Endoscopic management of sinonasal inverted papilloma

Since 1992, 42 patients at the University of Pennsylvania have been treated for inverted papilloma (IP). Thirty-three patients were managed endoscopically with or without a Caldwell Luc approach (CLA) and retrospectively analyzed. The CLA, which involves a gingivobuccal incision for access to the maxillary sinus, is distinguished from a formal Caldwell Luc procedure. These 33 patients with histologically confirmed IP were without evidence of malignancy. They also did not have evidence of intracranial, orbital, or frontal sinus IP. Seventeen of 33 patients (17/33) were without prior treatment (primary). Sixteen of 33 (16/33) presented from an outside institution with recurrent IP (secondary). The recurrence rate using this method to treat primary IP was 6% (1/17), and for secondary IP was 25% (4/16). Scheduled postoperative endoscopic surveillance permitted early detection of recurrence and continued endoscopic control of IP. All 33 patients were endoscopically free of disease at the end of the study. These preliminary data are encouraging for the use of intranasal endoscopy with and without CLA as a means of managing and controlling IP in selected cases.     

Squamous cell carcinoma antigen as a marker of sinonasal inverted papilloma

This prospective study aimed to evaluate the usefulness of squamous cell carcinoma antigen (SCCA) as a clinical marker of sinonasal inverted papilloma (IP). The potential benefit of SCCA in the diagnosis of unilateral nasal pathology and as a marker of hidden recurrence was evaluated as well. Blood samples from patients with sinonasal IP were examined to determine serum SCCA levels before surgery, the day after surgery, and every 6 months during follow-up. Preoperative and postoperative levels of SCCA were compared. Twenty consecutive patients with histologically confirmed IP were included in the study, conducted between 2000 and 2011. The mean age of the patients was 54.2 years (range 35–72). The mean serum SCCA level before surgery was 3.885 μg/l (range 0.7–7.6). A decrease of the SCCA level to 0.885 μg/l (range 0.1–1.9) was observed on the 1 day after a radical surgical procedure. A statistically significant difference between the preoperative and postoperative levels was observed (P < 0.001). Elevated levels of SCCA during long-term follow-up were observed in three patients. All of them had a recurrence of IP. We conclude that the serum level of SCCA is a useful clinical marker of the presence of sinonasal IP. The level of SCC antigen was significantly lower in patients after IP was completely removed. According to our results, SCCA level also appears to be useful for long-term follow-up (hidden recurrence diagnosis).     

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.     

Endonasal micro-endoscopic resection of sinonasal inverted papilloma

BACKGROUND: The goal of this study was to assess the potentials and limitations of endonasal micro-endoscopic surgery in the treatment of sinonasal inverted papilloma (IP) and to demonstrate long-term results. PATIENTS AND METHODS: From 1989 to 2005, 64 patients underwent resection of IP via an endonasal approach using either the endoscope or microscope. Charts were reviewed retrospectively for presenting symptoms, radiological and intraoperative data. All patients were followed by endoscopic and MRI control during a period of up to 174 months, median follow-up was 78 months. RESULTS: Our study group consisted of 26 male and 38 female patients with an average age of 54.3 years. The majority of the patients (67 %) complained of unilateral nasal obstruction. 52 patients (81 %) were referred for primary surgery. In 12 cases (19 %) recurrent tumors were operated. According to the Krouse classification for IP the tumors were staged as T1 = 11 (17 %) cases, T2 = 37 (58 %) and T3 = 14 (22 %). In two patients a squamous cell carcinoma was associated with an IP ( = T4 stage). Most tumors were localized within the nasal cavity (72 %) or the anterior ethmoid (62 %). In 10 patients an infiltration of the bony skull base was present. During the follow-up period 6 patients developed recurrencies corresponding to an overall recurrence rate of 9.4 %. CONCLUSIONS: The advances in endonasal micro-endoscopic surgery allow both safe and effective removal of IP with low morbidity, and therefore it should be the approach of the first choice. The osteoplastic approach combined with endonasal surgery is suitable in far lateral located IP. Close follow-up is mandatory to ensure the surgical success.     

