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Original Article
- Correlations and prognostic impacts of tumor spread through airspaces in surgically resected non–small cell lung cancer: a retrospective study from Jordan
- Ola Abu Al Karsaneh, Amani Al-Rousan, Sofian Al Shboul, Mohammed El-Sadoni, Anas Hayajneh, Moath Alrjoub, Sura Al-Rawabdeh, Tareq Saleh
- J Pathol Transl Med. 2026;60(1):92-106. Published online January 9, 2026
- DOI: https://doi.org/10.4132/jptm.2025.10.15
- 332 View
- 26 Download
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Abstract
PDF
Supplementary Material - Background
Spread through air spaces (STAS) has been identified as an invasion pattern in non–small cell lung cancer (NSCLC). This study evaluated the association between tumor STAS and various clinicopathological parameters of NSCLC, with emphasis on the prognostic role of STAS. Methods: We evaluated 96 cases of NSCLC for STAS. STAS-positive cases were graded according to the distance between the edge of the primary tumor and the furthest STAS, in millimeters, or the number of alveoli separating STAS from the tumor. Results: STAS was observed in 33 patients (34.4%). In 28 cases, STAS was located in airspaces >3 alveoli away from the primary tumor. In 18 cases, STAS was found in airspaces > 2.5 mm away from the edge of the primary tumor. Morphologically, 18 cases of STAS demonstrated a solid nest pattern, eight showed a micropapillary cluster pattern, and seven exhibited a single-cell pattern. In multivariate analysis, only high tumor grade (p = .001) was independently associated with STAS in NSCLC. The presence of STAS (p = .047), lymphovascular invasion (p = .001), positive surgical margin (p = .021), adenocarcinoma histology (p = .020), and postoperative therapy (p = .049) showed a statistically significant lower overall survival (OS). However, multivariate analyses showed that STAS is not an independent predictor of OS in NSCLC. In addition, STAS-positive cases with an extension of >2.5 mm had significantly lower disease-free survival (DFS) (p = .018). Conclusions: The findings demonstrated that STAS is independently associated with a higher tumor grade and appears to have an adverse impact on OS and DFS in the examined subpopulation.
Review
- 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
- 6,355 View
- 175 Download
- 8 Web of Science
- 6 Crossref
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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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Citations
Citations to this article as recorded by
- Proposal of real-world solutions for the implementation of predictive biomarker testing in patients with operable non-small cell lung cancer
Paul Hofman, Petros Christopoulos, Nicky D’Haene, John Gosney, Nicola Normanno, Ed Schuuring, Ming-Sound Tsao, Christine Quinn, Jayne Russell, Katherine E Keating, Fernando López-Ríos
Lung Cancer.2025; 201: 108107. CrossRef - Validation of ancillary procedures on formalin liquid fixed aspiration cytologic samples: from minimum to maximum
Orsolya Rideg, Tímea Dergez, Arnold Tóth, Tamás Tornóczky, Gábor Pavlovics, Endre Kálmán
American Journal of Clinical Pathology.2025;[Epub] CrossRef - Molecular testing of cytology specimens: Issues in specimen adequacy and clinical utility
Ghulam Ghous, Komal Ijaz, Magda Esebua, Lester J. Layfield
Diagnostic Cytopathology.2024; 52(2): 123. CrossRef - The updated College of American Pathologists principles of analytic validation of immunohistochemical assays: A step forward for cytopathology
Sinchita Roy‐Chowdhuri
Cancer Cytopathology.2024; 132(9): 547. CrossRef - Best-Practice Biomarker Testing of Oesophago-Gastric Cancer in the UK: Expert Consensus Recommendations Developed Using a Modified Delphi
N.P. West, W. Mansoor, P. Taniere, E. Smyth, M. Rodriguez-Justo, A. Oniscu, P. Carter
Clinical Oncology.2024; 36(11): 701. CrossRef - Next step of molecular pathology: next-generation sequencing in cytology
Ricella Souza da Silva, Fernando Schmitt
Journal of Pathology and Translational Medicine.2024; 58(6): 291. CrossRef
- Proposal of real-world solutions for the implementation of predictive biomarker testing in patients with operable non-small cell lung cancer
Original Articles
- Programmed death-ligand 1 expression and tumor-infiltrating lymphocytes in non-small cell lung cancer: association with clinicopathologic parameters
- Gaurav Garg, Kuruswamy Thurai Prasad, Navneet Singh, Parul Gupta, Valliappan Muthu, Ashim Das, Amanjit Bal
- J Pathol Transl Med. 2021;55(6):398-405. Published online October 6, 2021
- DOI: https://doi.org/10.4132/jptm.2021.08.08
- 5,344 View
- 167 Download
- 4 Web of Science
- 3 Crossref
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Abstract
PDFSupplementary Material
- Background
Data on the prevalence of programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs) in non–small cell lung cancer (NSCLC) and their clinical significance in Indian patients are limited.
Methods
Newly diagnosed NSCLC cases (adenocarcinoma or squamous cell carcinoma [SqCC] histology) were included in the present study. The TILs were evaluated based on morphology on hematoxylin and eosin–stained slides. PD-L1 expression in tumors was assessed using immunohistochemistry with rabbit monoclonal antibody (SP263) on the Ventana automated immunostainer. Tumors with PD-L1 expression > 50% on tumor cells were considered PD-L1–positive. Tumors in which TILs occupy > 25% of stroma were considered to have high TILs. The association of PD-L1 expression and TILs with various clinical parameters including overall survival (OS) was investigated.
Results
The present study included 128 cases of NSCLC (67 adenocarcinoma, 61 SqCC). PD-L1 positivity was observed in 17.2% of the patients with NSCLC. Baseline characteristics of PD-L1–positive subjects were similar to PD-L1–negative subjects except for a higher prevalence of liver metastasis (18.2% vs. 2.8%; p = .018) and a higher probability of diagnosis from extrapulmonary biopsies. High TILs were observed in 26.6% of the subjects. However, PD-L1 expression and high TIL did not affect OS.
