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Volume 54(2); March 2020
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Review
Introduction to digital pathology and computer-aided pathology
Soojeong Nam, Yosep Chong, Chan Kwon Jung, Tae-Yeong Kwak, Ji Youl Lee, Jihwan Park, Mi Jung Rho, Heounjeong Go
J Pathol Transl Med. 2020;54(2):125-134.   Published online February 13, 2020
DOI: https://doi.org/10.4132/jptm.2019.12.31
  • 12,085 View
  • 508 Download
  • 38 Citations
AbstractAbstract PDF
Digital pathology (DP) is no longer an unfamiliar term for pathologists, but it is still difficult for many pathologists to understand the engineering and mathematics concepts involved in DP. Computer-aided pathology (CAP) aids pathologists in diagnosis. However, some consider CAP a threat to the existence of pathologists and are skeptical of its clinical utility. Implementation of DP is very burdensome for pathologists because technical factors, impact on workflow, and information technology infrastructure must be considered. In this paper, various terms related to DP and computer-aided pathologic diagnosis are defined, current applications of DP are discussed, and various issues related to implementation of DP are outlined. The development of computer-aided pathologic diagnostic tools and their limitations are also discussed.

Citations

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  • A self-supervised contrastive learning approach for whole slide image representation in digital pathology
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  • A Matched-Pair Analysis of Nuclear Morphologic Features Between Core Needle Biopsy and Surgical Specimen in Thyroid Tumors Using a Deep Learning Model
    Faridul Haq, Andrey Bychkov, Chan Kwon Jung
    Endocrine Pathology.2022; 33(4): 472.     CrossRef
  • Development of quality assurance program for digital pathology by the Korean Society of Pathologists
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  • Whole Slide Image Quality in Digital Pathology: Review and Perspectives
    Romain Brixtel, Sebastien Bougleux, Olivier Lezoray, Yann Caillot, Benoit Lemoine, Mathieu Fontaine, Dalal Nebati, Arnaud Renouf
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  • Preference and Demand for Digital Pathology and Computer-Aided Diagnosis among Korean Pathologists: A Survey Study Focused on Prostate Needle Biopsy
    Soo Jeong Nam, Yosep Chong, Chan Kwon Jung, Tae-Yeong Kwak, Ji Youl Lee, Jihwan Park, Mi Jung Rho, Heounjeong Go
    Applied Sciences.2021; 11(16): 7380.     CrossRef
  • An SVM approach towards breast cancer classification from H&E-stained histopathology images based on integrated features
    M. A. Aswathy, M. Jagannath
    Medical & Biological Engineering & Computing.2021; 59(9): 1773.     CrossRef
  • Diagnosis prediction of tumours of unknown origin using ImmunoGenius, a machine learning-based expert system for immunohistochemistry profile interpretation
    Yosep Chong, Nishant Thakur, Ji Young Lee, Gyoyeon Hwang, Myungjin Choi, Yejin Kim, Hwanjo Yu, Mee Yon Cho
    Diagnostic Pathology.2021;[Epub]     CrossRef
  • Deep Learning for Automatic Subclassification of Gastric Carcinoma Using Whole-Slide Histopathology Images
    Hyun-Jong Jang, In-Hye Song, Sung-Hak Lee
