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
Improving diagnostic confidence in thyroid pathology in resource-limited settings: a practical guide for the general anatomical pathologist
Brendon Price
Diagnostic Histopathology.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 neoplastic pulmonary pathology 2026: updates on grading, staging and molecular testing: Andreas Tiefenbacher, Luka Brčić; J Pathol Transl Med. 2026;60(5):587-591. Published online August 31, 2026; DOI: https://doi.org/10.4132/jptm.2026.07.28

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Abstract PDF: Neoplastic pulmonary pathology has continued to advance in recent years, including the introduction of histologic grading systems for both adenocarcinoma and squamous cell carcinoma, implementation of the UICC TNM 9th Edition classification, expanded molecular testing requirements, refinements in neuroendocrine tumor classification, and improvements in mesothelioma diagnostics. This newsletter summarizes the most important developments relevant to practicing pathologists.

Original Article

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.

Newsletter

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.

Citations

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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

Review Article

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

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Abstract PDF

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

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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
Case report: Reactive nodular fibrous pseudotumor: report of 4 new cases including a rare pulmonary presentation and a literature review covering 40 cases
Xinyao Liu, Chenghui Wang, Weiran Kong, Bangdong Liu, Tianlun Li, Susu Shi, Linlin Zhang, Shuai Chen
Frontiers in Medicine.2026;[Epub] CrossRef
Clinical and hematological indices as prognosticators in localized solitary fibrous tumors: A retrospective study
Ariel Yoong Yi KOH, Ryan Mao Heng LIM, Jason Yongsheng CHAN
Therapeutic Advances in Medical Oncology.2026;[Epub] CrossRef
Intrapulmonary solitary fibrous tumor: clinicopathological analysis of 29 cases with emphasis on morphological spectrum and immunohistochemical profile
Xin Zeng, Xiaodong Lin, Lifang Ye, Zhenyong Wu, Zeyun Lin, Shuting Li
Diagnostic Pathology.2026;[Epub] CrossRef

Newsletter

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.

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FTU-Seek: Foundation Model-Guided Hard-Negative Learning for Sparse Functional Tissue Unit Segmentation
Zonghao Liu, Lei Su, Jiguang Yu, Xuqing Geng, Louis Shuo Wang, Jianmin Wang, Jingfeng Liu
Biomedicines.2026; 14(9): 1935. CrossRef
Lightweight deep learning models for histopathological image analysis in resource-constrained healthcare environments
Ahmed Adedeji Adeniyi, Steve Adetunji Adeshina, Yusuf Abass Aleshinloye, Roseline Oluwaseun Ogundokun, Pius Adewale Owolawi
Intelligence-Based Medicine.2026; 15: 100475. 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.

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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
Unveiling Remyelinating Properties of Roflumilast in CPZ‐Induced Neuronal Demyelination in Mice
Ahmed S. Kamel, Israa Sameh, Mohamed A. Khattab, Ayman E. El‐Sahar, Hala F. Zaki, Osama A. Badary, Sama M. Farrag
Drug Development Research.2026;[Epub] CrossRef
Bayes at the Bedside: Biomarkers in Situations of Clinical Uncertainty
Uwe Klaus Zettl, Michael Hecker
Diagnostics.2026; 16(11): 1699. CrossRef
Successful treatment with rituximab in unilateral relapsing primary CNS vasculitis: a case report
Ryo Morikawa, Katsuhiko Kunitake, Junichiro Suzuki, Noriyoshi Nakai, Mari Yoshida, Yasuhiro Ito
Rinsho Shinkeigaku.2026; 66(8): 553. CrossRef
Combined clemastine fumarate and selenomethionine promote remyelination via PI3K/Akt/mTOR signaling in experimental multiple sclerosis
Rohit Kumar Singh, Sidharth Mehan
Naunyn-Schmiedeberg's Archives of Pharmacology.2026;[Epub] CrossRef
White Matter in Crisis: Oligodendrocytes and the Pathophysiology of Multiple Sclerosis
Mario García-Domínguez
Cells.2025; 14(18): 1408. CrossRef
Tumefactive demyelinating lesions: a case report and literature review
Raneem Jaki, Zyad Al-Frejat, Ziad Bitar
BMC Neurology.2025;[Epub] CrossRef
Liquerologia: Uma ferramenta no diagnóstico de esclerose múltipla e outras doenças neurodegenerativas e desmielinizantes
Laura Maria de Araújo Pereira, Talyta Valeria Siqueira do Monte Guedes, Rafaell Batista Pereira, Davi Abrantes Lucena Messias, Marfran José Cunha Urtiga, Davi Rodrigues Vieira, Samuel da Costa Chaves Trindade Martins, José Guedes da Silva Júnior
Research, Society and Development.2025; 14(12): e72141249815. CrossRef