Conclusions
PD-L1 positivity and high TILs were observed in 20% and 25% of the patients with NSCLC, respectively, however, neither were predictors of survival in SqCC. -
Citations
Citations to this article as recorded by- PDL1 and IDO‐2 Immunohistochemistry in Bronchoalveolar Lavage Versus Bronchoscopic Biopsy of Non‐Small Cell Lung Cancer
Menna Allah Hesham Mohammed Fekry, Yosria Mohammed El‐Gohary, Hesham Radwan Abd‐Elaziz, Tarek Hamdy Hassan, Mona Mostafa Ahmed
Cytopathology.2025;[Epub] CrossRef - Multiplex plasma protein assays as a diagnostic tool for lung cancer
Mohammad Tanvir Ahamed, Jenny Forshed, Adrian Levitsky, Janne Lehtiö, Amanj Bajalan, Maria Pernemalm, Lars E. Eriksson, Björn Andersson
Cancer Science.2024; 115(10): 3439. CrossRef - Real-world prevalence of PD-L1 expression in non-small cell lung cancer: an Australia-wide multi-centre retrospective observational study
Prudence A. Russell, Alexandra L. Farrall, Sarita Prabhakaran, Khashayar Asadi, Wade Barrett, Caroline Cooper, Wendy Cooper, Samuel Cotton, Edwina Duhig, Matthew Egan, Stephen Fox, David Godbolt, Shilpa Gupta, Aniza Hassan, Connull Leslie, Trishe Leong, D
Pathology.2023; 55(7): 922. CrossRef
- PDL1 and IDO‐2 Immunohistochemistry in Bronchoalveolar Lavage Versus Bronchoscopic Biopsy of Non‐Small Cell Lung Cancer
- Robust home brew fragment sizing assay for detection of MET exon 14 skipping mutation in non–small cell lung cancer patients in resource constrained community hospitals
- Anurag Mehta, Shrinidhi Nathany, Aanchal Chopra, Sakshi Mattoo, Dushyant Kumar, Manoj Kumar Panigrahi
- J Pathol Transl Med. 2021;55(5):324-329. Published online September 2, 2021
- DOI: https://doi.org/10.4132/jptm.2021.07.15
- 6,202 View
- 132 Download
- 1 Web of Science
- 2 Crossref
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Abstract
PDF
- Background
A mutation/deletion involving donor or acceptor sites for exon 14 results in splicing out of exon 14 of the mesenchymal epithelial transition (MET) gene and is known as “MET exon 14 skipping” (ΔMET14). The two recent approvals with substantial objective responses and improved progression-free survival to MET inhibitors namely capmatinib and tepotinib necessitate the identification of this alteration upfront. We herein describe our experience of ΔMET14 detection by an mRNA-based assay using polymerase chain reaction followed by fragment sizing.
Methods
This is a home brew assay which was developed with the concept that the transcripts from true ΔMET14 will be shorter by ~140 bases than their wild type counterparts. The cases which were called MET exon 14 skipping positive on next-generation sequencing (NGS) were subjected to this assay, along with 13 healthy controls in order to establish the validity for true negatives.
Results
Thirteen cases of ΔMET14 mutation were detected on NGS using RNA-based sequencing. Considering NGS as a gold standard, the sizing assay using both gel and capillary electrophoresis that showed 100% specificity for both with concordance rates of 84.6% and 88.2% with NGS, respectively, were obtained.
Conclusions
Owing to the cost-effective nature and easy to use procedures, this assay will prove beneficial for small- and medium-sized laboratories where skilled technical personnel and NGS platforms are unavailable. -
Citations
Citations to this article as recorded by
- Peripheral type squamous cell carcinoma of the lung: clinicopathologic characteristics in comparison to the central type
- Yeoun Eun Sung, Uiju Cho, Kyo Young Lee
- J Pathol Transl Med. 2020;54(4):290-299. Published online June 17, 2020
- DOI: https://doi.org/10.4132/jptm.2020.05.04
- 10,700 View
- 208 Download
- 13 Web of Science
- 15 Crossref
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Abstract
PDF
- Background
Squamous cell carcinomas (SqCCs) of the lung are known to arise more often in a central area but reports of peripheral SqCCs have increased, with a pathogenesis that is obscured. In this study, the clinicopathologic characteristics of peripheral lung SqCCs were studied and compared with those of the central type.
Methods
This study included 63 peripheral lung SqCCs and 48 randomly selected central cases; hematoxylin and eosin-stained slides of surgically resected specimens were reviewed in conjunction with radiologic images and clinical history. Cytokeratin-7 immunohistochemical staining of key slides and epidermal growth factor receptor (EGFR)/KRAS mutations tested by DNA sequencing were also included.
Results
Stages of peripheral SqCCs were significantly lower than central SqCCs (p=.016). Cystic change of the mass (p=.007), presence of interstitial fibrosis (p=0.007), and anthracosis (p=.049) in the background lung were significantly associated with the peripheral type. Cytokeratin-7 positivity was also higher in peripheral SqCCs with cutoffs of both 10% and 50% (p=.011). Pathogenic mutations in EGFR and KRAS were observed in only one case out of the 72 evaluated. The Cox proportional hazard model indicated a significantly better disease-free survival (p=.009) and the tendency of better overall survival (p=.106) in the peripheral type.
Conclusions
In peripheral type, lower stage is a favorable factor for survival but more frequent interstitial fibrosis and older age are unfavorable factors. Multivariate Cox analysis revealed that peripheral type is associated with better disease-free survival. The pathogenesis of peripheral lung SqCCs needs further investigation, together with consideration of the background lung conditions. -
Citations
Citations to this article as recorded by- Assessing the performance of chest x‐ray screening in detecting early‐stage lung cancer in the general population
Choy‐Lye Chei, Sho Nakamura, Kaname Watanabe, Takashi Mizutani, Hiroto Narimatsu
International Journal of Cancer.2025; 156(11): 2127. CrossRef - Whole lung radiomic features are associated with overall survival in patients with locally advanced non-small cell lung cancer treated with definitive radiotherapy
Meng Yan, Zhen Zhang, Jia Tian, Jiaqi Yu, Andre Dekker, Dirk de Ruysscher, Leonard Wee, Lujun Zhao
Radiation Oncology.2025;[Epub] CrossRef - Imaging appearances, CT evolution patterns, and surgical prognosis of stage I lung squamous cell carcinoma
Wei-hua Zhao, Tian-you Luo, Fa-jin Lv, Qi Li
Cancer Imaging.2025;[Epub] CrossRef - Pulmonary squamous cell carcinoma and lymphoepithelial carcinoma – morphology, molecular characteristics and differential diagnosis
Sabina Berezowska, Marie Maillard, Mark Keyter, Bettina Bisig
Histopathology.2024; 84(1): 32. CrossRef - Assessment of seasonal variability of PM, BC and UFP levels at a highway toll stations and their associated health risks
Nazneen, Aditya Kumar Patra, Soma Sekhara Rao Kolluru, Abhishek Penchala, Sachidanand Kumar, Namrata Mishra, Naragam Bhanu Sree, Samrat Santra, Ravish Dubey
Environmental Research.2024; 245: 118028. CrossRef - Association between Airport Ultrafine Particles and Lung Cancer Risk: The Multiethnic Cohort Study
