Inverted Papilloma Research Articles

Background:In benign tumors with potential for malignant transformation, sampling error during pre-operative biopsy can significantly change patient counseling and surgical planning. Sinonasal inverted papilloma (IP) is the most common benign soft tissue tumor of the sinuses, yet it can undergo malignant transformation to squamous cell carcinoma (IP-SCC), for which the planned surgery could be drastically different. Artificial intelligence (AI) could potentially help with this diagnostic challenge.Methods:CT images from 19 institutions were used to train the Google Cloud Vertex AI platform to distinguish between IP and IP-SCC. The model was evaluated on a holdout test dataset of images from patients whose data were not used for training or validation. Performance metrics of area under the curve (AUC), sensitivity, specificity, accuracy, and F1 were used to assess the model.Results:Here we show CT image data from 958 patients and 41099 individual images that were labeled to train and validate the deep learning image classification model. The model demonstrated a 95.8 % sensitivity in correctly identifying IP-SCC cases from IP, while specificity was robust at 99.7 %. Overall, the model achieved an accuracy of 99.1%.Conclusions:A deep automated machine learning model, created from a publicly available artificial intelligence tool, using pre-operative CT imaging alone, identified malignant transformation of inverted papilloma with excellent accuracy.

To describe the radiological anatomy of patients with inverted papilloma (IP) and to evaluate the association between radiological findings and disease recurrence. Retrospective observational study of patients with inverted papilloma who underwent surgery between January 2010 and December 2019. Patients were grouped as primary and recurrent cases, and later at follow-up, depending on disease status, they were subcategorized into 'primary with no recurrence' (PnR), 'primary with recurrence' (PwR), 'recurrent with no further recurrence' (RnR) and 'recurrent with further recurrence' (RwR) groups. Radiological and surgical data were collected and analysed. Among the 117 patients, zygomatic recess was anatomically the most prevalent maxillary recess. Palatonasal was the most commonly affected recess in both primary and recurrent groups. Within the maxillary sinus, the most common sites of recurrence were the lateral wall and floor. Anterior ethmoid (p = 0.047), frontal recess (p = 0.017) and frontal sinus (p = 0.026) showed significantly higher radiological involvement in recurrent cases compared to primary cases. Among the recurrent cases, involvement of posterior ethmoid (p = 0.030), frontal recess (p = 0.017), intraorbital extraconal compartment (p = 0.036) and Krouse stage T4 (p = 0.002) were significantly higher in those with repeated disease recurrence (RwR). In recurrent IP, predictors of repeated recurrence include the site of initial recurrence being the frontal recess/sinus region, involvement of the posterior ethmoid, frontal recess and intraorbital extraconal compartment, and Krouse stage T4 at the time of diagnosis.

Aim:Sinonasal inverted papilloma is a benign yet locally aggressive tumor with potential for recurrence. Surgical resection is the primary treatment, and both endoscopic sinus surgery (ESS) and external approaches are employed depending on tumor location and stage. While clinical outcomes of both techniques have been studied, their economic implications remain underexplored.Materials & methods:A retrospective cost-effectiveness analysis was conducted on 50 patients treated for histologically confirmed inverted papilloma between 1995 and 2018. Patients underwent either ESS or an external approach. Direct medical costs were calculated from hospital records, and effectiveness was measured by 5-year disease-free survival (DFS). Cost-minimization and cost-effectiveness analyses were performed, including subgroup evaluation by Krouse stage.Results:The median total cost was significantly lower for the endoscopic group (€7567.23) compared with the external group (€11,456.40; p = 0.018). Endoscopic surgery resulted in an average savings of approximately €4000 per patient over a 5-year period. In localized disease tumors (Krouse I–II), ESS was both less costly and equally effective. Although the external approach showed a slightly higher DFS (77.2 vs 67.8%), the incremental cost-effectiveness ratio (ICER) was €40,837.13, suggesting limited cost-justification for this benefit.Conclusion:Endoscopic surgery resulted in an average saving of approximately €4000 per patient over a 5-year period. While external approaches showed slightly better disease-free survival, the endoscopic technique proved significantly more cost-effective, offering a better balance between clinical outcomes and resource use.

