Survival Outcomes of De Novo vs Inverted Papilloma-Associated Sinonasal Squamous Cell Carcinoma: A Systematic Review and Meta-analysis.

Importance: Overall, the prognosis of sinonasal squamous cell carcinoma (SCC) is poor. This malignancy can arise de novo or from inverted papillomas, but it is unclear whether survival differences between the 2 pathologies exist. Objective: To assess for survival differences between patients with sinonasal de novo SCC (dnSCC) and those with inverted papilloma-associated SCC (IPSCC). Data Sources: A search of Ovid MEDLINE, Embase, Scopus, and the Cochrane Library from inception to January 23, 2020, with cross-referencing of retrieved studies, was performed. Additional data were requested from authors. Study Selection: Inclusion and exclusion criteria were designed to capture studies with survival outcomes of adults with sinonasal SCC who underwent regular treatment. Clinical trials, cohort studies, case-control studies, and case series with more than 10 adults aged 18 years or older with sinonasal SCC were included. Exclusion criteria were studies on non-SCC sinonasal neoplasms, studies without histopathologic diagnoses, non-English language articles, nonhuman animal studies, and abstract-only articles. Two blinded investigators (J.J.L., A.M.P., T.W.E., or N.S.W.) screened each abstract and full text, and a third investigator (J.J.L. or P.P.) adjudicated discrepancies. Of 729 unique citations, 26 studies of 1194 total patients were included. Data Extraction and Synthesis: Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed. The Methodological Index for Nonrandomized Studies (MINORS) criteria were used to assess study quality. Two blinded investigators (J.J.L., A.M.P., T.W.E., or N.S.W.) independently extracted data from each study. Data were pooled using a random-effects model. Main Outcomes and Measures: The primary outcome was overall survival, and secondary outcomes were disease-free and disease-specific survival. Before data collection, it was hypothesized that the dnSCC cohort would have worse survival outcomes than the IPSCC cohort. Results: One study of patients with dnSCC, 12 studies of patients with IPSCC, and 5 studies with both cohorts were included in the meta-analysis of overall survival. The pooled 5-year overall survival rate for 255 patients with dnSCC was 56% (95% CI, 41%-71%; I2 = 83.8%) and for 475 patients with IPSCC was 65% (95% CI, 56%-73%; I2 = 75.7%). Five comparative studies of both cohorts totaling 240 patients with dnSCC and 155 patients with IPSCC were included in another meta-analysis. The pooled overall survival hazard ratio was 1.87 (95% CI, 1.24-2.84; I2 = 0%). Conclusions and Relevance: This systematic review and meta-analysis found that patients with dnSCC had almost a 2-fold increased risk of mortality compared with those with IPSCC. Large, multicenter studies are necessary to validate these findings before considering treatment alterations such as de-escalation based on histopathology.

Comparison of outcomes between patients with de-novo sinonasal squamous cell carcinoma vs malignant transformations from inverted papillomas.

BACKGROUND: The survival difference between de-novo sinonasal squamous cell carcinoma (DN-SNSCC) and SCC arising from inverted papillomas (IPs) is unclear. The purpose of this study was to compare the outcomes between DN-SNSCC and IP-transformed SNSCC (IP-SNSCC) patients. METHODS: In this retrospective review, we compared IP-SNSCC and DN-SNSCC cases from the Eye and ENT Hospital of Fudan University from 2010 to 2017. A total of 162 patients (39 IP-SNSCC and 123 DN-SNSCC) were included in our study. Demographics, tumor characteristics, treatment, and clinical outcomes were analyzed. RESULTS: The median follow-up time in all cohorts was 56 (range, 5-109) months. There was no difference in age, sex, smoking history, alcohol consumption, tumor primary site, or disease stage between the IP-SNSCC and DN-SNSCC patients. We also did not find significant differences in overall survival and disease-free survival between IP-SNSCC and DN-SNSCC patients (p = 0.584 and p = 0.238, respectively). The 5-year local failure rate was 52.8% for IP-SNSCC patients, which was significantly higher than for those with DN-SNSCC (31.9%; p = 0.013). The 5-year nodal failure rate was 19.0% for IP-SNSCC patients and 8.5% for DN-SNSCC patients (p = 0.211). The 5-year distant metastasis rate was 8.0% for IP-SNSCC patients and 16.1% for DN-SNSCC patients (p = 0.318). CONCLUSION: IP-SNSCC and DN-SNSCC patients have similar survival outcomes. IP-SNSCC seems to have exhibited a higher local failure rate in our study. We believe that IP-SNSCC is a highly aggressive disease that requires radical treatment. Prophylactic neck treatment should not be omitted in a subset of IP-SNSCC patients.