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

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

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Oncocytic Thyroid Tumours With Pathogenic FLCN Mutations Mimic Oncocytic Papillary Thyroid Carcinoma on Fine‐Needle Aspiration
Adeel M. Ashraf, Faisal Hassan, Adrian A. Dawkins, Julie C. Dueber, Derek B. Allison, Thèrése J. Bocklage
Cytopathology.2026; 37(1): 108. CrossRef
Using a new type of visible light-based emission fluorescence microscope to identify the benign and malignant nature of thyroid tissue during the surgical process: Analysis of diagnostic results
Yu Miao, Liu Xiaowei, Li Muyang, Gao Jian, Chen Lu
Photodiagnosis and Photodynamic Therapy.2026; 57: 105324. CrossRef
Clinical Behavior of Aggressive Variants of Papillary Thyroid Carcinoma: A Retrospective Case–Control Study
Jovan Ilic, Nikola Slijepcevic, Katarina Tausanovic, Bozidar Odalovic, Goran Zoric, Marija Milinkovic, Branislav Rovcanin, Milan Jovanovic, Matija Buzejic, Duska Vucen, Boban Stepanovic, Sara Ivanis, Milan Parezanovic, Milan Marinkovic, Vladan Zivaljevic
Cancers.2026; 18(2): 345. CrossRef
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
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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
Infiltrative follicular variant papillary thyroid carcinoma with bilateral cervical nodal metastases following benign cytology: Surgical management in a resource-limited setting
Anil Akulwar, Anjali Mane, Ashwini Kumar Rajkumar, Neha Misal
International Journal of Health & Allied Sciences.2026; 15(2): 120. CrossRef
Analysis of the value of contrast-enhanced ultrasound with CT imaging in the assessment of preoperative cervical lymph node metastases in papillary thyroid cancer
T. Yu, L. Liu, Z. Wang, R. Li, M. Zhang, C. Liu
International Journal of Radiation Research.2026; 24(2): 441. CrossRef
Non‐Oncocytic Thyroid Follicular Neoplasm: Cytological Atypia and Development of a Score for Malignancy Risk Stratification
Boris M. Shifman, Nadezhda M. Platonova, Fatima M. Abdulkhabirova, Ekaterina V. Bondarenko, Anastasia M. Lapshina, Liliya S. Urusova, Georgii S. Razmakhaev, Tatyana N. Kamneva, Ekaterina A. Troshina
Diagnostic Cytopathology.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
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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
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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
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A Case of Warthin-Like Variant of Papillary Thyroid Cancer
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Cureus.2025;[Epub] CrossRef
Propensity score-matched analysis of the ‘2+2’ parathyroid strategy in total thyroidectomy with central neck dissection
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Cytological Findings in Pediatric Thoracic Tumors: A Review of Diagnostic Insights and Pitfalls
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Acta Cytologica.2025; 70(3): 320. 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.

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Comparative analysis of robotic- and endoscopic-assisted minimally invasive nipple–areola complex–sparing mastectomy for breast cancer: a meta-analysis with subgroup analyses
Xiaohan Wang, Hua Tian, Min Zhang, Jiangyong Shen, Yangxu Ding, Yupei Dai, Huijuan Shi
Journal of Robotic Surgery.2026;[Epub] CrossRef
HER2-Low Breast Cancer: A Review of Epidemiology, Diagnostic Challenges, Targeted Therapies, and Clinical Outcomes
Maedeh Mirasheh, Zahra Shahabinia, Mai Abdel Haleem A. Abusalah, Afrooz Mazidimoradi, Leila Allahqoli, Hamid Salehiniya, Do-Youn Lee
Journal of Clinical Medicine.2026; 15(19): 7559. CrossRef

Review Articles

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.

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.

