
==== Front
Int J Surg Case Rep
Int J Surg Case Rep
International Journal of Surgery Case Reports
2210-2612
Elsevier

S2210-2612(24)00976-3
10.1016/j.ijscr.2024.110195
110195
Case Report
Malignant duodenal gastrointestinal neuroectodermal tumor (GNET): Case report and review of the literature
Fournier Antony Anthony.Fournier@usherbrooke.ca
a
Deslauriers Vicki Vicki.Deslauriers@usherbrooke.ca
b
Giguère Charlie Champagne Charlie.Champagne.Giguene@usherbrooke.ca
c
Borduas Martin Martin.Borduas@usherbrooke.ca
c
Collin Yves Yves.Collin@usherbrooke.ca
ab⁎
a Department of Surgery, University of Sherbrooke, Sherbrooke, Canada
b Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, Canada
c Department of Pathology, University of Sherbrooke, Sherbrooke, Canada
⁎ Corresponding author at: 580 Rue Bowen S, Sherbrooke, Quebec J1G 2E8, Canada. Yves.Collin@usherbrooke.ca
20 8 2024
10 2024
20 8 2024
123 11019529 6 2024
14 8 2024
17 8 2024
Crown Copyright © 2024 Published by Elsevier Ltd on behalf of IJS Publishing Group Limited.
2024

https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Introduction

Malignant gastrointestinal neuroectodermal tumor (GNET) is a rare malignancy primarily affecting the gastrointestinal tract. Upon cross-sectional imaging, it can be easily confused with other mesenchymal tumors. This article presents a case of duodenal GNET and reviews the current literature on this rare entity.

Presentation of case

A 73-year-old female patient presented with a 4 cm duodenal mass on CT scan. With a presumptive diagnosis of GIST, a D3-D4 duodenectomy with cholecystectomy were performed. Subsequent pathological analysis of the surgical specimen revealed a 4.5 cm malignant gastrointestinal neuroectodermal tumor (GNET), also known as clear cell sarcoma-like gastrointestinal tumor (CCSLGT).

Discussion

While there are less than 115 cases of GNET reported worldwide, prognosis is usually poor with a 50 % survival at 3 years, and mortality rate described is as high as 75 %. To the authors' knowledge, this duodenal GNET case represents the first one ever described for this location.

Conclusion

Early recognition of GNET is essential due to its poor prognosis and its ability to metastasize. Awareness of its existence and diagnostic criteria by every member of the medical team is key to obtain optimal patient care.

Highlights

• Importance of differentiate GNET between other NET.

• Strongly suggested to generate new tests for GNET detection.

• New therapies needed for poor prognosis described.

Keywords

GNET
Rare gastric tumor
Aggressive tumor surgery
Neuroendocrine tumor
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pmc1 Introduction

Malignant gastrointestinal neuroectodermal tumor (GNET), also referred to as clear cell sarcoma-like gastrointestinal tumor (CCSLGT), is an aggressive and rare tumor primarily affecting the bowel, stomach, and colon [[1], [2], [3], [4]]. Initially described as an osteoclast-rich tumor in 2003 by Zambrano et al., it exhibited partial immunohistochemical features of clear cell sarcoma (CCS) [5]. Similarly, by analyzing the CCS proportions in melanocytic markers, this tumor was first classified as GNET by Stockman et al. in 2012 [1,3,6,7]. To our knowledge, there are fewer than 115 cases reported worldwide in the literature [1,4,[7], [8], [9], [10]]. This case represents one of the few patients ever described, and this work has been reported in line with the SCARE criteria [11].

2 Case report

A 73-year-old female presented in early 2023 with a 15-pound weight loss over 4 months, along with intermittent abdominal pain. She was known for cardiovascular disease on aspirin, hypertension and had received an appendicectomy and three C-sections. Her physical examination revealed abdominal tenderness, but no signs of peritonism. Upon investigations, a large D3-D4 duodenal mass (4 cm) was found on CT scan (see Fig. 1). Initial primary care center pathologic analysis of specimens obtained via an upper endoscopy suggested an epithelioid stromal gastrointestinal tumor (GIST). However, on this same sample, subsequent microscopic procedures performed in our tertiary center revealed a very different and rare entity: malignant gastrointestinal neuroectodermal tumor (GNET). According to referring hospital analyses, a D3-D4 duodenectomy with cholecystectomy and latero-lateral duodeno-jejunal anastomosis were performed for a presumptive diagnosis of GIST. She was discharged four days after her surgery without any complications and received minor pain management.Fig. 1 Abdominal CT scan showing heterogenous D3-D4 duodenal mass.

Fig. 1

Final surgical pathology specimen consisted of an intestinal segment measured at 15 × 2.5 × 3.5 cm and a 7.5 cm gallbladder. A macroscopic protrusion measuring 4.5 × 3.5 × 3.5 cm was visible on the mesenteric side, with ulceration of the underlying mucosa (see Fig. 2, Fig. 3, Fig. 4). Histologic examination and immunohistochemistry (IHC) assays pointed to a diagnosis of GNET: the nested epithelioid tumor cells were positive for S100, SOX10, synaptophysin and CD56, and were negative for CD117 (c-kit), DOG-1, MelanA, HMB45, PanCK and chromogranin (see Fig. 5, Fig. 6). Ki67 proliferation index was at 30 %. Tumor length was evaluated at 4.5 cm with extension to the mucosa and sub-serosa, with free resected ends. Nerve involvement was also identified. The specimen contained one lymph node, which was negative for tumor contamination. Microscopic analysis of the gallbladder revealed no neoplastic involvement. Finally, a t(2; 22) (q33; q12) EWSR1-CREB1 translocation was detected, thus confirming the diagnosis of GNET.Fig. 2 Macroscopic examination showing a 4.5 cm exophytic mass on the mesenteric side of the duodenal resection specimen.

