Journal of Pathology and Translational Medicine

Review Articles

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

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

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.

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

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

Review

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

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Abstract PDF

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

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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 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

Establishing molecular pathology curriculum for pathology trainees and continued medical education: a collaborative work from the Molecular Pathology Study Group of the Korean Society of Pathologists: Jiwon Koh, Ha Young Park, Jeong Mo Bae, Jun Kang, Uiju Cho, Seung Eun Lee, Haeyoun Kang, Min Eui Hong, Jae Kyung Won, Youn-La Choi, Wan-Seop Kim, Ahwon Lee; J Pathol Transl Med. 2023;57(5):265-272. Published online September 15, 2023; DOI: https://doi.org/10.4132/jptm.2023.08.26

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Abstract PDF

Background
The importance of molecular pathology tests has increased during the last decade, and there is a great need for efficient training of molecular pathology for pathology trainees and as continued medical education.
Methods
The Molecular Pathology Study Group of the Korean Society of Pathologists appointed a task force composed of experienced molecular pathologists to develop a refined educational curriculum of molecular pathology. A 3-day online educational session was held based on the newly established structure of learning objectives; the audience were asked to score their understanding of 22 selected learning objectives before and after the session to assess the effect of structured education.
Results
The structured objectives and goals of molecular pathology was established and posted as a web-based interface which can serve as a knowledge bank of molecular pathology. A total of 201 pathologists participated in the educational session. For all 22 learning objectives, the scores of self-reported understanding increased after educational session by 9.9 points on average (range, 6.6 to 17.0). The most effectively improved items were objectives from next-generation sequencing (NGS) section: ‘NGS library preparation and quality control’ (score increased from 51.8 to 68.8), ‘NGS interpretation of variants and reference database’ (score increased from 54.1 to 68.0), and ‘whole genome, whole exome, and targeted gene sequencing’ (score increased from 58.2 to 71.2). Qualitative responses regarding the adequacy of refined educational curriculum were collected, where favorable comments dominated.
Conclusions
Approach toward the education of molecular pathology was refined, which would greatly benefit the future trainees.

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Presence of RB1 or Absence of LRP1B Mutation Predicts Poor Overall Survival in Patients with Gastric Neuroendocrine Carcinoma and Mixed Adenoneuroendocrine Carcinoma
In Hye Song, Bokyung Ahn, Young Soo Park, Deok Hoon Kim, Seung-Mo Hong
Cancer Research and Treatment.2025; 57(2): 492. CrossRef

Single-center study on clinicopathological and typical molecular pathologic features of metastatic brain tumor: Su Hwa Kim, Young Suk Lee, Sung Hak Lee, Yeoun Eun Sung, Ahwon Lee, Jun Kang, Jae-Sung Park, Sin Soo Jeun, Youn Soo Lee; J Pathol Transl Med. 2023;57(4):217-231. Published online July 11, 2023; DOI: https://doi.org/10.4132/jptm.2023.06.10

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Abstract PDF

Background
The metastatic brain tumor is the most common brain tumor. The aim of this study was to demonstrate the clinicopathological and molecular pathologic features of brain metastases (BM).
Methods
A total of 269 patients were diagnosed with BM through surgical resection at Seoul St. Mary’s Hospital from January 2010 to March 2020. We reviewed the clinicopathological features and molecular status of primary and metastatic brain tissues using immunohistochemistry and molecular pathology results.
Results
Among 269 patients, 139 males and 130 females were included. The median age of primary tumor was 58 years (range, 13 to 87 years) and 86 patients (32.0%) had BM at initial presentation. Median BM free interval was 28.0 months (range, 1 to 286 months). The most frequent primary site was lung 46.5% (125/269), and followed by breast 15.6% (42/269), colorectum 10.0% (27/269). Epidermal growth factor receptor (EGFR) mutation was found in 50.8% (32/63) and 58.0% (40/69) of lung primary and BM, respectively. In both breast primary and breast cancer with BM, luminal B was the most frequent subtype at 37.9% (11/29) and 42.9% (18/42), respectively, followed by human epidermal growth factor receptor 2 with 31.0% (9/29) and 33.3% (14/42). Triple-negative was 20.7% (6/29) and 16.7% (7/42), and luminal A was 10.3% (3/29) and 7.1% (3/42) of breast primary and BM, respectively. In colorectal primary and colorectal cancer with BM, KRAS mutation was found in 76.9% (10/13) and 66.7% (2/3), respectively.
Conclusions
We report the clinicopathological and molecular pathologic features of BM that can provide useful information for understanding the pathogenesis of metastasis and for clinical trials based on the tumor’s molecular pathology.

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Colorectal cancer metastasis to the brain: A scoping review of incidence, treatment, and outcomes
Hunter J Hutchinson, Melanie Gonzalez, Diana Feier, Colin E Welch, Brandon Lucke-Wold
World Journal of Gastrointestinal Pathophysiology.2025;[Epub] CrossRef

Reviews

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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Shidi Miao, Hexiang Dong, Jinyang Feng, Yuyang Jiang, Mengzhuo Sun, Zengyao Liu, Qiujun Wang, Xuemei Ding, Ruitao Wang
International Journal of Medical Informatics.2026; 212: 106348. CrossRef
Poorly cohesive carcinoma diffusely involving the whole gastrointestinal tract: a case report
Wei Gao, Yusheng Yang, Xinyi Hu, Yujuan Shi, Kai Liu, Minmin Gu, Jing Wang
Discover Oncology.2026;[Epub] CrossRef
Comprehensive Overview of Gastric Cancer Immunohistochemistry: Key Biomarkers, Advanced Detection Methods, and Perspectives
Bogdan Oprea
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Spatial and Temporal Tumor Heterogeneity in Gastric Cancer: Discordance of Predictive Biomarkers
Hye Seung Lee
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Yunjoo Cho, Soomin Ahn, Kyoung-Mee Kim
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Dong Jin Kim, Jeong Ho Song, Ji-Hyeon Park, Sojung Kim, Sin Hye Park, Cheol Min Shin, Yoonjin Kwak, Kyunghye Bang, Chung-sik Gong, Sung Eun Oh, Yoo Min Kim, Young Suk Park, Jeesun Kim, Ji Eun Jung, Mi Ran Jung, Bang Wool Eom, Ki Bum Park, Jae Hun Chung, S
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Emily E. Stroobant, Seong-Ho Kong, Maria Bencivenga, Takahiro Kinoshita, Tae-Han Kim, Takeshi Sano, Giovanni de Manzoni, Han-Kwang Yang, Yuko Kitagawa, Vivian E. Strong
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Hayemin Lee, Mi Ryeong Park, Junhyun Lee
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Mengyu Li, Bencong Zhu, Cheng Meng, Xiaodan Fan, Laura Cantini
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Jing Wang, Lin Chang, Dong-Feng Niu, Yan Yan, Chang-Qi Cao, Shi-Jie Li, Qi Wu
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SMMILe enables accurate spatial quantification in digital pathology using multiple-instance learning
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Biomarker testing of cytology specimens in personalized medicine for lung cancer patients: Hyojin Kim, Jin-Haeng Chung; J Pathol Transl Med. 2022;56(6):326-333. Published online November 9, 2022; DOI: https://doi.org/10.4132/jptm.2022.10.17

