Journal of Pathology and Translational Medicine

Case Study

Diagnostic conundrums of schwannomas: two cases highlighting morphological extremes and diagnostic challenges in biopsy specimens of soft tissue tumors: Chankyung Kim, Yang-Guk Chung, Chan Kwon Jung; J Pathol Transl Med. 2023;57(5):278-283. Published online August 24, 2023; DOI: https://doi.org/10.4132/jptm.2023.07.13

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Abstract PDF: Schwannomas are benign, slow-growing peripheral nerve sheath tumors commonly occurring in the head, neck, and flexor regions of the extremities. Although most schwannomas are easily diagnosable, their variable morphology can occasionally create difficulty in diagnosis. Reporting pathologists should be aware that schwannomas can exhibit a broad spectrum of morphological patterns. Clinical and radiological examinations can show correlation and should be performed, in conjunction with ancillary tests, when appropriate. Furthermore, deferring a definitive diagnosis until excision may be necessary for small biopsy specimens and frozen sections. This report underscores these challenges through examination of two unique schwannoma cases, one predominantly cellular and the other myxoid, both of which posed significant challenges in histological interpretation.

Review

Reevaluating diagnostic categories and associated malignancy risks in thyroid core needle biopsy: Chan Kwon Jung; J Pathol Transl Med. 2023;57(4):208-216. Published online July 11, 2023; DOI: https://doi.org/10.4132/jptm.2023.06.20

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As the application of core needle biopsy (CNB) in evaluating thyroid nodules rises in clinical practice, the 2023 Korean Thyroid Association Management Guidelines for Patients with Thyroid Nodules have officially recognized its value for the first time. CNB procures tissue samples preserving both histologic structure and cytologic detail, thereby supplying substantial material for an accurate diagnosis and reducing the necessity for repeated biopsies or subsequent surgical interventions. The current review introduces the risk of malignancy within distinct diagnostic categories, emphasizing the implications of noninvasive follicular thyroid neoplasm with papillary-like nuclear features on these malignancy risks. Prior research has indicated diagnostic challenges associated with follicular-patterned lesions, resulting in notable variation within indeterminate diagnostic categories. The utilization of mutation-specific immunostaining in CNB enhances the accuracy of lesion classification. This review underlines the essential role of a multidisciplinary approach in diagnosing follicular-patterned lesions and the potential of mutation-specific immunostaining to strengthen diagnostic consensus and inform patient management decisions.

Citations

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Diagnostic implication of thyroid spherules for cytological diagnosis of thyroid nodules
Heeseung Sohn, Kennichi Kakudo, Chan Kwon Jung
Cytopathology.2024; 35(3): 383. CrossRef
A Narrative Review of the 2023 Korean Thyroid Association Management Guideline for Patients with Thyroid Nodules
Eun Kyung Lee, Young Joo Park, Chan Kwon Jung, Dong Gyu Na
Endocrinology and Metabolism.2024; 39(1): 61. CrossRef
The Diagnostic Role of Repeated Biopsy of Thyroid Nodules with Atypia of Undetermined Significance with Architectural Atypia on Core-Needle Biopsy
Hye Hyeon Moon, Sae Rom Chung, Young Jun Choi, Tae-Yon Sung, Dong Eun Song, Tae Yong Kim, Jeong Hyun Lee, Jung Hwan Baek
Endocrinology and Metabolism.2024; 39(2): 300. CrossRef

Original Articles

Expression of specific microRNAs in tissue and plasma in colorectal cancer: Allan Fellizar, Vivencio Refuerzo, John Donnie Ramos, Pia Marie Albano; J Pathol Transl Med. 2023;57(3):147-157. Published online May 3, 2022; DOI: https://doi.org/10.4132/jptm.2022.02.19

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Abstract PDF

Background
MicroRNAs (miRNA/miR) play significant roles in the regulation of cell differentiation, cell cycle progression, and apoptosis. They become dysregulated during carcinogenesis and are eventually released into the circulation, enabling their detection in body fluids. Thus, this study compared the miRNA expression in tissue and plasma samples of colorectal cancer (CRC) patients and clinically healthy controls and determined miRNA expression as a potential CRC biomarker.
Methods
Using quantitative reverse transcription polymerase chain reaction (RT-qPCR), miR-21-5p, miR-29a-3p, miR-92a-3p, miR-135b-5p, miR-196b-5p, and miR-197-3p, expression was analyzed and compared between the malignant (n = 41) and the adjacent neoplasm free mucosal tissues (n = 41) of CRC patients. The findings were validated in plasma samples (n = 36) collected from the same CRC patients prior to surgery or any form of treatment and compared to plasma from their age and sex-matched controls (n = 36).
Results
MiR-21-5p, miR-29a-3p, miR-92a-3p, and miR- 196b-5p were upregulated and miR-135b-5p was downregulated in CRC malignant tissues compared to their expression in adjacent neoplasm-free tissue. This was further observed in the plasma of the same CRC cases compared to controls. MiR-92a-3p showed itself the most sensitive (0.93; p < .001) and most specific (0.95; p < .001) in detecting CRC in tissue. In plasma, miR-196b-5p was the most sensitive (0.97; p < .001) and specific (0.94; p < .001) in detecting CRC. Plasma miR-92a-3p and miR-196b-5p were the most sensitive (0.95; p < .001) and specific (0.94; p < .001) in the early detection of CRC.
Conclusions
Results show that specific miRNAs dysregulated in malignant tissues are released and can be detected in the circulation, supporting their potential as non-invasive biomarkers of CRC.

