The indolent nature of gastroblastoma. Report of an illustrative case with 28 years of follow-up showing previously unreported immunohistochemical and molecular features

We report the clinical, morphological, ultrastructural, and molecular features of a gastroblastoma diagnosed in a 27-year-old male describing some unreported findings that can help to better understand this very rare tumor. The clinical course lasting 28 years confirms the indolent nature of gastroblastoma, although the disease was metastatic to local lymph nodes and peritoneum at the time of diagnosis. The tumor displayed a predominant monophasic appearance, being composed of epithelial cells with only very rare spindle mesenchymal cells, confirmed at ultrastructural examination. Thorough immunohistochemical investigation demonstrated coexpression of cytokeratins (AE1/AE3, CAM5.2, CK8/18), podoplanin (D2-40), CD56, and NSE in absence of synaptophysin, chromogranin A, DOG1, CD117, CD34, SMA, desmin, vimentin, and S100. In addition, the expression of somatostatin receptor 2 A associated with positive octreoscan and 68 Ga-DOTATOC PET imaging may suggest the use of this nuclear medicine approach for the staging of the tumor and to select patients for possible therapy with somatostatin analogues. The tumor was mismatch repair proteins proficient and did not show any mutation in all 60 genes investigated. Interestingly, targeted RNA sequencing identified a previously unreported TAC3::GLI1 fusion that expands the spectrum of genetic aberrations of gastroblastoma.