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Abstract PDF

Every patient with advanced non–small cell lung cancer (NSCLC) should be tested for targetable driver mutations and gene arrangements that may open avenues for targeted therapy. As most patients with NSCLC in the advanced stage of the disease are not candidates for surgery, these tests have to be performed on small biopsies or cytology samples. A growing number of other genetic changes with targetable mutations may be treatable in the near future. To identify patients who might benefit from novel targeted therapy, relevant markers should be tested in an appropriate context. In addition, immunotherapy of lung cancer is guided by the status of programmed death-ligand 1 expression in tumor cells. The variety and versatility of cytological specimen preparations offer significant advantages for molecular testing; however, they frequently remain underused. Therefore, evaluating the utility and adequacy of cytologic specimens is important, not only from a lung cancer diagnosis, but also for the large number of ancillary studies that are necessary to provide appropriate clinical management. A large proportion of lung cancers is diagnosed by aspiration or exfoliative cytology specimens; thus, optimizing strategies to triage and best use the tissue for diagnosis and biomarker studies forms a critical component of lung cancer management. In this review, we discuss the opportunities and challenges of using cytologic specimens for biomarker testing of lung cancer and the role of cytopathology in the molecular era.

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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.

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Distinctive morphological and molecular features of urothelial carcinoma with an inverted growth pattern: Francesca Sanguedolce, Beppe Calò, Marco Chirico, Ugo Falagario, Gian Maria Busetto, Magda Zanelli, Alessandra Bisagni, Maurizio Zizzo, Stefano Ascani, Giuseppe Carrieri, Luigi Cormio; J Pathol Transl Med. 2021;55(4):239-246. Published online June 14, 2021; DOI: https://doi.org/10.4132/jptm.2021.04.20

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Abstract PDF

Urothelial carcinoma with an inverted growth pattern (UC-IGP) is a peculiar entity within the spectrum of urothelial lesions. While efforts have been made over the last few decades to unravel its carcinogenesis and relationship with conventional urothelial carcinoma, the exact classification of inverted urothelial lesions is a matter of debate. The morphological features of UC-IGP pose several issues in differential diagnosis with other mostly benign lesions. Various techniques, including immunohistochemistry, UroVysion, and many molecular methods, have been employed to study the exact nature of this lesion. The aim of this review is to provide a comprehensive overview of the morphological and immunophenotypical aspects of UC-IGP. Moreover, we present and discuss the immunohistochemical and molecular markers involved in diagnosis and prognosis of UC-IGP lesions.

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HER2 Expression in Bladder Cancer: A Focused View on Its Diagnostic, Prognostic, and Predictive Role
Francesca Sanguedolce, Magda Zanelli, Andrea Palicelli, Alessandra Bisagni, Maurizio Zizzo, Stefano Ascani, Maria Carmela Pedicillo, Angelo Cormio, Ugo Giovanni Falagario, Giuseppe Carrieri, Luigi Cormio
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Proteomic-Based Machine Learning Analysis Reveals PYGB as a Novel Immunohistochemical Biomarker to Distinguish Inverted Urothelial Papilloma From Low-Grade Papillary Urothelial Carcinoma With Inverted Growth
Minsun Jung, Cheol Lee, Dohyun Han, Kwangsoo Kim, Sunah Yang, Ilias P. Nikas, Kyung Chul Moon, Hyeyoon Kim, Min Ji Song, Bohyun Kim, Hyebin Lee, Han Suk Ryu
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Original Articles

Highly prevalent BRAF V600E and low-frequency TERT promoter mutations underlie papillary thyroid carcinoma in Koreans: Sue Youn Kim, Taeeun Kim, Kwangsoon Kim, Ja Seong Bae, Jeong Soo Kim, Chan Kwon Jung; J Pathol Transl Med. 2020;54(4):310-317. Published online June 15, 2020; DOI: https://doi.org/10.4132/jptm.2020.05.12

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Abstract PDF

Background
The presence of telomerase reverse transcriptase (TERT) promoter mutations have been associated with a poor prognosis in patients with papillary thyroid carcinomas (PTC). The frequency of TERT promoter mutations varies widely depending on the population and the nature of the study.
Methods
Data were prospectively collected in 724 consecutive patients who underwent thyroidectomy for PTC from 2018 to 2019. Molecular testing for BRAF V600E and TERT promoter mutations was performed in all cases.
Results
TERT promoter alterations in two hotspots (C228T and C250T) and C216T were found in 16 (2.2%) and 4 (0.6%) of all PTCs, respectively. The hotspot mutations were significantly associated with older age at diagnosis, larger tumor size, extrathyroidal extension, higher pathologic T category, lateral lymph node metastasis, and higher American Thyroid Association recurrence risk. The patients with C216T variant were younger and had a lower American Thyroid Association recurrence risk than those with hotspot mutations. Concurrent BRAF V600E was found in 19 of 20 cases with TERT promoter mutations. Of 518 microcarcinomas measuring ≤1.0 cm in size, hotspot mutations and C216T variants were detected in five (1.0%) and three (0.6%) cases, respectively.
Conclusions
Our study indicates a low frequency of TERT promoter mutations in Korean patients with PTC and supports previous findings that TERT promoter mutations are more common in older patients with unfavorable clinicopathologic features and BRAF V600E. TERT promoter mutations in patients with microcarcinoma are uncommon and may have a limited role in risk stratification. The C216T variant seems to have no clinicopathologic effect on PTC.

