Journal of Pathology and Translational Medicine

Case Study

Multiple Neuroendocrine Tumors in Stomach and Duodenum in a Multiple Endocrine Neoplasia Type 1 Patient: Bohyun Kim, Han-Kwang Yang, Woo Ho Kim; J Pathol Transl Med. 2018;52(2):126-129. Published online December 21, 2017; DOI: https://doi.org/10.4132/jptm.2017.09.16

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A 67-year-old woman with a history of subtotal parathyroidectomy, distal pancreatectomy, and total splenectomy 23 years prior underwent surgical gastric resection for neuroendocrine tumors of the stomach and duodenum. Meticulous examination of the entire stomach and duodenum revealed multiple scattered, minute neuroendocrine tumors. To the best of our knowledge, this is the first case report of a patient diagnosed with gastroduodenal neuroendocrine tumors associated with multiple endocrine neoplasia type 1 (MEN 1) in whom complete histologic mapping of the whole gastrectomy specimen was performed. The presence of MEN 1–associated neuroendocrine tumors in the stomach is very rare, but should be considered in patients diagnosed with MEN 1 who present with a new tumor in the stomach.

Citations

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A Case of Asymptomatic Multiple Endocrine Neoplasia Type I with Thymic Carcinoid
Suk Ki Park, Moon Won Lee, In Sub Han, Young Joo Park, Sung Yong Han, Joon Woo Park, Bong Eun Lee, Gwang Ha Kim, Sang Soo Kim
The Korean Journal of Helicobacter and Upper Gastrointestinal Research.2019; 19(1): 65. CrossRef

Original Article

Loss of Progesterone Receptor Expression Is an Early Tumorigenesis Event Associated with Tumor Progression and Shorter Survival in Pancreatic Neuroendocrine Tumor Patients: Sung Joo Kim, Soyeon An, Jae Hoon Lee, Joo Young Kim, Ki-Byung Song, Dae Wook Hwang, Song Cheol Kim, Eunsil Yu, Seung-Mo Hong; J Pathol Transl Med. 2017;51(4):388-395. Published online June 8, 2017; DOI: https://doi.org/10.4132/jptm.2017.03.19

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Abstract PDF

Background
Pancreatic neuroendocrine tumors (PanNETs) are the second most common pancreatic neoplasms and there is no well-elucidated biomarker to stratify their detection and prognosis. Previous studies have reported that progesterone receptor (PR) expression status was associated with poorer survival in PanNET patients.
Methods
To validate previous studies, PR protein expression was assessed in 21 neuroendocrine microadenomas and 277 PanNETs and compared with clinicopathologic factors including patient survival.
Results
PR expression was gradually decreased from normal islets (49/49 cases, 100%) to neuroendocrine microadenoma (14/21, 66.6%) to PanNETs (60/277, 21.3%; p < .001). PanNETs with loss of PR expression were associated with increased tumor size (p < .001), World Health Organization grade (p = .001), pT classification (p < .001), perineural invasion (p = .028), lymph node metastasis (p = .004), activation of alternative lengthening of telomeres (p = .005), other peptide hormonal expression (p < .001) and ATRX/DAXX expression (p = .015). PanNET patients with loss of PR expression (5-year survival rate, 64.1%) had significantly poorer recurrence-free survival outcomes than those with intact PR expression (90%) by univariate (p = .012) but not multivariate analyses. Similarly, PanNET patients with PR expression loss (5-year survival rate, 76%) had significantly poorer overall survival by univariate (p = .015) but not multivariate analyses.
Conclusions
Loss of PR expression was noted in neuroendocrine microadenomas and was observed in the majority of PanNETs. This was associated with increased grade, tumor size, and advanced pT and pN classification; and was correlated with decreased patient survival time by univariate but not multivariate analyses. Loss of PR expression can provide additional information on shorter disease-free survival in PanNET patients.

