Journal of Pathology and Translational Medicine

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

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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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
Indeterminate Bethesda System Category (Bethesda Category III) Thyroid Nodules: Cytomorphologic Subclassification and Its Impact on Malignancy Risk
Rinë Limani, Zgjim Limani, Shkelzen Reçica, Labinota Kondirolli, Etnik Bajraktari, Brikenë Blakaj Gashi, Drita Miftari Pazhari
Acta Cytologica.2026; : 1. CrossRef
Multimodal Diagnostic Cross-Check: A Correlative Study of Fine-Needle Aspiration Cytology, Ultrasonography, Thyroid Profile, and Histopathology in Thyroid Swellings
Farheen Khan, Nishi Tandon, Yoshita Agnihotri, Suboohi Khanam, Andleeb Zehra, Nirupma Lal
Cureus.2026;[Epub] 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 digital and computational pathology 2026: advances in adoption, standards, AI technologies, and clinical integration: Selim Sevim, Chadi Hajar, Snehal Sonawane; J Pathol Transl Med. 2026;60(3):364-370. Published online May 15, 2026; DOI: https://doi.org/10.4132/jptm.2026.04.27

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Abstract PDF: Digital and computational pathology are expanding rapidly worldwide, driven by advances in whole-slide imaging, AI algorithms, multimodal data integration, and improved digital infrastructure. Adoption continues to accelerate in the United States and internationally, supported by professional guidelines, emerging reimbursement pathways, and the growing need for remote workflows and collaborative diagnostics. Progress in interoperability standards, regulatory frameworks, and FDA approvals has strengthened the foundation for clinical deployment, while large-scale data repositories and federated learning approaches enable more robust and privacy-preserving model development. Foundation models, multimodal AI systems, and LLM-based copilots are reshaping diagnostic support, prognostication, workflow efficiency, clinical trials and drug discovery.

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
Deep Learning for Brain Tumour Analysis: A Systematic Review of CNN‐Transformer Hybrids in Multimodal Imaging
Solomon Buabeng Antwi, Peter Appiahene, Ben Beklisi Kwame Ayawli, Peter Nimbe, Vincenzo Positano
International Journal of Biomedical Imaging.2026;[Epub] CrossRef
The Price of Precision: A Critical Review of Molecular Diagnostics in Glioma, From Guidelines to Global Disparities
Maria Guarnaccia, Sebastiano Cavallaro
Annals of Clinical and Translational Neurology.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

Original Article

HER2-low and ultralow breast cancer: interobserver challenges and lessons from a consensus study: Jiwon Koh, Yoon Jin Cha, Eun Yoon Cho, Ahwon Lee, Ja Seung Koo, So Yeon Park, Min Hwan Kim, Jae Ho Jeong, Gyungyub Gong; J Pathol Transl Med. 2026;60(3):331-337. Published online March 20, 2026; DOI: https://doi.org/10.4132/jptm.2026.01.08

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Abstract PDF: Background
The recent approval of trastuzumab deruxtecan for human epidermal growth factor receptor 2 (HER2)–low and HER2-ultralow breast cancer mandates an adequate assessment of these categories. Methods: Seven breast pathologists from the Breast Pathology Study Group of the Korean Society of Pathologists held an on-site expert consensus meeting. Fifteen sets of virtual whole slide images (WSI) of hematoxylin and eosin stain and HER2 immunohistochemistry were provided. The pathologists were given 60 minutes to submit their diagnosis of HER2 expression into null, ultralow, 1+, 2+, or 3+. Afterwards, in-depth discussion and consensus diagnoses were made by real-time visualization of the WSI. Results: After the consensus meeting, unanimous 100% agreements were seen only in five (33.3%) of the examined cases, which consisted of three 1+ cases and two 2+ cases. Two cases (13.3%) had mild disagreement, with only one pathologist’s disagreement. Of note, eight cases (53.3%) showed significant disagreement, defined by more than two pathologists’ disagreement. All HER2-null cases were reclassified as ultralow after consensus review, suggesting potential widespread underclassification of ultralow cases in clinical practice. Conclusions: Experts had significant discrepancies in interpreting HER2-low/ultralow status. It is important to assess if the distinction between HER2-low and ultralow is strictly required and if HER2-null breast cancer exists in reality.

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.

Citations

Citations to this article as recorded by

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
Advantages of thyroid core needle biopsy: an emerging selective first-line biopsy modality
Jae Ho Shin, Yeseul Kim, Min Kyoung Lee, Jung Hwan Baek, So Lyung Jung
Ultrasonography.2026; 45(3): 205. CrossRef
Clinicopathological profile of high-grade differentiated thyroid carcinoma in an Indonesian tertiary hospital
Novita, Agnes Stephanie Harahap, Maria Francisca Ham, Alfianto Widiono, Chan Kwon Jung
Journal of Pathology and Translational Medicine.2026; 60(3): 338. CrossRef
Interpretable SVM-Based Integrated Ultrasound Model for Preoperative Thyroid Nodule Subtype Classification: Improved Identification of Follicular Variant Papillary Thyroid Carcinoma
Ran Zheng, Zhen Wang, Yongxin Li, Yuanqing Zhang, Fang Nie
Diagnostics.2026; 16(13): 1950. CrossRef
Papillary thyroid carcinoma in thyroglossal duct cyst: a Peruvian case series
José Luis Paz-Ibarra, Marialejandra Delgado Rojas, Edward Paucar Holgado, Jenyfer María Fuentes-Mendoza, Luis Concepción-Urteaga, Juan Eduardo Quiroz-Aldave, Marcio José Concepción-Zavaleta, José Somocurcio Peralta
Endocrinology, Diabetes & Metabolism Case Reports.2026;[Epub] CrossRef
Single-cell reveals age-dependent epithelial reprogramming and EMT vulnerability in THCA
Qiankun Zhang, Wei Pan, Xiaohua Gong, Qi Zhou
Endocrine-Related Cancer.2026;[Epub] 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
Parikshaa Gupta, Pranab Dey
Acta Cytologica.2025; 70(3): 320. CrossRef

Review Articles

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.

