Gastrointestinal clear cell sarcoma (GICCS)/malignant gastrointestinal neuroectodermal tumor (GNET) is an extremely rare form of cancer with aggressive clinical behavior. It has distinct pathological, immunohistochemical, ultrastructural, and molecular features. Herein, we present the case of a 20-year-old woman with no notable medical history who presented to the outpatient department with complaints of abdominal pain and vomiting. Symptoms had been evolving for 3 months. The physical examination revealed slight abdominal tenderness and melena. Biological investigations revealed iron-deficiency anemia. The upper and lower endoscopies showed no abnormalities. Magnetic resonance enterography revealed small bowel wall thickening of 15 mm × 2 mm. Exploratory laparotomy revealed an ileal mass with mesenteric lymphadenopathy. A wide resection of the mass was then performed. The final pathological report confirmed the diagnosis of small bowel GICCS/GNET. After 11 months of follow-up, the patient presented with mesenteric lymph node metastases.

Malignant gastrointestinal neuroectodermal tumors (GNETs) are mesenchymal tumors that typically arise in the digestive tract and harbor EWSR1::ATF1 or EWSR1::CREB1 fusions. We report a case of primary retroperitoneal GNET in a 38-year-old woman who presented with a month-long fever with increased serum IL-6 level. A right retroperitoneal mass of 7 cm consisting of diffuse sheets of small cells with a high nuclear-to-cytoplasmic ratio and scattered osteoclast-like multinucleated giant cells was confirmed apart from the digestive tract. Peripheral lymphoid cuff and focal pseudoangiomatous spaces were present, reminiscent of angiomatoid fibrous histiocytoma. The tumor cells were positive for S100 protein and SOX10 and negative for melanocytic markers. Fluorescent in situ hybridization revealed EWSR1 and CREM gene rearrangements, consistent with EWSR1::CREM fusion, which has never been reported in GNET. The patient lives with recurrent lesions for 8 months. This case was associated with several unusual features and contributes to the evolving GNET concept.

Malignant gastrointestinal neuroectodermal tumor (GNET) is an extremely rare soft tissue sarcoma and has been designated as a new entity recently. At present, GNET virtually exclusively occurs in the gastrointestinal tract. Here we report a case of extra-GNET that arose in the right heart. A 62-year-old male complained of chest distress and breathing difficulty while lying down at night for over 1 month at admission. The radiological findings revealed an occupying lesion involving the right atrium and the right ventricle without any abdominal abnormalities. The patient then underwent a surgical resection. Microscopically, neoplastic cells proliferated in the pattern of nests and sheets with fibrous separation. Focal areas with cellular dyscohesion imparted a vague pseudopapillary pattern. These tumor cells were small to medium in size with fine chromatin and predominantly pale eosinophilic cytoplasm. The nuclei were typically round to oval with somewhat irregular contours and contained small nucleoli. The mitotic figures were easily found. Immunohistochemically, the neoplastic cells were positive for S100 and SOX-10 but negative for HMB-45, A103, and CD99. EWSR1-AFTF1 rearrangement was detected by fluorescence in situ hybridization and further confirmed by whole-transcriptome sequence analysis. The patient had pulmonary metastasis 8 months later and soon died of the disease. The overall survival of the patient was 20 months. In summary, we reported an extremely rare case of cardiac GNET, indicating that the location of GNET should not be confined to the GI tract as initially defined. Due to the lack of a specific effective treatment and the occurrence of early metastasis, cardiac GNET conferred a poor prognosis. More clinical and experimental studies are warranted to better manage this disease in the future.

Malignant gastrointestinal neuroectodermal tumor (GNET) is a rare neoplasm with unknown etiology. It was previously referred to as Clear cell sarcoma of gastrointestinal tract. This tumor is characterized by a higher rate of local recurrence and metastasis. Due to its aggressive clinical course, distinguishing this entity from various other mimickers is very essential. Herein, we present a case of malignant GNET in a 33-year-old male patient.

Malignant gastrointestinal neuroectodermal tumors (GNETs), also called clear-cell sarcoma-like tumors of the gastrointestinal tract, are rare and highly aggressive tumors originating in the gastrointestinal tract. These tumors are generally immunohistochemically positive for S-100 protein (S-100) and SRY-related HMG-box 10 (SOX10), and often contain EWSR1-ATF1 or EWSR1-CREB1. The histological features of GNETs overlap with those of clear-cell sarcoma of the tendons and aponeuroses. However, GNETs immunohistochemically lack melanocyte-specific markers and often demonstrate positivity for CD56, synaptophysin and neuron-specific enolase. The present case reports a woman with a history of desmoplastic malignant melanoma exhibiting a BRAF mutation, which later transformed into a GNET of the small intestine with both a BRAF mutation and two subtypes of EWSR1-ATF1 fusion genes. Tumor cells were revealed to be weakly immunoreactive or negative for S-100 and SOX10, lacked markers of melanocytic differentiation and were focally positive for CD56. Combination therapy with dabrafenib mesylate and trametinib dimethyl sulfoxide proved to be temporarily effective against this tumor. The present case is relatively unique as, to the best of our knowledge, there is no case of GNET with a history of melanoma. Furthermore, there is no report of GNET exhibiting both a BRAF mutation and an EWSR1-ATF1 fusion gene. Further accumulation of similar cases is necessary to elucidate the pathological significance of this GNET having a BRAF mutation.

