Journal of Pathology and Translational Medicine

Original Articles

Clinicopathologic characterization of cervical metastasis from an unknown primary tumor: a multicenter study in Korea: Miseon Lee, Uiree Jo, Joon Seon Song, Youn Soo Lee, Chang Gok Woo, Dong-Hoon Kim, Jung Yeon Kim, Sun Och Yoon, Kyung-Ja Cho; J Pathol Transl Med. 2023;57(3):166-177. Published online May 10, 2023; DOI: https://doi.org/10.4132/jptm.2023.04.12

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Background
Research regarding cervical metastasis from an unknown primary tumor (CUP) according to human papillomavirus (HPV) and Epstein-Barr virus (EBV) status in Korea has been sporadic and small-scale. This study aims to analyze and understand the characteristics of CUP in Korea according to viral and p16 and p53 status through a multicenter study.
Methods
Ninety-five cases of CUP retrieved from six hospitals in Korea between January 2006 and December 2016 were subjected to high-risk HPV detection (DNA in situ hybridization [ISH] or real-time polymerase chain reaction), EBV detection (ISH), and immunohistochemistry for p16 and p53.
Results
CUP was HPV-related in 37 cases (38.9%), EBV-related in five cases (5.3%), and unrelated to HPV or EBV in 46 cases (48.4%). HPV-related CUP cases had the best overall survival (OS) (p = .004). According to the multivariate analysis, virus-unrelated disease (p = .023) and longer smoking duration (p < .005) were prognostic factors for poor OS. Cystic change (p = .016) and basaloid pattern (p < .001) were more frequent in HPV-related cases, and lymphoepithelial lesion was frequent in EBV-related cases (p = .010). There was no significant association between viral status and p53 positivity (p = .341), smoking status (p = .728), or smoking duration (p = .187). Korean data differ from Western data in the absence of an association among HPV, p53 positivity, and smoking history.
Conclusions
Virus-unrelated CUP in Korea had the highest frequency among all CUP cases. HPV-related CUP is similar to HPV-mediated oropharyngeal cancer and EBVrelated CUP is similar to nasopharyngeal cancer in terms of characteristics, respectively.

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Expansion of tumor-infiltrating lymphocytes from head and neck squamous cell carcinoma to assess the potential of adoptive cell therapy
Sangjoon Choi, Mofazzal Hossain, Hyun Lee, Jina Baek, Hye Seon Park, Chae-Lyul Lim, DoYeon Han, Taehyun Park, Jong Hyeok Kim, Gyungyub Gong, Mi-Na Kweon, Hee Jin Lee
Cancer Immunology, Immunotherapy.2024;[Epub] CrossRef

Sarcoma metastasis to the pancreas: experience at a single institution: Miseon Lee, Joon Seon Song, Seung-Mo Hong, Se Jin Jang, Jihun Kim, Ki Byung Song, Jae Hoon Lee, Kyung-Ja Cho; J Pathol Transl Med. 2020;54(3):220-227. Published online April 22, 2020; DOI: https://doi.org/10.4132/jptm.2020.03.04

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Abstract PDF

Background
Reports of metastatic sarcoma to the pancreas are limited. We reviewed the clinicopathologic characteristics of such cases.
Methods
We reviewed 124 cases of metastatic tumors to the pancreas diagnosed at Asan Medical Center between 2000 and 2017.
Results
Metastatic tumors to the pancreas consisted of 111 carcinomas (89.5%), 12 sarcomas (9.6%), and one melanoma (0.8%). Primary sarcoma sites were bone (n = 4); brain, lung, and soft tissue (n = 2 for each); and the uterus and pulmonary vein (n = 1 for each). Pathologically, the 12 sarcomas comprised 2 World Health Organization grade III solitary fibrous tumors/hemangiopericytomas, and one case each of synovial sarcoma, malignant solitary fibrous tumor, undifferentiated pleomorphic sarcoma, osteosarcoma, mesenchymal chondrosarcoma, intimal sarcoma, myxofibrosarcoma, myxoid liposarcoma, rhabdomyosarcoma, subtype uncertain, and high-grade spindle-cell sarcoma of uncertain type. The median interval between primary cancer diagnosis and pancreatic metastasis was 28.5 months. One case manifested as a solitary pancreatic osteosarcoma metastasis 15 months prior to detection of osteosarcoma in the femur and was initially misdiagnosed as sarcomatoid carcinoma of the pancreas.
Conclusions
The metastatic sarcoma should remain a differential diagnosis when spindle-cell malignancy is found in the pancreas, even for solitary lesions or in patients without prior history.

