathol Transl Med 2024;58(6):299

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PDF

Original Article

Characteristics of RET gene mutations in Vietnamese medullary thyroid carcinoma patients: a single-center analysis: Van Hung Pham, Quoc Thang Pham, Minh Nguyen, Hoa Nhat Ngo, Thao Thi Thu Luu, Nha Dao Thi Minh, Trâm Đặng, Anh Tu Thai, Hoang Anh Vu, Dat Quoc Ngo; J Pathol Transl Med. 2025;59(2):125-132. Published online March 14, 2025; DOI: https://doi.org/10.4132/jptm.2025.01.18

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Abstract PDF Supplementary Material: Background
The RET gene point mutation is the main molecular alteration involved in medullary thyroid carcinoma (MTC) tumorigenesis. Previous studies in Vietnam mainly consisted of case reports, with limited data on larger sample sizes. In this study, we investigated RET gene mutations in exons 10, 11, and 16 and analyzed clinicopathological features of a series of Vietnamese MTC patients. Methods: We collected 33 tissue samples from patients with MTC and analyzed RET mutations using the Sanger sequencing method. The relationship between hotspot RET mutations (exons 10, 11, 16) and clinicopathological features were investigated. Results: Among the 33 analyzed cases, 17 tumors (52%) harbored RET mutations in exon 10, 11, or 16. A total of 10 distinct genetic alterations were identified, including eight missense mutations and two short indels. Of these, seven were classified as pathogenic mutations based on previous publications, with p.M918T being the most frequent (4 cases), followed by p.C634R (3 cases) and p.C618R (3 cases). Mutations were significantly associated with specific histological patterns, such as the nested/insular pattern (p=.026), giant cells (p=.007), nuclear pleomorphism (p=.018), stippled chromatin (p=.044), and amyloid deposits (p=.024). No mutations were found in germline analyses, suggesting these were somatic alterations. Conclusions: Our results provided the first comprehensive analysis of RET mutations in Vietnamese MTC patients. The most frequent mutation was p.M918T, followed by p.C634R and p.C618R. Mutations in these three exons were linked to specific histopathological features. Information on mutational profiles of patients with MTC will further aid in the development of targeted therapeutics to ensure effective disease management.

Correspondence

Erratum: Breast fine-needle aspiration cytology in the era of core-needle biopsy: what is its role?: Ahrong Kim, Hyun Jung Lee, Jee Yeon Kim; J Pathol Transl Med. 2025;59(2):147-147. Published online March 14, 2025; DOI: https://doi.org/10.4132/jptm.2024.11.01.r; Corrects: J Pathol Transl Med 2025;59(1):26

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PDF

Case Study

Mucocele of the rectal stump: mucinous cystic neoplasm with low-grade dysplasia simulating low-grade appendiceal mucinous neoplasm: Hasan Basri Aydin, Maria Faraz, A. David Chismark, Haiyan Qiu, Hwajeong Lee; J Pathol Transl Med. 2025;59(2):139-146. Published online February 26, 2025; DOI: https://doi.org/10.4132/jptm.2024.12.27

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Abstract PDF: Mucoceles, commonly observed in the appendix, are mucin-filled, dilated structures arising from a range of etiologies. Cases associated with dysplastic or neoplastic epithelium can rupture and disseminate within the abdominopelvic cavity. Similar lesions in other parts of the colon are exceedingly rare, with only 16 colonic mucoceles having been reported. The first case of a colonic mucinous neoplasm with dysplasia resembling a low-grade appendiceal mucinous neoplasm involving rectal stump was described in 2016. Here, we present the second such case arising in the rectal stump, identified in a 44-year-old male with extensive surgical history. Microscopic examination revealed low-grade dysplastic epithelium lining the cyst and mucin dissecting into the stroma, without evidence of rupture or extramural mucin. The patient was followed for 16 months without recurrence or peritoneal disease. The exact etiology and outcome of these rare lesions remain unknown, requiring close follow-up.