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Edward B. Stelow, Hadi Yaziji
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Joo Young Kim, Sang Hwa Lee, Soyeon An, Sung Joo Kim, You-Na Sung, Ki-Byung Song, Dae Wook Hwang, Song Cheol Kim, Seung-Mo Hong
Virchows Archiv.2018; 472(5): 739. CrossRef
Prognostic value of progesterone receptor in solid pseudopapillary neoplasm of the pancreas: evaluation of a pooled case series
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Endocrinology&Metabolism International Journal.2018;[Epub] CrossRef

Review

Neuroendocrine Tumors of the Female Reproductive Tract: A Literature Review: Yi Kyeong Chun; J Pathol Transl Med. 2015;49(6):450-461. Published online October 13, 2015; DOI: https://doi.org/10.4132/jptm.2015.09.20

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Abstract PDF

Neuroendocrine tumors of the female reproductive tract are a heterogeneous group of neoplasms that display various histologic findings and biologic behaviors. In this review, the classification and clinicopathologic characteristics of neuroendocrine tumors of the female reproductive tract are described. Differential diagnoses are discussed, especially for non-neuroendocrine tumors showing high-grade nuclei with neuroendocrine differentiation. This review also discusses recent advances in our pathogenetic understanding of these disorders.

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Original Articles

Clinical and Prognostic Significances of Cytokeratin 19 and KIT Expression in Surgically Resectable Pancreatic Neuroendocrine Tumors: Eun-Mi Son, Joo Young Kim, Soyeon An, Ki-Byung Song, Song Cheol Kim, Eunsil Yu, Seung-Mo Hong; J Pathol Transl Med. 2015;49(1):30-36. Published online January 15, 2015; DOI: https://doi.org/10.4132/jptm.2014.10.23

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Abstract PDF

Background
Pancreatic neuroendocrine tumors (PanNETs) are malignant endocrine neoplasms that present diverse clinical behaviors. Therefore, identification of biomarkers of PanNETs is important for stratification of the prognosis of PanNET patients. Recently, cytokeratin 19 (CK19) and KIT expression were reported to have prognostic significance in PanNET patients. Methods: To identify their prognostic significance, CK19 and KIT protein expression were assessed in 182 surgically resected PanNETs and compared with clinicopathologic factors. Results: Of 182 PanNETs cases, CK19 and KIT expression was noted in 97 (53.3%) and 16 (8.8%) cases, respectively. PanNET patients with CK19 expression had larger tumors (p=.006), higher World Health Organization (WHO) grade (p=.002) and pT classification (p<.001), increased distant metastasis (p=.004), and lymphovascular (p=.012) and perineural (p=.019) invasion. Similarly, those with KIT expression had larger tumors (p=.030), higher WHO grade (p=.001), advanced pT classification (p<.001), distant metastasis (p=.001), and lymphovascular invasion (p=.014). The 5-year survival rate for PanNET patients with KIT expression was significantly lower (62%) than that of patients without KIT expression (77%, p=.011), as determined by univariate but not by multivariate analyses. Conclusions: CK19 and KIT expression correlate with higher metastatic potential and advanced disease stage, and KIT expression is associated with worse survival in PanNET patients.

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Tumor-associated nonmyelinating Schwann cell–expressed PVT1 promotes pancreatic cancer kynurenine pathway and tumor immune exclusion
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Diagnostic and prognostic impact of cytokeratin 19 expression analysis in human tumors: a tissue microarray study of 13,172 tumors
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Loss of Progesterone Receptor Expression Is an Early Tumorigenesis Event Associated with Tumor Progression and Shorter Survival in Pancreatic Neuroendocrine Tumor Patients
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Altered Expression of PTEN and Its Major Regulator MicroRNA-21 in Pulmonary Neuroendocrine Tumors: Hyoun Wook Lee, Seung Yeon Ha, Mee Sook Roh; Korean J Pathol. 2014;48(1):17-23. Published online February 25, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.1.17

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Abstract PDF

Background

Phosphatase and tensin homolog on chromosome ten (PTEN) is one of the most frequently inactivated tumor suppressors in various tumor types. MicroRNA-21 (miR-21) may affect tumor progression by post-transcriptional repression of expression of tumor suppressors, such as PTEN. This study was conducted to evaluate the significance of PTEN expression in pulmonary neuroendocrine (NE) tumors and to analyze the relationship between PTEN and miR-21 expressions.

