Journal of Pathology and Translational Medicine

Review

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

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

Original Articles

BRCA-mutated gastric adenocarcinomas are associated with chromosomal instability and responsiveness to platinum-based chemotherapy: Ji Hyun Oh, Chang Ohk Sung, Hyung-Don Kim, Sung-Min Chun, Jihun Kim; J Pathol Transl Med. 2023;57(6):323-331. Published online November 14, 2023; DOI: https://doi.org/10.4132/jptm.2023.10.22

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Abstract PDF Supplementary Material: Background
Homologous recombination defect is an important biomarker of chemotherapy in certain tumor types, and the presence of pathogenic or likely pathogenic mutations involving BRCA1 or BRCA2 (p-BRCA) mutations is the most well-established marker for the homologous recombination defect. Gastric cancer, one of the most prevalent tumor types in Asia, also harbors p-BRCA mutations.
Methods
To investigate the clinical significance of p-BRCA mutations, we analyzed 366 gastric cancer cases through next-generation sequencing. We determined the zygosity of p-BRCA mutations based on the calculated tumor purity through variant allelic fraction patterns and investigated whether the presence of p-BRCA mutations is associated with platinum-based chemotherapy and a certain molecular subtype.
Results
Biallelic p-BRCA mutation was associated with better response to platinum-based chemotherapy than heterozygous p-BRCA mutation or wild type BRCA genes. The biallelic p-BRCA mutations was observed only in the chromosomal instability subtype, while all p-BRCA mutations were heterozygous in microsatellite instability subtype.
Conclusions
In conclusion, patients with gastric cancer harboring biallelic p-BRCA mutations were associated with a good initial response to platinum-based chemotherapy and those tumors were exclusively chromosomal instability subtype. Further investigation for potential association with homologous recombination defect is warranted.

Extremely well-differentiated adenocarcinoma of the stomach: diagnostic pitfalls in endoscopic biopsy: Jongwon Lee, In-Seob Lee, Ji Yong Ahn, Young Soo Park, Jihun Kim; J Pathol Transl Med. 2022;56(2):63-72. Published online November 16, 2021; DOI: https://doi.org/10.4132/jptm.2021.10.12

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Abstract PDF Supplementary Material

Background
Extremely well-differentiated adenocarcinoma (EWDA) is a deceptively bland-looking adenocarcinoma of the stomach. It often causes diagnostic problems, especially in endoscopic biopsy samples. To better recognize this deceptively bland lesion, we carefully reviewed a series of EWDAs treated at our institution.
Methods
A total of 55 specimens from 19 patients were obtained. Endoscopic, gross and microscopic features defining EWDA were described and documented. For comparison, hyperplastic polyp specimens were randomly selected and analyzed.
Results
Most cases (18 of 19, 94.7%) were advanced gastric cancer (AGC) and primarily located in the body of the stomach (15 of 19, 79.0%). The majority of AGCs were non-ulcerated (11 of 18, 61.1%) with an undermining growth pattern and a relatively small mucosal involvement. Specific histologic features included an irregular glandular shape, an undulating apical cytoplasmic border, disproportionately large glands, a variably distended mucinous cytoplasm. Classical features, such as small infiltrating glands or desmoplastic reactions, were barely observed. Identification of irregularly spaced nuclei and disruption of the foveolar epithelial structure, along with atypical features described above were helpful in making a diagnosis especially in gastric forceps biopsies.
Conclusions
Awareness of the histomorphologic characteristics described in this report would lead to timely diagnosis and prevent repeated endoscopic procedures.

Citations

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Unusual or Uncommon Histology of Gastric Cancer
Jinho Shin, Young Soo Park
Journal of Gastric Cancer.2024; 24(1): 69. CrossRef
A case of gastric adenocarcinoma with pyloric gland-type infiltrating submucosa
Kaiho Hirata, Shusuke Yagi, Hideki Miyazaki, Kazuhiko Yamada, Naoki Akazawa, Naoki Enomoto, Kyoko Nohara, Chizu Yokoi, Toru Igari, Norihiro Kokudo
Surgical Case Reports.2024;[Epub] CrossRef

Case Study

Primary hepatic mixed germ cell tumor in an adult: Hyun-Jung Sung, Jihun Kim, Kyu-rae Kim, Shinkyo Yoon, Jae Hoon Lee, Hyo Jeong Kang; J Pathol Transl Med. 2021;55(5):355-359. Published online August 3, 2021; DOI: https://doi.org/10.4132/jptm.2021.06.16

