Journal of Pathology and Translational Medicine

Most-read articles are from the articles published in 2022 during the last three month.

Review

A stepwise approach to fine needle aspiration cytology of lymph nodes: Yosep Chong, Gyeongsin Park, Hee Jeong Cha, Hyun-Jung Kim, Chang Suk Kang, Jamshid Abdul-Ghafar, Seung-Sook Lee; J Pathol Transl Med. 2023;57(4):196-207. Published online July 11, 2023; DOI: https://doi.org/10.4132/jptm.2023.06.12

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The cytological diagnosis of lymph node lesions is extremely challenging because of the diverse diseases that cause lymph node enlargement, including both benign and malignant or metastatic lymphoid lesions. Furthermore, the cytological findings of different lesions often resemble one another. A stepwise diagnostic approach is essential for a comprehensive diagnosis that combines: clinical findings, including age, sex, site, multiplicity, and ultrasonography findings; low-power reactive, metastatic, and lymphoma patterns; high-power population patterns, including two populations of continuous range, small monotonous pattern and large monotonous pattern; and disease-specific diagnostic clues including granulomas and lymphoglandular granules. It is also important to remember the histological features of each diagnostic category that are common in lymph node cytology and to compare them with cytological findings. It is also essential to identify a few categories of diagnostic pitfalls that often resemble lymphomas and easily lead to misdiagnosis, particularly in malignant small round cell tumors, poorly differentiated squamous cell carcinomas, and nasopharyngeal undifferentiated carcinoma. Herein, we review a stepwise approach for fine needle aspiration cytology of lymphoid diseases and suggest a diagnostic algorithm that uses this approach and the Sydney classification system.

Citations

Citations to this article as recorded by

Immunocytochemical markers, molecular testing and digital cytopathology for aspiration cytology of metastatic breast carcinoma
Joshua J. X. Li, Gary M. Tse
Cytopathology.2024; 35(2): 218. CrossRef
Response to comment on “A stepwise approach to fine needle aspiration cytology of lymph nodes”
Yosep Chong, Gyeongsin Park, Hee Jeong Cha, Hyun-Jung Kim, Chang Suk Kang, Jamshid Abdul-Ghafar, Seung-Sook Lee
Journal of Pathology and Translational Medicine.2024; 58(1): 43. CrossRef
Comment on “A stepwise approach to fine needle aspiration cytology of lymph nodes”
Elisabetta Maffei, Valeria Ciliberti, Pio Zeppa, Alessandro Caputo
Journal of Pathology and Translational Medicine.2024; 58(1): 40. CrossRef
The Incidence of Thyroid Cancer in Bethesda III Thyroid Nodules: A Retrospective Analysis at a Single Endocrine Surgery Center
Iyad Hassan, Lina Hassan, Nahed Balalaa, Mohamad Askar, Hussa Alshehhi, Mohamad Almarzooqi
Diagnostics.2024; 14(10): 1026. CrossRef
Efficiency of Fine-Needle Aspiration (FNA) in Relation to Tru-Cut Biopsy of Lateral Neck Swellings
Mohammed S Al Olaimat, Fahad S Al Qooz, Zaid R Alzoubi, Elham M Alsharaiah, Ali S Al Murdif, Mohammad O Alanazi
Cureus.2024;[Epub] CrossRef
Pitfalls in the Cytological Diagnosis of Nodal Hodgkin Lymphoma
Uma Handa, Rasheeda Mohamedali, Rajpal Singh Punia, Simrandeep Singh, Ranjeev Bhagat, Phiza Aggarwal, Manveen Kaur
Diagnostic Cytopathology.2024; 52(12): 715. CrossRef
Rapid 3D imaging at cellular resolution for digital cytopathology with a multi-camera array scanner (MCAS)
Kanghyun Kim, Amey Chaware, Clare B. Cook, Shiqi Xu, Monica Abdelmalak, Colin Cooke, Kevin C. Zhou, Mark Harfouche, Paul Reamey, Veton Saliu, Jed Doman, Clay Dugo, Gregor Horstmeyer, Richard Davis, Ian Taylor-Cho, Wen-Chi Foo, Lucas Kreiss, Xiaoyin Sara J
npj Imaging.2024;[Epub] CrossRef

Newsletter

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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Cytologic and Clinicopathologic Features of Papillary Thyroid Carcinoma with Prominent Hobnail Features on FNAC
Deepali Saxena, Ravi Hari Phulware, Prashant Durgapal, Arvind Kumar, Amit Kumar Tyagi
Indian Journal of Otolaryngology and Head & Neck Surgery.2024; 76(5): 4885. CrossRef
FHL1: A novel diagnostic marker for papillary thyroid carcinoma
Yeting Zeng, Dehua Zeng, Xingfeng Qi, Hanxi Wang, Xuzhou Wang, Xiaodong Dai, Lijuan Qu
Pathology International.2024; 74(9): 520. CrossRef
Nouveautés en pathologie thyroïdienne : classification OMS 2022, système Bethesda 2023, biologie moléculaire et testing moléculaire
Mohamed Amine Bani, Sophie Moog, Voichita Suciu, Livia Lamartina, Abir Al Ghuzlan
Bulletin du Cancer.2024; 111(10): 10S5. CrossRef
Cytologic hallmarks and differential diagnosis of papillary thyroid carcinoma subtypes
Agnes Stephanie Harahap, Chan Kwon Jung
Journal of Pathology and Translational Medicine.2024; 58(6): 265. CrossRef