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.

Citations

Citations to this article as recorded by

Clinicopathological characteristics and prognosis of central nervous system solitary fibrous tumor: An analysis of 271 cases
Wanwan Gao, Ming Li, Xiaojia Liu, Lingyang Hua, Hong Chen, Haixia Cheng
Pathology - Research and Practice.2026; 284: 156520. CrossRef
Pelvic solitary fibrous tumor, historically classified as hemangiopericytoma, presenting with venous compression and pelvic congestion: A case report
Dejan Svilar, Jovana Đošić, Anđela Đurić, Bojan Stojanović
Halo 194.2026; 32(1): 31. CrossRef
Robot-assisted laparoscopic resection of giant pelvic solitary fibrous tumor: a case report with literature review
Binbin Wang, Gengchen Huang, Wei Wei, Tie Mao, Zihan Gao, Yutao Ma, Yiming Gu
Frontiers in Oncology.2026;[Epub] CrossRef
Laparoscopic Resection of a Mesorectal Solitary Fibrous Tumor: A Case Report and Review of the Literature
Atsushi Sugimoto, Hiroshi Tsuchihashi, Hiroyuki Fujimoto, Masayasu Kawasaki
Cureus.2026;[Epub] CrossRef
Construction and Characterization of Paired Patient-Derived Cell Models for Solitary Fibrous Tumors (SFTs)
Farhan Vahdat Azad, Paulina I. Trevino, Aishwarya Kappagantu, Maliha Mehjabin, Eleni Balla, Clark A. Meyer, Leonidas Bleris, Yi Li
Cancers.2026; 18(15): 2385. CrossRef

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

Review Article

Gene fusions in melanocytic lesions: an updated comprehensive review: Volha Lenskaya, Larisa Erikson, Victor G. Prieto, Woo Cheal Cho; J Pathol Transl Med. 2026;60(3):285-306. Published online May 8, 2026; DOI: https://doi.org/10.4132/jptm.2026.03.11

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Abstract PDF Supplementary Material

The scope of gene fusions in melanocytic neoplasms is broader than previously recognized, extending well beyond the Spitz-lineage neoplasms where kinase fusions involving ALK, ROS1, NTRK1/2/3, RET, MET, BRAF, and MAP3K8 define biologically and morphologically distinct tumors. Emerging studies demonstrate that a meaningful proportion of conventional non-Spitz lineage melanomas harbor oncogenic fusions. Such fusions may impact clinical behavior, histopathologic presentation and provide opportunities for targeted therapy. The World Health Organization classification of skin tumors, 5th edition, now incorporates fusion status into taxonomy and risk stratification, yet some important questions remain for further investigation: fusion-associated neoplasms can mimic non-melanocytic neoplasm; Spitz-type fusions appear in non-Spitz lesions; and melanocytic differentiation may occur in some other fusion-driven lesions. Broad-panel next-generation sequencing (including RNAseq), together with targeted fluorescence in situ hybridization and immunohistochemistry enhances detection of known and novel fusion partners. Early clinical evidence of TRK, ALK, and ROS1 inhibitor efficacy underscores the translational promise of fusion testing and opens avenues for personalized therapy. This review synthesizes current knowledge on the genomics, histopathology, diagnosis, and therapeutic implications of fusion-driven melanocytic neoplasms, highlighting consensus points and remaining controversies.

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Clinicopathologic and molecular characteristics of acral melanomas harboring RARA fusions
Mokhtar H. Abdelhammed, Richard K. Yang, Volha Lenskaya, Carlos A. Torres-Cabala, Woo Cheal Cho
Human Pathology.2026; 177: 106211. 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.

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.

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.

Citations

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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

Review Article

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

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Abstract PDF

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

Citations

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Immunodeficiency-autoimmunity syndromes
Gunnar Houen
Autoimmunity Reviews.2026; 25(6): 104059. CrossRef
Opioid Signaling in Multiple Sclerosis: Emerging Targets for Repair
Renata Perlikowska, Małgorzata Domowicz, Agnieszka Śliwińska, Mariusz Stasiołek
International Journal of Molecular Sciences.2026; 27(9): 4122. CrossRef
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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.

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
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Delia-Maria Bogheanu, Awatif Jaafar Sadeq Al Bayati, Mircea-Octavian Poenaru, Octavian Gabriel Olaru, Gabriel-Petre Gorecki, Andreea Gratiana Boiangiu, Bashar Haj Hamoud, Romina-Marina Sima, Liana Ples
Life.2026; 16(5): 809. CrossRef
From treatment to trauma: Womens lived experiences of adverse pregnancy outcomes following cervical intraepithelial neoplasia treatment in Zambia
Mwiinga-Kalusopa Victoria, E. Maree Johanna, N. Kwaleyela Concepta, Uwamahoro Marie-Claire, Mwila Musenge Emmanuel, Anila Nkhata Loveness, Katowa-Mukwato Patricia
International Journal of Nursing and Midwifery.2026; 18(2): 14. CrossRef
Cervical Cytological Findings and Vaginal Microbiota Alterations During Pregnancy: A Retrospective Analysis
Federica Cianfrini, Antonio d’Amati, Clelia Molinario, Belen Padial Urteta, Chiara Boccaccini, Antonio Benedetto Maria Donateo, Antonietta Vella, Rosaria Santangelo, Rosa Pasqualina De Vincenzo, Angela Santoro, Gian Franco Zannoni
Sage Open Pathology.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
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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 Articles