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Abstract PDF

Primary hepatic mixed germ cell tumor (GCT) is very rare, and less than 10 cases have been reported. We report a case of mixed GCT composed of a choriocarcinoma and yolk sac tumor, which occurred in the liver of a 40-year-old woman. A large mass was detected by computed tomography solely in the liver. Serum β-human chorionic gonadotropin (hCG) was highly elevated, otherwise, other serum tumor markers were slightly elevated or within normal limits. For hepatic choriocarcinoma, neoadjuvant chemotherapy was administered, followed by right lobectomy. Histologic features of the resected tumor revealed characteristic choriocarcinoma features with diffuse positivity for hCG in the syncytiotrophoblasts and diffuse positivity for α-fetoprotein and Sal-like protein 4 in the yolk sac tumor components. Primary malignant GCT in the liver is associated with a poor prognosis and requires specific treatment. Therefore, GCT should be considered during a differential diagnosis of a rapidly growing mass in the liver.

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Testicular Seminoma in Prostate: Case Report and Review of Literature
Peter Lesko, Jana Obertova, Karol Kajo, Katarina Rejlekova, Zuzana Orszaghova, Viera Lehotska, Martina Ondrusova, Michal Chovanec, Dalibor Ondrus, Michal Mego
Clinical Genitourinary Cancer.2024; 22(2): 210. CrossRef

Review

Standardization of the pathologic diagnosis of appendiceal mucinous neoplasms: Dong-Wook Kang, Baek-hui Kim, Joon Mee Kim, Jihun Kim, Hee Jin Chang, Mee Soo Chang, Jin-Hee Sohn, Mee-Yon Cho, So-Young Jin, Hee Kyung Chang, Hye Seung Han, Jung Yeon Kim, Hee Sung Kim, Do Youn Park, Ha Young Park, So Jeong Lee, Wonae Lee, Hye Seung Lee, Yoo Na Kang, Younghee Choi; J Pathol Transl Med. 2021;55(4):247-264. Published online July 8, 2021; DOI: https://doi.org/10.4132/jptm.2021.05.28

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Abstract PDF Supplementary Material

Although the understanding of appendiceal mucinous neoplasms (AMNs) and their relationship with disseminated peritoneal mucinous disease have advanced, the diagnosis, classification, and treatment of AMNs are still confusing for pathologists and clinicians. The Gastrointestinal Pathology Study Group of the Korean Society of Pathologists (GPSG-KSP) proposed a multicenter study and held a workshop for the “Standardization of the Pathologic Diagnosis of the Appendiceal Mucinous Neoplasm” to overcome the controversy and potential conflicts. The present article is focused on the diagnostic criteria, terminologies, tumor grading, pathologic staging, biologic behavior, treatment, and prognosis of AMNs and disseminated peritoneal mucinous disease. In addition, GPSG-KSP proposes a checklist of standard data elements of appendiceal epithelial neoplasms to standardize pathologic diagnosis. We hope the present article will provide pathologists with updated knowledge on how to handle and diagnose AMNs and disseminated peritoneal mucinous disease.

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Lower Gastrointestinal Bleeding Secondary to Appendiceal Mucinous Neoplasm: A Report of Two Cases and a Review of the Literature
Jesús Omar Soto Llanes, Samanta Kin Dosal Limón, Ana Jimena Iberri Jaime, Mario Zambrano Lara, Billy Jiménez Bobadilla
Cureus.2024;[Epub] CrossRef
Appendiceal perforation secondary to endometriosis with intestinal metaplasia: A case report
Minghua Wang, Jing Liu, Boxin Hu, Simin Wang, Ping Xie, Ping Li
Experimental and Therapeutic Medicine.2023;[Epub] CrossRef
Primary and secondary tumors of the peritoneum: key imaging features and differential diagnosis with surgical and pathological correlation
Javier Miguez González, Francesc Calaf Forn, Laura Pelegrí Martínez, Pilar Lozano Arranz, Rafael Oliveira Caiafa, Jordi Català Forteza, Lina Maria Palacio Arteaga, Ferrán Losa Gaspà, Isabel Ramos Bernadó, Pedro Barrios Sánchez, Juan Ramón Ayuso Colella
Insights into Imaging.2023;[Epub] CrossRef
Muzinöse Tumoren des Peritoneums
Anne Kristin Fischer, Andrea Tannapfel, Alexander Quaas
Die Chirurgie.2023; 94(10): 823. CrossRef
Landscape of Genetic Mutations in Appendiceal Cancers
Marian Constantin, Cristina Mătanie, Livia Petrescu, Alexandra Bolocan, Octavian Andronic, Coralia Bleotu, Mihaela Magdalena Mitache, Sorin Tudorache, Corneliu Ovidiu Vrancianu
Cancers.2023; 15(14): 3591. CrossRef
Delivery of an Incidental Appendiceal Mucinous Neoplasm
Madison Bowles, Jessica Y Ng, Hajir Nabi
Cureus.2022;[Epub] CrossRef
Unearthing novel fusions as therapeutic targets in solid tumors using targeted RNA sequencing
Sungbin An, Hyun Hee Koh, Eun Sol Chang, Juyoung Choi, Ji-Young Song, Mi-Sook Lee, Yoon-La Choi
Frontiers in Oncology.2022;[Epub] CrossRef

