ObjectivesThere is interest in identifying chronic rhinosinusitis (CRS) endotypes that align pathophysiology with clinical observation and outcomes. CRS with polyps (CRSwNP) has classically been studied with reference to tissue eosinophilia, but the role of other cellular infiltrates remains uncharacterized. No particular tissue prognosticators have been described for CRS without nasal polyps (CRSsNP). Predominance of leukocytes seen in surgical tissue may be useful for differentiating CRS subtypes, severity of inflammation, and outcomes.MethodsStructured histopathology reports were examined for 277 patients undergoing endoscopic sinus surgery for CRSwNP (n = 115), CRSsNP (n = 141), and recurrent acute rhinosinusitis (RARS, n = 21). Inflammatory predominance was examined for associations with nasal polyposis, asthma, allergic rhinitis, aspirin exacerbated respiratory disease (AERD), immune deficiency, preoperative Lund‐Mackay score, and outcome (SNOT‐22 score change).ResultsIn order of frequency, the prevalence of predominant inflammatory patterns accounting for 93.5% of CRS patients were: lymphoplasmocytic (n = 111), lymphocytic (n = 74), eosinophilic (n = 50), and lymphoplasmocytic with eosinophilic (n = 24). Eosinophilic predominance was 97.4% specific for nasal polyps (95% confidence interval [CI], 93.4%‐99.3%), although sensitivity was 43.4% (95% CI, 33.8%‐53.4%). The absence of eosinophilic predominance was 100% sensitive for RARS (95% CI, 82.4%‐100%), however specificity was 30.8% (95% CI 25.1%‐37.1%). There were no significant differences in preoperative SNOT‐22 scores or change postoperatively.ConclusionsEosinophilic inflammatory predominance was predictive for nasal polyps and against RARS. Nevertheless, the majority of CRSwNP patients had a different inflammatory predominance, demonstrating heterogeneity in CRS, even among patients with nasal polyps. Symptomatic outcomes were not associated with inflammatory predominance through 12 months follow up.Level of Evidence4.