[Inverted papilloma of the nose and paranasal sinuses : Diagnosis, treatment, and malignant transformation]. / Invertiertes Papillom der Nase und Nasennebenhöhlen : Diagnostik, Therapie und maligne Transformation.

Inverted papilloma (IP) are benign tumors that show a locally aggressive behavior, a high rate of recurrence, and a potential for malignant transformation. Specific radiological signs such as hyperostosis at the origin of the IP and convoluted cerebriform patterns, as well as the typical endoscopic aspect, can lead to diagnosis and enable preoperative planning of surgical access and the extent of surgery. Endonasal endoscopic techniques are considered the gold standard and the introduction of extended surgical techniques such as the prelacrimal approach, frontal drillout, or orbital transposition facilitate complete subperiosteal resection with preservation of important physiological structures. There is a risk of synchronous and metachronous squamous cell carcinomas (IP-SCC). Research focuses on radiological criteria to differentiate benign IP from IP-SCC, genetic and epigenetic factors in the process of malignant transformation, and estimation of the risk of IP progressing to IP-SCC.

A Large Pleomorphic Adenoma in Nasal Cavity Misdiagnosed as Inverted Papilloma.

Pleomorphic adenoma (PA) is a benign tumor characterized by slow-growing mixed tumors in the craniofacial area. It is relatively common in salivary glands; however, PA of the nasal cavity, which arises in the minor salivary glands, is rare. We present the case of a large PA in the nasal cavity of an adult immunocompetent woman with nasal obstruction and intermittent epistaxis. Based on preoperative radiologic examinations, she was misdiagnosed with an inverted papilloma. Endoscopic resection was performed under general anesthesia. Pathologically, the patient was confirmed to have PA, which has great cellularity and few stromal components. No complications or recurrences during the 1-year follow-up period were observed.

CD163 Immunohistochemical "Circle Sign" Staining Pattern Differentiates Sinonasal Papillomas From Morphologically Similar Non-neoplastic Lesions.

Sinonasal papillomas are a diverse group of benign epithelial neoplasms of the sinonasal tract. Inverted papilloma, in particular, must be distinguished from other lesions with no malignant potential. The aim of this study was to distinguish sinonasal papillomas from morphologically similar lesions using CD163 immunostaining. Cases from a 19-year period were identified. These included 49 inverted, 10 exophytic, and 12 oncocytic papillomas, 21 chronic sinusitides with squamous metaplasia, 27 inflammatory polyps, 5 verrucae vulgares, 5 respiratory epithelial adenomatoid hamartomas, and 6 DEK::AFF2 carcinomas of the sinonasal tract. A subset of biopsy cases (8 inverted papillomas, 5 inflammatory polyps) was separately analyzed. CD163 immunohistochemistry (IHC) was performed. A unique "circle" staining pattern was identified in the surface epithelium. After locating a hotspot, circles were quantified in 10 consecutive high-power fields. Circles were present in 66/71 (93%) cases of sinonasal papilloma, with a mean of 35 circles/10 HPF (range: 0 to 160/10 HPF) and a median of 19 circles/10 HPF. Circles were present in 20/58 (34%) non-neoplastic cases, with a mean of 2 circles/10 HPF (range: 0 to 27/10 HPF) and a median of 0. Considering all resection and biopsy cases, performance for distinguishing papillomas from non-neoplastic lesions was best at a cutoff of 10 circles/10 HPF (2-tailed P <0.0001) with sensitivity, specificity, positive predictive value, and negative predictive value of 66.2%, 93.1%, 92.1%, and 69.2%, respectively. The results were similar in the biopsy subset. One other neoplastic entity, the DEK::AFF2 carcinomas, also showed prominent CD163 circle staining. In summary, sinonasal papillomas demonstrate extensive CD163 "circle" staining in the epithelium compared with the non-neoplastic lesions studied. As such, the "circle sign" on CD163 IHC may be helpful in distinguishing between diagnoses, particularly on small biopsies or equivocal specimens.

Unique volatile metabolite signature of sinonasal inverted papilloma detectable in plasma and nasal secretions.

