Journal of Pathology and Translational Medicine

Review

Clinical practice recommendations for the use of next-generation sequencing in patients with solid cancer: a joint report from KSMO and KSP: Miso Kim, Hyo Sup Shim, Sheehyun Kim, In Hee Lee, Jihun Kim, Shinkyo Yoon, Hyung-Don Kim, Inkeun Park, Jae Ho Jeong, Changhoon Yoo, Jaekyung Cheon, In-Ho Kim, Jieun Lee, Sook Hee Hong, Sehhoon Park, Hyun Ae Jung, Jin Won Kim, Han Jo Kim, Yongjun Cha, Sun Min Lim, Han Sang Kim, Choong-Kun Lee, Jee Hung Kim, Sang Hoon Chun, Jina Yun, So Yeon Park, Hye Seung Lee, Yong Mee Cho, Soo Jeong Nam, Kiyong Na, Sun Och Yoon, Ahwon Lee, Kee-Taek Jang, Hongseok Yun, Sungyoung Lee, Jee Hyun Kim, Wan-Seop Kim; Received September 15, 2023 Accepted November 1, 2023 Published online January 10, 2024; DOI: https://doi.org/10.4132/jptm.2023.11.01 [Epub ahead of print]

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

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.

Fatty acid synthetase expression in triple-negative breast cancer: Jin Hee Park, Hye Seung Han, So Dug Lim, Wook Youn Kim, Kyoung Sik Park, Young Bum Yoo, Seung Eun Lee, Wan-Seop Kim; J Pathol Transl Med. 2022;56(2):73-80. Published online January 21, 2022; DOI: https://doi.org/10.4132/jptm.2021.10.27

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Abstract PDF

Background
Triple-negative breast cancer (TNBC) has a relatively poor prognosis. Research has identified potential metabolic targets, including fatty acid metabolism, in TNBC. The absence of effective target therapies for TNBC led to exploration of the role of fatty acid synthetase (FASN) as a potential target for TNBC therapy. Here, we analyzed the expression of FASN, a representative lipid metabolism–related protein, and investigated the association between FASN expression and Ki-67 and the programmed death ligand 1 (PD-L1) biomarkers in TNBC.
Methods
Immunohistochemical expression of FASN was analyzed in 166 patients with TNBC. For analytical purposes, patients with 0–1+ FASN staining were grouped as low-grade FASN and patients with 2–3+ FASN staining as high-grade FASN.
Results
FASN expression was observed in 47.1% of TNBC patients. Low and high expression of FASN was identified in 75.9% and 24.1%, respectively, and no statistically significant difference was found in T category, N category, American Joint Committee on Cancer stage, or recurrence rate between the low and high-FASN expression groups. Ki-67 proliferation level was significantly different between the low and high-FASN expression groups. FASN expression was significantly related to Ki-67 as the level increased. There was no significant difference in PD-L1 positivity between the low- and high-FASN expression groups.
Conclusions
We identified FASN expression in 166 TNBC patients. The Ki-67 proliferation index was positively correlated with FASN level, indicating higher proliferation activity as FASN increases. However, there was no statistical association with PD-L1 SP142, the currently FDA-approved assay, or FASN expression level.

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WITHDRAWN:A Clinicopathologic Study of 220 Cases of Pulmonary Sclerosing Pneumocytoma in Korea: A Nationwide Survey: Myunghee Kang, Seung Yeon Ha, Joung Ho Han, Mee Sook Roh, Se Jin Jang, Hee Jin Lee, Heae Surng Park, Geon Kook Lee, Kyo Young Lee, Jin-Haeng Chung, Yoo Duk Choi, Chang Hun Lee, Lucia Kim, Myoung Ja Chung, Soon Hee Jung, Gou Young Kim, Wan-Seop Kim; Received April 4, 2018 Accepted July 9, 2018 Published online July 16, 2018; DOI: https://doi.org/10.4132/jptm.2018.07.10 [Accepted]

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Review

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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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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Sunhee Chang, Hyo Sup Shim, Tae Jung Kim, Yoon-La Choi, Wan Seop Kim, Dong Hoon Shin, Lucia Kim, Heae Surng Park, Geon Kook Lee, Chang Hun Lee
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Original Article

Characteristics of Cutaneous Lymphomas in Korea According to the New WHO-EORTC Classification: Report of a Nationwide Study: Jae Ho Han, Young-Hyeh Ko, Yun Kyung Kang, Wan-Seop Kim, Yoon Jung Kim, Insun Kim, Hyun-Jung Kim, Soo Kee Min, Chan-Kum Park, Chan-Sik Park, Bong-Kyung Shin, Woo Ick Yang, Young-Ha Oh, Jong Sil Lee, Juhie Lee, Tae Hui Lee, Hyekyung Lee, Ho Jung Lee, Yoon Kyung Jeon, Hee Jeong Cha, Yoo-Duk Choi, Chul Woo Kim; Korean J Pathol. 2014;48(2):126-132. Published online April 28, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.2.126

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Abstract PDF

Background

Previously, cutaneous lymphomas were classified according to either the European Organization for the Research and Treatment of Cancer (EORTC) or the World Health Organization (WHO) classification paradigms. The aim of this study was to determine the relative frequency of Korean cutaneous lymphoma according to the new WHO-EORTC classification system.