Clinical Implications of Carcinoma In Situ in Sinonasal Inverted Papilloma.

OBJECTIVE: Sinonasal inverted papilloma (IP) is a typically benign sinonasal tumor with a tendency to recur and the potential for malignant transformation. Varying degrees of dysplasia may be present, of which carcinoma in situ (CIS) is most advanced. We hereby describe the biological and clinical behavior of IP with CIS (IPwCIS). STUDY DESIGN: Retrospective cohort. SETTING: Tertiary academic referral center. SUBJECTS AND METHODS: Patients who underwent surgical resection for IP between 2002 and 2017. Pertinent clinical data were obtained, and all IPwCIS cases were histologically confirmed. RESULTS: In total, 37 of 215 cases (17.2%) were identified with IPwCIS. Mean age was 57 years and 86.5% of patients were male. Median follow-up was 82 months, and the recurrence rate was 27%. The maxillary sinus was the most common primary site (37.8%) and 14 tumors (37.8%) demonstrated multifocal attachment, which was associated with recurrence (odds ratio [OR], 9.7; 95% confidence interval [CI], 1.4-112.8; P = .028). IPwCIS was also associated with multiple recurrences (OR, 2.71; 95% CI, 1.246-5.814; P = .021). Most patients were treated with surgery alone (89.1%) and 4 patients received adjuvant radiotherapy (8.1%). Only 1 patient (2.7%) demonstrated malignant transformation after definitive surgery. CONCLUSIONS: IPwCIS represents the most severe degree of dysplasia prior to malignant transformation and is associated with higher recurrence rate and multifocal involvement but low rate of conversion to invasive carcinoma. The need for adjuvant therapy remains controversial, and further research into the etiology of the disease is warranted.

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

BACKGROUND: This study aimed to analyze the prognostic factors and survival outcomes of squamous cell carcinoma (SCC) originating from sinonasal inverted papillomas (IPs), based on data from a single institution. METHODS: The data from 120 patients treated at the affiliated Beijing Tongren Hospital, Capital Medical University, for SCC originating from sinonasal IPs between 2005 and 2018 were retrospectively reviewed. Data related to demographic features, tumor characteristics, treatment modality, and clinical outcomes were collected. Survival data were investigated using the Kaplan-Meier method, Cox regression analysis, and the nomogram model predictive of survival probabilities. RESULTS: Among 1034 patients with sinonasal IPs, 120 patients (11.6%) with malignancy were identified. The overall survival (OS) and disease-free survival (DFS) rates at 5 years were 56.0% and 42.3%, respectively. Multivariate analysis showed that synchronous tumors and tumor stage were independent predictive factors for the risk of mortality (hazard ratio [HR], 1.954; 95% confidence interval [CI], 1.022-3.737, p = 0.043; HR, 1.737, 95% CI, 1.095-2.770, p = 0.020, respectively). The surgical margin was another important independent predictor, with patients with negative margins demonstrating a more than 2-fold improved survival compared to those with positive margins (HR, 2.095; 95% CI, 1.031-4.243; p = 0.041). CONCLUSION: The main factors affecting the prognosis and outcomes were synchronous tumors, advanced tumor stage, and positive surgical margins. These findings highlight the importance of tumor biology and early detection in patient outcomes. In addition, risk factors should be taken into consideration during treatment planning and subsequent tumor surveillance.

Outcomes of sinonasal squamous cell carcinoma with and without association of inverted papilloma: A multi-institutional analysis.