Case Study

Appendiceal actinomycosis mimicking appendiceal tumor, appendicitis or inflammatory bowel disease: You-Na Sung, Jihun Kim; J Pathol Transl Med. 2021;55(5):349-354. Published online June 26, 2020; DOI: https://doi.org/10.4132/jptm.2020.05.17

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Abstract PDF

Appendiceal actinomycosis is very rare and its diagnosis is often difficult even in surgically resected specimens. Here we report two cases of appendiceal actinomycosis confirmed by pathologic examination of surgically resected specimens. Characteristic histologic features included transmural chronic inflammation with Crohn-like lymphoid aggregates and polypoid mucosal protrusion into cecal lumen through fibrous expansion of the submucosa. Chronic active inflammation involved the mucosa of the appendix and cecum around the appendiceal orifice. Crohn’s disease with predominant cecal involvement and inflammatory pseudotumor were considered as differential diagnoses. Careful examination revealed a few actinomycotic colonies in the mucosa, confirming the diagnosis. A high index of suspicion with awareness of the characteristic histologic features might prompt careful inspection for the actinomycotic colonies, leading to the appropriate diagnosis of this rare disease.

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Appendicular actinomycosis: The first reported case of an uncommon finding of a common ailment from Nepal
Sujan Bohara, Manoj Khadka, Pawan Singh Bhat, Prajwal Syangtang, Badal Karki, Bhagawan Shrestha, Shoshan Arja Acharya, Khusbhu Khetan, Jyoti Rayamajhi, Sushil Bahadur Rawal
Clinical Case Reports.2023;[Epub] CrossRef
Abdominopelvic actinomycosis: An unexpected diagnosis in an elderly female with a destructive-appearing soft tissue mass
Elise Hyser, Drashti Antala, Harvey Friedman, Jonathan Stake
IDCases.2022; 28: e01479. CrossRef

Original Articles

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

Guanabenz Acetate Induces Endoplasmic Reticulum Stress–Related Cell Death in Hepatocellular Carcinoma Cells: Hyo Jeong Kang, Hyang Sook Seol, Sang Eun Lee, Young-Ah Suh, Jihun Kim, Se Jin Jang, Eunsil Yu; J Pathol Transl Med. 2019;53(2):94-103. Published online January 16, 2019; DOI: https://doi.org/10.4132/jptm.2019.01.14

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Abstract PDF Supplementary Material

Background
Development of chemotherapeutics for the treatment of advanced hepatocellular carcinoma (HCC) has been lagging. Screening of candidate therapeutic agents by using patient-derived preclinical models may facilitate drug discovery for HCC patients.
Methods
Four primary cultured HCC cells from surgically resected tumor tissues and six HCC cell lines were used for high-throughput screening of 252 drugs from the Prestwick Chemical Library. The efficacy and mechanisms of action of the candidate anti-cancer drug were analyzed via cell viability, cell cycle assays, and western blotting.
Results
Guanabenz acetate, which has been used as an antihypertensive drug, was screened as a candidate anti-cancer agent for HCC through a drug sensitivity assay by using the primary cultured HCC cells and HCC cell lines. Guanabenz acetate reduced HCC cell viability through apoptosis and autophagy. This occurred via inhibition of growth arrest and DNA damage-inducible protein 34, increased phosphorylation of eukaryotic initiation factor 2α, increased activating transcription factor 4, and cell cycle arrest.
Conclusions
Guanabenz acetate induces endoplasmic reticulum stress–related cell death in HCC and may be repositioned as an anti-cancer therapeutic agent for HCC patients.

