Journal of Pathology and Translational Medicine

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

Original Article

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

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

Citations

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Prevalence of Congenital Abnormalities in Abortuses and Stillbirths in India: A Systematic Review and Meta‐Analysis
Sushant Swaroop Das, Shalika Sharma, Reeha Mahajan, Sushruti Kaushal, Manupriya Sharma, Harsimranjit Singh, M. Ramkumar
Congenital Anomalies.2026;[Epub] CrossRef
Single Umbilical Artery with Symmetrical IUGR and Multiple Fetal Anomalies - An Interesting Case Report
Amulya Choudary Kotapati, Bhargavi Khandru, Vijayasree M.
Journal of Evolution of Medical and Dental Sciences.2025; : 10. CrossRef
Epidemiological and Histopathological Characteristics of Fetuses with Congenital Disorders: A Study in Greece
Despoina Nteli, Maria Nteli, Konstantinos Konstantinidis, Maria Ouzounidou, Paschalis Theotokis, Maria-Eleni Manthou, Iasonas Dermitzakis, Xeni Miliara, Chrysoula Gouta, Stamatia Angelidou, Dimosthenis Miliaras, Soultana Meditskou
Biology.2025; 14(6): 626. CrossRef

Newsletters

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.

Citations

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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

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

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Abstract PDF

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

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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
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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
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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
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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

Review

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

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Abstract PDF

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

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

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

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Abstract PDF

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

Citations

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

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.

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.

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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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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.

Review

Clinical practice recommendations for the use of next-generation sequencing in patients with solid cancer: a joint report from KSMO and KSP: Miso Kim, Hyo Sup Shim, Sheehyun Kim, In Hee Lee, Jihun Kim, Shinkyo Yoon, Hyung-Don Kim, Inkeun Park, Jae Ho Jeong, Changhoon Yoo, Jaekyung Cheon, In-Ho Kim, Jieun Lee, Sook Hee Hong, Sehhoon Park, Hyun Ae Jung, Jin Won Kim, Han Jo Kim, Yongjun Cha, Sun Min Lim, Han Sang Kim, Choong-Kun Lee, Jee Hung Kim, Sang Hoon Chun, Jina Yun, So Yeon Park, Hye Seung Lee, Yong Mee Cho, Soo Jeong Nam, Kiyong Na, Sun Och Yoon, Ahwon Lee, Kee-Taek Jang, Hongseok Yun, Sungyoung Lee, Jee Hyun Kim, Wan-Seop Kim; J Pathol Transl Med. 2024;58(4):147-164. Published online January 10, 2024; DOI: https://doi.org/10.4132/jptm.2023.11.01

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Abstract PDF

In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

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Apport de la génomique dans la prise en charge des cancers
Étienne Rouleau, Lucie Karayan-Tapon, Marie-Dominique Galibert, Alexandre Harlé, Isabelle Soubeyran
Revue Francophone des Laboratoires.2025; 2025(568): 67. CrossRef
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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.

Original Article

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

Review Article

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

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

Review

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

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Abstract PDF

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

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Evaluation of Breast Lesions on Cytology Using International Academy of Cytology Yokohama Standardized Reporting System
Manish Jaiswal, Anurag Gupta, Tripti Verma, Pradyumn Singh, Rita Yadav, Akash Agarwal, Ashish Singhal, Nuzhat Husain, Shamrendra Narayan, Neha Singh
Diagnostic Cytopathology.2026; 54(3): 184. CrossRef
Personalizing therapies over the course of hormone receptor‐positive/HER2‐negative metastatic breast cancer
Akshara Singareeka Raghavendra, Senthil Damodaran, Carlos H. Barcenas, Suzanne A. Fuqua, Rachel M. Layman, Debu Tripathy
CA: A Cancer Journal for Clinicians.2026;[Epub] CrossRef
Bulk-lysis protocols as a sensitive method for investigation of circulating CK19 cells in the peripheral blood of patients with breast cancer by flow cytometry
Daniella Serafin Couto Vieira, Laura Otto Walter, Maria Eduarda Cunha da Silva, Lisandra de Oliveira Silva, Heloísa Zorzi Costa, Chandra Chiappin Cardoso, Fernando Carlos de Lander Schmitt, Maria Cláudia Santos-Silva
Analytical Methods.2025; 17(23): 4771. CrossRef

Original Articles

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

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

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
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

Letter to the Editor

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

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PDF

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Gastrointestinal Stromal Tumor: History, Molecular Subtypes, and Risk Stratification
In Hye Song, Soomin Ahn, Hyung-Don Kim, Jeong-Hyeon Jo, Jinho Shin, Min-Hee Ryu, Young Soo Park
Journal of Gastric Cancer.2026; 26(2): 202. CrossRef

Reviews

Exploring histological predictive biomarkers for immune checkpoint inhibitor therapy response in non–small cell lung cancer: Uiju Cho, Soyoung Im, Hyung Soon Park; J Pathol Transl Med. 2024;58(2):49-58. Published online February 26, 2024; DOI: https://doi.org/10.4132/jptm.2024.01.31