Methods

Expressions of PTEN and miR-21 were investigated by immunohistochemistry and real time reverse transcription-polymerase chain reaction, respectively, in 75 resected pulmonary NE tumors (23 typical carcinoids [TCs], nine atypical carcinoids [ACs], 22 large cell NE carcinomas [LCNECs], and 21 small cell lung carcinomas [SCLCs]).

Results

Loss of PTEN expression was observed in four of 23 TCs (17.4%), four of nine ACs (44.4%), 16 of 22 LCNECs (72.7%) and nine of 21 SCLCs (42.9%) (p=.025). The expression level of miR-21 was significantly higher in high-grade NE carcinomas than in carcinoid tumors (p<.001). PTEN expression was inversely correlated with miR-21 expression (p<.001).

Conclusions

This study suggests that aberrant expression of PTEN in relation to miR-21 may represent an important step in the development and progression of pulmonary NE tumors.

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microRNA-21 promotes osteogenic differentiation of mesenchymal stem cells by the PI3K/β-catenin pathway
Yu-Bin Meng, Xue Li, Zhao-Yang Li, Jin Zhao, Xu-Bo Yuan, Yu Ren, Zhen-Duo Cui, Yun-De Liu, Xian-Jin Yang
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Inhibition of NADPH oxidase protects against metastasis of human lung cancer by decreasing microRNA-21
Song Yan, Gang Liu, Changyan Pei, Wenqing Chen, Pei Li, Qiang Wang, Xintian Jin, Jiajia Zhu, Mengzhu Wang, Xiyu Liu
Anti-Cancer Drugs.2015; 26(4): 388. CrossRef

Proposal for a Standardized Pathology Report of Gastroenteropancreatic Neuroendocrine Tumors: Prognostic Significance of Pathological Parameters: Mee-Yon Cho, Jin Hee Sohn, So Young Jin, Hyunki Kim, Eun Sun Jung, Mi-Jung Kim, Kyoung-Mee Kim, Woo Ho Kim, Joon Mee Kim, Yun Kyung Kang, Joon Hyuk Choi, Dae Young Kang, Youn Wha Kim, Eun Hee Choi; Korean J Pathol. 2013;47(3):227-237. Published online June 25, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.3.227

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Abstract PDF

Background

There is confusion in the diagnosis and biological behaviors of gastroenteropancreatic neuroendocrine tumors (GEP-NETs), because of independently proposed nomenclatures and classifications. A standardized form of pathology report is required for the proper management of patients.

Methods

We discussed the proper pathological evaluation of GEP-NET at the consensus conference of the subcommittee meeting for the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. We then verified the prognostic significance of pathological parameters from our previous nationwide collection of pathological data from 28 hospitals in Korea to determine the essential data set for a pathology report.

Results

Histological classification, grading (mitosis and/or Ki-67 labeling index), T staging (extent, size), lymph node metastasis, and lymphovascular and perineural invasion were significant prognostic factors and essential for the pathology report of GEP-NET, while immunostaining such as synaptophysin and chromogranin may be optional. Furthermore, the staging system, either that of the 2010 American Joint Cancer Committee (AJCC) or the European Neuroendocrine Tumor Society (ENETS), should be specified, especially for pancreatic neuroendocrine neoplasms.

Conclusions

A standardized pathology report is crucial for the proper management and prediction of prognosis of patients with GEP-NET.

