Hidden heterogeneity in complicated appendicitis: comparison of preoperative biomarker profiles across the histopathological spectrum of acute appendicitis

Complicated appendicitis, comprising gangrenous and perforated subtypes, is conventionally treated as a single category in biomarker studies. These subtypes may nonetheless represent distinct pathophysiological processes, and whether they exhibit different preoperative biomarker profiles has not been systematically investigated. This study compared preoperative biomarker profiles across the histopathological spectrum of acute appendicitis and evaluated the diagnostic role of immature granulocytes (IG). This retrospective single-centre study included 363 appendectomy patients classified as acute appendicitis ( n = 227), gangrenous appendicitis ( n = 59), perforated appendicitis ( n = 33), or negative appendectomy ( n = 44). A three-tiered framework compared negative appendectomy versus true appendicitis, uncomplicated versus complicated, and gangrenous versus perforated appendicitis. Laboratory parameters and composite indices were analysed by ROC analysis with DeLong confidence intervals and Holm-adjusted pairwise comparisons, and by multivariable logistic regression with Firth penalized and bootstrap-corrected sensitivity analyses. Gangrenous and perforated appendicitis exhibited divergent biomarker profiles. Neutrophil-based indices did not discriminate between subtypes, all confidence intervals including 0.50 (AUC 0.449–0.547), whereas CRP-based parameters and IG retained discriminatory capacity (AUC 0.756–0.853). CRP increased monotonically across the spectrum (15.7 → 39.4 → 157.0 mg/L), whereas NLR rose from acute to gangrenous appendicitis and showed no further increase thereafter ( p = 0.600). IG percentage outperformed neutrophil percentage (ΔAUC = 0.314, Holm-adjusted p < 0.001). CRP ( p < 0.001) and IG count ( p = 0.010; Firth p = 0.012) were independent predictors of perforated appendicitis, and adding IG count to CRP improved model fit ( p = 0.002). Neutrophil-based indices fail at the gangrenous-perforated boundary, whereas CRP and IG retain diagnostic value across the spectrum. All findings are exploratory: they derive from a single operated cohort and require external validation before clinical application. The principal implication is methodological: pooling these subtypes under one complicated category may cause signal loss in biomarker studies. Not applicable.