Inverted Papilloma Group Research Articles

The serum squamous cell carcinoma antigen level in inverted sinonasal papilloma and nasal polyps patients.

ObjectiveTo clarify whether the serum squamous cell carcinoma antigen (SCCA) levels of patients with inverted papilloma (IP) are different from patients with nasal polyps (NP) and rhinitis.Materials and methodsSerum SCCA levels were measured in 30 patients with IP and 30 patients with NP at one day before surgery and seven days after surgery and measured in 28 patients with rhinitis.ResultsElevated serum SCCA levels (>1.5 ng/ml) were found in 80.0% of patients in the IP group, 6.7% of patients in the NP group and 14.3% of patients in the rhinitis group, which was a significant difference. The medians of serum SCCA levels in the IP, NP and rhinitis groups were 3.9, 0.8 and 1.1 ng/ml, respectively, which was a significant difference. The SCCA level in IP group was not significantly correlated according to Krouse Staging. There was a significant difference in serum SCCA levels between the pre- and postoperative stages in the IP group, at 3.9 and 0.8 ng/ml, respectively, while in the NP group the levels were 0.8 and 1.0 ng/ml, not significantly different. With regard to the IP diagnosis in the IP and NP group based on the SCCA level (>1.5 ng/ml), sensitivity and specificity was 80.0% and 93.3%, respectively.ConclusionsThe serum SCCA level in patients with IP was elevated and then it decreased after surgery. This was different from NP and rhinitis patients who mostly had normal levels, which did not change.

Clinical Analysis of 382 Sinonasal Inverted Papilloma Cases Treated at A Single Tertiary Medical Center

Background and Objectives: Sinonasal inverted papilloma (IP) is a benign tumor with a locally aggressive nature and a propensity to recur. Many risk factors for recurrence have been reported, but they are still controversial. The aim of this study was to comprehensively assess the demographic data, clinical features, and potential risk factors for recurrence of IP.Subjects and Method: This work is a retrospective review of 382 patients diagnosed with and treated for sinonasal inverted papilloma between 1986 and 2017 at a single tertiary medical center. Demographic data, presence of associated malignancy, information about previous surgeries, tumor location, Krouse stage, surgical approach, follow-up duration, and data on recurrence were obtained.Results: In our study, 31 of 382 cases (8.1%) were associated with malignancy. Mean age was significantly higher in patients with associated malignancy compared to the benign IP group. Of the 351 benign cases, 263 (74.9%) were primary, and 88 (25.1%) were revision cases (residual or recurrent disease). Although the proportion of patients with high Krouse stage or multifocal involvement was high in the revision cases, there was no significant difference in recurrence rate. The 226 patients with a minimum follow-up of 1 year were included for recurrence analysis. Recurrence rate was significantly higher in the conventional surgery group (17.4%) compared to that of the endoscopic and combined surgery groups (8.1% and 3.6%, respectively). Also, the recurrence group showed significantly larger proportion of patients with high Krouse stage and multifocal involvement.Conclusion: Risk factors for recurrence of IP found in this study are comparable to those previously published. Generally, the factors associated with recurrence of IP were prior surgery, clinical stage, involved site, and surgical approach. Therefore, surgeons should always consider these risk factors to reduce the chance of recurrence.

The value of blood parameters as a diagnostic inflammatory biomarker for inverted papilloma

Aim: We aimed to determine the diagnostic value of blood parameters such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and mean platelet volume (MPV) values for sinonasal inverted papilloma (IP) and to investigate its relationship with severity of the disease.Material and Methods: In this retrospective study, 33 patients (22 males, 11 females; mean age 52.60±8.99 years) diagnosed with IP and 44 healthy individuals (25 males, 19 females; mean age 50.97±9.28 years) were included. NLR, PLR and MPV values of IP and control groups were calculated and compared statistically. In IP group, NLR values and stages of the disease in accordance with the Krouse Staging system were evaluated statistically. Results: NLR levels were significantly higher in the IP group than the control group. (Mean NLR: IP group= 2,484±1.132; Control group= 1.971±0.884; p=0.029). Lymphocyte, PLR and MPV values were not statistically significant between the two groups. A strong correlation was found between the NLR value and IP stages. Conclusion: In cases with inverted papilloma, the NLR value obtained by easy-to-perform and low-cost tests, can be used as a new inflammatory biomarker and to predict the severity of the disease. In order to confirm these findings, further studies with larger patient series are needed.