Citations

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Metástasis pancreática de sarcoma, un hallazgo infrecuente
Daniel Aparicio-López, Jorge Chóliz-Ezquerro, Carlos Hörndler-Algárate, Mario Serradilla-Martín
Gastroenterología y Hepatología.2023; 46(5): 376. CrossRef
Pancreatic metastasis from sarcoma, an infrequent finding
Daniel Aparicio-López, Jorge Chóliz-Ezquerro, Carlos Hörndler-Algárate, Mario Serradilla-Martín
Gastroenterología y Hepatología (English Edition).2023; 46(5): 376. CrossRef
Acute pancreatitis secondary to osteosarcoma metastasis
Pablo Salmón Olavarría, Ana Gordo Ortega, Maren Eizagirre Ubegun, Verónica Ubieto Capella, Elena Carracedo Vega, Juan Carrascosa Gil, David Ruiz-Clavijo García
Revista Española de Enfermedades Digestivas.2023;[Epub] CrossRef
First Recurrence of Synovial Sarcoma Presenting With Solitary Pancreatic Mass
Raja R Narayan, Greg W Charville, Daniel Delitto, Kristen N Ganjoo
Cureus.2022;[Epub] CrossRef
Intravenous Leiomyosarcoma of the Lower Extremity: As Peripheral as It Gets
Levent F Umur, Selami Cakmak, Mehmet Isyar, Hamdi Tokoz
Cureus.2021;[Epub] CrossRef
Could the burden of pancreatic cancer originate in childhood?
Smaranda Diaconescu, Georgiana Emmanuela Gîlcă-Blanariu, Silvia Poamaneagra, Otilia Marginean, Gabriela Paduraru, Gabriela Stefanescu
World Journal of Gastroenterology.2021; 27(32): 5322. CrossRef
Staged Surgical Resection of Primary Pulmonary Synovial Sarcoma with Synchronous Multiple Pancreatic Metastases: Report of a Rare Case and Review of the Literature
Panagiotis Dorovinis, Nikolaos Machairas, Stylianos Kykalos, Paraskevas Stamopoulos, George Agrogiannis, Nikolaos Nikiteas, Georgios C. Sotiropoulos
Journal of Gastrointestinal Cancer.2021; 52(3): 1151. CrossRef

Clinical Utility of a Fully Automated Microsatellite Instability Test with Minimal Hands-on Time: Miseon Lee, Sung-Min Chun, Chang Ohk Sung, Sun Y. Kim, Tae W. Kim, Se Jin Jang, Jihun Kim; J Pathol Transl Med. 2019;53(6):386-392. Published online October 11, 2019; DOI: https://doi.org/10.4132/jptm.2019.09.25

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Abstract PDF Supplementary Material

Background
Microsatellite instability (MSI) analysis is becoming increasingly important in many types of tumor including colorectal cancer (CRC). The commonly used MSI tests are either time-consuming or labor-intensive. A fully automated MSI test, the Idylla MSI assay, has recently been introduced. However, its diagnostic performance has not been extensively validated in clinical CRC samples.
Methods
We evaluated 133 samples whose MSI status had been rigorously validated by standard polymerase chain reaction (PCR), clinical nextgeneration sequencing (NGS) cancer panel test, or both. We evaluated the diagnostic performance of the Idylla MSI assay in terms of sensitivity, specificity, and positive and negative predictive values, as well as various sample requirements, such as minimum tumor purity and the quality of paraffin blocks.
Results
Compared with the gold standard results confirmed through both PCR MSI test and NGS, the Idylla MSI assay showed 99.05% accuracy (104/105), 100% sensitivity (11/11), 98.94% specificity (93/94), 91.67% positive predictive value (11/12), and 100% negative predictive value (93/93). In addition, the Idylla MSI assay did not require macro-dissection in most samples and reliably detected MSI-high in samples with approximately 10% tumor purity. The total turnaround time was about 150 minutes and the hands-on time was less than 2 minutes.
Conclusions
The Idylla MSI assay shows good diagnostic performance that is sufficient for its implementation in the clinic to determine the MSI status of at least the CRC samples. In addition, the fully automated procedure requires only a few slices of formalin-fixed paraffin-embedded tissue and might greatly save time and labor.