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Yujian Xia, Chaoran Yu, Ernest Johann Helwig, Yousheng Li
Technology in Cancer Research & Treatment.2023;[Epub] CrossRef
HNRNPA2B1-Mediated MicroRNA-92a Upregulation and Section Acts as a Promising Noninvasive Diagnostic Biomarker in Colorectal Cancer
Yiling Li, Kexin Li, Xiaoying Lou, Yue Wu, Samuel Seery, Danfei Xu, Yuqing Pei, Benheng Qian, Yuxin Wu, Shuang Liang, Kui Wu, Wei Cui
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Role of salivary miRNAs in the diagnosis of gastrointestinal disorders: a mini-review of available evidence
Maria Oana Săsăran, Claudia Bănescu
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Chau-Ming Kan, Xiao Meng Pei, Martin Ho Yin Yeung, Nana Jin, Simon Siu Man Ng, Hin Fung Tsang, William Chi Shing Cho, Aldrin Kay-Yuen Yim, Allen Chi-Shing Yu, Sze Chuen Cesar Wong
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Cancers.2023; 15(15): 3930. CrossRef

A multicenter study of interobserver variability in pathologic diagnosis of papillary breast lesions on core needle biopsy with WHO classification: Hye Ju Kang, Sun Young Kwon, Ahrong Kim, Woo Gyeong Kim, Eun Kyung Kim, Ae Ree Kim, Chungyeul Kim, Soo Kee Min, So Young Park, Sun Hee Sung, Hye Kyoung Yoon, Ahwon Lee, Ji Shin Lee, Hyang Im Lee, Ho Chang Lee, Sung Chul Lim, Sun Young Jun, Min Jung Jung, Chang Won Jung, Soo Youn Cho, Eun Yoon Cho, Hye Jeong Choi, So Yeon Park, Jee Yeon Kim, In Ae Park, Youngmee Kwon; J Pathol Transl Med. 2021;55(6):380-387. Published online October 6, 2021; DOI: https://doi.org/10.4132/jptm.2021.07.29

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Abstract PDF Supplementary Material

Background
Papillary breast lesions (PBLs) comprise diverse entities from benign and atypical lesions to malignant tumors. Although PBLs are characterized by a papillary growth pattern, it is challenging to achieve high diagnostic accuracy and reproducibility. Thus, we investigated the diagnostic reproducibility of PBLs in core needle biopsy (CNB) specimens with World Health Organization (WHO) classification.
Methods
Diagnostic reproducibility was assessed using interobserver variability (kappa value, κ) and agreement rate in the pathologic diagnosis of 60 PBL cases on CNB among 20 breast pathologists affiliated with 20 medical institutions in Korea. This analysis was performed using hematoxylin and eosin (H&E) staining and immunohistochemical (IHC) staining for cytokeratin 5 (CK5) and p63. The pathologic diagnosis of PBLs was based on WHO classification, which was used to establish simple classifications (4-tier, 3-tier, and 2-tier).
Results
On WHO classification, H&E staining exhibited ‘fair agreement’ (κ = 0.21) with a 47.0% agreement rate. Simple classifications presented improvement in interobserver variability and agreement rate. IHC staining increased the kappa value and agreement rate in all the classifications. Despite IHC staining, the encapsulated/solid papillary carcinoma (EPC/SPC) subgroup (κ = 0.16) exhibited lower agreement compared to the non-EPC/SPC subgroup (κ = 0.35) with WHO classification, which was similar to the results of any other classification systems.
Conclusions
Although the use of IHC staining for CK5 and p63 increased the diagnostic agreement of PBLs in CNB specimens, WHO classification exhibited a higher discordance rate compared to any other classifications. Therefore, this result warrants further intensive consensus studies to improve the diagnostic reproducibility of PBLs with WHO classification.