Aquaporin 1 promotes proliferation and migration of tumor by up-regulating claudin-1 expression in colon cancer: Wei Wei Xie, Lin Xu, Qian Li, Dao Quan Zhang, Yu Bao Zhou; J Pathol Transl Med. 2026;60(3):307-318. Published online March 20, 2026; DOI: https://doi.org/10.4132/jptm.2026.01.01

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Abstract PDF: Background
With the rising incidence of colon cancer, several studies have indicated that aquaporin 1 (AQP1) expression is associated with the development of colon cancer. This study aims to elucidate the potential molecular mechanisms between them. Methods: We screened data from The Cancer Genome Atlas (TCGA) database and retrospectively examined AQP1 protein expression in 127 colon cancer patients to analyze the relationship between AQP1 expression and pathological stages, prognosis. We created stable colon cancer cell lines with differential AQP1 expression, the effect of AQP1 expression on the proliferation and migration of colon cancer cells was assessed by in vitro and in vivo studies, and explored potential molecular mechanisms through Western blotting. Results: High AQP1 expression was associated with poorer survival (overall survival [OS], p = .028) in colon cancer patients from the TCGA database. Similarly, retrospective clinical data indicated that high AQP1 expression was associated with reduced disease-free survival and OS (p = .036 and p = .017, respectively). The low-expressing AQP1 colon cancer cells exhibited a decrease in proliferation and migration ability of colon cancer cells compared to the overexpressing AQP1 group (p < .05) in vitro and in vivo. Immunohistochemistry and western blotting experiments validated heightened expression of N-cadherin, vimentin, and claudin- 1 in the tumor tissues of the overexpressing AQP1 group. Conversely, reduced AQP1 expression resulted in decreased expression of claudin- 1. Conclusions: AQP1 correlates with unfavorable prognosis in colon cancer and potentially enhances the proliferation and migration of colon cancer by up-regulating claudin-1 expression.

Clinicopathological profile of high-grade differentiated thyroid carcinoma in an Indonesian tertiary hospital: Novita , Agnes Stephanie Harahap, Maria Francisca Ham, Alfianto Widiono, Chan Kwon Jung; J Pathol Transl Med. 2026;60(3):338-348. Published online April 23, 2026; DOI: https://doi.org/10.4132/jptm.2026.01.15

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Abstract PDF Supplementary Material: Background
High-grade differentiated thyroid carcinoma (HGDTC) is a recently recognized entity in the 2022 World Health Organization classification, representing a more aggressive subtype of differentiated thyroid carcinoma. Previously, high-grade features such as increased mitotic activity and tumor necrosis were often overlooked, despite being important independent prognostic factors. Although rare, HGDTC carries significant diagnostic, prognostic, and therapeutic implications. Data remain limited in Indonesia. Methods: This retrospective descriptive study reviewed 565 thyroid carcinoma cases diagnosed at Cipto Mangunkusumo Hospital from 2019 to 2024. Eleven cases (1.9%) met HGDTC criteria. Clinicopathological characteristics, histologic subtypes, Ki-67 proliferation index, molecular alterations, treatment modalities, and clinical outcomes were analyzed. Results: Patients had a mean age of 54.6 years, with a female-to-male ratio of 2.7:1. Papillary thyroid carcinoma was the main type (90.9%), with the tall cell subtype predominating. Mean tumor size was 6.4 cm. Lymphatic invasion, vascular invasion, and extrathyroidal extension were present in 54.5%, 18.2%, and 45.5% of cases, respectively. All tumors showed necrosis. Mean mitotic count was 3 per 2 mm². The Ki-67 index ranged from 5% to 45% (median, 14%). BRAFV600E and TERT promoter mutations were detected in 18.2% and 36.4% of cases, respectively, with co-mutations in 18.2%. Six cases (54.5%) had metastases at time of diagnosis. During a mean follow-up of 20.5 months, one patient (9.1%) developed new vertebral metastases and all patients (100%) remained alive. Conclusions: HGDTC presents with more aggressive characteristics and a worse prognosis. Accurate diagnosis, molecular profiling, and long-term monitoring are essential for optimal management.

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.

Citations

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Unraveling the nexus: Tumor mutational burden, PD‐L1 expression, and oncogenic alterations in non–small cell lung cancer cytology specimens
Min Dai, Francis Anthony San Lucas, Hector Alvarez, Leomar Ballester, Hui Chen, Keyur P. Patel, Asif Rashid, Shun Rao, Mark J. Routbort, Gloria Sura, Keith Sweeney, Gokce Toruner, Peng Wei, Richard Yang, Hyvan Dang, Rajyalakshmi Luthra, Sinchita Roy‐Chowd
Cancer Cytopathology.2026;[Epub] CrossRef
The critical role of accurate neoplastic cell percentage (NCP) assessment: investigating targeted training strategies for pulmonary biopsy and cytology specimens
Thi Mai Phuong Pham, Dieter Peeters, Jan von der Thüsen, Myriam Remmelink, Birgit Weynand, Elisabeth Dequeker
Virchows Archiv.2026;[Epub] CrossRef
Benign Biliary Tumors and Precursor Neoplasms: An Updated Clinicopathological and Molecular Review Based on the 2026 WHO Classification
Joon Hyuk Choi
Biomedicines.2026; 14(7): 1548. CrossRef
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; 70(2): 185. 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 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 Articles

Lymphomatoid papulosis: a practical review for pathologists: Mario L. Marques-Piubelli, Carlos A. Torres-Cabala, Roberto N. Miranda; J Pathol Transl Med. 2026;60(4):388-397. Published online July 15, 2026; DOI: https://doi.org/10.4132/jptm.2026.06.09

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Abstract PDF: Lymphomatoid papulosis (LyP) is a primary cutaneous CD30+ lymphoproliferative disorder characterized by a chronic and self-healing recurrent cluster of erythematous papules or nodules on the skin of the trunk and/or extremities. The disease has an indolent clinical course with spontaneous regression or waxing and waning clinical evolution. The histopathologic spectrum of LyP is vast and may show few to numerous atypical cells immersed in a mild to intense inflammatory background. The backbone for the diagnosis is the positivity for CD30, which is one of the criteria to define this group of lymphoproliferative disorders. The association of these different histological and immunophenotypical findings is used to subclassify this disease in different subtypes from A to E, associated with DUSP22/IRF4 rearrangement, and other rare forms. Although this differentiation is important to raise awareness of different differential diagnosis, it does not impact the prognosis or change the treatment, which is usually centered in symptom relief and faster regression. In this review, we aim to summarize the most updated information of the clinical, histopathological, and molecular characteristics of LyP and provide a practical assessment for the diagnostic features that could help with the main differential diagnosis.