BACKGROUND: Sinonasal inverted papilloma (SNIP) is a benign neoplasm with aggressive features, including a high recurrence rate and a propensity for malignant transformation. Accurate diagnosis with complete resection and the need for close long-term surveillance is widely accepted as standard management. In this study, we investigate whether SNIP produces a unique volatile metabolite signature, which may ultimately lead to a novel approach to diagnose and monitor SNIP. METHODS: Whole blood and nasal secretions from patients with SNIP and healthy age-, sex-, and smoking-status-matched controls, were collected. There were 56 blood samples and 42 nasal secretion samples collected. The volatile metabolite signature of SNIP plasma and nasal secretion samples were compared with those of healthy controls using chromatography. RESULTS: Seventy-two volatiles were identified in plasma samples. Multivariate analysis of variance results, even when controlled for smoking status, indicated toluene as a significant univariate result with lower levels of toluene identified in SNIP plasma samples than healthy control plasma samples. A linear discriminant analysis (LDA) model for plasma volatiles correctly classified 23 of 24 SNIP patients and 26 of 27 control patients, with a cross-validation error rate of 6.02%. Sixty-nine volatiles were identified in nasal samples. For nasal secretion samples, no single univariate response was significant. The LDA model correctly classified 21 of 21 SNIP patients and 11 of 12 control patients, with a cross-validation error rate of 6.55%. CONCLUSION: This study suggests that SNIP produces a unique, detectable volatile metabolite signature. With further investigation, this can have dramatic clinical implications for diagnosis and monitoring. Although most volatile metabolite studies have investigated solid-organ malignancy, this novel study addresses a benign sinonasal neoplasm by using nasal secretions and plasma as an analysis medium, representing the first such study.

Inverted urothelial papilloma in a cat.

A 12-year-old neutered female cat was referred with clinical signs referable to lower urinary tract disease. Clinical examination revealed a tense, painful urinary bladder, and proximal urethral thickening. Endoscopic studies showed a pedunculated mass with polypoid projections. Multiple full-thickness mucosal biopsies were obtained, and the mass was almost completely excised. The neoplasm was confined to the mucosa and consisted of epithelial cells arranged in anastomosing trabeculae and nests, growing downward into the lamina propria. Neoplastic cells showed minimal atypia and low mitotic activity. Histological findings were consistent with inverted urothelial papilloma. Feline papillomavirus DNA was not amplified from biopsies. One year later, the cat had no urological signs, and urinary bladder was normal at ultrasound. To the authors' knowledge, this is the first report of a case of inverted urothelial papilloma in a cat and is a differential diagnosis for low-grade urothelial carcinoma and other lesions with inverted growth pattern.

An unusual case of stridor: supraglottic inverted papilloma.

Inverted papillomas are rare benign neoplasms that typically originate in the sinonasal area of middle-aged men. We report the first case of a supraglottic inverted papilloma presenting with stridor.

Activating HRAS mutation in a case of inverted ductal papilloma of the salivary gland.

Inverted ductal papilloma (IDP) is one of the least common benign papillary/cystic neoplasms of the salivary duct system, being characterized histologically by florid hyperplasia of duct-type epithelial cells into a cystic lumen near the orifice with occasional endophytic growth of the surface squamous epithelium along the terminus of the affected excretory duct. Given its rarity, the exact etiology of IDP remains to be defined. We herein present the first evidence of oncogenic HRAS mutation in a case of oral IDP. This finding, together with the frequent and specific BRAF mutations in sialadenoma papilliferum reported in the recent literature, supports an active role of the MAP-kinase cascade in the pathogenesis of benign papillary neoplasms of terminal duct origin.

Treatment strategies for inverted papillomas with intracranial or intraorbital involvement.

OBJECTIVE: Sinonasal inverted papillomas are challenging benign tumours of the nasal cavity because of their high recurrence rates and the lifetime malignant transformation risk of 10 per cent as well as their locally aggressive behaviour. This study aimed to describe treatment strategies for inverted papillomas with intracranial or intraorbital involvement. METHOD: This was a prospective case series study of 18 patients with inverted papilloma with intracranial or intraorbital involvement. Patient demographic data, imaging, pathology, surgical technique and recurrences were recorded prospectively over a period of seven years. RESULTS: A total of 83 per cent of the patients in this study had been previously operated on, consisting of 8 cases with intracranial involvement, 1 case with intraorbital involvement and 9 with both. During follow up with a medium of 37 months (range, 13-115 months) there were two recurrences. CONCLUSION: It was postulated that intracranial or intraorbital involvement observed in this series was the result of multiple revisions. However, using accurate imaging protocols and the pedicle-oriented approach for tumour excision, complete tumour removal was achieved in most cases with minimal post-operative complications.