Citations

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Analysis of Prognostic Risk Factors of Endoscopic Submucosal Dissection (ESD) and Curative Resection of Gastrointestinal Neuroendocrine Neoplasms
Yuan Si, ChaoKang Huang, JingBin Yuan, XianHui Zhang, QingQiang He, ZhiJin Lin, Ling He, ZhongXin Liu, Yuvaraja Teekaraman
Contrast Media & Molecular Imaging.2022;[Epub] CrossRef
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,
Journal of Pathology and Translational Medicine.2021; 55(4): 247. CrossRef
Preoperative diagnosis of well‐differentiated neuroendocrine tumor in common hepatic duct by brush cytology: A case report
Jiwoon Choi, Kyong Joo Lee, Sung Hoon Kim, Mee‐Yon Cho
Diagnostic Cytopathology.2019; 47(7): 720. CrossRef
Primary renal well-differentiated neuroendocrine tumors: report of six cases with an emphasis on the Ki-67 index and mitosis
Bohyun Kim, Han-Seong Kim, Kyung Chul Moon
Diagnostic Pathology.2019;[Epub] CrossRef
Primary low‐grade neuroendocrine carcinoma of the skin: An exceedingly rare entity
Tiffany Y. Chen, Annie O. Morrison, Joe Susa, Clay J. Cockerell
Journal of Cutaneous Pathology.2017; 44(11): 978. CrossRef
Prognostic Validity of the American Joint Committee on Cancer and the European Neuroendocrine Tumors Staging Classifications for Pancreatic Neuroendocrine Tumors
Jae Hee Cho, Ji Kon Ryu, Si Young Song, Jin-Hyeok Hwang, Dong Ki Lee, Sang Myung Woo, Young-Eun Joo, Seok Jeong, Seung-Ok Lee, Byung Kyu Park, Young Koog Cheon, Jimin Han, Tae Nyeun Kim, Jun Kyu Lee, Sung-Hoon Moon, Hyunjin Kim, Eun Taek Park, Jae Chul Hw
Pancreas.2016; 45(7): 941. CrossRef
Early diagnosis and treatment of gastrointestinal neuroendocrine tumors
Hong Shen, Zhuo Yu, Jing Zhao, Xiu-Zhen Li, Wen-Sheng Pan
Oncology Letters.2016; 12(5): 3385. CrossRef
Recent Updates on Neuroendocrine Tumors From the Gastrointestinal and Pancreatobiliary Tracts
Joo Young Kim, Seung-Mo Hong
Archives of Pathology & Laboratory Medicine.2016; 140(5): 437. CrossRef
Pancreatic neuroendocrine tumors: Correlation between the contrast-enhanced computed tomography features and the pathological tumor grade
Koji Takumi, Yoshihiko Fukukura, Michiyo Higashi, Junnichi Ideue, Tomokazu Umanodan, Hiroto Hakamada, Ichiro Kanetsuki, Takashi Yoshiura
European Journal of Radiology.2015; 84(8): 1436. CrossRef
Tumeurs neuroendocrines du tube digestif et du pancréas : ce que le pathologiste doit savoir et doit faire en 2014
Jean-Yves Scoazec, Anne Couvelard
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Spectrum of Gastroenteropancreatic NENs in Routine Histological Examinations of Bioptic and Surgical Specimen: A Study of 161 Cases Collected from 17 Departments of Pathology in the Czech Republic
Václav Mandys, Tomáš Jirásek
Gastroenterology Research and Practice.2014; 2014: 1. CrossRef
p27 Loss Is Associated with Poor Prognosis in Gastroenteropancreatic Neuroendocrine Tumors
Hee Sung Kim, Hye Seung Lee, Kyung Han Nam, Jiwoon Choi, Woo Ho Kim
Cancer Research and Treatment.2014; 46(4): 383. CrossRef

Morphologic Analysis of Pulmonary Neuroendocrine Tumors: Seung Seok Lee, Myunghee Kang, Seung Yeon Ha, Jungsuk An, Mee Sook Roh, Chang Won Ha, Jungho Han; Korean J Pathol. 2013;47(1):16-20. Published online February 25, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.1.16

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Abstract PDF

Background

Few studies on how to diagnose pulmonary neuroendocrine tumors through morphometric analysis have been reported. In this study, we measured and analyzed the characteristic parameters of pulmonary neuroendocrine tumors using an image analyzer to aid in diagnosis.