Ganglioglioma and gangliocytoma: a review for pathologists: Gianfranco E. Umeres-Francia, Melissa Mejia-Bautista, Pouya Jamshidi, Jared T. Ahrendsen; J Pathol Transl Med. 2026;60(4):379-387. Published online July 15, 2026; DOI: https://doi.org/10.4132/jptm.2026.06.06

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Abstract PDF: Ganglioglioma and gangliocytoma are rare, predominantly low-grade neuroepithelial tumors that commonly present with epilepsy in children and young adults. Advances in molecular profiling have improved understanding of their pathogenesis, highlighting key roles for the mitogen-activated protein kinase/ERK signaling pathway. Diagnosis relies on a combination of clinical, radiologic, and histopathologic features, with complete surgical resection offering the best clinical outcomes. This review summarizes current knowledge on their epidemiology, etiology, clinical presentation, imaging characteristics, pathology, treatment strategies, and prognosis.

Angiomatoid fibrous histiocytoma: a review: Alexander N. Perez, Phyu P. Aung; J Pathol Transl Med. 2026;60(4):371-378. Published online July 15, 2026; DOI: https://doi.org/10.4132/jptm.2026.06.05

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Abstract PDF: Angiomatoid fibrous histiocytoma is a rare mesenchymal neoplasm of uncertain cell lineage with indeterminate behavior, hallmarked by EWSR1 translocations. This tumor typically arises in the subcutaneous or deep soft tissues and is composed of bland to mildly atypical histiocytoid cells with frequent intralesional hemorrhagic pseudocystic spaces. It affects both children and adults, without a significant sex predilection. Histologically, the tumor may be mistaken for a lymph node given the apparent predilection for node-bearing sites as well as the brisk lymphoid cuff featuring germinal centers. Surgical excision is often curative, with local recurrence occurring occasionally and metastasis only very rarely. A possible relationship to molecularly related entities arising primarily within the thoracic cavity and intracranial compartment has been proposed, although this association remains incompletely understood.

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.

Citations

Citations to this article as recorded by

The Practice of Cytopathology in India: Insights From a 2025 Nationwide Survey
Shruti Gupta, Ishan Gupta, Nalini Gupta, Bharat Rekhi
Diagnostic Cytopathology.2026;[Epub] CrossRef
Artificial intelligence in pathology: Perceived diagnostic utility and challenges from a cross-sectional survey in Northern India
Manupriya Sharma, Kavita Kumari, Navpreet, Rajneesh Kumari
Indian Journal of Pathology and Microbiology.2026; 69(2): 221. CrossRef

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

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 Articles

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

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Abstract PDF Supplementary Material

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

Citations

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ATP binding cassette subfamily D member 1: A highly sensitive diagnostic marker for solid pseudopapillary neoplasm of pancreas in biopsy samples——A multi-institutional study
Yuanhao Liu, Junya Peng, Ruizhe He, Xiaowei Xue, Jie Cui, Mengjie Li, Ying-ao Liu, Wanni Xu, Xiaohong Gao, Yingmei Wang, Zhe Zhang, Haizhen Lu, Zhigang Song, Peizhen Hu, Yupei Zhao, Wenze Wang
Human Pathology.2026; 174: 106125. CrossRef
Towards implementation of precision medicine biomarkers in early detection and prognostication of prostate cancer
Angela Yee, Jim Smith, Rajiv Kumar, Akash Sali, Euan J. Rodger, Aniruddha Chatterjee
Cancer and Metastasis Reviews.2026;[Epub] CrossRef
Phenotype-Oriented Characterization of NSC828786 Identifies Convergent HPN-AMACR-Associated Transcriptomic Signatures in Prostate Adenocarcinoma and Broad-Spectrum Antiproliferative Activity
Ya-Ting Wen, Rosario Trijuliamos Manalu, Han-Lin Hsu, Yu-Cheng Kuo, Ruey-Shyang Soong, Feng-Cheng Liu, Maryam Rachmawati Sumitra, Sheng-Liang Huang, Shih-Yu Lee, Sung-Ling Tang, I-Chuan Yen, Hong-Jaan Wang, Bashir Lawal, Alexander T. H. Wu, Hsu-Shan Huang
Cells.2026; 15(14): 1314. CrossRef
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

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.