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Leiomyosarcoma Involving the Calcaneum With Delayed Gastric and Sacroiliac Lesions: A Case Report
Asmita Kaur, Rajat Gupta, Harpreet Singh, Gurkirat S Bhatti
Cureus.2026;[Epub] CrossRef

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

Hyalinizing trabecular tumors with areas resembling noninvasive follicular thyroid neoplasm with papillary‑like nuclear features: an immunohistochemical and molecular analysis: Risa Kanematsu, Mitsuyoshi Hirokawa, Ayana Suzuki, Miyoko Higuchi, Satomi Usuki, Hiroshi Kamma, Takashi Akamizu; J Pathol Transl Med. 2026;60(4):436-443. Published online July 15, 2026; DOI: https://doi.org/10.4132/jptm.2026.06.07

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Abstract PDF: Background
The coexistence of hyalinizing trabecular tumor (HTT) and areas with a morphology of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) within a single thyroid nodule has not been previously reported. We aimed to determine whether such tumors represent two independent neoplasms or a single tumor exhibiting divergent morphology. Methods: Ten tumors containing both HTT and NIFTP-like areas were examined. The term “NIFTP-like” was used strictly as a descriptive morphological designation for areas that fulfill the histologic criteria of NIFTP. Immunohistochemical analyses of Ki-67 (MIB-1) and type IV collagen and targeted molecular testing were performed. Ten NIFTPs, 10 follicular adenomas, and three HTTs were used as controls. Results: HTT components consistently showed characteristic membranous Ki-67 staining and intra-trabecular type IV collagen deposition, whereas NIFTP-like areas lacked these features, except for focal apical Ki-67 staining. Intranuclear cytoplasmic inclusions in HTT were positive for type IV collagen. NIFTPs showed neither membranous Ki-67 nor intra-trabecular type IV collagen. Molecular analysis demonstrated identical profiles between HTT components and NIFTP-like areas: three tumors harbored PAX8::GLIS3 fusions, and none showed RAS mutations. Pure HTT controls exhibited the same pattern. Conclusions: Our findings indicate that these follicular-patterned areas represent a morphological variant within the spectrum of HTT rather than a true NIFTP-related component or two separate neoplasms. These findings expand the recognized histologic diversity of HTT and highlight a potential diagnostic pitfall in follicular-patterned thyroid tumors. Focal apical Ki-67 staining may serve as a useful clue for distinguishing HTT from NIFTP.

Newsletter

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

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Abstract PDF

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

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Opportunities and challenges in recurrent diffuse podocytopathy post-transplantation: the critical value of the definition
Rachel Nuccitelli, Amadea Toutoungis, Elena Martinelli, Simone Sanna-Cherchi, Astrid Weins, Heather K. Morris, Andrew S. Bomback, Ibrahim Batal
Frontiers in Immunology.2026;[Epub] CrossRef
Circulating Nephrin Antibodies and Post-Transplant Recurrence of Diffuse Podocytopathies: A Systematic Review
Noppawit Aiumtrakul, Charat Thongprayoon, Jing Miao, Wisit Cheungpasitporn
Kidney Medicine.2026; : 101521. 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
Targeted ALK inhibition achieving tumour control in metastatic melanoma: a case report
Cornelia Schuster, Irja Alida Oppedal , Liv Iren Vinnem, Eirin Lunden Abrahamsson, Torill Myklestad Barrett, Eli Sihn Samdal Steinskog, Hege Elisabeth Giercksky Russnes , Åslaug Helland
Acta Oncologica.2026; 65: 814. CrossRef

Original Article

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.

Review Article

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.

Original Articles

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
Development and validation of a predictive model for rapid renal function decline in early IgA nephropathy: a multicenter retrospective study
Junan Zhou, Yang Liu, Lixia Huo, Xu Wu, Zhelun Zhou, Haodong Liu, Rong Wu, Jiaai Zhang, Yiqing Yu, Deyong Fan, Xiaoyi Wang
Frontiers in Medicine.2026;[Epub] CrossRef

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.

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The Practice of Cytopathology in India: Insights From a 2025 Nationwide Survey
Shruti Gupta, Ishan Gupta, Nalini Gupta, Bharat Rekhi
Diagnostic Cytopathology.2026; 54(9): 644. 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
Assessment Instruments for Artificial Intelligence Literacy in Healthcare Professionals: A Scoping Review
Sergio Mies-Padilla, Claudio-Alberto Rodríguez-Suárez, Héctor González-de la Torre
Information.2026; 17(9): 914. CrossRef

Review Article

Sentinel lymph node biopsy in melanoma: pathologic evaluation and diagnostic considerations: Dre Barnachea, Bonnie Lee; J Pathol Transl Med. 2026;60(5):493-501. Published online September 1, 2026; DOI: https://doi.org/10.4132/jptm.2026.07.01