    Cancers.2021; 13(15): 3811.     CrossRef
  • A novel evaluation method for Ki-67 immunostaining in paraffin-embedded tissues
    Eliane Pedra Dias, Nathália Silva Carlos Oliveira, Amanda Oliveira Serra-Campos, Anna Karoline Fausto da Silva, Licínio Esmeraldo da Silva, Karin Soares Cunha
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  • Assessment of Digital Pathology Imaging Biomarkers Associated with Breast Cancer Histologic Grade
    Andrew Lagree, Audrey Shiner, Marie Angeli Alera, Lauren Fleshner, Ethan Law, Brianna Law, Fang-I Lu, David Dodington, Sonal Gandhi, Elzbieta A. Slodkowska, Alex Shenfield, Katarzyna J. Jerzak, Ali Sadeghi-Naini, William T. Tran
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    Hyun-Jong Jang, Ahwon Lee, Jun Kang, In Hye Song, Sung Hak Lee
    World Journal of Gastroenterology.2021; 27(44): 7687.     CrossRef
  • Clustered nuclei splitting based on recurrent distance transform in digital pathology images
    Lukasz Roszkowiak, Anna Korzynska, Dorota Pijanowska, Ramon Bosch, Marylene Lejeune, Carlos Lopez
    EURASIP Journal on Image and Video Processing.2020;[Epub]     CrossRef
  • Current Trends of Artificial Intelligence for Colorectal Cancer Pathology Image Analysis: A Systematic Review
    Nishant Thakur, Hongjun Yoon, Yosep Chong
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  • A bird’s-eye view of deep learning in bioimage analysis
    Erik Meijering
    Computational and Structural Biotechnology Journal.2020; 18: 2312.     CrossRef
  • Pathomics in urology
    Victor M. Schuettfort, Benjamin Pradere, Michael Rink, Eva Comperat, Shahrokh F. Shariat
    Current Opinion in Urology.2020; 30(6): 823.     CrossRef
  • Model Fooling Attacks Against Medical Imaging: A Short Survey
    Tuomo Sipola, Samir Puuska, Tero Kokkonen
    Information & Security: An International Journal.2020; 46(2): 215.     CrossRef
  • Recommendations for pathologic practice using digital pathology: consensus report of the Korean Society of Pathologists
    Yosep Chong, Dae Cheol Kim, Chan Kwon Jung, Dong-chul Kim, Sang Yong Song, Hee Jae Joo, Sang-Yeop Yi
    Journal of Pathology and Translational Medicine.2020; 54(6): 437.     CrossRef
  • A machine-learning expert-supporting system for diagnosis prediction of lymphoid neoplasms using a probabilistic decision-tree algorithm and immunohistochemistry profile database
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    Journal of Pathology and Translational Medicine.2020; 54(6): 462.     CrossRef
Original Articles
Colorectal epithelial neoplasm associated with gut-associated lymphoid tissue
Yo Han Jeon, Ji Hyun Ahn, Hee Kyung Chang
J Pathol Transl Med. 2020;54(2):135-145.   Published online January 29, 2020
DOI: https://doi.org/10.4132/jptm.2019.11.06
  • 5,185 View
  • 177 Download
AbstractAbstract PDF
Background
Colorectal epithelial neoplasm extending into the submucosal gut-associated lymphoid tissue (GALT) can cause difficulties in the differential diagnosis. Regarding GALT-associated epithelial neoplasms, a few studies favor the term “GALT carcinoma” while other studies have mentioned the term “GALT-associated pseudoinvasion/epithelial misplacement (PEM)”.
Methods
The clinicopathologic characteristics of 11 cases of colorectal epithelial neoplasm associated with submucosal GALT diagnosed via endoscopic submucosal dissection were studied.
