Expression of serotonergic (5HT) receptors in patients with chronic rhinosinusitis with nasal polyposis and in normal nasal mucosa: a case-control study.Background Chronic rhinosinusitis with nasal polyposis is one of the challenging conditions regarding treatment and management. Many recent studies introduced new modalities for treatment like targeted immunomodulating drugs rather than antihistamines, local and systemic steroids, and endoscopic sinus surgery. Understanding the pathology behind the disease by studying its immunologic pathways and substances that take part in the inflammatory process can help in the introduction of new treatment options that can improve outcomes and decrease the costs of treatment.Objective The aim of our study is to demonstrate the presence of 5-HT receptors in nasal polyps and inferior turbinate mucosa in patients with chronic rhinosinusitis with nasal polyposis and then compare this expression of 5-HT receptors with inferior turbinate mucosa of the normal control group.Methods A case-control study was conducted on 80 patients. Specimens from nasal polypi and turbinate mucosa of patients with chronic rhinosinusitis (cases) and specimens from normal turbinate mucosa (controls) were stained with serotonin receptor Immunohistochemical staining by automated immunostainer in the pathology department laboratory in Ain Shams University Hospital with ratio 1:200–400 as recommended by the manufacturing company. Then, compared as regards stain distribution and intensity of mucosal lining, glands, and blood vessels.Results There was a significant difference between polyp cases and controls as regards lining epithelium and mucosal gland stain distribution and stain intensity. Also significant difference between the polyp cases and controls as regards blood vessel strain distribution. However, no significant difference was found as regards blood vessel stain intensity. There was a significant difference between turbinate cases and controls as regards lining epithelium stain distribution, and stain intensity. There was no significant difference between turbinate cases and controls as regards gland stain distribution. However, a significant difference was found between turbinate and controls as regards gland stain intensity. There was a significant difference between turbinate cases and controls as regards blood vessel stain distribution; however, no significant difference was present as regards stain intensity. There was no significant difference between polyp and turbinate cases as regards lining epithelium and blood vessel stain distribution and stain intensity. There was no significant difference between polyp and turbinate cases as regards gland stain distribution; however, a highly significant difference between polyp and turbinate cases as regards gland stain intensity.Conclusion Serotonin receptors are highly expressed in patients with chronic rhinosinusitis with nasal polyposis in both turbinate and polypoidal tissues which proves that serotonin has a strong role in the formation and growth of nasal polypi and allergic reactions. Hence serotonin modulating drugs can be studied as a new therapy for chronic rhinosinusitis with nasal polyposis.