A Case Series of Metastatic Malignant Gastrointestinal Neuroectodermal Tumors and Comprehensive Genomic Profiling Analysis of 20 Cases

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.

Automated summary

Malignant gastrointestinal neuroectodermal tumor (GNET) is an ultra-rare soft tissue sarcoma that often goes misdiagnosed and currently lacks standard treatment options. This study reports on 3 cases of metastatic GNET with different clinical courses, supporting the notion that GNET is a spectrum of diseases with varying biology and prognosis. Surgical management may be appropriate for GNET with an indolent nature in cases of recurrent or metastatic disease. The response to systemic treatments, including chemotherapy and targeted therapies, is variable and likely influenced by the heterogeneous biology of GNET.