Cutaneous inverted papilloma is rarely reported in avian species. In this study, an oriental turtle dove presented with subcutaneous masses in the neck, thorax, and leg. Histopathological examination revealed an inverted proliferation of basaloid squamous epithelial cells in a cord-like, lobulated growth pattern containing Civatte/colloid body-like structures, which extend into the abundant stroma with melanosis. Proteomic analysis of formalin-fixed paraffin-embedded tissues identified Keratins 14- and 5-like proteins, with lower levels of Keratins 6A-, and 4-like proteins. Immunohistochemistry confirmed strong reactivity of Keratin 14 in the basal layers of the tumor. This case of cutaneous inverted papilloma was distinguished by unique Civatte/colloid body-like structures and the accumulation of several keratins.

Inverted papilloma (IP) is typically a benign sinonasal tumor with a propensity to recur. The surgical treatment of IP arising from the frontal sinus is complicated by proximity to the orbit and skull base. The objective of this study is to describe the surgical challenges when managing this disease and report treatment outcomes in a multicenter cohort. A retrospective review was performed on frontal sinus IP resected from 1993 to 2023. Demographic and clinicopathologic data, complications, surgical approach, and outcomes were analyzed. Ninety-eight patients (60 males, 38 females) were identified. Mean age was 59 years, with a median follow-up of 44 months. Histopathologic evaluation identified 13 lesions with carcinoma insitu or invasive carcinoma (13.3%). Bilateral involvement was found in 28 patients (28.6%). Overall, 17 patients (17.3%) had recurrent disease with a median recurrence time of 29.2 months. Fourteen patients (14.3%) underwent staged procedures, with a median time to the second procedure of 7.7 months. Twenty-three patients (23.5%) presented with skull base dehiscence on perioperative imaging. Skull base dehiscence had a significant effect on intraoperative cerebrospinal fluid leak (OR 9.1, 95% CI 3.0-27.4 p < 0.001). Frontal sinus IP is commonly attached at the skull base and associated with skull base dehiscence, CSF leak, and often requires operative repair and staged procedures. Complete tumor removal can be challenging and may necessitate a combined open and endoscopic approach. Careful surgical planning and close follow-up in the postoperative period are essential for disease control. Level 4.

Inverted papilloma (IP) is a benign, but locally aggressive sinonasal tumor with a high recurrence rate and potential for malignant transformation into squamous cell carcinoma ex-IP (SCC). Currently, no reliable biomarkers exist to predict recurrence or severity. Matrix metalloproteinase-11 (MMP11) has been implicated in tumor progression and extracellular matrix remodeling in various malignancies and has been shown to be progressively upregulated in IP transformation. This study investigates the relationship between MMP11 expression and IP histologic severity and recurrence risk. Patient demographics and tumor characteristics were collected retrospectively at a tertiary care center from 2008 to 2023. Patient specimens were categorized into normal sinus tissue (NST), IP without dysplasia (IPND), IP with severe dysplasia (IPSD), and SCC. Immunohistochemical staining for MMP11 was performed, and quantitative analysis was conducted using DAB-Quant software. A total of 52 patients were included, with a mean follow-up of 68.8 months. MMP11 expression was significantly elevated in IPSD and SCC compared to IPND (36.7% and 36.5% vs. 21.1%, p = 0.02 and p = 0.01). Patients with recurrence exhibited higher MMP11 expression in their initial resection specimens compared to non-recurrent cases (31.1% vs. 18.1%, p < 0.01). High MMP11 expression (> 50%) was associated with a shorter time to recurrence (17.5 vs. 32 months, p = 0.03), independent of histologic grade. MMP11 expression correlates with increased IP histologic grade, risk of recurrence, and shorter time to recurrence. Elevated MMP11 expression may identify patients at higher risk for recurrence, allowing for targeted surveillance strategies and treatment options.

Is There Utility in Testing Pathologic Specimen for HPV in Sinonasal Inverted Papilloma?

This study aimed to evaluate the clinical characteristics associated with post-operative recurrence in patients with sinonasal inverted papilloma (IP), focusing on the prognostic factors influencing recurrence-free survival (RFS). We retrospectively reviewed clinical records from patients who underwent surgery for IP between January 1, 2007, and August 31, 2023. RFS was analyzed using Kaplan-Meier method and Cox proportional hazard regression analyses to identify the prognostic factors for recurrence. Variables, including age, sex, symptoms, timing of diagnosis, radiological findings, Krouse staging, previous surgery history, surgical method, and tumor origin site, were analyzed. Among the 315 patients with IP, 48 experienced recurrences. The survival analysis revealed 1-, 3-, and 5-year RFS rates of 88.88%, 82.84%, and 69.47%, respectively, and indicated that headache, diagnosis during or following surgery, high Krouse staging, intracranial extension, and frontal sinus origin reduce median RFS or the 5-year RFS rate. Multivariate Cox regression showed that headache, diagnoses made during or after surgery, intracranial extension, and frontal sinus origin significantly increased recurrence risk. If IP is suspected, a biopsy should be performed, and an appropriate surgical approach should be planned. To select the appropriate surgical method, determining the tumor origin site using radiological imaging is crucial, particularly in cases involving the frontal sinus or intracranial extension. Additionally, vigilant monitoring is essential for identifying recurrences early in patients with significant risk factors.