IMP3 Immunohistochemical Expression in Inverted Papilloma and Inverted Papilloma-Associated Sinonasal Squamous Cell Carcinoma.

Sinonasal inverted papilloma (IP) has a propensity for malignant transformation. Although the IP-associated squamous cell carcinoma (SCC) is rare, it has a poor prognosis. To the best of our knowledge, this is the first study to assess IMP3 immunohistochemical (IHC) expression in sinonasal tumors and to compare it to the Ki-67 IHC expression and to other established clinicopathological parameters. A retrospective study was conducted on three groups which consisted of 72 cases of sinonasal IP, 20 age-matched samples of normal respiratory epithelium, and 15 cases of sinonasal SCC associated with IP, which were obtained from the archives of the Pathology Lab of Ain Shams University Specialized and Ain Shams University Hospitals during the period from January 2012 to December 2019. An IHC study was performed to evaluate IMP3 and Ki-67 expression in the three groups, with correlation of IMP3 expression to established clinicopathological parameters of sinonasal SCC on top of IP. Both IMP3 and Ki-67 showed a sharp rise in expression in the sinonasal SCC group. In addition, there were statistically significant differences in expression values between the 3 groups (P = 0.001). Receiver Operating Characteristic (ROC) analysis revealed that IMP3 and Ki-67 could be used to discriminate sinonasal SCC from control and IP lesions, with sensitivity and specificity of 100% and 81.5% for IMP3, respectively, and 100% and 62.5% for Ki-67, respectively. Spearman's rho revealed that both IMP3 and Ki-67 were significantly related to the lymph node and tumor stages but not to the tumor grade. ROC analysis was performed to select cut-off scores for progression and survival for IMP3, and accordingly, Kaplan-Meier analysis showed correlation between IMP3 and overall survival, local recurrence-free survival, and metastasis-free survival in sinonasal SCC cases at the selected cut-off values. Based on our results, IMP3 could serve as a promising diagnostic, prognostic, and therapeutic marker for IP-associated sinonasal SCC.

MRI Predictors of Malignant Transformation in Patients with Inverted Papilloma: A Decision Tree Analysis Using Conventional Imaging Features and Histogram Analysis of Apparent Diffusion Coefficients.

OBJECTIVE: Preoperative differentiation between inverted papilloma (IP) and its malignant transformation to squamous cell carcinoma (IP-SCC) is critical for patient management. We aimed to determine the diagnostic accuracy of conventional imaging features and histogram parameters obtained from whole tumor apparent diffusion coefficient (ADC) values to predict IP-SCC in patients with IP, using decision tree analysis. MATERIALS AND METHODS: In this retrospective study, we analyzed data generated from the records of 180 consecutive patients with histopathologically diagnosed IP or IP-SCC who underwent head and neck magnetic resonance imaging, including diffusion-weighted imaging and 62 patients were included in the study. To obtain whole tumor ADC values, the region of interest was placed to cover the entire volume of the tumor. Classification and regression tree analyses were performed to determine the most significant predictors of IP-SCC among multiple covariates. The final tree was selected by cross-validation pruning based on minimal error. RESULTS: Of 62 patients with IP, 21 (34%) had IP-SCC. The decision tree analysis revealed that the loss of convoluted cerebriform pattern and the 20th percentile cutoff of ADC were the most significant predictors of IP-SCC. With these decision trees, the sensitivity, specificity, accuracy, and C-statistics were 86% (18 out of 21; 95% confidence interval [CI], 65-95%), 100% (41 out of 41; 95% CI, 91-100%), 95% (59 out of 61; 95% CI, 87-98%), and 0.966 (95% CI, 0.912-1.000), respectively. CONCLUSION: Decision tree analysis using conventional imaging features and histogram analysis of whole volume ADC could predict IP-SCC in patients with IP with high diagnostic accuracy.

[Unilateral diseases of the maxillary sinus]. / Einseitige Erkrankungen der Kieferhöhle.