Methods

A total of 517 patients were recruited during a recent 5 year-period (2006-2010) from 21 institutes and classified according to the WHO-EORTC criteria.

Results

The patients included 298 males and 219 females, and the mean age at diagnosis was 49 years. The lesions preferentially affected the trunk area (40.2%). The most frequent subtypes in order of decreasing prevalence were mycosis fungoides (22.2%), peripheral T-cell lymphoma (17.2%), CD30+ T-cell lymphoproliferative disorder (13.7%), and extranodal natural killer/T (NK/T) cell lymphoma, nasal type (12.0%). Diffuse large B-cell lymphoma accounted for 11.2% of cases, half of which were secondary cutaneous involvement; other types of B-cell lymphoma accounted for less than 1% of cases.

Conclusions

In comparison with data from Western countries, this study revealed relatively lower rates of mycosis fungoides and B-cell lymphoma in Korean patients, as well as higher rates of subcutaneous panniculitis-like T-cell lymphoma and NK/T cell lymphoma.

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Brief Case Report

Neuroendocrine Dysplasia Combined in a Tubular Adenoma of Rectum: A Case Report: So-Young Lee, Dae-Yong Hwang, Tae Sook Hwang, Wan-Seop Kim, So Dug Lim, Wook Youn Kim, Se-Hun Kim, Hye Seung Han; Korean J Pathol. 2013;47(5):495-498. Published online October 25, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.5.495

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Inayat GILL, Christienne SHAMS, Elisa QUIROZ, Subhashree M. KRISHNAN, Susanna GAIKAZIAN
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Review & Perspective

Guideline Recommendations for EGFR Mutation Testing in Lung Cancer: Proposal of the Korean Cardiopulmonary Pathology Study Group: Hyo Sup Shim, Jin-Haeng Chung, Lucia Kim, Sunhee Chang, Wan-Seop Kim, Geon Kook Lee, Soon-Hee Jung, Se Jin Jang; Korean J Pathol. 2013;47(2):100-106. Published online April 24, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.2.100

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Abstract PDF

Mutations of the epidermal growth factor receptor (EGFR) are the strongest predictive factor for response to EGFR tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib. EGFR TKIs are approved in Korea as a first-line treatment for lung cancer patients with mutated EGFR. Rapid and accurate EGFR mutation testing is essential for patient selection and establishing targeted therapies with EGFR TKIs. Thus, a standard set of guideline recommendations for EGFR mutation testing suitable for the Korean medical community is necessary. In this article, we propose a set of guideline recommendations for EGFR mutation testing that was discussed and approved by the Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists.

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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
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Original Article

Interobserver Variability in Diagnosing High-Grade Neuroendocrine Carcinoma of the Lung and Comparing It with the Morphometric Analysis: Seung Yeon Ha, Joungho Han, Wan-Seop Kim, Byung Seong Suh, Mee Sook Roh; Korean J Pathol. 2012;46(1):42-47. Published online February 23, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.1.42

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Abstract PDF

Background

Distinguishing small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC) of the lung is difficult with little information about interobserver variability.

Methods

One hundred twenty-nine cases of resected SCLC and LCNEC were independently evaluated by four pathologists and classified according to the 2004 World Health Organization criteria. Agreement was regarded as "unanimous" if all four pathologists agreed on the classification. The kappa statistic was calculated to measure the degree of agreement between pathologists. We also measured cell size using image analysis, and receiver-operating-characteristic curve analysis was performed to evaluate cell size in predicting the diagnosis of high-grade neuroendocrine (NE) carcinomas in 66 cases.

Results

Unanimous agreement was achieved in 55.0% of 129 cases. The kappa values ranged from 0.35 to 0.81. Morphometric analysis reaffirmed that there was a continuous spectrum of cell size from SCLC to LCNEC and showed that tumors with cells falling in the middle size range were difficult to categorize and lacked unanimous agreement.

Conclusions

Our results provide an objective explanation for considerable interobserver variability in the diagnosis of high-grade pulmonary NE carcinomas. Further studies would need to define more stringent and objective definitions of cytologic and architectural characteristics to reliably distinguish between SCLC and LCNEC.