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Abstract PDF: Sentinel lymph node biopsy (SLNB) is a widely used staging procedure in melanoma that provides important prognostic information and guides clinical management. The sentinel lymph node (SLN), defined as the first lymph node in the lymphatic drainage pathway from a primary tumor, represents the most likely site of early regional metastasis. Accordingly, identification of metastatic melanoma within SLNs has significant implications for staging and risk stratification and is associated with worse clinical outcomes. The SLNB procedure involves preoperative and intraoperative lymphatic mapping techniques, including radiotracer localization with or without blue dye injection, which allow identification of SLNs. Histopathologic evaluation includes careful gross examination, serial sectioning, and immunohistochemical analysis using melanocytic markers such as SOX10, Melan-A, HMB45, and occasionally PRAME to detect metastatic disease. In addition, prognostic features such as tumor burden, extranodal extension, and microanatomic location of metastases within the lymph node further refine risk assessment. This review provides an overview of SLNB in melanoma, with emphasis on clinical indications, histopathologic evaluation, and key diagnostic and prognostic considerations.

Original Articles

Diagnostic performance of fine needle aspiration cytology in the preoperative identification of mucoepidermoid carcinoma: a cross-sectional diagnostic analytical study: Sumaya , Dishant Ramkrishna Sonuwane, Amita Krishnappa; J Pathol Transl Med. 2026;60(5):549-557. Published online September 15, 2026; DOI: https://doi.org/10.4132/jptm.2026.07.08

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Abstract PDF Supplementary Material: Background
Mucoepidermoid carcinoma (MEC), the most common malignant tumor of the salivary gland, accounts for 5%–10% of all salivary gland tumors. MEC shows extensive cytomorphological diversity, making preoperative diagnosis challenging. Hence, the present study was conducted to assess the diagnostic accuracy of fine-needle aspiration cytology (FNAC) in diagnosing MEC preoperatively and to discuss the cytological pitfalls in diagnosing mucoepidermoid carcinoma. Methods: The present study was a cross-sectional diagnostic analytical study conducted over a period of five years, which included confirmed cases of MEC. Each case was classified according to the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) and individual cytomorphological features were noted. All cases were compared by considering histopathology as the gold standard for diagnosis. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FNAC in diagnosing MEC were calculated to evaluate the diagnostic accuracy of FNAC. Results: All 42 cases of MEC were reclassified according to MSRSGC as follows: category II, one case; category III, one case; category IVA, two cases; category IVb, one case; category V, four cases; and category VI, 33 cases. Discordant cases (5 cases) were mainly due to cystic change, low cellularity, and overlapping features with benign lesions. The sensitivity, specificity, PPV, NPV, and diagnostic accuracy were found to be 88.1%, 100%, 100%, 97.4%, and 97.8%, respectively. Conclusions: FNAC is an important preoperative diagnostic investigation for MEC as reflected by its high specificity, sensitivity, and overall diagnostic accuracy in the present study. Careful attention to individual cytomorphological features and clinicoradiological correlation can significantly improve the diagnostic accuracy by directing the clinicians for further management.

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
Prevalence of Claudin 18.2 Expression in Gastric and Gastroesophageal Junction Adenocarcinoma: A Systematic Review and Meta-Analysis
Fazal Elahi Khan, Rajendranandini Majumdar, Mohan Dodeja, Gabriel Amorim Moreira Alves, Amr Harby, Rida Siddiqui, Shahbaz Madappattuparambil
Journal of Gastrointestinal Cancer.2026;[Epub] CrossRef

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.

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.

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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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
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Isabel L. Macêdo, Liz A. Cerqueira, Yasmin N. G. Fonseca, Antonizete R. Souza, Ana L. G. L. Chisté, Márcio B. Castro
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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.

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HER2-Low Breast Cancer: A Review of Epidemiology, Diagnostic Challenges, Targeted Therapies, and Clinical Outcomes
Maedeh Mirasheh, Zahra Shahabinia, Mai Abdel Haleem A. Abusalah, Afrooz Mazidimoradi, Leila Allahqoli, Hamid Salehiniya, Do-Youn Lee
Journal of Clinical Medicine.2026; 15(19): 7559. CrossRef

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.

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.

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.