Original Articles

Association study of TYMS gene expression with TYMS and ENOSF1 genetic variants in neoadjuvant chemotherapy response of gastric cancer: Khadijeh Arjmandi, Iman Salahshourifar, Shiva Irani, Fereshteh Ameli, Mohsen Esfandbod; J Pathol Transl Med. 2025;59(2):105-114. Published online February 25, 2025; DOI: https://doi.org/10.4132/jptm.2024.11.05

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Abstract PDF

Background
The present research was designed to study the associations between genetic variants of TYMS and ENOSF1 genes with TYMS and ENOSF1 gene expression in neoadjuvant chemotherapy response among patients with gastric cancer. Methods: Formalin-embedded and paraffin-fixed matched tumor and normal gastric cancer tissue samples from patients who received neoadjuvant 5-fluorouracil (5-FU) treatment were obtained. DNA and RNA were extracted for all samples. A 28-bp variable number tandem repeat (VNTR) at the 5' untranslated region of TYMS gene and rs2612091 and rs2741171 variants in the ENOSF1 gene were genotyped for normal tissue samples. The real-time polymerase chain reaction method was used to study the expression of ENOSF1 and TYMS genes in both normal and tumor tissues. Data were analyzed using REST 2000 and SPSS ver. 26.0 software programs. Results: A significant association between TYMS 2R3R VNTR genotypes and 5-FU therapy was found (p = .032). The 3R3R and 2R2R genotypes were significantly associated with increased and decreased survival time, respectively (p = .003). The 3R3R genotype was significantly associated with TYMS overexpression (p < .001). Moreover, a significant association was found between the rs2612091 genotype and treatment outcome (p = .017). Conclusions: This study highlights the impact of TYMS and ENOSF1 genes as predictive indicators for survival and response to 5-FU–based neoadjuvant chemotherapy in gastric cancer patients.

Citations

Citations to this article as recorded by

Innovative biomaterial strategies for mitigating radiotherapy toxicity: multidimensional mechanistic interventions of nano-microscale materials and hydrogels
Yifan Liu, Fengdi Jiang, Jie Song, Huaijin Qiao, Junlong Dai, Hao Bai, Shuyu Zhang
Coordination Chemistry Reviews.2026; 549: 217313. CrossRef

Low Ki-67 labeling index is a clinically useful predictive factor for recurrence-free survival in patients with papillary thyroid carcinoma: Takashi Masui, Katsunari Yane, Ichiro Ota, Kennichi Kakudo, Tomoko Wakasa, Satoru Koike, Hirotaka Kinugawa, Ryuji Yasumatsu, Tadashi Kitahara; J Pathol Transl Med. 2025;59(2):115-124. Published online February 18, 2025; DOI: https://doi.org/10.4132/jptm.2024.11.08

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Abstract PDF

Background
We report a new risk stratification of invasive stage papillary thyroid carcinomas (PTCs) by combining invasive status, using extrathyroid invasion (Ex) status, and tumor growth speed using the Ki-67 labeling index (LI). Methods: We examined tumor recurrence in 167 patients with PTC who were surgically treated at the Kindai University Nara Hospital between 2010 and 2022. The patients were classified according to the degree of invasion [negative (Ex0) or positive (Ex1, Ex2, and Ex3)] and tumor growth speed expressed with Ki-67 LI, as low (<5%) or high (>5%). This study confirmed previous findings that the disease-free survival (DFS) rate in PTCs significantly differed between patients with a high and low Ki-67 index. Results: When combining Ex status (negative or positive) and Ki-67 proliferation status (low or high), the DFS rate of invasion in the negative, low Ki-67 LI group was only 1.1%, while that of invasion in the positive, high Ki-67 LI was 44.1%. This study reports for the first time that recurrence risks can be stratified accurately when combining carcinoma’s essential two features of extrathyroid invasion status and tumor growth speed. Conclusions: We believe the evidence for low tumor recurrence risk may contribute to use of more conservative treatment options for invasive-stage PTCs and help alleviate patient anxiety about tumor recurrence and death.

