Poorly differentiated clusters (PDCs), defined as solid cancer nests comprising ≥ 5 cancer cells lacking tubular formation, may reflect the phenotype of epithelial-mesenchymal transition. The diagnostic utility in pathological practice and clinical significance in pancreatic ductal carcinoma (PDAC) has not been fully explored. This study aimed to investigate the presence of PDCs in PDAC and evaluate their clinical implications. We examined the presence of PDCs in 102 cases with PDAC. Tumor clusters with ≥ 5 clusters were classified as high PDCs and < 5 were classified as low PDCs. The association of pathological parameters and survival was assessed for high and low PDCs. Subgroup analyses were also performed for 37 cases following neoadjuvant chemotherapy (NAT). High PDCs were significantly associated with larger tumors, advanced pT category (≥ T3), lymphatic and vascular invasion, positive surgical margins, high tumor budding (TB), elevated CA19-9 levels, and increased recurrence risk (P = 0.014, 0.021, 0.011, 0.013, 0.026, < 0.001, 0.016, 0.027, respectively). Moreover, this was associated with worse overall survival and disease-free survival of PDAC, especially in cases following NAT (P < 0.001). Additionally, high PDCs in cases following NAT was an independent prognostic factor for shorter overall (Hazard ratio (HR): 9.131, P = 0.012) and disease-free survival (HR: 3.896, P = 0.018) in multivariable Cox regression analysis, exceeding TB in prognostic impact. PDCs in the actual pathological diagnosis are more useful as a prognostic marker for PDAC than TB. Due to the limited sample size and broad confidence intervals, the findings of this study should be interpreted with caution and require validation in larger, independent cohorts.
Uchihara et al. (Fri,) studied this question.