Citations

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Invasive papillary carcinoma of the breast
Shijing Wang, Qingfu Zhang, Xiaoyun Mao
Frontiers in Oncology.2024;[Epub] CrossRef
Encapsulated papillary carcinoma of the breast: A single institution experience
Liang Xu, Qixin Mao, Qiuming Liu, Yufeng Gao, Lihua Luo, Chungen Guo, Wei Qu, Ningning Yan, Yali Cao
Oncology Letters.2023;[Epub] CrossRef
High-risk and selected benign breast lesions diagnosed on core needle biopsy: Evidence for and against immediate surgical excision
Aparna Harbhajanka, Hannah L. Gilmore, Benjamin C. Calhoun
Modern Pathology.2022; 35(11): 1500. CrossRef

Review

Liquid biopsy using extracellular vesicle–derived DNA in lung adenocarcinoma: In Ae Kim, Jae Young Hur, Hee Joung Kim, Seung Eun Lee, Wan Seop Kim, Kye Young Lee; J Pathol Transl Med. 2020;54(6):453-461. Published online October 8, 2020; DOI: https://doi.org/10.4132/jptm.2020.08.13

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Abstract PDF

Blood liquid biopsy has emerged as a way of overcoming the clinical limitations of repeat biopsy by testing for the presence of acquired resistance mutations to therapeutic agents. Despite its merits of repeatability and non-invasiveness, this method is currently only used as a supplemental test due to a relatively low sensitivity rate of 50%–60%, and cannot replace tissue biopsy. The circulating tumor DNAs used in blood liquid biopsies are passive products of fragmented DNA with a short half-life released following tumor cell death; the low sensitivity seen with liquid blood biopsy results from this instability, which makes increasing the sensitivity of this test fundamentally difficult. Extracellular vesicles (EVs) are ideal carriers of cancer biomarkers, as cancer cells secret an abundance of EVs, and the contents of tumor cell-originated EVs reflect the molecular and genetic composition of parental cells. In addition, EV-derived DNAs (EV DNAs) consist of large-sized genomic DNAs and tumor-specific oncogenic mutant DNAs. For these reasons, liquid biopsy using EV DNA has the potential to overcome issues arising from tissue shortages associated with small biopsies, which are often seen in lung cancer patients, and the biopsy product can be used in other diagnostic methods, such as epidermal growth factor receptor (EGFR) mutation testing and next-generation sequencing (NGS). A higher sensitivity can be achieved when EV DNAs obtained from bronchoalveolar lavage fluid (BALF) are used rather than those from blood. BALF, when obtained close to the tumor site, is a promising liquid biopsy tool, as it enables the gathering of both cellular and non-cellular fractions of the tumor microenvironment, and provides increased diagnostic sensitivity when compared to blood.

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Irène Tatischeff
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Isolation of extracellular vesicles from human plasma samples: The importance of controls
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Jae Young Hur, Kye Young Lee
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Original Article

A scoring system for the diagnosis of non-alcoholic steatohepatitis from liver biopsy: Kyoungbun Lee, Eun Sun Jung, Eunsil Yu, Yun Kyung Kang, Mee-Yon Cho, Joon Mee Kim, Woo Sung Moon, Jin Sook Jeong, Cheol Keun Park, Jae-Bok Park, Dae Young Kang, Jin Hee Sohn, So-Young Jin; J Pathol Transl Med. 2020;54(3):228-236. Published online April 15, 2020; DOI: https://doi.org/10.4132/jptm.2020.03.07

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Abstract PDF

Background
Liver biopsy is the essential method to diagnose non-alcoholic steatohepatitis (NASH), but histological features of NASH are too subjective to achieve reproducible diagnoses in early stages of disease. We aimed to identify the key histological features of NASH and devise a scoring model for diagnosis.
Methods
Thirteen pathologists blindly assessed 12 histological factors and final histological diagnoses (‘not-NASH,’ ‘borderline,’ and ‘NASH’) of 31 liver biopsies that were diagnosed as non-alcoholic fatty liver disease (NAFLD) or NASH before and after consensus. The main histological parameters to diagnose NASH were selected based on histological diagnoses and the diagnostic accuracy and agreement of 12 scoring models were compared for final diagnosis and the NAFLD Activity Score (NAS) system.
Results
Inter-observer agreement of final diagnosis was fair (κ = 0.25) before consensus and slightly improved after consensus (κ = 0.33). Steatosis at more than 5% was the essential parameter for diagnosis. Major diagnostic factors for diagnosis were fibrosis except 1C grade and presence of ballooned cells. Minor diagnostic factors were lobular inflammation ( ≥ 2 foci/ × 200 field), microgranuloma, and glycogenated nuclei. All 12 models showed higher inter-observer agreement rates than NAS and post-consensus diagnosis (κ = 0.52–0.69 vs. 0.33). Considering the reproducibility of factors and practicability of the model, summation of the scores of major (× 2) and minor factors may be used for the practical diagnosis of NASH.
Conclusions
A scoring system for the diagnosis of NAFLD would be helpful as guidelines for pathologists and clinicians by improving the reproducibility of histological diagnosis of NAFLD.

