Malignant transformation of sinonasal inverted papilloma and related genetic alterations: a systematic review

Abstract

Schneiderian papillomas are uncommon tumors which may develop within the nasal cavity and comprise three well-defined histological types: sinonasal inverted papilloma (SNIP), exophytic papilloma, and oncocytic papilloma. It is well known the rate of Schneiderian papilloma may also present a malignant degeneration and SNIP represents the most important subgroup in consideration of its frequency and malignant propensity. Although HPV infection is always considered the first event favoring the development of SNIP, however, it is not established as an eventual connection between viral actions and malignant transformation. In fact, different molecular mechanisms are suspected to play a crucial role in this process and, currently, many authors agree that only by improving our knowledge about these mechanisms it will be possible to achieve new and effective targeted therapies. So the aim of this study was firstly to systematically review the literature focusing on different biomarkers that could be implicated in the stages of SNIP malignant degeneration. Secondly, a systematic review with meta-analysis was performed to better define the incidence of sinonasal malignancies originating from Schneiderian papilloma (SNIP, exophytic papilloma, and oncocytic papilloma). Twenty-nine studies comprising a total of 3177 patients were statistically analyzed. Results showed a 9% (95% CI = 7-11) overall rate of malignant transformation from Schneiderian papilloma. In conclusion, this analysis confirmed that the potential malignancy of Schneiderian papilloma should not be underestimated. On the other hand, our review showed the paucity of studies investigating the molecular alterations which may be related with the malignant transformation of SNIP.

Survival outcomes and prognostic factors of squamous cell carcinomas arising from sinonasal inverted papillomas: a retrospective analysis of 120 patients

“…In our study, the incidence of malignancy among patients with IPs was 11.6%; the tumors were synchronous and metachronous in 6.5% and 5.1% of patients, respectively. This finding coincides with those of previous reports . To our knowledge, few studies have evaluated the difference in survival between these patients.…”

Squamous cell carcinoma associated with inverted papilloma: Recurrence and prognostic factors

“…The current literature suggests that the incidence of malignancy among patients with IP varies widely and ranges from 2-27% (6). Although adenocarcinomas, mucoepidermoid carcinomas, nasal undifferentiated carcinomas, small cell carcinomas, and NOS (not specifically specified) were also associated with IP, major histological findings most often confirmed SCC (12). The number of males with SCC associated with IP was larger than the number of women (13).…”

Comprehensive analysis of HPV infection, EGFR exon 20 mutations and LINE1 hypomethylation as risk factors for malignant transformation of sinonasal‐inverted papilloma to squamous cell carcinoma

“…Sinonasal papillomas, which account for approximately 1%–5% of sinonasal tumours, include inverted sinonasal papillomas (ISPs), exophytic sinonasal papillomas (ESPs) and oncocytic sinonasal papillomas (OSPs). While ESPs are only rarely associated with sinonasal squamous cell carcinomas (SCCs), ISPs and OSPs show malignant transformations in 2%–27% of cases and can be associated with synchronous or metachronous SCCs (ISP‐SCC) . Moreover, sinonasal SCCs may also arise as primary malignant tumours without clinical or pathological evidence of an associated papilloma ( de novo SCC), and are characterised by a poor prognosis with a high tendency to recur and metastasize to various distant sites .…”

“…While ESPs are only rarely associated with sinonasal squamous cell carcinomas (SCCs), ISPs and OSPs show malignant transformations in 2%–27% of cases and can be associated with synchronous or metachronous SCCs (ISP‐SCC) . Moreover, sinonasal SCCs may also arise as primary malignant tumours without clinical or pathological evidence of an associated papilloma ( de novo SCC), and are characterised by a poor prognosis with a high tendency to recur and metastasize to various distant sites . Surgical resection is the treatment of choice for such neoplasms and, in selected cases of malignancies, adjuvant treatments can be associated to improve survival rates and reduce the risk of recurrences …”