Results
Eight cases (72.7%) were in males. The median age was 59 years, and age ranged from 53 to 73. All cases had a submucosal tumor component more compatible with GALT-associated PEM. Eight cases (72.7%) were located in the right colon. Ten cases (90.9%) had a non-protruding endoscopic appearance. Nine cases (81.8%) showed continuity between the submucosal and surface adenomatous components. Nine cases showed (81.8%) focal defects or discontinuation of the muscularis mucosae adjacent to the submucosal GALT. No case showed hemosiderin deposits in the submucosa or desmoplastic reaction. No case showed single tumor cells or small clusters of tumor cells in the submucosal GALT. Seven cases (63.6%) showed goblet cells in the submucosa. No cases showed oncocytic columnar cells lining submucosal glands.
Conclusions
Our experience suggests that pathologists should be aware of the differential diagnosis of GALT-associated submucosal extension by colorectal adenomatous neoplasm. Further studies are needed to validate classification of GALT-associated epithelial neoplasms.
Double cocktail immunostains with high molecular weight cytokeratin and GATA-3: useful stain to discriminate in situ involvement of prostatic ducts or acini from stromal invasion by urothelial carcinoma in the prostate
Junghye Lee, Youngeun Yoo, Sanghui Park, Min-Sun Cho, Sun Hee Sung, Jae Y. Ro
J Pathol Transl Med. 2020;54(2):146-153.   Published online February 10, 2020
DOI: https://doi.org/10.4132/jptm.2019.11.12
  • 4,293 View
  • 93 Download
  • 1 Citations
AbstractAbstract PDF
Background
Distinguishing prostatic stromal invasion (PSI) by urothelial carcinoma (UC) from in situ UC involving prostatic ducts or acini with no stromal invasion (in situ involvement) may be challenging on hematoxylin and eosin stained sections. However, the distinction between them is important because cases with PSI show worse prognosis. This study was performed to assess the utility of double cocktail immunostains with high molecular weight cytokeratin (HMWCK) and GATA-3 to discriminate PSI by UC from in situ UC involvement of prostatic ducts or acini in the prostate.
Methods
Among 117 radical cystoprostatectomy specimens for bladder UCs, 25 cases showed secondary involvement of bladder UC in prostatic ducts/acini only or associated stromal invasion and of these 25 cases, seven cases revealed equivocal PSI. In these seven cases with equivocal PSI, HMWCK, and GATA-3 double immunohistochemical stains were performed to identify whether this cocktail stain is useful to identify the stromal invasion.
Results
In all cases, basal cells of prostate glands showed strong cytoplasmic staining for HMWCK and UC cells showed strong nuclear staining for GATA-3. In cases with stromal invasion of UC, GATA-3-positive tumor cells in the prostatic stroma without surrounding HMWCK-positive basal cells were highlighted and easily recognized. Among seven equivocal cases, two cases showed PSI and five in situ UC in the prostate. In two cases, the original diagnoses were revised.
Conclusions
Our study suggested that HMWCK and GATA-3 double stains could be utilized as an adjunct method in the distinction between PSI by UC from in situ UC involving prostatic ducts or acini.

