Cancer Research and Treatment

Original Articles

Pancreatic High-Grade Neuroendocrine Neoplasms in the Korean Population: A Multicenter Study: Haeryoung Kim, Soyeon An, Kyoungbun Lee, Sangjeong Ahn, Do Youn Park, Jo-Heon Kim, Dong-Wook Kang, Min-Ju Kim, Mee Soo Chang, Eun Sun Jung, Joon Mee Kim, Yoon Jung Choi, So-Young Jin, Hee Kyung Chang, Mee-Yon Cho, Yun Kyung Kang, Myunghee Kang, Soomin Ahn, Youn Wha Kim, Seung-Mo Hong, on behalf of the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists; Cancer Res Treat. 2020;52(1):263-276. Published online July 12, 2019; DOI: https://doi.org/10.4143/crt.2019.192

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Purpose
The most recent 2017 World Health Organization (WHO) classification of pancreatic neuroendocrine neoplasms (PanNENs) has refined the three-tiered 2010 scheme by separating grade 3 pancreatic neuroendocrine tumors (G3 PanNETs) from poorly differentiated pancreatic neuroendocrine carcinomas (PanNECs). However, differentiating between G3 Pan- NETs and PanNECs is difficult in clinical practice.
Materials and Methods
Eighty-two surgically resected PanNENs were collected from 16 institutions and reclassified according to the 2017 WHO classification based on the histological features and proliferation index (mitosis and Ki-67). Immunohistochemical stains for ATRX, DAXX, retinoblastoma, p53, Smad4, p16, and MUC1 were performed for 15 high-grade PanNENs.
Results
Re-classification resulted in 20 G1 PanNETs (24%), 47 G2 PanNETs (57%), eight G3 well-differentiated PanNETs (10%), and seven poorly differentiated PanNECs (9%). PanNECs showed more frequent diffuse nuclear atypia, solid growth patterns and apoptosis, less frequent organoid growth and regular vascular patterns, and absence of low-grade PanNET components than PanNETs. The Ki-67 index was significantly higher in PanNEC (58.2%± 15.1%) compared to G3 PanNET (22.6%±6.1%, p < 0.001). Abnormal expression of any two of p53, p16, MUC1, and Smad4 could discriminate PanNECs from G3 PanNETs with 100% specificity and 87.5% sensitivity.
Conclusion
Histological features supporting the diagnosis of PanNECs over G3 PanNETs were the absence of a low-grade PanNET component in the tumor, the presence of diffuse marked nuclear atypia, solid growth pattern, frequent apoptosis and markedly increased proliferative activity with homogeneous Ki-67 labeling. Immunohistochemical stains for p53, p16, MUC1, and Smad4 may be helpful in distinguishing PanNECs from G3 PanNETs in histologically ambiguous cases, especially in diagnostic practice when only small biopsied tissues are available.

