Journal of Pathology and Translational Medicine

Most-download articles are from the articles published in 2024 during the last three month.

Newsletter

What's new in molecular genetic pathology 2026: emerging biomarkers for personalized cancer therapies: Umberto Maccio; J Pathol Transl Med. 2026;60(2):280-283. Published online January 3, 2026; DOI: https://doi.org/10.4132/jptm.2026.01.03

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Abstract PDF: New and emerging biomarkers and current molecular assays for the most prevalent and lethal cancers worldwide—breast, lung, prostate, and colorectal cancer—are described. Notably, HER2-low breast cancer and HER2-mutated non-small cell lung cancer have recently been recognized as targetable entities. In addition, various tissue-based analyses are now available to assess prognosis and the risk of relapse in prostate cancer.

Original Article

Clinicopathological and molecular mechanisms of CLDN18.2 in gastric cancer aggressiveness: a high-risk population study with multi-omics profiling: Hengquan Wu, Mei Li, Gang Wang, Peiqing Liao, Peng Zhang, Luxi Yang, Yumin Li, Tao Liu, Wenting He; J Pathol Transl Med. 2026;60(1):47-57. Published online January 5, 2026; DOI: https://doi.org/10.4132/jptm.2025.09.11

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Abstract PDF Supplementary Material: Background
The tight junction protein claudin18.2 (CLDN18.2) has been implicated in poor prognosis and suboptimal immunotherapy response in gastric cancer (GC). This study investigates the clinicopathological relevance of CLDN18.2 expression and its association with molecular subtypes in GC patients from a high-incidence region, combining transcriptomic and proteomic approaches to explore how CLDN18.2 contributes to progression and metastasis.
Methods
A retrospective cohort of 494 GC patients (2019–2024) underwent immunohistochemical analysis for CLDN18.2, Epstein-Barr virus (Epstein–Barr virus–encoded RNA), p53, human epidermal growth factor receptor 2 (HER2), and mismatch repair proteins (MLH1, MSH2, PMS2, and MSH6). CLDN18.2 positivity was defined as moderate to strong (2+/3+) membranous staining in ≥75% of tumor cells. Clinicopathological correlations, biomarker associations, and survival outcomes were evaluated. Transcriptomic and proteomic sequencing was performed to explore molecular mechanisms.
Results
CLDN18.2 positivity was observed in 26.9% (133/494) of gastric adenocarcinomas. CLDN18.2-positive tumors correlated with TNM stage (p = .003) and shorter overall survival (p = .018). No associations were identified with age, sex, HER2 status, microsatellite instability, or Epstein-Barr virus infection. Transcriptomic profiling revealed CLDN18.2-high tumors enriched in pathways involving cell junction disruption, signaling regulation, and immune modulation. Proteomic profiling showed that tumors with high CLDN18.2 were enriched in multiple mechanism-related pathways such as integrated metabolic reprogramming, cytoskeletal recombination, immune microenvironment dysregulation, and pro-survival signaling. These mechanisms may collectively contribute to tumor progression and metastasis.
Conclusions
CLDN18.2 overexpression is associated with poor prognosis in GC patients. Transcriptomic and proteomic analyses demonstrate that CLDN18.2 promotes tumor progression and metastasis, underscoring its potential as an independent prognostic factor in regions with a high incidence of GC.

Review Article

Solitary fibrous tumor: an updated review: Joon Hyuk Choi; J Pathol Transl Med. 2026;60(1):20-46. Published online December 29, 2025; DOI: https://doi.org/10.4132/jptm.2025.10.08

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Abstract PDF: Solitary fibrous tumor (SFT) is a fibroblastic neoplasm characterized by a branching, thin-walled dilated staghorn-shaped (hemangiopericytoma-like) vasculature and a NAB2::STAT6 gene fusion. SFTs can occur in almost any anatomical location, including superficial and deep soft tissues, visceral organs, and bone. They most commonly occur in extrapleural locations, equally affect both sexes, and are typically present in adults. Although metastasis is rare, SFTs frequently show local recurrence. The diagnosis of SFTs is difficult because of their broad histological and morphological overlap with other neoplasms. An accurate diagnosis is important for guiding disease management and prognosis. Despite advances in molecular diagnostics and therapeutic strategies, the biological complexity and unpredictable clinical behavior of SFTs present significant challenges. This review provides an updated overview of SFT, with a focus on its molecular genetics, histopathological features, and diagnostic considerations.

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.

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Molecular Pathogenesis and Targeted Therapies for Myeloproliferative Hypereosinophilic Neoplasms
Colette Hanna, Joe Rizkallah, Nicole Charbel, Shereen Sakkal, Fadi G. Haddad
Current Hematologic Malignancy Reports.2026;[Epub] CrossRef

Original Articles

The significance of papillary architecture in the follow-up biopsies of patients with progestin-treated atypical endometrial hyperplasia: Wangpan J. Shi, Oluwole Fadare; J Pathol Transl Med. 2026;60(1):58-68. Published online January 8, 2026; DOI: https://doi.org/10.4132/jptm.2025.09.12

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Abstract PDF: Background
Follow-up biopsies in patients with progestin-treated atypical endometrial hyperplasia/endometrioid intraepithelial neoplasia (AH/EIN) may show papillary structures, the significance of which is unclear. Methods: The authors reviewed 253 serial specimens of 84 consecutive patients diagnosed with AH/EIN, inclusive of each patient's pre-progestin treatment sample and all post-treatment specimens. We assessed the predictive relationship between papillary architecture in a post-treatment biopsy and two study outcomes: AH/EIN or carcinoma in at least one sample subsequent to the one in which papillae were identified, and/or the last specimen received for that patient. Results: Papillae were identified in only 51.5% of pre-treatment samples but were present in at least one subsequent post-treatment sample for all patients. Post-treatment samples that exhibited papillae and no glandular crowding were associated with AH/EIN in at least one subsequent specimen in 39.7% (29/73) of cases, compared to 24.0% (6/25) in samples with neither papillae nor glandular crowding (p = .227) and 64.0% (16/25) in samples with concurrent gland crowding and papillae (p = .048). Univariate logistic regression analyses showed that the presence of papillae was not associated with study outcomes (odds ratio [OR], 0.99; 95% confidence interval [CI], 0.49 to 1.99; p = .985), as compared with gland crowding (OR, 1.54; 95% CI, 1.04 to 2.27; p = .031), or concurrent papillae and gland crowding (OR, 2.36; 95% CI, 1.01 to 5.52; p = .048). Conclusions: In post-treatment samples of progestin-treated AH/EIN, the presence of papillary architecture was not demonstrably associated with study outcomes independent of gland crowding, although the concurrent presence of both features may be significantly predictive.