Citations

Citations to this article as recorded by  
  • Utility of D2-40, Cytokeratin 5/6, and High–Molecular-weight Cytokeratin (Clone 34βE12) in Distinguishing Intraductal Spread of Urothelial Carcinoma From Prostatic Stromal Invasion
    Oleksii A. Iakymenko, Laurence M. Briski, Katiana S. Delma, Merce Jorda, Oleksandr N. Kryvenko
    American Journal of Surgical Pathology.2022; 46(4): 454.     CrossRef
Programmed death-ligand 1 expression and its correlation with clinicopathological parameters in gallbladder cancer
Ji Hye Kim, Kyungbin Kim, Misung Kim, Young Min Kim, Jae Hee Suh, Hee Jeong Cha, Hye Jeong Choi
J Pathol Transl Med. 2020;54(2):154-164.   Published online February 10, 2020
DOI: https://doi.org/10.4132/jptm.2019.11.13
  • 5,950 View
  • 146 Download
  • 10 Citations
AbstractAbstract PDF
Background
Immunomodulatory therapies targeting the interaction between programmed cell death protein 1 and programmed death-ligand 1 (PD-L1) have become increasingly important in anticancer treatment. Previous research on the subject of this immune response has established an association with tumor aggressiveness and a poor prognosis in certain cancers. Currently, scant information is available on the relationship between PD-L1 expression and gallbladder cancer (GBC).
Methods
We investigated the expression of PD-L1 in 101 primary GBC cases to determine the potential association with prognostic impact. PD-L1 expression was immunohistochemically assessed using a single PD-L1 antibody (clone SP263). Correlations with clinicopathological parameters, overall survival (OS), or progression- free survival (PFS) were analyzed.
Results
PD-L1 expression in tumor cells at cutoff levels of 1%, 10%, and 50% was present in 18.8%, 13.8%, and 7.9% of cases. Our study showed that positive PD-L1 expression at any cutoff was significantly correlated with poorly differentiated histologic grade and the presence of lymphovascular invasion (p < .05). PD-L1 expression at cutoff levels of 10% and 50% was significantly positive in patients with perineural invasion, higher T categories, and higher pathologic stages (p < .05). Additionally, there was a significant association noted between PD-L1 expression at a cutoff level of 50% and worse OS or PFS (p = .049 for OS, p = .028 for PFS). Other poor prognostic factors included histologic grade, T category, N category, pathologic stage, lymphovascular invasion, perineural invasion, growth pattern, and margin of resection (p < .05).
Conclusions
The expression of PD-L1 in GBC varies according to cutoff level but is valuably associated with poor prognostic parameters and survival. Our study indicates that the overexpression of PD-L1 in GBC had a negative prognostic impact.