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Abstract PDF

Treatment challenges persist in advanced lung cancer despite the development of therapies beyond the traditional platinum-based chemotherapy. The early 2000s marked a shift to tyrosine kinase inhibitors targeting epidermal growth factor receptor, ushering in personalized genetic-based treatment. A further significant advance was the development of immune checkpoint inhibitors (ICIs), especially for non–small cell lung cancer. These target programmed death-ligand 1 (PD-L1) and cytotoxic T lymphocyte antigen 4, which enhanced the immune response against tumor cells. However, not all patients respond, and immune-related toxicities arise. This review emphasizes identifying biomarkers for ICI response prediction. While PD-L1 is a widely used, validated biomarker, its predictive accuracy is imperfect. Investigating tumor-infiltrating lymphocytes, tertiary lymphoid structure, and emerging biomarkers such as high endothelial venule, Human leukocyte antigen class I, T-cell immunoreceptors with Ig and ITIM domains, and lymphocyte activation gene-3 counts is promising. Understanding and exploring additional predictive biomarkers for ICI response are crucial for enhancing patient stratification and overall care in lung cancer treatment.

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Machine learning methods for histopathological image analysis: Updates in 2024
Daisuke Komura, Mieko Ochi, Shumpei Ishikawa
Computational and Structural Biotechnology Journal.2025; 27: 383. CrossRef
Beyond single biomarkers: multi-omics strategies to predict immunotherapy outcomes in blood cancers
Mohammad Pirouzbakht, Soroosh Hamzeh, Hamed Soleimani Samarkhazan
Clinical and Experimental Medicine.2025;[Epub] CrossRef
Temporal changes in tongue color during immune checkpoint inhibitor therapy in patients with non-small-cell lung cancer: a prospective observational study using digital tongue diagnosis
Eunbyul Cho, Woosu Choi, Jun Hyeok Lim, Ji Woong Son, Seung Hun Jang, Seung Hyeun Lee, Jong Gwon Choi, In-Jae Oh, Tae-Won Jang, Seong Hoon Yoon, Seung Joon Kim, Chang-Min Choi, Sung Yong Lee, Mi Mi Ko, Mi-Kyung Jeong
Oncology Reviews.2025;[Epub] CrossRef

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

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Abstract PDF

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

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HPV in Pregnancy: Implications for Screening, Vaccination, and Maternal–Fetal Health
Suman Kumar, Swati, Swati Salila, Akanksha Raj, Pratima Gupta, Neha Sharad, Nidhi Chaudhary
Journal of Pregnancy.2026;[Epub] CrossRef
Approaches to Intraepithelial Cervical Neoplasia Management in Pregnancy: A Narrative Review
Delia-Maria Bogheanu, Awatif Jaafar Sadeq Al Bayati, Mircea-Octavian Poenaru, Octavian Gabriel Olaru, Gabriel-Petre Gorecki, Andreea Gratiana Boiangiu, Bashar Haj Hamoud, Romina-Marina Sima, Liana Ples
Life.2026; 16(5): 809. CrossRef
The significance of biological samples from pregnant women in cervical intraepithelial neoplasia
Xue Mi, Maharjan Rashmi, Zangyu Pan, Di Wu, Jinwei Miao
Frontiers in Medicine.2025;[Epub] CrossRef
Oncologic and pregnancy outcomes of cervical high-grade intraepithelial lesions and delivery mode
Olga P. Matylevich, Ilya A. Tarasau, Sviatlana Y. Shelkovich, Aliaksandr F. Martsinkevich
Academia Oncology.2025;[Epub] CrossRef

Original Article

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

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Abstract PDF Supplementary Material

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

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International Liver Transplantation Society/Liver Intensive Care Group of Europe guidelines for cardiovascular assessment before liver transplantation
Emmanuel Weiss, Gonzalo Crespo, Alexandra Anderson, Gianni Biancofiore, Ryan Chadha, Jacek B. Cywinski, Andrea De Gasperi, James Findlay, Marc Giménez-Milà, Constantine Karvellas, Michael Kaufman, Ashish Malik, Marina Moguilevitch, Sher-Lu Pai, Koen Reynt
American Journal of Transplantation.2026; 26(2): 219. CrossRef
Segmental thoracic aorta calcification in diabetic patients: Relationship with coronary atherosclerosis burden
Wasan Kadhum Abbas, Abdulameer A. Al-Mosawi, Ali M. Al-Shirazi, Hussein Nafakhi, Hayder Nafakhi
Journal of Diabetes & Metabolic Disorders.2026;[Epub] CrossRef

