Systemic immune-inflammation index as an independent predictor of malignancy in 4-6 cm adrenal incidentalomas

Adrenal incidentalomas (AI) measuring 4-6 cm present a diagnostic challenge, as size alone inadequately predicts malignancy and creates uncertainty in surgical decisions.

To evaluate the Systemic Immune-Inflammation Index (SII) as a predictor of malignancy in adrenal tumors ≥4 cm, with a focus on the 4-6 cm "gray zone."

Retrospective single-center cohort of 91 adrenalectomy patients with AI ≥ 4 cm (ACC n = 19, ACA n = 72). A predefined subgroup included 46 patients with 4-6 cm tumors (ACC n = 9, ACA n = 37). SII was calculated from preoperative complete blood counts (CBC) as platelets × neutrophils / lymphocytes. Predictive performance was assessed using ROC analysis and logistic regression.

In the ≥4 cm cohort, SII was higher in ACC vs. ACA (1107.4 vs. 711.3, p < 0.001). SII independently predicted ACC (per 100-unit increase: OR 0.78, 95% CI 0.67-0.90; p = 0.002). SII showed AUC 0.778 with a cut-off of 811 (sensitivity 78.9%, specificity 73.6%). Tumor size was not predictive (AUC ≈ 0.50). In the 4-6 cm subgroup, SII remained an independent predictor (per 100-unit increase: OR 0.61, 95% CI 0.45-0.82; p = 0.004), with AUC 0.898 at a cut-off of 945 (sensitivity 88.9%, specificity 83.8%).

SII-derived from routine CBC-is a low-cost, adjunctive biomarker that improves preoperative malignancy risk stratification beyond size in AI, particularly in 4-6 cm tumors. External prospective validation is warranted before routine implementation.