Citations

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  • CD73 and PD-L1 as Potential Therapeutic Targets in Gallbladder Cancer
    Lu Cao, Kim R. Bridle, Ritu Shrestha, Prashanth Prithviraj, Darrell H. G. Crawford, Aparna Jayachandran
    International Journal of Molecular Sciences.2022; 23(3): 1565.     CrossRef
  • Evolving Role of Immunotherapy in Advanced Biliary Tract Cancers
    Sandra Kang, Bassel F. El-Rayes, Mehmet Akce
    Cancers.2022; 14(7): 1748.     CrossRef
  • Gallbladder carcinomas: review and updates on morphology, immunohistochemistry, and staging
    Whayoung Lee, Vishal S. Chandan
    Human Pathology.2022;[Epub]     CrossRef
  • Novel immune scoring dynamic nomograms based on B7-H3, B7-H4, and HHLA2: Potential prediction in survival and immunotherapeutic efficacy for gallbladder cancer
    Chao Lv, Shukun Han, Baokang Wu, Zhiyun Liang, Yang Li, Yizhou Zhang, Qi Lang, Chongli Zhong, Lei Fu, Yang Yu, Feng Xu, Yu Tian
    Frontiers in Immunology.2022;[Epub]     CrossRef
  • PD-1 inhibitors plus nab-paclitaxel-containing chemotherapy for advanced gallbladder cancer in a second-line setting: A retrospective analysis of a case series
    Sirui Tan, Jing Yu, Qiyue Huang, Nan Zhou, Hongfeng Gou
    Frontiers in Oncology.2022;[Epub]     CrossRef
  • Expression of HER2 and Mismatch Repair Proteins in Surgically Resected Gallbladder Adenocarcinoma
    You-Na Sung, Sung Joo Kim, Sun-Young Jun, Changhoon Yoo, Kyu-Pyo Kim, Jae Hoon Lee, Dae Wook Hwang, Shin Hwang, Sang Soo Lee, Seung-Mo Hong
    Frontiers in Oncology.2021;[Epub]     CrossRef
  • Programmed Death Ligand-1 (PD-L1) Is an Independent Negative Prognosticator in Western-World Gallbladder Cancer
    Thomas Albrecht, Fritz Brinkmann, Michael Albrecht, Anke S. Lonsdorf, Arianeb Mehrabi, Katrin Hoffmann, Yakup Kulu, Alphonse Charbel, Monika N. Vogel, Christian Rupp, Bruno Köhler, Christoph Springfeld, Peter Schirmacher, Stephanie Roessler, Benjamin Goep
    Cancers.2021; 13(7): 1682.     CrossRef
  • Immune Microenvironment in Gallbladder Adenocarcinomas
    Pallavi A. Patil, Kara Lombardo, Weibiao Cao
    Applied Immunohistochemistry & Molecular Morphology.2021; 29(8): 557.     CrossRef
  • Molecular Targets and Emerging Therapies for Advanced Gallbladder Cancer
    Matteo Canale, Manlio Monti, Ilario Giovanni Rapposelli, Paola Ulivi, Francesco Giulio Sullo, Giulia Bartolini, Elisa Tiberi, Giovanni Luca Frassineti
    Cancers.2021; 13(22): 5671.     CrossRef
  • Overview of current targeted therapy in gallbladder cancer
    Xiaoling Song, Yunping Hu, Yongsheng Li, Rong Shao, Fatao Liu, Yingbin Liu
    Signal Transduction and Targeted Therapy.2020;[Epub]     CrossRef
Adjunctive markers for classification and diagnosis of central nervous system tumors: results of a multi-center neuropathological survey in Korea
Yoon Jin Cha, Se Hoon Kim, Na Rae Kim
J Pathol Transl Med. 2020;54(2):165-170.   Published online February 20, 2020
DOI: https://doi.org/10.4132/jptm.2020.02.04
  • 5,091 View
  • 201 Download
  • 1 Citations
AbstractAbstract PDFSupplementary Material
Background
The revised 4th 2016 World Health Organization (WHO) classification of tumors of the central nervous system (CNS) classification has adopted integrated diagnosis encompassing the histology and molecular features of CNS tumors. We aimed to investigate the immunohistochemistry, molecular testing, and testing methods for diagnosis of CNS tumors in pathological labs of tertiary centers in Korea, and evaluate the adequacy of tests for proper diagnosis in daily practice.
Methods
A survey, composed of eight questions concerning molecular testing for diagnosis of CNS tumors, was sent to 10 neuropathologists working in tertiary centers in Korea.
Results
For diagnosis of astrocytic and oligodendroglial tumors, all 10 centers performed isocitrate dehydrogenase mutations testing and 1p/19q loss of heterozygosity. For glioneuronal tumors, immunohistochemistry (IHC) assays for synaptophysin (n = 9), CD34 (n = 7), BRAF(VE1) (n = 5) were used. For embryonal tumors, particularly in medulloblastoma, four respondents used IHC panel (growth factor receptor bound protein 2-associated protein 1, filamin A, and yes-associated protein 1) for molecular subclassification. Regarding meningioma, all respondents performed Ki-67 IHC and five performed telomerase reverse transcriptase promoter mutation.
Conclusions
Most tertiary centers made proper diagnosis in line with 2016 WHO classification. As classification of CNS tumors has evolved to be more complex and more ancillary tests are required, these should be performed considering the effect of necessity and justification.