Review

Follicular lymphoma: updates for pathologists: Mahsa Khanlari, Jennifer R. Chapman; J Pathol Transl Med. 2022;56(1):1-15. Published online December 27, 2021; DOI: https://doi.org/10.4132/jptm.2021.09.29

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Abstract PDF

Follicular lymphoma (FL) is the most common indolent B-cell lymphoma and originates from germinal center B-cells (centrocytes and centroblasts) of the lymphoid follicle. Tumorigenesis is believed to initiate early in precursor B-cells in the bone marrow (BM) that acquire the t(14;18)(q32;q21). These cells later migrate to lymph nodes to continue their maturation through the germinal center reaction, at which time they acquire additional genetic and epigeneticabnormalities that promote lymphomagenesis. FLs are heterogeneous in terms of their clinicopathologic features. Most FLs are indolent and clinically characterized by peripheral lymphadenopathy with involvement of the spleen, BM, and peripheral blood in a substantial subset of patients, sometimes accompanied by constitutional symptoms and laboratory abnormalities. Diagnosis is established by the histopathologic identification of a B-cell proliferation usually distributed in an at least partially follicular pattern, typically, but not always, in a lymph node biopsy. The B-cell proliferation is biologically of germinal center cell origin, thus shows an expression of germinal center-associated antigens as detected by immunophenotyping. Although many cases of FLs are typical and histopathologic features are straightforward, the biologic and histopathologic variability of FL is wide, and an accurate diagnosis of FL over this disease spectrum requires knowledge of morphologic variants that can mimic other lymphomas, and rarely non-hematologic malignancies, clinically unique variants, and pitfalls in the interpretation of ancillary studies. The overall survival for most patients is prolonged, but relapses are frequent. The treatment landscape in FL now includes the application of immunotherapy and targeted therapy in addition to chemotherapy.

Citations

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The follicular lymphoma tumor microenvironment at single-cell and spatial resolution
Andrea J. Radtke, Mark Roschewski
Blood.2024; 143(12): 1069. CrossRef
Chronic pancreatitis for the clinician: complications and special forms of the disease. Interdisciplinary position paper of the Catalan Society of Digestology (SCD) and the Catalan Pancreatic Society (SCPanc)
Xavier MOLERO, Juan R. AYUSO, Joaquim BALSELLS, Jaume BOADAS, Juli BUSQUETS, Anna CASTERÀS, Mar CONCEPCIÓN, Míriam CUATRECASAS, Gloria FERNÀNDEZ ESPARRACH, Esther FORT, Francisco GARCIA BOROBIA, Àngels GINÈS, Lucas ILZARBE, Carme LORAS, Miquel MASACHS, Xa
Minerva Gastroenterology.2024;[Epub] CrossRef
Concurrent identification of follicular lymphoma and papillary thyroid carcinoma
Lama A. Alzelfawi, Norah ALhumaidan, Abrar H. Alageel, Buthaina J. Yahya, Saud D. Alrasheedi, Adel S. Alqahtani
International Journal of Surgery Case Reports.2024; 122: 110009. CrossRef
Impact of Primary Disease Site of Involvement by Early-Stage Follicular Lymphoma on Patient Outcomes
Olivia Davis, Carmen Lessani, Rana Kasht, Andrew Cohoon, Sami Ibrahimi, Adam Asch, Silas Day, Taha Al-Juhaishi
Clinical Lymphoma Myeloma and Leukemia.2024;[Epub] CrossRef
Recent developments in CD19-targeted therapies for follicular lymphoma
Aditi Saha, Julio C. Chavez
Expert Opinion on Biological Therapy.2024; 24(10): 1049. CrossRef
Transformation of low-grade follicular lymphoma to a high-grade follicular lymphoma with the histopathological diagnosis from oral biopsy: a case report
Gabriela Silveira de Araujo, Leandro Dorigan de Macedo, Alfredo Ribeiro-Silva, Hilton Marcos Alves Ricz, Lara Maria Alencar Ramos Innocentini
Hematology, Transfusion and Cell Therapy.2023;[Epub] CrossRef
Clinical features and prognostic factors in 49 patients with follicular lymphoma at a single center: A retrospective analysis
Hao Wu, Hui-Cong Sun, Gui-Fang Ouyang
World Journal of Clinical Cases.2023; 11(14): 3176. CrossRef
A rare case of follicular lymphoma of the bladder
Matthew DeSanto, Robert Strait, Jared Zopp, Kevin Brown, Samuel Deem
Urology Case Reports.2023; 51: 102542. CrossRef
Analysis of immunophenotypic features in hyaline vascular type Castleman disease
Yu Chang, Yu Ma, Chen Chang, Wensheng Li
Diagnostic Pathology.2023;[Epub] CrossRef
A Review of the Totality of Evidence in the Development of ABP 798, A Rituximab Biosimilar
Patrick Cobb, Dietger Niederwieser, Stanley Cohen, Caroline Hamm, Gerd Burmester, Neungseon Seo, Sonya G Lehto, Vladimir Hanes
Immunotherapy.2022; 14(9): 727. CrossRef