Citations

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Fei Qi, Minghang Zhang, Yi Han, Juan Du, Hongjie Yang, Hongmei Zhang, Yong Zhang, Tongmei Zhang
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Pancreatic neuroendocrine neoplasms (pNENs): Genetic and environmental biomarkers for risk of occurrence and prognosis
Matteo Tacelli, Manuel Gentiluomo, Paolo Biamonte, Justo P. Castano, Maja Cigrovski Berković, Mauro Cives, Sanja Kapitanović, Ilaria Marinoni, Sonja Marinovic, Ilias Nikas, Lenka Nosáková, Sergio Pedraza-Arevalo, Eleonora Pellè, Aurel Perren, Jonathan Str
Seminars in Cancer Biology.2025; 112: 112. CrossRef
Malignant potential of neuroendocrine microtumor of the pancreas harboring high-grade transformation: lesson learned from a patient with von Hippel-Lindau syndrome
Jongwon Lee, Kyung Jin Lee, Dae Wook Hwang, Seung-Mo Hong
Journal of Pathology and Translational Medicine.2024; 58(2): 91. CrossRef
Rapid Evolution of Metastases in Patients with Treated G3 Neuroendocrine Tumors Associated with NEC-Like Transformation and TP53 Mutation
Atsuko Kasajima, Nicole Pfarr, Eva-Maria Mayr, Ayako Ura, Elisa Moser, Alexander von Werder, Abbas Agaimy, Marianne Pavel, Günter Klöppel
Endocrine Pathology.2024; 35(4): 313. CrossRef
The Complex Histopathological and Immunohistochemical Spectrum of Neuroendocrine Tumors—An Overview of the Latest Classifications
Ancuța-Augustina Gheorghișan-Gălățeanu, Andreea Ilieșiu, Ioana Maria Lambrescu, Dana Antonia Țăpoi
International Journal of Molecular Sciences.2023; 24(2): 1418. CrossRef
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Mauro D. Donadio, Ângelo B. Brito, Rachel P. Riechelmann
Therapeutic Advances in Medical Oncology.2023;[Epub] CrossRef
MicroRNAs associated with postoperative outcomes in patients with limited stage neuroendocrine carcinoma of the esophagus
Tomoyuki Okumura, Tsutomu Fujii, Kenji Terabayashi, Takashi Kojima, Shigeru Takeda, Tomomi Kashiwada, Kazuhiro Toriyama, Susumu Hijioka, Tatsuya Miyazaki, Miho Yamamoto, Shunsuke Tanabe, Yasuhiro Shirakawa, Masayuki Furukawa, Yoshitaka Honma, Isamu Hoshin
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Yongkang Liu, Jiangchuan Wang, Hao Zhou, Zicheng Wei, Jianhua Wang, Zhongqiu Wang, Xiao Chen
BMC Gastroenterology.2023;[Epub] CrossRef
An analysis of 130 neuroendocrine tumors G3 regarding prevalence, origin, metastasis, and diagnostic features
Atsuko Kasajima, Björn Konukiewitz, Anna Melissa Schlitter, Wilko Weichert, Günter Klöppel
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An update on genetically engineered mouse models of pancreatic neuroendocrine neoplasms
Tiago Bordeira Gaspar, José Manuel Lopes, Paula Soares, João Vinagre
Endocrine-Related Cancer.2022; 29(12): R191. CrossRef
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Kelli N. Patterson, Andrew T. Trout, Archana Shenoy, Maisam Abu-El-Haija, Jaimie D. Nathan
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Tiziana Feola, Roberta Centello, Franz Sesti, Giulia Puliani, Monica Verrico, Valentina Di Vito, Cira Di Gioia, Oreste Bagni, Andrea Lenzi, Andrea M. Isidori, Elisa Giannetta, Antongiulio Faggiano
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CD56 Expression Is Associated with Biological Behavior of Pancreatic Neuroendocrine Neoplasms

Xin Chen, Chuangen Guo, Wenjing Cui, Ke Sun, Zhongqiu Wang, Xiao Chen
Cancer Management and Research.2020; Volume 12: 4625. CrossRef
Prognostic and predictive factors on overall survival and surgical outcomes in pancreatic neuroendocrine tumors: recent advances and controversies
Lingaku Lee, Tetsuhide Ito, Robert T Jensen
Expert Review of Anticancer Therapy.2019; 19(12): 1029. CrossRef

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Inter-observer Reproducibility in the Pathologic Diagnosis of Gastric Intraepithelial Neoplasia and Early Carcinoma in Endoscopic Submucosal Dissection Specimens: A Multi-center Study: Joon Mee Kim, Jin Hee Sohn, Mee-Yon Cho, Woo Ho Kim, Hee Kyung Chang, Eun Sun Jung, Myeong-Cherl Kook, So-Young Jin, Yang Seok Chae, Young Soo Park, Mi Seon Kang, Hyunki Kim, Jae Hyuk Lee, Do Youn Park, Kyoung Mee Kim, Hoguen Kim, Young Ju Suh, Sang Yong Seol, Hwoon-Yong Jung, Deuck–Hwa Kim, Na Rae Lee, Seung-Hee Park, Ji Hye You; Cancer Res Treat. 2019;51(4):1568-1577. Published online April 1, 2019; DOI: https://doi.org/10.4143/crt.2019.019