Arthur Bookstein, Justine Po, Chiuchen Tseng, Timothy V. Larson, Juan Yang, Sung-shim L. Park, Jun Wu, Salma Shariff-Marco, Pushkar P. Inamdar, Ugonna Ihenacho, Veronica W. Setiawan, Mindy C. DeRouen, Loïc Le Marchand, Daniel O. Stram, Jonathan Samet, Bea
Cancer Epidemiology, Biomarkers & Prevention.2024; 33(5): 703. CrossRef - Clinical and Bronchoscopy Assessment in Diagnosing the Histopathology Type of Primary Central Lung Tumors
Mia Elhidsi, Jamal Zaini, Lisnawati Rachmadi, Asmarinah Asmarinah, Aria Kekalih, Noni Soeroso, Menaldi Rasmin
The Open Respiratory Medicine Journal.2024;[Epub] CrossRef - Possible thoracic metastasis from squamous cell carcinoma of the external auditory canal: A case report
Hiroshi Takehara, Ken Kodama, Toru Momozane, Masashi Takeda, Kaichi Shigetsu, Hiroki Kishima
Clinical Case Reports.2024;[Epub] CrossRef - Radiological precursor lesions of lung squamous cell carcinoma: Early progression patterns and divergent volume doubling time between hilar and peripheral zones
Haruto Sugawara, Yasushi Yatabe, Hirokazu Watanabe, Hiroyuki Akai, Osamu Abe, Shun-ichi Watanabe, Masahiko Kusumoto
Lung Cancer.2023; 176: 31. CrossRef - Loss of GSTO2 contributes to cell growth and mitochondria function via the p38 signaling in lung squamous cell carcinoma
Ryusuke Sumiya, Masayoshi Terayama, Teruki Hagiwara, Kazuaki Nakata, Keigo Sekihara, Satoshi Nagasaka, Hideki Miyazaki, Toru Igari, Kazuhiko Yamada, Yuki I. Kawamura
Cancer Science.2022; 113(1): 195. CrossRef - Primary tumor location in lung cancer: the evaluation and administration
Xueqi Xie, Xiaolin Li, Wenjie Tang, Peng Xie, Xuefen Tan
Chinese Medical Journal.2022; 135(2): 127. CrossRef - Pulmonary squamous cell carcinoma with a lepidic-pagetoid growth pattern
Claudio Guerrieri, Mark Lindner, Joanna Sesti, Abhishek Chakraborti, Rachel Hudacko
Pathologica.2022; 114(4): 304. CrossRef - Deposition modeling of ambient particulate matter in the human respiratory tract
Salman Khan, Bhola Ram Gurjar, Veerendra Sahu
Atmospheric Pollution Research.2022; 13(10): 101565. CrossRef - Selection of the surgical approach for patients with cStage IA lung squamous cell carcinoma: A population-based propensity score matching analysis
Shengteng Shao, Guisong Song, Yuanyong Wang, Tengfei Yi, Shuo Li, Fuhui Chen, Yang Li, Xiaotong Liu, Bin Han, Yuhong Liu
Frontiers in Oncology.2022;[Epub] CrossRef - Virus Nanoparticles & Different Nanoparticles Affect Lung Cancer- A New Approach
Ranajit Nath, Ratna Roy, Soubhik bhattacharyya, Sourav Datta
International Journal of Scientific Research in Science and Technology.2021; : 867. CrossRef
- Assessing the performance of chest x‐ray screening in detecting early‐stage lung cancer in the general population
- Gene variant profiles and tumor metabolic activity as measured by FOXM1 expression and glucose uptake in lung adenocarcinoma
- Ashley Goodman, Waqas Mahmud, Lela Buckingham
- J Pathol Transl Med. 2020;54(3):237-245. Published online March 4, 2020
- DOI: https://doi.org/10.4132/jptm.2020.02.08
- 7,082 View
- 120 Download
- 2 Web of Science
- 1 Crossref
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Abstract
PDF
- Background
Cancer cells displaying aberrant metabolism switch energy production from oxidative phosphorylation to glycolysis. Measure of glucose standardized uptake value (SUV) by positron emission tomography (PET), used for staging of adenocarcinoma in high-risk patients, can reflect cellular use of the glycolysis pathway. The transcription factor, FOXM1 plays a role in regulation of glycolytic genes. Cancer cell transformation is driven by mutations in tumor suppressor genes such as TP53 and STK11 and oncogenes such as KRAS and EGFR. In this study, SUV and FOXM1 gene expression were compared in the background of selected cancer gene mutations.
Methods
Archival tumor tissue from cases of lung adenocarcinoma were analyzed. SUV was collected from patient records. FOXM1 gene expression was assessed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Gene mutations were detected by allele-specific PCR and gene sequencing.
Results
SUV and FOXM1 gene expression patterns differed in the presence of single and coexisting gene mutations. Gene mutations affected SUV and FOXM1 differently. EGFR mutations were found in tumors with lower FOXM1 expression but did not affect SUV. Tumors with TP53 mutations had increased SUV (p = .029). FOXM1 expression was significantly higher in tumors with STK11 mutations alone (p < .001) and in combination with KRAS or TP53 mutations (p < .001 and p = .002, respectively).
Conclusions
Cancer gene mutations may affect tumor metabolic activity. These observations support consideration of tumor cell metabolic state in the presence of gene mutations for optimal prognosis and treatment strategy. -
Citations
Citations to this article as recorded by- Prognostic value of combining clinical factors, 18F-FDG PET-based intensity, volumetric features, and deep learning predictor in patients with EGFR-mutated lung adenocarcinoma undergoing targeted therapies: a cross-scanner and temporal validation study
Kun-Han Lue, Yu-Hung Chen, Sung-Chao Chu, Chih-Bin Lin, Tso-Fu Wang, Shu-Hsin Liu
Annals of Nuclear Medicine.2024; 38(8): 647. CrossRef
- Prognostic value of combining clinical factors, 18F-FDG PET-based intensity, volumetric features, and deep learning predictor in patients with EGFR-mutated lung adenocarcinoma undergoing targeted therapies: a cross-scanner and temporal validation study
- MicroRNA-374a Expression as a Prognostic Biomarker in Lung Adenocarcinoma
- Yeseul Kim, Jongmin Sim, Hyunsung Kim, Seong Sik Bang, Seungyun Jee, Sungeon Park, Kiseok Jang
- J Pathol Transl Med. 2019;53(6):354-360. Published online October 24, 2019
- DOI: https://doi.org/10.4132/jptm.2019.10.01
- 6,573 View
- 130 Download
- 5 Web of Science
- 6 Crossref
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Abstract
PDF
- Background
Lung cancer is the most common cause of cancer-related death, and adenocarcinoma is the most common histologic subtype. MicroRNA is a small non-coding RNA that inhibits multiple target gene expression at the post-transcriptional level and is commonly dysregulated in malignant tumors. The purpose of this study was to analyze the expression of microRNA-374a (miR-374a) in lung adenocarcinoma and correlate its expression with various clinicopathological characteristics.
Methods
The expression level of miR-374a was measured in 111 formalin-fixed paraffin-embedded lung adenocarcinoma tissues using reverse transcription-quantitative polymerase chain reaction assays. The correlation between miR-374a expression and clinicopathological parameters, including clinical outcome, was further analyzed.
Results
High miR-374 expression was correlated with advanced pT category (chi-square test, p=.004) and pleural invasion (chi-square test, p=.034). Survival analysis revealed that patients with high miR-374a expression had significantly shorter disease-free survival relative to those with low miR-374a expression (log-rank test, p=.032).