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Adjunctive markers for classification and diagnosis of central nervous system tumors: results of a multi-center neuropathological survey in Korea: Yoon Jin Cha, Se Hoon Kim, Na Rae Kim; J Pathol Transl Med. 2020;54(2):165-170. Published online February 20, 2020; DOI: https://doi.org/10.4132/jptm.2020.02.04

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Abstract PDF Supplementary Material

Background
The revised 4th 2016 World Health Organization (WHO) classification of tumors of the central nervous system (CNS) classification has adopted integrated diagnosis encompassing the histology and molecular features of CNS tumors. We aimed to investigate the immunohistochemistry, molecular testing, and testing methods for diagnosis of CNS tumors in pathological labs of tertiary centers in Korea, and evaluate the adequacy of tests for proper diagnosis in daily practice.
Methods
A survey, composed of eight questions concerning molecular testing for diagnosis of CNS tumors, was sent to 10 neuropathologists working in tertiary centers in Korea.
Results
For diagnosis of astrocytic and oligodendroglial tumors, all 10 centers performed isocitrate dehydrogenase mutations testing and 1p/19q loss of heterozygosity. For glioneuronal tumors, immunohistochemistry (IHC) assays for synaptophysin (n = 9), CD34 (n = 7), BRAF(VE1) (n = 5) were used. For embryonal tumors, particularly in medulloblastoma, four respondents used IHC panel (growth factor receptor bound protein 2-associated protein 1, filamin A, and yes-associated protein 1) for molecular subclassification. Regarding meningioma, all respondents performed Ki-67 IHC and five performed telomerase reverse transcriptase promoter mutation.
Conclusions
Most tertiary centers made proper diagnosis in line with 2016 WHO classification. As classification of CNS tumors has evolved to be more complex and more ancillary tests are required, these should be performed considering the effect of necessity and justification.

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Exploring the role of epidermal growth factor receptor variant III in meningeal tumors
Rashmi Rana, Vaishnavi Rathi, Kirti Chauhan, Kriti Jain, Satnam Singh Chhabra, Rajesh Acharya, Samir Kumar Kalra, Anshul Gupta, Sunila Jain, Nirmal Kumar Ganguly, Dharmendra Kumar Yadav, Timir Tripathi
PLOS ONE.2021; 16(9): e0255133. CrossRef

Double cocktail immunostains with high molecular weight cytokeratin and GATA-3: useful stain to discriminate in situ involvement of prostatic ducts or acini from stromal invasion by urothelial carcinoma in the prostate: Junghye Lee, Youngeun Yoo, Sanghui Park, Min-Sun Cho, Sun Hee Sung, Jae Y. Ro; J Pathol Transl Med. 2020;54(2):146-153. Published online February 10, 2020; DOI: https://doi.org/10.4132/jptm.2019.11.12

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Abstract PDF

Background
Distinguishing prostatic stromal invasion (PSI) by urothelial carcinoma (UC) from in situ UC involving prostatic ducts or acini with no stromal invasion (in situ involvement) may be challenging on hematoxylin and eosin stained sections. However, the distinction between them is important because cases with PSI show worse prognosis. This study was performed to assess the utility of double cocktail immunostains with high molecular weight cytokeratin (HMWCK) and GATA-3 to discriminate PSI by UC from in situ UC involvement of prostatic ducts or acini in the prostate.
Methods
Among 117 radical cystoprostatectomy specimens for bladder UCs, 25 cases showed secondary involvement of bladder UC in prostatic ducts/acini only or associated stromal invasion and of these 25 cases, seven cases revealed equivocal PSI. In these seven cases with equivocal PSI, HMWCK, and GATA-3 double immunohistochemical stains were performed to identify whether this cocktail stain is useful to identify the stromal invasion.
Results
In all cases, basal cells of prostate glands showed strong cytoplasmic staining for HMWCK and UC cells showed strong nuclear staining for GATA-3. In cases with stromal invasion of UC, GATA-3-positive tumor cells in the prostatic stroma without surrounding HMWCK-positive basal cells were highlighted and easily recognized. Among seven equivocal cases, two cases showed PSI and five in situ UC in the prostate. In two cases, the original diagnoses were revised.
Conclusions
Our study suggested that HMWCK and GATA-3 double stains could be utilized as an adjunct method in the distinction between PSI by UC from in situ UC involving prostatic ducts or acini.

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Review

Molecular characteristics of meningiomas: Young Suk Lee, Youn Soo Lee; J Pathol Transl Med. 2020;54(1):45-63. Published online January 15, 2020; DOI: https://doi.org/10.4132/jptm.2019.11.05

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Abstract PDF

Meningioma is the most common primary intracranial tumor in adults. The grading of meningioma is based on World Health Organization criteria, which rely on histopathological features alone. This grading system is unable to conclusively predict the clinical behavior of these tumors (i.e., recurrence or prognosis in benign or atypical grades). Advances in molecular techniques over the last decade that include genomic and epigenomic data associated with meningiomas have been used to identify genetic biomarkers that can predict tumor behavior. This review summarizes the molecular characteristics of meningioma using genetic and epigenetic biomarkers. Molecular alterations that can predict meningioma behavior may be integrated into the upcoming World Health Organization grading system.

