Case report: A EWSR1-CREM-Rearranged Gastric Mesenchymal Tumor Accompanied by Gastritis Cystica Profunda and with Probable Benign Behavior

Background:Genomic rearrangements involving EWSR1 and the CREB family of transcription factors are increasingly detected in an array of mesenchymal neoplasms, including clear cell sarcoma-like tumors of the gastrointestinal tract (CCSLGT), a gastrointestinal malignancy. Gastritis cystica profunda (GCP) is a rare disease characterized by cystic dilatation of gastric glands into the submucosa and generally regarded as a precursor to tumor.Case presentation:Herein, we report a peculiar case in which a EWSR1-CREM-rearranged gastric mesenchymal tumor was admixed with GCP in a gastric fundic mass in a 64-year-old woman. Histologically, the mass showed readily distinguishable epithelial and mesenchymal components. All layers of the gastric wall were invaded, although no lymph node or neural invasion, or tumoral vascular emboli was noted. The epithelial component consisted of foveolar-type glands interspersed with pyloric-type ones, with glands showing metaplastic growth. Most glands were elongated with irregular contour, with some forming cystic structures containing eosinophilic secretory material. The epithelial cells showed focally atypical hyperchromatic nuclei, inconspicuous nucleoli, slightly eosinophilic cytoplasm, and infrequent mitosis. The mesenchymal component consisted of monomorphic, ovoid-shaped cells often arranged in sheets surrounding the glands. These cells displayed scanty cytoplasm, regular nuclei, and rare mitotic figures. Immunohistochemically, the epithelial cells were uniformly positive for cytokeratins and negative for markers of neuroendocrine differentiation, and the mesenchymal neoplasm showed focal positivity for CD10, CD117 and CD56 as well as negativity for cytokeratin, neuroendocrine markers, DOG-1, CD34, SMA, desmin, HMB-45, Melan A, and S-100. An EWSR1-CREM fusion was identified with genomic profiling and confirmed with fluorescence in situ hybridization in the tumor. Given the low mitotic activity, absence of nodal or distant spread and vascular or neural invasion, and the disease-free status at 28-month follow-up, both lesions were likely benign. Conclusions:To our knowledge, this is the first to report a EWSR1-CREM fusion in a gastric mesenchymal tumor with accompanying GCP. Whether this case suggests a novel entity or falls into one of proposed classes awaits report of more similar cases and insights into the relationship between GCP pathogenesis and oncogenesis.