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IgA Nephropathy: Mechanisms, Risk Stratification, and Precision Therapy
Sami Alobaidi
Diagnostics.2026; 16(9): 1259. CrossRef

Incidental serrated lesions of the appendix: analysis of 2,137 appendectomy specimens: Ömer Atmış, Ecem Dokuzlu Küçük, Hanife Seda Mavili, Fatma Seher Pehlivan, Ayça Tan, Semin Ayhan; J Pathol Transl Med. 2026;60(3):349-355. Published online May 4, 2026; DOI: https://doi.org/10.4132/jptm.2026.02.08

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Abstract PDF: Background
Serrated lesions of the appendix are rare, often incidental findings in routine appendectomy specimens. Their true frequency, histopathologic spectrum, and anatomic distribution remain incompletely characterized, partly due to variability in sampling practices. Methods: We retrospectively reviewed 2,137 appendectomy specimens (2015–2025) from a single tertiary pathology center. Cases with histologically confirmed serrated lesions were reexamined, classified as hyperplastic polyp (HP) or sessile serrated lesion/polyp (SSL/P), and assessed for clinicopathologic parameters including lesion size, location, and associated pathologies. Nonparametric tests were used, with statistical significance defined as p < .05. Results: Serrated lesions were identified in 34 cases (1.6%) with 36 serrated lesions, comprising 17 HPs (0.8%) and 19 SSL/Ps (0.9%). SSL/Ps were significantly larger than HPs (median 10.0 vs. 2.7 mm, p < .001) and were more frequently located in the distal appendix (68.4% vs. 33.3%, p = .045, one-tailed Fisher’s exact test). No dysplasia or traditional serrated adenoma was detected. Acute appendicitis was present in 88% of cases, and associated neoplasms in 9%. Conclusions: Appendiceal serrated lesions are uncommon and often incidental. In this large appendectomy series, SSL/Ps differed from HPs by larger size and distal predilection. These findings primarily support diagnostic awareness and optimized sampling/grossing practices—particularly careful evaluation of the distal appendix—rather than clinical risk stratification. Further studies incorporating systematic clinical correlation and molecular/immunohistochemistry analyses are warranted.

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.

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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
Transforming Breast Cancer Control in East Africa by Integrating Cytomorphology and Genetics Into National Policy
Josephine N Rioki, Mwangi Joseph, Rency Lel, Marshal Mweu, Lucy Muchiri
Cureus.2026;[Epub] CrossRef
Prélèvements mammaires percutanés
A. Ribrag, R. Foucher
EMC - Gynécologie.2026; 41(3): 1. CrossRef
Age and tumor size as independent predictors of malignancy in BI-RADS 4 and 5 breast lesions: A cross-sectional study in Vietnam
De Van Nguyen, Trung Van Pham, Tam Huu Dinh, Dung Ngoc Tran, Chung Thanh Dang, Dongling Wu
PLOS One.2026; 21(7): e0352690. CrossRef
Selective medical intelligence: Optimising AI-based breast cancer diagnosis classification through adaptive data filtering
Nicholas Christakis, Panagiotis Tirchas, Dimitris Drikakis
Neurocomputing.2026; 700: 134471. CrossRef
Diagnostic Performance of the International Academy of Cytology Yokohama System for Reporting Breast Fine-Needle Aspirates: A Cytology-Histopathology Correlation Study From Central India
Aditi Rathore, Archana Shrivastava, Maneesh Sulya
Cureus.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

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.

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Current status and epidemiology of endemic parasitic infections in Korea as of 2026: a narrative review
Sun Huh
Journal of the Korean Medical Association.2026; 69(3): 240. CrossRef
Occurrence of Spirometra mansoni in Domestic Dogs from Rural Ecuador and Its Public Health Relevance
Roberto D. Coello Peralta, Zully Baquerizo Orrala, Aldo Rubén Andrada, Davis Calle Atariguana, Geraldine Ramallo, Alicia Rojas
Animals.2026; 16(13): 2049. CrossRef

Case Study

Phenotypic plasticity in plasma cell myeloma: a CD138-negative case with a rare BRAF G469R mutation: Sun-Ju Oh, So-Hak Chung; J Pathol Transl Med. 2026;60(4):451-455. Published online April 22, 2026; DOI: https://doi.org/10.4132/jptm.2026.02.02

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Abstract PDF: CD138-negative plasma cell myeloma harboring a BRAF G469R mutation is described in a 76-year-old male presenting with multiple osteolytic lesions. Histologically, the lesion exhibited epithelioid to plasmacytoid morphology with prominent mitotic activity and vascular-like spaces. Immunophenotyping demonstrated strong vimentin and CD31 expression but absence of CD138 and other endothelial markers. Light-chain in situ hybridization confirmed a clonal κ-restricted plasma cell population. Bone marrow examination revealed near-complete replacement by atypical plasma cells, retaining CD138 negativity and demonstrating focal CD20 positivity, indicative of intratumoral heterogeneity. Next-generation sequencing identified a rare BRAF G469R variant. The patient exhibited poor response to bortezomib, lenalidomide, and dexamethasone therapy, necessitating a switch to carfilzomib-based treatment. This case underscores the diagnostic challenges of CD138-negative myeloma and highlights the importance of integrating morphology, immunophenotyping, and molecular profiling to inform accurate diagnosis and guide therapeutic strategies.

Original Articles

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.

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The evolving role of OMICS in gastrointestinal tumor biology and clinical practice
Qing Li, Junfeng Zhang, Junli Chen, Qiang Zhang, Ruihan Liu, Jialin Zhu, Yi Qing, Xi Wei, Jianpeng Sheng
Molecular Cancer.2026;[Epub] CrossRef
Pretreatment Claudin-18.2 Expression Predicts Poorer Survival Outcomes in Locally Advanced Gastric Cancer Treated with Perioperative Chemotherapy
Gürkan Gül, Özlem Kutlu, Asuman Argon, Halil Taşkaynatan, Özlem Özdemir
Diagnostics.2026; 16(9): 1277. CrossRef

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

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Abstract PDF Supplementary Material

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

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Cytology and small biopsy diagnosis of pancreatic ductal adenocarcinoma
Maria Pimenova, Matthew W. Rosenbaum
Seminars in Diagnostic Pathology.2026; 43(2): 150992. CrossRef

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.