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Original Articles

The Prognostic Impact of Synchronous Ipsilateral Multiple Breast Cancer: Survival Outcomes according to the Eighth American Joint Committee on Cancer Staging and Molecular Subtype: Jinah Chu, Hyunsik Bae, Youjeong Seo, Soo Youn Cho, Seok-Hyung Kim, Eun Yoon Cho; J Pathol Transl Med. 2018;52(6):396-403. Published online October 23, 2018; DOI: https://doi.org/10.4132/jptm.2018.10.03

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103 Download
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Abstract PDF

Background
In the current American Joint Committee on Cancer staging system of breast cancer, only tumor size determines T-category regardless of whether the tumor is single or multiple. This study evaluated if tumor multiplicity has prognostic value and can be used to subclassify breast cancer.
Methods
We included 5,758 patients with invasive breast cancer who underwent surgery at Samsung Medical Center, Seoul, Korea, from 1995 to 2012.
Results
Patients were divided into two groups according to multiplicity (single, n = 4,744; multiple, n = 1,014). Statistically significant differences in lymph node involvement and lymphatic invasion were found between the two groups (p < .001). Patients with multiple masses tended to have luminal A molecular subtype (p < .001). On Kaplan-Meier survival analysis, patients with multiple masses had significantly poorer disease-free survival (DFS) (p = .016). The prognostic significance of multiplicity was seen in patients with anatomic staging group I and prognostic staging group IA (p = .019 and p = .032, respectively). When targeting patients with T1-2 N0 M0, hormone receptor–positive, and human epidermal growth factor receptor 2 (HER2)–negative cancer, Kaplan-Meier survival analysis also revealed significantly reduced DFS with multiple cancer (p = .031). The multivariate analysis indicated that multiplicity was independently correlated with worse DFS (hazard ratio, 1.23; 95% confidence interval, 1.03 to 1.47; p = .025). The results of this study indicate that tumor multiplicity is frequently found in luminal A subtype, is associated with frequent lymph node metastasis, and is correlated with worse DFS.
Conclusions
Tumor multiplicity has prognostic value and could be used to subclassify invasive breast cancer at early stages. Adjuvant chemotherapy would be necessary for multiple masses of T1–2 N0 M0, hormone-receptor-positive, and HER2-negative cancer.

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Beyond Pathology: MRI-Derived Metrics Unlock Preoperative Prognostic Risk Stratification in Breast Cancer
Mehrad Zare Gholinejad, Alisa Mohebbi, Afshin Mohammadi, Seyed Mohammad Tavangar
Clinical Breast Cancer.2026;[Epub] CrossRef
The Role of Serum Beta-Human Chorionic Gonadotropin (β-hCG) in Differentiating Benign and Malignant Breast Lesions at a Tertiary Care Center in Jharkhand
Neyaz Ahmad, Khushboo Rani, Zenith Kerketta, Krishna Murari, Anish Baxla, Ujala Murmu, Amit Nishant, Shreya .
Cureus.2025;[Epub] CrossRef
Role of Large Format Histology in Diagnosis of Breast Carcinoma
Hari Shankar Pandey, Sanya Bhasin, Suman Kumari Pandey
NMO Journal.2025; 19(2): 189. CrossRef
Prognostic Impact of Multiple Synchronous T1 Breast Cancer
Hongki Gwak, Sung Hoo Jung, Young Jin Suh, Seok Jin Nam, Jai Hong Han, Se Jeong Oh, Eun Hwa Park, Seong Hwan Kim
Cancers.2024; 16(23): 4019. CrossRef
Deep learning-based system for automatic prediction of triple-negative breast cancer from ultrasound images
Alexandre Boulenger, Yanwen Luo, Chenhui Zhang, Chenyang Zhao, Yuanjing Gao, Mengsu Xiao, Qingli Zhu, Jie Tang
Medical & Biological Engineering & Computing.2023; 61(2): 567. CrossRef
Multicentre prospective cohort study of unmet supportive care needs among patients with breast cancer throughout their cancer treatment trajectory in Penang: a PenBCNeeds Study protocol
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Tibor Tot, Maria Gere, Syster Hofmeyer, Annette Bauer, Ulrika Pellas
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Editorial for “Synchronous Breast Cancer: Phenotypic Similarities on MRI”
Uma Sharma
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Synchronous Multiple Breast Cancers—Do We Need to Reshape Staging?
Minodora Onisâi, Adrian Dumitru, Iuliana Iordan, Cătălin Aliuș, Oana Teodor, Adrian Alexandru, Daniela Gheorghiță, Iulian Antoniac, Adriana Nica, Alexandra-Ana Mihăilescu, Sebastian Grădinaru
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Protein Phosphatase Magnesium-Dependent 1δ (PPM1D) Expression as a Prognostic Marker in Adult Supratentorial Diffuse Astrocytic and Oligodendroglial Tumors: Hui Jeong Jeong, Chang Gok Woo, Bora Lee, Shin Kwang Khang, Soo Jeong Nam, Jene Choi; J Pathol Transl Med. 2018;52(2):71-78. Published online October 18, 2017; DOI: https://doi.org/10.4132/jptm.2017.10.21

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Abstract PDF Supplementary Material

Background
Protein phosphatase magnesium-dependent 1δ (PPM1D) is a p53-induced serine/ threonine phosphatase, which is overexpressed in various human cancers. A recent study reported that a mutation in the PPM1D gene is associated with poor prognosis in brainstem gliomas. In this study, we evaluated the utility of PPM1D as a prognostic biomarker of adult supratentorial diffuse astrocytic and oligodendroglial tumors.
Methods
To investigate PPM1D protein expression, mRNA expression, and copy number changes, immunohistochemistry, RNAscope in situ hybridization, and fluorescence in situ hybridization were performed in 84 adult supratentorial diffuse gliomas. We further analyzed clinical characteristics and overall survival (OS) according to PPM1D protein expression, and examined its correlation with other glioma biomarkers such as isocitrate dehydrogenase (IDH) mutation, and p53 expression.
Results
Forty-six cases (54.8%) were PPM1D-positive. PPM1D expression levels were significantly correlated with PPM1D transcript levels (p= .035), but marginally with PPM1D gene amplification (p=.079). Patients with high-grade gliomas showed a higher frequency of PPM1D expression than those with low-grade gliomas (p <.001). Multivariate analysis demonstrated that PPM1D expression (hazard ratio [HR], 2.58; p=.032), age over 60 years (HR, 2.55; p=.018), and IDH1 mutation (HR, 0.18; p=.002) were significantly independent prognostic factors; p53 expression had no prognostic significance (p=.986). The patients with tumor expressing PPM1D showed a shorter OS (p=.003). Moreover, patients with tumor harboring wild-type IDH1 and PPM1D expression had the worst OS (p<.001).
Conclusions
Our data suggest that a subset of gliomas express PPM1D; PPM1D expression is a significant marker of poor prognosis in adult supratentorial diffuse astrocytic and oligodendroglial tumors.