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Current trends and future prospects of drug repositioning in gastrointestinal oncology
Nayeralsadat Fatemi, Mina Karimpour, Hoda Bahrami, Mohammad Reza Zali, Vahid Chaleshi, Andrea Riccio, Ehsan Nazemalhosseini-Mojarad, Mehdi Totonchi
Frontiers in Pharmacology.2024;[Epub] CrossRef
The integrated stress response in cancer progression: a force for plasticity and resistance
Caleb L. Lines, Morgan J. McGrath, Tanis Dorwart, Crystal S. Conn
Frontiers in Oncology.2023;[Epub] CrossRef
Endoplasmic reticulum stress: Multiple regulatory roles in hepatocellular carcinoma
Jiacheng Wu, Shan Qiao, Yien Xiang, Menying Cui, Xiaoxiao Yao, Ruixin Lin, Xuewen Zhang
Biomedicine & Pharmacotherapy.2021; 142: 112005. CrossRef
The two faces of the Integrated Stress Response in cancer progression and therapeutic strategies
Eugenia Licari, Luis Sánchez-del-Campo, Paola Falletta
The International Journal of Biochemistry & Cell Biology.2021; 139: 106059. CrossRef
Repurposing of Guanabenz acetate by encapsulation into long-circulating nanopolymersomes for treatment of triple-negative breast cancer
Yusuf A. Haggag, Mohamed Yasser, Murtaza M. Tambuwala, Suleiman S. El Tokhy, Mohammad Isreb, Ahmed A. Donia
International Journal of Pharmaceutics.2021; 600: 120532. CrossRef
Endoplasmic reticulum stress: New insights into the pathogenesis and treatment of retinal degenerative diseases
Marina S. Gorbatyuk, Christopher R. Starr, Oleg S. Gorbatyuk
Progress in Retinal and Eye Research.2020; 79: 100860. CrossRef
Delineating the role of eIF2α in retinal degeneration
Christopher R. Starr, Marina S. Gorbatyuk
Cell Death & Disease.2019;[Epub] CrossRef
Repositioning of Guanabenz in Conjugation with Gold and Silver Nanoparticles against Pathogenic Amoebae Acanthamoeba castellanii and Naegleria fowleri
Areeba Anwar, Mohammad Ridwane Mungroo, Ayaz Anwar, William J. Sullivan, Naveed Ahmed Khan, Ruqaiyyah Siddiqui
ACS Infectious Diseases.2019; 5(12): 2039. CrossRef

Utility of BRAF VE1 Immunohistochemistry as a Screening Tool for Colorectal Cancer Harboring BRAF V600E Mutation: Jeong-Hwa Kwon, Byung-Kwan Jeong, Yong Sik Yoon, Chang Sik Yu, Jihun Kim; J Pathol Transl Med. 2018;52(3):157-163. Published online March 29, 2018; DOI: https://doi.org/10.4132/jptm.2018.03.28

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Abstract PDF Supplementary Material

Background
BRAF mutation has been recognized as an important biomarker of colorectal cancer (CRC) for targeted therapy and prognosis prediction. However, sequencing for every CRC case is not cost-effective. An antibody specific for BRAF V600E mutant protein has been introduced, and we thus examined the utility of BRAF VE1 immunohistochemistry for evaluating BRAF mutations in CRC.
Methods
Fifty-one BRAF-mutated CRCs and 100 age and sexmatched BRAF wild-type CRCs between 2005 and 2015 were selected from the archives of Asan Medical Center. Tissue microarrays were constructed and stained with BRAF VE1 antibody.
Results
Forty-nine of the 51 BRAF-mutant CRCs (96.1%) showed more than moderate cytoplasmic staining, except for two weakly stained cases. Six of 100 BRAF wild-type cases also stained positive with BRAF VE1 antibody; four stained weakly and two stained moderately. Normal colonic crypts showed nonspecific weak staining, and a few CRC cases exhibited moderate nuclear reactivity (3 BRAF-mutant and 10 BRAF wild-type cases). BRAF-mutated CRC patients had higher pathologic stages and worse survival than BRAF wild-type patients.
Conclusions
BRAF VE1 immunohistochemistry showed high sensitivity and specificity, but occasional nonspecific staining in tumor cell nuclei and normal colonic crypts may limit their routine clinical use. Thus, BRAF VE1 immunohistochemistry may be a useful screening tool for BRAF V600E mutation in CRCs, provided that additional sequencing studies can be done to confirm the mutation in BRAF VE1 antibody-positive cases.