Newsletter

What’s new in breast pathology 2022: WHO 5th edition and biomarker updates: Kristen Muller, Julie M. Jorns, Gary Tozbikian; J Pathol Transl Med. 2022;56(3):170-171. Published online May 15, 2022; DOI: https://doi.org/10.4132/jptm.2022.04.25

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1,417 Download
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Abstract PDF

The 5th edition WHO Classification of Breast Tumours (2019) has introduced changes to our practices. Highlights are presented below, with a focus on modifications to morphological subtype categorization. In addition, we summarize important updates to ER and PR testing made in the 2020 ASCO/CAP guidelines, and briefly discuss PD-L1 and Ki-67 testing in breast cancer.

Citations

Citations to this article as recorded by

Correlation of Histopathology and Radiological Findings Among the Diverse Breast Lesions in a Tertiary Care Centre
Ranjani Mohan, Sathish Selvakumar A, Ragupathy S, Meenakshisundaram K, Shanmugapriya S, Rajeswari Kathiah, Rajeswari T, Priavadhana Rajan Prasaad, Dinesh Kumar S, Sarika K
Cureus.2024;[Epub] CrossRef
Diagnostic Challenge in Veterinary Pathology: Metastatic Mammary Tumor in a Female Tiger (Panthera Tigris)
Charisha Fraser, Mun Keong Kok, Intan Shameha Abdul Razak, Yulianna Puspitasari, Annas Salleh
Veterinary Pathology.2024; 61(4): 508. CrossRef
Expression of cell surface zinc transporter LIV1 in triple negative breast cancer is an indicator of poor prognosis and therapy failure
Roshni Saravanan, Vaishnavi Balasubramanian, Sandhya Sundaram, Bhawna Dev, Pavithra Vittalraj, Ravi Shankar Pitani, Gouthaman Shanmugasundaram, Suresh Kumar Rayala, Ganesh Venkatraman
Journal of Cellular Physiology.2024;[Epub] CrossRef
Oral Soft Tissue Metastasis from Breast Cancer as the Only Primary Source: Systematic Review
Nausheen Aga, Ruchira Shreevats, Sonia Gupta, Harman Sandhu, Muna E.M. Hassan, Harnisha V. Prajapati
Avicenna Journal of Medicine.2024; 14(01): 022. CrossRef
Influence of tumor microenvironment on the different breast cancer subtypes and applied therapies
Cristina Ferreira Almeida, Georgina Correia-da-Silva, Natércia Teixeira, Cristina Amaral
Biochemical Pharmacology.2024; 223: 116178. CrossRef
Specific feature recognition on group specific networks (SFR-GSN): a biomarker identification model for cancer stages
Bolin Chen, Yuxin Wang, Jinlei Zhang, Yourui Han, Hamza Benhammouda, Jun Bian, Ruiming Kang, Xuequn Shang
Frontiers in Genetics.2024;[Epub] CrossRef
BREAST CANCER IN THE POLTAVA REGION: CLINICAL AND MORPHOLOGICAL ASPECTS
K. R. Novykov, L. P. Lytvynenko, B. M. Fylenko, N. V. Roiko, O. K. Prylutskyi, S. A. Proskurnia
Bulletin of Problems Biology and Medicine.2024; 1(2): 9. CrossRef
