Shivji S, et al. Histopathology 2020 - Review.
Poorly differentiated clusters (PDC), defined as small groups of ≥ 5 tumor cells without glandular differentiation, have gained recent attention as a promising prognostic factor in colorectal cancer (CRC). Numerous studies have shown PDC to be significantly associated with other adverse histopathologic features and worse clinical outcomes. PDC may hold particular promise in stage II colon cancer, where risk stratification plays a critical role in patient selection for adjuvant chemotherapy. In
addition, emerging evidence suggests that PDC can predict lymph node metastasis in endoscopically resected pT1 CRC, potentially helping the selection of patients for oncologic resection. In "head-to-head" comparisons, PDC grade has consistently outperformed conventional histologic grading systems both in terms of risk stratification and reproducibility. With a number of large scale studies now available, this review evaluates the evidence regarding the prognostic significance of PDC, considers its relationship with other emerging invasive front prognostic markers (such as tumor budding and stroma type), and assesses its "practice readiness", addressing issues such as interobserver reproducibility, scoring methodologies, and special histologic subtypes (e.g. micropapillary and mucinous carcinoma), and draws attention to ongoing challenges and areas in need of further study. Finally, emerging data on the role of PDC in non-colorectal cancers are briefly considered.