Citations

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  • Exploring the role of epidermal growth factor receptor variant III in meningeal tumors
    Rashmi Rana, Vaishnavi Rathi, Kirti Chauhan, Kriti Jain, Satnam Singh Chhabra, Rajesh Acharya, Samir Kumar Kalra, Anshul Gupta, Sunila Jain, Nirmal Kumar Ganguly, Dharmendra Kumar Yadav, Timir Tripathi
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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
  • 4,924 View
  • 179 Download
AbstractAbstract 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
Case Studies
Inconspicuous longitudinal tears of the intracranial vertebral artery in traumatic basal subarachnoid hemorrhage
Seongho Kim
J Pathol Transl Med. 2020;54(2):179-183.   Published online November 8, 2019
DOI: https://doi.org/10.4132/jptm.2019.10.15
  • 6,201 View
  • 154 Download
AbstractAbstract PDF
Blunt force trauma to the head or neck region can cause traumatic basal subarachnoid hemorrhage (TBSAH), which can result in rapid loss of consciousness and death; however, detecting such a vascular injury is difficult. Posterior neck dissection was performed to investigate the bleeding focus in TBSAH cases 2018 and 2019. In all four cases, autopsies revealed a longitudinal tear in the midsection of the vertebral artery’s intracranial portion. The midportion of the intracranial vertebral artery appears to be most vulnerable to TBSAH. Interestingly, three of the cases showed only a vaguely visible longitudinal fissure in the artery without a grossly apparent tear; rupture was confirmed by microscopic examination. Longitudinal fissures of the intracranial vertebral artery, which are difficult to identify without detailed examination, may be overlooked in some cases of TBSAH. Thus, careful gross and microscopic examination of the vertebral artery is recommended in cases of TBSAH.
Primary carcinoid tumor in the external auditory canal
Dong Hae Chung, Gyu Cheol Han, Na Rae Kim
J Pathol Transl Med. 2020;54(2):184-187.   Published online November 13, 2019
DOI: https://doi.org/10.4132/jptm.2019.11.07
  • 4,300 View
  • 149 Download
  • 2 Citations
AbstractAbstract PDF
A 39-year-old man visited the department of otolaryngology due to an ongoing hearing disturbance that had lasted for 1 year. Temporal bone computed tomography revealed soft tissue density nearly obliterating the left external auditory canal (EAC). The mass was composed of sheets of round tumor cells containing moderate amounts of fine granular cytoplasm and salt and pepper chromatin. Neither mitosis nor necrosis was found. The Ki-67 proliferation index was less than 2%. Cells were positive for CD56 and synaptophysin but negative for chromogranin, cytokeratin (CK) 20, and CK7. Based on these findings, the tumor was diagnosed as a carcinoid tumor, well differentiated neuroendocrine carcinoma, grade 1 (G1) according to current World Health Organization (WHO) classification of head and neck tumors; and a neuroendocrine tumor, G1 according to neuroendocrine neoplasm (NEN)-2018 WHO standard classification. He remained free of local recurrence and metastasis after 20 months of follow up. To date, only six cases of primary NENs in the EAC have been reported. Metastatic tumor should be included in the differential diagnoses. Because of its rarity, the prognosis and treatment have not yet been clarified.

Citations

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  • Incidental finding of a neuroendocrine neoplasm in a suspected ear canal exostosis
    Alexander Wieck Fjaeldstad, Gerda Elisabeth Villadsen, Gitte Dam, Stephen Jacques Hamilton-Dutoit, Thomas Winther Frederiksen
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    Özge Erol Fenercioğlu, Ediz Beyhan, Rahime Şahin, Mehmet Can Baloğlu, Tevfik Fikret Çermik
    Clinical Nuclear Medicine.2022; 47(8): e552.     CrossRef
Brief Case Reports
Tumor-to-tumor metastasis: metastatic invasive lobular carcinoma of the breast within adenocarcinoma of the lung
Myoung Jae Kang, Ae Ri An, Myoung Ja Chung, Kyoung Min Kim
J Pathol Transl Med. 2020;54(2):188-191.   Published online September 16, 2019
DOI: https://doi.org/10.4132/jptm.2019.09.07
  • 3,639 View
  • 141 Download
  • 2 Citations
PDF

Citations

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  • Lobular to Lobule: Metastatic Breast Carcinoma to Olfactory Neuroblastoma
    Kent M. Swimley, Silvana Di Palma, Lester D. R. Thompson
    Head and Neck Pathology.2021; 15(2): 642.     CrossRef
  • A case of colorectal cancer with intratumoral metastasis to primary lung cancer
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Pseudomesotheliomatous carcinoma of the lung in the parietal pleura
Ae Ri An, Kyoung Min Kim, Jong Hun Kim, Gong Yong Jin, Young Hoon Choe, Myoung Ja Chung
J Pathol Transl Med. 2020;54(2):192-195.   Published online January 29, 2020
DOI: https://doi.org/10.4132/jptm.2019.11.14
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Corrigendum
Correction of acknowledgments: PD-L1 testing in non-small cell lung cancer: past, present, and future
Hyojin Kim, Jin-Haeng Chung
J Pathol Transl Med. 2020;54(2):196-196.   Published online March 10, 2020
DOI: https://doi.org/10.4132/jptm.2020.02.17
Corrects: J Pathol Transl Med 2019;53(4):199
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  • 68 Download
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JPTM : Journal of Pathology and Translational Medicine