Expression pattern of estroprogestinic receptors in sinonasal inverted papilloma.

Inverted papilloma (IP) is a locally destructive, benign neoplasm of the nose and paranasal sinuses with a high tendency for recurrence, a significant potential for malignancy, and an etiology that today is still uncertain. The expression of hormonal receptors in neoplastic tissues has been the focus of intensive research for its potential diagnostic, prognostic, and therapeutic significance. The aim of this study was to assess the potential estroprogestinic receptor expression in patients undergoing sinus surgery for IP. A retrospective study was carried out, on surgical specimens of 73 patients who underwent endoscopic sinus surgery for first manifestation of sinonasal IP (primitive IP group) and in 21 subjects who had developed a recurrence (relapsed IP group). The results of the immunohistochemical analysis of the first group showed the absence of receptor expression for PGR in all cases analyzed and the presence of a low positivity for ER in 11 cases (P > 0.082). Similarly, in the second group the results showed a low presence of ER receptors in 3 of the 21 cases (P > 0.068), while there was no evidence of PGR receptors in the examined samples. In addition, in 11 of the cases only 3 were considered positive (27.2%) showing a recurrence during follow-up (P > 0.068).Our results suggest that the sinonasal IP is a benign tumor independent of estrogen and progesterone, and the receptors for these hormones are therefore unsuitable as predictors of relapse or possible prognostic indicators and therapeutic targets.

Telomerase reverse transcriptase (TERT) promoter mutation analysis of benign, malignant and reactive urothelial lesions reveals a subpopulation of inverted papilloma with immortalizing genetic change.

To understand more clearly the genetic ontogeny of inverted papilloma of urinary bladder, we analysed telomerase reverse transcriptase (TERT) promoter mutation status in a group of 26 inverted papillomas in comparison with the mutation status of urothelial carcinoma with inverted growth (26 cases), conventional urothelial carcinoma (36 Ta non-invasive urothelial carcinoma, 35 T2 invasive urothelial carcinoma) and cystitis glandularis (25 cases). TERT promoter mutations in inverted papilloma, urothelial carcinoma with inverted growth, urothelial carcinoma and cystitis glandularis were found in 15% (four of 26), 58% (15 of 26), 63% (45 of 71) and 0% (none of 25), respectively. C228T mutations were the predominant mutations (97%) found in bladder tumours, while C250T aberrations occurred in approximately 3% of bladder tumours. In the inverted papilloma group, TERT mutation occurred predominantly in female patients (P = 0.006). Among urothelial carcinomas, TERT promoter mutation status did not correlate with gender, histological grade or pathological stage. TERT promoter mutations were found in 15% of inverted papillomas. Our data suggest that there is a subpopulation of inverted papilloma that shares a carcinogenetic pathway with urothelial carcinoma with inverted growth and conventional urothelial carcinomas. Caution is warranted in exploring TERT promoter mutation status as a screening or adjunct diagnostic test for bladder cancer.

Human papillomavirus infection and immunohistochemical expression of cell cycle proteins pRb, p53, and p16(INK4a) in sinonasal diseases.

