Clinicogenomic analysis of rare histologic variants of pancreatic carcinoma: Undifferentiated carcinomas with and without osteoclast-like giant cells.

• DOI: 10.1200/jco.2023.41.16_suppl.e16001
• Publication Date: 2023-06-04T15:38:35Z
• Authors: Jamie Mills; Valerie Gunchick; Jiaqi Shi; Aaron M. Udager; Timothy Frankel; Vaibhav Sahai; Mark Zalupski
• Keywords: 03 medical and health sciences; 0302 clinical medicine; 3. Good health

e16001 Background: Undifferentiated carcinoma (UC) is a rare subtype of pancreatic and can present with or without osteoclast-like giant cells (OGC). This 2010 delineation complicates interpretation prior studies comparing UC to ductal adenocarcinomas (PDAC). Limited retrospective data suggest UC-OGC tumors correspond younger age, larger size, worse prognosis compared UC. The role OGC hypothesized alter the immune microenvironment tumors, leading different response therapy PDAC. Methods: aim study was assess clinical outcomes, histology (H&E), targeted genomics panel, transcriptomics (RNA panel CIBERSORT-X), multiplex immunofluorescence (mIF) tumor milieu in cohort adult patients Results: We identified 32 15 treated at Michigan Medicine between 2005 2021. demographics, presenting symptoms, CA 19-9 were similar cohorts. In advanced cancers, median survival 2.6 months (N = 22) vs 8.13 2) for UC-OGC, respectively (p 0.27). R0 resection completed 10 (31%) 13 (87%) UC-OGC; 17.0 145.0 months, 0.03). Genomic landscape PDAC (TCGA; N 159), KRAS TP53 mutations rates. However, transcriptome revealed significantly increased M2 macrophages CD4 - 8 (γδ) T-cells decreased regulatory (Tregs) UC/UC-OGC 10) < 0.05). These corroborated by mIF reduced Tregs 0.046) trend toward 0.055) 17), but not CD8 + T cells, which enriched 0.0001; 17). Conclusions: Overall, this demonstrates longer both resected patients. Increased pro-tumorigenic macrophage infiltration suggests potential inhibitors other immune-modulatory therapies combination chemotherapy these variants cancer.