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Importance of clinical, ultrasound and cytological characteristics in predicting malignancy in thyroid nodules with indeterminate cytology
Gabriel Gonçalves dos Santos, Wendy Muller Tirapani, Cínthia Minatel Riguetto, Icleia Siqueira Barreto, Denise Engelbrecht Zantut-Wittmann
Annals of Medicine.2026;[Epub] 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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Prevalence of Congenital Abnormalities in Abortuses and Stillbirths in India: A Systematic Review and Meta‐Analysis
Sushant Swaroop Das, Shalika Sharma, Reeha Mahajan, Sushruti Kaushal, Manupriya Sharma, Harsimranjit Singh, M. Ramkumar
Congenital Anomalies.2026;[Epub] CrossRef
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

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 Article

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

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.

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

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.

Citations

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Machine learning-assisted SERS for rapid and accurate early screening of cervical cancer
Dawei Cao, Fanfeng Shi, Yuting Huang, Li Zhang, Meng Ge, Hongmei Lu
Analytical and Bioanalytical Chemistry.2026;[Epub] CrossRef

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.

Reviews

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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Organ Preservation for Gastroesophageal Junction and Gastric Cancers: Ready for Primetime?
Winta Mehtsun, Lola Van Doosselaere, Ugwuji N. Maduekwe
American Society of Clinical Oncology Educational Book.2026;[Epub] CrossRef
Deep Learning Analysis Based on Dual-energy CT-Derived Iodine Map for Predicting PD-L1 Expression in Gastric Cancer: A Multicenter Study
Lihong Chen, Yuncong Zhao, Xiaomin Tian, Deye Zeng, Yongxiu Tong, Haiping Xu, Yaru You, Caiming Weng, Sen Lin, Keru Chen, Yilin Chen, Yunjing Xue
Academic Radiology.2026; 33(4): 1324. CrossRef
Artificial intelligence for biomarker prediction in gastric cancer: from histopathology to multimodal integration
Yesul Jeong, Sangjeong Ahn, Sung Hak Lee
Frontiers in Oncology.2026;[Epub] CrossRef
The research progress of the synergistic effect of Epstein-Barr virus and Helicobacter pylori infection in the occurrence and development of gastric cancer
Liming Gan, Liping Gong, Shan Wei, Junshan Deng
Frontiers in Oncology.2026;[Epub] CrossRef
Adjuvant immunotherapy in patients with resected gastric and oesophagogastric junction cancer following preoperative chemotherapy with high risk for recurrence (ypN+ and/or R1): European Organisation of Research and Treatment of Cancer (EORTC) 1707 VESTIG
F. Lordick, M.E. Mauer, G. Stocker, C.A. Cella, I. Ben-Aharon, G. Piessen, L. Wyrwicz, G. Al-Haidari, T. Fleitas-Kanonnikoff, V. Boige, R. Lordick Obermannová, U.M. Martens, C. Gomez-Martin, P. Thuss-Patience, V. Arrazubi, A. Avallone, K.K. Shiu, P. Artru
Annals of Oncology.2025; 36(2): 197. CrossRef
PD-L1 as a Biomarker in Gastric Cancer Immunotherapy
Yunjoo Cho, Soomin Ahn, Kyoung-Mee Kim
Journal of Gastric Cancer.2025; 25(1): 177. CrossRef
PD-L1 importance in malignancies comprehensive insights into the role of PD-L1 in malignancies: from molecular mechanisms to therapeutic opportunities
Mojdeh Soltani, Mohammad Abbaszadeh, Hamed Fouladseresht, Mark J. M. Sullman, Nahid Eskandari
Clinical and Experimental Medicine.2025;[Epub] CrossRef
CLDN18.2 expression in gastroesophageal adenocarcinoma: prevalence, heterogeneity, and prognostic implications in Spanish patients
Carolina Martinez-Ciarpaglini, María Ortega, Sandra Pérez-Buira, Aitana Bolea, Beatriz Casado Guerra, Carmen Herencia Bellido, Paula Tornero Piñero, Dolores Naranjo-Hans, Brenda Palomar, Hernán Quiceno, Amanda Sardón Fernández, Ariadna Torner Calvo, Feder
Virchows Archiv.2025; 487(6): 1337. CrossRef
Distinct clinicopathological and survival profiles of CLDN18.2 and PD-L1 expression in advanced gastric cancer and gastroesophageal junction adenocarcinoma
D.R. Castillo, M. Guo, P. Shah, M. Hazeltin, D. Tai, F. Al-Manaseer, S. Mlamba, D. Perez, S. Yeremian, S. Guzman, R. Mannan, C. Crook, C. Lau, N. Tawar, G. Brar, M. Raoof, Y. Woo, S.P. Wu, D. Li
ESMO Gastrointestinal Oncology.2025; 10: 100261. CrossRef
Best Practice PD-L1 Staining and Interpretation in Gastric Cancer Using PD-L1 IHC PharmDx 22C3 and PD-L1 IHC PharmDx 28-8 Assays, with Reference to Common Issues and Solutions
Soomin Ahn, Inwoo Hwang, Yuyeon Kim, Somin Lee, Yunjoo Cho, So Young Kang, Deok Geun Kim, Jeeyun Lee, Kyoung-Mee Kim
Biomedicines.2025; 13(11): 2824. CrossRef
Intraperitoneal immune microenvironment and efficacy of intraperitoneal chemotherapy in patients with gastric cancer and peritoneal metastasis
Tomoya Nakanishi, Motohiro Imano, Masashi Kohda, Hiroaki Kato, Naoko Kounami, Atsushi Yamada, Masuhiro Terada, Yoko Hiraki, Osamu Shiraishi, Atsushi Yasuda, Masayuki Shinkai, Takushi Yasuda
Scientific Reports.2025;[Epub] CrossRef
PD-L1 thresholds predict efficacy of immune checkpoint inhibition in first-line treatment of advanced gastroesophageal adenocarcinoma. A systematic review and meta-analysis of seven phase III randomized trials
V. Formica, C. Morelli, L. Fornaro, S. Riondino, M. Rofei, E. Fontana, E.C. Smyth, M. Roselli, H.-T. Arkenau
ESMO Open.2024; 9(11): 103967. CrossRef

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.