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Changes in indications for outpatient percutaneous liver biopsy over 5 years: from hepatitis C to fatty liver disease
Marlone Cunha-Silva, Luíza D. Torres, Mariana F. Fernandes, Tirzah de M. Lopes Secundo, Marina C.G. Moreira, Ademar Yamanaka, Leonardo T. Monici, Larissa B. Eloy da Costa, Daniel F. Mazo, Tiago Sevá-Pereira
Gastroenterología y Hepatología.2022; 45(8): 579. CrossRef
Changes in indications for outpatient percutaneous liver biopsy over 5 years: from hepatitis C to fatty liver disease
Marlone Cunha-Silva, Luíza D. Torres, Mariana F. Fernandes, Tirzah de M. Lopes Secundo, Marina C.G. Moreira, Ademar Yamanaka, Leonardo T. Monici, Larissa B. Eloy da Costa, Daniel F. Mazo, Tiago Sevá-Pereira
Gastroenterología y Hepatología (English Edition).2022; 45(8): 579. CrossRef

Review

Current status and future perspectives of liquid biopsy in non-small cell lung cancer: Sunhee Chang, Jae Young Hur, Yoon-La Choi, Chang Hun Lee, Wan Seop Kim; J Pathol Transl Med. 2020;54(3):204-212. Published online April 15, 2020; DOI: https://doi.org/10.4132/jptm.2020.02.27

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Abstract PDF

With advances in target therapy, molecular analysis of tumors is routinely required for treatment decisions in patients with advanced non-small cell lung cancer (NSCLC). Liquid biopsy refers to the sampling and analysis of circulating cell-free tumor DNA (ctDNA) in various body fluids, primarily blood. Because the technique is minimally invasive, liquid biopsies are the future in cancer management. Epidermal growth factor receptor (EGFR) ctDNA tests have been performed in routine clinical practice in advanced NSCLC patients to guide tyrosine kinase inhibitor treatment. In the near future, liquid biopsy will be a crucial prognostic, predictive, and diagnostic method in NSCLC. Here we present the current status and future perspectives of liquid biopsy in NSCLC.

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Original Article

Contribution of cytologic examination to diagnosis of poorly differentiated thyroid carcinoma: Na Rae Kim, Jae Yeon Seok, Yoo Seung Chung, Joon Hyop Lee, Dong Hae Chung; J Pathol Transl Med. 2020;54(2):171-178. Published online February 5, 2020; DOI: https://doi.org/10.4132/jptm.2019.12.03

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Abstract PDF

Background
The cytologic diagnosis of poorly differentiated thyroid carcinoma (PDTC) is difficult because it lacks salient cytologic findings and shares cytologic features with more commonly encountered neoplasms. Due to diverse cytologic findings and paucicellularity of PDTC, standardization of cytologic diagnostic criteria is limited. The purpose of this study is to investigate and recognize diverse thyroid findings of fine needle aspiration (FNA) cytology and frozen smear cytology in diagnosis of this rare but aggressive carcinoma.
Methods
The present study included six cases of FNA cytology and frozen smears of histologically diagnosed PDTCs.
Results
PDTC showed cytologic overlap with well-differentiated thyroid carcinomas (WDTCs). Five of six cases showed dedifferentiation arising from well differentiated thyroid carcinomas. Only one de novo PDTC showed highly cellular smears composed of discohesive small cells, high nuclear/cytoplasmic (N/C) ratio, prominent micronucleoli, and irregular nuclei. Retrospectively reviewed, these findings are highly suspicious for PDTC. Cytologic findings of nuclear atypia, pleomorphism, and irregularity were frequently found, whereas scattered small cells were seen only in the de novo case.
Conclusions
Heterogeneous cytologic findings of PDTCs are shared with those of WDTCs and contribute to difficult preoperative cytologic diagnoses. Most PDTCs show dedifferentiation from WDTCs. Albeit rare, de novo PDTC should be considered with cytology showing discohesive small cells with high N/C ratio. This will enable precise diagnosis and prompt treatment of this aggressive malignancy

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Non-papillary thyroid carcinoma diagnoses in The Bethesda System for Reporting Thyroid Cytopathology categories V and VI: An institutional experience
Myunghee Kang, Na Rae Kim, Jae Yeon Seok
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JCEM Case Reports.2023;[Epub] CrossRef
Revisiting the cytomorphological features of poorly differentiated thyroid carcinoma: a comparative analysis with indeterminate thyroid fine-needle aspiration samples
Yazeed Alwelaie, Ali Howaidi, Mohammed Tashkandi, Ahmad Almotairi, Hisham Saied, Moammar Muzzaffar, Doaa Alghamdi
Journal of the American Society of Cytopathology.2023; 12(5): 331. CrossRef
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Review

2019 Practice guidelines for thyroid core needle biopsy: a report of the Clinical Practice Guidelines Development Committee of the Korean Thyroid Association: Chan Kwon Jung, Jung Hwan Baek, Dong Gyu Na, Young Lyun Oh, Ka Hee Yi, Ho-Cheol Kang; J Pathol Transl Med. 2020;54(1):64-86. Published online January 15, 2020; DOI: https://doi.org/10.4132/jptm.2019.12.04

