Sinonasal inverted papilloma: rate of recurrence and malignant transformation in 44 operated patients

IntroductionAlthough sinonasal inverted papillomas are benign lesions, they are locally aggressive and have a potential malignant transformation ranging from 5% to 15%, with a high recurrence rate.ObjectiveThe aim of this article is to describe the rate of recurrence and malignant transformation in patients with a diagnosis of inverted papilloma who underwent surgery in a tertiary hospital in São Paulo.MethodsWe performed a retrospective analysis of patients diagnosed with sinonasal papilloma who had undergone surgery in a tertiary hospital in São Paulo, between August 1998 and August 2017. A patient chart review was conducted to assess data of patients’ demographics, tumors characteristics, follow-up appointments, recurrence and malignancy. Inverted papillomas were analyzed and classified under the Krouse staging system.ResultsA total of 69 surgeries were performed in patients with diagnosis of sinonasal papilloma. Inverted papilloma was the most prevalent subtype (49 cases ? 80.33%), followed by exophytic papilloma (6 cases ? 9.84%) and by oncocytic papilloma (6 cases – 9.84%). The recurrence rate was 34.09% for inverted papilloma (15/44) and the mean time of recurrence was 24.6 months. Malignant transformation occurred in 6 patients (13.64%). Three of these patients presented carcinoma in the first surgery and three patients developed carcinoma during the follow-up.ConclusionThe high recurrence rate and malignancy potential allow us to consider inverted papillomas as aggressive tumors. In a tertiary hospital in São Paulo the recurrence rate the mean time to recurrence is 24.6 months. The recurrence after 10 years implies was 34.09% and the need for long-term follow up. It is possible that the high recurrence rate and the high malignant transformation rate we found are due to the large number of tumors discovered at an advanced stage (most of them staged T3 and T4), secondary to poor access to health system, in developing countries.     

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

BACKGROUND: 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. OBJECTIVES: 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. RESULTS: 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. CONCLUSIONS: 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.     

Long-term results of endonasal sinus surgery in sinonasal papillomas

OBJECTIVE: To assess the value of endonasal sinus surgery in the management of sinonasal papillomas. STUDY DESIGN: Retrospective study including 43 patients operated on for sinonasal papilloma in a long-term follow-up. METHODS: In 26 cases (60%) an endonasal approach, in eight cases (19%) an external approach, and in four cases (9%) a combined procedure was performed to remove these tumors. Five septal lesions (12%) were resected under direct vision. The original sections and charts of all patients were reviewed to assess clinical data. Follow-up information was available for 42 of our patients (98%) with a mean follow-up of 62 months. RESULTS: Histologic examination revealed 34 cases of inverted papilloma (79%), five cases of exophytic papilloma (12%), and four cases of columnar cell papilloma (9%). Malignancy occurred in 4 of 43 patients (9%), and recurrences developed in 8 of 42 patients (19%). Two of these recurrences happened after endoscopic sinus surgery (two inverted papillomas), three after lateral rhinotomy (three inverted papillomas), one after a combined procedure (one inverted papilloma), and two after simple resection (two exophytic papilloma). CONCLUSIONS: In keeping with our experience, the endonasal endoscopic approach, often in combination with a medial maxillectomy, is favored for the treatment of sinonasal papilloma because of a lower recurrence rate and a better cosmetic result. In some larger tumors and lesions in difficult locations, better visualization can be obtained by a combined external and endonasal approach.     

Human papilloma virus and p53 expression in carcinomas associated with sinonasal papillomas: a Danish Epidemiological study 1980-1998

OBJECTIVES: To determine a putative role and relation between human papilloma virus (HPV) and p53 in the etiology of sinonasal carcinomas associated with papillomas. STUDY DESIGN: The study group consists of all patients with sinonasal carcinomas associated with papillomas diagnosed in Denmark from 1980 to 1998. After reviewing our national pathological files, tumor tissues from 36 patients were collected, comprising 15% of the total cases of sinonasal carcinomas. In 35 cases a squamous cell carcinoma was demonstrated and in one case an adenocarcinoma was evident. Inverted papilloma was associated with carcinoma in 31 cases and exophytic papillomas in 5 cases. The material was investigated for HPV using polymerase chain reaction analyses with two sets of consensus primers (GP5+/GP6+ and MY09/MY11). The HPV-positive cases were submitted to dot-blot hybridization to establish the HPV type. Using immunohistochemistry, the p53 expression was determined. A p53 overexpression is defined as positive staining in 10% or more of the tumor cells. RESULTS: Among 30 examined cases of carcinomas associated with inverted papillomas, 4 cases were HPV-positive (13%). P53 overexpression was not shown among the HPV-positive cases, whereas p53 overexpression was seen in 21 of the 24 (88%) examined HPV-negative cases. Among the 5 carcinomas associated with exophytic papillomas, HPV was demonstrated together with p53 overexpression in 3 cases (60%). In addition, one case more was with p53 overexpression. CONCLUSION: An inverse relation between HPV and p53 overexpression in sinonasal carcinomas associated with inverted papillomas appears to have been demonstrated. HPV and p53 might also have an etiological role among the carcinomas associated with exophytic papillomas.     