INTRODUCTION: Sinonasal squamous cell carcinoma (SCC) accounts for <1% of all malignancies but represents 70% of sinonasal cancer. Up to 10% of SCCs are associated with inverted papilloma (IPSCC). Studies that compare patients, treatment, and outcomes of SCC and IPSCC are absent in the literature. METHODS: A retrospective review of patients with SCC and those with IPSCC at Cleveland Clinic and Indiana University from 1995 to 2015. The records were analyzed for demographics, tumor characteristics, treatment, and outcomes. RESULTS: The study comprised 117 patients with SCC, of whom, 29 had IPSCC. The mean age at diagnosis was similar: 63 and 64 years for patients with SCC and patients with IPSCC, respectively; with female patients representing 36% and 34%, respectively (p > 0.99).Smokers represented 64% of the patients with SCC and 55% of patients with IPSCC (p = 0.3); excessive alcohol intake was noted in 16% of the patients with SCC and 21% of the patients with IPSCC (p = 0.56).The maxillary sinus was most commonly involved, followed by the nasal cavity (51% versus 35% SCC, 45% versus 38% IPSCC). Frontal ethmoid and sphenoid sinuses contained primary tumors only in patients with SCC. Upfront treatment was surgery in 84% of patients with SCC and 97% of patients with IPSCC (p = 0.18); 68 and 55% received radiation, respectively, and 25 and 21% received chemotherapy, respectively.Overall survival averaged 5.5 and 3.4 years for patients with SCC and patients with IPSCC, respectively (p = 0.12); disease-free survival was 4.8 and 2.9 years, respectively (p = 0.18). Nodal metastasis was more likely in patients with SCC (18 versus 0%; p = 0.02). When divided into high- and low-stage disease: more common nodal metastases were demonstrated in high-stage SCC than in low-stage disease (p = 0.03). Overall survival was decreased between high- and low-grade disease but not when subdivided between SCC and IPSCC. CONCLUSION: Although SCC with and without IP association are considered different diseases, their demographics and outcomes seem similar. Nodal metastasis was noted to be higher in the SCC cohort, which may indicate different tumor biology. Further study is warranted.

Atypical presentations of sinonasal inverted papilloma: Surgical management and influence on the recurrence rate.

BACKGROUND: Sinonasal inverted papilloma (SNIP), classically, is a unilateral benign tumor of the nasal lateral wall. Numerous variations have been observed, depending on location, bilateral presentation, or association with nasal polyposis. OBJECTIVE: The aim of this work was to describe atypical presentations of SNIPs with their management specificities and to assess their influence on the recurrence rate in a large case series. METHODS: A retrospective single center study of 110 patients treated for SNIP. Atypical inverted papillomas were identified according to the following criteria: (1) unusual location (frontal, posterior, anterior), (2) bilateral involvement, and (3) association with nasal polyposis. Surgical management was detailed, and the influence of each atypical group on recurrence was assessed by using Kaplan-Meier survival curves and the log-rank test. RESULTS: Distribution of atypical presentations was as follows: frontal sinus localization (10.9%); posterior localization, including sphenoid sinus (9%); nasal anterior localization (3.6%); bilateral involvement (3.6%); and nasal polyposis association (10%). The surgical approach was endoscopic (74.5%), external (5.5%), or combined endoscopic and external (20%). Except for nasal anterior localization, all the groups were associated with a higher recurrence rate, without reaching statistical significance. CONCLUSION: Recurrence rates for these atypical presentations arise from their specific surgical challenges. The choice of the surgical technique is guided by tumor location and extension, and by the surgeon's experience; the main objective is a complete resection. The endoscopic endonasal approach is the most frequent procedure.

Survival Outcome of Squamous Cell Carcinoma Arising from Sinonasal Inverted Papilloma.

BACKGROUND: Sinonasal inverted papilloma (IP) is a rare benign tumor of the nasal cavities and paranasal sinuses. It is destructive or bone-remodeling, tends to recur after surgical resection, and has a significant malignant potential. The present study aimed to perform a retrospective analysis of patients with squamous cell carcinoma (SCC) arising from IP, including characteristics, survival outcome, and predictors of associated malignancy. METHODS: The medical records of 213 patients diagnosed with IP from January 1970 to January 2014 were retrospectively reviewed. Eighty-seven patients were diagnosed with SCC/IP; their clinical characteristics, treatments, and survival outcomes were analyzed. RESULTS: Of the 87 patients with SCC/IP, the 5- and 10-year overall survival outcomes were 39.6% and 31.8%, respectively. Twenty-nine of these patients received surgery and 58 received combined surgery and radiation. Of the patients with stages III-IV, the 5-year survival rate was 30.7% for those treated with surgery only and 39.9% for those given the combination treatment (P = 0.849). Factors associated with significantly poor prognosis were advanced-stage, metachronous tumors, or with cranial base and orbit invasion. Age, synchronous or metachronous tumors, and pathological stage were independent risk factors for mortality, shown by multivariate analysis. CONCLUSION: Patients with SCC/IP had low overall survival outcomes. Advanced age, stage, and metachronous tumors are the main factors affecting prognosis. Treatment planning should consider high-risk factors to improve survival outcome.

Management of the orbit during endoscopic sinonasal tumor surgery.