Citations

Citations to this article as recorded by

Primary biliary cholangitis: Beyond classical histopathology - diagnostic challenges in native and transplanted livers
Ivana Juskova, Andrea Vajsova, John Jackson, Ondrej Fabian, Eva Sticova
Annals of Diagnostic Pathology.2026; 85: 152683. CrossRef
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 Article

Expression of PD-1/PD-L1 pathway molecules in human cardiac allograft according to acute cellular rejection status: insights from a Korean Heart Transplant Cohort: Jeemin Yim, Yoon Kyung Jeon, Doo Hyun Chung, Jaemoon Koh; J Pathol Transl Med. 2026;60(3):319-330. Published online March 27, 2026; DOI: https://doi.org/10.4132/jptm.2026.01.02

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Abstract PDF: Background
Acute cellular rejection (ACR) following heart transplantation (TPL) compromises graft function and survival. The programmed cell death-1 (PD-1)/PD-1 ligand-1 (PD-L1) pathway represents an immune checkpoint that maintains peripheral immune tolerance, but its expression and significance in human cardiac allografts with ACR remain unclear. Thus, we investigated PD-1/ PD-L1 expression in endomyocardial biopsies from heart TPL recipients to clarify the role of this pathway in the ACR of human cardiac allografts and explore the potential of therapeutic modulation of PD-1/PD-L1 in this setting. Methods: Endomyocardial biopsies of 78 patients with heart TPL were subjected to immunohistochemistry for PD-L1, PD-1, CD4, and CD8. PD-L1 expression and quantities of PD-1+, CD4+, and CD8+ infiltrating lymphocytes were evaluated according to clinicopathological features, ACR presence, and clinical outcomes. Results: Allografts with high-grade ACR (International Society for Heart and Lung Transplantation grades 2R and 3R) demonstrated markedly higher PD-L1 expression than did those without ACR (62.5% vs. 16.1%, p < .001). PD-L1 expression was positively associated with CD4+ lymphocyte infiltration (p = .025), whereas CD8 and PD-1+ lymphocyte counts were higher in PD-L1-positive allografts without reaching statistical significance (p = .059 and p = .390, respectively). Serial biopsies revealed that PD-L1 expression was upregulated in patients with high-grade ACR compared with that in previous non-ACR tissues, and follow-up biopsies were performed after ACR resolution. Conclusions: The PD-1/PD-L1 pathway is involved in ACR regulation in human cardiac allografts. Increased PD-L1 expression during ACR may represent a counteractive mechanism to limit alloimmune-mediated tissue injury, supporting PD-1/PD-L1 as a potential therapeutic target in heart TPL recipients.

Case Study

Multidimensional analysis of concurrent proximal bronchiolar adenoma and lung carcinoma: Lu-Yao Li, Gong-Ming Dong, Yun-Peng Zhang, Ting-Ting Wang, Fu-Quan Jia, Guan-Jun Zhang; J Pathol Transl Med. 2026;60(3):356-363. Published online March 23, 2026; DOI: https://doi.org/10.4132/jptm.2025.12.31

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Abstract PDF Supplementary Material: Bronchiolar adenoma (BA) is a rare type of lung tumor characterized by bilayered epithelial cells having a continuous basal layer and a luminal layer. It resembles mucinous adenocarcinoma (MA) on frozen section, with difficulty in distinguishing the basal layer. Immunohistochemistry is the best choice for verifying the diagnosis. This study aimed to comprehensively characterize three cases of BA-combined carcinoma using clinical, histopathological, and genetic features. BA and carcinoma sections were subjected to next-generation sequencing, respectively. It was hypothesized that while different mutation forms matched different regions, BA and lung adenocarcinoma shared the same gene mutation when they co-occurred in the same location. BA with extensive carcinoma is extremely rare and presents diagnostic challenges due to its overlap with conditions such as MA. Because of its distinctive morphological characteristics, BA may be regarded as a low-grade malignancy, particularly during a confusing evaluation. A multifaceted examination of clinical, radiological, immunohistochemical, and genetic data is necessary for an accurate diagnosis.

Original Articles

The impairment of CD3⁺ T lymphocytes in sentinel lymph node of high-risk cutaneous melanoma patients in stage IIB and IIC: Emilija Filipović, Katarina Mirjačić Martinović, Ognjen Živković, Nataša Medić Milijić, Ana Lazarević, Zoran Bukumirić, Marko Jevrić, Milan Žegarac; J Pathol Transl Med. 2026;60(4):422-435. Published online July 15, 2026; DOI: https://doi.org/10.4132/jptm.2026.04.02

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Abstract PDF: Background
The sentinel lymph node (SLN) in melanoma is almost always the first site of metastasis and its histopathological assessment is essential for the determination of staging and clinical outcome. Furthermore, this procedure offers the investigation of the early immune response in SLN as melanoma-derived factors suppress the immunity in an early stage that may facilitate metastasis. A better understanding of the immunological changes in SLN may help in the therapeutic stimulation of melanoma immunity to prevent tumor metastasis. Methods: SLN tissues without malignant cells from 74 cutaneous melanoma patients (stage I and II) were analyzed. By flow cytometry, we measured the percentage of natural killer cells, CD3+ T lymphocytes, and their expression of interferon-γ (IFN-γ) and inhibitory immune checkpoint molecules (ICMs), and the percentage of CD4+Foxp3+ regulatory T cells (Tregs). Results: Melanoma patients with worse prognosis, in stage IIB–C, had decreased percentage of total CD3+ and CD3+CD8+ T lymphocytes, trend of IFN-γ decrease, increased inhibitory programmed cell death 1 and T cell immunoglobulin and mucin-domain containing 3 ICMs, and higher percentage of Tregs in their SLNs compared with stage I-IIA patients. Furthermore, patients with nodular melanoma had decreased CD3+CD8+ cells compared with patients with superficial spreading melanoma and together with patients with localization of primary tumor on extremities had an increase in the expression of analyzed ICMs. Conclusions: This study provides new results of the impairment of immune response in SLN of cutaneous melanoma patients with high risk for metastasis and could help in the introduction of new immunotherapies that could restore immunity and prevent metastasis in SLN.