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Abstract PDF

Ultrasound-guided core needle biopsy (CNB) has been increasingly used for the pre-operative diagnosis of thyroid nodules. Since the Korean Society of the Thyroid Radiology published the ‘Consensus Statement and Recommendations for Thyroid CNB’ in 2017 and the Korean Endocrine Pathology Thyroid CNB Study Group published ‘Pathology Reporting of Thyroid Core Needle Biopsy’ in 2015, advances have occurred rapidly not only in the management guidelines for thyroid nodules but also in the diagnostic terminology and classification schemes. The Clinical Practice Guidelines Development Committee of the Korean Thyroid Association (KTA) reviewed publications on thyroid CNB from 1995 to September 2019 and updated the recommendations and statements for the diagnosis and management of thyroid nodules using CNB. Recommendations for the resolution of clinical controversies regarding the use of CNB were based on expert opinion. These practical guidelines include recommendations and statements regarding indications for CNB, patient preparation, CNB technique, biopsy-related complications, biopsy specimen preparation and processing, and pathology interpretation and reporting of thyroid CNB.

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Xuejiao Su, Can Yue, Wanting Yang, Buyun Ma
Frontiers in Endocrinology.2024;[Epub] CrossRef
A Narrative Review of the 2023 Korean Thyroid Association Management Guideline for Patients with Thyroid Nodules
Eun Kyung Lee, Young Joo Park, Chan Kwon Jung, Dong Gyu Na
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Doing more with less: integrating small biopsies in cytology practice
Anjali Saqi, Michiya Nishino, Mauro Saieg, Amy Ly, Abberly Lott Limbach
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Liping Wang, Yuan Wang, Wenliang Lu, Dong Xu, Jincao Yao, Lijing Wang, Lei Xu
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Tapoi Dana Antonia, Lambrescu Ioana Maria, Gheorghisan-Galateanu Ancuta-Augustina
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2023 Korean Thyroid Association Management Guidelines for Patients with Thyroid Nodules
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Reevaluating diagnostic categories and associated malignancy risks in thyroid core needle biopsy
Chan Kwon Jung
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Korean Journal of Radiology.2022; 23(2): 280. CrossRef
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Original Article

Analysis of the molecular subtypes of preoperative core needle biopsy and surgical specimens in invasive breast cancer: Ye Sul Jeong, Jun Kang, Jieun Lee, Tae-Kyung Yoo, Sung Hun Kim, Ahwon Lee; J Pathol Transl Med. 2020;54(1):87-94. Published online November 13, 2019; DOI: https://doi.org/10.4132/jptm.2019.10.14

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Abstract PDF

Background
Accurate molecular classification of breast core needle biopsy (CNB) tissue is important for determining neoadjuvant systemic therapies for invasive breast cancer. The researchers aimed to evaluate the concordance rate (CR) of molecular subtypes between CNBs and surgical specimens.
Methods
This study was conducted with invasive breast cancer patients who underwent surgery after CNB at Seoul St. Mary’s Hospital between December 2014 and December 2017. Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki67 were analyzed using immunohistochemistry. ER and PR were evaluated by Allred score (0–8). HER2 was graded from 0 to +3, and all 2+ cases were reflex tested with silver in situ hybridization. The labeling index of Ki67 was counted by either manual scoring or digital image analysis. Molecular subtypes were classified using the above surrogate markers.
Results
In total, 629 patients were evaluated. The CRs of ER, PR, HER2, and Ki67 were 96.5% (kappa, 0.883; p<.001), 93.0% (kappa, 0.824; p<.001), 99.7% (kappa, 0.988; p<.001), and 78.7% (kappa, 0.577; p<.001), respectively. Digital image analysis of Ki67 in CNB showed better concordance with Ki67 in surgical specimens (CR, 82.3%; kappa, 0.639 for digital image analysis vs. CR, 76.2%; kappa, 0.534 for manual counting). The CRs of luminal A, luminal B, HER2, and triple negative types were 89.0%, 70.0%, 82.9%, and 77.2%, respectively.
Conclusions
CNB was reasonably accurate for determining ER, PR, HER2, Ki67, and molecular subtypes. Using digital image analysis for Ki67 in CNB produced more accurate molecular classifications.

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Chiara Rossi, Sara Fraticelli, Marianna Fanizza, Alberta Ferrari, Elisa Ferraris, Alessia Messina, Angelica Della Valle, Chiara Annunziata Pasqualina Anghelone, Angioletta Lasagna, Gianpiero Rizzo, Lorenzo Perrone, Maria Grazia Sommaruga, Giulia Meloni, S
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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
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Concordance between core needle biopsy and surgical excision specimens for Ki‐67 in breast cancer – a systematic review of the literature
Jahnavi Kalvala, Ruth M Parks, Andrew R Green, Kwok‐Leung Cheung
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İnvaziv Meme Kanserinde Preoperatif Kor İğne Biyopsi ile Postoperatif Cerrahi Spesmenler Arasında ER, PR, HER2 ve Ki67 Açısından Karşılaştırma
Pınar CELEPLİ, Pelin Seher ÖZTEKİN, Salih CELEPLİ, İrem BİGAT, Sema HÜCÜMENOĞLU
Akdeniz Medical Journal.2022; : 179. CrossRef
Concordance of breast cancer biomarker testing in core needle biopsy and surgical specimens: A single institution experience
Jessica A. Slostad, Nicole K. Yun, Aimee E. Schad, Surbhi Warrior, Louis F. Fogg, Ruta Rao
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Shuai Li, Xiaosong Chen, Kunwei Shen
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Review