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Research Progress on the Correlation between Three Biomarkers, Ki-67, CAIX and VEGF and Clear Cell Renal Cell Carcinoma
锦容马
Advances in Clinical Medicine.2025; 15(09): 326. CrossRef
Immunophenotypic Panel for Comprehensive Characterization of Aggressive Thyroid Carcinomas
Mihail Ceausu, Mihai Alin Publik, Dana Terzea, Carmen Adina Cristea, Dumitru Ioachim, Dana Manda, Sorina Schipor
Cells.2025; 14(19): 1554. CrossRef
High Ki-67 labeling index correlates with aggressive clinicopathological features in papillary thyroid carcinoma: a retrospective study
Defi Nurlia Erdian, Maria Francisca Ham, Dina Khoirunnisa, Agnes Stephanie Harahap
Thyroid Research.2025;[Epub] CrossRef

Categorizing high-grade serous ovarian carcinoma into clinically relevant subgroups using deep learning–based histomic clusters: Byungsoo Ahn, Eunhyang Park; J Pathol Transl Med. 2025;59(2):91-104. Published online February 18, 2025; DOI: https://doi.org/10.4132/jptm.2024.10.23

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Abstract PDF Supplementary Material

Background
High-grade serous ovarian carcinoma (HGSC) exhibits significant heterogeneity, posing challenges for effective clinical categorization. Understanding the histomorphological diversity within HGSC could lead to improved prognostic stratification and personalized treatment approaches. Methods: We applied the Histomic Atlases of Variation Of Cancers model to whole slide images from The Cancer Genome Atlas dataset for ovarian cancer. Histologically distinct tumor clones were grouped into common histomic clusters. Principal component analysis and K-means clustering classified HGSC samples into three groups: highly differentiated (HD), intermediately differentiated (ID), and lowly differentiated (LD). Results: HD tumors showed diverse patterns, lower densities, and stronger eosin staining. ID tumors had intermediate densities and balanced staining, while LD tumors were dense, patternless, and strongly hematoxylin-stained. RNA sequencing revealed distinct patterns in mitochondrial oxidative phosphorylation and energy metabolism, with upregulation in the HD, downregulation in the LD, and the ID positioned in between. Survival analysis showed significantly lower overall survival for the LD compared to the HD and ID, underscoring the critical role of mitochondrial dynamics and energy metabolism in HGSC progression. Conclusions: Deep learning-based histologic analysis effectively stratifies HGSC into clinically relevant prognostic groups, highlighting the role of mitochondrial dynamics and energy metabolism in disease progression. This method offers a novel approach to HGSC categorization.

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Learning Disabilities in the 21st Century: Integrating Neuroscience, Education, and Technology for Better Outcomes
Syed Mohammed Basheeruddin Asdaq, Ahmad H. Alhowail, Syed Imam Rabbani, Naira Nayeem, Syed Mohammed Emaduddin Asdaq, Faiqa Nausheen
SAGE Open.2025;[Epub] CrossRef

PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in nasopharyngeal carcinoma: Ranran Feng, Yilin Guo, Meilin Chen, Ziying Tian, Yijun Liu, Su Jiang, Jieyu Zhou, Qingluan Liu, Xiayu Li, Wei Xiong, Lei Shi, Songqing Fan, Guiyuan Li, Wenling Zhang; J Pathol Transl Med. 2025;59(1):68-83. Published online January 15, 2025; DOI: https://doi.org/10.4132/jptm.2024.11.27

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Abstract PDF Supplementary Material

Background
Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear.
Methods
We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP).
Results
We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin.
Conclusions
PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