Breast cancer metastasizing to salivary glands: Systematic review
Sonia Gupta, Mayur Manoharrao Shingade, Manasi Pangarkar, Annie Evangelin Nithiakumar, Pallavi Sharma, Nausheen Aga, Kinza Qureshi, Muna Eisa Mohamed Hassan, Achla Bharti Yadav
National Journal of Maxillofacial Surgery.2024; 15(2): 199. CrossRef
Granular cell tumour of the breast
Nicole Ellen James, Yue Guan, Fawaz Musa, Giulio Cuffolo
BMJ Case Reports.2024; 17(8): e258326. CrossRef
Primary extra – nodal DLBCL at rare sites: A case series
Shruti Vijayakumar, Shalini Kuruvilla, Kavitha Kanjirakkattu Mana Parameswaran, Shahin Hameed
Indian Journal of Pathology and Oncology.2024; 11(3): 289. CrossRef
Molecular Targets of Minor Cannabinoids in Breast Cancer: In Silico and In Vitro Studies
Cristina Ferreira Almeida, Andreia Palmeira, Maria João Valente, Georgina Correia-da-Silva, Anne Marie Vinggaard, Maria Emília Sousa, Natércia Teixeira, Cristina Amaral
Pharmaceuticals.2024; 17(9): 1245. CrossRef
Immune checkpoint inhibitor resistance in hepatocellular carcinoma
Zhijie Wang, Yichuan Wang, Peng Gao, Jin Ding
Cancer Letters.2023; 555: 216038. CrossRef
Demographic and Clinical Features of Patients with Metastatic Breast Cancer: A Retrospective Multicenter Registry Study of the Turkish Oncology Group
Izzet Dogan, Sercan Aksoy, Burcu Cakar, Gul Basaran, Ozlem Ercelep, Nil Molinas Mandel, Taner Korkmaz, Erhan Gokmen, Cem Sener, Adnan Aydiner, Pinar Saip, Yesim Eralp
Cancers.2023; 15(6): 1667. CrossRef
The role of tumor microenvironment in drug resistance: emerging technologies to unravel breast cancer heterogeneity
Vincenzo Salemme, Giorgia Centonze, Lidia Avalle, Dora Natalini, Alessio Piccolantonio, Pietro Arina, Alessandro Morellato, Ugo Ala, Daniela Taverna, Emilia Turco, Paola Defilippi
Frontiers in Oncology.2023;[Epub] CrossRef
Unraveling the Role of Adiponectin Receptors in Obesity-Related Breast Cancer
Giuseppina Daniela Naimo, Alessandro Paolì, Francesca Giordano, Martina Forestiero, Maria Luisa Panno, Sebastiano Andò, Loredana Mauro
International Journal of Molecular Sciences.2023; 24(10): 8907. CrossRef
Novel Molecular Targets for Immune Surveillance of Hepatocellular Carcinoma
Pietro Guerra, Andrea Martini, Patrizia Pontisso, Paolo Angeli
Cancers.2023; 15(14): 3629. CrossRef
Breast metastasis as the first presentation of an anorectal melanoma diagnosed on fine needle aspiration cytology: a case report
Adil Aziz Khan, Shaivy Malik, Sana Ahuja, Mukul Singh
Surgical and Experimental Pathology.2023;[Epub] CrossRef
Meme Kanserinde Ki67 İndeks Ölçümlerinin Manuel ve Dijital Yöntemler Açısından Kıyaslanması
Zuhal SİLAV
İstanbul Gelişim Üniversitesi Sağlık Bilimleri Dergisi.2023; (20): 397. CrossRef