BACKGROUND: The primary aims of the study were to report preoperative imaging characteristics and intraoperative management of the orbit during endoscopic resection of benign and malignant sinonasal tumors. METHODS: This study was a case series at an academic tertiary care center. Retrospective chart review and prospective imaging assessment was performed on 159 cases treated between July 2009 and December 2012. RESULTS: A total of 41 patients met predetermined inclusion criteria. Squamous cell carcinoma (17.1%) and inverted papilloma (31.7%) were the most common malignant and benign histology, respectively. Preoperative computed tomography (CT) scanning most commonly demonstrated erosion of the lamina papyracea (80.5%), whereas magnetic resonance imaging (MRI) most commonly illustrated loss of fat plane between tumor and extraocular muscle (53.1%). Endoscopic procedures to address the orbital interface included lamina papyracea resection (85.4%), dacryocystorhinostomy (26.8%), periorbita resection (26.8%), optic nerve decompression (7.3%), and orbital exenteration (2.4%). Oculoplastic surgery involvement was required in 31.7% of cases. Orbital complications included epiphora in 3 (7.3%) and diplopia in 2 (5.1%) patients. Postoperatively, no recurrences were noted in the benign group, whereas 6 (28.6%) recurrences were noted in 21 patients in the malignant group treated with intent to cure. Two patients died of disease due to distant metastases from mucosal melanoma and squamous cell carcinoma. CONCLUSION: This represents the largest series to date on endoscopic management of the orbit in benign and malignant sinonasal tumors. A majority of these cases can be managed by a purely endoscopic approach with low complication and recurrence rates, although a subset still require adjunct open approaches for successful tumor extirpation.

Factors affecting recurrence of sinonasal inverted papilloma.

The aim is to study clinical characteristics and recurrence rates for sinonasal inverted papilloma (NIP), to evaluate relevant factors for its recurrence, and to compare the curative rates of different surgical approaches. The Krouse classification for the 156 follow-up cases of the patients with NIP was as following: 26 cases in T1, 33 cases in T2, 94 cases in T3, and 3 cases in T4. A total number of 99 cases of endoscopic sinus surgery were included, of which 26 cases of lateral rhinotomy approach were combined with Caldwell Luc approach, and 31 cases of nasal endoscopy combined with traditional surgery, with average postoperative follow-up of 3-11 years. Of the 156 studied patients with NIP, male:female = 1.69:1, age varied from 18 to 77 years, with average of 56 years, 19 cases showed postoperative recurrence, of which 8 cases developed to be squamous cell carcinoma. Among these 8 cases, 3 patients showed no recurrence after treatment in 5 years, and the other 5 patients died in 3-2 years period. Tumor recurrence rates for different surgical approach are: 9.09 % for endoscopic surgical group, 23.08 % for traditional surgical group, and 12.12 % for combined surgical group; tumor malignancy rates for different surgical approach are: 2.02 % for endoscopic surgical group, 11.54 % traditional surgical group, and 9.09 % for combined group, and Chi-square test showed that the differences in recurrence and malignancy rates for NIP patients with different surgical treatments were not statistically significant (P > 0.05). Recurrence rates for different stages are: T1 at 3.85 %, T2 at 12.12 %, T3 at 14.89 %, and T4 at 0.00 %, and the differences in the recurrence rates for different stages were not statistically significant (P > 0.05) by Chi-square test. There are clear clinical features for NIP, and the recurrence is related to the thoroughness of the first time surgical removal of lesions and is less relevant with Krouse classification stage and surgical approaches.

Clinical and histologic features of inverted papilloma-associated malignancy.

The objectives of the study were to analyze the clinical features of inverted papillomas (IP) associated with malignancy and to evaluate the correlation of tumor stage, survival and histolologic features. We conducted a retrospective review of 18 IP associated with malignancy patients. In addition, we compared histopathologic characteristics (tumor differentiation and malignant cell proportion) with clinical outcomes. Eleven of the tumors were present on the nasal cavity and 7 on the maxillary sinus. The rates of synchronous and metachronous malignancy were 10.1 and 1.1%, respectively. The disease-free survival rate was 83.3%. The tumors were staged as T1 (5/18), T2 (2/18), T3 (8/18), and T4 (3/18). According to the percentage of the malignant cell in the entire tumor tissue, 4 patients (22%) were in grade I, 4 patients (22%) were in grade II, 3 patients (17%) were in grade III, and 7 patients (39%) were in grade IV. There was no relationship between recurrence- and/or disease-free survival and histologic findings including tumor differentiation and malignant proportion. IP-associated malignancy tends to occur synchronously and have more favorable prognosis compared to other sinonasal malignancy. Furthermore, the proportion of malignant cell to IP and tumor stage seems not to affect the clinical outcome of IP-associated malignancy.

