Journal of Pathology and Translational Medicine

Original Article

Primary Merkel cell carcinoma of the salivary gland: a clinicopathologic study of four cases with a review of literature: Gyuheon Choi, Joon Seon Song, Hee Jin Lee, Gi Hwan Kim, Young Ho Jung, Yoon Se Lee, Kyung-Ja Cho; J Pathol Transl Med. 2025;59(3):171-179. Published online April 30, 2025; DOI: https://doi.org/10.4132/jptm.2025.03.25

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Abstract PDF: Background
Primary Merkel cell carcinoma of the salivary gland is currently not listed in the World Health Organization classification. However, cases of Merkel cell type neuroendocrine carcinomas of the salivary gland with perinuclear cytokeratin 20 positivity have been intermittently reported. We here investigated the clinicopathologic features of additional cases.
Methods
Data of four cases of Merkel cell type small cell neuroendocrine carcinoma of the salivary gland were retrieved. To confirm the tumors’ primary nature, clinical records and pathologic materials were reviewed. Optimal immunohistochemical staining was performed to support the diagnosis.
Results
All tumors were located in the parotid gland. Possibilities of metastasis were excluded in all cases through a meticulous clinicopathological review. Tumor histology was consistent with the diagnosis of small cell neuroendocrine carcinoma. Tumors’ immunohistochemical phenotypes were consistent with Merkel cell carcinoma, including Merkel cell polyomavirus large T antigen positivity in two of the four cases.
Conclusions
Merkel cell carcinomas can originate in salivary glands and are partly associated with Merkel cell polyomavirus infection as in cutaneous Merkel cell carcinomas.

Case Studies

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; J Pathol Transl Med. 2024;58(2):91-97. Published online March 13, 2024; DOI: https://doi.org/10.4132/jptm.2024.02.13

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Pancreatic neuroendocrine microtumor (PNEMT) is a neuroendocrine tumor (NET) < 0.5 cm in diameter, and it is considered benign. We report a PNEMT with high-grade transformation (HGT). A man in his 60s with von Hippel-Lindau syndrome underwent surgical resection of a NET. A second sub-centimeter nodule with a nodule-in-nodule pattern was discovered. The 0.4 cm outer nodule contained clear columnar cells with round nuclei and indistinct nucleoli, while the 0.1 cm inner nodule had eosinophilic cells with an increased nuclear to cytoplasmic ratio, vesicular nuclei, and prominent nucleoli. Tumor cells in the outer and inner nodules were synaptophysin and chromogranin positive. Only the inner nodule was p53 positive, while the outer nodule was exclusively positive for carbonic anhydrase 9 and vimentin. The Ki-67 labeling indices for the outer and inner nodules were 2.1% (grade 1) and 44.3% (grade 3), respectively. This nodule was determined to be a PNEMT with HGT. Our findings suggest that a PNEMT may not always be benign and can undergo HGT.

Citations

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Molecular Basis of Pancreatic Neuroendocrine Tumors
Alesia Maluchenko, Denis Maksimov, Zoia Antysheva, Julia Krupinova, Ekaterina Avsievich, Olga Glazova, Natalia Bodunova, Nikolay Karnaukhov, Ilia Feidorov, Diana Salimgereeva, Mark Voloshin, Pavel Volchkov
International Journal of Molecular Sciences.2024; 25(20): 11017. CrossRef

Primary carcinoid tumor in the external auditory canal: Dong Hae Chung, Gyu Cheol Han, Na Rae Kim; J Pathol Transl Med. 2020;54(2):184-187. Published online November 13, 2019; DOI: https://doi.org/10.4132/jptm.2019.11.07

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Abstract PDF

A 39-year-old man visited the department of otolaryngology due to an ongoing hearing disturbance that had lasted for 1 year. Temporal bone computed tomography revealed soft tissue density nearly obliterating the left external auditory canal (EAC). The mass was composed of sheets of round tumor cells containing moderate amounts of fine granular cytoplasm and salt and pepper chromatin. Neither mitosis nor necrosis was found. The Ki-67 proliferation index was less than 2%. Cells were positive for CD56 and synaptophysin but negative for chromogranin, cytokeratin (CK) 20, and CK7. Based on these findings, the tumor was diagnosed as a carcinoid tumor, well differentiated neuroendocrine carcinoma, grade 1 (G1) according to current World Health Organization (WHO) classification of head and neck tumors; and a neuroendocrine tumor, G1 according to neuroendocrine neoplasm (NEN)-2018 WHO standard classification. He remained free of local recurrence and metastasis after 20 months of follow up. To date, only six cases of primary NENs in the EAC have been reported. Metastatic tumor should be included in the differential diagnoses. Because of its rarity, the prognosis and treatment have not yet been clarified.