Significance of KM55 immunohistochemical staining in the diagnosis and prognosis of IgA nephropathy: Hoe In Jeong, Beom Jin Lim, Minsun Jung; J Pathol Transl Med. 2026;60(1):69-82. Published online January 14, 2026; DOI: https://doi.org/10.4132/jptm.2025.09.17

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Abstract PDF: Background
Galactose-deficient IgA1 (Gd-IgA1) plays a crucial role in IgA nephropathy (IgAN). The monoclonal antibody KM55 has emerged as a simplified method for detecting Gd-IgA1; however, the clinicopathological significance of immunohistochemistry for Gd-IgA1 remains underexplored. This study evaluated the prognostic and clinicopathological significance of KM55 immunohistochemistry in IgAN. Methods: A total of 114 native kidney biopsies showing at least mild mesangial IgA positivity on immunofluorescence were retrospectively analyzed. Patients were categorized as having IgAN or non-IgAN diseases. The KM55 immunohistochemical staining was graded as 0, 1+, 2+, 3, or 4+. Data on Oxford classification, laboratory parameters, and renal outcomes were collected. Results: The IgAN group showed significantly higher KM55 scores than the non-IgAN group (median: 3 vs. 1; p < .001). IgAN cases were further stratified into KM55-high (≥3+, n = 38) and -low groups (≤2+, n = 37). The KM55-high group had significantly higher diastolic blood pressure, blood urea nitrogen, creatinine, urine protein/creatinine ratio, and Oxford mesangial hypercellularity scores, along with lower estimated glomerular filtration rate (eGFR) and serum albumin. Cox analysis revealed significantly poorer outcomes in the KM55-high group for chronic kidney disease stage 4 (p = .015), end-stage renal disease (p = .024), and 75% eGFR decline (p = .016). Conclusions: Mesangial Gd-IgA1 deposition graded by KM55 immunohistochemistry may be a useful adjunct for IgAN diagnosis and a potential prognostic biomarker.

Case Study

Drug-induced phospholipidosis of the kidney suspected to be caused by atomoxetine: Sung-Eun Choi, Kee Hyuck Kim, Minsun Jung, Jeong Hae Kie; J Pathol Transl Med. 2026;60(1):124-128. Published online January 14, 2026; DOI: https://doi.org/10.4132/jptm.2025.12.10

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Abstract PDF

Drug-induced phospholipidosis (DIP) is characterized by intracellular accumulation of phospholipids with lamellar body formation secondary to drug-altered lipid metabolism, which can trigger inflammation and histopathological changes. Fabry disease and DIP both exhibit zebra bodies on electron microscopy, complicating differential diagnosis. A 17-year-old male with microscopic hematuria and proteinuria had received atomoxetine (40 mg) for 11 months to treat attention-deficit hyperactivity disorder. Light microscopy showed one glomerulus with perihilar sclerosis and periglomerular fibrosis. Kidney biopsy revealed zebra bodies in podocytes, initially suggesting Fabry disease. However, α-galactosidase A enzyme activity was normal on tandem mass spectrometry. Next-generation sequencing of GLA identified only three benign variants. This represents the first reported case of atomoxetine-induced DIP. When zebra bodies are observed, clinicians should consider DIP caused by cationic amphiphilic drugs alongside Fabry disease. Atomoxetine meets the structural criteria for inducing DIP, and awareness of this potential complication is essential.

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Atomoxetine

Reactions Weekly.2026; 2095(1): 19. CrossRef

Newsletters

What’s new in thyroid pathology 2024: updates from the new WHO classification and Bethesda system: Andrey Bychkov, Chan Kwon Jung; J Pathol Transl Med. 2024;58(2):98-101. Published online March 13, 2024; DOI: https://doi.org/10.4132/jptm.2024.03.06

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Abstract PDF

In line with the release of the 5th edition WHO Classification of Tumors of Endocrine Organs (2022) and the 3rd edition of the Bethesda System for Reporting Thyroid Cytopathology (2023), the field of thyroid pathology and cytopathology has witnessed key transformations. This digest brings to the fore the refined terminologies, newly introduced categories, and contentious methodological considerations pivotal to the updated classification.

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Impact of thyroid Bethesda category IV (follicular neoplasm) terminology unification on atypia of undetermined significance reporting patterns in thyroid fine-needle aspiration
Shirin Abbasi, Lorena Marcano-Bonilla, Syed Z. Ali
Journal of the American Society of Cytopathology.2026; 15(2): 107. CrossRef
Clinical implication of the 2025 ATA risk stratification in follicular thyroid carcinoma: A comparison with the 2015 ATA risk stratification
Hyunju Park, Bo Ram Kim, Ji Hyun Yoo, Sun Wook Kim, Jae Hoon Chung, Bogyeong Han, Myoung Kyoung Kim, Jun Ho Choe, Man Ki Chung, Tae Hyuk Kim, Young Lyun Oh
Oral Oncology.2026; 175: 107912. CrossRef
Diagnosis and management of thyroid nodule
Suganya Sekar, Deepak Thomas Abraham
Current Opinion in Endocrinology, Diabetes & Obesity.2025; 32(5): 167. CrossRef
Diagnostic Challenges, Prognostic Assessment, and Treatment Strategies in High-Grade Differentiated Thyroid Carcinoma
Chan Kwon Jung, Agnes Stephanie Harahap
Endocrinology and Metabolism.2025; 40(6): 830. CrossRef
Cytologic and Clinicopathologic Features of Papillary Thyroid Carcinoma with Prominent Hobnail Features on FNAC
Deepali Saxena, Ravi Hari Phulware, Prashant Durgapal, Arvind Kumar, Amit Kumar Tyagi
Indian Journal of Otolaryngology and Head & Neck Surgery.2024; 76(5): 4885. CrossRef
FHL1: A novel diagnostic marker for papillary thyroid carcinoma
Yeting Zeng, Dehua Zeng, Xingfeng Qi, Hanxi Wang, Xuzhou Wang, Xiaodong Dai, Lijuan Qu
Pathology International.2024; 74(9): 520. CrossRef
Nouveautés en pathologie thyroïdienne : classification OMS 2022, système Bethesda 2023, biologie moléculaire et testing moléculaire
Mohamed Amine Bani, Sophie Moog, Voichita Suciu, Livia Lamartina, Abir Al Ghuzlan
Bulletin du Cancer.2024; 111(10): 10S5. CrossRef
Cytologic hallmarks and differential diagnosis of papillary thyroid carcinoma subtypes
Agnes Stephanie Harahap, Chan Kwon Jung
Journal of Pathology and Translational Medicine.2024; 58(6): 265. CrossRef
Surgical and Pathological Challenges in Thyroidectomy after Thermal Ablation of Thyroid Nodules
Ting-Chun Kuo, Kuen-Yuan Chen, Hsiang-Wei Hu, Jie-Yang Jhuang, Ming-Tsan Lin, Chin-Hao Chang, Ming-Hsun Wu
Thyroid®.2024; 34(12): 1503. CrossRef

What’s new in neuropathology 2024: CNS WHO 5th edition updates: Heather Smith, Jared T. Ahrendsen; J Pathol Transl Med. 2024;58(6):346-349. Published online September 30, 2024; DOI: https://doi.org/10.4132/jptm.2024.09.11

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Abstract PDF

The fifth edition of the World Health Organization (WHO) Classification of Central Nervous System (CNS) Tumors was released in 2021, just five years following the updated fourth edition. Advanced molecular testing such as next-generation sequencing, RNA fusion analysis, and DNA methylation profiling has led to more precise grading and classification of pre-existing tumor types as well as the recognition of new ones. Herein, we outline the major updates of the 2021 WHO Classification of CNS tumors, with emphasis on the expanded molecular characterization of CNS tumors.