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Immunohistochemistry as a Surrogate Marker of Underlying Molecular Derangements in Sporadic Colorectal Carcinoma in Children – A Series of Three Cases
Priyanka Maity, Aniket Halder, Ranajoy Ghosh, Uttara Chatterjee, Shibsankar Barman, Ruchirendra Sarkar
Fetal and Pediatric Pathology.2022; 41(1): 98. CrossRef
Risk assessment and genetic counseling for Lynch syndrome – Practice resource of the National Society of Genetic Counselors and the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer
Spring Holter, Michael J. Hall, Heather Hampel, Kory Jasperson, Sonia S. Kupfer, Joy Larsen Haidle, Maureen E. Mork, Selvi Palaniapppan, Leigha Senter, Elena M. Stoffel, Scott M. Weissman, Matthew B. Yurgelun
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Current concepts in ameloblastoma-targeted therapies in B-raf proto-oncogene serine/threonine kinase V600E mutation: Systematic review
Rogelio González-González, Sandra López-Verdín, Jesús Lavalle-Carrasco, Nelly Molina-Frechero, Mario Isiordia-Espinoza, Ramón G Carreón-Burciaga, Ronell Bologna-Molina
World Journal of Clinical Oncology.2020; 11(1): 31. CrossRef
Genetic and histopathological analysis of a case of primary intraosseous carcinoma, NOS with features of both ameloblastic carcinoma and squamous cell carcinoma
Akane Yukimori, Maiko Tsuchiya, Akane Wada, Yasuyuki Michi, Kou Kayamori, Kei Sakamoto, Tohru Ikeda
World Journal of Surgical Oncology.2020;[Epub] CrossRef

Case Study

Hepatocellular Carcinoma Arising in a Huge Hepatocellular Adenoma with Bone Marrow Metaplasia: Hyo Jeong Kang, Hui Jeong Jeong, So-Woon Kim, Eunsil Yu, Young-Joo Lee, So Yeon Kim, Jihun Kim; J Pathol Transl Med. 2018;52(4):226-231. Published online December 27, 2017; DOI: https://doi.org/10.4132/jptm.2017.11.12

5,955 View
146 Download
5 Web of Science
6 Crossref

Abstract PDF

Hepatocellular adenoma (HCA) is the most common type of benign liver tumor, and its major complication is malignant transformation to hepatocellular carcinoma (HCC). Here, we report a case of HCC arising in HCA with bone marrow metaplasia in a 24-year-old Korean woman who presented with abdominal discomfort. A huge liver mass was found on abdominal ultrasonography. She underwent surgical hepatic resection, and the resected specimen was entirely involved by a 20-cm-sized tumor. Histological review revealed a well differentiated HCC arising from inflammatory HCA with β-catenin nuclear positivity and bone marrow metaplasia that contained hematopoietic cells. This case was unique because malignant transformation, inflammatory type HCA, β-catenin nuclear staining, and bone marrow metaplasia were simultaneously observed. Additionally, it should be noted that a large HCA with β-catenin activation can undergo malignant transformation and should be surgically resected in a timely manner.

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Adult Hepatocellular Carcinoma Coexisting with Extramedullary Hematopoiesis
Hirotsugu Noguchi, Michiyo Higashi, Ryo Desaki, Takashi Tasaki, Mari Kirishima, Ikumi Kitazono, Kazuhiro Tabata, Akihide Tanimoto
International Journal of Surgical Pathology.2022; 30(3): 339. CrossRef
Spontaneous Occurrence of Various Types of Hepatocellular Adenoma in the Livers of Metabolic Syndrome-Associated Steatohepatitis Model TSOD Mice
Wenhua Shao, Orgil Jargalsaikhan, Mayuko Ichimura-Shimizu, Qinyi Cai, Hirohisa Ogawa, Yuko Miyakami, Kengo Atsumi, Mitsuru Tomita, Mitsuko Sutoh, Shunji Toyohara, Ryoji Hokao, Yasusei Kudo, Takeshi Oya, Koichi Tsuneyama
International Journal of Molecular Sciences.2022; 23(19): 11923. CrossRef
Bilateral Diffuse Nodular Pulmonary Ossification Mimicking Metastatic Disease in a Patient with Fibrolamellar Hepatocellular Carcinoma
Pattamon Sutthatarn, Cara E. Morin, Jessica Gartrell, Wayne L. Furman, Max R. Langham, Teresa Santiago, Andrew J. Murphy
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Hepatocellular carcinoma arising from hepatic adenoma in a young woman
Haythem Yacoub, Hela Kchir, Dhouha Cherif, Hajer Hassine, Slim Haouet, Asma Ayari, Habiba Mizouni, Saber Mannai, Mohamed Tahar Khalfallah, Nadia Maamouri
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Review