Citations

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First Report on a Rare Poorly Differentiated Neuroendocrine Tumour of the External Auditory Canal Involving Pinna
Akash Varshney, Amit Kumar Tyagi, Prashant Durgapal, Kajal Mahto, Akhilesh Chandra Yadav, Ankita Semwal
Indian Journal of Otolaryngology and Head & Neck Surgery.2025; 77(4): 1922. CrossRef
Incidental finding of a neuroendocrine neoplasm in a suspected ear canal exostosis
Alexander Wieck Fjaeldstad, Gerda Elisabeth Villadsen, Gitte Dam, Stephen Jacques Hamilton-Dutoit, Thomas Winther Frederiksen
Otolaryngology Case Reports.2022; 22: 100394. CrossRef
68Ga-DOTATATE Uptake in Well-Differentiated Neuroendocrine Tumor of the External Auditory Canal
Özge Erol Fenercioğlu, Ediz Beyhan, Rahime Şahin, Mehmet Can Baloğlu, Tevfik Fikret Çermik
Clinical Nuclear Medicine.2022; 47(8): e552. CrossRef

Combined Hepatocellular Carcinoma and Neuroendocrine Carcinoma with Ectopic Secretion of Parathyroid Hormone: A Case Report and Review of the Literature: Hyun Jung Kwon, Ji-Won Kim, Haeryoung Kim, YoungRok Choi, Soomin Ahn; J Pathol Transl Med. 2018;52(4):232-237. Published online May 25, 2018; DOI: https://doi.org/10.4132/jptm.2018.05.17

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Abstract PDF

Primary combined hepatocellular carcinoma (HCC) and neuroendocrine carcinoma is a rare entity, and so is hypercalcemia due to ectopic parathyroid hormone (PTH) secretion by tumor. A 44-year old man with hepatitis B virus associated chronic liver disease presented with a hepatic mass. Hemihepatectomy discovered the mass as combined HCC and poorly differentiated cholangiocarcinoma. During adjuvant chemoradiation therapy, he presented with nausea, and multiple systemic metastases were found. Laboratory tests revealed hypercalcemia with markedly elevated PTH and neuron specific enolase. Parathyroid scan showed normal uptake in parathyroid glands, suggestive of ectopic PTH secretion. Subsequently, immunohistochemistry of neuroendocrine marker was performed on the primary lesion, and confirmed the neuroendocrine differentiation in non-HCC component. The patient died 71 days after surgery. This report may suggest the possibility of ectopic PTH secretion by neuroendocrine carcinoma of hepatic origin causing hypercalcemia. Caution for neuroendocrine differentiation should be exercised when diagnosing poorly differentiated HCC.

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Daniela Sambataro, Sandro Bellavia, Paolo Di Mattia, Danilo Centonze, Carmela Emmanuele, Annalisa Bonasera, Giuseppe Caputo, Andrea Maria Onofrio Quattrocchi, Ernesto Vinci, Vittorio Gebbia, Maria Rosaria Valerio
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Magalie Haissaguerre, Estelle Louiset, Christofer C Juhlin, Adam Stenman, Christophe Laurent, Hélène Trouette, Hervé Lefebvre, Antoine Tabarin
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Claudio Luchini, Giuseppe Pelosi, Aldo Scarpa, Paola Mattiolo, Deborah Marchiori, Roberta Maragliano, Fausto Sessa, Silvia Uccella
Pathologica.2021; 113(1): 28. CrossRef
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Hong Wang, Dan Yang, Zhenru Wu, Yan Luo, Wenwu Ling
Frontiers in Medicine.2021;[Epub] CrossRef
Combined primary hepatic neuroendocrine carcinoma and hepatocellular carcinoma: case report and literature review
Akira Nakano, Kenichi Hirabayashi, Hiroshi Yamamuro, Taro Mashiko, Yoshihito Masuoka, Seiichiro Yamamoto, Soji Ozawa, Toshio Nakagohri
World Journal of Surgical Oncology.2021;[Epub] CrossRef
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Hsuan Yeh, Chung-Cheng Chiang, Tzung-Hai Yen
World Journal of Gastroenterology.2021; 27(26): 4104. CrossRef
Severe hypercalcaemia from ectopic intact parathyroid hormone secretion treated with continuous renal replacement therapy in a patient with two malignancies
Nathaniel Hocker, Maria Story, Alysa Lerud, Sarat Kuppachi
BMJ Case Reports.2021; 14(6): e242172. CrossRef
Parathyroid Carcinoma and Ectopic Secretion of Parathyroid hormone
Filomena Cetani, Elena Pardi, Claudio Marcocci
Endocrinology and Metabolism Clinics of North America.2021; 50(4): 683. CrossRef
Primary hepatic neuroendocrine cancer coexisted with hepatocellular carcinoma: a case report
Chikara Ebisutani, Seitetsu Yoon, Toshiki Hyodo, Takafumi Watanabe, Hirofumi Okada, Yutaka Shirakawa, Yoshio Sakamoto, Shigeya Hirohata
Kanzo.2020; 61(3): 122. CrossRef
Two-in-one: A pooled analysis of primary hepatic neuroendocrine carcinoma combined/collided with hepatocellular carcinoma
Jia-Xi Mao, Fei Teng, Ke-Yan Sun, Cong Liu, Guo-Shan Ding, Wen-Yuan Guo
Hepatobiliary & Pancreatic Diseases International.2020; 19(4): 399. CrossRef
Primary hepatic neuroendocrine carcinoma coexisting with distal cholangiocarcinoma
Qi Xin, Rong Lv, Cheng Lou, Zhe Ma, Gui-Qiu Liu, Qin Zhang, Hai-Bo Yu, Chuan-Shan Zhang
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Mixed hepatocellular carcinoma-neuroendocrine carcinoma—A diagnostic and therapeutic challenge
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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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Abstract PDF