Reviews

Aneurysmal bone cyst: a review: Elham Nasri, John David Reith; J Pathol Transl Med. 2023;57(2):81-87. Published online March 14, 2023; DOI: https://doi.org/10.4132/jptm.2023.02.23

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Abstract PDF

Aneurysmal bone cyst (ABC) is a benign locally destructive bone neoplasm composed of multi-loculated blood-filled cystic spaces. The most common sites of involvement are the meta-diaphysis of the long bones and posterior elements of the vertebrae. Secondary, ABC-like changes can complicate a variety of other benign and malignant primary bone neoplasms, including giant cell tumor, fibrous dysplasia, and osteosarcoma. About two-third of primary ABCs have a rearrangement of the USP6 gene, which is not present in the ABC-like changes that occur secondary to other primary bone tumors (i.e., secondary ABC). Primary ABC of bone carries a variable but generally high rate of local recurrence. This paper provides an overview of the pathophysiology, clinical presentation, radiographic and pathologic findings, treatment, and prognosis of ABC.

Citations

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Management of aggressive recurrent thoracic spine aneurysmal bone cyst in a 7-year-old male: A case report and review of the literature
Pedram Jahangiri, Faramarz Roohollahi, Zohreh Habibi, Mohammad Hosein Mirbolouk, Mohsen Rostami
Surgical Neurology International.2024; 15: 30. CrossRef
Intraosseous hemangioma with aneurysmal bone cyst-like changes of the hyoid bone: Case report and literature review
Jeonghyun Oh, Song Iy Han, Sung-Chul Lim
Medicine.2024; 103(6): e37137. CrossRef
Fibrous dysplasia with aneurysmal bone cyst-like change occurring in pediatric orbit: case report and literature review
Xinyao Wang, Wenbin Guan, Haibo Zhang, Lei Bao, Xiaoqiang Wang
Oral and Maxillofacial Surgery.2024; 28(2): 999. CrossRef
Pathological Fractures in Aneurysmal Bone Cysts: A Systematic Review
Doriana Di Costa, Elena Gabrielli, Mariagrazia Cerrone, Emidio Di Gialleonardo, Giulio Maccauro, Raffaele Vitiello
Journal of Clinical Medicine.2024; 13(9): 2485. CrossRef
Quiste óseo aneurismático torácico, descompresión mediante costotransversectomía, corpectomía y caja telescópica expandible. Reporte de un caso y revisión de literatura
Karoll Ortíz-Guillén, José M García-De la Rosa, Everardo García, Adriana Vargas-Oviedo
Cirugía de Columna.2024; 2(3): 188. CrossRef
The Role of Denosumab Treatment in Recurrent Giant Cell Bone Tumor of the Orbit
Arjav Gupta, Bruce Colwell, David B. Clarke, Emad A. Massoud, Sidney Croul, Ahsen Hussain
Ophthalmic Plastic & Reconstructive Surgery.2024; 40(5): e161. CrossRef
Denosumab Re-Challenge and Long-Term Efficacy for Aneurysmal Bone Cyst of the Spine: Enhanced Treatment Algorithm
Gisberto Evangelisti, Franziska C. S. Altorfer, Luigi Falzetti, Emanuela Palmerini, Cristiana Griffoni, Riccardo Ghermandi, Stefano Boriani, Annalisa Monetta, Marilena Cesari, Toni Ibrahim, Alessandro Gasbarrini
Journal of Clinical Medicine.2024; 13(15): 4522. CrossRef
Rare Aneurysmal Bone Cyst Presentation in the Orbit: A Systematic Review of the Literature with an Illustrative Case Report
Sean O'Leary, Fakhar Hayat, Saketh Amasa, Muhammad Ammar Haider, Saad Akram Asbeutah, Usama AlDallal, Umaru Barrie, Mohamed Ismail
World Neurosurgery.2024; 191: 1. CrossRef
Primary osseous leiomyosarcoma of humerus misinterpreted as aneurysmal bone cyst: A case report and literature review
Yong Jin Cho, Young Kwon Koh, Sung-Chul Lim
Medicine.2024; 103(38): e39762. CrossRef
Metastatic patellar bone tumor due to gastric cancer resembling a primary or secondary aneurysmal bone cyst: A case report
T. Furuta, T. Sakuda, K. Yoshioka, K. Arihiro, N. Adachi
International Journal of Surgery Case Reports.2023; 108: 108379. CrossRef
Clear cell chondrosarcoma: a review of clinicopathologic characteristics, differential diagnoses, and patient management
Borislav A. Alexiev, Erica R. Vormittag-Nocito, Terrance D. Peabody, Jonathan Samet, William B. Laskin
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Malignant transformation of an aneurysmal bone cyst of the femoral neck: A case report
Xiaoyang Song, Yongjie Qiao, Haoqiang Zhang, Lirong Sha, Jinpeng Lou, Xinyuan Yu, Hao Liu, Langfeng Zhu, Shenghu Zhou
Experimental and Therapeutic Medicine.2023;[Epub] CrossRef

Development of CytoAcademy: a new web- and mobile-based E-learning platform for cytopathologists and cytotechnologists by the Korean Society for Cytopathology in the post-pandemic era: Ran Hong, Yosep Chong, Seung Wan Chae, Seung-Sook Lee, Gyungyub Gong; J Pathol Transl Med. 2024;58(6):261-264. Published online November 7, 2024; DOI: https://doi.org/10.4132/jptm.2024.10.02

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Abstract PDF: Since the late 1990s, online e-learning has offered unparalleled convenience and affordability, becoming increasingly popular among pathologists. Traditional learning theories have been successfully applied to web/mobile-based learning systems, with mobile technologies even enhancing conventional offline education. In cytopathology, hands-on microscope training has traditionally been paramount, complemented by real-case presentations and lectures. However, the coronavirus disease 2019 (COVID-19) pandemic disrupted regular academic activities, making online e-learning platforms essential. We designed a web/mobile-based learning platform to enhance continued medical education in cytopathology at various levels, particularly during the era of COVID-19 and beyond. Since 2021, we have integrated curriculum materials, virtual education files, and whole-slide images (WSIs) of cytopathology, submitted from over 200 institutions across Korea, with the support of numerous instructors. We develop a new e-learning platform named “CytoAcademy” composed of a basic session for each organ and level across the range of morphologic findings; on-demand lectures to enhance cytopathologic knowledge; WSI archives that allow users to explore various histologically confirmed cases; and a self-assessment test to help organize diagnostic knowledge acquired through the web/mobile-friendly learning system. The platform provides not just an opportunity to achieve a correct diagnosis, but also a learning experience based on problem-solving point. Members interact, identify their deficiencies, and focus on specific educational materials. In this manner, all participants can actively engage in creating and maintaining knowledge and foster a proactive approach to learning.