BackgroundWe aimed to clarify the possible role of human papillomavirus (HPV) infection in the malignant transformation of sinonasal inverted papilloma (IP).MethodsSubjects comprised 32 patients with chronic rhinosinusitis (CRS), 17 with IP, 5 with IP and squamous cell carcinoma (IP + SCC), and 16 with primary sinonasal SCC. HPV presence, viral loads, and physical status were investigated using polymerase chain reaction. Retinoblastoma (pRb), p53, and p16INK4a gene products were investigated by immunohistochemistry.ResultsHPV DNA was detected in 6.3 % of cases with CRS, 29.4 % with IP, 40 % with IP + SCC, and 25 % with SCC. IP cases had significantly higher HPV presence than CRS cases (p = 0.04). High-risk HPV-16 was the most frequently encountered subtype (10/13, 76.9 %). HPV-16 viral loads varied from 2.5 to 7953 E6 copies/50 ng genomic DNA. Patients in the SCC and IP + SCC groups had significantly higher viral loads than those in the IP and CRS groups (p < 0.01). All SCC and IP + SCC patients with HPV-16 demonstrated mixed-type integration, whereas 4 of 5 HPV-16 patients in the IP and CRS groups showed episomal type infection (p = 0.04). Positivity to pRb was found in 78.1 % of CRS, 35.3 % of IP, and 68.8 % of SCC cases. The presence of HPV DNA negatively correlated with pRb expression in SCC (p = 0.029) and IP (P = 0.049) groups. Although 62.5 % of SCC cases exhibited p53 positivity, only 5.9 % of IP, and no CRS cases were positive. Regardless of HPV status, p16INK4a positivity was frequently detected in IP cases (82.4 %), less in SCC (12.5 %) cases, and was not detected in the CRS group. Neither the IP nor SCC cohorts showed any correlation between HPV presence and the expression of either p53 or p16INK4a.ConclusionsHPV infection was more frequent in the IP, IP + SCC, and SCC groups than the CRS group. Higher viral loads and integration observed in the IP + SCC and SCC groups, and an inverse correlation between HPV presence and positive pRb indicated that persistent infection and integration play a part in tumorigenesis and malignant transformation in certain IP cases. However, p16INK4a is not a reliable surrogate marker for HPV infection in IP.

Differentiation of squamous cell carcinoma and inverted papilloma using non-invasive MR perfusion imaging.

To investigate the diagnostic value of tumour blood flow (TBF) obtained with pseudocontinuous arterial spin labelling for the differentiation of squamous cell carcinoma (SCC) and inverted papilloma (IP) in the nasal or sinonasal cavity. We retrospectively analysed the cases of 33 patients with SCC and 8 patients with IP in the nasal or sinonasal cavity. Pseudocontinuous arterial spin labelling scanning was performed for all patients using a 3.0-T MR unit. Quantitative TBF values were measured by two neuroradiologists by respectively delineating the whole-tumour regions of interest, and the mean of them was determined as TBF value in each patient. Additionally, the presence of imaging findings of convoluted cerebriform pattern (CCP) on MR T2 weighted images was determined in all patients. As a subgroup analysis, patients with IP were divided into aggressive and non-aggressive IPs depending on their progression range. First, an intraclass correlation coefficient (ICC) of TBF values between two neuroradiologists was determined. Next, a statistical comparison of the TBF value by a Mann-Whitney U test between the patients with SCC and IP was performed. Additionally, the comparison by an ANOVA with a post hoc test of Tukey's method among the SCC, non-aggressive IP and aggressive IP groups was also performed. If significance was observed, the diagnostic accuracy to differentiate SCCs from IPs was calculated. Diagnostic accuracy by CCP findings alone and by the combination of CCP findings and TBF were also assessed. The ICC of TBF values between two neuroradiologists was 0.82. The mean TBF values in the patients with SCC, all patients with IP, those with aggressive IP and those with non-aggressive IP were 141.2 ± 33.1, 77.8 ± 31.5, 109.4 ± 16.7 and 58.8 ± 19.9 ml 100 g⁻¹ min⁻¹, respectively. A significant difference was observed between SCC and IP (p < 0.001), SCC and non-aggressive IP (p < 0.01) and non-aggressive IP and aggressive IP (p < 0.01). The diagnostic accuracy values obtained with receiver operating characteristic curve analysis for the differentiation of SCC from IP and for SCC from non-aggressive IP were 0.90 and 0.92, respectively. The diagnostic accuracy was elevated (0.95 from 0.88) by adding the TBF value to CCP findings. The pseudocontinuous arterial spin labelling technique can be a useful non-invasive diagnostic tool to differentiate SCC from IP in nasal or sinonasal cavity.