Methods

Sixteen cases of typical carcinoid tumor, 5 cases of atypical carcinoid tumor, 15 cases of small cell carcinoma, and 51 cases of large cell neuroendocrine carcinoma were analyzed. Using an image analyzer, we measured the nuclear area, perimeter, and the major and minor axes.

Results

The mean nuclear area was 0.318±0.101 µm² in typical carcinoid tumors, 0.326±0.119 µm² in atypical carcinoid tumors, 0.314±0.107 µm² in small cell carcinomas, and 0.446±0.145 µm² in large cell neuroendocrine carcinomas. The mean nuclear circumference was 2.268±0.600 µm in typical carcinoid tumors, 2.408±0.680 µm in atypical carcinoid tumors, 2.158±0.438 µm in small cell carcinomas, and 3.247±1.276 µm in large cell neuroendocrine carcinomas. All parameters were useful in distinguishing large cell neuroendocrine carcinoma from other tumors (p=0.001) and in particular, nuclear circumference was the most effective (p=0.001).

Conclusions

Pulmonary neuroendocrine tumors showed nuclear morphology differences by subtype. Therefore, evaluation of quantitative nuclear parameters improves the accuracy and reliability of diagnosis.

Citations

Citations to this article as recorded by

Clinical Significance of Persistent Tumor in Bone Marrow during Treatment of High-risk Neuroblastoma
Young Bae Choi, Go Eun Bae, Na Hee Lee, Jung-Sun Kim, Soo Hyun Lee, Keon Hee Yoo, Ki Woong Sung, Hong Hoe Koo
Journal of Korean Medical Science.2015; 30(8): 1062. CrossRef
Morphologic Alteration of Metastatic Neuroblastic Tumor in Bone Marrow after Chemotherapy
Go Eun Bae, Yeon-Lim Suh, Ki Woong Sung, Jung-Sun Kim
Korean Journal of Pathology.2013; 47(5): 433. CrossRef

Nuclear Image Analysis Study of Neuroendocrine Tumors: Meeja Park, Taehwa Baek, Jongho Baek, Hyunjin Son, Dongwook Kang, Jooheon Kim, Hyekyung Lee; Korean J Pathol. 2012;46(1):38-41. Published online February 23, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.1.38

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Abstract PDF

Background

There is a subjective disagreement about nuclear chromatin in the field of pathology. Objective values of red, green, and blue (RGB) light intensities for nuclear chromatin can be obtained through a quantitative analysis using digital images.

Methods

We examined 10 cases of well differentiated neuroendocrine tumors of the rectum, small cell lung carcinomas, and moderately differentiated squamous cell lung carcinomas respectively. For each case, we selected 30 representative cells and captured typical microscopic findings. Using an image analyzer, we determined the longest nuclear line profiles and obtained graph files and Excel data on RGB light intensities. We assessed the meaningful differences in graph files and Excel data among the three different tumors.

Results

The nucleus of hematoxylin and eosin-stained tumor cells was expressed as a combination of RGB light sources. The highest intensity was from blue, whereas the lowest intensity was from green. According to the graph files, green showed the most noticeable change in the light intensity, which is consistent with the difference in standard deviations.

Conclusions

The change in the light intensity for green has an important implication for differentiating between tumors. Specific features of the nucleus can be expressed in specific values of RGB light intensities.