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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Adjuvant immunotherapy in patients with resected gastric and oesophagogastric junction cancer following preoperative chemotherapy with high risk for recurrence (ypN+ and/or R1): European Organisation of Research and Treatment of Cancer (EORTC) 1707 VESTIG
F. Lordick, M.E. Mauer, G. Stocker, C.A. Cella, I. Ben-Aharon, G. Piessen, L. Wyrwicz, G. Al-Haidari, T. Fleitas-Kanonnikoff, V. Boige, R. Lordick Obermannová, U.M. Martens, C. Gomez-Martin, P. Thuss-Patience, V. Arrazubi, A. Avallone, K.K. Shiu, P. Artru
Annals of Oncology.2024;[Epub] CrossRef
PD-L1 thresholds predict efficacy of immune checkpoint inhibition in first-line treatment of advanced gastroesophageal adenocarcinoma. A systematic review and meta-analysis of seven phase III randomized trials
V. Formica, C. Morelli, L. Fornaro, S. Riondino, M. Rofei, E. Fontana, E.C. Smyth, M. Roselli, H.-T. Arkenau
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Perspectives on single-nucleus RNA sequencing in different cell types and tissues: Nayoung Kim, Huiram Kang, Areum Jo, Seung-Ah Yoo, Hae-Ock Lee; J Pathol Transl Med. 2023;57(1):52-59. Published online January 10, 2023; DOI: https://doi.org/10.4132/jptm.2022.12.19

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Abstract PDF

Single-cell RNA sequencing has become a powerful and essential tool for delineating cellular diversity in normal tissues and alterations in disease states. For certain cell types and conditions, there are difficulties in isolating intact cells for transcriptome profiling due to their fragility, large size, tight interconnections, and other factors. Single-nucleus RNA sequencing (snRNA-seq) is an alternative or complementary approach for cells that are difficult to isolate. In this review, we will provide an overview of the experimental and analysis steps of snRNA-seq to understand the methods and characteristics of general and tissue-specific snRNA-seq data. Knowing the advantages and limitations of snRNA-seq will increase its use and improve the biological interpretation of the data generated using this technique.

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Muhammad Junaid, Eun Jeong Lee, Su Bin Lim
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Adriana M.S. Andresen, Richard S. Taylor, Unni Grimholt, Rose Ruiz Daniels, Jianxuan Sun, Ross Dobie, Neil C. Henderson, Samuel A.M. Martin, Daniel J. Macqueen, Johanna H. Fosse
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Impaired cortical neuronal homeostasis and cognition after diffuse traumatic brain injury are dependent on microglia and type I interferon responses
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Molecular and Cellular Endocrinology.2023; 578: 112066. CrossRef
Analyzing alternative splicing in Alzheimer’s disease postmortem brain: a cell-level perspective
Mohammad-Erfan Farhadieh, Kamran Ghaedi
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Original Article

Artificial intelligence algorithm for neoplastic cell percentage estimation and its application to copy number variation in urinary tract cancer: Jinahn Jeong, Deokhoon Kim, Yeon-Mi Ryu, Ja-Min Park, Sun Young Yoon, Bokyung Ahn, Gi Hwan Kim, Se Un Jeong, Hyun-Jung Sung, Yong Il Lee, Sang-Yeob Kim, Yong Mee Cho; J Pathol Transl Med. 2024;58(5):229-240. Published online August 9, 2024; DOI: https://doi.org/10.4132/jptm.2024.07.13

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Abstract PDF Supplementary Material: Background
Bladder cancer is characterized by frequent mutations, which provide potential therapeutic targets for most patients. The effectiveness of emerging personalized therapies depends on an accurate molecular diagnosis, for which the accurate estimation of the neoplastic cell percentage (NCP) is a crucial initial step. However, the established method for determining the NCP, manual counting by a pathologist, is time-consuming and not easily executable.
Methods
To address this, artificial intelligence (AI) models were developed to estimate the NCP using nine convolutional neural networks and the scanned images of 39 cases of urinary tract cancer. The performance of the AI models was compared to that of six pathologists for 119 cases in the validation cohort. The ground truth value was obtained through multiplexed immunofluorescence. The AI model was then applied to 41 cases in the application cohort that underwent next-generation sequencing testing, and its impact on the copy number variation (CNV) was analyzed.
Results
Each AI model demonstrated high reliability, with intraclass correlation coefficients (ICCs) ranging from 0.82 to 0.88. These values were comparable or better to those of pathologists, whose ICCs ranged from 0.78 to 0.91 in urothelial carcinoma cases, both with and without divergent differentiation/ subtypes. After applying AI-driven NCP, 190 CNV (24.2%) were reclassified with 66 (8.4%) and 78 (9.9%) moved to amplification and loss, respectively, from neutral/minor CNV. The neutral/minor CNV proportion decreased by 6%.
Conclusions
These results suggest that AI models could assist human pathologists in repetitive and cumbersome NCP calculations.