Provisional Guideline Recommendation for EGFR Gene Mutation Testing in Liquid Samples of Lung Cancer Patients: A Proposal by the Korean Cardiopulmonary Pathology Study Group: Dong Hoon Shin, Hyo Sup Shim, Tae Jung Kim, Heae Surng Park, Yun La Choi, Wan Seop Kim, Lucia Kim, Sun Hee Chang, Joon Seon Song, Hyo jin Kim, Jung Ho Han, Chang Hun Lee, Geon Kook Lee, Se Jin Jang; J Pathol Transl Med. 2019;53(3):153-158. Published online February 28, 2019; DOI: https://doi.org/10.4132/jptm.2019.02.22

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Abstract PDF

Liquid biopsy for detection of mutation from circulating tumor DNA is a new technology which is attractive in that it is non-invasive. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) is an effective first line drug for advanced non-small cell lung cancer patients who harbor activating EGFR mutation. During the course of treatment, resistance against TKI arises which can be contributed to EGFR T790M mutation in about 50–60% of patients. Third generation TKI may overcome the resistance. In patients who cannot undergo tissue biopsy due to variable reasons, liquid biopsy is an excellent alternative for the detection of EGFR T790M mutation. However, this relatively novel method requires standardization and vigorous quality insurance. Thus, a standard set of guideline recommendations for liquid biopsy for EGFR mutation testing suitable for the Korean medical community is necessary. In this article, we propose a set of provisional guideline recommendations that was discussed and approved by the Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists.

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Improving non-small-cell lung cancer survival through molecular characterization: Perspective of a multidisciplinary expert panel
M.G.O. Fernandes, A.S. Vilariça, B. Fernandes, C. Camacho, C. Saraiva, F. Estevinho, H. Novais e Bastos, J.M. Lopes, P. Fidalgo, P. Garrido, S. Alves, S. Silva, T. Sequeira, F. Barata
Pulmonology.2024; 30(1): 4. CrossRef
Exosomes in Lung Cancer: Actors and Heralds of Tumor Development
Amaia Sandúa, Estibaliz Alegre, Álvaro González
Cancers.2021; 13(17): 4330. CrossRef
Molecular biomarker testing for non–small cell lung cancer: consensus statement of the Korean Cardiopulmonary Pathology Study Group
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
Journal of Pathology and Translational Medicine.2021; 55(3): 181. CrossRef
Current status and future perspectives of liquid biopsy in non-small cell lung cancer
Sunhee Chang, Jae Young Hur, Yoon-La Choi, Chang Hun Lee, Wan Seop Kim
Journal of Pathology and Translational Medicine.2020; 54(3): 204. CrossRef
Prevalence of T790M mutation among TKI-therapy resistant Lebanese lung cancer patients based on liquid biopsy analysis: a first report from a major tertiary care center
Hazem Assi, Arafat Tfayli, Nada Assaf, Sarah Abou Daya, Aram H. Bidikian, Dima Kawsarani, Puzant Fermanian, Ghazi Zaatari, Rami Mahfouz
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Original Articles

The Usefulness of Immunocytochemistry of CD56 in Determining Malignancy from Indeterminate Thyroid Fine-Needle Aspiration Cytology: Hyunseo Cha, Ju Yeon Pyo, Soon Won Hong; J Pathol Transl Med. 2018;52(6):404-410. Published online October 15, 2018; DOI: https://doi.org/10.4132/jptm.2018.09.20