A single-institution demographic study of pathologically proven renal disease in kidney transplant recipients over the last 33 years: Hyejin Noh, Jiyeon Kim, Yeong Jin Choi; J Pathol Transl Med. 2026;60(4):398-412. Published online May 26, 2026; DOI: https://doi.org/10.4132/jptm.2026.03.28

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Abstract PDF Supplementary Material: Background
While the number of kidney transplants for end-stage renal disease (ESRD) is increasing, studies examining the long-term demographic analyses based on pathological diagnosis of transplant kidney remain limited. Methods: We conducted a retrospective analysis of 4,188 transplant recipients who underwent either biopsy or nephrectomy from 1991 to 2023 at Seoul St. Mary’s Hospital. Results: Among 7,229 pathologically confirmed cases, rejection was the most prevalent (37.7%), followed by tubulointerstitial (25.4%), glomerular, drug toxicity, and vascular diseases. In 7,053 transplant biopsies, rejection was predominant across all age groups, with T-cell mediated (TCM) category being the most common (60.1%), followed by antibody-mediated and mixed. Drug toxicity increased with age (p = .047), while glomerular and tubulointerstitial diseases were highest in recipients under 20 (p < .001). Among glomerular diseases, IgA-related glomerulonephritis (45.2%) was the most common. In 176 transplant nephrectomies, the most common diagnosis was rejection (33.5%), followed by renal infarction (19.9%), tubulointerstitial, vascular, glomerular disease, and drug toxicity. “Others” included infarction, ESRD, and lymphangiectasia, which increased with age (p = .011). In nephrectomy cases, rejection decreased over time, with chronic TCM rejection (40.7%) being the most frequent. Conclusions: This study provides valuable insights into transplant kidney disease in South Korea. The number of transplant biopsies has increased over the past 33 years, while the number of nephrectomies has remained unchanged. Rejection was the most common finding in all age groups in biopsies, but decreased with age in nephrectomies, with TCM being the most common and observed more often in younger recipients.

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

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Abstract PDF

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

Citations

Citations to this article as recorded by

Clinicopathological, proliferative, molecular, and prognostic characteristics of differentiated high-grade thyroid carcinoma: a multicenter retrospective study
Wenwen Cui, Lihang Xing, Zhenzhen Li, Xinjun Li, Junzhi Li
Frontiers in Oncology.2026;[Epub] CrossRef
Integrating Digital Ki-67 Labeling Index and K-TIRADS for Malignancy Risk Stratification in Thyroid Core Needle Biopsies
Yujin Cha, Sue Youn Kim, Chankyung Kim, Ja Seong Bae, Dong-Jun Lim, So-Lyung Jung, Chan Kwon Jung
Cancers.2026; 18(14): 2260. CrossRef
The Association of Interstitial Fibrosis and Ki67 Marker Expression in Papillary Thyroid Carcinoma with Histopathological Findings and Prognosis of Total Thyroidectomy
Osman Anıl Savaş, Selçuk Mercan, Amir Mahdi Akbari, Mehrdad Sheikhvatan
Journal of Clinical Medicine.2026; 15(14): 5703. CrossRef
Research Progress on the Correlation between Three Biomarkers, Ki-67, CAIX and VEGF and Clear Cell Renal Cell Carcinoma
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Advances in Clinical Medicine.2025; 15(09): 326. CrossRef
Immunophenotypic Panel for Comprehensive Characterization of Aggressive Thyroid Carcinomas
Mihail Ceausu, Mihai Alin Publik, Dana Terzea, Carmen Adina Cristea, Dumitru Ioachim, Dana Manda, Sorina Schipor
Cells.2025; 14(19): 1554. CrossRef
High Ki-67 labeling index correlates with aggressive clinicopathological features in papillary thyroid carcinoma: a retrospective study
Defi Nurlia Erdian, Maria Francisca Ham, Dina Khoirunnisa, Agnes Stephanie Harahap
Thyroid Research.2025;[Epub] CrossRef

Case Study

SDH-deficient renal cell carcinoma with intracytoplasmic mucinous material: a case report and literature review: Ryosuke Yoshioka, Kosuke Miyai, Kimi Kato, Keiichi Ito, Kimiya Sato, Susumu Matsukuma; J Pathol Transl Med. 2026;60(4):456-461. Published online July 15, 2026; DOI: https://doi.org/10.4132/jptm.2026.04.23

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Abstract PDF: Succinate dehydrogenase (SDH)–deficient renal cell carcinoma (RCC) is a rare, molecularly defined neoplasm. We report a 45-year-old man with a right renal mass treated by nephrectomy. Grossly, a 38-mm gray-white-to-brown solid cystic tumor was observed in the lower pole of the kidney. Microscopically, the tumor consisted of sheets and nested proliferation of eosinophilic cells with low-grade nuclei and bubbly or flocculent cytoplasm. No sarcomatoid or rhabdoid features were observed. Abundant extracellular and focal intracytoplasmic mucinous material was observed in the tumor, which was positive for Alcian blue and mucicarmine staining, but negative for periodic acid–Schiff staining. Immunohistochemistry showed complete loss of succinate dehydrogenase subunit B in tumor cells. These findings supported the diagnosis of RCC consistent with SDH-deficient RCC. This case expands the morphological spectrum of SDH-deficient RCC and highlights the diagnostic pitfalls of renal tumors with mucinous material.

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