ErbB1 and ErbB2 overexpression in patients with sinonasal inverted papilloma and inverted papilloma with squamous cell carcinoma in China

Abstract

Background: Currently, the expression patterns of epidermal growth factor receptor (EGFR) family genes in sinonasal inverted papilloma (SNIP) and inverted papilloma with squamous cell carcinoma (IPwSCC) are not clear.

Objective: This study aimed to investigate the expression of EGFR family members and their ligands in SNIP and IPwSCC and to analyze their correlations with SNIP histological grade and Krouse stage.

Materials and methods: Data from 25 cases of inverted papilloma patients in China were collected and divided into 16 cases in the SNIP group and 9 in the IPwSCC group. In addition, eight cases of normal nasal mucosa (NNM) were collected and used as the control group. The expression levels of EGFR family members and their ligands in the NNM and SNIP groups and EGFR family members in the IPwSCC group were evaluated using immunohistochemistry and qRT-PCR. In addition, their correlations with the SNIP histological grade and Krouse stage were analyzed. The statistical analysis was performed using the GraphPad Prism 7.0 statistical software.

Results: The ErbB1 and ErbB2 mRNA and protein expression levels were significantly higher in the SNIP group than in the NNM group (p?<?.01). The ErbB1 and ErbB2 protein expression levels were significantly higher in the IPwSCC group than those in the NNM and SNIP groups (p?<?.01). The ErbB1 and ErbB2 mRNA and protein expression levels in the SNIP group were positively correlated with the SNIP dysplasia grade.

Conclusion: Upregulation of ErbB1 and ErbB2 expression may be associated with SNIP pathogenesis and carcinogenesis.     

组织病理学参数与鼻腔及鼻窦内翻性乳头状瘤复发的相关性

目的 确定可预测鼻腔及鼻窦内翻性乳头状瘤(inverted papilloma,IP)在5年内复发的可能性大小的临床及病理组织学参数.方法 对37例可随访的IP的部分临床资料和病理组织学特点包括年龄,性别,发病部位,鳞状上皮增生,过度角化,核分裂像,肿瘤性上皮成分的体积与间质成分的体积之比,骨浸润和炎性息肉的出现情况进行回顾性分析和观察.结果 IP在5年内复发的可能性的大小与发病部位和鳞状上皮增生这两个参数有关,5年内复发组与5年内未复发组的发病部位存在显著性差异(P=0.003),两组的重度鳞状上皮增生程度存在显著性差异(P=0.004),IP在5年内复发的可能性的大小与患者的年龄(P=0.067),性别(P=0.067),过角化(P=1.000),核分裂像(P=0.726),肿瘤性上皮成分的体积与间质成分的体积之比(P=0.430),骨浸润(P=1.000)和炎性息肉(P=0.196)的出现情况无关.结论 综合考虑部分病理组织学参数可预测IP在5年内复发的可能性的大小.累及鼻窦者,伴重度鳞状上皮增生者5年内复发的可能性大.     

Desmoglein 3 is overexpressed in inverted papilloma and squamous cell carcinoma of sinonasal cavity

Objectives/Hypothesis:

We sought to investigate the role of desmoglein 3 in pathogenesis of sinonasal inverted papilloma (IP) and its malignant transformation.

Methods:

Fifteen subjects with sinonasal IP and 15 subjects of normal sphenoid sinus mucosa were enrolled. Each specimen was divided into two portions: one for mRNA expression analysis by real‐time polymerase chain reaction, and the other for detection of targeted proteins by immunohistochemistry analysis. In addition, another 10 cases of IP with squamous cell carcinoma (SCC) were added for immunohistochemistry analysis.

Results:

The mRNA expression level of desmoglein 3 was significantly higher in IP tissues than in the normal sinus mucosa (P < .001). In immunohistochemistry study, desmoglein 3 was detected in plasma membrane areas of IP and IP with SCC tissues, but no obvious expression was found in normal sinus mucosa (total score; both P < .001). Positive desmoglein 3 staining was strongly present in nearly all malignant transformation areas of IP with SCC cases (90%), but only in scattered areas of some cases of IP (53%) (total score; P < .001).