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Abstract PDF

Background
Fine-needle aspiration cytology serves as a safe, economical tool in evaluating thyroid nodules. However, about 30% of the samples are categorized as indeterminate. Hence, many immunocytochemistry markers have been studied, but there has not been a single outstanding marker. We studied the efficacy of CD56 with human bone marrow endothelial cell marker-1 (HBME-1) in diagnosis in the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) category III.
Methods
We reviewed ThinPrep liquid-based cytology (LBC) samples with Papanicolaou stain from July 1 to December 31, 2016 (2,195 cases) and selected TBSRTC category III cases (n = 363). Twenty-six cases were histologically confirmed as benign (six cases, 23%) or malignant (20 cases, 77%); we stained 26 LBC slides with HBME-1 and CD56 through the cell transfer method. For evaluation of reactivity of immunocytochemistry, we chose atypical follicular cell clusters.
Results
CD56 was not reactive in 18 of 20 cases (90%) of malignant nodules and showed cytoplasmic positivity in five of six cases (83%) of benign nodules. CD56 showed high sensitivity (90.0%) and relatively low specificity (83.3%) in detecting malignancy (p = .004). HBME-1 was reactive in 17 of 20 cases (85%) of malignant nodules and was not reactive in five of six cases (83%) of benign nodules. HBME-1 showed slightly lower sensitivity (85.0%) than CD56. The specificity in detecting malignancy by HBME-1 was similar to that of CD56 (83.3%, p = .008). CD56 and HBME-1 tests combined showed lower sensitivity (75.0% vs 90%) and higher specificity (93.8% vs 83.3%) in detecting malignancy compared to using CD56 alone.
Conclusions
Using CD56 alone showed relatively low specificity despite high sensitivity for detecting malignancy. Combining CD56 with HBME-1 could increase the specificity. Thus, we suggest that CD56 could be a useful preoperative marker for differential diagnosis of TBSRTC category III samples.

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Preoperative evaluation of thyroid nodules – Diagnosis and management strategies
Tapoi Dana Antonia, Lambrescu Ioana Maria, Gheorghisan-Galateanu Ancuta-Augustina
Pathology - Research and Practice.2023; 246: 154516. CrossRef
Immunocytochemistry in thyroid cytology and its multiple roles: a systematic review
Federica Policardo, Pietro Tralongo, Angela Feraco, Federica Vegni, Angela Carlino, Alfredo Pontecorvi, Celestino Pio Lombardi, Marco Raffaelli, Francesco Pierconti, Luigi Maria Larocca, Esther Diana Rossi
Diagnostic Histopathology.2023; 29(8): 386. CrossRef
Paving the path toward multi-omics approaches in the diagnostic challenges faced in thyroid pathology
Isabella Piga, Vincenzo L’Imperio, Giulia Capitoli, Vanna Denti, Andrew Smith, Fulvio Magni, Fabio Pagni
Expert Review of Proteomics.2023; 20(12): 419. CrossRef
CD56 Expression in Papillary Thyroid Carcinoma Is Highly Dependent on the Histologic Subtype: A Potential Diagnostic Pitfall
Uiju Cho, Yourha Kim, Sora Jeon, Chan Kwon Jung
Applied Immunohistochemistry & Molecular Morphology.2022; 30(5): 389. CrossRef

Molecular Screening of Small Biopsy Samples Using Next-Generation Sequencing in Korean Patients with Advanced Non-small Cell Lung Cancer: Korean Lung Cancer Consortium (KLCC-13-01): Bo Mi Ku, Mi Hwa Heo, Joo-Hang Kim, Byoung Chul Cho, Eun Kyung Cho, Young Joo Min, Ki Hyeong Lee, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, Tae Jung Kim, Ho Yun Lee, Hojoong Kim, Kyung-Jong Lee, Myung-Ju Ahn; J Pathol Transl Med. 2018;52(3):148-156. Published online March 26, 2018; DOI: https://doi.org/10.4132/jptm.2018.03.12

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Abstract PDF

Background
Non-small cell lung cancer (NSCLC) is a common type of cancer with poor prognosis. As individual cancers exhibit unique mutation patterns, identifying and characterizing gene mutations in NSCLC might help predict patient outcomes and guide treatment. The aim of this study was to evaluate the clinical adequacy of molecular testing using next-generation sequencing (NGS) for small biopsy samples and characterize the mutational landscape of Korean patients with advanced NSCLC.
Methods
DNA was extracted from small biopsy samples of 162 patients with advanced NSCLC. Targeted NGS of genomic alterations was conducted using Ion AmpliSeq Cancer Hotspot Panel v2.
Results
The median age of patients was 64 years (range, 32 to 83 years) and the majority had stage IV NSCLC at the time of cancer diagnosis (90%). Among the 162 patients, 161 patients (99.4%) had novel or hotspot mutations (range, 1 to 21 mutated genes). Mutations were found in 41 genes. Three of the most frequently mutated genes were TP53 (151, 93.2%), KDR (104, 64.2%), and epidermal growth factor receptor (EGFR; 69, 42.6%). We also observed coexistence of EGFR and other oncogene (such as KRAS, PIC3CA, PTEN, and STK11) mutations. Given that 69.6% (48/69) of EGFR mutant patients were treated with EGFR tyrosine kinase inhibitors, EGFR mutant status had higher prognostic ability in this study.
Conclusions
These results suggest that targeted NGS using small biopsy samples is feasible and allows for the detection of both common and rare mutations in NSCLC.