Citations

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Difference of the Nuclear Green Light Intensity between Papillary Carcinoma Cells Showing Clear Nuclei and Non-neoplastic Follicular Epithelia in Papillary Thyroid Carcinoma
Hyekyung Lee, Tae Hwa Baek, Meeja Park, Seung Yun Lee, Hyun Jin Son, Dong Wook Kang, Joo Heon Kim, Soo Young Kim
Journal of Pathology and Translational Medicine.2016; 50(5): 355. CrossRef
Comparison of diagnostic accuracy between CellprepPlus® and ThinPrep® liquid‐based preparations in effusion cytology
Yong‐Moon Lee, Ji‐Yong Hwang, Seung‐Myoung Son, Song‐Yi Choi, Ho‐Chang Lee, Eun‐Joong Kim, Hye‐Suk Han, Jin young An, Joung‐Ho Han, Ok‐Jun Lee
Diagnostic Cytopathology.2014; 42(5): 384. CrossRef

Case Report

CK20 Negative and CK7 Positive Merkel Cell Carcinoma of the Conjunctiva: Brief Case Report.: Jung Ha Shin, Jae Young Park, Hyun Seung Kim, Ok Ran Shin, Kyo Young Lee; Korean J Pathol. 2010;44(6):675-678.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.6.675

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Abstract PDF: Merkel cell carcinoma (MCC) is an uncommon but potentially aggressive neuroendocrine carcinoma of the skin. It typically develops on sun-exposed areas of the head and neck, particularly the eyelid, periorbital region, and extremities. We report a case of unusually located MCC, presenting as a conjunctival mass, which has only been reported once in the English literature. An 83-year-old male presented with a 0.8 x 0.7 cm sized mass protruding from the lower fornix of the right conjunctiva. The mass was excised. The tumor was located in the submucosa without connection to the overlying mucosa. Light microscopic findings showed a carcinoma with undifferentiated small round cells and the presence of cytokeratin (CK AE1/3, CK7) and neuroendocrine markers. We established a diagnosis of MCC. As reported in the literature, the majority of MCCs are positive for CK20 but negative for CK7. But, this case showed an uncommon cytokeratin immunohistochemical profile of positive for CK7 and negative for CK20, suggesting a new immunophenotypic MCC variant.

Original Article

Differential Expression of Glut1 in Pulmonary Neuroendocrine Tumors: Correlation with Histological Grade.: Hyun Ju Lee, Seol Bong Yoo, Won Woo Lee, Doo Hyun Chung, Jeong Wook Seo, Jin Haeng Chung; Korean J Pathol. 2009;43(3):201-205.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.3.201

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Abstract PDF

BACKGROUND
Increased glucose uptake, a process that is mediated by glucose transporter (Glut1) proteins, is an important metabolic feature in a variety of cancer cells. The overexpression of Glut1 in human cancers is known to be related to a variety of histopathological parameters, including histological grade, proliferation rate, and lymphatic invasion. The principal objective of this study was to evaluate Glut1 expression in the spectrum of pulmonary neuroendocrine (NE) tumors including typical carcinoid tumor (TC), atypical carcinoid tumor (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell carcinoma (SCC), and to characterize the relationship between Glut1 expression and the histologic grade of NE tumors.
METHODS
19 TC, 7 AC, 13 LCNEC, and 6 SCC patients were included in this study. The percentages of Glut1-positive tumor cells in these patients were determined. For statistical analysis, Glut1 expression was subdivided into a Glut1-low expression group (0-30%) and a Glut1-high expression group (31-90%).
RESULTS
In our subgroup analyses, the histological grade of pulmonary neuroendocrine (NE) tumors was significantly correlated with Glut1 expression; TC (n=19, 3.6+/-4.2%), AC (n=7, 20.0+/-4.9%), LCNEC (n=13, 60.0+/-21.1%), and SCC (n=6, 74.2+/-16.9%). Glut1-high expression was significantly associated with high-grade NE tumors such as LCNEC and SCC (n=19, 62.6+/-21.0%) (p=0.000).
CONCLUSIONS
The results of this study appear to indicate that Glut1 overexpression is a consistent feature of high-grade NE lung tumors.