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Purpose
The diagnostic criteria of gastric intraepithelial neoplasia (IEN) are controversial across the world. We investigated how many discrepancies occur in the pathologic diagnosis of IEN and early gastric carcinoma in endoscopic submucosal dissection (ESD) specimens, and evaluated the reasons of the discordance.
Materials and Methods
We retrospectively reviewed 1,202 ESD specimens that were originally diagnosed as gastric IEN and early carcinoma at 12 institutions.
Results
The final consensus diagnosis of carcinoma were 756 cases, which were originally 692 carcinomas (91.5%), 43 high-grade dysplasias (5.7%), 20 low-grade dysplasias (2.6%), and 1 others (0.1%), respectively. High- and low-grade dysplasia were finally made in 63 and 342 cases, respectively. The diagnostic concordance with the consensus diagnosis was the highest for carcinoma (91.5%), followed by low-grade dysplasia (86.3%), others (63.4%) and high-grade dysplasia (50.8%). The general kappa value was 0.83, indicating excellent concordance. The kappa values of individual institutions ranged from 0.74 to 1 and correlated with the proportion of carcinoma cases. The cases revised to a final diagnosis of carcinoma exhibited both architectural abnormalities and cytologic atypia. The main differential points between low- and high-grade dysplasias were the glandular distribution and glandular shape. Additional features such as the glandular axis, surface maturation, nuclear stratification and nuclear polarity were also important.
Conclusion
The overall concordance of the diagnosis of gastric IEN and early carcinoma in ESD specimens was excellent. It correlated with the proportion of carcinoma cases, demonstrating that the diagnostic criteria for carcinoma are more reproducible than those for dysplasia.

Citations

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Ricardo Gonzalez, Ashirbani Saha, Clinton J.V. Campbell, Peyman Nejat, Cynthia Lokker, Andrew P. Norgan
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Young Soo Park, Myeong-Cherl Kook, Baek-hui Kim, Hye Seung Lee, Dong-Wook Kang, Mi-Jin Gu, Ok Ran Shin, Younghee Choi, Wonae Lee, Hyunki Kim, In Hye Song, Kyoung-Mee Kim, Hee Sung Kim, Guhyun Kang, Do Youn Park, So-Young Jin, Joon Mee Kim, Yoon Jung Choi,
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Ga-Yeong Shin, Jun Young Park, Sung Hak Lee, Yu Kyung Cho, Myung-Gyu Choi, Jae Myung Park, Alessandro Rizzo
PLOS ONE.2023; 18(1): e0280735. CrossRef
A Standardized Pathology Report for Gastric Cancer: 2nd Edition
Young Soo Park, Myeong-Cherl Kook, Baek-hui Kim, Hye Seung Lee, Dong-Wook Kang, Mi-Jin Gu, Ok Ran Shin, Younghee Choi, Wonae Lee, Hyunki Kim, In Hye Song, Kyoung-Mee Kim, Hee Sung Kim, Guhyun Kang, Do Youn Park, So-Young Jin, Joon Mee Kim, Yoon Jung Choi,
Journal of Gastric Cancer.2023; 23(1): 107. CrossRef
Accuracy of administrative claim data for gastric adenoma after endoscopic resection
Ga-Yeong Shin, Hyun Ho Choi, Jae Myung Park, Sang Yoon Kim, Jun Young Park, Donghoon Kang, Yu Kyung Cho, Sung Soo Kim, Myung-Gyu Choi
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Sangjoon Choi, Seokhwi Kim
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Establishment and validation of a clinical diagnostic model for gastric low-grade intraepithelial neoplasia
Ting Sun, Xi-quan Ke, Meng Wang, Qi-zhi Wang
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Assessment of deep learning assistance for the pathological diagnosis of gastric cancer
Wei Ba, Shuhao Wang, Meixia Shang, Ziyan Zhang, Huan Wu, Chunkai Yu, Ranran Xing, Wenjuan Wang, Lang Wang, Cancheng Liu, Huaiyin Shi, Zhigang Song
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Deep learning for automatic diagnosis of gastric dysplasia using whole-slide histopathology images in endoscopic specimens
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Gastric Cancer.2022; 25(4): 751. CrossRef
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Gastroenterología y Hepatología.2021; 44(1): 67. CrossRef
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Gastroenterología y Hepatología (English Edition).2021; 44(1): 67. CrossRef