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The Potential Role of SP-G and PLUNC in Tumor Pathogenesis and Wound Healing in the Human Larynx
Aurelius Scheer, Lars Bräuer, Markus Eckstein, Heinrich Iro, Friedrich Paulsen, Fabian Garreis, Martin Schicht, Antoniu-Oreste Gostian
Biomedicines.2025; 13(5): 1240. CrossRef
Role of DEAD/DEAH-box helicases in immunity, infection and cancers
Rex Devasahayam Arokia Balaya, Saptami Kanekar, Shreya Kumar, Richard K. Kandasamy
Cell Communication and Signaling.2025;[Epub] CrossRef
CHIP modulates Wnt/β-catenin signalling in colorectal cancer through proteasomal degradation of DDX17
Sunny Kumar, Sayani Ghosh, Malini Basu, Mrinal K. Ghosh
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research.2025; 1872(8): 120049. CrossRef

Reviews

Post-transplant liver biopsies: a concise and practical approach for beginners: Mohamad Besher Ourfali, David Hirsch, Marianna Scranton, Tony El Jabbour; J Pathol Transl Med. 2025;59(1):1-10. Published online January 15, 2025; DOI: https://doi.org/10.4132/jptm.2024.11.15

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Abstract PDF

Exposure to post-transplant liver biopsies varies among pathology residencies and largely depends on the institution's training program, particularly if the hospital has a liver transplant program. The interpretation of biopsies from transplanted livers presents its own set of challenges, even for those with a solid understanding of non-transplant medical liver biopsies. In this review, we aim to provide a succinct, step-by-step approach to help you interpret liver transplant biopsies. This article may be beneficial for residents interested in liver pathology, gastrointestinal and liver pathology fellows in the early stages of training, clinical gastroenterology and hepatology fellows, hepatologists and general pathologists who are curious about this niche.

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Histological and Molecular Evaluation of Liver Biopsies: A Practical and Updated Review
Joon Hyuk Choi
International Journal of Molecular Sciences.2025; 26(16): 7729. CrossRef

Professional biobanking education in Korea based on ISO 20387: Jong Ok Kim, Chungyeul Kim, Sangyong Song, Eunah Shin, Ji-Sun Song, Mee Sook Roh, Dong-chul Kim, Han-Kyeom Kim, Joon Mee Kim, Yeong Jin Choi; J Pathol Transl Med. 2025;59(1):11-25. Published online January 15, 2025; DOI: https://doi.org/10.4132/jptm.2024.11.04

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Abstract PDF

To ensure high-quality bioresources and standardize biobanks, there is an urgent need to develop and disseminate educational training programs in accordance with ISO 20387, which was developed in 2018. The standardization of biobank education programs is also required to train biobank experts. The subdivision of categories and levels of education is necessary for jobs such as operations manager (bank president), quality manager, practitioner, and administrator. Essential training includes programs tailored for beginner, intermediate, and advanced practitioners, along with customized training for operations managers. We reviewed and studied ways to develop an appropriate range of education and training opportunities for standard biobanking education and the training of experts based on KS J ISO 20387. We propose more systematic and professional biobanking training programs in accordance with ISO 20387, in addition to the certification programs of the National Biobank and the Korean Laboratory Accreditation System. We suggest various training programs appropriate to a student’s affiliation or work, such as university biobanking specialized education, short-term job training at unit biobanks, biobank research institute symposiums by the Korean Society of Pathologists, and education programs for biobankers and researchers. Through these various education programs, we expect that Korean biobanks will satisfy global standards, meet the needs of users and researchers, and contribute to the advancement of science.

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Development of a big data platform for collecting and utilizing clinical information from the Korea Biobank Network
Yun Seon Im, Seol Whan Oh, Ki Hoon Kim, Wona Choi, In Young Choi
BMC Medical Informatics and Decision Making.2025;[Epub] CrossRef
Frozen section histopathology and preanalytical factors affecting nucleic acid integrity in biobanked fresh-frozen human cancer tissues
Soungeun Kim, Jaewon Kang, Boyeon Kim, Yoonjin Kwak, Hye Seung Lee
Journal of Pathology and Translational Medicine.2025; 59(6): 398. CrossRef