Importance of Human Papillomavirus Integration in Malignant Transformation of Inverted Papilloma

Objectives: This study investigated the role of human papillomavirus (HPV) in malignant transformation of paranasal inverted papilloma (IP). Methods: HPV presence and viral load and physical status of HPV-16 were examined by polymerase chain reaction-based methods using fresh frozen samples or paraffin-embedded samples obtained from 17 patients with IP (IP group), 5 with IP and squamous cell carcinoma (IP+SCC group), 16 with SCC (SCC group), and 67 with chronic inflammatory lesions (inflammatory group). Results: The presence of the HPV genome was detected in 29.4%, 40.0%, 25.0%, and 6.0% of patients in the IP, IP+SCC, SCC, and inflammatory groups, respectively. The IP group showed significantly higher HPV-positive rates than the inflammatory group. All types of HPV detected were high-risk HPV, especially HPV-16. The relative HPV-16 copy numbers varied from 2.5 to 7953 per 50 ng genomic DNA. Viral load was higher in the IP+SCC group than in the inflammatory group. In the IP group, no significant relationship was found between HPV-16 viral load and clinical characteristics. All patients with IP+SCC and SCC showed integration of HPV-16. Conclusions: High viral load and integration of HPV have an important role in malignant lesion in association with IP.

Squamous Cell Carcinoma Antigen Production in Nasal Inverted Papilloma

The clinical importance of serum squamous cell carcinoma antigen (SCCA) and SCCA subclasses has not been established for treating inverted papilloma (IP). The aim of this study was to clarify the clinical importance of serum SCCA and its subclasses in IP, compared with maxillary squamous cell carcinoma and inflammatory disease. Serum SCCA was measured in 22 patients with IP (IP group), 11 with maxillary squamous cell carcinoma (carcinoma group), and 22 with inflammatory disease (inflammatory group). mRNA expression of SCCA subclasses was examined using quantitative real-time polymerase chain reaction. In the IP group, 81.8% showed elevated serum SCCA, and 90.3% with recurrent IP showed elevated SCCA. The preoperative SCCA value (mean ± SD, 3.99 ± 4.39) in the IP group was significantly higher than in the carcinoma (1.28 ± 0.88; p = 0.012) and inflammatory (0.60 ± 0.31; p < 0.001) groups. mRNA expression of SCCA1 and SCCA2 in the IP group was higher than in the carcinoma and inflammatory groups. The SCCA2/SCCA1 ratio of mRNA expression (0.11 ± 0.06) in the IP group was similar to that (0.11 ± 0.09) in the inflammatory group, although the ratio (0.20 ± 0.12) in the carcinoma group was significantly higher than in the IP and inflammatory groups. The receiver operating characteristic curve analysis for the SCCA2/SCCA1 ratio to detect carcinoma yielded an area under the curve of 0.760 (95% confidence interval, 0.626-0.894). The serum level of SCCA is effective for detecting IP, including recurrent IP. In contrast, the SCCA2/SCCA1 ratio is useful for detecting squamous cell carcinoma among other sinonasal diseases.

Human papillomavirus load and physical status in sinonasal inverted papilloma and squamous cell carcinoma

Background: This study investigated prospectively the role of human papillomavirus (HPV) in paranasal inverted papilloma (IP). Methods: HPV presence and viral load and physical status of HPV-16 were examined by polymerase chain reaction-based methods using fresh frozen samples obtained from 13 patients with IP (IP group), 11 with squamous cell carcinoma in the maxillary sinus (SCC group) and 39 with chronic inflammatory lesions (inflammatory group). Results: The presence of the HPV genome was detected in 46.1%, 27.3% and 7.6% of patients in the IP, SCC and inflammatory groups, respectively. The IP group showed significantly higher HPV-positive rates than the inflammatory group. All types of HPV detected were high-risk HPV, especially HPV-16. The relative HPV-16 copy numbers varied from 2.5 to 1524.1 per 50 ng genomic DNA. The viral load was higher in the IP and SCC groups than in the inflammatory group. In the IP group, no significant relationship was found between HPV-16 viral load and clinical characteristics, or between physical status and clinical characteristics. One patient with IP and concomitant squamous cell carcinoma, however, showed high viral load and integration. Conclusions: HPV infection is involved in the pathogenesis of IP, and high viral load and integration of HPV have an important role in malignant lesion in association with IP.