Unilateral diseases of the maxillary sinus are among the most common rhinologic diagnoses. The diversity of these diseases can represent a challenge for the treating physician. The spectrum ranges from harmless maxillary sinus cysts that seldom require treatment, to highly aggressive malignant tumors. Special attention should be given to the management of inverted papilloma. These benign tumors are characterized by high recurrence rates and the potential for malignant transformation. The key to minimizing recurrence is precise surgical intervention. Other unilateral maxillary sinus diseases such as the antrochoanal polyp and the fungus ball (aspergilloma) are also discussed in depth.

Clinical evidence based review and systematic scientific review in the identification of malignant transformation of inverted papilloma.

BACKGROUND: Inverted papilloma (IP) is an unusual type of benign tumor that has high recurrence rates and the potential to transform into squamous cell carcinomas (SCC). The mechanism of the transformation process from IP to IP-SCC is uncertain and there is no consensus regarding the best practice for IP-SCC detection. The goal of this study is to identify the best clinical methods to detect for IP-SCC. METHODS: An evidence-based review was performed using Medline and Ovid to obtain all articles up to October 10th, 2019 pertaining to identification of IP malignant transformation. All manuscripts discussing clinical methods or biomarkers were included. RESULTS: Based on clinical research studies, convoluted cerebriform pattern and apparent diffusion coefficient values on Magnetic Resonance Imaging (MRI) can help differentiate benign IP from SCC and increased SUVmax on PET/CT is associated with higher probability of malignancy although not as specific. No consensus about the best biomarker for IP-SCC has been reached among researchers and continues to be exploratory. CONCLUSION: Endoscopy with biopsy is the gold standard practice to identify IP-SCC; however, MRI is the preferred imaging modality to recognize malignant transformation in cases where biopsy is difficult. Multiple biomarkers have shown positive results, but no single indicator with clinical significance for monitoring malignant transformation process has been found.

Inverted papilloma of the urinary bladder shows fluorescence on photodynamic diagnosis using 5-aminolevulinic acid.

Photodynamic diagnosis (PDD) of non-muscle invasive bladder cancer using 5-aminolevulinic acid (5-ALA) has recently attracted attention as a diagnostic method for observing cancer lesions based on fluorescence emission using a fluorescent endoscope. However, there are few reports of false positives associated with benign bladder neoplasms. Here, we provide report of two cases of inverted papillomas of the bladder that were fluorescent on PDD using 5-ALA. In each case, a surface-smooth, pedunculated bladder tumor was observed, which fluoresced red on PDD after oral administration of 5-ALA. Histopathological findings demonstrated inverted papilloma of the bladder. Although inverted papilloma of the bladder is usually regarded as a benign neoplasm, some recent studies have revealed that it could be a risk factor for urothelial carcinoma. Our present report may support the hypothesis that inverted papilloma of the bladder has malignant potential.

Stathmin and EGFR correlates to HPV status and clinical outcome in sinonasal inverted papilloma.

BACKGROUND: Inverted papilloma (IP) is a locally destructive benign tumour of the sinonasal mucosa with a tendency for malignant transformation. Stathmin and epidermal growth factor receptor (EGFR) are important markers in cancer prognosis. Here we investigate if expression of stathmin and EGFR correlate to dysplasia, recurrence and HPV in IP. METHODS: 98 patients with IP diagnosed 2000-2010 were analyzed for stathmin and EGFR by immunohistochemistry (IHC) and HPV by polymerase chain reaction assay (PCR). RESULTS: All IPs expressed stathmin while its expression was absent or weak in normal mucosa. Dysplasia was present in 26,7% of IPs with high stathmin expression while only 7.4% of IPs with low stathmin expression showed dysplasia. Stathmin positive IPs showed a trend towards earlier recurrences. 57.1% of IP expressed EGFR but no significant association was seen between EGFR-positivity and recurrence or dysplasia. EGFR was expressed by 91.7% of the HPV-positive IPs compared to 52,3% of the HPV negative IPs. CONCLUSIONS: EGFR expression is significantly higher in HPV positive IP. Stathmin is expressed by all IP tumour cells. Stathmin was also associated with dysplasia and a trend towards a correlation between stathmin positivity and recurrence was found. Stathmin and EGFR might therefore be considered therapeutic targets.

Pediatric naso-sinusal inverted papilloma: report of a case and literature review.

Inverted papilloma is a rare nasosinusal tumor that mainly occurs in adults during the 5th decade. The occurrence in children is exceptional and only few cases have been reported in the litterature. Clinical and radiological findings mimic other benign nasosinusal pathologies; therefore, diagnosis is based on histopathology either via biopsy or following surgical excision. Here we present a rare case of pediatric inverted papilloma in a 11-year-old child and we discuss clinical, radiological, therapeutic and evolutionary features through a literature review.