Sinonasal Papillomas: Clinicopathologic Review of 40 Patients With Inverted and Oncocytic Schneiderian Papillomas

Objective To evaluate the pathological features and variations of sinonasal inverted and oncocytic papillomas and correlate the microscopic findings with the clinical behavior. Study Design A retrospective review and pathological assessment. Methods A retrospective review and pathological assessment were performed on 40 patients with a diagnosis of inverted papilloma treated by the senior author (w.l.) between 1994 and 2001. Results Forty cases were identified and reviewed. Seven patients developed recurrences (18%), and four underwent malignant transformations (10%). Pathological assessment revealed 34 (85%) inverted papillomas and 6 (15%) oncocytic schneiderian papillomas. Dysplasia was present in 26 cases (65%), including 9 cases (22%) of high‐grade dysplasia (moderate to severe). Metaplasia of the sinonasal mucosa adjacent to inverted papillomas and oncocytic schneiderian papillomas was seen in 18 (45%) cases. Recurrence developed in two patients with oncocytic schneiderian papillomas (33%) and five patients with inverted papillomas (15%). Four cases (10%) of carcinoma ex papilloma were seen; one arose from oncocytic schneiderian papilloma (17%), and three arose from inverted papilloma (9%). Oncocytic schneiderian papilloma was more often mixed with typical inverted papilloma, rather than presenting in its pure form. Conclusions Although oncocytic schneiderian papilloma is uncommon relative to inverted papilloma, the results suggest that they have higher rates of both recurrence and malignant transformation. The common admixture of oncocytic schneiderian papilloma with inverted papilloma speaks for a common etiological factor of these two lesions. A larger number of cases for analysis would be necessary to confirm the trend noted in our data. Nonetheless, pathological findings consistent with oncocytic schneiderian papilloma should be explicit in any classification system and justify aggressive treatment and careful postoperative surveillance.     

Evaluation of p53, p63, p21, p27, ki-67 in paranasal sinus squamous cell carcinoma and inverted papilloma

Using a molecular genetic approach, we try to confirm the molecular alterations of inverted papilloma and clarify its status as a putative precursor lesion of sinonasal squamous cell carcinoma. To better understand its genetics, we investigated the immunohistochemical protein expression patterns of cell-cycle-regulators p53, p63, p21, p27 and proliferation marker Ki-67 in 22 inverted papilloma and 9 squamous cell carcinoma of the sinonasal tract. Significantly elevated levels of p53 and p63 in squamous cell carcinoma of sinonasal tract compared with inverted papilloma were revealed. Ki-67-stained neoplastic cell nuclei were found in a significantly higher percentage of squamous cell carcinoma of sinonasal tract than in inverted papilloma, whereas no variation of p21 and p27 expression was identified. This work first examined the immunohistochemical overexpression of p63 in sinonasal inverted papilloma and squamous cell carcinoma. In conclusion, this is a first study shedding light on the expression of p63 in tumors of paranasal sinuses.     

Detection of human papillomavirus in temporal bone inverted papilloma by polymerase chain reaction

There is debate about the role of human papillomavirus in the induction of rare inverted papillomas involving the temporal bone and in the higher recurrence rates and association with squamous cell carcinoma of temporal bone inverted papillomas compared with sinonasal inverted papillomas. An exhaustive review of the literature revealed that eight cases of temporal bone inverted papilloma have been analysed for human papillomavirus. None of the cases studied with in situ hybridization proved positive. Only one case was found to be positive using the more sensitive polymerase chain reaction assay. We present the first two cases of Schneiderian-type papilloma involving the temporal bone to be analysed by type-specific polymerase chain reaction methods for human papillomavirus.     