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

Review

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

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Abstract PDF

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

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Unraveling the nexus: Tumor mutational burden, PD‐L1 expression, and oncogenic alterations in non–small cell lung cancer cytology specimens
Min Dai, Francis Anthony San Lucas, Hector Alvarez, Leomar Ballester, Hui Chen, Keyur P. Patel, Asif Rashid, Shun Rao, Mark J. Routbort, Gloria Sura, Keith Sweeney, Gokce Toruner, Peng Wei, Richard Yang, Hyvan Dang, Rajyalakshmi Luthra, Sinchita Roy‐Chowd
Cancer Cytopathology.2026;[Epub] CrossRef
The critical role of accurate neoplastic cell percentage (NCP) assessment: investigating targeted training strategies for pulmonary biopsy and cytology specimens
Thi Mai Phuong Pham, Dieter Peeters, Jan von der Thüsen, Myriam Remmelink, Birgit Weynand, Elisabeth Dequeker
Virchows Archiv.2026;[Epub] CrossRef
The World Health Organization Reporting System for Lymph Node, Spleen, and Thymus Cytopathology: Part 1 – Lymph Node
Immacolata Cozzolino, Mats Ehinger, Maria Calaminici, Andrea Ronchi, Mousa A. Al-Abbadi, Helena Barroca, Beata Bode-Lesniewska, David F. Chhieng, Ruth L. Katz, Oscar Lin, L. Jeffrey Medeiros, Martha Bishop Pitman, Arvind Rajwanshi, Fernando C. Schmitt, Ph
Acta Cytologica.2025; 70(2): 185. CrossRef
The impact of cytological preparation techniques on RNA quality: A comparative study on smear samples
Cisel Aydin Mericoz, Gulsum Caylak, Elif Sevin Sanioglu, Zeynep Seçil Satilmis, Ayse Humeyra Dur Karasayar, Ibrahim Kulac
Cancer Cytopathology.2025;[Epub] CrossRef
Reimagining cytopathology in the molecular era: Integration or fragmentation?
Sumanta Das, R. Naveen Kumar, Biswajit Dey, Pranjal Kalita
Cytojournal.2025; 22: 94. CrossRef

Original Articles

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

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

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

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

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.

Identification of invasive subpopulations using spatial transcriptome analysis in thyroid follicular tumors: Ayana Suzuki, Satoshi Nojima, Shinichiro Tahara, Daisuke Motooka, Masaharu Kohara, Daisuke Okuzaki, Mitsuyoshi Hirokawa, Eiichi Morii; J Pathol Transl Med. 2024;58(1):22-28. Published online January 10, 2024; DOI: https://doi.org/10.4132/jptm.2023.11.21

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Abstract PDF

Background
Follicular tumors include follicular thyroid adenomas and carcinomas; however, it is difficult to distinguish between the two when the cytology or biopsy material is obtained from a portion of the tumor. The presence or absence of invasion in the resected material is used to differentiate between adenomas and carcinomas, which often results in the unnecessary removal of the adenomas. If nodules that may be follicular thyroid carcinomas are identified preoperatively, active surveillance of other nodules as adenomas is possible, which reduces the risk of surgical complications and the expenses incurred during medical treatment. Therefore, we aimed to identify biomarkers in the invasive subpopulation of follicular tumor cells.
Methods
We performed a spatial transcriptome analysis of a case of follicular thyroid carcinoma and examined the dynamics of CD74 expression in 36 cases.
Results
We identified a subpopulation in a region close to the invasive area, and this subpopulation expressed high levels of CD74. Immunohistochemically, CD74 was highly expressed in the invasive and peripheral areas of the tumor.
Conclusions
Although high CD74 expression has been reported in papillary and anaplastic thyroid carcinomas, it has not been analyzed in follicular thyroid carcinomas. Furthermore, the heterogeneity of CD74 expression in thyroid tumors has not yet been reported. The CD74-positive subpopulation identified in this study may be useful in predicting invasion of follicular thyroid carcinomas.

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Carbonic Anhydrase 12 as a Novel Prognostic Biomarker and Therapeutic Target for High‐Risk Follicular Thyroid Carcinoma
Masashi Tanida, Tsuyoshi Takashima, Shinichiro Tahara, Masaharu Kohara, Haruka Kanai, Masami Suzuki, Motoyuki Suzuki, Mitsuyoshi Hirokawa, Ayana Suzuki, Shinya Sato, Daisuke Okuzaki, Satoshi Nojima, Takahiro Matsui, Hidenori Inohara, Eiichi Morii
Cancer Science.2026; 117(1): 257. CrossRef
An emerging role of CD74 in thyroid follicular cells in Hashimoto´s thyroiditis
Pablo Sacristán-Gómez, Ana Serrano-Somavilla, Nuria Sánchez de la Blanca, Andrea Álvarez-Rodríguez, Eduardo Martínez-Parra, Miguel Sampedro-Nuñez, Fernando Sebastián-Valles, Mónica Marazuela, Rebeca Martínez-Hernández
Biomedicine & Pharmacotherapy.2026; 194: 118945. CrossRef
Diagnosis of invasive encapsulated follicular variant papillary thyroid carcinoma by protein-based machine learning
Truong Phan-Xuan Nguyen, Minh-Khang Le, Sittiruk Roytrakul, Shanop Shuangshoti, Nakarin Kitkumthorn, Somboon Keelawat
Journal of Pathology and Translational Medicine.2025; 59(1): 39. CrossRef
Spatial Transcriptomics in Thyroid Cancer: Applications, Limitations, and Future Perspectives
Chaerim Song, Hye-Ji Park, Man S. Kim
Cells.2025; 14(12): 936. CrossRef
A New Tool to Decrease Interobserver Variability in Biomarker Annotation in Solid Tumor Tissue for Spatial Transcriptomic Analysis
Sravya Palavalasa, Emily Baker, Jack Freeman, Aditri Gokul, Weihua Zhou, Dafydd Thomas, Wajd N. Al-Holou, Meredith A. Morgan, Theodore S. Lawrence, Daniel R. Wahl
Current Issues in Molecular Biology.2025; 47(7): 531. CrossRef