Transcriptionally Active HPV and Targetable EGFR Mutations in Sinonasal Inverted Papilloma: An Association Between Low-risk HPV, Condylomatous Morphology, and Cancer Risk?

Sinonasal inverted papillomas (IPs) commonly recur, and transform to malignancy in 5% to 10% of patients. It has long been debated whether IPs are caused by high-risk or low-risk (lr) human papillomavirus (HPV) and whether the HPV is transcriptionally active. EGFR mutations have also been recently implicated in the pathogenesis of IP with an unclear relationship to HPV status. IP cases over a 10-year period were tested for p16 by immunohistochemistry and for transcriptionally active hrHPV and lrHPV by reverse-transcriptase real-time polymerase chain reaction and RNA in situ hybridization, respectively. EGFR tyrosine kinase domain Sanger sequencing was performed on all lrHPV RNA positive and 15 randomly selected lrHPV RNA negative IPs. Seven sinonasal nonkeratinizing squamous cell carcinomas (SCCs) without associated IP were included as controls. Of the 44 IPs, 5 (11.4%) were associated with SCC, all keratinizing type. All IPs and associated SCCs were negative for p16 and hrHPV. lrHPV RNA was detected in 5/42 (12%) cases, including 3/5 (60%) with associated SCC (P=0.009). All 5 lrHPV RNA positive IPs involved the nasal cavity, had a distinct, condylomatous morphology, and were EGFR wild-type. In contrast, 11/15 (73.3%) lrHPV RNA negative IPs that were sequenced had EGFR exon 19 or 20 mutations. All control nonkeratinizing SCCs were lrHPV RNA negative, but 5/7 (71.4%) were p16 and high-risk HPV RNA positive. This study shows that a subset of IPs involving the nasal cavity have transcriptionally active lrHPV, condylomatous morphology, and possibly increased risk of malignancy. Furthermore, lrHPV positivity is mutually exclusive with EGFR mutations, which suggests alternate mechanisms of pathogenesis.

[Inverted papilloma: a study of 13 cases in the Oto-Rhino-Laryngology at the National University Hospital of Fann]. / Papillome inversé: à propos de 13 cas au Service d'Oto-Rhino-Laryngologie du Centre Hospitalier National Universitaire de Fann.

INTRODUCTION: Inverted Papilloma (IP) is a rare benign tumour of the nose and paranasal sinuses histologically characterized by invagination of the outer layer of the epithelium in the underlying chorion. Its most distinctive feature is a strong local aggressiveness, a tendency to recur and an unpredictable risk of association with epidermoid carcinoma. The purpose of this study was to report the epidemiological, clinical, paraclinical data as well as to assess the outcomes of endoscopic endonasal surgery. METHODS: We conducted a retrospective study on a series of 13 patients whose data were collected in the Oto-Rhino-Laryngology at the National University Hospital Center of Fann, from 1st January 2012 to 31st December 2017. All patients followed up for inverted papilloma confirmed by anathomopathological examination were included in the study. RESULTS: The average age of patients was 44 years, the sex-ratio was 2.25. All patients had nasal obstruction; 53% of them had rhinorrhea followed by epistaxis in 30% of cases. Right-sided symptoms were reported by 69% of patients, left-sided symptoms by 23% and bilateral symptoms by 7% of patients. Anterior rhinoscopy showed endonasal mass in all patients. All patients underwent CT scan; the MRI was performed in a single patient. Endoscopic resection of IP was performed in 10 patients (76.9%) while external approach was used in 23% of cases. Surgery helped to clarify where the tumor had originated: in 46% of cases in the maxillary sinus, in 15% in the lower nasal turbinate, in 15% in the mid-turbinate, in 7% in the ethmoid bulla and in 7% in the lateral wall of the nasal fossa. One patient had recurrence after an average period of 26 months. Malignant transformation to squamous cell carcinoma occurred in one patient. CONCLUSION: Inverted papilloma is a very aggressive tumor. CT scan is essential to highlight its spread, especially to bone. The advent of endoscopic surgery has revolutionised treatment, providing excellent results. But, there is nevertheless a risk of recurrence after surgery which motivates an indication for long term monitoring.