Radiation Therapy in the Treatment of Sinonasal Inverted Papilloma: A Review of Current Evidence

Detecting malignant transformation of sinonasal inverted papilloma (SIP) into squamous cell carcinoma (SIP-SCC) before surgery is a clinical need. We aimed to explore the value of deep learning (DL) that leverages nasal endoscopy and T2-weighted magnetic resonance imaging (T2W-MRI) for automated tumor segmentation and differentiation between SIP and SIP-SCC. We conducted a retrospective analysis of 174 patients diagnosed with SIPs, who were divided into a training cohort (n = 121) and a testing cohort (n = 53). Three DL architectures were utilized to train automated segmentation models for endoscopic and T2W-MRI images. DL scores predicting SIP-SCC were generated using DenseNet121 from both modalities and combined to create a dual-modality DL nomogram. The diagnostic performance of the DL models was assessed alongside two radiologists, evaluated through the area under the receiver operating characteristic curve (AUROC), with comparisons made using the Delong method. In the testing cohort, the FCN_ResNet101 and VNet exhibited superior performance in automated segmentation, achieving mean dice similarity coefficients of 0.95 ± 0.03 for endoscopy and 0.93 ± 0.02 for T2W-MRI, respectively. The dual-modality DL nomogram based on automated segmentation demonstrated the highest predictive performance for SIP-SCC (AUROC 0.865), outperforming the radiology resident (AUROC 0.672, p = 0.071) and the attending radiologist (AUROC 0.707, p = 0.066), with a trend toward significance. Notably, both radiologists improved their diagnostic performance with the assistance of the DL nomogram (AUROCs 0.734 and 0.834). The DL framework integrating endoscopy and T2W-MRI offers a fully automated predictive tool for SIP-SCC. The integration of endoscopy and T2W-MRI within a well-established DL framework enables fully automated prediction of SIP-SSC, potentially improving decision-making for patients with suspicious SIP. Detecting the transformation of SIP into SIP-SCC before surgery is both critical and challenging. Endoscopy and T2W-MRI were integrated using DL for predicting SIP-SCC. The dual-modality DL nomogram outperformed two radiologists. The nomogram may improve decision-making for patients with suspicious SIP.

Inverted papilloma (IP) is a benign neoplasm of the nasal cavity and paranasal sinuses, known for its variable risk of recurrence and potential for developing carcinoma. Emerging evidence has shown high rates of activating EGFR mutation, and a smaller subset is associated with low-risk human papillomavirus (lrHPV). While certain morphologic features, including an inverted growth pattern, are well-established, the presence of condylomatous features, such as large fungating lesions with thick undulating surface epithelium, hyperkeratosis, cytoplasmic clearing, raisinoid nuclei, and binucleation (koilocytic changes) in low-risk HPV-associated IP suggests that these tumors may be a distinct subtype of sinonasal papilloma (SP) with features similar to low-risk HPV-associated anogenital condylomas. This study presents a series of SP with condylomatous morphology and explores the association with lrHPV, the clinicopathologic features, and the rates of carcinoma development. In total, 17 cases of SP exhibiting condylomatous morphology were retrospectively identified. We performed lrHPV and high-risk HPV (hrHPV) RNA in situ hybridization and p16 immunohistochemistry and gathered detailed clinical and pathologic data along with treatment, disease follow-up, and outcomes. These condylomatous papillomas almost all developed in active smokers, were large, were primarily located in the nasal cavity (47%), and showed frequent transformation to invasive squamous cell carcinoma (29%). This malignant transformation rate is much higher than what has been reported for inverted, exophytic, and oncocytic papillomas. The tumors were almost uniformly associated with transcriptionally-active lrHPV (94%) and were consistently negative for p16 and hrHPV. This study shows that a subgroup of IPs with condylomatous morphology have a predilection for the nasal cavity, strong association with lrHPV, and high rates of carcinoma. These findings support the concept that these tumors are a distinct (fourth) type of SP with a higher risk of malignant transformation.