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.

Fine needle aspiration cytology diagnoses of follicular thyroid carcinoma: results from a multicenter study in Asia: Hee Young Na, Miyoko Higuchi, Shinya Satoh, Kaori Kameyama, Chan Kwon Jung, Su-Jin Shin, Shipra Agarwal, Jen-Fan Hang, Yun Zhu, Zhiyan Liu, Andrey Bychkov, Kennichi Kakudo, So Yeon Park; J Pathol Transl Med. 2024;58(6):331-340. Published online November 7, 2024; DOI: https://doi.org/10.4132/jptm.2024.10.12

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Abstract PDF Supplementary Material

Background
This study was designed to compare diagnostic categories of thyroid fine needle aspiration cytology (FNAC) and incidence of thyroid tumors in the multi-institutional Asian series with a special focus on diagnostic category IV (suspicious for a follicular neoplasm) and follicular thyroid carcinomas (FTCs). Methods: Distribution of FNAC categories, incidence of thyroid tumors in resection specimens and cytologic diagnoses of surgically confirmed follicular adenomas (FAs) and FTCs were collected from 10 institutes from five Asian countries and were compared among countries and between FAs and FTCs. Results: The frequency of category IV diagnoses (3.0%) in preoperative FNAC were significantly lower compared to those in Western countries (10.1%). When comparing diagnostic categories among Asian countries, category IV was more frequent in Japan (4.6%) and India (7.9%) than in Taiwan (1.4%), Korea (1.4%), and China (3.6%). Similarly, incidence of FAs and FTCs in surgical resection specimens was significantly higher in Japan (10.9%) and India (10.1%) than in Taiwan (5.5%), Korea (3.0%), and China (2.5%). FTCs were more commonly diagnosed as category IV in Japan (77.5%) than in Korea (33.3%) and China (35.0%). Nuclear pleomorphism, nuclear crowding, microfollicular pattern, and dyshesive cell pattern were more common in FTCs compared with FAs. Conclusions: Our study highlighted the difference in FNAC diagnostic categories of FTCs among Asian countries, which is likely related to different reporting systems and thyroid cancer incidence. Cytologic features such as nuclear pleomorphism, nuclear crowding, microfollicular pattern, and dyshesive cell pattern were found to be useful in diagnosing FTCs more effectively.

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Deep Learning-Based Multimodal Fusion of Ultrasound, Cytology, and Clinical Features to Distinguish Follicular Thyroid Carcinoma from Adenoma: A Multicenter Study
Xiao-Fei Guo, Li Zhou, Xin-Yi Bao, Shui-Qing Liu, Jia-Wei Feng, You-Long Zhu, Yong Jiang, Shu-Ying Zhang
Academic Radiology.2026;[Epub] CrossRef
Molecular Testing in Indeterminate Thyroid Nodules: Genomic Landscape, Diagnostic Performance, and Integrated Risk-Stratified Management
Sayaka Tanaka, Naomi Kitayama, Kyouko Kawamoto, Tomoko Wakasa, Yanhua Bai, Kennichi Kakudo
Cancers.2026; 18(10): 1661. CrossRef
Misdiagnosed follicular adenoma with 11 year postoperative liver and lung metastases a case report and literature review
Kai-Li Yang, Heng-Tong Han, Shou-Hua Li, Xiao-Xiao Li, Ze Yang, Li-Bin Ma, Yong-Xun Zhao
Discover Oncology.2025;[Epub] CrossRef

Review Article

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

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

Case Study

Colorectal cancer with a germline BRCA1 variant inherited paternally: a case report: Kyoung Min Kim, Min Ro Lee, Ae Ri Ahn, Myoung Ja Chung; J Pathol Transl Med. 2024;58(6):341-345. Published online September 5, 2024; DOI: https://doi.org/10.4132/jptm.2024.08.14

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Abstract PDF

BRCA genes have well-known associations with breast and ovarian cancers. However, variations in the BRCA gene, especially germline variations, have also been reported in colorectal cancer (CRC). We present the case of a rectal cancer with a germline BRCA1 variation inherited from the paternal side. A 39-year-old male was admitted with rectal cancer. The patient underwent surgical resection and the pathologic diagnosis was adenocarcinoma. Next-generation sequencing was performed and a BRCA1 variant was detected. Reviewing the public database and considering the young age of the patient, the variant was suggested to be germline. The patient’s father had had prostate cancer and next-generation sequencing testing revealed an identical BRCA1 variant. In the BRCA cancer group, there is relatively little attention paid to male cancers. The accumulation of male CRC cases linked to BRCA variations may help clarify the potential pathological relationship between the two.