Conclusions
miR-374a expression may serve as a potential prognostic biomarker for predicting recurrence in early stage lung adenocarcinoma after curative surgery. -
Citations
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Jing Ma, Lu Gan, Hongying Chen, Lihao Chen, Yu Hu, Chao Luan, Kun Chen, Jiaan Zhang
Cellular Signalling.2024; 119: 111171. CrossRef - Association between the expression level of miRNA‑374a and TGF‑β1 in patients with colorectal cancer
Noha El Din, Reem El‑Shenawy, Rehab Moustafa, Ahmed Khairy, Sally Farouk
World Academy of Sciences Journal.2024;[Epub] CrossRef - Cell-free plasma miRNAs analysis for low invasive lung cancer diagnostics
M. Yu. Konoshenko, P. P. Laktionov, Yu. A. Lancuhaj, S. V. Pak, S. E. Krasilnikov, O. E. Bryzgunova
Advances in Molecular Oncology.2023; 10(2): 78. CrossRef - MicroRNA‑mediated regulation in lung adenocarcinoma: Signaling pathways and potential therapeutic implications (Review)
Jiye Liu, Fei Zhang, Jiahe Wang, Yibing Wang
Oncology Reports.2023;[Epub] CrossRef - Dysregulation of miR-374a is involved in the progression of diabetic retinopathy and regulates the proliferation and migration of retinal microvascular endothelial cells
Zhanhong Wang, Xiao Zhang, Yanjun Wang, Dailing Xiao
Clinical and Experimental Optometry.2022; 105(3): 287. CrossRef - MicroRNA Profile for Diagnostic and Prognostic Biomarkers in Thyroid Cancer
Jong-Lyul Park, Seon-Kyu Kim, Sora Jeon, Chan-Kwon Jung, Yong-Sung Kim
Cancers.2021; 13(4): 632. CrossRef
- Upregulated miR-374a-5p drives psoriasis pathogenesis through WIF1 downregulation and Wnt5a/NF-κB activation
- p40 Immunohistochemistry Is an Excellent Marker in Primary Lung Squamous Cell Carcinoma
- Khairunisa Ahmad Affandi, Nur Maya Sabrina Tizen, Muaatamarulain Mustangin, Reena Rahayu MdReena Rahayu Md Zin
- J Pathol Transl Med. 2018;52(5):283-289. Published online August 31, 2018
- DOI: https://doi.org/10.4132/jptm.2018.08.14
- 25,637 View
- 346 Download
- 33 Web of Science
- 37 Crossref
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Abstract
PDF
- Background
Lung cancer is the third most common cancer worldwide. With major advances in the molecular testing of lung cancers and the introduction of targeted therapies, the distinction between adenocarcinoma and squamous cell carcinoma as well as pathologic subtyping has become important. Recent studies showed that p40 is highly specific for squamous and basal cells and is superior to p63 for diagnosing lung squamous cell carcinoma. The aim of this study was to evaluate the use of p40 immunohistochemical stain in the diagnosis of non-small cell lung carcinoma and its potential to replace current p63 antibody as the best immunohistochemical squamous marker.
Methods
Seventy formalin-fixed paraffin-embedded cases previously diagnosed as primary lung squamous cell carcinoma (n = 35) and lung adenocarcinoma (n = 35) from January 2008 to December 2016 were retrieved. The results of tumour cell immunoreactivity for p40 and p63 antibodies in lung squamous cell carcinoma and lung adenocarcinoma were compared.
Results
p40 was expressed in 27 cases of lung squamous cell carcinoma (77.1%). All cases of lung adenocarcinoma (35/35, 100%) were negative for p40. p63 expression was positive in 30 cases of lung squamous cell carcinoma (85.7%) and 13 cases of lung adenocarcinoma (37.1%). Reactivity for both p40 and p63 in lung squamous cell carcinoma was strong and diffuse, whereas variable reactivity was observed in lung adenocarcinoma.
Conclusions
p40 is an excellent marker for distinguishing lung squamous cell carcinoma from adenocarcinoma, and p40 expression is equivalent to p63 expression in lung squamous cell carcinoma. -
Citations
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Jessie Xiong, Erik Polsdofer, Jian Jing
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- Differential MicroRNA Expression between EGFR T790M and L858R Mutated Lung Cancer
- Ji Yeon Kim, Woo Jeong Lee, Ha Young Park, Ahrong Kim, Dong Hoon Shin, Chang Hun Lee
- J Pathol Transl Med. 2018;52(5):275-282. Published online August 16, 2018
- DOI: https://doi.org/10.4132/jptm.2018.07.29
- 8,225 View
- 129 Download
- 6 Web of Science
- 5 Crossref
-
Abstract
PDFSupplementary Material
- Background
MicroRNAs (miRNAs) are short, non-coding RNAs that mediate post-transcriptional gene regulation. They are commonly deregulated in human malignancies, including non-small cell lung cancer (NSCLC). The aim of this study is to investigate miRNA expression in T790M-mutated NSCLC resistant to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors.
Methods
Six cases of resected NSCLC harboring the T790M mutation were examined. We performed miRNA time polymerase chain reaction (PCR) array profiling using EGFR T790M-mutated NSCLC and L858R-mutated NSCLC. Once identified, miRNAs that were differentially expressed between the two groups were validated by quantitative real-time polymerase chain reaction (qRT-PCR).
Results
miRNA PCR array profiling revealed three up-regulated miRNAs whose expression levels were altered 4.0-fold or more in the EGFR T790M mutation group than in the L858R group: miR-1 (fold change, 4.384), miR-196a (fold change, 4.138), and miR-124 (fold change, 4.132). The three differentially expressed miRNAs were validated by qRT-PCR, and they were found to be overexpressed in the T790M group relative to L858R group. In particular, expression levels of miR-1 and miR-124 were significantly higher in the T790M group (p-value of miR-1 = .004, miR-124 = .007, miR-196a = .096).
Conclusions
MiR-1, miR-124, and miR-196a are overexpressed in EGFR T790M mutated NSCLC. -
Citations
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- Whole exome sequencing and MicroRNA profiling of lung adenocarcinoma identified risk prediction features for tumors at stage I and its substages
- 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]
- 5,626 View
- 63 Download
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
- 17,882 View
- 616 Download
- 28 Web of Science
- 28 Crossref
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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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Original Article
- Transformation to Small Cell Lung Cancer of Pulmonary Adenocarcinoma: Clinicopathologic Analysis of Six Cases
- Soomin Ahn, Soo Hyun Hwang, Joungho Han, Yoon-La Choi, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn, Woong-Yang Park
- J Pathol Transl Med. 2016;50(4):258-263. Published online May 10, 2016
- DOI: https://doi.org/10.4132/jptm.2016.04.19
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Abstract
PDF
- Background
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are considered the first line treatment for a subset of EGFR-mutated non-small cell lung cancer (NSCLC) patients. Although transformation to small cell lung cancer (SCLC) is one of the known mechanisms of resistance to EGFR TKIs, it is not certain whether transformation to SCLC is exclusively found as a mechanism of TKI resistance in EGFR-mutant tumors.
Methods
We identified six patients with primary lung adenocarcinoma that showed transformation to SCLC on second biopsy (n = 401) during a 6-year period. Clinicopathologic information was analyzed and EGFR mutation results were compared between initial and second biopsy samples.
Results
Six patients showed transformation from adenocarcinoma to SCLC, of which four were pure SCLCs and two were combined adenocarcinoma and SCLCs. Clinically, four cases were EGFR-mutant tumors from non-smoking females who underwent TKI treatment, and the EGFR mutation was retained in the transformed SCLC tumors. The remaining two adenocarcinomas were EGFR wild-type, and one of these patients received EGFR TKI treatment.