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Primary CNS Neuroblastoma, FOXR2‐Activated: Clinicopathological Study of Two Cases With Immunohistochemical Characterization and Literature Review
Sumanta Das, Sunita Ahlawat, Komal Agrawal, Salman Shaikh, Rakesh Kumar Gupta, Suman S. Karanth, Sandeep Vaishya, Rana Patir, Mehar Chand Sharma
Neuropathology.2026;[Epub] CrossRef
Bioinformatics insights into ACSL1 and ACSL5: prognostic and immune roles in low-grade glioma
Cheng Zhang, Zhonghua Lv, Hongsheng Liang, Fulan Hu, Haoran Bi
BMC Cancer.2025;[Epub] CrossRef
Current Understanding of the Exosomes and Their Associated Biomolecules in the Glioblastoma Biology, Clinical Treatment, and Diagnosis
Aghdas Ramezani, Maryam Rahnama, Fatemeh Mahmoudian, Fatemeh Shirazi, Mahmoud Ganji, Shohreh Bakhshi, Bahman Khalesi, Zahra Sadat Hashemi, Saeed Khalili
Journal of Neuroimmune Pharmacology.2025;[Epub] CrossRef
Diagnostic Utility of Intratumoral Susceptibility Signals in Adult Diffuse Gliomas: Tumor Grade Prediction and Correlation with Molecular Markers Within the WHO CNS5 (2021) Classification
José Ignacio Tudela Martínez, Victoria Vázquez Sáez, Guillermo Carbonell, Héctor Rodrigo Lara, Florentina Guzmán-Aroca, Juan de Dios Berna Mestre
Journal of Clinical Medicine.2025; 14(11): 4004. CrossRef
Glioblastoma in Puerto Rico: A 21-year population-based study
Carlos E Calderon-Valero, Esteban Rivera, Odaly Balasquide, Alejandro E Cedeño-Moran, Aixa De Jesus, Miguel Mayol Del Valle
Neuro-Oncology Advances.2025;[Epub] CrossRef
Brain Tumors, AI and Psychiatry: Predicting Tumor-Associated Psychiatric Syndromes with Machine Learning and Biomarkers
Matei Șerban, Corneliu Toader, Răzvan-Adrian Covache-Busuioc
International Journal of Molecular Sciences.2025; 26(17): 8114. CrossRef
Engineered bacteria/bacterial components strategy for glioma
Yan Zhu, Meilin Shen, Qi Chen, Huanghao Yang
Chemical Engineering Journal.2025; 525: 170539. CrossRef

Review Article

A comprehensive review of ossifying fibromyxoid tumor: insights into its clinical, pathological, and molecular landscape: Kyriakos Chatzopoulos, Antonia Syrnioti, Mohamed Yakoub, Konstantinos Linos; J Pathol Transl Med. 2026;60(1):6-19. Published online January 14, 2026; DOI: https://doi.org/10.4132/jptm.2025.10.02

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Abstract PDF: Ossifying fibromyxoid tumor (OFMT) is a rare mesenchymal neoplasm first described in 1989. It typically arises in the superficial soft tissues of the extremities as a slow-growing, painless mass. Histologically, it is commonly characterized by a multilobular architecture composed of uniform epithelioid cells embedded in a fibromyxoid matrix, often surrounded by a rim of metaplastic bone. While classic cases are readily identifiable, the tumor's histopathological heterogeneity can mimic a range of benign and malignant neoplasms, posing significant diagnostic challenges. Molecularly, most OFMTs harbor PHF1 rearrangements, commonly involving fusion partners such as EP400, MEAF6, or TFE3. This review underscores the importance of an integrated diagnostic approach- incorporating histopathological, immunohistochemical, and molecular data- to accurately classify OFMT and distinguish it from its mimics. Expanding awareness of its morphologic and molecular spectrum is essential for precise diagnosis, optimal patient management, and a deeper understanding of this enigmatic neoplasm.

Original Article

Correlations and prognostic impacts of tumor spread through airspaces in surgically resected non–small cell lung cancer: a retrospective study from Jordan: Ola Abu Al Karsaneh, Amani Al-Rousan, Sofian Al Shboul, Mohammed El-Sadoni, Anas Hayajneh, Moath Alrjoub, Sura Al-Rawabdeh, Tareq Saleh; J Pathol Transl Med. 2026;60(1):92-106. Published online January 9, 2026; DOI: https://doi.org/10.4132/jptm.2025.10.15

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Abstract PDF Supplementary Material: Background
Spread through air spaces (STAS) has been identified as an invasion pattern in non–small cell lung cancer (NSCLC). This study evaluated the association between tumor STAS and various clinicopathological parameters of NSCLC, with emphasis on the prognostic role of STAS. Methods: We evaluated 96 cases of NSCLC for STAS. STAS-positive cases were graded according to the distance between the edge of the primary tumor and the furthest STAS, in millimeters, or the number of alveoli separating STAS from the tumor. Results: STAS was observed in 33 patients (34.4%). In 28 cases, STAS was located in airspaces >3 alveoli away from the primary tumor. In 18 cases, STAS was found in airspaces > 2.5 mm away from the edge of the primary tumor. Morphologically, 18 cases of STAS demonstrated a solid nest pattern, eight showed a micropapillary cluster pattern, and seven exhibited a single-cell pattern. In multivariate analysis, only high tumor grade (p = .001) was independently associated with STAS in NSCLC. The presence of STAS (p = .047), lymphovascular invasion (p = .001), positive surgical margin (p = .021), adenocarcinoma histology (p = .020), and postoperative therapy (p = .049) showed a statistically significant lower overall survival (OS). However, multivariate analyses showed that STAS is not an independent predictor of OS in NSCLC. In addition, STAS-positive cases with an extension of >2.5 mm had significantly lower disease-free survival (DFS) (p = .018). Conclusions: The findings demonstrated that STAS is independently associated with a higher tumor grade and appears to have an adverse impact on OS and DFS in the examined subpopulation.

Review Articles

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.

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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
Liquerologia: Uma ferramenta no diagnóstico de esclerose múltipla e outras doenças neurodegenerativas e desmielinizantes
Laura Maria de Araújo Pereira, Talyta Valeria Siqueira do Monte Guedes, Rafaell Batista Pereira, Davi Abrantes Lucena Messias, Marfran José Cunha Urtiga, Davi Rodrigues Vieira, Samuel da Costa Chaves Trindade Martins, José Guedes da Silva Júnior
Research, Society and Development.2025; 14(12): e72141249815. CrossRef

The evolving role of TRPS1 in dermatopathology: insights from the past 4 years: Mokhtar H. Abdelhammed, Woo Cheal Cho; J Pathol Transl Med. 2026;60(2):129-143. Published online January 29, 2026; DOI: https://doi.org/10.4132/jptm.2025.11.25

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Abstract PDF: Over the past 4 years, trichorhinophalangeal syndrome type 1 (TRPS1) has rapidly gained attention among practicing pathologists, with numerous studies emerging that both support and question its diagnostic utility. Initially regarded as a highly specific marker for tumors of mammary origin, TRPS1 is now recognized to have broader expression patterns, including in a variety of cutaneous neoplasms. This is likely due to embryologic parallels between breast tissue and skin adnexal structures, an overlap that was underappreciated in early investigations. Although TRPS1 lacks absolute specificity—even among cutaneous neoplasms—it can still offer meaningful diagnostic value when interpreted alongside conventional immunohistochemical markers and within the appropriate morphologic context. Noteworthy diagnostic applications include mammary Paget disease, primary extramammary Paget disease, rare adnexal neoplasms such as endocrine mucin-producing sweat gland carcinoma and primary cutaneous NUT adnexal carcinoma, and cutaneous metastases from breast carcinoma. In this review, we present the most comprehensive and up-to-date evaluation of the utility and limitations of TRPS1 immunohistochemistry in dermatopathology. Our aim is to deepen understanding of this emerging marker and provide practical guidance on its optimal integration with established immunohistochemical panels to enhance diagnostic accuracy in routine practice.