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 Article

T-lymphoblastic leukemia/lymphoma: a comprehensive review of pathology, molecular features, and differential diagnosis: David Danielson, Ian T. Lagerstrom, Max Rogers, Kyle Simon, Nadine S. Aguilera, Aaron Auerbach; J Pathol Transl Med. 2026;60(5):502-515. Published online September 15, 2026; DOI: https://doi.org/10.4132/jptm.2026.08.01

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Abstract PDF: T-lymphoblastic leukemia/lymphoma (T-ALL/LBL) is an aggressive neoplasm of immature T-lymphoid precursors that is classified as T-cell acute lymphoblastic leukemia when the primary site of involvement is the bone marrow and peripheral blood and as T-cell lymphoblastic lymphoma when it presents as a solid mass, most commonly in the anterior mediastinum. The neoplastic cells are defined by expression of T-lineage antigens (cytoplasmic or surface CD3) together with one or more markers of immaturity (terminal deoxynucleotidyl transferase, CD1a, CD34, CD99, or CD117) and must not fulfill criteria for early T-cell precursor acute lymphoblastic leukemia (ALL). This entity shows a marked male predominance (male:female ≈ 2:1) and predominantly affects children, adolescents, and young adults, accounting for approximately 15% of childhood ALL and 20%–25% of adult ALL cases. Pathologic diagnosis increasingly relies on recurrent molecular alterations such as activating NOTCH1 mutations (>60% of cases), transcription factor rearrangements, and cell-cycle regulator inactivation. Although intensive multiagent chemotherapy regimens have substantially improved outcomes, particularly in pediatric patients, adults and high-risk molecular subgroups continue to experience inferior survival. This review provides a practical, pathology-oriented update on the epidemiology, pathogenesis, diagnostic criteria, differential diagnosis, prognostic factors, and current treatment approaches for T-ALL/LBL.

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.

Citations

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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

Review

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

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Abstract PDF Supplementary Material

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

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Winta Mehtsun, Lola Van Doosselaere, Ugwuji N. Maduekwe
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Shang Li, Jiaxin Huang, Rui Fang, Ming Zhang, Yucui Jin, Yi Zhu, Changyan Ma
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A deep learning-derived risk score model from digital pathology to forecast nivolumab outcomes in gastric carcinoma
Yiyu Hong, Inwoo Hwang, Min-Ji Kim, Yuyeon Kim, Soomin Ahn, Jeeyun Lee, Kyoung-Mee Kim
British Journal of Cancer.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
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Mojdeh Soltani, Mohammad Abbaszadeh, Hamed Fouladseresht, Mark J. M. Sullman, Nahid Eskandari
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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
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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
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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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Serdar Aslan, Merve Nur Tasdemir, Ertugrul Cakir, Ural Oguz, Birgul Tok
Abdominal Radiology.2025; 50(10): 4700. CrossRef
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Case Study

Non-keratinizing immature squamous metaplasia in the pancreas mimicking malignancy: a diagnostic pitfall in cytology: Hiroko Hayashi, Tomoaki Kubo, Takuya Hara, Saeko Jinnai, Keisuke Iwasaki; J Pathol Transl Med. 2026;60(4):444-450. Published online July 15, 2026; DOI: https://doi.org/10.4132/jptm.2026.02.19

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Abstract PDF: This report describes a challenging case in which atypical immature squamous metaplasia was misinterpreted as malignancy. A 69-year-old man presented with abdominal pain and loss of appetite. Imaging revealed mild pancreatic duct dilation, parenchymal enlargement, and increased fat attenuation in the transverse mesocolon. Endoscopic ultrasound revealed a hypoechoic lesion in the pancreatic body. The serum amylase level was markedly elevated (1,785 U/L), consistent with acute pancreatitis. Repeated pancreatic juice cytology examinations demonstrated atypical epithelial clusters, which raised concerns about possible pancreatic ductal adenocarcinoma. Therefore, distal pancreatectomy with splenectomy and transverse colon resection were performed. However, histopathological examination revealed only atypical immature squamous metaplasia. Retrospective review of the cytological specimens showed overlapping cell clusters with coarse chromatin, prominent nucleoli, nuclear pleomorphism, and peripheral dissociation in a neutrophilic background with focal hemorrhagic necrosis. Although rarely encountered, squamous metaplastic cells can appear in pancreatic cytology and represent a potential pitfall by mimicking adenocarcinoma.