Conclusions
NSCLC can acquire a neuroendocrine phenotype with or without EGFR TKI treatment. -
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Case Study
- Sclerosing Perivascular Epithelioid Cell Tumor of the Lung: A Case Report with Cytologic Findings
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- J Pathol Transl Med. 2016;50(3):238-242. Published online April 11, 2016
- DOI: https://doi.org/10.4132/jptm.2016.02.19
- 10,071 View
- 109 Download
- 7 Web of Science
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Abstract
PDF
- Benign perivascular epithelioid cell tumor (PEComa) of the lung is a rare benign neoplasm, a sclerosing variant of which is even rarer. We present a case of 51-year-old man who was diagnosed with benign sclerosing PEComa by percutaneous fine needle aspiration cytology and biopsy. The aspirate revealed a few cell clusters composed of bland-looking polygonal or spindle cells with fine granular or clear cytoplasm. Occasional fine vessel-like structures with surrounding hyalinized materials were seen. The patient later underwent wedge resection of the lung. The histopathological study of the resected specimen revealed sheets of polygonal cells with clear vacuolated cytoplasm, variably sized thin blood vessels, and densely hyalinized stroma. In immunohistochemical studies, reactivity of tumor cells for human melanoma black 45 and Melan-A further supported the diagnosis of benign sclerosing PEComa. To the best of our knowledge, this is the first case of benign sclerosing PEComa described in lung.
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Citations
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Original Article
- Analysis of Mutations in Epidermal Growth Factor Receptor Gene in Korean Patients with Non-small Cell Lung Cancer: Summary of a Nationwide Survey
- Sang Hwa Lee, Wan Seop Kim, Yoo Duk Choi, Jeong Wook Seo, Joung Ho Han, Mi Jin Kim, Lucia Kim, Geon Kook Lee, Chang Hun Lee, Mee Hye Oh, Gou Young Kim, Sun Hee Sung, Kyo Young Lee, Sun Hee Chang, Mee Sook Rho, Han Kyeom Kim, Soon Hee Jung, Se Jin Jang, The Cardiopulmonary Pathology Study Group of Korean Society of Pathologists
- J Pathol Transl Med. 2015;49(6):481-488. Published online October 13, 2015
- DOI: https://doi.org/10.4132/jptm.2015.09.14
- 12,630 View
- 107 Download
- 22 Web of Science
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Abstract
PDF
- Background
Analysis of mutations in the epidermal growth factor receptor gene (EGFR) is important for predicting response to EGFR tyrosine kinase inhibitors. The overall rate of EGFR mutations in Korean patients is variable. To obtain comprehensive data on the status of EGFR mutations in Korean patients with lung cancer, the Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists initiated a nationwide survey. Methods: We obtained 1,753 reports on EGFR mutations in patients with lung cancer from 15 hospitals between January and December 2009. We compared EGFR mutations with patient age, sex, history of smoking, histologic diagnosis, specimen type, procurement site, tumor cell dissection, and laboratory status. Results: The overall EGFR mutation rate was 34.3% in patients with non-small cell lung cancer (NSCLC) and 43.3% in patients with adenocarcinoma. EGFR mutation rate was significantly higher in women, never smokers, patients with adenocarcinoma, and patients who had undergone excisional biopsy. EGFR mutation rates did not differ with respect to patient age or procurement site among patients with NSCLC. Conclusions: EGFR mutation rates and statuses were similar to those in published data from other East Asian countries. -
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Review
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- J Pathol Transl Med. 2015;49(4):300-309. Published online June 16, 2015
- DOI: https://doi.org/10.4132/jptm.2015.06.16
- 16,673 View
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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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Original Articles
KRAS Mutation Detection in Non-small Cell Lung Cancer Using a Peptide Nucleic Acid-Mediated Polymerase Chain Reaction Clamping Method and Comparative Validation with Next-Generation Sequencing- Boram Lee, Boin Lee, Gangmin Han, Mi Jung Kwon, Joungho Han, Yoon-La Choi
- Korean J Pathol. 2014;48(2):100-107. Published online April 28, 2014
- DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.2.100
- 13,979 View
- 104 Download
- 17 Crossref
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Abstract
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Background KRAS is one of commonly mutated genetic "drivers" in non-small cell lung cancers (NSCLCs). Recent studies indicate that patients withKRAS -mutated tumors do not benefit from adjuvant chemotherapy, so there is now a focus on targetingKRAS -mutated NSCLCs. A feasible mutation detection method is required in order to accurately test forKRAS status.Methods We compared direct Sanger sequencing and the peptide nucleic acid (PNA)-mediated polymerase chain reaction (PCR) clamping method in 134 NSCLCs and explored associations with clinicopathological factors. Next-generation sequencing (NGS) was used to validate the results of discordant cases. To increase the resolution of low-level somatic mutant molecules, PNA-mediated PCR clamping was used for mutant enrichment prior to NGS.
Results Twenty-one (15.7%) cases were found to have the
KRAS mutations using direct sequencing, with two additional cases by the PNA-mediated PCR clamping method. The frequencies ofKRAS mutant alleles were 2% and 4%, respectively, using conventional NGS, increasing up to 90% and 89%, using mutant-enriched NGS. TheKRAS mutation occurs more frequently in the tumors of smokers (p=.012) and in stage IV tumors (p=.032).Conclusions Direct sequencing can accurately detect mutations, but, it is not always possible to obtain a tumor sample with sufficient volume. The PNA-mediated PCR clamping can rapidly provide results with sufficient sensitivity.
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- Usual Interstitial Pneumonia with Lung Cancer: Clinicopathological Analysis of 43 Cases
- Dae Hyun Song, In Ho Choi, Sang Yun Ha, Kang Min Han, Jae Jun Lee, Min Eui Hong, Kyeongman Jeon, Man Pyo Chung, Jhingook Kim, Joungho Han
- Korean J Pathol. 2014;48(1):10-16. Published online February 25, 2014
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Abstract
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Background Previous studies have suggested an association between usual interstitial pneumonia (UIP) and lung cancer (Ca). However, clinical and histological information is not enough to determine such an association, due to the low incidence and short survival time of patients with both conditions.
Methods We retrospectively reviewed the clinical and histological records of Ca patients with UIP between January 1999 and August 2013 at the Samsung Medical Center, Seoul, Korea. We found 43 patients who had Ca with UIP (UIP-Ca). Previously reported data of eighty-four patients with UIP-only were included as a comparison group.
Results Smoking is related to poor prognosis in patients with UIP-Ca, and the number of patients with a high smoking index of more than 30 pack-years significantly increased in UIP-Ca patients compared with UIP-only patients. There is no significant prognostic differentiation between UIP-Ca patients and UIP-only patients. Microscopically, UIP-Ca patients showed characteristically heterogeneous histological patterns and degrees of differentiation. There were many foci of squamous metaplasia or dysplasia at the peripheral area of squamous cell carcinomas.
Conclusions We report 43 cases of UIP-Ca. Our results suggest that smoking is related to cancer occurrence in UIP patients and poor prognosis in UIP-Ca patients.
