Expanding the Spectrum of GLI1-rearranged Neoplasms of the Gastrointestinal Tract to Include Monophasic Keratin-positive Epithelial Neoplasms

Am J Surg Pathol. 2024 Nov 1;48(11):1389-1394. doi: 10.1097/PAS.0000000000002303. Epub 2024 Sep 18.

Abstract

GLI1-altered tumors form a diverse group occurring in various anatomic locations. In the alimentary tract, the most established are gastroblastoma, a biphasic epithelial-mesenchymal neoplasm of the stomach, and plexiform fibromyxoma, a pure spindle cell neoplasm. The spectrum of GLI1-rearranged gastrointestinal tumors has recently expanded with reports of cases in other parts of the GI tract, some exhibiting gastroblastoma-like features and others being pure mesenchymal neoplasms. These tumors often display a nonspecific immunophenotype, with only CD56 and cyclin D1 expression being common. Biphasic GLI1-altered tumors show diffuse keratin positivity in the epithelial component only, and GLI1-altered mesenchymal tumors typically lack or show only focal keratin expression. This study details 2 GLI1-rearranged gastrointestinal tract tumors with diffuse keratin and CD56 expression, composed entirely of epithelial cells with a nested growth pattern and finely stippled monotonous nuclei, leading to an initial suspicion of neuroendocrine tumor in both cases, despite lack of synaptophysin and chromogranin expression. Diffuse strong nuclear cyclin D1 expression was seen in both cases, and conversely, strong cyclin D1 staining was only seen in 5.4% (4/74) of well-differentiated neuroendocrine tumors tested. These 2 GI tract neoplasms highlight a widened spectrum of GLI1-rearranged tumors, now including monophasic epithelial neoplasms with diffuse keratin expression.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Biomarkers, Tumor* / analysis
  • Biomarkers, Tumor* / genetics
  • Female
  • Gastrointestinal Neoplasms / genetics
  • Gastrointestinal Neoplasms / pathology
  • Gene Rearrangement*
  • Humans
  • Immunohistochemistry*
  • In Situ Hybridization, Fluorescence
  • Keratins* / analysis
  • Keratins* / metabolism
  • Male
  • Middle Aged
  • Zinc Finger Protein GLI1* / genetics
  • Zinc Finger Protein GLI1* / metabolism

Substances

  • Zinc Finger Protein GLI1
  • Biomarkers, Tumor
  • GLI1 protein, human
  • Keratins