Citations

Citations to this article as recorded by

GLUT1: A novel tool reflecting proliferative activity of lung neuroendocrine tumors?
Nazim Benzerdjeb, Pascal Berna, Henri Sevestre
Pathology International.2017; 67(1): 32. CrossRef
Oncocytic carcinoid tumor of the lung with intense F-18 fluorodeoxyglucose (FDG) uptake in positron emission tomography–computed tomography (PET/CT)
Yuki Tanabe, Yoshifumi Sugawara, Rieko Nishimura, Kohei Hosokawa, Makoto Kajihara, Teruhiko Shimizu, Tadaaki Takahashi, Shinya Sakai, Shigeki Sawada, Motohiro Yamashita, Haruhiko Ohtani
Annals of Nuclear Medicine.2013; 27(8): 781. CrossRef

Review

Fine Needle Aspiration Cytologic Findings of Pulmonary Neuroendocrine Tumors.: Jae Soo Koh; Korean J Cytopathol. 2008;19(1):9-15.; DOI: https://doi.org/10.3338/kjc.2008.19.1.9

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Abstract PDF: The major categories of neuroendocrine tumors of lung are typical carcinoid, atypical carcinoid, large cell neuroendocrine carcinoma, and small cell carcinoma. The histologic classification criteria of neuroendocrine tumors are well documented in the "WHO Classification of Tumors" based on mitotic figures and necrosis. Cytologic characteristics of neuroendocrine tumors are trabecular, acinar, and solid arrangement of tumor cells and occasional rosette formation. Nuclear chromatin patterns are characteristically described as "salt and pepper chromatin pattern". Many of cytologic classifications documented in the literature are before the "WHO Classification". In this review, the cytologic features of pulmonary neuroendocrine tumors are documented according to the WHO classification, and recent concepts of neuroendocrine tumors of lung are discussed.

Original Articles

Large Cell Neuroendocrine Carcinoma of the Lung: Report of three cases.: Jai Hyang Go, Sun Ree Jung, Dong Hwan Shin, Woo Hee Jung; Korean J Pathol. 1995;29(4):511-516.

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Abstract PDF: We report three cases of neuroendocrine tumors of the lung characterized by large pleomorphic cell with frequent mitosis, which show neuroendocrine differentiation by both light microscopy or electron microscopy and iminunohistochemistry. These tumors have been categorized as large cell neuroendocrine carcinoma by Travis et al.(1991) in contrast with non-small cell lung cancer with neuroendocrine differentiation. In the latter, neuroendocrine differentiation is not evident by light microscopy and must be demonstrated by imunohistochemstry or by electron microscopy. The prognosis of large cell neuroendocrine carcinoma, together with non-small cell lung cancer with neuroendocrine differentiation, appears to be worse than cancer without neuroendocrine differentiation and intermediate between atypical carcinoid and small cell lung cancer. Larger numbers of patients will be needed to demonstrate significant differences in survival.

Large Cell Neuroendocrine Carcinoma of the Lung 2 cases including one presented as an ovarian mass.: Yun Jung Kim, Jung Weon Shim, Hye Kyung Ahn, Young Euy Park; Korean J Pathol. 1997;31(3):257-262.

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Abstract PDF: Pulmonary tumors exhibiting neuroendocrine differentiation are classified as typical carcinoid, atypical carcinoid, and small cell lung carcinoma(SCLC). Travis et al. proposed a fourth category of large cell neuroendocrine carcinoma, which is characterized by light microscopic neuroendocrine appearance, cells of large size, polygonal shape, low nuclear cytoplasmic ratio, coarse nuclear chromatin, with prominent nucleoli high mitotic rate and frequent necrosis; and neuroendocrine features by immunohistochemistry or electron microscopy. High grade neuroendocrine carcinoma (LCAC-NE) revealed aggressive clinical course. We report two cases of neuroendocrine tumors of the lung characterized by a trabecular pattern of large pleomorphic cells with frequent mitoses and wide necrosis. The frequent metastatic sites of atypical carcinoid were liver, bone and brain. One of our case is presented, at first, as an ovarian mass, which shows multifocal rosettes and revealed metastasis from lung. Both cases expressed neuroendocrine differentiation by light microscopy and immunohistochemistry. However clinical neuroendocrine symptom were not present.