Conclusions:

Desmoglein 3 was overexpressed in IP and IP with SCC, and the overexpression was correlated with malignant transformation of IP. It may provide valuable insight into the pathobiology of this disease, and can potentially provide a venue to predict malignant transformation in sinonasal IP. Laryngoscope, 2010     

Staging of surgical approach of sinonasal inverted papilloma

OBJECTIVE: In this study, we tried to make the staging of surgical approach of inverted papilloma (IP) and investigated the recurrence rate of IP. PATIENTS AND METHODS: Operating staging was as follows: When the IP was limited to the middle meatus, anterior and posterior ethmoid, or sphenoethmoid recess, standard endoscopic sinus surgery (SESS) was performed. When the lesion extended from the middle meatus into the maxillary sinus or originated from the medial wall of the maxillary sinus, radical endoscopic sinus surgery (RESS) was performed. And, when the IP originated from or involved the posterolateral, anterior, inferior wall of the maxillary sinus, intraorbital involvement, extensive growth of the lesion into the frontal or sphenoid sinus, or intradural invasion, external approach with endoscope assistance (Ex+E) was performed. RESULTS: 14 (36%) patients underwent SESS, 9 (23%) patients underwent RESS, and 16 (41%) patients underwent Ex+E. Malignancy occurred in no patient, and recurrences developed in four patients (10%). One of these recurrences happened after SESS, one after RESS and two after Ex+E. CONCLUSION: In this study, there was no significance of recurrence rate in each group. Better visualization can be obtained by combining the endonasal operation with an external procedure.     

鼻腔鼻窦内翻性乳头状瘤中Survivin及Bcl-2的表达

目的：探讨细胞凋亡抑制蛋白Survivin在鼻腔鼻窦内翻性乳头状瘤中的表达及其与Bcl-2表达的相关性。方法：采用免疫组织化学Envision二步法检测30例鼻腔鼻窦内翻性乳头状瘤,10例鼻腔鳞状细胞癌及10例正常下鼻甲黏膜标本中Survivin和Bcl-2的表达。结果：鼻腔鼻窦内翻性乳头状瘤和鼻腔鳞状细胞癌组织中Survivin的表达分别为73.3%和80.0%,均显著高于正常下鼻甲黏膜组织（均P〈0.01）。鼻腔鳞状细胞癌组织中Bcl-2的表达率为90.0%,显著高于正常下鼻甲黏膜组织的表达率（20.0%）（P〈0.01）。鼻腔鼻窦内翻性乳头状瘤组织中Bcl-2的表达率为46.7%,高于正常下鼻甲黏膜,但两者之间的差异无统计学意义（P〉0.05）。Survivin表达与Bcl-2表达呈正相关（P〈0.01）。结论：Survivin在鼻腔鼻窦内翻性乳头状瘤和鼻腔鳞状细胞癌的发生、发展中起重要作用,可能成为鼻腔鼻窦内翻性乳头状瘤和鼻腔鳞状细胞癌基因治疗的靶点。Survivin可能与Bcl-2在鼻腔内翻性乳头状瘤的发展中起协同作用。     

Preoperative staging and surgical approaches for sinonasal inverted papilloma

OBJECTIVES: We sought to determine the value of preoperative staging by magnetic resonance imaging (MRI) assessment in the surgical management of sinonasal inverted papillomas (IPs). METHODS: Preoperative MRI staging was used to assess 22 patients with IPs. In addition to the Krouse staging system, T3 cases were categorized as subgroup T3-B if tumors extended into the frontal sinus or the supraorbital recess; otherwise, they were categorized as T3-A. Standard endoscopic sinus surgery (ESS) was the first choice for T1 and T2 cases. Endoscopic approaches, including ESS combined with endoscope-assisted transantral approach and endoscopic medial maxillectomy, were considered in T3-A cases, and external approaches were considered in T3-B cases. Patients were followed for a minimum of 1 year after surgery. RESULTS: Preoperative MRI staging and postoperative staging were coincident in 21 of the 22 patients (95%). All 8 T2 cases were treated by an endoscopic approach. Of 10 T3-A cases, 9 (90%) were treated by an endoscopic approach and 1 (residual case) was treated by an external approach. All 3 of the T3-B cases underwent an external approach. One T4 case with malignant transformation underwent an external approach followed by radiotherapy. After a median follow-up period of 22 months, none of the 22 patients had had a recurrence. No major complications were observed after endoscopic approaches, but epiphora or hemorrhage requiring transfusion occurred in 3 of the 5 patients (60%) who underwent external approaches. CONCLUSIONS: Preoperative staging of IP by MRI is useful for selecting cases that can be managed by endoscopic approaches, resulting in lower rates of tumor recurrence and morbidity.     