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Integration of rapid PCR testing as an adjunct to NGS in diagnostic pathology services within the UK: evidence from a case series of non-squamous, non-small cell lung cancer (NSCLC) patients with follow-up
Alison Finall, Gareth Davies, Trevor Jones, Gwion Emlyn, Pearl Huey, Anna Mullard
Journal of Clinical Pathology.2023; 76(6): 391. CrossRef
Analytical Validation and Clinical Utilization of the Oncomine Comprehensive Assay Plus Panel for Comprehensive Genomic Profiling in Solid Tumors
Catherine I. Dumur, Ramakrishnan Krishnan, Jorge A. Almenara, Kathleen E. Brown, Kailyn R. Dugan, Christiana Farni, Fatima Z. Ibrahim, Naomi A. Sanchez, Sumra Rathore, Dinesh Pradhan, Jonathan H. Hughes
Journal of Molecular Pathology.2023; 4(2): 109. CrossRef
Performance of Immunohistochemical and Molecular Methods in Detecting Microsatellite Instability in Gastric Cancer: A Multicenter Study
Diogo Sousa Marques, Irene Gullo, Luís Mascarenhas-Lemos, João Ricardo Silva, Catarina Neto do Nascimento, Patrícia Pontes, Lídia Pinho, Luis Cirnes, Xiaogang Wen, Marília Cravo, Fátima Carneiro
Pathobiology.2023; 90(6): 389. CrossRef
Diagnostic mutationnel rapide Idylla™ : applications théranostiques actuelles et futures
Amélie Bourhis, Annabelle Remoué, Laura Samaison, Arnaud Uguen
Annales de Pathologie.2022; 42(4): 329. CrossRef
Comparison of the Idylla™ MSI assay with the Promega™ MSI Analysis System and immunohistochemistry on formalin-fixed paraffin-embedded tissue of endometrial carcinoma: results from an international, multicenter study
Sonia Gatius, Ana Velasco, Mar Varela, Miriam Cuatrecasas, Pedro Jares, Lisa Setaffy, Benjamin Bonhomme, Almudena Santon, Kristina Lindemann, Sabrina Croce, Ben Davidson, Sigurd Lax, Jose Palacios, Xavier Matias-Guiu
Virchows Archiv.2022; 480(5): 1031. CrossRef
Idylla MSI test combined with immunohistochemistry is a valuable and cost effective strategy to search for microsatellite instable tumors of noncolorectal origin
Laura Samaison, Arnaud Uguen
Pathology International.2022; 72(4): 234. CrossRef
Detection of microsatellite instability in a panel of solid tumours with the Idylla MSI Test using extracted DNA
Adrien Pécriaux, Loetitia Favre, Julien Calderaro, Cécile Charpy, Jonathan Derman, Anaïs Pujals
Journal of Clinical Pathology.2021; 74(1): 36. CrossRef
Idylla microsatellite instability assay versus mismatch repair immunohistochemistry: a retrospective comparison in gastric adenocarcinoma
Luke Farmkiss, Ilona Hopkins, Mary Jones
Journal of Clinical Pathology.2021; 74(9): 604. CrossRef
Multi-center real-world comparison of the fully automated Idylla™ microsatellite instability assay with routine molecular methods and immunohistochemistry on formalin-fixed paraffin-embedded tissue of colorectal cancer
Ana Velasco, Fatma Tokat, Jesper Bonde, Nicola Trim, Elisabeth Bauer, Adam Meeney, Wendy de Leng, George Chong, Véronique Dalstein, Lorand L. Kis, Jon A. Lorentzen, Snjezana Tomić, Keeley Thwaites, Martina Putzová, Astrid Birnbaum, Romena Qazi, Vanessa Pr
Virchows Archiv.2021; 478(5): 851. CrossRef
Detection of microsatellite instability with Idylla MSI assay in colorectal and endometrial cancer
Iiris Ukkola, Pirjo Nummela, Annukka Pasanen, Mia Kero, Anna Lepistö, Soili Kytölä, Ralf Bützow, Ari Ristimäki
Virchows Archiv.2021; 479(3): 471. CrossRef
Managing Difficulties of Microsatellite Instability Testing in Endometrial Cancer-Limitations and Advantages of Four Different PCR-Based Approaches
Janna Siemanowski, Birgid Schömig-Markiefka, Theresa Buhl, Anja Haak, Udo Siebolts, Wolfgang Dietmaier, Norbert Arens, Nina Pauly, Beyhan Ataseven, Reinhard Büttner, Sabine Merkelbach-Bruse
Cancers.2021; 13(6): 1268. CrossRef
Evaluation of Micro Satellite Instability and Mismatch Repair Status in Different Solid Tumors: A Multicenter Analysis in a Real World Setting
Umberto Malapelle, Paola Parente, Francesco Pepe, Caterina De Luca, Pasquale Pisapia, Roberta Sgariglia, Mariantonia Nacchio, Gianluca Gragnano, Gianluca Russo, Floriana Conticelli, Claudio Bellevicine, Elena Vigliar, Antonino Iaccarino, Claudia Covelli,
Cells.2021; 10(8): 1878. CrossRef
Novel Biocartis Idylla™ cartridge-based assay for detection of microsatellite instability in colorectal cancer tissues
Andres E. Mindiola-RomeroMD, Donald C. GreenBS, M. Rabie Al-TurkmaniPhD, Kelley N. GodwinBS, Anna C. MackayBS, Laura J. TafeMD, Bing RenMD, Gregory J. TsongalisPhD
Experimental and Molecular Pathology.2020; 116: 104519. CrossRef
Evaluation of 3 molecular-based assays for microsatellite instability detection in formalin-fixed tissues of patients with endometrial and colorectal cancers
Pauline Gilson, Julien Levy, Marie Rouyer, Jessica Demange, Marie Husson, Céline Bonnet, Julia Salleron, Agnès Leroux, Jean-Louis Merlin, Alexandre Harlé
Scientific Reports.2020;[Epub] CrossRef