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ALK Gene Rearrangement in Lung Cancer: A Proposal of the Korean Cardiopulmonary Pathology Study Group - Hyojin Kim, Hyo Sup Shim, Lucia Kim, Tae-Jung Kim, Kun Young Kwon, Geon Kook Lee, Jin-Haeng Chung
- Korean J Pathol. 2014;48(1):1-9. Published online February 25, 2014
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Abstract
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Rearrangement of anaplastic lymphoma kinase (
ALK ) gene is the best predictor of response to crizotinib, an ALK tyrosine kinase inhibitor. However, the prevalence of theALK fusion is low, so accurate patient identification is crucial for successful treatment using ALK inhibitors. Furthermore, most patients with lung cancer present with advanced-stage disease at the time of diagnosis, so it is important for pathologists to detectALK -rearranged patients while effectively maximizing small biopsy or cytology specimens. In this review, we propose a guideline recommendation for ALK testing approved by the Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists.-
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Original Articles
- Comparison of Direct Sequencing, PNA Clamping-Real Time Polymerase Chain Reaction, and Pyrosequencing Methods for the Detection of
EGFR Mutations in Non-small Cell Lung Carcinoma and the Correlation with Clinical Responses to EGFR Tyrosin - Hyun Ju Lee, Xianhua Xu, Hyojin Kim, Yan Jin, Pingli Sun, Ji Eun Kim, Jin-Haeng Chung
- Korean J Pathol. 2013;47(1):52-60. Published online February 25, 2013
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Abstract
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Background The aims of this study were to evaluate the abilities of direct sequencing (DS), peptide nucleic acid (PNA) clamping, and pyrosequencing methods to detect epidermal growth factor receptor (
EGFR ) mutations in formalin-fixed paraffin-embedded (FFPE) non-small cell lung carcinoma (NSCLC) samples and to correlateEGFR mutational status as determined by each method with the clinical response toEGFR tyrosine kinase inhibitors (TKIs).Methods Sixty-one NSCLC patients treated with EGFR TKIs were identified to investigate somatic mutations in the
EGFR gene (exons 18-21).Results Mutations in the
EGFR gene were detected in 38 of the 61 patients (62%) by DS, 35 (57%) by PNA clamping and 37 (61%) by pyrosequencing. A total of 44 mutations (72%) were found by at least one of the three methods, and the concordances among the results were relatively high (82-85%; kappa coefficient, 0.713 to 0.736). There were 15 discordant cases (25%) among the three different methods.Conclusions All three
EGFR mutation tests had good concordance rates (over 82%) for FFPE samples. These results suggest that if the DNA quality and enrichment of tumor cells are assured, then DS, PNA clamping, and pyrosequencing are appropriate methods for the detection ofEGFR mutations.-
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- Alteration of the E-Cadherin/β-Catenin Complex Is an Independent Poor Prognostic Factor in Lung Adenocarcinoma
- Hyojin Kim, Seol Bong Yoo, Pingli Sun, Yan Jin, Sanghoon Jheon, Choon Taek Lee, Jin-Haeng Chung
- Korean J Pathol. 2013;47(1):44-51. Published online February 25, 2013
- DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.1.44
- 11,954 View
- 63 Download
- 35 Crossref
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Abstract
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Background Epithelial-mesenchymal transition (EMT) is an important step in the invasion and progression of cancer and in the development of chemoresistance by cancer cells.
Methods To address the clinical significance of the EMT pathway in lung adenocarcinoma and the association of the pathway with histological subtype, we examined 193 surgically resected lung adenocarcinoma samples for the expression of representative EMT-related proteins (E-cadherin, β-catenin, and vimentin) by immunohistochemistry. Histological subtypes were classified according to the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. The results for EMT-related protein expression were analyzed for correlation with clinicopathological features and with survival.
Results The loss of E-cadherin expression and aberrant β-catenin expression were significantly associated with larger tumor size, pleural invasion, lymphatic/vascular invasion, and advanced pathological stage (p<0.05). The alteration of the E-cadherin/β-catenin complex was least frequently observed in the lepidic-predominant group, but these associations were not statistically significant. In the multivariate analysis, altered E-cadherin/β-catenin complex expression was found to be an independent poor prognostic factor (p=0.017; hazard ratio, 1.926; 95% confidence interval, 1.119 to 3.314).
Conclusions The alteration of the expression of the E-cadherin/β-catenin complex was associated with aggressive tumor behavior in lung adenocarcinoma.
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- Prognostic significance of stem cell-related marker expression and its correlation with histologic subtypes in lung adenocarcinoma
Case Report
- Diffuse Pulmonary Meningotheliomatosis: A Case Report.
- Jungsuk An, Heejung Park, Joungho Han, Tae Sung Kim, Yong Soo Choi, Moon Seok Choi, Sang Won Um
- Korean J Pathol. 2011;45:S32-S35.
- DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.S1.S32
- 5,074 View
- 43 Download
- 1 Crossref
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Abstract
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- Diffuse pulmonary meningotheliomatosis (DPM) is an extremely rare condition. We herein report a unique case of DPM in a 54-year-old woman with a previous history of hepatocellular carcinoma. A chest computed tomography showed diffuse bilateral nodular infiltration, suggesting miliary spread of metastatic hepatocellular carcinoma. The patient underwent a video-assisted thoracoscopic surgery for diagnostic purposes. The cut surface of the lung specimen showed multiple dispersed small nodules, consisting of variably sized nests or whorls of bland epithelioid cells often along the walls of alveolar septa or in a perivascular network within the alveolar interstitium. The tumor cells showed immunoreactivity for epithelial membrane antigen, vimentin, and progesterone receptor. DPM should be included in the differential diagnosis of diffuse multiple small nodules or a reticular pattern in the radiologic studies.
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Citations
Citations to this article as recorded by- Minute Pulmonary Meningothelial-Like Nodules Simulating Hematogenous Lung Metastasis: A Case Report
Sang Kook Lee, Gi Jeong Kim, Young Jae Kim, Ah Young Leem, Eu Dong Hwang, Se Kyu Kim, Joon Chang, Young Ae Kang, Song Yee Kim
Tuberculosis and Respiratory Diseases.2013; 75(2): 67. CrossRef
- Minute Pulmonary Meningothelial-Like Nodules Simulating Hematogenous Lung Metastasis: A Case Report
Original Article
- Mucoepidermoid Carcinoma of Tracheobronchial Tree: Clinicopathological Study of 31 Cases.
- Sang Yun Ha, Joungho Han, Jae Jun Lee, Young Eun Kim, Yoon La Choi, Hong Kwan Kim
- Korean J Pathol. 2011;45(2):175-181.
- DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.2.175
- 5,135 View
- 33 Download
- 8 Crossref
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Abstract
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- BACKGROUND
All aspects of mucoepidermoid carcinoma (MEC) of the lung including histologic grading, clinical behavior and its differentiation from adenosquamous cell carcinoma are still not fully understood.
METHODS
We reviewed the hematoxylin-eosin stained slides and medical records of 31 cases of MEC of the lungs. The cases were classified as low and high grade according to the quantitative grading system formulated for MEC. High grade tumors were tested for an epidermal growth factor receptor (EGFR) mutation.
RESULTS
Twenty eight cases were classified as low grade and 3 cases as high grade. Histologically, lower glandular component, cellular atypia, necrosis, mitoses >4/10 high power fields, and endolymphatic tumor emboli were typical characteristics of a high grade tumor. Although some tumors showed histologic features mimicking high grade tumors, they were classified as low grade tumors according to this quantitative grading system. Low grade tumors showed no recurrence or metastasis. However, among three patients with a high grade tumor, two had distant metastases and one died of disease. Additionally, an EGFR mutation was not detected.