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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Mwiinga-Kalusopa Victoria, E. Maree Johanna, N. Kwaleyela Concepta, Uwamahoro Marie-Claire, Mwila Musenge Emmanuel, Anila Nkhata Loveness, Katowa-Mukwato Patricia
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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
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The significance of biological samples from pregnant women in cervical intraepithelial neoplasia
Xue Mi, Maharjan Rashmi, Zangyu Pan, Di Wu, Jinwei Miao
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Oncologic and pregnancy outcomes of cervical high-grade intraepithelial lesions and delivery mode
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Case Study

Fibrosarcoma of bone masquerading as fibrous dysplasia: diagnostic pitfall and molecular correlates of aggressive behavior: Wangpan J. Shi, Brady K. Huang, Li Lei; J Pathol Transl Med. 2026;60(5):578-586. Published online August 3, 2026; DOI: https://doi.org/10.4132/jptm.2026.05.29

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Abstract PDF Supplementary Material: Low-grade fibro-osseous lesions can be challenging to classify. A 33-year-old man presented with synchronous lesions involving the ilium and T2 vertebra. Because of an impending pathologic fracture, he received several doses of denosumab. Initial biopsies showed bland fibro-osseous lesions lacking GNAS or MDM2 alterations and were favored to represent polyostotic fibrous dysplasia. Subsequent iliac curettage revealed a fascicular spindle cell proliferation with subtle atypia and focal ossification, leading to a revised diagnosis of low-grade fibrosarcoma. Re-biopsy of the T2 lesion demonstrated a similar spindle cell proliferation without ossification. Sequencing identified copy number gains involving KIT, PDGFRA, and TERT. At 16-month follow-up, two metastatic pulmonary nodules developed, one responsive to chemotherapy. The patient remains alive with disease at 27 months after presentation. This case highlights a diagnostic pitfall in which low-grade fibrosarcoma with denosumab-associated ossification may mimic fibrous dysplasia and underscores the prognostic value of molecular profiling beyond histologic grading.

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.

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

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Abstract PDF

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

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Pheochromocytomas with Aggressive Histopathological Features Have Reduced Apelin and Increased VEGF Expression: Diagnostic and Prognostic Implications
Hatice Çalışkan Burgucu, Tuğba Günler, Ethem Ömeroğlu, Yaşar Ünlü, Oğuzhan Aksu
Pathophysiology.2026; 33(4): 72. CrossRef

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.

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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
Sub-Saharan African Prostate Cancer Patient-Derived Cell Lines and High-Throughput Drug Screening: Addressing Ancestry Underrepresentation in Oncobiology Research
Carla S. Dos Santos, Ana C. Magalhães, Veronica Fernandes, António Pombinho, Lurdes Torres, Margarida André, Adelaide Sousa, Pedro Sequeira, Daniel Pinto, Cláudia Pereira, Paulo M. Costa, Lúcio Lara Santos, Luisa Pereira
Cancers.2026; 18(15): 2452. CrossRef
Prostate Cancer with Pleural Metastasis: A Case Report
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Journal of Clinical Personalized Medicine.2026; 05(04): 190. CrossRef
Pathology-Guided Transcriptomic Profiling of Prostate Cancer Identifies Grade-Associated Proliferative and Immune Signatures in a MENA Cohort
Ranyah Al-Hakm, Alaa Muayad Altaie, Reem Sami Alhamidi, Anania Boghossian, Nival Ali, Alaa Mohamed Hamad, Eman Sheta, Nagwa Mashali, Riyad Bendardaf, Timo Gemoll, Iman M. Talaat, Rifat Hamoudi
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Pathogenesis-Guided Biomarker Assessment: A Shift in Prostate Cancer Diagnostics
Jessica M. Logan, Victoria Malone, John J. O’Leary, Doug A. Brooks
International Journal of Molecular Sciences.2025; 26(24): 11786. CrossRef

Case Studies

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.

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

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.

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.