Abstract BACKGROUND. Inverted papilloma is a clinically significant benign tumor of the sinonasal tract due to its locally aggressive behaviour, potential for malignant transformation, and frequent involvement of anatomically complex regions. Its presentation often mimics other inflammatory or neoplastic conditions, making early diagnosis and tailored surgical management essential for preventing functional and structural complications. CASE REPORT. This case presents a rare and extensive bilateral sinonasal inverted papilloma with externalization through the nasal vestibule, occurring in a patient with a history of prior sinonasal surgery and significant anatomical distortion. The tumor’s aggressive local expansion, associated bone remodelling, and metaplastic ossification posed considerable diagnostic and surgical challenges, successfully managed through advanced endoscopic techniques.

High- and low-risk human papillomavirus prevalence in sinonasal inverted papilloma, a retrospective study.

Objectives: Sinonasal inverted papilloma (SNIP) is a rare benign tumor that has potential for malignant transformation, usually into squamous cell carcinoma (SCC). The pre-operative differentiation between SNIP and SNIP-SCC is essential in determining the therapeutic strategy, but it is a challenge, as biopsies may fail to recognize the malignant part of the tumor. Further, a SNIP can also be locally aggressive and thus mimic a malignant tumor. This retrospective study compares the pre-operative differences in computed tomography (CT) and histologic findings between patients with a benign SNIP and those with a SNIP-SCC. Methods: Eight patients with SNIP-SCC were selected from the hospital registries of the Department of Otorhinolaryngology, Helsinki University Hospital (Helsinki, Finland). For each case a comparable SNIP case without malignancy was selected. Five histopathologic samples of both the SNIP and SNIP-SCC tumors were retrieved. CT images and the histopathologic samples were re-evaluated by two observers. Results: The nasal cavity and ethmoid and maxillary sinuses were the most common sites for both tumor types. The SNIP tumors were mostly unilateral, and the SNIP-SCC tumors were both unilateral and bilateral. Only SNIP-SCC tumors demonstrated bone defects and orbital or intracranial invasion. Dysplastic findings such as dyskeratosis, nuclear atypia, and maturation disturbances were seen only in the SNIP-SCC tumors. Conclusions: Bony destruction and invasion of adjacent structures in pre-operative CT images seem to be pathognomonic signs of SNIP-SCC based on this series. To differentiate between SNIP and SNIP-SCC tumors all available pre-operative investigations are warranted.

Background The supraorbital ethmoid cell (SOEC) is a pneumatized extension of the anterior ethmoid sinus that may harbor residual disease after surgery, making complete surgical clearance challenging. Objectives To evaluate the surgical and prognostic relevance of SOEC involvement in frontal sinus (FS) inverted papilloma (IP), particularly its association with revision surgery and recurrence. Methods Data from 147 IP patients, including 32 with FS involvement, were retrospectively reviewed to identify true FS origin, FS extension, and SOEC involvement based on operative records and CT scans. Results True FS mucosal origin was identified in 2 patients (6.25%), while SOEC involvement was observed in 8 (25%), all of whom had prior surgeries. Among the 19 patients with previous surgeries, 8 (42.1%) had SOEC involvement, compared to none of the 13 without (p = 0.007). Patients with SOEC involvement underwent significantly more surgeries (median: 2 vs. 1; p = 0.041). True FS origin rates did not differ significantly (p = 0.345). After a median follow-up of 40.5 months, recurrence was not observed in patients with SOEC involvement (0/8), compared to 6 recurrences among those without (6/24; p = 0.149). Conclusions and Significance SOEC involvement was more common in revision cases and linked to multiple prior surgeries, highlighting its importance in surgical planning and follow-up.