Detection of Human Papillomavirus in Temporal Bone Inverted Papilloma by Polymerase Chain Reaction

There is debate about the role of human papillomavirus in the induction of rare inverted papillomas involving the temporal bone and in the higher recurrence rates and association with squamous cell carcinoma of temporal bone inverted papillomas compared with sinonasal inverted papillomas. An exhaustive review of the literature revealed that eight cases of temporal bone inverted papilloma have been analysed for human papillomavirus. None of the cases studied with in situ hybridization proved positive. Only one case was found to be positive using the more sensitive polymerase chain reaction assay. We present the first two cases of Schneiderian-type papilloma involving the temporal bone to be analysed by type-specific polymerase chain reaction methods for human papillomavirus.     

Sinonasal papillomas: A report of 82 cases in copenhagen county,including a longitudinal epidemiological and clinical study

The present epidemiological and clinical study comprises 82 patients with sinonasal papillomas diagnosed from 1975 to 1993. Histology showed 58 cases of inverted papillomas including 5 cases of associated carcinoma, 19 cases of exophytic papilloma, and 5 cases of columnar cell papilloma. The incidence of sinonasal papillomas in Copenhagen County was 0.74 per 100,000 inhabitants per year. The inverted and columnar cell papillomas were typically located in the middle meatus with a varying degree of involvement of the adjacent sinuses. The exophytic papillomas were predominantly located multicentrically on the nasal septum. Good results of treatment, especially with regard to inverted papillomas, were not correlated to the aggressiveness of surgery. A lateral rhinotomy with medial maxillectomy was performed as primary surgery in 28 patients. In 50% of these patients there were recurrences. The preliminary results of endonasal endoscopic surgery revealed a high success rate, i.e., no recurrences in 5 cases so far. The septal papillomas were typically resected by a simple endonasal procedure. There were recurrences in 66% of these cases. The midfacial degloving procedure may be advocated instead of or as a supplement to the lateral rhinotomy if the tumor cannot be visualized sufficiently by endoscopy. Smoking may dispose to sinonasal papillomas.     

Apoptosis and p53 in inverting papilloma of the sinonasal tract

The objective of this study was to identify apoptotic bodies and p53 positivity in inverting papilloma lesions to study these two as biomarkers in premalignant lesions. Archival specimens of 15 patients with inverting papilloma between the years 1992 and 1995 were retrieved. In situ end labeling technique was used to identify apoptotic bodies. Immunohistochemistry was used to detect p53 in the same specimens. The clinical course was evaluated conducting a retrospective chart review in these patients. Compared to normal epithelium, inverting papilloma lesions had a greater proportion of apoptotic bodies, which was nearly statistically significant (average 0.506/100 cells for inverting papilloma compared with 0.1/100 cells for the normal surrounding tissue). Four cases of inverting papilloma were p53 positive. There was, however, no association between p53 positive staining and the apoptotic rate. The minimum follow-up for patients was 2 years. All had a uniformly good clinical outcome with only one patient who was p53 positive showing concurrent squamous cell carcinoma. We concluded that inverting papilloma contained a higher average number of apoptotic bodies compared with normal surrounding sinonasal tissue. This showed a trend toward a positive between the apoptotic rate and premalignancy, suggesting both increased cellular proliferation and increased cell death may occur in such lesions. In this study p53 did not show a positive association with the apoptotic rate, suggesting that p53 may not be directly involved in the apoptotic regulatory pathway in inverting papillomas.     

Biologically aggressive papillomas of the nasal cavity: the role of radiation therapy

Five patients were irradiated at the University of Florida for advanced and/or recurrent papillomas of the nasal cavity and paranasal sinuses from December 1969 through December 1981. Three patients were irradiated either before or after resection and two patients were treated with radiation therapy alone. Two patients had pure inverted papilloma, one patient had inverted papilloma associated with a focus of squamous cell carcinoma, and two patients had cylindrical cell papillomas. Four patients are alive and continuously disease free at 3, 3, 4, and 11 years following treatment. One patient died of intercurrent disease nine years following treatment without evidence of recurrent tumor.     

Human papillomavirus in sinonasal papillomas and squamous cell carcinoma.