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Characteristic analysis and identification of novel molecular biomarkers in elderly glioblastoma patients using the 2021 WHO Classification of Central Nervous System Tumors
Yaning Wang, Junlin Li, Yaning Cao, Wenlin Chen, Hao Xing, Xiaopeng Guo, Yixin Shi, Yuekun Wang, Tingyu Liang, Liguo Ye, Delin Liu, Tianrui Yang, Yu Wang, Wenbin Ma
Frontiers in Neuroscience.2023;[Epub] CrossRef
Metal-dependent Ser/Thr protein phosphatase PPM family: Evolution, structures, diseases and inhibitors
Rui Kamada, Fuki Kudoh, Shogo Ito, Itsumi Tani, Jose Isagani B. Janairo, James G. Omichinski, Kazuyasu Sakaguchi
Pharmacology & Therapeutics.2020; 215: 107622. CrossRef

Reviews

Molecular Testing of Brain Tumor: Sung-Hye Park, Jaekyung Won, Seong-Ik Kim, Yujin Lee, Chul-Kee Park, Seung-Ki Kim, Seung-Hong Choi; J Pathol Transl Med. 2017;51(3):205-223. Published online May 12, 2017; DOI: https://doi.org/10.4132/jptm.2017.03.08

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Abstract PDF

The World Health Organization (WHO) classification of central nervous system (CNS) tumors was revised in 2016 with a basis on the integrated diagnosis of molecular genetics. We herein provide the guidelines for using molecular genetic tests in routine pathological practice for an accurate diagnosis and appropriate management. While astrocytomas and IDH-mutant (secondary) glioblastomas are characterized by the mutational status of IDH, TP53, and ATRX, oligodendrogliomas have a 1p/19q codeletion and mutations in IDH, CIC, FUBP1, and the promoter region of telomerase reverse transcriptase (TERTp). IDH-wildtype (primary) glioblastomas typically lack mutations in IDH, but are characterized by copy number variations of EGFR, PTEN, CDKN2A/B, PDGFRA, and NF1 as well as mutations of TERTp. High-grade pediatric gliomas differ from those of adult gliomas, consisting of mutations in H3F3A, ATRX, and DAXX, but not in IDH genes. In contrast, well-circumscribed low-grade neuroepithelial tumors in children, such as pilocytic astrocytoma, pleomorphic xanthoastrocytoma, and ganglioglioma, often have mutations or activating rearrangements in the BRAF, FGFR1, and MYB genes. Other CNS tumors, such as ependymomas, neuronal and glioneuronal tumors, embryonal tumors, meningothelial, and other mesenchymal tumors have important genetic alterations, many of which are diagnostic, prognostic, and predictive markers and therapeutic targets. Therefore, the neuropathological evaluation of brain tumors is increasingly dependent on molecular genetic tests for proper classification, prediction of biological behavior and patient management. Identifying these gene abnormalities requires cost-effective and high-throughput testing, such as next-generation sequencing. Overall, this paper reviews the global guidelines and diagnostic algorithms for molecular genetic testing of brain tumors.

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Molecular Testing of Lymphoproliferative Disorders: Current Status and Perspectives: Yoon Kyung Jeon, Sun Och Yoon, Jin Ho Paik, Young A Kim, Bong Kyung Shin, Hyun-Jung Kim, Hee Jeong Cha, Ji Eun Kim, Jooryung Huh, Young-Hyeh Ko; J Pathol Transl Med. 2017;51(3):224-241. Published online May 10, 2017; DOI: https://doi.org/10.4132/jptm.2017.04.09

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713 Download
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Abstract PDF

Molecular pathologic testing plays an important role for the diagnosis, prognostication and decision of treatment strategy in lymphoproliferative disease. Here, we briefly review the molecular tests currently used for lymphoproliferative disease and those which will be implicated in clinical practice in the near future. Specifically, this guideline addresses the clonality test for B- and T-cell proliferative lesions, molecular cytogenetic tests for malignant lymphoma, determination of cell-of-origin in diffuse large B-cell lymphoma, and molecular genetic alterations incorporated in the 2016 revision of the World Health Organization classification of lymphoid neoplasms. Finally, a new perspective on the next-generation sequencing for diagnostic, prognostic, and therapeutic purpose in malignant lymphoma will be summarized.

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Good Laboratory Standards for Clinical Next-Generation Sequencing Cancer Panel Tests: Jihun Kim, Woong-Yang Park, Nayoung K. D. Kim, Se Jin Jang, Sung-Min Chun, Chang-Ohk Sung, Jene Choi, Young-Hyeh Ko, Yoon-La Choi, Hyo Sup Shim, Jae-Kyung Won; J Pathol Transl Med. 2017;51(3):191-204. Published online May 10, 2017; DOI: https://doi.org/10.4132/jptm.2017.03.14

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1,122 Download
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Abstract PDF

Next-generation sequencing (NGS) has recently emerged as an essential component of personalized cancer medicine due to its high throughput and low per-base cost. However, no sufficient guidelines for implementing NGS as a clinical molecular pathology test are established in Korea. To ensure clinical grade quality without inhibiting adoption of NGS, a taskforce team assembled by the Korean Society of Pathologists developed laboratory guidelines for NGS cancer panel testing procedures and requirements for clinical implementation of NGS. This consensus standard proposal consists of two parts: laboratory guidelines and requirements for clinical NGS laboratories. The laboratory guidelines part addressed several important issues across multistep NGS cancer panel tests including choice of gene panel and platform, sample handling, nucleic acid management, sample identity tracking, library preparation, sequencing, analysis and reporting. Requirements for clinical NGS tests were summarized in terms of documentation, validation, quality management, and other required written policies. Together with appropriate pathologist training and international laboratory standards, these laboratory standards would help molecular pathology laboratories to successfully implement NGS cancer panel tests in clinic. In this way, the oncology community would be able to help patients to benefit more from personalized cancer medicine.