Review

A standardized pathology report for gastric cancer: 2nd edition: Young Soo Park, Myeong-Cherl Kook, Baek-hui Kim, Hye Seung Lee, Dong-Wook Kang, Mi-Jin Gu, Ok Ran Shin, Younghee Choi, Wonae Lee, Hyunki Kim, In Hye Song, Kyoung-Mee Kim, Hee Sung Kim, Guhyun Kang, Do Youn Park, So-Young Jin, Joon Mee Kim, Yoon Jung Choi, Hee Kyung Chang, Soomin Ahn, Mee Soo Chang, Song-Hee Han, Yoonjin Kwak, An Na Seo, Sung Hak Lee, Mee-Yon Cho; J Pathol Transl Med. 2023;57(1):1-27. Published online January 15, 2023; DOI: https://doi.org/10.4132/jptm.2022.12.23

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Abstract PDF Supplementary Material

The first edition of ‘A Standardized Pathology Report for Gastric Cancer’ was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements. The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies.

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Genomic and Transcriptomic Characterization of Gastric Cancer with Bone Metastasis
Sujin Oh, Soo Kyung Nam, Keun-Wook Lee, Hye Seung Lee, Yujun Park, Yoonjin Kwak, Kyu Sang Lee, Ji-Won Kim, Jin Won Kim, Minsu Kang, Young Suk Park, Sang-Hoon Ahn, Yun-Suhk Suh, Do Joong Park, Hyung Ho Kim
Cancer Research and Treatment.2024; 56(1): 219. CrossRef
Microscopic tumor mapping of post-neoadjuvant therapy pancreatic cancer specimens to predict post-surgical recurrence: A prospective cohort study
Yeshong Park, Yeon Bi Han, Jinju Kim, MeeYoung Kang, Boram Lee, Eun Sung Ahn, Saemi Han, Haeryoung Kim, Hee-Young Na, Ho-Seong Han, Yoo-Seok Yoon
Pancreatology.2024; 24(4): 562. CrossRef
Effect of Neoadjuvant Chemotherapy on Tumor-Infiltrating Lymphocytes in Resectable Gastric Cancer: Analysis from a Western Academic Center
Elliott J. Yee, Danielle Gilbert, Jeffrey Kaplan, Sachin Wani, Sunnie S. Kim, Martin D. McCarter, Camille L. Stewart
Cancers.2024; 16(7): 1428. CrossRef
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
Journal of Pathology and Translational Medicine.2024; 58(3): 103. CrossRef
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Moonsik Kim, Byung Woog Kang, Jihyun Park, Jin Ho Baek, Jong Gwang Kim
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Baek-hui Kim, Sung Hak Lee
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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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Abstract PDF: Background
The umbilical cord forms the connection between the fetus and the placenta at the feto-maternal interface and normally comprises two umbilical arteries and one umbilical vein. In some cases, only a single umbilical artery (SUA) is present. This study was conducted to evaluate associations between SUA and other congenital malformations discovered in perinatal autopsies and to ascertain the existence of preferential associations between SUA and certain anomalies.
Methods
We evaluated records of all fetuses sent for autopsy to the Department of Pathology during the 10-year period from 2013 through 2022 (n = 1,277). The data were obtained from the hospital’s pathology laboratory records. The congenital anomalies were grouped by organ or system for analysis and included cardiovascular, urinary tract, nervous system, gastrointestinal tract, musculoskeletal, and lung anomalies.
Results
A SUA was present in 8.61% of the autopsies. The gestational age of the affected fetuses ranged between 13 to 40 weeks. An SUA presented as an isolated single anomaly in 44 cases (3.4%). Of the 110 SUA cases, 60% had other congenital anomalies. There was a significant association between birth defects and SUAs (p < .001). Strong associations between SUA and urinary tract, lung, and musculoskeletal anomalies were observed.
Conclusions
A SUA is usually seen in association with other congenital malformations rather than as an isolated defect. Therefore, examination for associated anomalies when an SUA is detected either antenatally or postnatally is imperative. The findings of this study should be helpful in counseling expectant mothers and their families in cases of SUA.

Review

A review of liver fibrosis and cirrhosis regression: Michael J. Lee; J Pathol Transl Med. 2023;57(4):189-195. Published online June 20, 2023; DOI: https://doi.org/10.4132/jptm.2023.05.24

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Abstract PDF

Cirrhosis has traditionally been considered an irreversible process of end-stage liver disease. With new treatments for chronic liver disease, there is regression of fibrosis and cirrhosis, improvement in clinical parameters (i.e. liver function and hemodynamic markers, hepatic venous pressure gradient), and survival rates, demonstrating that fibrosis and fibrolysis are a dynamic process moving in two directions. Microscopically, hepatocytes push into thinning fibrous septa with eventual perforation leaving behind delicate periportal spikes in the portal tracts and loss of portal veins. Obliterated portal veins during progressive fibrosis and cirrhosis due to parenchymal extinction, vascular remodeling and thrombosis often leave behind a bile duct and hepatic artery within the portal tract. Traditional staging classification systems focused on a linear, progressive process; however, the Beijing classification system incorporates both the bidirectional nature for the progression and regression of fibrosis. However, even with regression, vascular lesions/remodeling, parenchymal extinction and a cumulative mutational burden place patients at an increased risk for developing hepatocellular carcinoma and should continue to undergo active clinical surveillance. It is more appropriate to consider cirrhosis as another stage in the evolution of chronic liver disease as a bidirectional process rather than an end-stage, irreversible state.