Original Articles

PSMA expression in hepatic colorectal cancer metastasis: Eundong Park, Michel Kmeid, Xin Wang, Haiyan Qiu, Clifton G. Fulmer, Marcello P. Toscano, Nusret Bekir Subasi, Maciej Gracz, Hwajeong Lee; J Pathol Transl Med. 2026;60(1):107-123. Published online January 14, 2026; DOI: https://doi.org/10.4132/jptm.2025.10.20

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Abstract PDF Supplementary Material

Background
Prostate-specific membrane antigen (PSMA) is expressed in the neovasculature of various malignancies, such as colorectal cancer (CRC) and hepatocellular carcinoma (HCC). However, PSMA expression in hepatic CRC metastasis has not been studied in detail. Methods: The PSMA expression in primary CRC and corresponding hepatic metastasis was evaluated by immunohistochemistry in a metastatic CRC cohort (n = 56), which was divided into subgroups according to treatment history and timing of metastasis. Demographic and histological characteristics of primary CRC were collected and their relationships with PSMA expression were examined. Additionally, the PSMA expression in resected HCC (n = 76) was compared with that of hepatic CRC metastasis. Results: In primary CRC, PSMA level showed a positive association with tumor size. Lower PSMA expression in hepatic metastasis was associated with higher primary CRC grade, advanced pTNM stage at the time of CRC resection, presence of tumor deposit, and unresectability of metastatic lesion. PSMA expression in primary CRC correlated with that in hepatic metastasis only in concurrent and untreated metastasis subgroup. PSMA expression in primary CRC and hepatic metastasis, regardless of treatment history and timing of metastasis, was not significantly different from that of HCC. Conclusions: Several adverse pathological features of primary CRC were associated with a lower PSMA expression in hepatic metastasis. PSMA expression in hepatic metastasis correlated with that of primary CRC only in concurrent and untreated subgroup. Primary HCC and hepatic CRC metastasis show comparable levels of PSMA expression.

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Incidental detection of PDAC via 18F-PSMA PET/CT in a patient with recurrent prostate cancer. A case report
Giordano Savelli, Mattia Bonacina, Alberto Soffientini, Elvira Archiati, Claudio Bnà, Alberto Zaniboni
Frontiers in Nuclear Medicine.2026;[Epub] CrossRef

Revisiting human sparganosis: a pathologic review from a single institution: Jeemin Yim, Young A Kim, Jeong Hwan Park, Hye Eun Park, Hyun Beom Song, Ji Eun Kim; J Pathol Transl Med. 2026;60(1):83-91. Published online January 9, 2026; DOI: https://doi.org/10.4132/jptm.2025.10.14

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Abstract PDF: Background
Sparganosis is a rare parasitic infection caused by Spirometra species. Although it was relatively common in the past, it is now often overlooked. In this study, we review cases diagnosed through histopathological examination at a single institution in recent years to raise awareness of this neglected parasitic disease. Methods: We retrospectively analyzed cases of human sparganosis identified in the pathology archives of a single institution in South Korea between 2004 and 2025. A comprehensive review was conducted, including demographic data, clinical features, lesion locations, imaging findings, exposure history (such as dietary habits), and histopathologic findings. Results: A total of 15 patients were identified, including 10 females and 5 males, with a mean age of 65.1 years. Lesions were most commonly located in the lower extremities and breast. Imaging findings were largely nonspecific, with ultrasonography being the most frequently used modality. In most cases, clinical suspicion of sparganosis was absent, and excision was performed under the impression of a benign or malignant tumor. Histologically, variably degenerated parasitic structures were identified within granulomatous inflammation. However, preserved features such as calcospherules and tegumental structures facilitated definitive diagnosis. Conclusions: This study underscores the importance of recognizing the characteristic histopathological features of sparganosis, which can allow for accurate diagnosis even in the absence of clinical suspicion. Although rare, sparganosis remains a relevant diagnostic consideration in endemic regions, particularly in East Asia.

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.

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.

Review

Cytologic hallmarks and differential diagnosis of papillary thyroid carcinoma subtypes: Agnes Stephanie Harahap, Chan Kwon Jung; J Pathol Transl Med. 2024;58(6):265-282. Published online November 7, 2024; DOI: https://doi.org/10.4132/jptm.2024.10.11

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Abstract PDF

Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy, characterized by a range of subtypes that differ in their cytologic features, clinical behavior, and prognosis. Accurate cytologic evaluation of PTC using fine-needle aspiration is essential but can be challenging due to the morphologic diversity among subtypes. This review focuses on the distinct cytologic characteristics of various PTC subtypes, including the classic type, follicular variant, tall cell, columnar cell, hobnail, diffuse sclerosing, Warthin-like, solid/trabecular, and oncocytic PTCs. Each subtype demonstrates unique nuclear features, architectural patterns, and background elements essential for diagnosis and differentiation from other thyroid lesions. Recognizing these distinct cytologic patterns is essential for identifying aggressive subtypes like tall cell, hobnail, and columnar cell PTCs, which have a higher risk of recurrence, metastasis, and poorer clinical outcomes. Additionally, rare subtypes such as diffuse sclerosing and Warthin-like PTCs present unique cytologic profiles that must be carefully interpreted to avoid diagnostic errors. The review also highlights the cytologic indicators of lymph node metastasis and high-grade features, such as differentiated high-grade thyroid carcinoma. The integration of molecular testing can further refine subtype diagnosis by identifying specific genetic mutations. A thorough understanding of these subtype-specific cytologic features and molecular profiles is vital for accurate diagnosis, risk stratification, and personalized management of PTC patients. Future improvements in diagnostic techniques and standardization are needed to enhance cytologic evaluation and clinical decision-making in thyroid cancer.