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

Combined Adenosquamous and Large Cell Neuroendocrine Carcinoma of the Gallbladder: Jiyoon Jung, Yang-Seok Chae, Chul Hwan Kim, Youngseok Lee, Jeong Hyeon Lee, Dong-Sik Kim, Young-Dong Yu, Joo Young Kim; J Pathol Transl Med. 2018;52(2):121-125. Published online October 5, 2017; DOI: https://doi.org/10.4132/jptm.2017.08.20

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Abstract PDF

Large cell neuroendocrine carcinoma (LCNEC) of the gallbladder is extremely rare and usually combined with other type of malignancy, mostly adenocarcinoma. We report an unusual case of combined adenosquamous carcinoma and LCNEC of the gallbladder in a 54-year-old woman. A radical cholecystectomy specimen revealed a 4.3×4.0 cm polypoid mass in the fundus with infiltration of adjacent liver parenchyma. Microscopically, the tumor consisted of two distinct components. Adenosquamous carcinoma was predominant and abrupt transition from adenocarcinoma to squamous cell carcinoma was observed. LCNEC showed round cells with large, vesicular nuclei, abundant mitotic figures, and occasional pseudorosette formation. The patient received adjuvant chemotherapy. However, multiple liver metastases were identified at 3-month follow-up. Metastatic nodules were composed of LCNEC and squamous cell carcinoma components. Detecting LCNEC component is important in gallbladder cancer, because the tumor may require a different chemotherapy regimen and show early metastasis and poor prognosis.

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Does the size of the neuroendocrine-carcinoma component determine the prognosis of gallbladder cancer?
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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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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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Elia Guadagno, Gaetano De Rosa, Marialaura Del Basso De Caro
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Nicolas M. Orsi, Mini Menon
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Original Article

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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Brief Case Report

A Ciliated Cyst with Müllerian Differentiation Arising in the Posterior Mediastinum: So Jung Lee, Chung Su Hwang, Do Youn Park, Gi Young Huh, Chang Hun Lee; Korean J Pathol. 2014;48(5):401-404. Published online October 27, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.5.401