The Prognostic Significance of Neuroendocrine Differentiation for Treating Prostatic Carcinoma in 699 Cases of Radical Prostatectomy.: Tae Hoon Kang, Eun Shin, Baek Hee Kim, Gheeyoung Choe; Korean J Pathol. 2008;42(6):381-388.

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Abstract PDF: BACKGROUND
Neuroendocrine differentiation of prostatic carcinoma is known to be associated with a poor prognosis, tumor progression and androgen-independency, and there is currently no successful therapy for this type of tumor. The purpose of this study is to evaluate the prognostic implications of neuroendocrine differentiation in prostatic carcinoma in Korean men. METHODS: Six hundreds and ninety nine consecutive cases of radical prostatectomy specimens were systematically processed for topographic mapping. Neuroendocrine differentiation was detected by immunohistochemistry by using antibody to chromogranin. We analyzed the relationship between neuroendocrine differentiation and the clinicopathological prognostic factors, as well as biochemical failure. The neuroendocrine differentiation was evaluated according to the presence of chromogranin-positive cells, the pattern of neuroendocrine cells and the number of neuroendocrine cells, respectively.
RESULTS
Neuroendocrine differentiation was detected in 150 out of 699 cases (21.5%). The presence of neuroendocrine differentiation as well as the pattern of neuroendocrine cells was correlated with biochemical failure and the other clinicopathological prognostic factors such as the Gleason score, the pathologic stage, the tumor volume, angiolymphatic invasion, perineural invasion, and the Ki-67 proliferative index (p<0.05). CONCLUSIONS: We suggest that neuroendocrine differentiation of prostatic carcinoma is a prognostic factor even in radical prostatectomy specimens for localized prostate cancer. Evaluation of the presence of neuroendocrine differentiation as well as the pattern of neuroendocrine cells is recommended in radical prostatectomy specimens.

Case Report

Duodenal Somatostatinoma: A case report.: Mee Hye Oh, Yi Kyeong Chun, Hye Jae Cho, Jin Ho Lee, Hong Yong Kim, Ill Hyang Ko; Korean J Pathol. 1993;27(6):645-649.

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Abstract PDF: Somatostatinoma is rare endocrine tumor that was first described in 1977 by Ganda et al. and Larsson et al. simultaneously. It seems nonfunctioning at clinical level. But it may present with diabetes, diarrhea, cholelithiasis, steatorrhea, indigestion, hypochlorhydria, and anemia. In contrast with pancreatic somatostatinoma, duodenal somatostatinoma, in general, is clinically silent. Duodenal endocrine tumors show similar histologic pattern. Therefore, the definite diagnosis is performed by immunohistochemistry and electron microscopic examination. We have experienced a case of somatostatinoma of duodenum in a 62-year-old male. He has complained generalized pruritus for one year and jaundice for 2 weeks. Grossly, the mass was a intraluminary protruding, polypoid lesion with focal mucosal erosion at immediately distal to Ampulla of Vater. Histologically, it showed tall, cylindrical cells with distinct cell membranes, having granular cytoplasm and small innocent looking nuclei. No mitosis was seen. The tumor cells were arraged in small solid groups and trabeculae, separated by fibrovascular stroma. Immunohistochemically, the tumor cells were strongly positive with somatostatin and negative with several other hormonal and neuroendocrine markers. Ultrastructurally, the cytoplasm contains numerous, homogeneous low electron dense secretory granules, which are essentially similar to those seen in normal delta cells.

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