Objective This study aimed to evaluate the epidemiological characteristics, clinical presentation, diagnostic methods, and surgical outcomes of sinonasal inverted papillomas (IPs) and to compare these findings with those in the existing literature. Methods A retrospective review was performed involving 25 patients diagnosed with IPs and treated by a single surgeon at Antalya Education and Research Hospital, a tertiary care center, between January 2015 and December 2021. Data regarding demographics, presenting symptoms, imaging findings, and postoperative outcomes were analyzed. Results Of the 25 patients, 23 were male and two were female (male-to-female ratio: 11.5:1). The mean age of the cohort was 54.7 years. The most common symptom was nasal obstruction. The tumor most frequently originated from the medial wall of the maxilla (40%). Pure endoscopic resection was performed in 20 patients, while four (16%) required revision surgery. Malignant transformation occurred in two patients - one with microinvasive squamous cell carcinoma and another with carcinoma in situ. Conclusions Although histologically benign, inverted papillomas demonstrate locally aggressive behavior and carry a risk of malignant transformation. Endoscopic surgical techniques offer favorable outcomes with low recurrence rates, but long-term surveillance remains critical.

Role of SCCA and CYFRA 21-1 in the differential diagnosis of sinonasal benign and malignant diseases.

Abstract Inverted papilloma is a benign tumor that can become malignant. It most commonly develops on the lateral rhinosinusal wall and has a maximum incidence in the ethmoid cells. In most cases, it occurs unilaterally, the main symptom being nasal obstruction. Treatment can generally be performed through endoscopic sinus surgery, involving total resection due to its malignancy potential and risk of recurrence. Given the increased interest in this pathology, we present the most important aspects of sinonasal inverted papilloma, from etiology to therapeutic management, exemplifying with a case from our own experience.

To develop a novel MRI-based deep learning (DL) diagnostic model, utilizing multicenter large-sample data, for the preoperative differentiation of sinonasal inverted papilloma (SIP) from SIP-transformed squamous cell carcinoma (SIP-SCC). This study included 568 patients from four centers with confirmed SIP (n = 421) and SIP-SCC (n = 147). Deep learning models were built using T1WI, T2WI, and CE-T1WI. A combined model was constructed by integrating these features through an attention mechanism. The diagnostic performance of radiologists, both with and without the model's assistance, was compared. Model performance was evaluated through receiver operating characteristic (ROC) analysis, calibration curves, and decision curve analysis (DCA). The combined model demonstrated superior performance in differentiating SIP from SIP-SCC, achieving AUCs of 0.954, 0.897, and 0.859 in the training, internal validation, and external validation cohorts, respectively. It showed optimal accuracy, stability, and clinical benefit, as confirmed by Brier scores and calibration curves. The diagnostic performance of radiologists, especially for less experienced ones, was significantly improved with model assistance. The MRI-based deep learning model enhances the capability to predict malignant transformation of sinonasal inverted papilloma before surgery. By facilitating earlier diagnosis and promoting timely pathological examination or surgical intervention, this approach holds the potential to enhance patient prognosis. Questions Sinonasal inverted papilloma (SIP) is prone to malignant transformation locally, leading to poor prognosis; current diagnostic methods are invasive and inaccurate, necessitating effective preoperative differentiation. Findings The MRI-based deep learning model accurately diagnoses malignant transformations of SIP, enabling junior radiologists to achieve greater clinical benefits with the assistance of the model. Clinical relevance A novel MRI-based deep learning model enhances the capability of preoperative diagnosis of malignant transformation in sinonasal inverted papilloma, providing a non-invasive tool for personalized treatment planning.

Background: Frontal sinus inverted papilloma (IP) is a particularly rare form of IP and its management is challenging, with a high rate of recurrence. Objectives: Our aim was to evaluate the recurrence rate of frontal sinus IP after surgery and compare this rate according to the surgical modality (purely endoscopic sinus surgery vs. a combined/open approach). Design: A systematic review without meta-analysis conducted by a working group of the Young Otolaryngologists of the International Federation of Otorhinolaryngological Societies (yo-IFOS). Data Sources and Methods: A systematic analysis of the literature was performed and reported following the criteria laid down in the SWiM guidelines. The review was registered on Prospero, a dedicated software was used for screening (Covidence), and R (v.4.2.2) was used for statistical analysis. Eligible articles were studies reporting at least five cases of frontal sinus IP surgically treated. Results: A total of 2925 studies were identified based on the MeSH equation, and 39 studies were included (n = 642 patients). Among the studies included, the recurrence rate was 18.4% (118/642) with a mean time to recurrence of 25.6 (±11.7) months. The difference between surgical modalities was not statistically significant in terms of recurrence rate (14.7% vs. 16.5%; p = 0.675). Conclusions: The recurrence rate of frontal sinus IP is not different between surgical modalities. However, it does not reduce the need for a tailored therapeutic strategy, as other factors also need to be considered (time to recurrence, complications, quality of life) when choosing the most appropriate approach.