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Oncocytic Thyroid Tumours With Pathogenic FLCN Mutations Mimic Oncocytic Papillary Thyroid Carcinoma on Fine‐Needle Aspiration
Adeel M. Ashraf, Faisal Hassan, Adrian A. Dawkins, Julie C. Dueber, Derek B. Allison, Thèrése J. Bocklage
Cytopathology.2026; 37(1): 108. CrossRef
Using a new type of visible light-based emission fluorescence microscope to identify the benign and malignant nature of thyroid tissue during the surgical process: Analysis of diagnostic results
Yu Miao, Liu Xiaowei, Li Muyang, Gao Jian, Chen Lu
Photodiagnosis and Photodynamic Therapy.2026; 57: 105324. CrossRef
Clinical Behavior of Aggressive Variants of Papillary Thyroid Carcinoma: A Retrospective Case–Control Study
Jovan Ilic, Nikola Slijepcevic, Katarina Tausanovic, Bozidar Odalovic, Goran Zoric, Marija Milinkovic, Branislav Rovcanin, Milan Jovanovic, Matija Buzejic, Duska Vucen, Boban Stepanovic, Sara Ivanis, Milan Parezanovic, Milan Marinkovic, Vladan Zivaljevic
Cancers.2026; 18(2): 345. CrossRef
Nuclear pseudoinclusion is associated with BRAFV600E mutation: Analysis of nuclear features in papillary thyroid carcinoma
Agnes Stephanie Harahap, Dina Khoirunnisa, Salinah, Maria Francisca Ham
Annals of Diagnostic Pathology.2025; 75: 152434. CrossRef
2025 Korean Thyroid Association Clinical Management Guideline on Active Surveillance for Low-Risk Papillary Thyroid Carcinoma
Eun Kyung Lee, Min Joo Kim, Seung Heon Kang, Bon Seok Koo, Kyungsik Kim, Mijin Kim, Bo Hyun Kim, Ji-hoon Kim, Shin Je Moon, Kyorim Back, Young Shin Song, Jong-hyuk Ahn, Hwa Young Ahn, Ho-Ryun Won, Won Sang Yoo, Min Kyoung Lee, Jeongmin Lee, Ji Ye Lee, Kyo
International Journal of Thyroidology.2025; 18(1): 30. CrossRef
Structure-based molecular screening and dynamic simulation of phytocompounds targeting VEGFR-2: a novel therapeutic approach for papillary thyroid carcinoma
Shuai Wang, Lingqian Zhang, Wenjun Zhang, Xiong Zeng, Jie Mei, Weidong Xiao, Lijie Yang
Frontiers in Pharmacology.2025;[Epub] CrossRef
2025 Korean Thyroid Association Clinical Management Guideline on Active Surveillance for Low-Risk Papillary Thyroid Carcinoma
Eun Kyung Lee, Min Joo Kim, Seung Heon Kang, Bon Seok Koo, Kyungsik Kim, Mijin Kim, Bo Hyun Kim, Ji-hoon Kim, Shinje Moon, Kyorim Back, Young Shin Song, Jong-hyuk Ahn, Hwa Young Ahn, Ho-Ryun Won, Won Sang Yoo, Min Kyoung Lee, Jeongmin Lee, Ji Ye Lee, Kyon
Endocrinology and Metabolism.2025; 40(3): 307. CrossRef
A Case of Warthin-Like Variant of Papillary Thyroid Cancer
Amy Chow, Israa Laklouk
Cureus.2025;[Epub] CrossRef
Propensity score-matched analysis of the ‘2+2’ parathyroid strategy in total thyroidectomy with central neck dissection
Hao Gong, Simei Yao, Tianyuchen Jiang, Yi Yang, Yuhan Jiang, Zhujuan Wu, Anping Su
Frontiers in Endocrinology.2025;[Epub] CrossRef
Cytological Findings in Pediatric Thoracic Tumors: A Review of Diagnostic Insights and Pitfalls
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Acta Cytologica.2025; : 1. CrossRef

Original Article

Mutational status of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP): molecular analysis should be performed for NIFTPs with nuclear score 3: Ayaka Sako, Mitsuyoshi Hirokawa, Michiko Matsuse, Miyoko Higuchi, Akira Miyauchi, Takashi Akamizu, Atsushi Kawakami, Norisato Mitsutake; J Pathol Transl Med. 2026;60(2):214-219. Published online February 23, 2026; DOI: https://doi.org/10.4132/jptm.2025.12.06

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Abstract PDF: Background
The classification of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was introduced to prevent the overtreatment of indolent tumors that were formerly diagnosed as non-invasive encapsulated follicular variant papillary thyroid carcinomas (NIEFV-PTCs). Although NIFTP was initially estimated to account for 10%–20% of papillary thyroid carcinomas in Western populations, its incidence is substantially lower in Asian cohorts. However, a multi-institutional Japanese study revealed that 31.0% of tumors previously diagnosed as follicular adenomas (FAs) were reclassified as NIFTPs. NIFTP diagnosis requires a nuclear score (NS) of 2–3, and according to the recent World Health Organization criteria, molecular analysis is recommended, but not mandatory, to exclude high-risk subtypes, namely cases with the BRAFV600E mutation, particularly for NS3 tumors. Methods: We performed genetic analysis on 92 archival thyroid tumor samples, including 69 previously diagnosed as FA, of which 34 remained as FA upon re-evaluation (group A) and 35 were reclassified as NIFTP with NS2 (group B). Additional 23 tumors previously diagnosed as NIEFV-PTC were reclassified as NIFTP with NS3 (group C). Results: RAS mutations were detected in 8.8%, 34.3%, and 21.7% of the tumor samples in groups A, B, and C, respectively, whereas BRAF mutations were present in 43.5% of the tumor samples in group C only. Conclusions: These findings suggest the presence of two distinct tumor subsets within NIFTP-NS3, underscoring the need for routine molecular diagnostics in NIFTP-NS3 to facilitate appropriate clinical management.

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.

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.

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Opportunities and challenges in recurrent diffuse podocytopathy post-transplantation: the critical value of the definition
Rachel Nuccitelli, Amadea Toutoungis, Elena Martinelli, Simone Sanna-Cherchi, Astrid Weins, Heather K. Morris, Andrew S. Bomback, Ibrahim Batal
Frontiers in Immunology.2026;[Epub] CrossRef

Original Articles

International Academy of Cytology standardized reporting of breast fine-needle aspiration cytology with cyto-histopathological correlation of breast carcinoma: Shweta Pai; J Pathol Transl Med. 2024;58(5):241-248. Published online September 13, 2024; DOI: https://doi.org/10.4132/jptm.2024.07.14

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Abstract PDF: Background
The International Academy of Cytology (IAC) has developed a standardized approach for reporting the findings of breast fine-needle aspiration cytology (FNAC). Accordingly, there are five chief categories of breast lesions, C1 (insufficient material), C2 (benign), C3 (atypical), C4 (suspicious), and C5 (malignant). The prognostication and management of breast carcinoma can be performed readily on the basis of this classification system. The aim of this study was to classify various breast lesions into one of the above-named categories and to further grade the C5 lesions specifically using the Robinson system. The latter grades were then correlated with modified Scarff-Bloom-Richardson (SBR) grades.
Methods
This retrospective study was undertaken in the pathology department of a hospital located in the urban part of the city of Bangalore. All FNAC procedures performed on breast lumps spanning the year 2020 were included in the study.
Results
A total of 205 breast lesions was classified according to the IAC guidelines into C1 (6 cases, 2.9%), C2 (151 cases, 73.7%), C3 (13 cases, 6.3%), C4 (5 cases, 2.5%), and C5 (30 cases, 14.6%) groups. The C5 cases were further graded using Robinson’s system. The latter showed a significant correlation with the SBR system (concordance=83.3%, Spearman correlation=0.746, Kendall’s tau-b=0.736, kappa=0.661, standard error=0.095, p≤.001).
Conclusions
A standardized approach for FNAC reporting of breast lesions, as advocated for by the IAC, improves the quality and clarity of the reports and assures diagnostic reproducibility on a global scale. Further, the cytological grading of C5 lesions provides reliable cyto-prognostic scores that can help assess a tumor’s aggressiveness and predict its histological grade.