Good Laboratory Standards for Clinical Next-Generation Sequencing Cancer Panel Tests: Jihun Kim, Woong-Yang Park, Nayoung K. D. Kim, Se Jin Jang, Sung-Min Chun, Chang-Ohk Sung, Jene Choi, Young-Hyeh Ko, Yoon-La Choi, Hyo Sup Shim, Jae-Kyung Won; J Pathol Transl Med. 2017;51(3):191-204. Published online May 10, 2017; DOI: https://doi.org/10.4132/jptm.2017.03.14

22,941 View
1,056 Download
30 Web of Science
31 Crossref

Abstract PDF

Next-generation sequencing (NGS) has recently emerged as an essential component of personalized cancer medicine due to its high throughput and low per-base cost. However, no sufficient guidelines for implementing NGS as a clinical molecular pathology test are established in Korea. To ensure clinical grade quality without inhibiting adoption of NGS, a taskforce team assembled by the Korean Society of Pathologists developed laboratory guidelines for NGS cancer panel testing procedures and requirements for clinical implementation of NGS. This consensus standard proposal consists of two parts: laboratory guidelines and requirements for clinical NGS laboratories. The laboratory guidelines part addressed several important issues across multistep NGS cancer panel tests including choice of gene panel and platform, sample handling, nucleic acid management, sample identity tracking, library preparation, sequencing, analysis and reporting. Requirements for clinical NGS tests were summarized in terms of documentation, validation, quality management, and other required written policies. Together with appropriate pathologist training and international laboratory standards, these laboratory standards would help molecular pathology laboratories to successfully implement NGS cancer panel tests in clinic. In this way, the oncology community would be able to help patients to benefit more from personalized cancer medicine.

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Case Study

IgG4-Related Disease Presented as a Mural Mass in the Stomach: Chang Gok Woo, Jeong Hwan Yook, Ah Young Kim, Jihun Kim; J Pathol Transl Med. 2016;50(1):67-70. Published online September 30, 2015; DOI: https://doi.org/10.4132/jptm.2015.07.28

8,119 View
84 Download
21 Web of Science
21 Crossref

Abstract PDF

Isolated gastric IgG4-related disease (IgG4-RD) is a very rare tumefactive inflammatory condition, with only a few cases reported to date. A 48-year-old woman was incidentally found to have a subepithelial tumor in the stomach. Given a presumptive diagnosis of gastrointestinal stromal tumor or neuroendocrine tumor, she underwent wedge resection. The lesion was vaguely nodular and mainly involved the submucosa and proper muscle layer. Microscopically, all classical features of type I autoimmune pancreatitis including lymphoplasmacytic infiltration, storiform fibrosis, obliterative phlebitis, and numerous IgG4-positive plasma cells were seen. She had no evidence of IgG4-RD in other organs. Although very rare, IgG4-RD should be considered one of the differential diagnoses in the setting of gastric wall thickening or subepithelial mass-like lesion. Deep biopsy with awareness of this entity might avoid unnecessary surgical intervention.