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Aggressive Right-Sided Colon Cancer in a Young Adult: Triple-Whammy Mutations (POLE, KRAS, BRCA1/2) Highlight Emerging Genetic Associations
Ravi Patel, Ganesh Kumar, Yash Shah, Dushyant Singh Dahiya, Sumant Inamdar
ACG Case Reports Journal.2026;[Epub] CrossRef

Original Articles

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

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Abstract PDF Supplementary Material

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

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Ovarian Cancer: Epidemiology, Disease Mechanisms, New Diagnosis and Treatment Strategies, and Research Directions
Zunera Khalid, Weirong Fan, Farah Nazir, Yixiang Xing, Tengchuan Jin
iNew Medicine.2026;[Epub] CrossRef
Learning Disabilities in the 21st Century: Integrating Neuroscience, Education, and Technology for Better Outcomes
Syed Mohammed Basheeruddin Asdaq, Ahmad H. Alhowail, Syed Imam Rabbani, Naira Nayeem, Syed Mohammed Emaduddin Asdaq, Faiqa Nausheen
SAGE Open.2025;[Epub] CrossRef

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

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

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Abstract PDF

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

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Importance of clinical, ultrasound and cytological characteristics in predicting malignancy in thyroid nodules with indeterminate cytology
Gabriel Gonçalves dos Santos, Wendy Muller Tirapani, Cínthia Minatel Riguetto, Icleia Siqueira Barreto, Denise Engelbrecht Zantut-Wittmann
Annals of Medicine.2026;[Epub] CrossRef

Newsletter

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

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Abstract PDF

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

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

Original Articles

TERT mutations and aggressive histopathologic characteristics of radioiodine-refractory papillary thyroid cancer: Ju Yeon Pyo, Yoon Jin Cha, SoonWon Hong; J Pathol Transl Med. 2024;58(6):310-320. Published online September 12, 2024; DOI: https://doi.org/10.4132/jptm.2024.07.29

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Abstract PDF

Background
Radioiodine (RI) ablation following thyroid-stimulating hormone suppression is an effective treatment for papillary thyroid cancer (PTC), typically leading to favorable outcomes. However, RI-refractory tumors exhibit aggressive behavior and poor prognoses. Recent studies highlight the role of genetic abnormalities in PTC signaling pathways, including the activation of telomerase reverse transcriptase (TERT), and the correlation of mutations with adverse outcomes.
Methods
This study analyzed mutations in BRAF V600E and the TERT-promoter genes, comparing clinicopathological features between RI-refractory and RI-responsive PTCs. Among 82 RI-refractory patients, formalin-fixed, paraffin-embedded tissues from initial surgeries were available for 26. Another 89 without distant metastasis over 5 years formed a matched RI-responsive control group.
Results
Histopathologically, RI-refractory PTCs showed increased frequencies of small tumor clusters without fibrovascular cores, hobnail features, and a high height-to-width ratio of tumor cells. These tumors were more likely to exhibit necrosis, mitosis, lymph node metastasis, extrathyroidal extension, and involvement of resection margins. TERT-promoter mutations were statistically significantly associated with these aggressive clinicopathologic features. Immunohistochemically, decreased expression of sodium iodide symporter and thyroglobulin stimulating hormone receptor proteins was common in RI-refractory PTCs, along with lower levels of oncogenic proteins such as vascular endothelial cell growth factor, vascular endothelial cell growth factor receptor 2, and nuclear factor kappa-light-chain-enhancer of activated B cells. Total loss of PTEN expression was occasionally observed. In contrast, all cases tested positive for cytoplasmic β-catenin.
Conclusions
RI-refractory PTCs are linked to TERT mutations and exhibit specific aggressive histopathologic features, particularly in tumor centers.