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Prognostic Significance of Defining L-Cell Type on the Biologic Behavior of Rectal Neuroendocrine Tumors in Relation with Pathological Parameters: The Gastrointestinal Pathology Study Group of Korean Society of Pathologists, Jin Hee Sohn, Mee-Yon Cho, Yangsoon Park, Hyunki Kim, Woo Ho Kim, Joon Mee Kim, Eun Sun Jung, Kyoung-Mee Kim, Jae Hyuk Lee, Hee Kyung Chan, Do Youn Park, Mee Joo, Sujin Kim, Woo Sung Moon, Mi Seon Kang, So-Young Jin, Yun Kyung Kang, Sun Och Yoon, HyeSeung Han, EunHee Choi; Cancer Res Treat. 2015;47(4):813-822. Published online February 26, 2015; DOI: https://doi.org/10.4143/crt.2014.238

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Purpose
In 2010, the World Health Organization categorized L-cell type neuroendocrine tumors (NETs) as tumors of uncertain malignancy, while all others were classified as malignant. However, the diagnostic necessity of L-cell immunophenotyping is unclear, as are tumor stage and grade that may guide diagnosis and management. To clarify the predictive markers of rectal neuroendocrine neoplasms (NENs), 5- and 10-year overall survival (OS) was analyzed by pathological parameters including L-cell phenotype. Materials and Methods A total of 2,385 rectal NENs were analyzed from our previous multicenter study and a subset of 170 rectal NENs was immunophenotyped.
Results
In univariate survival analysis, tumor grade (p < 0.0001), extent (p < 0.0001), size (p < 0.0001), lymph node metastasis (p=0.0063), and L-cell phenotype (p < 0.0001) showed significant correlation with the prognosis of rectal NENs; however, none of these markers achieved independent significance in multivariate analysis. The 10-year OS of tumors of NET grade 1, < 10 mm, the mucosa/submucosa was 97.58%, 99.47%, and 99.03%, respectively. L-Cell marker, glucagon II (GLP-1&2), with a cut off score of > 10, is useful in defining L-Cell type. In this study, an L-cell immunophenotype was found in 83.5% of all rectal NENs and most, but not all L-cell type tumors were NET G1, small (< 10 mm) and confined to the mucosa/submucosa. Conclusion From these results, the biological behavior of rectal NENs does not appear to be determined by L-cell type alone but instead by a combination of pathological parameters.

Citations

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Is There a Relationship between the Staining Pattern of Classical Neuroendocrine Markers and Clinicopathological Findings in Neuroendocrine Tumors of the Appendix?
Merve CİN, Enver YARIKKAYA, Selçuk CİN, Özgecan GÜNDOĞAR
Bezmialem Science.2025; 13(1): 65. CrossRef
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Luvy Delfin, Shereen Ezzat, Sylvia L. Asa
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Somatostatin receptor 2 (SSTR2) expression is associated with better clinical outcome and prognosis in rectal neuroendocrine tumors
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Scientific Reports.2024;[Epub] CrossRef
The Clinicopathological Significance of Tumor Cell Subtyping in Appendiceal Neuroendocrine Tumors: A Series of 135 Tumors
Ozgur Mete, David W. Dodington, Daniel L. Shen, Sylvia L. Asa
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Cauda Equina Neuroendocrine Tumors
Sylvia L. Asa, Ozgur Mete, Ulrich Schüller, Biswarathan Ramani, Kanish Mirchia, Arie Perry
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Case Report