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Glena Travis, Eileen M. McGowan, Ann M. Simpson, Deborah J. Marsh, Najah T. Nassif
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Barbara Melosky, Kato Kambartel, Maik Häntschel, Margherita Bennetts, Dana J. Nickens, Julia Brinkmann, Antonin Kayser, Michael Moran, Federico Cappuzzo
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Jeonghyo Lee, Yeon Bi Han, Hyun Jung Kwon, Song Kook Lee, Hyojin Kim, Jin-Haeng Chung
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Suitability of transbronchial brushing cytology specimens for next‐generation sequencing in peripheral lung cancer
Naoki Furuya, Shingo Matsumoto, Kazutaka Kakinuma, Kei Morikawa, Takeo Inoue, Hisashi Saji, Koichi Goto, Masamichi Mineshita
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KLHL38 involvement in non-small cell lung cancer progression via activation of the Akt signaling pathway
Yitong Xu, Chenglong Wang, Xizi Jiang, Yao Zhang, Hongbo Su, Jun Jiang, Hongjiu Ren, Xueshan Qiu
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Preoperative Cytologic Diagnosis of Warthin-like Variant of Papillary Thyroid Carcinoma: Jisup Kim, Beom Jin Lim, Soon Won Hong, Ju Yeon Pyo; J Pathol Transl Med. 2018;52(2):105-109. Published online February 12, 2018; DOI: https://doi.org/10.4132/jptm.2017.12.26

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Abstract PDF

Background
Warthin-like variant of papillary thyroid carcinoma (WLV-PTC) is a relatively rare variant of papillary thyroid carcinoma with favorable prognosis. However, preoperative diagnosis using fine-needle aspiration (FNA) specimens is challenging especially with lymphocytic thyroiditis characterized by Hürthle cells and lymphocytic background. To determine a helpful cytological differential point, we compared WLV-PTC FNA findings with conventional papillary thyroid carcinoma with lymphocytic thyroiditis (PTC-LT) and conventional papillary thyroid carcinoma without lymphocytic thyroiditis (PTC) regarding infiltrating inflammatory cells and their distribution. Preoperative diagnosis or potential for WLV-PTC will be helpful for surgeons to decide the scope of operation.
Methods
Of the 8,179 patients treated for papillary thyroid carcinoma between January 2007 and December 2012, 16 patients (0.2%) were pathologically confirmed as WLV-PTC and four cases were available for cytologic review. For comparison, we randomly selected six PTC-LT cases and five PTC cases during the same period. The number of intratumoral and background lymphocytes, histiocytes, neutrophils, and the presence of giant cells were evaluated and compared using conventional smear and ThinPrep preparations.
Results
WLV-PTC showed extensive lymphocytic smear with incorporation of thyroid follicular tumor cell clusters and frequent histiocytes. WLV-PTC was associated with higher intratumoral and background lymphocytes and histiocytes compared with PTC-LT or PTC. The difference was more distinct in liquid-based cytology.
Conclusions
The lymphocytic smear pattern and the number of inflammatory cells of WLV-PTC are different from those of PTC-LT or PTC and will be helpful for the differential diagnosis of WLV-PTC in preoperative FNA.

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Warthin-like variant of papillary thyroid carcinoma with lymph node metastases: a case report and review of the literature
Andrii Hryshchyshyn, Andrii Bahrii, Pavlina Botsun, Volodymyr Chuba
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Warthin-like papillary thyroid carcinoma: a case report and comprehensive review of the literature
Abdel Mouhaymen Missaoui, Fatma Hamza, Wafa Belabed, Manel Mellouli, Mohamed Maaloul, Slim Charfi, Issam Jardak, Tahya Sellami-Boudawara, Nabila Rekik, Mohamed Abid
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The Warthin-like variant of papillary thyroid carcinomas: a clinicopathologic analysis report of two cases
Xing Zhao, Yijia Zhang, Pengyu Hao, Mingzhen Zhao, Xingbin Shen
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Challenges in Cytology Specimens With Hürthle Cells
Eleni Thodou, Sule Canberk, Fernando Schmitt
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Warthin-like variant of Papillary thyroid carcinoma—Case report of an uncommon tumour with review of literature
Pradyumna Kumar Sahoo, Rashmi Patnayak, Perwez Alam Khan, Amitabh Jena
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Review

Extracellular Vesicles and the Promise of Continuous Liquid Biopsies: Don Armstrong, Derek E. Wildman; J Pathol Transl Med. 2018;52(1):1-8. Published online January 15, 2018; DOI: https://doi.org/10.4132/jptm.2017.05.21

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Abstract PDF

The rapid and accurate diagnosis of patients with minimally invasive procedures was once only found in science fiction. However, the discovery of extracellular vesicles (EVs) and their near ubiquity in body fluids, coupled with the advent of inexpensive next generation sequencing techniques and EV purification protocols, promises to make science fiction a reality. Purifying and sequencing the RNA content of EV from routine blood draws and urine samples are likely to enable pathologists and physicians to diagnose and track the progress of diseases in many inaccessible tissues in the near future. Here we present the evolutionary background of EV, summarize the biology of EV formation and cargo selection, and discuss the current barriers to making continuous liquid biopsies through the use of EV a science reality.

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