Citations

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Calcifying nested stromal-epithelial tumor of the liver: Report of two cases revealing novel WT1 mutation and distinct epigenetic features
Andrea Strakova-Peterikova, Franco Fedeli, Boris Rychly, Jiri Soukup, Michael Michal, Petr Martinek, Marian Grendar, Elaheh Mosaieby, Nikola Ptakova, Maryna Slisarenko, Michal Michal, Kvetoslava Michalova
Virchows Archiv.2026; 488(4): 801. CrossRef
Characterizing thyroid carcinomas in the elderly: Histological subtypes and TERT promoter mutation analysis based on the latest WHO classification
Myoung Ju Koh, Songmi Noh, Jin Kyong Kim, Gi Jeong Kim
Annals of Diagnostic Pathology.2026; 80: 152578. CrossRef
Insulin resistance and metabolic dysfunction in thyroid nodules and differentiated thyroid cancer
Stefano Iuliano, Maria Mirabelli, Stefania Giuliano, Antonio Brunetti
Current Opinion in Oncology.2026; 38(1): 1. CrossRef
Differentiated high-grade thyroid carcinoma (DHGTC): clinicopathological analysis of a new entity in a chilean center
Marlín Solórzano, Ignacio Fuentes, José Miguel González, Nicole Lustig, Lorena Mosso, Joel Falcón, Catalina Ruiz, Joaquín Viñambres, Rodolfo Cabello, Hernán González, Pablo H Montero, Francisco Cruz, Rodrigo Jaimovich, Juan Carlos Quintana, Antonieta Sola
Endocrine.2026;[Epub] CrossRef
Characteristics and outcome of pediatric and adult differentiated thyroid cancer with distant metastases
Ali S. Alzahrani, Lulu Alobaid, Eman Albasri, Afnan Hadadi, Abdulrhman Hakami, Fayha Abothenain, Deema Alturki, Najla Ewain, Ali Howaidi, Hindi Alhindi, Ghada Alskait, Yasser Aljufan, Shatha Alghaihb, Azzam Alkhalifah, Leenah AlAyoubi, Amani Abualnaja
Frontiers in Endocrinology.2026;[Epub] CrossRef
TERT promoter–mutated thyroid carcinomas: prognostic and histologic insights according to the WHO 2022 classification
Seung Eun Lee, Bogyeong Han, Jung‐Sun Kim, Young Lyun Oh
Histopathology.2026;[Epub] 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
ARMS‐qPCR‐Based Detection of BRAF and TERT Promoter Mutations: A Cost‐Effective Strategy for Molecular Diagnosis of Papillary Thyroid Carcinoma
Yuanyuan Jia, Yajun Zhang, Dandan Sun, Jiabao Yang, Mengshi Zhou, Min Gao, Rui Li, Xiaoyu Song
International Journal of Endocrinology.2026;[Epub] CrossRef
The ability of anexelekto (AXL) expression and TERT promoter mutation to predict radioiodine-refractory differentiated thyroid carcinoma
Hasrayati Agustina, Tutik Nur Ayni, Yohana Azhar, Erwin Affandi Soeriadi, Bethy Suryawathy Hernowo
Diagnostic Pathology.2025;[Epub] CrossRef
Clinicopathologic characteristics of papillary thyroid carcinoma, tall cell subtype and subtype with tall cell features, an institutional experience
Xueting Jin, Shunsuke Koga, Xiao Zhou, Niaz Z. Khan, Zubair W. Baloch
Human Pathology.2025; 161: 105867. CrossRef

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

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

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

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Abstract PDF

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

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

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.

Case Study

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

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

Newsletter

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

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Abstract PDF

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

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

Case Study

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

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

Review

Welcoming the new, revisiting the old: a brief glance at cytopathology reporting systems for lung, pancreas, and thyroid: Rita Luis, Balamurugan Thirunavukkarasu, Deepali Jain, Sule Canberk; J Pathol Transl Med. 2024;58(4):165-173. Published online July 15, 2024; DOI: https://doi.org/10.4132/jptm.2024.06.11

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Abstract PDF

This review addresses new reporting systems for lung and pancreatobiliary cytopathology as well as the most recent edition of The Bethesda Reporting System for Thyroid Cytopathology. The review spans past, present, and future aspects within the context of the intricate interplay between traditional morphological assessments and cutting-edge molecular diagnostics. For lung and pancreas, the authors discuss the evolution of reporting systems, emphasizing the bridge between past directives and more recent collaborative efforts of the International Academy of Cytology and the World Health Organization in shaping universal reporting systems. The review offers a brief overview of the structure of these novel systems, highlighting their strengths and pinpointing areas that require further refinement. For thyroid, the authors primarily focus on the third edition of The Bethesda System for Reporting Thyroid Cytopathology, also considering the two preceding editions. This review serves as an invaluable resource for cytopathologists, offering a panoramic view of the evolving landscape of cytopathology reporting and pointing out the integrative role of the cytopathologist in an era of rapid diagnostic and therapeutic advancements.

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WHO Reporting System for Lung Cytopathology: Insights Into the Insufficient/Inadequate/Non‐Diagnostic, Atypical and Suspicious for Malignancy Categories and How to Use Them
Zahra Maleki, Sule Canberk, Andrew Field
Cytopathology.2025; 36(5): 434. CrossRef
Reproducibility of the Bethesda system for reporting thyroid cytopathology (TBSRTC): An observational study of 100 patients
Kishori Moni Panda, Reena Naik, Mohd Ghouse Mohiddin
Indian Journal of Pathology and Oncology.2024; 11(4): 385. CrossRef

Newsletter

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

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

Original Articles

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

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Abstract PDF Supplementary Material

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

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

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

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Abstract PDF Supplementary Material

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

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

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.

