<scp> <i>GLI1</i> </scp> ‐Altered Mesenchymal Tumor of the Duodenum With a Novel <i>TNFAIP3::GLI1</i> Gene Fusion: Report of a Diagnostically Challenging Case Associated With Late Metastasis

We report a GLI1-altered mesenchymal tumor of the duodenum with a novel TNFAIP3::GLI1 gene fusion, deceptive morphology, and late recurrence. The patient was a 72-year-old female who was found to have a polypoid 3.7 cm duodenal mass which, based on epithelioid morphology and focal immunoreactivity for cytokeratin, was diagnosed as invasive adenocarcinoma following review by an academic consultant. Sixty-seven months later, the patient presented with multiple liver nodules representing metastatic disease. RNA sequencing demonstrated a novel TNFAIP3::GLI1 gene fusion in the liver lesion, which had higher mitotic activity but showed similar pure epithelioid morphology and immunophenotype as the original small bowel lesion. In addition to expanding the spectrum of GLI1-associated gene fusions, this case highlights the potential for misdiagnosis of epithelioid GLI1-altered mesenchymal tumors as adenocarcinoma (particularly given the variable immunoreactivity for cytokeratin), and the need for long-term follow up of these typically slowly growing neoplasms.