Increased Neutrophil Infiltration and Epithelial Cell Proliferation in Sinonasal Inverted Papilloma Compared to Contralateral Nasal Polyps

Abstract

Background Sinonasal inverted papilloma (IP) is a rare and benign epithelial tumor in the sinonasal tract. Recent study suggested the potential role of chronic inflammation in the pathogenesis of IP. This study aims to compare the inflammatory pattern, the capacity of epithelial cell proliferation and EGFR mutation status of unilateral IP with contralateral polyp tissue. Methods Sixteen patients with unilateral IP and contralateral nasal polyps (NP) were identified through a retrospective chart review. The neutrophil and eosinophil infiltration in IP and NP were assessed by immunostaining for neutrophil elastase and major basic protein (MBP). Immunohistochemistry was also used to assess the expression of FoxM1, Ki67 and cyclin D1 in IP tissue and contralateral NP. Sanger sequencing was used to evaluate the EGFR mutations. Results The neutrophil count in IP was significantly higher than contralateral NP and 68.8% patients presented with neutrophilic inflammation, whereas only 37.5% contralateral NP tissue showed neutrophilic inflammation. The percentage of positive FoxM1-staining cells was significantly increased in IP, and positively correlated with the percentage of cells with positive staining for cyclin D1 and ki67 as well as neutrophil counts. EGFR exon 20 insertions were detected in 14 (87.5%) IP samples and no EGFR mutations were found in contralateral NP sample. Conclusion Our study demonstrated distinct inflammatory pattern between IP and contralateral NP and implied the oncogenic role of neutrophils in the pathogenesis of IP. EGFR mutations may be the early event to initiate IP development by enhancing epithelial cell proliferation.

Unusual presentation and histopathology of bilateral nasal polypi; cavernous hemangioma (right) and inverted papilloma (left)

“…Recently, some authors demonstrated the distinct inflammatory pattern of the inverted papilloma, implying the oncogenic role of the acute inflammatory cells, neutrophils, in the pathogenesis of the inverted papilloma. 22 As the incidence of malignant transformation has been reported variably, ranging from 5% to 80%, so it is mandatory to continue follow-up with endoscopic surveillance for early detection of recurrence. The patient with this reported condition had no evidence of recurrence or suspicious lesions after the complete excision of both lesions during a 2-years follow-up period.…”

“…EGFR mutations might be the early event initiating this tumor's development by enhancing epithelial cell proliferation, and numerous factors, including viral infection (such as HPV), smoking, and chronic inflammation, can contribute to nasal inverted papilloma, however, the pathogenesis of the inverted papilloma is still unclear. Recently, some authors demonstrated the distinct inflammatory pattern of the inverted papilloma, implying the oncogenic role of the acute inflammatory cells, neutrophils, in the pathogenesis of the inverted papilloma 22 …”

Identification and Potential Value of Candidate Genes in Patients with Sinonasal inverted papilloma

“…However, there have been few studies focused on etiology and pathogenesis. One recent study suggested the potential role of chronic in ammation [6,7] and viral (human papillomavirus and Epstein-Barr virus) infection in the etiology of SNIP [8][9][10]. At the molecular level, several cell cycle and angiogenic factors, such as Ki67, vascular endothelial growth factor (VEGF), and Akt/mTOR have been implicated in the development and progression of SNIP [11].…”

Continuum robots for endoscopic sinus surgery: Recent advances, challenges, and prospects

“…The average prevalence of chronic sinusitis ranges from 4.6% to 16.9% annually depending on the study methodology and sample size 8 . Nasopharyngeal carcinoma, papilloma, adenocarcinoma, and esthesioneuroblastoma are the common tumors involved in the sinonasal region 9,10 . Surgical interventions are performed to treat sinus diseases, especially for patients who fail appropriate medical therapy.…”