The spectrum of microvascular patterns in adult diffuse glioma and their correlation with tumor grade: Soni , Vaishali Walke, Deepti Joshi, Tanya Sharma, Adesh Shrivastava, Amit Agrawal; J Pathol Transl Med. 2024;58(3):127-133. Published online May 14, 2024; DOI: https://doi.org/10.4132/jptm.2024.03.11

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Abstract PDF

Background
Primary brain tumors constitute the leading cause of cancer-related mortality. Among them, adult diffuse gliomas are the most common type, affecting the cerebral hemispheres and displaying a diffuse infiltrative pattern of growth in the surrounding neuropil that accounts for about 80% of all primary intracranial tumors. The hallmark feature of gliomas is blood vessel proliferation, which plays an important role in tumor growth, tumor biological behavior, and disease outcome. High-grade gliomas exhibit increased vascularity, the worst prognosis, and lower survival rates. Several angiogenic receptors and factors are upregulated in glioblastomas and stimulate angiogenesis signaling pathways by means of activating oncogenes and/or down-regulating tumor-suppressor genes. Existing literature has emphasized that different microvascular patterns (MVPs) are displayed in different subtypes of adult diffuse gliomas.
Methods
We examined the distribution and biological characteristics of different MVPs in 50 patients with adult diffuse gliomas. Haematoxylin and eosin staining results, along with periodic acid–Schiff and CD34 dual-stained sections, were examined to assess the vascular patterns and correlate with different grades of diffuse glioma.
Results
The present observational study on adult diffuse glioma evaluated tumor grade and MVPs. Microvascular sprouting was the most common pattern, while a bizarre pattern (type 2) was associated with the presence of a high-grade glioma. Vascular mimicry was observed in 6% of cases, all of which were grade 4 gliomas.
Conclusions
This study supplements the role of neo-angiogenesis and aberrant vasculature patterns in the grading and progression of adult diffuse gliomas, which can be future targets for planning treatment strategies.

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Unlocking therapeutic potential: Exploring nuclear receptors in brain cancer treatment
Sujitha Jayaprakash, Hiu Yan Lam, Ravichandran Vishwa, Bandari BharathwajChetty, Kenneth C-H Yap, Mohammed S. Alqahtani, Mohamed Abbas, Gautam Sethi, Alan Prem Kumar, Ajaikumar B. Kunnumakkara
Chinese Medical Journal.2025; 138(21): 2722. CrossRef
Uptake patterns of Adult-type Non-Enhanced diffuse gliomas on [11C] methionine positron emission tomography
Shoji Yasuda, Naoya Imai, Hirohito Yano, Yuka Ikegame, Soko Ikuta, Takashi Maruyama, Noriyuki Nakayama, Morio Kumagai, Yoshihiro Muragaki, Jun Shinoda, Tsuyoshi Izumo
Neuroradiology.2025; 67(10): 2611. CrossRef
Loss of Fibronectin Fiber Tension in Glioblastoma is Associated with Microvascular Proliferations and Immune Cell Infiltration
Michele Crestani, Isabel Gerber, Arnaud Mieville, Katrin Frauenknecht, Theoni Maragkou, Tibor Hortobagyi, Viola Vogel
Advanced Science.2025;[Epub] CrossRef
High ORC6 expression is a prognostic indicator of poor survival in glioma patients
Mengjie Wang, Song Feng, Chen Zhang, Feng Jin
Scientific Reports.2025;[Epub] CrossRef
Consequences of Hypoxic Events, Necrosis, and Microvascular Density, in Astrocytoma IDH-Mutant, CNS WHO Grade 4
Cristian Ionut Orasanu, Madalina Bosoteanu, Sorin Vamesu, Raluca Ioana Voda, Anamaria Sincu, Mariana Deacu
Medical Sciences.2025; 14(1): 6. CrossRef
Association of PD-L1 expression with adverse pathological features in adult diffuse astrocytoma
Rania K. Elsaid, Maha M. Abuhashim, Sylvia A. Ashamallah, Khaled M. Abouelkhair, Marwa M. Zaki
Egyptian Journal of Basic and Applied Sciences.2025; 12(1): 526. CrossRef

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

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

Review

Diagnosis of interstitial lung diseases: from Averill A. Liebow to artificial intelligence: Eunhee S. Yi, Paul Wawryko, Jay H. Ryu; J Pathol Transl Med. 2024;58(1):1-11. Published online January 10, 2024; DOI: https://doi.org/10.4132/jptm.2023.11.17

