RESUMEN
Alpha-smooth muscle actin (α-SMA) expression in the stroma is linked to the presence of cancer-associated fibroblasts and is known to correlate with worse outcomes in various tumors. In this study, using a GeoMx digital spatial profiling approach, we characterized the gene expression of the tumor and α-SMA-expressing stromal cell compartments in pancreatic neuroendocrine tumors (PanNETs). The profiling was performed on tissues from eight retrospective cases (three grade 1, four grade 2, and one grade 3). Selected regions of interest were segmented geometrically based on tissue morphology and fluorescent signals from synaptophysin and α-SMA markers. The α-SMA-expressing stromal-cell-associated genes were involved in pathways of extracellular matrix modification, whereas, in tumor cells, the gene expression profiles were associated with pathways involved in cell proliferation. The comparison of gene expression profiles across all three PanNET grades revealed that the differences between grades are not only present at the level of the tumor but also in the α-SMA-expressing stromal cells. Furthermore, the tumor cells from regions with a rich presence of adjacent α-SMA-expressing stromal cells revealed an upregulation of matrix metalloproteinase-9 (MMP9) expression in grade 3 tumors. This study provides an in-depth characterization of gene expression profiles in α-SMA-expressing stromal and tumor cells, and outlines potential crosstalk mechanisms.
RESUMEN
BACKGROUND Neuroendocrine tumors (NETs) primarily originating from the extrahepatic biliary (EB) tree are a medical rarity, accounting for less than 100 recorded instances globally. This case report outlines an encounter with this uncommon condition, demonstrating the complexities of diagnosis and management. CASE REPORT A 42-year-old woman presented at our Emergency Department with a 3-week history of itching and symptoms of obstructive jaundice. Initial laboratory tests showed hyperbilirubinemia and elevated liver transaminases. Abdominal ultrasonography indicated choledocholithiasis. Magnetic resonance imaging suggested either Mirizzi syndrome or a proximal common bile duct neoplasm. Abdominal computed tomography showed cholestasis, suggesting choledocholithiasis or cholangiocarcinoma (type-1). An endoscopic retrograde cholangiopancreatography with biliary and pancreatic duct stenting was performed for drainage, with brush cytology confirming adenocarcinoma. The patient was referred for surgical resection of the bile duct tumor, involving extrahepatic bile duct resection, en bloc cholecystectomy, lymphadenectomy, Roux-en-Y anastomosis, and biliary drainage. Histopathology identified a neuroendocrine carcinoma. Following surgery, the patient underwent eight cycles of FOLFOX6 chemotherapy, with no disease relapse post-treatment. CONCLUSIONS This case emphasizes multidisciplinary teamwork importance in managing rare diseases like EB bile duct NETs. These tumors' rarity and symptom ambiguity necessitate histological examination for accurate diagnosis. This report aims to guide healthcare professionals facing similar future cases.