Breast fine-needle aspiration cytology in the era of core-needle biopsy: what is its role?: Ahrong Kim, Hyun Jung Lee, Jee Yeon Kim; J Pathol Transl Med. 2025;59(1):26-38. Published online January 15, 2025; DOI: https://doi.org/10.4132/jptm.2024.11.01; Correction in: J Pathol Transl Med 2025;59(2):147

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Abstract PDF

Fine-needle aspiration cytology (FNAC) has long been recognized as a minimally invasive, cost-effective, and reliable diagnostic tool for breast lesions. However, with the advent of core-needle biopsy (CNB), the role of FNAC has diminished in some clinical settings. This review aims to re-evaluate the diagnostic value of FNAC in the current era, focusing on its complementary use alongside CNB, the adoption of new approaches such as the International Academy of Cytology Yokohama System, and the implementation of rapid on-site evaluation to reduce inadequate sample rates. Advances in liquid-based cytology, receptor expression testing, molecular diagnostics, and artificial intelligence are discussed, highlighting their potential to enhance the diagnostic accuracy of FNAC. Despite challenges, FNAC remains a valuable diagnostic method, particularly in low-resource settings and specific clinical scenarios, and its role continues to evolve with technology.

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Bulk-lysis protocols as a sensitive method for investigation of circulating CK19 cells in the peripheral blood of patients with breast cancer by flow cytometry
Daniella Serafin Couto Vieira, Laura Otto Walter, Maria Eduarda Cunha da Silva, Lisandra de Oliveira Silva, Heloísa Zorzi Costa, Chandra Chiappin Cardoso, Fernando Carlos de Lander Schmitt, Maria Cláudia Santos-Silva
Analytical Methods.2025; 17(23): 4771. CrossRef

Original Article

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; J Pathol Transl Med. 2025;59(1):60-67. Published online January 15, 2025; DOI: https://doi.org/10.4132/jptm.2024.10.01

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Abstract PDF: 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.

Case Study

Primary renal BCOR::CCNB3 sarcoma in a female patient: case report: Somang Lee, Binnari Kim; J Pathol Transl Med. 2025;59(1):84-90. Published online January 15, 2025; DOI: https://doi.org/10.4132/jptm.2024.09.30

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Abstract PDF

BCOR-rearranged sarcoma was classified by the World Health Organization in 2020 as a new subgroup of undifferentiated small round-cell sarcoma. It is known to occur very rarely in the kidney. This report presents the first case of a primary renal BCOR::CCNB3 sarcoma in a 22-year-old woman. An 8-cm cystic mass was identified in the left kidney by abdominal pelvic computed tomography. Histopathologic examination revealed the mass to be composed of small round to oval or spindle cells with fibrous septa and a delicate vascular network. A BCOR::CCNB3 fusion was detected by next-generation sequencing–based molecular testing. BCOR::CCNB3 sarcoma presents diagnostic difficulties, highlighting the importance of recognizing its histological features. Immunohistochemical markers are helpful for diagnosis, but genetic molecular testing is necessary for accurate diagnosis. These tumors have a very poor and aggressive prognosis, and an optimal therapeutic regimen has not yet been defined. Therefore, further studies are needed.

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Update on the management of BCOR::CCNB3 sarcoma
Jungo Imanishi, Kenji Sato, Yoshinao Kikuchi, Asako Yamamoto, Shiori Watabe, Taisuke Matsuyama, Chiaki Sato, Hiroshi Kobayashi, Hirotaka Kawano
Japanese Journal of Clinical Oncology.2025; 55(10): 1097. CrossRef

Reviews

Next step of molecular pathology: next-generation sequencing in cytology: Ricella Souza da Silva, Fernando Schmitt; J Pathol Transl Med. 2024;58(6):291-298. Published online November 7, 2024; DOI: https://doi.org/10.4132/jptm.2024.10.22

