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A Case Series of Metastatic Malignant Gastrointestinal Neuroectodermal Tumors and Comprehensive Genomic Profiling
Taylor Kandler1, Eliane Cortez2, Lani Clinton3
1Department of Medicine, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Abstract:
Malignant gastrointestinal neuroectodermal tumor (GNET) is an ultra-rare soft tissue sarcoma, therefore often misdiagnosed and has no available standard treatment. Here, we report 3 cases of metastatic GNET with variable clinical courses. Our small case series as well as extensive literature review, further support that GNET is a spectrum of diseases with variable inherent biology and prognosis. Surgical management in the setting of recurrent/metastatic disease may be appropriate for GNET with indolent nature. Response to systemic treatments including chemotherapy and targeted treatments is variable, likely related to heterogenous biology as well. Furthermore, we retrospectively identified 20 additional GNET cases from Foundation Medicine's genomic database and expanded on their clinicopathological and genomic features. Comprehensive genomic profiling (CGP) with DNA and RNA sequencing of this cohort, in the course of clinical care, demonstrated recurrent EWSR1 chromosomal rearrangements and a sparsity of additional recurrent or driver genomic alterations. All cases had low tumor mutational burden (TMB) and were microsatellite stable.
Insights
Malignant gastrointestinal neuroectodermal tumor (GNET) is a rare sarcoma often misdiagnosed. Genomic profiling reveals EWSR1 rearrangements but few other drivers, suggesting GNET is a diverse disease spectrum.
Area of Science:
- Oncology
- Genomics
- Pathology
Background:
- Malignant gastrointestinal neuroectodermal tumor (GNET) is an ultra-rare soft tissue sarcoma.
- GNET is frequently misdiagnosed due to its rarity and lacks standard treatment protocols.
Observation:
- This study reports on 3 metastatic GNET cases with varied clinical outcomes.
- An additional 20 GNET cases were identified and analyzed from a genomic database.
Findings:
- GNET represents a spectrum of diseases with diverse biology and prognoses.
- Comprehensive genomic profiling (CGP) revealed recurrent EWSR1 chromosomal rearrangements.
- Cases exhibited low tumor mutational burden (TMB) and microsatellite stability.
Implications:
- Surgical management may be suitable for indolent GNET with recurrent or metastatic disease.
- Variable responses to systemic therapies highlight the heterogeneous biology of GNET.
- Understanding GNET's genomic landscape can inform future diagnostic and therapeutic strategies.