Citations

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Value of High‐Frequency Ultrasonography in the Qualitative and Semi‐Quantitative Assessment of Immunoglobulin G4‐Related Submandibular Sialadenitis
Lei Chen, Lin Nong, Jumei Liu, Luzeng Chen, Yuhong Shao, Xiuming Sun
Journal of Ultrasound in Medicine.2023; 42(10): 2235. CrossRef
IgG4-related pseudotumours: a series of 12 cases and a review of the literature
Andrea Maccagno, Bianca Grosser, László Füzesi, Björn Konukiewitz, Dmytro Vlasenko, Dorothea Weckermann, Stephan Raab, Johannes Zenk, Abbas Agaimy, Bruno Märkl
Pathology.2022; 54(5): 563. CrossRef
IgG4-Related Disease With Gastrointestinal Involvement: Case Reports and Literature Review
Xinhe Zhang, Xing Jin, Lin Guan, Xuyong Lin, Xuedan Li, Yiling Li
Frontiers in Immunology.2022;[Epub] CrossRef
Clinicopathological characteristics of gastric IgG4‐related disease: Systematic scoping review
Haruki Sawada, Torrey Czech, Krixie Silangcruz, Landon Kozai, Adham Obeidat, Eric Andrew Wien, Midori Filiz Nishimura, Asami Nishikori, Yasuharu Sato, Yoshito Nishimura
Journal of Gastroenterology and Hepatology.2022; 37(10): 1865. CrossRef
Utility of gastric biopsy in diagnosing IgG4‐related gastrointestinal disease
Kaori Uchino, Kenji Notohara, Takeshi Uehara, Yasuhiro Kuraishi, Junya Itakura, Akihiro Matsukawa
Pathology International.2021; 71(2): 124. CrossRef
A reappraisal of sclerosing nodular and/or polypoid lesions of the gastrointestinal tract rich in IgG4‐positive plasma cells
Runjan Chetty
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Gastric IgG4-related disease presenting as a mass lesion and masquerading as a gastrointestinal stromal tumor
Banumathi Ramakrishna, Rohan Yewale, Kavita Vijayakumar, Patta Radhakrishna, Balakrishnan Siddartha Ramakrishna
Journal of Pathology and Translational Medicine.2020; 54(3): 258. CrossRef
IgG4-related Sclerosing Disease Forming a Gastric Submucosal Tumor Diagnosed after Laparoscopic Endoscopic Cooperative Surgery—Report of a Case—
Tatsuki ISHIKAWA, Katsunori NAKANO, Masafumi OSAKA, Yayoi KADOTANI, Kaori OKUGAWA, Kiyokazu AKIOKA, Kenta SHIGEMORI, Yohei HOSOKAWA
Nihon Rinsho Geka Gakkai Zasshi (Journal of Japan Surgical Association).2020; 81(2): 254. CrossRef
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Donald Turbiville, Xu-Chen Zhang
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A Suspected Case of IgG4-Related Appendiceal Pseudotumor
Yudai Hojo, Yoshiharu Shirakata, Ai Izumi, Jun Matsui, Tokuyuki Yamashita, Hikaru Aoki, Makoto Kurimoto, Masaaki Hirata, Naoki Goda, Hiroaki Ito, Jun Tamura
The Japanese Journal of Gastroenterological Surgery.2020; 53(12): 976. CrossRef
Immunoglobulin G4-related gastric pseudotumor – An impostor: Case report
Manuel Santiago Mosquera, Andrea Suarez Gómez, Hugo Herrera, Karen Moreno-Medina, Alejandro González-Orozco, Carlos J-Perez Rivera
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Dai Inoue, Norihide Yoneda, Kotaro Yoshida, Hiromi Nuka, Jun Kinoshita, Sachio Fushida, Fumihito Toshima, Tetsuya Minami, Masayuki Takahira, Shoko Hamaoka, Hiroko Ikeda, Toshifumi Gabata, Mitsuhiro Kawano
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Immunoglobulin G4-Related Gastric Ulcer Mimicking Advanced Stomach Cancer in a Patient with Type I Autoimmune Pancreatitis
Joung Ha Park, Jin Hee Noh, Jang ho Lee, Goeun Lee, Seung-Mo Hong, Kwang Bum Cho, Myung-Hwan Kim
The Korean Journal of Medicine.2019; 94(3): 287. CrossRef
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Raquel Sánchez-Oro, Elsa María Alonso-Muñoz, Lidia Martí Romero
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Revisión de la enfermedad relacionada con la IgG4
Raquel Sánchez-Oro, Elsa María Alonso-Muñoz, Lidia Martí Romero
Gastroenterología y Hepatología.2019; 42(10): 638. CrossRef
Gastrointestinal manifestation of immunoglobulin G4-related disease: clarification through a multicenter survey
Kenji Notohara, Terumi Kamisawa, Kazushige Uchida, Yoh Zen, Mitsuhiro Kawano, Satomi Kasashima, Yasuharu Sato, Masahiro Shiokawa, Takeshi Uehara, Hajime Yoshifuji, Hiroko Hayashi, Koichi Inoue, Keisuke Iwasaki, Hiroo Kawano, Hiroyuki Matsubayashi, Yukitos
Journal of Gastroenterology.2018; 53(7): 845. CrossRef
IgG4-Related Disease Mimicking Crohn’s Disease: A Case Report and Review of Literature
Fabiana Ciccone, Antonio Ciccone, Mirko Di Ruscio, Filippo Vernia, Gianluca Cipolloni, Gino Coletti, Giuseppe Calvisi, Giuseppe Frieri, Giovanni Latella
Digestive Diseases and Sciences.2018; 63(4): 1072. CrossRef
IgG4-related Disease in the Stomach which Was Confused with Gastrointestinal Stromal Tumor (GIST): Two Case Reports and Review of the Literature
Ho Seok Seo, Yoon Ju Jung, Cho Hyun Park, Kyo Young Song, Eun Sun Jung
Journal of Gastric Cancer.2018; 18(1): 99. CrossRef
Multivisceral IgG4-related disease presenting as recurrent massive gastrointestinal bleeding: a case report and literature review
Xuexue Deng, Ronghua Fang, Jianshu Zhang, Rongqiong Li
BMC Gastroenterology.2018;[Epub] CrossRef
IgG4-Related Sclerosing Disease Presenting as a Gastric Submucosal Tumor
Takashi Masuda, Toshifumi Matsumoto, Yushi Kaishakuji, Hirotada Tajiri, Akinori Egashira, Hirofumi Kawanaka
The Japanese Journal of Gastroenterological Surgery.2018; 51(10): 599. CrossRef
A rare case of IgG4-related disease: a gastric mass, associated with regional lymphadenopathy
Dimitar Bulanov, Elena Arabadzhieva, Sasho Bonev, Atanas Yonkov, Diana Kyoseva, Tihomir Dikov, Violeta Dimitrova
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Review

