Pancreatic Ductal Adenocarcinoma and Its Variants

Two rare cancers of the exocrine pancreas: to treat or not to treat like ductal adenocarcinoma?

“…Based upon this data, we have initiated a Phase 2 study of Minnelide for ASCP patients, which is currently in recruitment (NCT04896073) [114] . ASCP has been noted to have expression of PD-L1 in the squamous components and a more tumor inflamed phenotype than standard PDAC [51,57,58] . Another Phase 2 study (NCT05216120) is testing the anti-PD-1 antibody retifanlimab (INCMGA00012) in ASCP patients with hopes that this tumor type will be more responsive to immunotherapy than PDAC.…”

“…Under light microscopy, ASCP is more likely to have increased necrosis, to be poorly differentiated and to have increased vascular invasion compared to PDAC [ 51 ] . Malignant glandular components of ASCP appear similar to PDAC, while the squamous component has well-defined cell borders with intercellular bridges and keratinization of the cytoplasm [ 52 ] . Representative H&E-stained images of ASCP are shown in Figure 1 .…”

“…The glandular component stains positive for CK8/18, CK7, CEA, and CA19-9, similar to PDAC, while appreciable expression of CK5/6, p63, and p40 is seen in the squamous component. The squamous area also exhibits frequent loss of E-cadherin and p16, and increased EGFR and vimentin expression [ 52 – 55 ] . Positive nuclear p63 expression has been validated as a more sensitive marker for ASCP in tumors that are difficult to classify by routine H&E stains [ 52 ] .…”

“…The squamous area also exhibits frequent loss of E-cadherin and p16, and increased EGFR and vimentin expression [ 52 – 55 ] . Positive nuclear p63 expression has been validated as a more sensitive marker for ASCP in tumors that are difficult to classify by routine H&E stains [ 52 ] . Others have noted that metastases from an ASCP primary may appear as a pure adenocarcinoma, or even dedifferentiate to giant cell or pleomorphic-appearing anaplastic carcinomas with multi-nucleated forms, markedly bizarre nuclei, and prominent nucleoli [ 45 ] .…”