Human papillomavirus load and physical status in sinonasal inverted papilloma and squamous cell carcinoma

This study investigated prospectively the role of human papillomavirus (HPV) in paranasal inverted papilloma (IP). HPV presence and viral load and physical status of HPV-16 were examined by polymerase chain reaction-based methods using fresh frozen samples obtained from 13 patients with IP (IP group), 11 with squamous cell carcinoma in the maxillary sinus (SCC group) and 39 with chronic inflammatory lesions (inflammatory group). The presence of the HPV genome was detected in 46.1%, 27.3% and 7.6% of patients in the IP, SCC and inflammatory groups, respectively. The IP group showed significantly higher HPV-positive rates than the inflammatory group. All types of HPV detected were high-risk HPV, especially HPV-16. The relative HPV-16 copy numbers varied from 2.5 to 1524.1 per 50 ng genomic DNA. The viral load was higher in the IP and SCC groups than in the inflammatory group. In the IP group, no significant relationship was found between HPV-16 viral load and clinical characteristics, or between physical status and clinical characteristics. One patient with IP and concomitant squamous cell carcinoma, however, showed high viral load and integration. HPV infection is involved in the pathogenesis of IP, and high viral load and integration of HPV have an important role in malignant lesion in association with IP.

Immunohistochemical Analysis of PCNA, Ki67 and p53 in Nasal Polyposis and Sinonasal Inverted Papillomas

Immunoreactivity of proliferating cell nuclear antigen (PCNA), Ki67 and p53 in inflammatory nasal polyp and inverted papilloma tissues was investigated. Immunohistochemistry was performed using a standard avidin-biotin-peroxidase method, and the immunoreactivity of PCNA, Ki67 and p53 was quantified by counting immunostained nuclei in at least 1000 epithelial cells. The mean labelling index (percentage of immunostained cells) for PCNA was 40.68 in the inverted papilloma group and 14.73 in the nasal polyp group, and for Ki67 was 15.43 in the inverted papilloma group and 2.64 in the nasal polyp group. Both of these differences between the inverted papilloma and nasal polyp groups were significant. Immunoreactivity for p53 was detected in five (35.7%) inverted papilloma patients and two (9.5%) nasal polyp patients. The increase in epithelial cell proliferation seemed to be greater in inverted papillomas than in inflammatory nasal polyps. Increased epithelial cell proliferation may be involved in the development of inverted papillomas.

Do Nasal Polyps and Inverted Papilloma have Similar Disorders in Cell Cycle Regulation?

The aim of this study was to determine the expression of cell cycle regulation genes in patients with inverted papilloma (IP) and compare this with expression in patients with nasal polyps (NPs). Tissue from 18 patients with IP and 5 patients with NPs were stained by immunohistochemistry techniques for p53 and p27. Measurement of the gene expression was performed by three assessors, who we blinded with respect to the specimens. The mean score for p53 expression (3.33) was significantly higher in the IP group than the NP group (1.46). The mean difference between IP and NPs was 1.80 (CI, 1.15-2.46; p = 0.003). Additionally, we showed in a number of individuals variation in the p53 expression within the same specimen. There was no difference in the mean scores for p27, with the mean difference 0.79 (CI, 0.30-1.89; p = 0.147). Our study established a significantly increased expression of p53 in IP when compared with NPs. Additionally, there appear to be two different cell populations identified within the same specimens, which exhibited variation in their p53 expression.

Temporal bone and sinonasal inverted papilloma: the same pathological entity?

Inverted papilloma involving the temporal bone is an extremely rare occurrence. Reports in the literature suggest a higher recurrence rate and association with squamous cell carcinoma in Schneiderian-type papillomas of the middle ear than in sinonasal Schneiderian-type papillomas. To investigate the expression of apoptosis-related proteins, markers of cell proliferation activity, and sex hormone receptors in temporal bone inverted papillomas and to compare this entity with sinonasal papillomas. Design and Subjects We investigated 2 rare cases of inverted papilloma of the temporal bone and a control group of 6 cases of sinonasal inverted papilloma. The expression of p53, Mib-1, p27, and progesterone and estrogen receptors was determined. In the 2 cases of temporal bone inverted papilloma, p53 expression was 43.75% and 4.92%; p27 expression was higher in temporal bone inverted papilloma (82.45% and 70.53%) than in the sinonasal inverted papilloma group. One of our 2 cases of temporal bone Schneiderian-type papilloma was positive for progesterone receptor. The expression of progesterone receptor in 1 of our 2 cases and in the only other case reported in the literature may imply some degree of hormonal dependence of temporal bone inverted papilloma. Our analysis of the expression of apoptosis-related proteins, markers of cell proliferation activity, and sex hormone receptors does not allow us to demonstrate that temporal bone and sinonasal inverted papilloma are different pathological entities.