A peculiar mimicker of gastro-entero-pancreatic neuroendocrine tumors: Malignant Gastrointestinal Neuroectodermal Tumor – literature review and one case report
Alexandra Ondu
https://orcid.org/0009-0001-7221-7722
Vlad Herlea
https://orcid.org/0000-0002-0125-7815
Florin Botea
https://orcid.org/0000-0001-7104-747X
Gabriel Becheanu
https://orcid.org/0000-0003-1627-8907
Mihai-Mircea Diculescu
https://orcid.org/0000-0003-0073-5990
https://orcid.org/0009-0001-7221-7722
Vlad Herlea
https://orcid.org/0000-0002-0125-7815
Florin Botea
https://orcid.org/0000-0001-7104-747X
Gabriel Becheanu
https://orcid.org/0000-0003-1627-8907
Mihai-Mircea Diculescu
https://orcid.org/0000-0003-0073-5990
Abstract
Malignant gastrointestinal neuroectodermal tumor (GNET) is a distinctive and relatively newly described neoplasm that is seldom encountered in routine clinical practice. It is characterized by a predominantly monomorphic population of polyhedral to epithelioid cells, exhibiting pale eosinophilic or clear cytoplasm, rounded nuclei with vesicular chromatin, and occasionally prominent eosinophilic nucleoli. These cells are arranged in a heterogeneous pattern, forming small nests, compact solid areas, and pseudo-papillary or pseudo-microcystic structures. Within the tumor, osteoclast-like giant cells may be a notable feature, although their presence is variable. This tumor consistently demonstrates positivity for S100, SOX10, and vimentin, while it is invariably negative for Melan-A, HMB45, desmin, CD117, and pan-cytokeratin. Additionally, it exhibits variable expression of the following immunohistochemical markers: synaptophysin, chromogranin, CD56, neuron-specific enolase (NSE), and neurofilament protein (NFP). A specific mutation in the Ewing’s sarcoma breakpoint region 1 (EWSR1) gene has been described for GNET, characterized by EWSR1-CREB1 and EWSR1-ATF1 fusions. This article discusses the clinical, pathological, immunophenotypic, and genetic features of one clinical case of GNET, followed by a literature review of 127 cases published in the PubMed database, for which full-length articles were accessible. According to this review, approximately 10% of GNETs have been initially misdiagnosed, with about 6% being misclassified as neuroendocrine tumors or neuroendocrine carcinomas.
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Keywords
malignant gastrointestinal neuroectodermal tumor (GNET), clear cell sarcoma-like tumor of the gastrointestinal tract (CCSTGT), differential diagnostic of neuroendocrine tumor, NET mimicker, EWSR1 fusions, GIST differential diagnostic, neural crest origin, osteoclast-like giant cells
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5. Chang B, Yu L, Guo WW, et al. Malignant Gastrointestinal Neuroectodermal Tumor: Clinicopathologic, Immunohistochemical, and Molecular Analysis of 19 Cases. Am J Surg Pathol. 2020 Apr;44(4):456-466. doi: 10.1097/PAS.0000000000001396. PMID: 31651526.
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7. Huang GX, Chen QY, Zhong LL, et al. Primary malignant gastrointestinal neuroectodermal tumor occurring in the ileum with intra-abdominal granulomatous nodules: A case report and review of the literature. Oncol Lett. 2019 Apr;17(4):3899-3909. doi: 10.3892/ol.2019.10060. PMID: 30930990; PMCID: PMC6425295.
8. Thway K, Fisher C. Tumors with EWSR1-CREB1 and EWSR1-ATF1 fusions: the current status. Am J Surg Pathol. 2012 Jul;36(7):e1-e11. doi: 10.1097/PAS.0b013e31825485c5. PMID: 22510762.
9. Kandler T, Cortez E, Clinton L, et al. A Case Series of Metastatic Malignant Gastrointestinal Neuroectodermal Tumors and Comprehensive Genomic Profiling Analysis of 20 Cases. Curr Oncol. 2022 Feb 21;29(2):1279-1297. doi: 10.3390/curroncol29020109. PMID: 35200608; PMCID: PMC8870546.
10. Su D, Yang H, Zhao M, et al. Malignant gastrointestinal neuroectodermal tumor: a case report and literature review. Ann Med Surg (Lond). 2023 Oct 12;85(12):6196-6201. doi: 10.1097/MS9.0000000000001400. PMID: 38098564; PMCID: PMC10718339.
11. Kervarrec T, Lecointre C, Kerdraon R, et al. Tumeur neuroectodermique gastro-intestinale (GNET) : à propos d'un cas de tumeur du grêle avec métastases hépatiques [Gastro-intestinal neuroectodermal tumor (GNET): A case report of a small intestine tumor with hepatic metastases]. Ann Pathol. 2015 Dec;35(6):506-10. French. doi: 10.1016/j.annpat.2015.09.006. PMID: 26586017.
12. Sankar S, Lessnick SL. Promiscuous partnerships in Ewing's sarcoma. Cancer Genet. 2011 Jul;204(7):351-65. doi: 10.1016/j.cancergen.2011.07.008. PMID: 21872822; PMCID: PMC3164520.
13. Sadler TW (Thomas W). Langman's medical embryology. Langman’s Medical Embryology. 12th ed. T.W. Sadler. Philadelphia : Wolters Kluwer Health/Lippincott Williams & Wilkins, c2012.
English. 407 p. ISBN: 9781451113426. NLM ID: 101562744
14. Rosai J. The origin of neuroendocrine tumors and the neural crest saga. Mod Pathol. 2011 Apr;24 Suppl 2:S53-7. doi: 10.1038/modpathol.2010.166. PMID: 21455201.
15. Kosemehmetoglu K, Folpe AL. Clear cell sarcoma of tendons and aponeuroses, and osteoclast-rich tumor of the gastrointestinal tract with features resembling clear cell sarcoma of soft parts: a review and update. J Clin Pathol. 2010 May;63(5):416-23. doi: 10.1136/jcp.2008.057471. PMID: 20418233.
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How to Cite
Ondu, A., Herlea, V., Botea, F., Becheanu, G., & Diculescu, M.-M. (2025). A peculiar mimicker of gastro-entero-pancreatic neuroendocrine tumors: Malignant Gastrointestinal Neuroectodermal Tumor – literature review and one case report. Archive of Clinical Cases, 12(2), 66-74. https://doi.org/10.22551/2025.47.1202.10316
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How to Cite
Ondu, A., Herlea, V., Botea, F., Becheanu, G., & Diculescu, M.-M. (2025). A peculiar mimicker of gastro-entero-pancreatic neuroendocrine tumors: Malignant Gastrointestinal Neuroectodermal Tumor – literature review and one case report. Archive of Clinical Cases, 12(2), 66-74. https://doi.org/10.22551/2025.47.1202.10316