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HER2-Low Breast Cancer: A Review of Epidemiology, Diagnostic Challenges, Targeted Therapies, and Clinical Outcomes
Maedeh Mirasheh, Zahra Shahabinia, Mai Abdel Haleem A. Abusalah, Afrooz Mazidimoradi, Leila Allahqoli, Hamid Salehiniya, Do-Youn Lee
Journal of Clinical Medicine.2026; 15(19): 7559. CrossRef

Review Article

Obesity-driven adipokine signaling in breast cancer: mechanistic insights, therapeutic challenges, and opportunities for precision oncology: Vadakke Kunnumma Soonu, Praveen Kumar Shenoy, Valiyaparampil Gopi Deepak Roshan, Vipin Gopinath, Krishnan Sreejith; J Pathol Transl Med. 2026;60(5):476-492. Published online September 9, 2026; DOI: https://doi.org/10.4132/jptm.2026.06.30

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Abstract PDF: Breast cancer is the leading cause of illness and death among women worldwide, with more than 2.3 million new cases diagnosed each year. The incidence and fatality rates are steadily increasing, notably in Asian countries. Obesity has been established as a major and growing risk factor for breast cancer progression. The World Health Organization reports that adult obesity rates have doubled since 1990. Obesity promotes tumor growth by inhibiting adipokine production and activating cancer-promoting pathways. In obese people, the microenvironment surrounding breast cancer cells is drastically altered. This is mostly due to the malfunctioning of adipocytes (fat cells) and macrophages. These defective cells' adipokines alter signaling pathways required for cancer cell proliferation, survival, and inflammation. This dysregulation has a significant role in tumor development, metastasis, and resistance to traditional cancer treatments, particularly in obese patients. This review highlights the role of adipokines in breast cancer, with a focus on disease progression, therapeutic challenges, and knowledge gaps. Clarifying how obesity alters tumor biology is key to advancing personalized and effective treatments for obese patients.

Case Study

Clinicopathological characteristics of primary malignant cutaneous perivascular epithelioid cell tumor: case report and literature review: Huaming Li, Dan Zhang, Shiwu Zhang; J Pathol Transl Med. 2026;60(5):572-577. Published online July 20, 2026; DOI: https://doi.org/10.4132/jptm.2026.05.10

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Abstract PDF: Primary cutaneous malignant perivascular epithelioid cell tumors (PEComas) are extremely rare. Accurate diagnosis is critical for prognostic evaluation and guiding clinical management. Here, we report a case of a 19-year-old woman with a 1.1 cm exophytic red mass on her left upper limb. Histological examination revealed a dermal tumor composed of clear cells with prominent nucleoli. The tumor cells displayed cytologic atypia, nuclear pleomorphism, multinucleated giant cells, mitoses and invasive growth, with a multinodular distribution within the dermis and vascular invasion. Immunohistochemically, the tumor cells expressed cathepsin K, HMB45, and CD10. Based on morphological and immunohistochemical findings, we classified it as a primary malignant cutaneous PEComa. To date, only eight reported cases have been described as primary malignant cutaneous PEComas. The present case appears to be the youngest patient reported among all malignant PEComas.

Review Article

Spread through air spaces as a marker of nonlinear evolutionary trajectories in lung cancer: implications for the 9th edition TNM classification: Jin-Haeng Chung; J Pathol Transl Med. 2026;60(5):463-475. Published online September 15, 2026; DOI: https://doi.org/10.4132/jptm.2026.06.16

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Abstract PDF: Recent advancements in the diagnosis and therapeutic management of lung cancer have contributed to an evolution in pathological reporting standards. The 8th edition of the TNM classification of lung tumors has introduced the invasive size of adenocarcinoma—rather than total tumor size—as the primary determinant for staging. Concurrently, histological grading criteria proposed by the International Association for the Study of Lung Cancer (IASLC), based on predominant and highest-grade architectural patterns, appear to offer improved clinical utility over legacy systems. In addition, tumor spread through air spaces (STAS) has emerged as an actively investigated pattern of invasion, characterized by the presence of neoplastic cells beyond the main tumor mass within the adjacent pulmonary parenchyma. STAS is frequently observed in advanced-stage and node-positive non–small cell lung cancer and often correlates with distant metastasis. Recognizing its clinical relevance, the IASLC Staging Project recently recommended incorporating STAS as a histologic T descriptor in the 9th edition of the TNM classification. Expanding upon this framework, this review explores STAS not merely as a prognostic indicator, but as a potential reflection of divergent evolutionary trajectories influenced by underlying driver mutations. Accordingly, this review aims to comprehensively synthesize the prevailing controversies and recent academic milestones regarding STAS, the current limitations in preoperative STAS risk prediction, the logistical hurdles of intraoperative diagnosis, and critically evaluates the need for prospective clinical trials to validate STAS as a predictive biomarker for adjuvant systemic therapy.