Successful Chemotherapy Following Autologous Stem Cell Transplantation in Multiple Myeloma and Multi-organ Dysfunction with Infiltration of Eosinophils: A Case Report: Ho Sup Lee, Lee Chun Park, Seong Hoon Shin, Sang Uk Lee, Hee Kyung Chang, Bang Huh, Gyoo Sik Jung, Mi Hyang Kim, Yang Soo Kim; Cancer Res Treat. 2011;43(3):199-203. Published online September 30, 2011; DOI: https://doi.org/10.4143/crt.2011.43.3.199

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Eosinophils are derived from hematopoietic stem cells. Peripheral blood eosinophilia is defined as an absolute eosinophil count of > or =0.5x10(9)/L. Eosinophilia is classified into primary or clonal eosinophilia, secondary eosinophilia, and idiopathic categories including idiopathic hypereosinophilic syndrome. Both hematopoietic and solid neoplasms may be associated with peripheral blood eosinophilia, but multiple myeloma is rarely associated with eosinophilia. We now report the case of a 31-year-old man with multiple myeloma associated with marked eosinophilia who developed multiple organ dysfunction with infiltration of eosinophils. He recovered after treatment with chemotherapy followed by autologous stem cell transplantation.

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Subepidermal Bullous Dermatosis Associated With IgA Multiple Myeloma
Qiang Zhou, Hao Jiang, Kejian Zhu, Rui Han, Hao Cheng
The American Journal of Dermatopathology.2013; 35(3): e49. CrossRef

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Original Article

Prognostic Significance of Histologic Features, DNA Content, Expression of Proliferating Cell Nuclear Antigen (PCNA), c-fos Protein and Transforming Growth Factor (TGF)-alpha and -beta in Giant Cell Tumor of Bone: Hee Kyung Chang, Sung Hun Yoon, Jae Do Kim, Man Ha Huh; J Korean Cancer Assoc. 1997;29(2):266-279.

Abstract PDF: PURPOSE
This study was attempted to investigate the prevalence of the expression of c-fos protein, TGF-alpha and -beta, PCNA , DNA ploidy pattern and histopathological parameters of giant cell tumor (GCT) of bone and to correlate with prognosis and to extend our understanding on tumorigenesis of GCT.
MATERIALS AND METHODS
Twenty eight cases of paraffin-embedded tissue were studied, classified as recurrent (5 cases) and non-recurrent group (12cases) within the limits of the cases which afforded surgical material on first operation.
RESULTS
No significant difference was observed in cellularity of stromal cells, atypia of stromal and giant cells, presence of hemorrhage and necrosis between recurrent and non-recurrent group. However, presence of more than 10 mitotic figures in 10 high power fields in recurrent group was significantly higher than non-recurrent group (p<0.05). The immunoreactivity for PCNA was seen only in nuclei of stromal cells, whereas nuclei of giant cells showed negative staining. The positivity of PCNA revealed no significant difference between non-recurrent (mean; 40.9%) and recurrent group (34.4%). The expression of c-fos oncogene was seen in 5 cases (100%) in recurrent group, and 8 cases (66.7%) in non-recurrent group, and no significant difference was seen. No significant difference of expression of TGF-alpha was seen in 5 cases (100%) in recurrent group and in 11 cases (91.7%) in non-recurrent group. The expression of TGF-beta in stromal cells was significantly higher in non-recurrent group (80%) compared to recurrent group (100%) (p<0.05). In DNA analysis out of 18 cases, 4 cases (22.2%) were aneuploidy and 14 cases (77.8%) were diploidy. Among 4 aneuploidy cases, 3 cases (75%) had no recurrence, and 1 case (25%) had metastasis to lung and expired. No significant difference of DNA ploidy pattern was seen between the recurrent and non-recurrent group.
CONCLUSION
Presence of more than 10 mitotic figures in 10 high power fields and less expression of TGF-beta are related to higher possibility of recurrence and it is suggested that the number of mitotic figure (more than 10/10HPF) and expression of TGF-beta could be helpful parameters in predicting recurrence of GCT.

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