Correlation between HER2 gene copy number and immunohistochemistry categories in HER2-negative breast cancer: diagnostic utility for differentiating HER2-null, ultralow, and low tumors: Min Chong Kim, Young Kyung Bae; J Pathol Transl Med. 2026;60(2):193-201. Published online February 25, 2026; DOI: https://doi.org/10.4132/jptm.2025.11.07

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Abstract PDF: Background
The recent recognition of human epidermal growth factor receptor 2 (HER2)–low and HER2-ultralow breast cancers (BCs) has expanded the therapeutic relevance of HER2 testing in the antibody-drug conjugate era. However, the biological continuum of HER2 expression measured by immunohistochemistry (IHC) and its relationship with the HER2 gene copy number remain unclear. Methods: We retrospectively analyzed 135 HER2-negative invasive BCs and reclassified them as HER2-null (IHC 0), HER2-ultralow (0+), or HER2-low (1+ or 2+ without amplification). HER2 gene copy number was determined using silver-enhanced in situ hybridization. Statistical analyses were performed to compare HER2 copy number among IHC categories and evaluate the discriminatory value of HER2 copy number for distinguishing IHC subgroups. Results: The mean HER2 copy number increased stepwise across IHC categories: 1.95 ± 0.54 (null), 2.03 ± 0.43 (ultralow), 2.25 ± 0.65 (low, 1+), and 3.29 ± 1.05 (low, 2+). Significant differences were observed between the ultralow and low groups (p = .003) and between the null and low groups (p < .001), but not between the null and ultralow groups or between the ultralow and 1+ groups. Conclusions: HER2 gene copy number was positively correlated with protein expression as reflected by IHC categories. Although HER2 gene copy number was statistically higher in HER2-low than in HER2-null tumors, the substantial overlap in copy number ranges likely limits its utility in distinguishing HER2-low from HER2- null BCs.

Prevalence of HER2-ultralow breast cancer in South Korea: a multicenter study by reassessment of HER2-zero cases: Min Chong Kim, Eun Yoon Cho, Hee Jin Lee, Ji Shin Lee, Jee Yeon Kim, Wan Seop Kim, Chungyeul Kim, Sun-Young Jun, Hye Jeong Choi, So Mang Lee, Ahrong Kim, Ji-Young Kim, Jeong Yun Shim, Gyungyub Gong, Young Kyung Bae; J Pathol Transl Med. 2026;60(2):184-192. Published online February 23, 2026; DOI: https://doi.org/10.4132/jptm.2025.10.22

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

Newsletter

What’s new in genitourinary pathology 2023: WHO 5th edition updates for urinary tract, prostate, testis, and penis: Bonnie Choy, Maria Tretiakova, Debra L. Zynger; J Pathol Transl Med. 2024;58(1):45-48. Published online December 27, 2023; DOI: https://doi.org/10.4132/jptm.2023.12.11

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Abstract PDF

The 5th edition WHO Classification of Urinary and Male Genital Tumours (2022) introduced many significant changes relevant to urologic daily practice, mainly to renal tumors which was covered in the What’s New newsletter in September 2022. In this newsletter, we summarize the notable changes to bladder, prostate, testis, and penis based on the 5th edition of the WHO.

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Predicting variant histology in bladder cancer: the role of multiparametric MRI and vesical imaging-reporting and data system (VI-RADS)
Serdar Aslan, Merve Nur Tasdemir, Ertugrul Cakir, Ural Oguz, Birgul Tok
Abdominal Radiology.2025; 50(10): 4700. CrossRef
Pictorial review of multiparametric MRI in bladder urothelial carcinoma with variant histology: pearls and pitfalls
Yuki Arita, Sungmin Woo, Lisa Ruby, Thomas C. Kwee, Keisuke Shigeta, Ryo Ueda, Sunny Nalavenkata, Hiromi Edo, Kosuke Miyai, Jeeban Das, Pamela I. Causa Andrieu, Hebert Alberto Vargas
Abdominal Radiology.2024; 49(8): 2797. CrossRef
Oncological outcomes and prognostic implications of T1 histo-anatomic substaging in the management of high-Grade non-muscle invasive bladder cancer: results from a large single centre series
Marco Finati, Antonio Fanelli, Francesco Cinelli, Nicola Schiavone, Ugo Giovanni Falagario, Anna Ricapito, Nicola d’Altilia, Richard Naspro, Angelo Porreca, Felice Crocetto, Biagio Barone, Ciro Imbimbo, Carlo Bettocchi, Francesca Sanguedolce, Luigi Cormio
World Journal of Urology.2024;[Epub] CrossRef

Original Article

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.

Review

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.

Citations

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Evaluation of Breast Lesions on Cytology Using International Academy of Cytology Yokohama Standardized Reporting System
Manish Jaiswal, Anurag Gupta, Tripti Verma, Pradyumn Singh, Rita Yadav, Akash Agarwal, Ashish Singhal, Nuzhat Husain, Shamrendra Narayan, Neha Singh
Diagnostic Cytopathology.2026; 54(3): 184. CrossRef
Personalizing therapies over the course of hormone receptor‐positive/HER2‐negative metastatic breast cancer
Akshara Singareeka Raghavendra, Senthil Damodaran, Carlos H. Barcenas, Suzanne A. Fuqua, Rachel M. Layman, Debu Tripathy
CA: A Cancer Journal for Clinicians.2026;[Epub] CrossRef
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

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.

Newsletter

What’s new in adrenal gland pathology: WHO 5th edition for adrenal cortex: Carol N. Rizkalla, Maria Tretiakova; J Pathol Transl Med. 2024;58(4):201-204. Published online June 25, 2024; DOI: https://doi.org/10.4132/jptm.2024.06.07

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Abstract PDF

The 5th edition of WHO Classification of Endocrine and Neuroendocrine Tumors (2022) introduced many significant changes relevant to endocrine daily practice. In this newsletter, we summarize the notable changes to the adrenal cortex based on the 5th edition of the WHO classification [1].

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Ectopic adrenal gland in the liver leading to a misdiagnosis of hepatocellular carcinoma: A case report
Min-Qiu Qin, Yi-Peng Zhao, Ju-Ping Xie
World Journal of Hepatology.2025;[Epub] CrossRef

Original Article

Progastrin, annexin A2, and tumor-associated macrophages in gastric adenocarcinoma: Konstantinos Christofidis, Rodanthi Fioretzaki, Stylianos Mavropoulos Papoudas, Nikolaos Charalampakis, Nikolaos Kavantzas, Dimitrios Schizas, Stratigoula Sakellariou; J Pathol Transl Med. 2026;60(2):263-279. Published online March 10, 2026; DOI: https://doi.org/10.4132/jptm.2025.12.20

