The Association Between Neutrophil-to-Lymphocyte Ratio and Histological Tumor Differentiation in Solid Malignancies: A Systematic Review.

Background: The neutrophil-to-lymphocyte ratio (NLR) has been the focus of extensive research in recent years as an inexpensive inflammatory biomarker with prognostic value in oncology, but its relationship with tumor grade across solid malignancies remains uncertain. Methods: This systematic review evaluated original clinical studies reporting the association between peripheral blood NLR and histological tumor grade in solid tumors. PubMed and Web of Science were searched using Boolean strategies, and eligible full-text studies were synthesized qualitatively because of heterogeneity in tumor type, grading system, NLR threshold, and statistical reporting. Results: The qualitative synthesis included 13 retrospective primary studies comprising 5394 patients. Eight studies reported statistically significant associations between higher NLR and higher tumor grade or poorer differentiation, most consistently in bladder cancer and in single studies of prostate cancer, soft tissue sarcoma, renal cell carcinoma, pancreatic cancer, breast cancer, and colorectal cancer with synchronous liver metastases. Four studies reported no statistically significant grade-related association, mainly in heterogeneous breast cancer and ovarian cancer cohorts, whereas a small colorectal adenocarcinoma cohort study showed a non-significant positive trend. Conclusions: The available evidence suggests a possible relationship between systemic inflammation and tumor grade in selected malignancies, but the evidence remains preliminary, tumor-specific, retrospective, and vulnerable to confounding. NLR should not be interpreted as a surrogate for histological grade.