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Abstract PDF

Histopathologic criteria of usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF) were defined over the years and endorsed by leading organizations decades after Dr. Averill A. Liebow first coined the term UIP in the 1960s as a distinct pathologic pattern of fibrotic interstitial lung disease. Novel technology and recent research on interstitial lung diseases with genetic component shed light on molecular pathogenesis of UIP/IPF. Two antifibrotic agents introduced in the mid-2010s opened a new era of therapeutic approaches to UIP/IPF, albeit contentious issues regarding their efficacy, side effects, and costs. Recently, the concept of progressive pulmonary fibrosis was introduced to acknowledge additional types of progressive fibrosing interstitial lung diseases with the clinical and pathologic phenotypes comparable to those of UIP/IPF. Likewise, some authors have proposed a paradigm shift by considering UIP as a stand-alone diagnostic entity to encompass other fibrosing interstitial lung diseases that manifest a relentless progression as in IPF. These trends signal a pendulum moving toward the tendency of lumping diagnoses, which poses a risk of obscuring potentially important information crucial to both clinical and research purposes. Recent advances in whole slide imaging for digital pathology and artificial intelligence technology could offer an unprecedented opportunity to enhance histopathologic evaluation of interstitial lung diseases. However, current clinical practice trends of moving away from surgical lung biopsies in interstitial lung disease patients may become a limiting factor in this endeavor as it would be difficult to build a large histopathologic database with correlative clinical data required for artificial intelligence models.

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Advances and Research Progress in the Application of Artificial Intelligence for Progressive Pulmonary Fibrosis in Connective Tissue Disease-Associated Interstitial Lung Disease
佳琳王
Advances in Clinical Medicine.2026; 16(05): 2107. CrossRef
Identification of early genes in the pathophysiology of fibrotic interstitial lung disease in a new model of pulmonary fibrosis
Nathan Hennion, Corentin Bedart, Léonie Vandomber, Frédéric Gottrand, Sarah Humez, Cécile Chenivesse, Jean-Luc Desseyn, Valérie Gouyer
Cellular and Molecular Life Sciences.2025;[Epub] CrossRef
Radiological Insights into UIP Pattern: A Comparison Between IPF and Non-IPF Patients
Stefano Palmucci, Miriam Adorna, Angelica Rapisarda, Alessandro Libra, Sefora Fischetti, Gianluca Sambataro, Letizia Antonella Mauro, Emanuele David, Pietro Valerio Foti, Claudia Mattina, Corrado Spatola, Carlo Vancheri, Antonio Basile
Journal of Clinical Medicine.2025; 14(12): 4162. CrossRef

Original Article

Histopathologic classification and immunohistochemical features of papillary renal neoplasm with potential therapeutic targets: Jeong Hwan Park, Su-Jin Shin, Hyun-Jung Kim, Sohee Oh, Yong Mee Cho; J Pathol Transl Med. 2024;58(6):321-330. Published online September 12, 2024; DOI: https://doi.org/10.4132/jptm.2024.07.31

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Abstract PDF

Background
Papillary renal cell carcinoma (pRCC) is the second most common histological subtype of renal cell carcinoma and is considered a morphologically and molecularly heterogeneous tumor. Accurate classification and assessment of the immunohistochemical features of possible therapeutic targets are needed for precise patient care. We aimed to evaluate immunohistochemical features and possible therapeutic targets of papillary renal neoplasms
Methods
We collected 140 papillary renal neoplasms from three different hospitals and conducted immunohistochemical studies on tissue microarray slides. We performed succinate dehydrogenase B, fumarate hydratase, and transcription factor E3 immunohistochemical studies for differential diagnosis and re-classified five cases (3.6%) of papillary renal neoplasms. In addition, we conducted c-MET, p16, c-Myc, Ki-67, p53, and stimulator of interferon genes (STING) immunohistochemical studies to evaluate their pathogenesis and value for therapeutic targets.
Results
We found that c-MET expression was more common in pRCC (classic) (p = .021) among papillary renal neoplasms and Ki-67 proliferation index was higher in pRCC (not otherwise specified, NOS) compared to that of pRCC (classic) and papillary neoplasm with reverse polarity (marginal significance, p = .080). Small subsets of cases with p16 block positivity (4.5%) (pRCC [NOS] only) and c-Myc expression (7.1%) (pRCC [classic] only) were found. Also, there were some cases showing STING expression and those cases were associated with increased Ki-67 proliferation index (marginal significance, p = .063).
Conclusions
Our findings suggested that there are subsets of pRCC with c-MET, p16, c-MYC, and STING expression and those cases could be potential candidates for targeted therapy.

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Tissue-Based Biomarkers Important for Prognostication and Management of Genitourinary Tumors, Including Surrogate Markers of Genomic Alterations
Leonie Beauchamp, Shreeya Indulkar, Eric Erak, Mohammad Salimian, Andres Matoso
Surgical Pathology Clinics.2025; 18(1): 175. CrossRef
Papillary renal neoplasm with reverse polarity: a case report and literature review
Diego Gonzalez, Kris Kokoneshi, Sam Kwon, Ryan Thomas Mathews, Ryan Michael Antar, Maher Ali, Abiye Kassa, Michael Whalen
Frontiers in Oncology.2025;[Epub] CrossRef

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