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Abstract PDF

The evolving landscape of precision oncology underscores the pivotal shift from morphological diagnosis to treatment decisions driven by molecular profiling. Recent guidelines from the European Society for Medical Oncology recomend the use of next-generation sequencing (NGS) across a broader range of cancers, reflecting its superior efficiency and clinical value. NGS not only updates oncology testing by offering quicker, sample-friendly, and sensitive analysis but also reduces the need for multiple individual tests. Cytology samples, often obtained through less invasive methods, can yield high-quality genetic material suitable for molecular analysis. This article focuses on optimizing the use of cytology samples in NGS, and outlines their potential benefits in identifying actionable molecular alterations for targeted therapies across various solid tumors. It also addresses the need for validation studies and the strategies to incorporate or combine different types of samples into routine clinical practice. Integrating cytological and liquid biopsies into routine clinical practice, alongside conventional tissue biopsies, offers a comprehensive approach to tumor genotyping, early disease detection, and monitoring of therapeutic responses across various solid tumor types. For comprehensive biomarker characterization, all patient specimens, although limited, is always valuable.

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The World Health Organization Reporting System for Lymph Node, Spleen, and Thymus Cytopathology: Part 1 – Lymph Node
Immacolata Cozzolino, Mats Ehinger, Maria Calaminici, Andrea Ronchi, Mousa A. Al-Abbadi, Helena Barroca, Beata Bode-Lesniewska, David F. Chhieng, Ruth L. Katz, Oscar Lin, L. Jeffrey Medeiros, Martha Bishop Pitman, Arvind Rajwanshi, Fernando C. Schmitt, Ph
Acta Cytologica.2025; : 1. CrossRef
The impact of cytological preparation techniques on RNA quality: A comparative study on smear samples
Cisel Aydin Mericoz, Gulsum Caylak, Elif Sevin Sanioglu, Zeynep Seçil Satilmis, Ayse Humeyra Dur Karasayar, Ibrahim Kulac
Cancer Cytopathology.2025;[Epub] CrossRef
Reimagining cytopathology in the molecular era: Integration or fragmentation?
Sumanta Das, R. Naveen Kumar, Biswajit Dey, Pranjal Kalita
Cytojournal.2025; 22: 94. CrossRef

Cervical intraepithelial neoplasia and cervical cytology in pregnancy: Ji-Young Kim, Jeong Yun Shim; J Pathol Transl Med. 2024;58(6):283-290. Published online November 7, 2024; DOI: https://doi.org/10.4132/jptm.2024.10.17

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Abstract PDF

Cervical cancer screening during pregnancy presents unique challenges for cytologic interpretation. This review focuses on pregnancy-associated cytomorphological changes and their impact on diagnosis of cervical intraepithelial neoplasia (CIN) and cervical cancer. Pregnancy-induced alterations include navicular cells, hyperplastic endocervical cells, immature metaplastic cells, and occasional decidual cells or trophoblasts. These changes can mimic abnormalities such as koilocytosis, adenocarcinoma in situ, and high-grade squamous intraepithelial lesions, potentially leading to misdiagnosis. Careful attention to nuclear features and awareness of pregnancy-related changes are crucial for correct interpretation. The natural history of CIN during pregnancy shows higher regression rates, particularly for CIN 2, with minimal risk of progression. Management of abnormal cytology follows modified risk-based guidelines to avoid invasive procedures, with treatment typically deferred until postpartum. The findings reported in this review emphasize the importance of considering pregnancy status in cytological interpretation, highlight potential problems, and provide guidance on differentiating benign pregnancy-related changes from true abnormalities. Understanding these nuances is essential for accurate diagnosis and proper management of cervical abnormalities in pregnant women.

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The significance of biological samples from pregnant women in cervical intraepithelial neoplasia
Xue Mi, Maharjan Rashmi, Zangyu Pan, Di Wu, Jinwei Miao
Frontiers in Medicine.2025;[Epub] CrossRef
Oncologic and pregnancy outcomes of cervical high-grade intraepithelial lesions and delivery mode
Olga P. Matylevich, Ilya A. Tarasau, Sviatlana Y. Shelkovich, Aliaksandr F. Martsinkevich
Academia Oncology.2025;[Epub] CrossRef

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