Association between p53 Expression and Amount of Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer: Miseon Lee, In Ah Park, Sun-Hee Heo, Young-Ae Kim, Gyungyub Gong, Hee Jin Lee; J Pathol Transl Med. 2019;53(3):180-187. Published online March 11, 2019; DOI: https://doi.org/10.4132/jptm.2019.02.08

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Abstract PDF

Background
Most triple-negative breast cancers (TNBCs) have a high histologic grade, are associated with high endoplasmic stress, and possess a high frequency of TP53 mutations. TP53 missense mutations lead to the production of mutant p53 protein and usually show high levels of p53 protein expression. Tumor-infiltrating lymphocytes (TILs) accumulate as part of the anti-tumor immune response and have a strong prognostic and predictive significance in TNBC. We aimed to elucidate the association between p53 expression and the amount of TILs in TNBC.
Methods
In 678 TNBC patients, we evaluated TIL levels and expression of endoplasmic stress molecules. Immunohistochemical examination of p53 protein expression was categorized into three groups: no, low, and high expression.
Results
No, low, and high p53 expression was identified in 44.1% (n = 299), 20.1% (n = 136), and 35.8% (n = 243) of patients, respectively. Patients with high p53 expression showed high histologic grade (p < .001), high TIL levels (p = .009), and high expression of endoplasmic reticulum stress-associated molecules (p-eIF2a, p = .013; XBP1, p = .007), compared to patients with low p53 expression. There was no significant difference in disease-free (p = .406) or overall survival rates (p = .444) among the three p53 expression groups.
Conclusions
High p53 expression is associated with increased expression of endoplasmic reticulum stress molecules and TIL influx.

Citations

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