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Original Articles

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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Monu Pandey, Abhirup Mukhopadhyay, Surender K. Sharawat, Sachin Kumar
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Neuroendocrine Tumors Are Enriched in Cowden Syndrome
Alison Greidinger, Susan Miller-Samuel, Veda N. Giri, Michele Sue-Ann Woo, Saranya Akumalla, Charnita Zeigler-Johnson, Scott W. Keith, Daniel P. Silver
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Prognostic and predictive role of the PI3K–AKT–mTOR pathway in neuroendocrine neoplasms
P. Gajate, T. Alonso-Gordoa, O. Martínez-Sáez, J. Molina-Cerrillo, E. Grande
Clinical and Translational Oncology.2018; 20(5): 561. CrossRef
Genetic and epigenetic drivers of neuroendocrine tumours (NET)
Annunziata Di Domenico, Tabea Wiedmer, Ilaria Marinoni, Aurel Perren
Endocrine-Related Cancer.2017; 24(9): R315. CrossRef
Expression of hsa-let-7b-5p, hsa-let-7f-5p, and hsa-miR-222-3p and their putative targets HMGA2 and CDKN1B in typical and atypical carcinoid tumors of the lung
Pietro Di Fazio, Moritz Maass, Silvia Roth, Christian Meyer, Joana Grups, Peter Rexin, Detlef K Bartsch, Andreas Kirschbaum
Tumor Biology.2017; 39(10): 101042831772841. CrossRef
The regulatory role of aberrant Phosphatase and Tensin Homologue and Liver Kinase B1 on AKT/mTOR/c-Myc axis in pancreatic neuroendocrine tumors
Tsung-Ming Chang, Yan-Shen Shan, Pei-Yi Chu, Shih Sheng Jiang, Wen-Chun Hung, Yu-Lin Chen, Hsiu-Chi Tu, Hui-You Lin, Hui-Jen Tsai, Li-Tzong Chen
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Pulmonary atypical carcinoid in a patient with Cowden syndrome
Hiroaki Tsunezuka, Kaori Abe, Junichi Shimada, Masayoshi Inoue
Interactive CardioVascular and Thoracic Surgery.2016; 22(6): 860. CrossRef
Differential miRNA-Expression as an Adjunctive Diagnostic Tool in Neuroendocrine Tumors of the Lung
Melanie Demes, Christoph Aszyk, Holger Bartsch, Joachim Schirren, Annette Fisseler-Eckhoff
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microRNA-21 promotes osteogenic differentiation of mesenchymal stem cells by the PI3K/β-catenin pathway
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Inhibition of NADPH oxidase protects against metastasis of human lung cancer by decreasing microRNA-21
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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.

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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
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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
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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
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Early diagnosis and treatment of gastrointestinal neuroendocrine tumors
Hong Shen, Zhuo Yu, Jing Zhao, Xiu-Zhen Li, Wen-Sheng Pan
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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.

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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

Clinicopathological Analysis of 21 Thymic Neuroendocrine Tumors: Soomin Ahn, Jae Jun Lee, Sang Yun Ha, Chang Ohk Sung, Jhingook Kim, Joungho Han; Korean J Pathol. 2012;46(3):221-225. Published online June 22, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.3.221

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Abstract PDF

Background

Thymic neuroendocrine carcinomas (NECs) are uncommon, for which there is no established information available because of a limited number of epidemiological study in Asia.

Methods

We reviewed 21 cases of surgically resected thymic NECs, and evaluated their pathological and clinical features.

Results

It showed male predominance (male/female ratio, 15/6) with wide age range from 20 to 72 years (mean age, 49 years). All 21 cases were divided into two types according to the World Health Organization criteria: atypical carcinoid (n=18) and large cell NEC (n=3). Three cases of atypical carcinoid (AC) were associated with ectopic Cushing's syndrome. All the patients (3/3) with large cell NEC (3/3) and 16.7% (3/18) of those with AC died of tumor progression. Common sites of metastasis included lung, lymph node, brain, lumbar spine, mediastinum, bone, and liver.

Conclusions

In conclusion, thymic neuroendocrine tumors carry a poor prognosis. Regarding the tumor classification, our results showed that a vast majority of carcinoids in the thymus correspond to ACs. In addition, our results also indicate that typical carcinoid is a very rare entity. Some cases of AC exhibited a large size, solid pattern and they showed aggressive clinical behavior, which highlights the spectrum of histologic appearances of thymic NECs.

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Interobserver Variability in Diagnosing High-Grade Neuroendocrine Carcinoma of the Lung and Comparing It with the Morphometric Analysis: Seung Yeon Ha, Joungho Han, Wan-Seop Kim, Byung Seong Suh, Mee Sook Roh; Korean J Pathol. 2012;46(1):42-47. Published online February 23, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.1.42

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Abstract PDF

Background

Distinguishing small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC) of the lung is difficult with little information about interobserver variability.

Methods

One hundred twenty-nine cases of resected SCLC and LCNEC were independently evaluated by four pathologists and classified according to the 2004 World Health Organization criteria. Agreement was regarded as "unanimous" if all four pathologists agreed on the classification. The kappa statistic was calculated to measure the degree of agreement between pathologists. We also measured cell size using image analysis, and receiver-operating-characteristic curve analysis was performed to evaluate cell size in predicting the diagnosis of high-grade neuroendocrine (NE) carcinomas in 66 cases.

Results

Unanimous agreement was achieved in 55.0% of 129 cases. The kappa values ranged from 0.35 to 0.81. Morphometric analysis reaffirmed that there was a continuous spectrum of cell size from SCLC to LCNEC and showed that tumors with cells falling in the middle size range were difficult to categorize and lacked unanimous agreement.

Conclusions

Our results provide an objective explanation for considerable interobserver variability in the diagnosis of high-grade pulmonary NE carcinomas. Further studies would need to define more stringent and objective definitions of cytologic and architectural characteristics to reliably distinguish between SCLC and LCNEC.

Citations

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