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Molecular Testing of Lung Cancers: Hyo Sup Shim, Yoon-La Choi, Lucia Kim, Sunhee Chang, Wan-Seop Kim, Mee Sook Roh, Tae-Jung Kim, Seung Yeon Ha, Jin-Haeng Chung, Se Jin Jang, Geon Kook Lee; J Pathol Transl Med. 2017;51(3):242-254. Published online April 21, 2017; DOI: https://doi.org/10.4132/jptm.2017.04.10

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618 Download
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28 Crossref

Abstract PDF

Targeted therapies guided by molecular diagnostics have become a standard treatment of lung cancer. Epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements are currently used as the best predictive biomarkers for EGFR tyrosine kinase inhibitors and ALK inhibitors, respectively. Besides EGFR and ALK, the list of druggable genetic alterations has been growing, including ROS1 rearrangements, RET rearrangements, and MET alterations. In this situation, pathologists should carefully manage clinical samples for molecular testing and should do their best to quickly and accurately identify patients who will benefit from precision therapeutics. Here, we grouped molecular biomarkers of lung cancers into three categories—mutations, gene rearrangements, and amplifications—and propose expanded guidelines on molecular testing of lung cancers.

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Molecular Testing for Gastrointestinal Cancer: Hye Seung Lee, Woo Ho Kim, Yoonjin Kwak, Jiwon Koh, Jeong Mo Bae, Kyoung-Mee Kim, Mee Soo Chang, Hye Seung Han, Joon Mee Kim, Hwal Woong Kim, Hee Kyung Chang, Young Hee Choi, Ji Y. Park, Mi Jin Gu, Min Jin Lhee, Jung Yeon Kim, Hee Sung Kim, Mee-Yon Cho; J Pathol Transl Med. 2017;51(2):103-121. Published online February 19, 2017; DOI: https://doi.org/10.4132/jptm.2017.01.24

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Abstract PDF

With recent advances in molecular diagnostic methods and targeted cancer therapies, several molecular tests have been recommended for gastric cancer (GC) and colorectal cancer (CRC). Microsatellite instability analysis of gastrointestinal cancers is performed to screen for Lynch syndrome, predict favorable prognosis, and screen patients for immunotherapy. The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor has been approved in metastatic CRCs with wildtype RAS (KRAS and NRAS exon 2–4). A BRAF mutation is required for predicting poor prognosis. Additionally, amplification of human epidermal growth factor receptor 2 (HER2) and MET is also associated with resistance to EGFR inhibitor in metastatic CRC patients. The BRAF V600E mutation is found in sporadic microsatellite unstable CRCs, and thus is helpful for ruling out Lynch syndrome. In addition, the KRAS mutation is a prognostic biomarker and the PIK3CA mutation is a molecular biomarker predicting response to phosphoinositide 3-kinase/AKT/mammalian target of rapamycin inhibitors and response to aspirin therapy in CRC patients. Additionally, HER2 testing should be performed in all recurrent or metastatic GCs. If the results of HER2 immunohistochemistry are equivocal, HER2 silver or fluorescence in situ hybridization testing are essential for confirmative determination of HER2 status. Epstein-Barr virus–positive GCs have distinct characteristics, including heavy lymphoid stroma, hypermethylation phenotype, and high expression of immune modulators. Recent advances in next-generation sequencing technologies enable us to examine various genetic alterations using a single test. Pathologists play a crucial role in ensuring reliable molecular testing and they should also take an integral role between molecular laboratories and clinicians.

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The Utilization of Cytologic Fine-Needle Aspirates of Lung Cancer for Molecular Diagnostic Testing: Michael H. Roh; J Pathol Transl Med. 2015;49(4):300-309. Published online June 16, 2015; DOI: https://doi.org/10.4132/jptm.2015.06.16

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Abstract PDF

In this era of precision medicine, our understanding and knowledge of the molecular landscape associated with lung cancer pathogenesis continues to evolve. This information is being increasingly exploited to treat advanced stage lung cancer patients with tailored, targeted therapy. During the management of these patients, minimally invasive procedures to obtain samples for tissue diagnoses are desirable. Cytologic fine-needle aspirates are often utilized for this purpose and are important not only for rendering diagnoses to subtype patients’ lung cancers, but also for ascertaining molecular diagnostic information for treatment purposes. Thus, cytologic fine-needle aspirates must be utilized and triaged judiciously to achieve both objectives. In this review, strategies in utilizing fine-needle aspirates will be discussed in the context of our current understanding of the clinically actionable molecular aberrations underlying non-small cell lung cancer and the molecular assays applied to these samples in order to obtain treatment-relevant molecular diagnostic information.

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Molecular Imaging in the Era of Personalized Medicine: Kyung-Ho Jung, Kyung-Han Lee; J Pathol Transl Med. 2015;49(1):5-12. Published online January 15, 2015; DOI: https://doi.org/10.4132/jptm.2014.10.24

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Abstract PDF

Clinical imaging creates visual representations of the body interior for disease assessment. The role of clinical imaging significantly overlaps with that of pathology, and diagnostic workflows largely depend on both fields. The field of clinical imaging is presently undergoing a radical change through the emergence of a new field called molecular imaging. This new technology, which lies at the intersection between imaging and molecular biology, enables noninvasive visualization of biochemical processes at the molecular level within living bodies. Molecular imaging differs from traditional anatomical imaging in that biomarkers known as imaging probes are used to visualize target molecules-of-interest. This ability opens up exciting new possibilities for applications in oncologic, neurological and cardiovascular diseases. Molecular imaging is expected to make major contributions to personalized medicine by allowing earlier diagnosis and predicting treatment response. The technique is also making a huge impact on pharmaceutical development by optimizing preclinical and clinical tests for new drug candidates. This review will describe the basic principles of molecular imaging and will briefly touch on three examples (from an immense list of new techniques) that may contribute to personalized medicine: receptor imaging, angiogenesis imaging, and apoptosis imaging.

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Original Articles

The Clinicopathologic Features of Molecular Apocrine Breast Cancer: Yoon Jin Cha, Woo-Hee Jung, Ja Seung Koo; Korean J Pathol. 2012;46(2):169-176. Published online April 25, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.2.169

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Abstract PDF

Background

To elucidate the clinicopathologic features and their implications on the immunohistochemistry in cases of molecular apocrine breast cancer (MABC).