CONCLUSIONS
A high grade MEC was consistently different from a low grade tumor with regard to malignant histologic features and poor prognosis. Therefore, correct histologic grading is important in predicting the prognosis to avoid unnecessary treatment. -
Citations
Citations to this article as recorded by- A rare case of endobronchial mucoepidermoid carcinoma of the lung presenting as non-resolving pneumonia
Toolsie Omesh, Ranjan Gupta, Anjali Saqi, Joshua Burack, Misbahuddin Khaja
Respiratory Medicine Case Reports.2018; 25: 154. CrossRef - Cutaneous Involvement by Nasal Mucoepidermoid Carcinoma: The Tip of the Iceberg Phenomenon
Ge Zhao, Oliver Chang, John Streidl, Amit Bhrany, Kyle Garton, Timothy H. McCalmont, Paul E. Swanson, Zsolt Argenyi, Michi M. Shinohara
Journal of Cutaneous Pathology.2017; 44(2): 113. CrossRef - Surgical outcomes of pulmonary mucoepidermoid carcinoma: A review of 41 cases
Chih-Cheng Hsieh, Yung-Han Sun, Shih-Wei Lin, Yi-Chen Yeh, Mei-Lin Chan, Pei-Yi Chu
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Boram Lee, Taebum Lee, Se-Hoon Lee, Yoon-La Choi, Joungho Han
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Yong Won Park, Seon Bin Yoon, Mi Ju Cheon, Young Min Koh, Hyeon Sik Oh, Se Joong Kim, Seung Hyeun Lee
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Sang Yun Ha, So-Jung Choi, Jong Ho Cho, Hye Joo Choi, Jinseon Lee, Kyungsoo Jung, Darry Irwin, Xiao Liu, Maruja E. Lira, Mao Mao, Hong Kwan Kim, Yong Soo Choi, Young Mog Shim, Woong Yang Park, Yoon-La Choi, Jhingook Kim
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Russell J. Miller, Septimiu D. Murgu
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Iain D. O’Neill
Lung Cancer.2012; 78(1): 125. CrossRef
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Case Report
- The Fine Needle Aspiration Cytology of a Metastatic Pulmonary Adrenocortical Carcinoma Mimicking Primary Large Cell Carcinoma of the Lung.
- Na Rae Kim, Dong Hae Chung, Jae Ik Lee, Seung Yeon Ha
- Korean J Pathol. 2010;44(5):558-563.
- DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.5.558
- 3,240 View
- 17 Download
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Abstract
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- Adrenocortical carcinoma is a rare neoplasm and it has an invariably lethal prognosis. We report here on the fine needle aspiration cytologic findings of a solitary metastatic pulmonary adrenocortical carcinoma in a 24-year-old woman. The aspirate smears were very cellular and they were composed of a monomorphic population of large polyhedral cells with abundant granular or vacuolated cytoplasm, and the cells were predominantly singly scattered in a necrotic background. Multinucleated pleomorphic tumor cells were also found. Pleomorphic nuclei with thickened nuclear membranes were impinging on the cell membranes. Mitotic activity was occasionally seen. The cytologic findings of pleomorphic cells with microvacuolated cytoplasm and the presence of vague gland-like sheets, as well as the patient's history of undergoing adrenalectomy for primary adrenocortical carcinoma helped the pathologist reach the diagnosis of metastatic adrenocortical carcinoma. Here, we focus on the cytologic differential points of metastastic pulmonary adrenocortical carcinoma and primary pulmonary carcinoma, especially large cell carcinoma.
Original Article
- Differential Expression of Glut1 in Pulmonary Neuroendocrine Tumors: Correlation with Histological Grade.
- Hyun Ju Lee, Seol Bong Yoo, Won Woo Lee, Doo Hyun Chung, Jeong Wook Seo, Jin Haeng Chung
- Korean J Pathol. 2009;43(3):201-205.
- DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.3.201
- 4,888 View
- 39 Download
- 2 Crossref
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Abstract
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- BACKGROUND
Increased glucose uptake, a process that is mediated by glucose transporter (Glut1) proteins, is an important metabolic feature in a variety of cancer cells. The overexpression of Glut1 in human cancers is known to be related to a variety of histopathological parameters, including histological grade, proliferation rate, and lymphatic invasion. The principal objective of this study was to evaluate Glut1 expression in the spectrum of pulmonary neuroendocrine (NE) tumors including typical carcinoid tumor (TC), atypical carcinoid tumor (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell carcinoma (SCC), and to characterize the relationship between Glut1 expression and the histologic grade of NE tumors.
METHODS
19 TC, 7 AC, 13 LCNEC, and 6 SCC patients were included in this study. The percentages of Glut1-positive tumor cells in these patients were determined. For statistical analysis, Glut1 expression was subdivided into a Glut1-low expression group (0-30%) and a Glut1-high expression group (31-90%).
RESULTS
In our subgroup analyses, the histological grade of pulmonary neuroendocrine (NE) tumors was significantly correlated with Glut1 expression; TC (n=19, 3.6+/-4.2%), AC (n=7, 20.0+/-4.9%), LCNEC (n=13, 60.0+/-21.1%), and SCC (n=6, 74.2+/-16.9%). Glut1-high expression was significantly associated with high-grade NE tumors such as LCNEC and SCC (n=19, 62.6+/-21.0%) (p=0.000).
CONCLUSIONS
The results of this study appear to indicate that Glut1 overexpression is a consistent feature of high-grade NE lung tumors. -
Citations
Citations to this article as recorded by- GLUT1: A novel tool reflecting proliferative activity of lung neuroendocrine tumors?
Nazim Benzerdjeb, Pascal Berna, Henri Sevestre
Pathology International.2017; 67(1): 32. CrossRef - Oncocytic carcinoid tumor of the lung with intense F-18 fluorodeoxyglucose (FDG) uptake in positron emission tomography–computed tomography (PET/CT)
Yuki Tanabe, Yoshifumi Sugawara, Rieko Nishimura, Kohei Hosokawa, Makoto Kajihara, Teruhiko Shimizu, Tadaaki Takahashi, Shinya Sakai, Shigeki Sawada, Motohiro Yamashita, Haruhiko Ohtani
Annals of Nuclear Medicine.2013; 27(8): 781. CrossRef
- GLUT1: A novel tool reflecting proliferative activity of lung neuroendocrine tumors?
Review
- Fine Needle Aspiration Cytologic Findings of Pulmonary Neuroendocrine Tumors.
- Jae Soo Koh
- J Pathol Transl Med. 2008;19(1):9-15.
- DOI: https://doi.org/10.3338/kjc.2008.19.1.9
- 2,736 View
- 18 Download
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Abstract
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- The major categories of neuroendocrine tumors of lung are typical carcinoid, atypical carcinoid, large cell neuroendocrine carcinoma, and small cell carcinoma. The histologic classification criteria of neuroendocrine tumors are well documented in the "WHO Classification of Tumors" based on mitotic figures and necrosis. Cytologic characteristics of neuroendocrine tumors are trabecular, acinar, and solid arrangement of tumor cells and occasional rosette formation. Nuclear chromatin patterns are characteristically described as "salt and pepper chromatin pattern". Many of cytologic classifications documented in the literature are before the "WHO Classification". In this review, the cytologic features of pulmonary neuroendocrine tumors are documented according to the WHO classification, and recent concepts of neuroendocrine tumors of lung are discussed.