Absence of high-risk human papilloma virus in p16 positive inverted sinonasal papilloma

ObjectivesSinonasal inverted papilloma (SIP) is a relatively rare disease, and its etiology is not understood. It is characterized by locally aggressive growth and a strong tendency to recur despite its benign histology.AimsThe aim of this study was to identify the presence of human papilloma virus (HPV) and its surrogate marker p16 in SIP tissue samples from a regional cohort.Material and methodsSubjects were identified from our regional center cohort of 88 SIP patients treated between 1984–2014. From these subjects, 54 were included in this study. Of these, 53 biopsies were analyzed with PCR, and 54 samples were immunohistochemically stained for p16. DNA was extracted from histopathologically verified SIP. Genotype screening for 13 high risk-, 5 oncogenic and 6 low risk HPV types was performed using the PapilloCheck® HPV-screening test.ResultsHPV analysis was successful for 38 of 53 samples. Of the 38 successfully analyzed samples, only 2 samples were positive for HPV 11. Notably, p16 was present in the epithelia in all samples, and in the papilloma lesions in 37 samples.ConclusionSince only 2 out of 38 SIPs were positive for HPV (type 11), and at the same time p16 was positive in epithelia in all samples and in 37 of 38 papilloma lesions of the samples, it is concluded that p16 cannot be used as a surrogate marker for high-risk HPV-infection in SIP. We are currently planning a prospective, multicenter study in order to increase the study power and in order to be able to better evaluate the clinical implications of HPV-and p16 in SIP.     

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.     

CT和MRI对鼻腔鼻窦内翻性乳头状瘤的诊断价值

目的　分析鼻腔鼻窦内翻性乳头状瘤的CT和MRI表现,探讨其诊断价值。方法　回顾37例经病理证实的鼻腔鼻窦内翻性乳头状瘤的CT和MRI影像,并与术中所见、术后病理及随访结果比较。结果　37例中,起源于上颌窦10例,筛窦8例,额窦6例,鼻甲6例,窦口鼻道复合体3例,蝶窦1例,不能确认起源3例。CT表现：单侧鼻腔鼻窦软 组织病变,骨炎征的出现率为62.16%,与起源部位一致的72.00%,3例出现眶纸板或前颅底骨质破坏,与恶变相关。MRI表现：36例出现脑回征,根据脑回征逆向回溯法,32例准确预测起源部位。结论　CT与MRI相结合,对于判断鼻腔鼻窦内翻性乳头状瘤的起源、范围及是否合并恶变更具有诊断价值。     

鼻腔鼻窦内翻性乳头状瘤生发中心的CT诊断

目的 术前通过CT值对内翻性乳头状瘤的根蒂即生发中心定位,尽可能完整切除肿瘤,降低术后复发概率。方法 回顾性分析25例鼻腔鼻窦内翻性乳头状瘤的CT资料,计算术中确定的肿瘤根蒂部位CT值与非根蒂部CT值,并观察肿瘤在CT图像上的灰度变化。结果 肿瘤根蒂部组织CT值平均为(36.87±10.21)HU, 在CT图像上可表现出较高密度影,呈现灰白色,肿瘤非根蒂部组织CT值平均为(25.32±10.69)HU,在CT图像上可表现出较低密度影,呈现灰黑色,经配对t检验,两组数据差异有统计学意义(P<0.05);20例初发病例中局部骨增生者6例(30%),其中有4例与肿瘤根蒂一致,一致性达66.7%,25例中有气泡征者6例(24%),骨质移位者14例(56%),骨质破坏者10例(40%)。结论 鼻腔鼻窦内翻性乳头状瘤的肿瘤根蒂部CT值较高,CT图像上为高密度影,可联合骨质变化及气泡征来判断肿瘤根蒂部位,制定手术方案。