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Abstract PDF Supplementary Material: Background
Gastric adenocarcinoma is a major cause of cancer mortality worldwide, and reliable biomarkers remain insufficient. This study investigates the immunohistochemical expression of progastrin (hPG) and annexin A2 (ANXA2) and the polarization of tumor-associated macrophages in gastric adenocarcinoma to explore their potential prognostic and biological significance. Methods: A retrospective analysis was conducted on formalin-fixed, paraffin-embedded tissue samples from 60 patients with gastric adenocarcinoma (primary tumors, lymph node metastases, and non-tumoral gastric mucosa) and gastric biopsies from 23 healthy controls. The expression of hPG and ANXA2 was quantified using the H-score, and the CD163/human leukocyte antigen–DR (HLA-DR) ratio was used to represent macrophage polarization (M2/M1). Statistical analyses included non-parametric tests, Spearman correlations, Kaplan-Meier survival curves, and Cox proportional-hazards models. Results: ANXA2 expression was significantly elevated in cancer cells from primary tumors and lymph node metastases, compared with the non-tumoral gastric mucosa tissues and gastric mucosa tissues from healthy controls. ANXA2 expression increased with the tumor grade. High ANXA2 levels were associated with shorter overall and disease-free survival, but they did not have independent prognostic value. Although hPG expression correlated positively with ANXA2, it showed no significant prognostic association. The CD163/HLA-DR ratio increased with tumor progression and negatively correlated with ANXA2, but it did not influence survival outcomes. Conclusions: This study is the first to demonstrate the adverse prognostic impact of ANXA2 overexpression in gastric adenocarcinoma tissues from Caucasian patients. Our results suggest that ANXA2 might have utility as a prognostic biomarker and therapeutic target, if further large-scale studies validate and expand our findings.

Review

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

Original Articles

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.

Multicenter evaluation of the PASS score as a negative predictive tool and the impact of inter-observer variability in pheochromocytoma and paraganglioma risk stratification: Sungyeon Jung, Hye-Ri Shin, Su-Jin Shin, Hee Young Na, Soon-Won Hong, So Yeon Park, Chan Kwon Jung, Kyeong Cheon Jung, Young Lyun Oh, Jae-Kyung Won; J Pathol Transl Med. 2026;60(2):202-213. Published online February 23, 2026; DOI: https://doi.org/10.4132/jptm.2025.11.05

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Abstract PDF: Background
The Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) is widely used for risk stratification in pheochromocytoma and paraganglioma (PPGL), but its clinical utility is limited by inter-observer variability of its parameters and inconsistent predictive performance. Methods: We conducted a multicenter retrospective study of 1,518 patients with PPGL from five tertiary referral centers in Korea. Prognostic utility of PASS system was assessed using logistic regression, Kaplan-Meier analysis, and receiver operating characteristic (ROC) curve analysis. Inter-observer variability was inferred by comparing area under the ROC curve (AUCs) across institutions. Simplified PASS systems were developed based on multivariable analysis of key histopathological parameters. Results: The PASS system was a significant predictor of adverse events and recurrence-free survival. Although the PASS system demonstrated only modest discriminative ability (AUC, 0.673), it showed a high negative predictive value (NPV, 0.885), supporting its usefulness as a screening tool for benign behavior. However, there was significant inter-institutional variability in PASS performance (AUC; range, 0.513 to 0.727; p < .05). The 3-factor Simple PASS, which incorporates necrosis, spindling, and mitotic figures, exhibited less inter-observer variation. The 4-factor Simple PASS, which adds vascular invasion to the 3-factor model, also showed reduced inter-observer variability and improved AUC and NPV compared to the original PASS system. Conclusions: In this multicenter cohort, the PASS system demonstrated high NPV and screening potential, but significant inter-observer variability remains a challenge. Simplification of the PASS system and enhanced pathologist training may improve reproducibility and clinical utility in PPGL risk stratification.

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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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.

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Pathogenesis-Guided Biomarker Assessment: A Shift in Prostate Cancer Diagnostics
Jessica M. Logan, Victoria Malone, John J. O’Leary, Doug A. Brooks
International Journal of Molecular Sciences.2025; 26(24): 11786. CrossRef

Review Article

Cutaneous soft tissue tumors in the 5th edition of the World Health Organization classification of skin tumors: key updates and new entities: Joon Hyuk Choi; J Pathol Transl Med. 2026;60(2):144-183. Published online March 13, 2026; DOI: https://doi.org/10.4132/jptm.2026.01.09

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Abstract PDF: The 5th edition of the World Health Organization (WHO) classification of skin tumors introduces a dedicated chapter on cutaneous soft tissue tumors, providing a comprehensive, standardized reference with updated diagnostic criteria that directly inform routine dermatopathology practice and molecular diagnostics. This edition incorporates several key changes, including newly recognized entities such as EWSR1::SMAD3-rearranged fibroblastic tumor, neurotrophic tyrosine receptor kinase (NTRK)–rearranged spindle cell neoplasm, superficial CD34-positive fibroblastic tumor, and CRTC1::TRIM11 cutaneous tumor. Diagnostic terminology has also been refined; for example, the term ‘atypical intradermal smooth muscle neoplasm’ replaces ‘cutaneous leiomyosarcoma’ for lesions confined to the dermis, whereas the designation leiomyosarcoma is reserved for tumors with overt subcutaneous infiltration. In addition, epithelioid fibrous histiocytoma has been reassigned to the family of tumors of uncertain differentiation. This review summarizes the key updates and newly recognized entities in the chapter on cutaneous soft tissue tumors in the 5th edition of the WHO classification of skin tumors, emphasizing their clinicopathological and molecular implications.

Original Articles

Can micro-CT distinguish between solid lung tumors? A comparative evaluation including solid adenocarcinoma, non-keratinizing squamous cell carcinoma, and carcinoid tumor: Selim Sevim, Serpil Dizbay Sak, Kaan Orhan, Arda Buyuksungur, Duru Karasoy, Hilal Ozakinci, Ayten Kayi Cangir; J Pathol Transl Med. 2026;60(2):231-245. Published online March 10, 2026; DOI: https://doi.org/10.4132/jptm.2025.12.16

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Abstract PDF Supplementary Material: Background
Some pulmonary carcinomas display a solid pattern, and immunohistochemistry is commonly used for tumor differentiation. Micro–computed tomography (micro-CT), with its ability to produce detailed three-dimensional images using small voxel sizes, may offer additional insights. This study investigates whether three solid tumor types, solid adenocarcinoma (sAC), non-keratinizing squamous cell carcinoma, and carcinoid tumor (CaT), can be differentiated using micro-CT. Methods: Fifteen paraffin blocks, five for each type, were scanned with micro-CT (Skyscan 1275, Bruker). These images were compared to whole slide images (WSIs) of the same tumors. Consequently, tumoral (n = 74) and non-tumoral (n = 49) regions of interest (tumor ROIs [tROIs] and non-tumor ROIs [ntROIs]) were selected on the micro-CT images and evaluated in terms of certain structural variables (percent object volume, structure model index, structure thickness, structure linear density, connectivity, connectivity density, open porosity, closed porosity) to investigate whether tumors can be differentiated from normal parenchyma and from each other. Results: Although detailed images comparable to WSIs could not be obtained, it was considered an important advantage to be able to examine the entire depth of the paraffin blocks. tROIs and ntROIs could be distinguished based on all variables (p < .001). Additionally, sAC showed a notable difference from CaT in “percent object volume” (p = .011). Conclusions: With ongoing technological advancements, improving image quality without compromising tissue integrity will likely accelerate the adoption of micro-CT in pathology labs. Moreover, structural variables derived from micro-CT images may support differentiation among tumor types.