Case Reports
- Emphysematous Cystic Pulmonary Metastasis of Angiosarcoma.
- Tae Heon Kim, Ji Sun Song, Soon Hee Jung, Ki Jun Sung, Eun Gi Kim
- Korean J Pathol. 2001;35(6):544-546.
- 1,998 View
- 10 Download
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Abstract
- Pulmonary metastatic angiosarcoma usually reveals multiple nodular lesions associated with parenchymal hemorrhage. It is presented, in rare cases, as multiple emphysematous cystic lesions, complicated by pneumothorax. We experienced a case of pulmonary metastastasis from angiosarcoma of the scalp in a 58-year-old male showing multiple thin-walled emphysematous cystic lesions. The tumor cells spread along the subpleural and interlobular septa, focally surrounding the cystic lesions. This case suggests that a rare metastatic pattern seen in angiosarcoma of the scalp should be considered as a differential diagnosis of bullous emphysematous lesion.
- Pulmonary Lymphangioleiomyomatosis and Micronodular Pneumocyte Hyperplasia associated with Tuberous Sclerosis: A Case Report.
- Gou Young Kim, Juhie Lee, Yong Koo Park, Youn Wha Kim, Jae Hoon Park, Moon Ho Yang
- Korean J Pathol. 2002;36(1):51-54.
- 2,157 View
- 16 Download
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Abstract
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- Lymphangioleiomyomatosis (LAM) is characterized by a hamartomatous proliferation of smooth muscle cells in the lung, mediastium, and abdomen. In the lung, an abnormal proliferation of smooth muscle is seen along the airways, blood vessels, and lymphatics, resulting in honeycombing of the lung. It occurs in 0.1-1% of tuberous sclerosis (TSC) patients. Micronodular pneumocyte hyperplasia (MNPH) is a rare but distinctive pulmonary manifestation of TSC, and appears to be a hamartomatous proliferation of the type II pneumocytes. We report a case of pulmonary LAM and MNPH associated with TSC and bilateral renal angiomyolipoma in a 26-year-old woman. Immunohistochemically, the spindle cells of LAM were positive for HMB-45, but the type II pneumocytes of MNPH were negative.
Original Articles
- Loss of PTEN Expression in Primary Lung Cancer.
- Mee Sook Roh
- Korean J Pathol. 2002;36(5):286-291.
- 1,883 View
- 12 Download
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Abstract
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- BACKGROUND
The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene, a candidate tumor suppressor, is localized to chromosome 10q23 and shares extensive homology with cytoskeletal proteins auxilin and tensin. It appears to have multifunctional roles involved in cell proliferation, migration, and invasion. The role of PTEN alteration in the lung cancer and its relationship with other suppressor genes are not well established.
METHODS
Formalin-fixed, paraffin-embedded tissues from 105 patients with diagnosed with primary lung cancer were evaluated for PTEN and p53 protein expression using immunohistochemical methods. The results of the expression pattern of PTEN were compared with clinicopathological parameters and the expression pattern of p53.
RESULTS
Forty-seven (44.8%) of 105 cases had loss of PTEN expression. Loss of PTEN expression was significantly associated with histologic type (p<0.05), but did not correlate with tumor size, lymph node metastasis, and stage. There was no significant relationship between loss of PTEN expression and p53 expression, and no significant difference in clinicopathologic characteristics between particular groups of patterns with the four possible tumor carrying PTEN/p53 phenotypes.
CONCLUSION
It is suggested that loss of PTEN expression occurs commonly in primary lung cancers and correlates with histologic type. Our results also support the proposed role of PTEN as a candidate tumor suppressor in lung cancer, and we suggest that there is a need for further study of this gene.
- Expression of Thymidylate Synthase in Non-Small Cell Lung Cancer.
- Jinyoung Yoo, Suzi Kim, Byoung Yong Shim, Sung Hwan Kim, So Hyang Song, Deog Gon Cho, Meyung Im Ahn, Chi Hong Kim, Kyu Do Cho, Seok Jin Kang, Hoon Kyo Kim
- Korean J Pathol. 2005;39(6):412-417.
- 2,194 View
- 14 Download
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Abstract
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- BACKGROUND
Thymidylate synthase (TS) catalyzes the methylation of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP), and this is an essential step in DNA biosynthesis. The present investigation was designed to determine the expression of TS in the patients with non-small cell lung cancer (NSCLC) and to assess the possible associations between the TS status and the p53 or proliferative index (PI).
METHODS
The archival tumor tissues from 56 previously untreated NSCLC patients were examined by immunohistochemistry for TS, p53 and Ki-67.
RESULTS
Forty-one men and 15 women (age range: 35 to 79 years, mean age: 62 years) were included in this study. The TS expression was high in 40 patients (71.4%) and low in 16 patients (28.6%). The aberrant expression of p53 was detected in 35 patients (62.5%). The mean PI for all the patients was 31.4+/-12.1. The TS-high tumors tended to be more poorly differentiated (p=0.069). The TS expression by a semiquantitative fourscale grading system was significantly correlated with the PIs (p=0.003). No correlation was established between the TS expression and the p53 status (p=0.806) or survival (p=0.951). CONCLUSIONS: TS was not confirmed to be a useful marker for determining the prognosis of NSCLC patients. However, our data suggest that the tumor cells with higher TS expression have a higher proliferative activity.
- Expression of bcl-2, p53 and VEGF in Non-Small Cell Lung Carcinomas: Their Relation with the Microvascular Density and Prognosis.
- Jinyoung Yoo, Ji Han Jung, Hyun Joo Choi, Seok Jin Kang, Chang Suk Kang
- Korean J Pathol. 2005;39(2):74-80.
- 2,137 View
- 20 Download
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Abstract
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- BACKGROUND
The aim of this study was to investigate the expression of bcl-2, p53 and vascular endothelial growth factor (VEGF) in non-small cell lung cancer (NSCLC), and to examine the relationship between those protein expressions and neovascularization. We also analyzed the prognostic impact of these biological parameters on the patients' overall survival rate.
METHODS
The archival tumor tissues from 147 previously untreated patients with NSCLC were examined by immunohistochemistry for bcl-2, p53 and VEGF proteins. The vascularity was measured by the average microvascular density (MVD) of the CD34-positive vessels. Clinical information was obtained through the computerized retrospective database from the tumor registry.
RESULTS
Immunoreactivity for bcl-2 was detected in 17% (25/147), p53 in 72% (106/147) and VEGF in 75% (110/147) of the tumors. An inverse association was found between bcl-2 expression and VEGF expression (p=0.012). There was a significant correlation between the bcl-2 expression and the MVD (p=0.009), and also between the p53 expression and the MVD (p=0.045). The mean survival time was associated with the patients' age (p=0.032), the T status (p=0.038), the tumor stage (p=0.009), and expressions of bcl-2 (p=0.016) and VEGF (p=0.039). On multivariate analysis, only the tumor stage and VEGF expression maintained their prognostic influence.
CONCLUSIONS
Our data suggest that bcl-2 and p53 alterations are involved in the angiogenesis of NSCLC, and are either dependent on or independent of VEGF. It is further noteworthy that the tumor stage and VEGF expression may be useful in predicting patients' survival.
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