Original Articles

Increased Toll-like receptor 9 expression associated with cellular proliferation and poor prognosis in pleural mesothelioma: Ali Omar Abdelaziz, Dina Moustafa Thabit, Rehab Mohamed Kamal, Hend Moness, Rasha Fouad Ahmed, Mariana Fathy Gayyed, Fatma El Zahraa Ammar Mohamed; J Pathol Transl Med. 2026;60(4):413-421. Published online May 26, 2026; DOI: https://doi.org/10.4132/jptm.2026.04.01

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Background
Pleural mesothelioma is an aggressive malignancy with a poor prognosis. The epithelioid subtype is the most common and can be challenging to distinguish from metastatic lung adenocarcinoma (MLAC). The role of Toll-like receptor 9 (TLR9) in the progression of pleural mesothelioma remains unclear. Methods: A total of 30 pleural biopsy specimens were collected, comprising 10 cases of pleural epithelioid mesothelioma and 20 cases of MLAC. The mRNA expression levels of TLR9 and proliferating cell nuclear antigen (PCNA) were quantified. In addition, sixty archived formalin-fixed, paraffin-embedded tissue blocks (40 epithelioid mesothelioma and 20 MLAC) were analyzed via immunohistochemistry using an anti-TLR9 antibody in relation to various clinicopathological parameters. Results: TLR9 expression was significantly higher in epithelioid mesothelioma cases than in MLAC cases (p < .001), with mean values of 1.54 ± 0.09 and 1.02 ± 0.08, respectively. A significant positive correlation was observed between TLR9 and PCNA expression levels specifically in the epithelioid mesothelioma cohort (p < .001, r = 0.8). Furthermore, immunohistochemical analysis confirmed that high TLR9 immunoexpression was significantly more prevalent in epithelioid mesothelioma (36/40 cases; 90%) than in MLAC (3/20 cases; 15%) (p < .001). Notably, elevated TLR9 expression was associated with a significantly shorter overall survival (p = .001). Conclusions: In conclusion, TLR9 expression is significantly elevated in epithelioid mesothelioma compared to MLAC at both the molecular and cellular levels, and its expression correlates with increased tumor proliferation and poorer prognosis. Our data suggest that TLR9 could represent a promising diagnostic and prognostic biomarker, warranting further investigation into its potential therapeutic applicability.

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Damage-Associated Molecular Patterns in Mesothelioma: Drivers of Inflammation and Therapeutic Targets
Annamaria Molinario, Francesca Caprioglio, Angela A. Rilievo, Marco E. Bianchi, Rosanna Mezzapelle
International Journal of Molecular Sciences.2026; 27(17): 7859. CrossRef

Ki-67 index and galectin-3 as surrogate markers for predicting disease-free survival in luminal-type breast carcinoma treated with neoadjuvant chemotherapy: Ho-Chang Lee, Wonshik Han, Seock-Ah Im, In Ae Park; J Pathol Transl Med. 2026;60(5):539-548. Published online September 11, 2026; DOI: https://doi.org/10.4132/jptm.2026.06.22

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Abstract PDF Supplementary Material: Background
Residual cancer burden (RCB) is an important marker for patients with breast carcinoma treated with neoadjuvant chemotherapy (NACT). However, the association between RCB and prognosis is relatively less significant in residual luminal-type breast carcinoma (LTBC). Associations between clinicopathological variables, including RCB class, and immunohistochemical (IHC) markers with disease-free survival (DFS) were analyzed. Methods: Expression of Ki-67, calreticulin, clusterin, galectin-3, mucin-1, and p27 was assessed in tissue microarray slides of 55 post-NACT resection specimens from LTBC patients treated with docetaxel and doxorubicin. Patients’ age, pre-NACT progesterone receptor status, lymphovascular invasion, histologic grade, ypT category, ypN category, RCB class, and IHC markers were analyzed for their association with DFS using Kaplan-Meier analysis and Cox proportional hazards models. Results: Twenty of the 55 patients developed recurrence or distant metastasis. A Ki-67 index > 2.7% and high galectin-3 expression were associated with shorter DFS on Kaplan-Meier analysis (p < .001 and p = .018, respectively). Other clinicopathological and IHC markers were not significantly associated with DFS. In the multivariate Cox proportional hazards model, a Ki-67 index > 2.7% (hazard ratio, 7.23; p < .001) and high galectin-3 expression (hazard ratio, 4.51; p = .007) remained independent predictors of shorter DFS. Conclusions: The Ki-67 index and high galectin-3 expression in post-NACT resection specimens may serve as surrogate markers for predicting recurrence in LTBC.

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