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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Yuko Kinowaki, Charlotte Wang, Yuki Fukumura, Maria Ganci, M Lisa Zhang, Masanori Kobayashi, Keiichi Akahoshi, Atsushi Kudo, Keiichi Kinowaki, Keita Kai, Yumi Mihara, Ayumi Murakami, Hung Ngoc Nguyen, Ryoichi Hanazawa, Akihiro Hirakawa, Liang Minggao, Mor
Am J Clin Pathol.2026;[Epub] CrossRef
Prognostic and Predictive Significance of Selected Gene Mutations in Pancreatic and Intestinal Neuroendocrine Tumors
Jan Musiałkiewicz, Bartłomiej Budny, Aleksandra Anioła, Adam Maciejewski, Paweł Komarnicki, Joanna Maciejewska, Paweł Gut, Marek Ruchała
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Therapeutic Advances in Medical Oncology.2025;[Epub] CrossRef
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
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MicroRNAs associated with postoperative outcomes in patients with limited stage neuroendocrine carcinoma of the esophagus
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Yongkang Liu, Jiangchuan Wang, Hao Zhou, Zicheng Wei, Jianhua Wang, Zhongqiu Wang, Xiao Chen
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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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Neuroendocrine Carcinomas with Atypical Proliferation Index and Clinical Behavior: A Systematic Review
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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Risk of cancer in patients with recurrent aphthous stomatitis in Korea
Ki Jin Kwon, Su Jin Jeong, Young-Gyu Eun, In Hwan Oh, Young Chan Lee
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Digestive Well-Differentiated Grade 3 Neuroendocrine Tumors: Current Management and Future Directions
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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.

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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

Abstract PDF PubReader ePub

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.

Citations

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Eosinophilic granulomatosis with polyangiitis coexisting with multiple myeloma: independent entities or coexistence? A case report
Longyan Qin, Yi Yin, Pengjia Wu, Aifei Zhang, Na Li, Jun Liu, Ling Huang, Jun Cao, Jiashun Zeng
Frontiers in Immunology.2026;[Epub] CrossRef
Case Report: A case of non-secretory multiple myeloma presenting with eosinophilia: diagnostic challenges and a focused literature review
Jirui Zhong, Xikun Liu, Jiduo Liu, Shanshan Xiao, Xuekui Gu, Zenghui Liu
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DRESS Is Not a Rare Complication during the Initial Treatment of Newly Diagnosed Multiple Myeloma: The Experience of Two Medical Institutes
Jiao Yang, Qingqing Hu, Jiaqing Lu, Jian Wang, Die Wu, Xiaoming Fei, Lixia Wang, Xianqiu Yu, Yu Tang
Acta Haematologica.2025; 148(6): 699. CrossRef
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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