Inverted papilloma with associated carcinoma of the nasal cavity and paranasal sinuses: treatment outcomes.

CONCLUSIONS: Degenerated inverted papilloma is a rare, aggressive, and lethal disease. To avoid missing the target, it is absolutely necessary to consider the microscopic extension even in cases of complete exeresis and to irradiate the whole of the adjacent sinuses. A dose increase may lead to better locoregional control. OBJECTIVE: To evaluate overall survival and progression-free survival of external radiotherapy in the management of nasal cavity and paranasal sinus inverted papilloma with associated carcinoma. METHODS: Clinical data from 11 patients treated by surgery followed by external radiotherapy (three-dimensional conformational radiotherapy until 2007 then intensity-modulated radiation therapy) for degenerated inverted papilloma in the Léon Bérard Cancer Centre between 1985 and 2009 were retrospectively analyzed. RESULTS: Five patients (45%) had a local recurrence and died from their recurrence. Three had a premature recurrence, just before or during radiotherapy. We could not determine the prognostic factors for overall survival and progression-free survival.

Survival outcomes of squamous cell carcinoma arising from sinonasal inverted papilloma: report of 6 cases with systematic review and pooled analysis.

BACKGROUND: Inverted papilloma (IP) is an uncommon sinonasal tumor. Squamous cell carcinoma (SCC) is associated with IP in about 7% of cases. To date, there has been no pooled analysis to formulate a survival outcome associated with this rare condition. PATIENTS AND METHODS: We retrospectively reviewed the medical records of patients with IP and SCC treated at our institution during 1999-2007. Including our series, a systematic review of literature on Medline database and pooled analysis were performed to establish a survival estimate. RESULTS: Six patients were identified. Squamous cell carcinoma was metachronous to the initial diagnosis of IP in 1 case and synchronous in 5 cases. Of 5 patients who had completed therapy at the time of this report, only 1 remained disease-free at 74 months. The median overall survival in our series was 33 months. Three patients developed distant metastases in brain, lung, bone, and liver. Literature review and pooled survival analysis consisting of 76 cases indicated a median overall survival of 126 months with 3- and 5-year survival rates of 63% and 61%, respectively. CONCLUSION: Although the survival outcome of SCC arising from IP seems comparable with sinonasal SCCs, some patients with this disease do have a highly aggressive disease, including hematogenous distant metastasis. Overall, about 40% of patients will die of the disease within the first 3 years.

Expression of p53 in inverted papilloma and malignancy associated with inverted papilloma.

OBJECTIVE: To determine the association of p53 protein in malignant cases of inverted papilloma compared with cases of benign inverted papilloma of the sinonasal tract. DESIGN: Case-control study of archived pathologic material. SETTING: Tertiary care hospital. METHODS: Archived pathologic material of cases of malignancy associated with inverted papilloma and controls of benign inverted papilloma were obtained from Mount Sinai Hospital. These were subjected to immunohistochemistry for p53. Clinical correlation was obtained by retrospective chart review. MAIN OUTCOME MEASURES: Staining of pathologic specimens for p53 and survival or recurrence. RESULTS: Four of the five cases of malignancy associated with inverted papilloma demonstrated overexpression of p53. None of the benign cases of inverted papilloma demonstrated overexpression. Only two of the five patients with malignancy associated with inverted papilloma were alive at 2 years. CONCLUSIONS: Overexpression of p53 may serve as a marker for malignant transformation of inverted papilloma.

Squamous cell carcinoma arising in inverted papilloma.

A retrospective review of all cases of inverted papilloma at the University of Michigan from 1975 to 1992 revealed 51 cases of inverted papilloma. Of these, 14 (27%) had an associated squamous cell carcinoma (SCC). Eight (16%) were metachronous and 6 (11%) were synchronous. At a mean follow-up of 53 months, the disease-free survival of patients with carcinoma limited to the nasal cavity and paranasal sinuses was 57% (4/7) compared to 14% (1/7) of those patients presenting with disease extending beyond the nasal cavity and paranasal sinuses. The data also support the lateral rhinotomy approach with medial maxillectomy and ethmoidectomy as a minimum procedure followed by postoperative radiation therapy. The mean interval between the diagnosis of inverted papilloma and development of SCC was 63 months (range, 6 months to 13 years). Therefore, long-term follow-up with clinical examination and computed tomography (CT) scan is indicated for all patients with inverted papilloma.