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Tamer A. Addissouky, Majeed M. A. Ali, Ibrahim El Tantawy El Sayed, Yuliang Wang
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Maria S. Zhigalova, Vladimir V. Kiselev, Alla A. Ryk, Petr A. Yartsev
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Cyriac Abby Philips
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Original Article

Diagnostic challenges in the assessment of thyroid neoplasms using nuclear features and vascular and capsular invasion: a multi-center interobserver agreement study: Agnes Stephanie Harahap, Mutiah Mutmainnah, Maria Francisca Ham, Dina Khoirunnisa, Abdillah Hasbi Assadyk, Husni Cangara, Aswiyanti Asri, Diah Prabawati Retnani, Fairuz Quzwain, Hasrayati Agustina, Hermawan Istiadi, Indri Windarti, Krisna Murti, Muhammad Takbir, Ni Made Mahastuti, Nila Kurniasari, Nungki Anggorowati, Pamela Abineno, Yulita Pundewi Setyorini, Kennichi Kakudo; J Pathol Transl Med. 2024;58(6):299-309. Published online September 12, 2024; DOI: https://doi.org/10.4132/jptm.2024.07.25

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Abstract PDF Supplementary Material: Background
The diagnosis of thyroid neoplasms necessitates the identification of distinct histological features. Various education/hospital centers located in cities across Indonesia likely result in discordances among pathologists when diagnosing thyroid neoplasms.
Methods
This study examined the concordance among Indonesian pathologists in assessing nuclear features and capsular and vascular invasion of thyroid tumors. Fifteen pathologists from different centers independently assessed the same 14 digital slides of thyroid tumor specimens. All the specimens were thyroid neoplasms with known BRAFV600E and RAS mutational status, from a single center. We evaluated the pre- and post-training agreement using the Fleiss kappa. The significance of the training was evaluated using a paired T-test.
Results
Baseline agreement on nuclear features was slight to fair based on a 3-point scoring system (k = 0.14 to 0.28) and poor to fair based on an eight-point system (k = –0.02 to 0.24). Agreements on vascular (κ = 0.35) and capsular invasion (κ = 0.27) were fair, whereas the estimated molecular type showed substantial agreement (κ = 0.74). Following the training, agreement using the eight-point system significantly improved (p = 0.001).
Conclusions
The level of concordance among Indonesian pathologists in diagnosing thyroid neoplasm was relatively poor. Consensus in pathology assessment requires ongoing collaboration and education to refine diagnostic criteria.

Review

Infections and immunity: associations with obesity and related metabolic disorders: Amitabha Ray, Melissa J. L. Bonorden, Rajashree Pandit, Katai J. Nkhata, Anupam Bishayee; J Pathol Transl Med. 2023;57(1):28-42. Published online January 15, 2023; DOI: https://doi.org/10.4132/jptm.2022.11.14

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219 Download
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Abstract PDF

About one-fourth of the global population is either overweight or obese, both of which increase the risk of insulin resistance, cardiovascular diseases, and infections. In obesity, both immune cells and adipocytes produce an excess of pro-inflammatory cytokines that may play a significant role in disease progression. In the recent coronavirus disease 2019 (COVID-19) pandemic, important pathological characteristics such as involvement of the renin-angiotensin-aldosterone system, endothelial injury, and pro-inflammatory cytokine release have been shown to be connected with obesity and associated sequelae such as insulin resistance/type 2 diabetes and hypertension. This pathological connection may explain the severity of COVID-19 in patients with metabolic disorders. Many studies have also reported an association between type 2 diabetes and persistent viral infections. Similarly, diabetes favors the growth of various microorganisms including protozoal pathogens as well as opportunistic bacteria and fungi. Furthermore, diabetes is a risk factor for a number of prion-like diseases. There is also an interesting relationship between helminths and type 2 diabetes; helminthiasis may reduce the pro-inflammatory state, but is also associated with type 2 diabetes or even neoplastic processes. Several studies have also documented altered circulating levels of neutrophils, lymphocytes, and monocytes in obesity, which likely modifies vaccine effectiveness. Timely monitoring of inflammatory markers (e.g., C-reactive protein) and energy homeostasis markers (e.g., leptin) could be helpful in preventing many obesity-related diseases.

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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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