Fig. 2

Fig. 3 Opened duodenal segment revealing ulceration of the mucosa overhanging the mural mass.

Fig. 3

Fig. 4 Cross-section of formalin-fixed specimen showing the mural mass in relation to the overhanging ulcerated duodenal mucosa (left) and corresponding histologic section (right).

Fig. 4

Fig. 5 High-power light microscopy tumor examination showing nested, large round basophilic nuclei with vesicular chromatin and some prominent nucleoli. Cytoplasms contain eosinophilic fibrillary processes with clear spaces. A neuroblastic rosette is seen at bottom left.

Fig. 5

Fig. 6 IHC assays showed diffuse and strong tumor cells positivity for S100 (shown here), SOX10, synaptophysin and CD56.

Fig. 6

On postoperative day 25, the patient consulted in the emergency department for a wound infection and was treated with antibiotics. One week later, her clinical evaluation revealed no signs of complications. Subsequent follow-ups were unremarkable, and a 6-month postoperative CT scan showed no signs of intra-abdominal recurrence. After consultations with oncologic experts, no adjuvant treatment was given to our patient.

3 Discussion

Malignant gastrointestinal neuroectodermal tumor (GNET) is an extremely rare disease affecting primarily young adults aged 33 to 36 years-old [1,8]. Clinical findings include abdominal pain, obstruction, distension, vomiting and non-specific systemic manifestations [1,3]. Most cases involve the small intestine, stomach or colon, with a 29 % likelihood of metastatic disease to the liver or lymph nodes [1,3,8].

Typical appearance on cross sectional imaging is not well documented, but Morani et al. found that GNET can present as heterogenous enhancing and exoenteric GI tract masses, while smaller constrictive lesions tend to be homogenous [1]. Although it has an important role in diagnosis, imaging does not clearly exclude differential diagnoses such as neuroendocrine tumors, gastrointestinal stromal tumors (GISTs), adenocarcinoma or other mesenchymal tumors. An endoscopic ulcerated pattern, when present, can also mimic common carcinomas [4] (see Fig. 3). This situation was also encountered in our patient's care, where further analysis was necessary to distinguish GNET from other duodenal pathology e.g. GIST.

Although it is debated whether GNET and the clear cell sarcoma (CCS) share a common morphological spectrum, Green C et al. and Bosoteanu et al. established that these two entities could be distinguished through immunohistochemical and morphological findings [8,12]. In fact, GNET express S100 protein almost systematically, with possibility of SOX10, synaptophysin, NSE, CD56–57 positivity while lacking melanocytic-specific markers [1,2,8,12]. Presence of MelanA and HMB45 could rather suggest a CCS diagnosis, but true pathological differentiation between the two entities is still debated in current literature [1,2,6]. Genetic hallmarks include EWSR1-CREB1 or EWSR1-ATF1 fusion caused by t(2;22)(q33;q12) and t(12;22)(q13;q12) translocations respectively [2,8,13], which are crucial for diagnosis. Interestingly, these same histologic and genetic features confirmed the diagnosis in our patient and eliminated GIST as a potential disease.

Treatment primarily involves radical resection with wide lymphadenectomy [1,4,14]. Adjuvant therapy remains unclear, but multitarget receptor tyrosine kinase inhibitors and chemotherapy could improve survival. Chang et al. reported 2 patients with partial response and stable disease to apatinib treatment, and 1 patient with partial response to anlotinib treatment [3]. Singh et al. published a case of localized GNET with 7-years disease-free survival after platinum-based chemotherapy [14]. Prognosis is poor, with a 50 % survival rate at three years and high mortality rates [2]. After consultations with oncologic experts, no adjuvant treatment was deemed necessary for our patient.

4 Conclusion

Malignant duodenal gastrointestinal neuroectodermal tumor (GNET) is a rare entity, histologically different from gastrointestinal stromal tumors (GIST). Early recognition is essential due to its poor prognosis and its ability to metastasize. With fewer than 115 cases reported worldwide, our paper emphasizes the importance of considering and identifying GNET as a potential diagnosis for a small bowel, stomach, or colon mass. This article also advocates a multimodal approach between pathologists, radiologists, clinicians, and primary oncologic care centers for optimal patient care.

Ethical approval

Approval for this study was obtained from the local ethics committee as well as written informed consent from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review on request.

Funding

No funding was used for this paper.

Author contribution

Antony Fournier, Vicki Deslauriers, Charlie Champagne Giguère, Martin Borduas and Yves Collin have contributed to study designing and data collection, data analysis and writing.

Guarantor

Dr Yves Collin, Department of Surgery, University of Sherbrooke, and Centre Intégré Universitaire de Santé et de Services Sociaux de l’Estrie - Centre Hospitalier Universitaire de Sherbrooke (CIUSSSE – CHUS)”, is the Guarantor for this work.

Research registration number

No Unique Identifying number or registration ID needed.

Conflict of interest statement

None.

Acknowledgement

We would like to acknowledge the patient who participated in this study and the staff of the CIUSS de l’Estrie-CHUS research center for their valuable guidance and support throughout the research and publication process.
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