Methods

Immunohistochemical (IHC) staining for estrogen receptor (ER), human epidermal growth factor receptor 2 (HER-2), cytokeratin (CK) 5/6, epidermal growth factor receptor (EGFR), androgen receptor (AR), gamma-glutamyltrasferase 1 (GGT1) and Ki-67 was performed on tissue microarray breast cancer samples from 204 patients. Phenotypes of breast cancer were divided based on the IHC status of ER, AR and GGT1 into the following: luminal type, ER positive and AR and/or GGT1 positive; basal type, ER, AR, and GGT1 negative; non-basal type, ER positive and AR and GGT1 negative; and MABC type, ER negative and AR and/or GGT1 positive.

Results

In our series of patients (n=204), there were 26 cases of MABC. Besides, there were 18, 60, and 100 cases of luminal type, basal type and non-basal type, respectively. The MABC demonstrated apocrine histology and a higher prevalence of HER-2 positivity than other phenotypes. With the basal type, the MABC manifested a more frequent expression of CK5/6 and EGFR and a higher Ki-67 index than other phenotypes (p<0.001). There were no significant differences in patient prognosis between the phenotypes of breast cancer.

Conclusions

MABC are distinguishable from other phenotypes based on the apocrine histology and a higher expression rate of HER-2.

Citations

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Burak Ilhan, Selman Emiroğlu, Rustu Türkay, Rıdvan Ilhan
Current Problems in Cancer.2020; 44(2): 100501. CrossRef
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Thomas Grellety
Bulletin du Cancer.2020; 107(4): 506. CrossRef
Triple‐negative apocrine carcinoma: A rare pathologic subtype with a better prognosis than other triple‐negative breast cancers
Cletus A. Arciero, Albert H. Diehl, Yuan Liu, Qin Sun, Theresa Gillespie, Xiaoxian Li, Preeti Subhedar
Journal of Surgical Oncology.2020; 122(6): 1232. CrossRef
Apocrine lesions of the breast: part 2 of a two-part review. Invasive apocrine carcinoma, the molecular apocrine signature and utility of immunohistochemistry in the diagnosis of apocrine lesions of the breast
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Journal of Clinical Pathology.2019; 72(1): 7. CrossRef
Enhancing Abiraterone Acetate Efficacy in Androgen Receptor–positive Triple-negative Breast Cancer: Chk1 as a Potential Target
Thomas Grellety, Celine Callens, Elodie Richard, Adrien Briaux, Valérie Vélasco, Marina Pulido, Anthony Gonçalves, Pierre Gestraud, Gaetan MacGrogan, Hervé Bonnefoi, Bruno Cardinaud
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A clinicopathologic study of invasive apocrine carcinoma of the breast: A single-center experience
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The Breast Journal.2018; 24(6): 1105. CrossRef
Dose invasive apocrine adenocarcinoma has worse prognosis than invasive ductal carcinoma of breast: evidence from SEER database
Ning Zhang, Hanwen Zhang, Tong Chen, Qifeng Yang
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Pure Apocrine Carcinomas Represent a Clinicopathologically Distinct Androgen Receptor–Positive Subset of Triple-Negative Breast Cancers
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Xiaozhen Liu, Yang Yang, Xiaolong Feng, Honghong Shen, Jian Liu, Xia Liu, Yun Niu
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Molecular and diagnostic features of apocrine breast lesions
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Claudia Janeth Rodríguez-Silva, José Luis González-Vela, Ascary Alcides Velázquez-Pacheco
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Comparison of the DNA Preservation in Neutral-Buffered Formalin Fixed Paraffin-Embedded Tissue and in Non-Buffered Formalin Fixed Paraffin-Embedded Tissue.: An Na Seo, Jae Hoon Kim, Dakeun Lee, Ji Yun Jeong, Ji Young Park; Korean J Pathol. 2011;45(6):549-556.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.6.549

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Abstract PDF

BACKGROUND
The preservation of optimized DNA and its extraction from formalin-fixed, paraffin-embedded (FFPE) tissues are important issues. There has been some doubt over whether 10% neutral-buffered formalin is an ideal fixation solution for DNA preservation over non-buffered formalin, as conventionally recommended. In this study, the correlation between the efficiency of DNA extraction from FFPE tissues and buffered formalin was evaluated.
METHODS
Several tissues with same conditions except fixatives were fixed in four different formalin solution groups and were routinely processed as paraffin-embedding protocols. DNAs were extracted from four different FFPE tissues that were stored for over 3 months and over 9 months. The quantity and quality of the DNAs were assessed with a NanoDrop ND-1000 spectrophotometer, and the polymerase chain reaction (PCR) amplification and degradation were analyzed via microchip electrophoresis. KRAS mutation analysis and microsatellite instability (BAT25) PCR were performed with each sample.
RESULTS
The results showed no remarkable difference in the four groups.
CONCLUSIONS
The study findings demonstrate that DNA preservation is fairly unaffected by a neutral buffer where there is short formalin manufacture period and an adequate formalin fixation time before embedding in paraffin.

Citations

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Kangana Aggarwal, Nidhi Sharma, Braja Kishore Mohapatra, Kamal Chauhan, Harpreet Singh, Chittaranjan Behera
Forensic Science, Medicine and Pathology.2025;[Epub] CrossRef
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Hyun Ju Lee, Xianhua Xu, Hyojin Kim, Yan Jin, Pingli Sun, Ji Eun Kim, Jin-Haeng Chung
Korean Journal of Pathology.2013; 47(1): 52. CrossRef

CD56 and High Molecular Weight Cytokeratin as Diagnostic Markers of Papillary Thyroid Carcinoma.: Mi Kyung Shin, Jeong Won Kim, Young Su Ju; Korean J Pathol. 2011;45(5):477-484.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.5.477

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Abstract PDF

BACKGROUND
The incidence of papillary thyroid carcinoma (PTC) has been increasing recently and a precise diagnosis is essential for optimal treatment. Ancillary immunohistochemical stains are important for diagnosing some difficult cases.
METHODS
The dignostic value of CD56, high molecular weight cytokeratin (HMCK), galectin-3 (GAL3), and cytokeratin 19 (CK19) were evaluated to distinguish PTC from other benign thyroid lesions (BTL). We studied 23 cases of papillary thyroid overt carcinomas, 57 papillary thyroid microcarcinomas, five follicular adenomas, five cases of Hashimoto's thyroiditis, and 12 nodular hyperplasias.
RESULTS
The statistical analysis showed significantly different expressions of CD56, HMCK, GAL3, and CK19 in PTC vs other BTL. The diagnostic specificity of HMCK and CD56 (90.9% and 72.7%, respectively) was higher than that of GAL3 and CK19 (50.0% and 36.4%, respectively). However, the sensitivity of HMCK and CD56 detection (92.5% and 95.0%, respectively) was lower than that of GAL3 and CK19 (98.8% and 100.0%, respectively). The combined use of CD56, HMCK, GAL3, and CK19 showed 87.5% sensitivity, 100.0% specificity, and 100.0% positive predictive value in differentiating PTC from other BTL.
CONCLUSIONS
Although the differential diagnosis of thyroid follicular lesions are based on histological and cytomorphological criteria, CD56 and HMCK might be useful markers for diagnosing PTC.