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.

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Day surgery mode of multi-modal image AI fusion targeted transperineal biopsy technique using electromagnetic navigation tracking system under local anesthesia
Zhiyong Liu, Jianhe Wu, Yuanwei Li, Qiang Lu, Yongjun Yang
BMC Urology.2026;[Epub] CrossRef

Review

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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HPV in Pregnancy: Implications for Screening, Vaccination, and Maternal–Fetal Health
Suman Kumar, Swati, Swati Salila, Akanksha Raj, Pratima Gupta, Neha Sharad, Nidhi Chaudhary
Journal of Pregnancy.2026;[Epub] CrossRef
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

Original Article

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.

Review Article

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.

Review

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

Original Articles

Single umbilical artery and associated birth defects in perinatal autopsies: prenatal diagnosis and management: Manushree Saxena, Bhagyashri Hungund; J Pathol Transl Med. 2024;58(5):214-218. Published online July 9, 2024; DOI: https://doi.org/10.4132/jptm.2024.07.03

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Abstract PDF

Background
The umbilical cord forms the connection between the fetus and the placenta at the feto-maternal interface and normally comprises two umbilical arteries and one umbilical vein. In some cases, only a single umbilical artery (SUA) is present. This study was conducted to evaluate associations between SUA and other congenital malformations discovered in perinatal autopsies and to ascertain the existence of preferential associations between SUA and certain anomalies.
Methods
We evaluated records of all fetuses sent for autopsy to the Department of Pathology during the 10-year period from 2013 through 2022 (n = 1,277). The data were obtained from the hospital’s pathology laboratory records. The congenital anomalies were grouped by organ or system for analysis and included cardiovascular, urinary tract, nervous system, gastrointestinal tract, musculoskeletal, and lung anomalies.
Results
A SUA was present in 8.61% of the autopsies. The gestational age of the affected fetuses ranged between 13 to 40 weeks. An SUA presented as an isolated single anomaly in 44 cases (3.4%). Of the 110 SUA cases, 60% had other congenital anomalies. There was a significant association between birth defects and SUAs (p < .001). Strong associations between SUA and urinary tract, lung, and musculoskeletal anomalies were observed.
Conclusions
A SUA is usually seen in association with other congenital malformations rather than as an isolated defect. Therefore, examination for associated anomalies when an SUA is detected either antenatally or postnatally is imperative. The findings of this study should be helpful in counseling expectant mothers and their families in cases of SUA.

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Single Umbilical Artery with Symmetrical IUGR and Multiple Fetal Anomalies - An Interesting Case Report
Amulya Choudary Kotapati, Bhargavi Khandru, Vijayasree M.
Journal of Evolution of Medical and Dental Sciences.2025; : 10. CrossRef
Epidemiological and Histopathological Characteristics of Fetuses with Congenital Disorders: A Study in Greece
Despoina Nteli, Maria Nteli, Konstantinos Konstantinidis, Maria Ouzounidou, Paschalis Theotokis, Maria-Eleni Manthou, Iasonas Dermitzakis, Xeni Miliara, Chrysoula Gouta, Stamatia Angelidou, Dimosthenis Miliaras, Soultana Meditskou
Biology.2025; 14(6): 626. CrossRef

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.

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.

Original Article

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.

Review

Interpretation of PD-L1 expression in gastric cancer: summary of a consensus meeting of Korean gastrointestinal pathologists: Soomin Ahn, Yoonjin Kwak, Gui Young Kwon, Kyoung-Mee Kim, Moonsik Kim, Hyunki Kim, Young Soo Park, Hyeon Jeong Oh, Kyoungyul Lee, Sung Hak Lee, Hye Seung Lee; J Pathol Transl Med. 2024;58(3):103-116. Published online April 25, 2024; DOI: https://doi.org/10.4132/jptm.2024.03.15

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Abstract PDF Supplementary Material

Nivolumab plus chemotherapy in the first-line setting has demonstrated clinical efficacy in patients with human epidermal growth factor receptor 2–negative advanced or metastatic gastric cancer, and is currently indicated as a standard treatment. Programmed death-ligand 1 (PD-L1) expression is an important biomarker for predicting response to anti–programmed death 1/PD-L1 agents in several solid tumors, including gastric cancer. In the CheckMate-649 trial, significant clinical improvements were observed in patients with PD-L1 combined positive score (CPS) ≥ 5, determined using the 28-8 pharmDx assay. Accordingly, an accurate interpretation of PD-L1 CPS, especially at a cutoff of 5, is important. The CPS method evaluates both immune and tumor cells and provides a comprehensive assessment of PD-L1 expression in the tumor microenvironment of gastric cancer. However, CPS evaluation has several limitations, one of which is poor interobserver concordance among pathologists. Despite these limitations, clinical indications relying on PD-L1 CPS are increasing. In response, Korean gastrointestinal pathologists held a consensus meeting for the interpretation of PD-L1 CPS in gastric cancer. Eleven pathologists reviewed 20 PD-L1 slides with a CPS cutoff close to 5, stained with the 28-8 pharmDx assay, and determined the consensus scores. The issues observed in discrepant cases were discussed. In this review, we present cases of gastric cancer with consensus PD-L1 CPS. In addition, we briefly touch upon current practices and clinical issues associated with assays used for the assessment of PD-L1 expression in gastric cancer.

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Original Article

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.

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.

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.

Original Article

3-Dimensional reconstruction reveals frequent intraluminal growth of submucosal veins in surgically resected pT1 colorectal cancers: Jihyun Park, Mi-Ju Kim, Yeon Wook Kim, Byong-Wook Lee, Junyoung Shin, Jinho Shin, Chan-Gi Pack, Dong-Hoon Yang, Jihun Kim, In Ja Park, Ralph H. Hruban, Seung-Mo Hong; J Pathol Transl Med. 2026;60(2):246-262. Published online March 10, 2026; DOI: https://doi.org/10.4132/jptm.2025.12.19

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Abstract PDF: Background
Although venous invasion (VI) is associated with distant metastasis and observed in >50% of pT2–4 colorectal cancers (CRCs), the role of VI in pT1 CRCs is not well-defined. Methods: Thirty-four surgically resected pT1 CRCs were reevaluated for 2-dimensional (2D) VI using hematoxylin and eosin (H&E)–stained slides with additional elastic and desmin immunohistochemical staining (cohort A). Additionally, 27 pT1 CRCs without knowing VI status were selected for 3-dimensional (3D) VI evaluation only (cohort B). All 61 cases (cohorts A and B) were studied in 3D using tissue clearing. Results: VI was detected more commonly in 3D (17/34, 50.0%) than in 2D H&E slide evaluation (9/34, 26.5%, p = .047). When VI was identified in 3D (27/61, 44.3%), the most common phase was that of intraluminal growth (22/27, 81.5%), followed by intravasation (7/27, 25.9%) and extravasation (5/27, 18.5%). E-cadherin expression was characterized in 3D in foci of VI and varied in each phase of invasion. Conclusions: All three phases were observed in VI of pT1 CRCs. The extravasation of neoplastic cells from foci of VI in pT1 CRC suggests that VI could be a route of intratumoral spreading in a subset of pT1 CRCs.

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