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Immunohistochemical Staining With Neuroendocrine Markers is Essential in the Diagnosis of Neuroendocrine Neoplasms of the Esophagogastric Junction
Dea N.M. Jepsen, Anne-Marie K. Fiehn, Rajendra S. Garbyal, Ulla Engel, Jakob Holm, Birgitte Federspiel
Applied Immunohistochemistry & Molecular Morphology.2021; 29(6): 454. CrossRef
Improving differential diagnosis of pulmonary large cell neuroendocrine carcinoma and small cell lung cancer via a transcriptomic, biological pathway-based machine learning model
Junhong Guo, Likun Hou, Wei Zhang, Zhengwei Dong, Lei Zhang, Chunyan Wu
Translational Oncology.2021; 14(12): 101222. CrossRef
Are neuroendocrine negative small cell lung cancer and large cell neuroendocrine carcinoma with WT RB1 two faces of the same entity?
Dmitriy Sonkin, Anish Thomas, Beverly A Teicher
Lung Cancer Management.2019; 8(2): LMT13. CrossRef
Ki-67 labeling index of neuroendocrine tumors of the lung has a high level of correspondence between biopsy samples and surgical specimens when strict counting guidelines are applied
Alessandra Fabbri, Mara Cossa, Angelica Sonzogni, Mauro Papotti, Luisella Righi, Gaia Gatti, Patrick Maisonneuve, Barbara Valeri, Ugo Pastorino, Giuseppe Pelosi
Virchows Archiv.2017; 470(2): 153. CrossRef
The Use of Immunohistochemistry Improves the Diagnosis of Small Cell Lung Cancer and Its Differential Diagnosis. An International Reproducibility Study in a Demanding Set of Cases
Erik Thunnissen, Alain C. Borczuk, Douglas B. Flieder, Birgit Witte, Mary Beth Beasley, Jin-Haeng Chung, Sanja Dacic, Sylvie Lantuejoul, Prudence A. Russell, Michael den Bakker, Johan Botling, Elisabeth Brambilla, Erienne de Cuba, Kim R. Geisinger, Kenzo
Journal of Thoracic Oncology.2017; 12(2): 334. CrossRef
Reply to Letter “The Use of Immunohistochemistry Improves the Diagnosis of Small Cell Lung Cancer and Its Differential Diagnosis. An International Reproducibility Study in a Demanding Set of Cases.”
Erik Thunnissen, Birgit I. Witte, Masayuki Noguchi, Yasushi Yatabe
Journal of Thoracic Oncology.2017; 12(6): e70. CrossRef
What clinicians are asking pathologists when dealing with lung neuroendocrine neoplasms?
Giuseppe Pelosi, Alessandra Fabbri, Mara Cossa, Angelica Sonzogni, Barbara Valeri, Luisella Righi, Mauro Papotti
Seminars in Diagnostic Pathology.2015; 32(6): 469. CrossRef
Unraveling Tumor Grading and Genomic Landscape in Lung Neuroendocrine Tumors
Giuseppe Pelosi, Mauro Papotti, Guido Rindi, Aldo Scarpa
Endocrine Pathology.2014; 25(2): 151. CrossRef
Grading the neuroendocrine tumors of the lung: an evidence-based proposal
G Rindi, C Klersy, F Inzani, G Fellegara, L Ampollini, A Ardizzoni, N Campanini, P Carbognani, T M De Pas, D Galetta, P L Granone, L Righi, M Rusca, L Spaggiari, M Tiseo, G Viale, M Volante, M Papotti, G Pelosi
Endocrine-Related Cancer.2014; 21(1): 1. CrossRef
Controversial issues and new discoveries in lung neuroendocrine tumors
Giuseppe Pelosi, Kenzo Hiroshima, Mari Mino-Kenudson
Diagnostic Histopathology.2014; 20(10): 392. CrossRef
BAI3, CDX2 and VIL1: a panel of three antibodies to distinguish small cell from large cell neuroendocrine lung carcinomas
Muhammad F Bari, Helen Brown, Andrew G Nicholson, Keith M Kerr, John R Gosney, William A Wallace, Irshad Soomro, Salli Muller, Danielle Peat, Jonathan D Moore, Lesley A Ward, Maxim B Freidin, Eric Lim, Manu Vatish, David R J Snead
Histopathology.2014; 64(4): 547. CrossRef
Neuroendocrine tumours—challenges in the diagnosis and classification of pulmonary neuroendocrine tumours
M A den Bakker, F B J M Thunnissen
Journal of Clinical Pathology.2013; 66(10): 862. CrossRef
Morphologic Analysis of Pulmonary Neuroendocrine Tumors
Seung Seok Lee, Myunghee Kang, Seung Yeon Ha, Jungsuk An, Mee Sook Roh, Chang Won Ha, Jungho Han
Korean Journal of Pathology.2013; 47(1): 16. CrossRef
Altered expression of microRNA miR‐21, miR‐155, and let‐7a and their roles in pulmonary neuroendocrine tumors
Hyoun Wook Lee, Eun Hee Lee, Seung Yeon Ha, Chang Hun Lee, Hee Kyung Chang, Sunhee Chang, Kun Young Kwon, Il Seon Hwang, Mee Sook Roh, Jeong Wook Seo
Pathology International.2012; 62(9): 583. CrossRef

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