Malignant gastrointestinal neuroectodermal tumor (M-GNET) and clear cell sarcoma (CCS) of soft tissue represent closely related, extremely rare, malignant mesenchymal neoplasm of uncertain differentiation. Both entities are characterized genetically by the same molecular alterations represented by the presence of EWSR1-ATF1 and, more rarely, EWSR1-CREB1 fusion genes. The latter translocation seems to be more represented in M-GNET that, despite significant morphologic overlap with CCS, tends to lack overt features of melanocytic differentiation. Most M-GNET occur in the lower gastrointestinal tract, whereas occurrence in the upper tract has been reported only exceptionally. The differential diagnosis represents a major challenge, and accurate diagnosis impact significantly on therapeutic planning. We herein report the clinicopathologic features of a molecularly confirmed M-GNET that arose at the base of the tongue and review the pertinent literature.

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Malignant gastrointestinal neuroectodermal tumors (GNETs) are rare aggressive malignant neoplasms that exclusively occur within the wall of the gastrointestinal tract. The GNET was first described as an \'osteoclast-rich tumor of the gastrointestinal tract with features resembling clear cell sarcoma (CCS) of soft parts\' in 2003. Although the GNET shares certain histological features with CCS, it is characterized by a lack of melanocytic differentiation and the presence of non-tumoral osteoclast-like giant cells (OLGCs). The present study reports a case of a GNET of the ileum with intra-abdominal granulomatous nodules, an uncommon accompanying finding, and summarizes the current literature. A 30-year-old woman presented with the symptoms of intestinal obstruction, and a mass was found within the ileum wall. Multiple grey-white nodules were found adhering to the omentum and serosa of the ileum. Histologically, the tumor was located in the muscularis propria and infiltrated the mucosa and the serosa. Tumor cells presented with oval or polygonal nuclei and prominent nucleoli, and were predominantly arranged in nested and pseudopapillary patterns, with the presence of cluster of differentiation (CD)68-positive, scattered OLGC. Immunohistochemically, it was determined that the tumor cells expressed Vimentin, CD56, S-100 and transcription factor SOX-10, while being negative for pan-cytokeratin, cytokeratin (CK)7, CK20, synaptophysin, chromogranin-A, CD117, anoctamin-1, CD34, human melanoma black-45, Melan-A, smooth muscle actin, CD3 and CD20 expression. Ewing sarcoma breakpoint region 1 gene rearrangement was identified by fluorescence in situ hybridization analysis. Ultrastructurally, no typical melanosomes were identified. In addition, the intra-abdominal grey-white nodules were microscopically identified as chronic granulomatous inflammation. The patient received four cycles of adjuvant chemotherapy following routine tumor resection. Due to its rarity and histological similarity with other neoplasms, unfamiliarity with the features of GNETs by surgical pathologists can easily lead to a misdiagnosis. Therefore, comprehensive assessments, including morphology and ancillary studies, are required for an accurate diagnosis of GNET.

BACKGROUND: Malignant gastrointestinal neuroectodermal tumor (GNET) is an extremely rare entity that was first described by Zambrano et al. in 2003 as \"Clear cell sarcoma-like tumor of the gastrointestinal tract\". It shares some of the histological features of clear cell sarcoma (CCS) but lacks the immunohistochemical reactivity for melanocytic markers. We report a case of GNET that was initially misdiagnosed as gastrointestinal stromal tumor (GIST). Recognizing this entity is important to avoid misdiagnosis.
METHODS: A case of an 18-year-old male presented with a small intestinal tumor. Histologically it was characterized by polygonal cells arranged in pseudoalveolar pattern and situated in the muscularis propria. Scattered osteoclast-like multinucleated giant cells were also noted. The neoplastic cells were positive for S-100 protein and negative for HMB-45, Melan A, smooth muscle actin, desmin and CD117. EWSR1 gene rearrangement was detected by fluorescence in situ hybridization (FISH) analysis. The patient returned with recurrence after 36 months\' management by surgical resection and died one year later.
CONCLUSIONS: GNET can be mistaken histologically for other non-epithelial gastrointestinal tumors. Awareness of its existence and diagnostic criteria by the pathologist is necessary to avoid misdiagnosis, particularly as GIST, CCS or malignant peripheral nerve sheath tumor (MPNST).

Malignant gastrointestinal neuroectodermal tumor (GNET) is a rare soft tissue sarcoma, previously referred to as clear cell sarcoma-like gastrointestinal tumor (CCSLGT) and also commonly reported in the literature as clear cell sarcoma of the gastrointestinal tract (CCS-GI). The current study reports a case of GNET arising in the stomach of a 17-year-old male, who presented with symptoms of fatigue, anemia and low temperature. Examination with positron emission tomography-computed tomography revealed a soft tissue mass in the gastric antrum. Subsequently, radical distal gastric resection was performed, and the mass measured 6.0×4.0×3.5 cm3. Histopathological analysis revealed that the tumor cells were arranged in nests and focally formed fascicular, pseudopapillary, pseudoalveolar and rosette-like growth patterns. Osteoclast-like giant cells were also observed. Immunohistochemically, the tumor cells were positive for S-100 protein, vimentin and BCL-2, and negative for HMB45, Melan-A, CD117, CD34 and CD99. Additionally, the osteoclast-like giant cells were positive for CD68. Fluorescence in situ hybridization demonstrated EWSR1 gene rearrangement. After 10 months of follow-up, no evidence of recurrence or metastasis was observed. As GNET is currently classified differently and under various names in the literature, the information provided by this case study and review is predicted to be useful towards the accurate diagnosis, treatment and prognosis of this rare tumor type.