Pathology-MRI Correlation of Hepatocarcinogenesis: Recent Update: Jimi Huh, Kyung Won Kim, Jihun Kim, Eunsil Yu; J Pathol Transl Med. 2015;49(3):218-229. Published online May 15, 2015; DOI: https://doi.org/10.4132/jptm.2015.04.15

22,544 View
301 Download
11 Web of Science
9 Crossref

Abstract PDF

Understanding the important alterations during hepatocarcinogenesis as well as the characteristic magnetic resonance imaging (MRI) and histopathological features will be helpful for managing patients with chronic liver disease and hepatocellular carcinoma. Recent advances in MRI techniques, such as fat/iron quantification, diffusion-weighted images, and gadoxetic acid-enhanced MRI, have greatly enhanced our understanding of hepatocarcinogenesis.

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Kathryn J. Fowler, Adam Burgoyne, Tyler J. Fraum, Mojgan Hosseini, Shintaro Ichikawa, Sooah Kim, Azusa Kitao, Jeong Min Lee, Valérie Paradis, Bachir Taouli, Neil D. Theise, Valérie Vilgrain, Jin Wang, Claude B. Sirlin, Victoria Chernyak
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Jimi Huh, Su Jung Ham, Young Chul Cho, Bumwoo Park, Bohyun Kim, Chul-Woong Woo, Yoonseok Choi, Dong-Cheol Woo, Kyung Won Kim
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Chiara Briani, Marco Di Pietropaolo, Massimo Marignani, Francesco Carbonetti, Paola Begini, Vincenzo David, Elsa Iannicelli
Journal of Gastrointestinal Cancer.2018; 49(3): 302. CrossRef

Case Report

Intracranial Fibromatosis: A Case Report.: Jeong Ju Lee, Jeoung Hun Kim, Shin Kwang Khang, Kyung Ja Cho, Jihun Kim; Korean J Pathol. 2011;45:S89-S92.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.S1.S89

2,987 View
20 Download
1 Crossref

Abstract PDF

Fibromatosis can occur at various sites, but intracranial fibromatosis is exceptionally rare. Here, we report a case of intracranial fibromatosis arising in the suprasellar area of a 52-year-old woman who had undergone a surgery at that site. A computed tomography scan revealed a heavily calcified, highly enhancing, poorly demarcated mass in the left sellar area that extended into the left suprasellar, parasellar areas, and orbital apex and completely encased the left distal inferior cerebral artery. Histologic and immunohistochemical features were compatible with those of fibromatosis, although the cellularity was focally higher than usual. The etiology of extra-abdominal fibromatosis is unknown, but physical injuries such as trauma and irradiation have been reported to be associated with its occurrence. Although fibromatosis is rare in the intracranial area, it should be considered as a differential diagnosis when an intracranial mass occurs at a previously injured site.

Citations

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Infantile Intracranial Aggressive Fibromatosis: Report of Two Cases with a Review of the Literature
Baocheng Wang, Jie Ma, Huiming Jin
Pediatric Neurosurgery.2012; 48(3): 181. CrossRef

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