The diagnostic and prognostic relevance of human papillomavirus (HPV) types 6, 11, 16, and 18 in squamous papilloma, inverted papilloma, and squamous carcinoma of the sinonasal epithelium was examined using the polymerase chain reaction (PCR) technique. Four (15%) of 26 squamous papillomas, 7 (24%) of 29 inverted papillomas, and 1 (4%) of 24 squamous carcinomas were positive for HPV when examined using the PCR amplification technique. Human papillomavirus 6 was present in 5 specimens (3 squamous and 2 inverted papillomas); HPV-11 was present in 6 specimens (1 squamous and 5 inverted papillomas); and HPV-18 was present in 1 of 24 squamous carcinomas. HPV-16 was not identified in any specimen. The proportion of tissue samples showing HPV presence, and the association of HPV types 6 and 11 with benign lesions and HPV-18 with malignant lesions, are both in accord with findings from prior investigations. Two major questions regarding nasal papilloma are the probability for lesion recurrence after surgical excision and the risk for malignant transformation. There is no unanimity of opinion regarding the prognostic value of histopathologic dysplasia to forecast these outcomes. HPV is etiologically related to a subset of sinonasal papillomas and squamous carcinoma, and those with benign and malignant clinical course are separable on basis of HPV type. Because of the paucity of these nasal lesions, a multi-institutional prospective collaborative study is the ideal way to address these questions.     

Differentiation-related p53 protein expression in nondysplastic sinonasal inverted papillomas.

To clarify p53 protein expression in nondysplastic sinonasal inverted papillomas, archived surgical specimens from 19 patients were studied using immunohistochemistry. Staining results were compared between inverted papillomas and adjacent, nonpapillomatous nasal mucosa. Further, immunoreactivity was compared between columnar (respiratory), transitional (cuboidal), and squamous epithelium in inverted papillomas. Positive staining was found in 17 of 19 inverted papillomas (89%). Immunoreactivity involved predominantly basal and parabasal cells and was either comparable or higher in inverted papillomas compared with adjacent mucosa. In 65% of immunoreactive inverted papillomas comparable staining results were seen between columnar (respiratory), transitional (cuboidal), and squamous epithelium. In 35% of p53 protein-positive inverted papillomas, enhanced immunoreactivity was observed in transitional (cuboidal) and squamous epithelium compared with columnar (respiratory) epithelium. Within these cases, immunoreactivity was either comparable or higher in squamous compared with transitional (cuboidal) epithelium. Conclusively, the expression of p53 protein is present in 89% of nondysplastic sinonasal inverted papillomas and also involves the adjacent, nonpapillomatous nasal mucosa. A tendency toward increasing p53 protein expression from nonpapillomatous nasal mucosa to inverted papilloma as well as along the metaplastic process from columnar (respiratory) to transitional (cuboidal) and finally squamous epithelium within inverted papillomas can be postulated.     

Inverted papilloma of the nose and paranasal sinuses: a study of 67 patients

Retrospectively, 67 patients with inverted nasal papillomas were studied. In 12, the lesions were localized exclusively on the nasal septum. In 55, the lesion involved the lateral wall and/or the paranasal sinuses. There was a male predominance of 3:1. After histological revision the most dominating epithelial type was found to be transitional. Inverted papilloma was in one patient associated with squamous cell carcinoma. Ten per cent suffered recurrences from 6 to 37 months after the primary surgical procedure. We found that limited septal lesions could be managed by an intranasal procedure but lateral rhinotomy is recommended as the procedure of choice in the treatment of inverted papilloma of the lateral wall.     

Molecular pathologic study of human papillomavirus infection in inverted papilloma and squamous cell carcinoma of the nasal cavities and paranasal sinuses

Nasal inverted papilloma is a rare benign tumor occasionally associated with squamous cell carcinoma. To determine the etiological role of human papillomavirus in inverted papilloma, and to clarify the relationship between human papillomavirus and malignant transformation of this benign tumor, we retrospectively analyzed inverted papillomas from 26 patients, 7 of whom had squamous cell carcinoma. We used an immunohistochemical method and molecular pathologic techniques, or dot-blot hybridization of DNA extracted from paraffin-embedded tissues, in situ hybridization, and polymerase chain reaction. Human papillomavirus was detected in 5 of 26 patients (19%), 3 patients with human papillomavirus 11 and 2 patients with human papillomavirus 16. The latter 2 patients had inverted papillomas associated with squamous cell carcinoma. We speculate that human papillomavirus may be related to the malignant transformation of inverted papillomas.     

Endonasal endoscopic surgical treatment of paranasal sinus inverted papilloma--first experiences.