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Pallavi Priyadarshini, Manoj Kumar Patro, Prasanta Kumar Das
MGM Journal of Medical Sciences.2023; 10(2): 176. CrossRef
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Uiju Cho, Yourha Kim, Sora Jeon, Chan Kwon Jung
Applied Immunohistochemistry & Molecular Morphology.2022; 30(5): 389. CrossRef
CD-56 IMMUNOREACTIVITY IN FOLLICULAR CELL DERIVED LESIONS OF THYROID
Elvin Merin Cherian, Priya P. V, Sankar S
Journal of Evolution of Medical and Dental Sciences.2018; 7(17): 2066. CrossRef
Diagnostic utility of CK19 and CD56 in the differentiation of thyroid papillary carcinoma from its mimics
Nehal S. Abouhashem, Suzan M. Talaat
Pathology - Research and Practice.2017; 213(5): 509. CrossRef
Use of CD56 and cyclin D1 in differentiating thyroid hyperplasia from papillary thyroid carcinoma
Maha E. Salama, Wael S. Ibrahim
Egyptian Journal of Pathology.2016; 36(1): 39. CrossRef
CD56, HBME-1 and cytokeratin 19 expressions in papillary thyroid carcinoma and nodular thyroid lesions
Senay Erdogan-Durmus, Deniz Ozcan, Enver Yarikkaya, Ali Kurt, Aynur Arslan
Journal of Research in Medical Sciences.2016;[Epub] CrossRef
Defining the value of CD56, CK19, Galectin 3 and HBME-1 in diagnosis of follicular cell derived lesions of thyroid with systematic review of literature
Duško Dunđerović, Jasmina Marković Lipkovski, Ivan Boričic, Ivan Soldatović, Vesna Božic, Dubravka Cvejić, Svetislav Tatić
Diagnostic Pathology.2015;[Epub] CrossRef
Utility of immunohistochemical markers in differential diagnosis of follicular cell-derived thyroid lesions
HananAlSaeid Alshenawy
Journal of Microscopy and Ultrastructure.2014; 2(3): 127. CrossRef
Utility of Immunohistochemical Markers in Diagnosis of Follicular Cell Derived Thyroid Lesions
Hanan AlSaeid Alshenawy
Pathology & Oncology Research.2014; 20(4): 819. CrossRef
Potential diagnostic utility of CD56 and claudin-1 in papillary thyroid carcinoma and solitary follicular thyroid nodules
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Editorial

Molecular Biologic Techniques in Cytopathologic Diagnosis.: Tae Sook Hwang; Korean J Pathol. 2009;43(5):387-392.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.5.387

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Abstract PDF

Molecular diagnosis is an application of the knowledge on molecular mechanisms of disease to diagnosis, therapeutic decision-making, and prognostication. Basically any molecular diagnostic technique could be used in molecular diagnostic cytopathology. Currently applicable molecular techniques in the cytopathology field include PCR based molecular techniques (SSCP, DHPLC, RFLP, LOH, MSI, RT-PCR, QRT-PCR, allele-specific PCR, sequencing, and methylation analysis), FISH, cDNA microarray, aCGH, and reverse-phase protein microarray, etc. Exfoliative cytology as well as fine needle aspiration cytology specimen can be used for analysis. In order to obtain a successful result, collection of target cells without contamination of the blood cells, inflammatory cells including histiocytes, and stromal cells, and a good DNA yield are most important. Molecular diagosis finds its full meaning when interpreted by those who can combine the clinical background of the disease with morphological, immunocytochemical, and molecular diagnostic results. Therefore, these assays would fulfill their full potential when interpreted by the cytopathologists.

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Original Article

The Utility of HMW-CK and CK5/6 Immunohistochemical Stains for Differentiating Ductal Proliferative Lesions and Ducal Carcinoma of the Breast.: Sung Hee Son, Ju Yeon Song, Hye Kyoung Yoon; Korean J Pathol. 2008;42(1):21-26.

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Abstract PDF: BACKGROUND
Basal-type cytokeratins may help to distinguish benign from malignant intraductal proliferative lesions. The basal-type cytokeratins expression is markedly decreased or absent in atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and invasive ductal carcinomas (IDC). However, the expression patterns vary according to the antibodies that are used for staining.
METHODS
HMW-CK (clone 34 E12) was applied to 175 lesions, and CK5/6 (clone D5/16B4) was applied to 145 lesions. The specimens were IDC (n=165), DCIS (n=35), ADH (n=37), florid ductal hyperplasia (FDH) (n=38) and columnar cell lesion (CCL) (n=45). The expression patterns of HMW-CK and CK5/6 were categorized as negative, focal positive and positive.
RESULTS
Loss of the HMW-CK expression was noted in 76% (66/87) of the IDC, 78% (21/27) of the DCIS, 78% (21/28) of the ADH, and 55% (10/18) of the FDH. Loss of the CK5/6 expression was found in 96% (75/78) of the IDC, in all the DCIS (n=8) and ADH (n=9), and in none of the FDH (n=20). Loss of the CK5/6 expression is more reliable than that of the HMW-CK expression for differentiating FDH, ADH and malignant intraductal proliferatve lesions. Eleven (73%) of 15 CCLs revealed the loss of the HMW-CK expression, but all the CCLs (n=30) were negative for CK5/6 (p=0.0161).
CONCLUSION
CK5/6 antibody is more reliable than HMW-CK antibody for differentiating FDH from ADH or DCIS, and for discriminating CCL.

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