PURPOSE: Surgical excision is generally regarded as the treatment of choice for inverted papilloma. However, the approach and extent of surgery has been subject of much debate. The purpose of this study is to evaluate the results of endoscopic sinus surgery in the treatment of paranasal sinus inverted papilloma. PATIENTS AND METHODS: Thirteen cases of inverted papilloma of the paranasal sinuses treated via endoscopic sinus surgery were evaluated. The follow-up averaged from 9 months to 48 months with a mean of 27 months. RESULTS: A close follow-up of all patients was maintained. Seventy-seven per cent (10/13) of the patients had no recurrence after the initial endoscopic procedure. Three patients had recurrences of their tumor within 11 months after surgery, which means a rate of 23% (3/13). In 2 patients, the recurrences were treated endoscopically. In one patient, recurrence and malignant transformation (squamous cell carcinoma) developed after 36 months, which means that the associated carcinoma rate was 7% (1/13). This patient underwent radical maxillectomy and postoperative radiotherapy. None of the patients died of inverted papilloma. CONCLUSION: Endoscopic sinus surgery is a viable treatment alternative for paranasal sinus inverted papilloma in selected cases. This approach should be performed by experienced surgeons and a close follow-up is mandatory. When the disease is more extensive, it should be approached by radical surgery, e.g. en-bloc excision by medial maxillectomy via lateral rhinotomy or mid-facial degloving.     

鼻颅沟通瘤的手术入路

目的探讨鼻颅沟通瘤的手术治疗方法，以选择最佳的手术入路。方法上颌、鼻转位合并额或颞下入路11例，其中鳞状细胞癌8例，乳头状癌2例及脑膜瘤1例；颅面联合入路5例，4例为鳞状细胞癌，1例为恶性嗅神经上皮瘤；鼻锥额骨转位切除1例为鼻颅沟通脑膜瘤。结果17例患者中，2例脑膜瘤患者中的1例脑膜瘤累及海绵窦的部分肿瘤未能切除，另1例完整切除术后7年无复发迹象；15例恶性肿瘤患者，经上颌鼻锥转位合并额或颞下入路10例，术后1年余死亡1例，存活3年以上7例，5年以上5例；颅面联合入路5例，术后6个月余死亡1例，术后存活3年以上4例，5年以上2例。全部病例术后伤口均一期愈合。结论上颌鼻锥转位合并额或颞下入路是切除鼻颅沟通瘤的最佳入路，鼻锥额窦前骨壁转位适于切除额窦发育良好颅内侵犯较局限的鼻颅沟通瘤，颅面联合入路适于面骨被累的鼻颅沟通瘤。     

鳞状细胞癌抗原在鼻腔鼻窦鳞癌患者血清中的表达及临床意义

目的 探讨鼻腔鼻窦鳞癌患者血清中鳞状细胞癌抗原(SCC Ag)的表达及其临床意义。方法 对35例鼻腔鼻窦鳞癌、20例鼻内翻性乳头状瘤和30例鼻息肉患者采用微粒子酶免疫法检测血清SCC值,结合临床资料分析该抗原改变的临床意义。结果 鼻腔鼻窦鳞癌、鼻内翻性乳头状瘤、鼻息肉患者SCC阳性率分别为54.29%、35.0%和6.67%,差异有统计学意义(P<0.05); 鼻腔鼻窦鳞癌患者的病理分级及临床分期均与SCC有相关关系(P<0.05)。结论 检测鼻腔鼻窦鳞癌患者血清SCC表达水平对判断病情、临床分期等有一定的临床意义。     

Molecular transformation of recurrent respiratory papillomatosis: viral typing and p53 overexpression

Recurrent respiratory papillomatosis (RRP) is a histologically benign disease of the larynx, trachea, and bronchi. Here we report on the histologic and molecular characteristics of 7 cases of malignant transformation of RRP to squamous cell carcinoma (SCCA). The clinical histories of 7 patients with RRP who developed SCCA were carefully reviewed. Sequential biopsies were available from 5 of the 7 cases of spontaneous transformation of RRP to SCCA and were reviewed. In addition, p53 protein overexpression and human papillomavirus (HPV) typing for all cases was examined. The average age of patients with juvenile-onset RRP was 3 years, and that of patients with adult-onset RRP was 31 years. The average age of onset of transformation to SCCA was 28 years. All patients had laryngeal involvement with RRP, and 3 of the 7 patients had tracheal extension of disease. Five patients were tracheotomy-dependent. Four of the 7 patients developed SCCA of the lung, while 3 patients developed laryngeal SCCA. There was no consistent histologic progression from squamous papilloma to papilloma with dysplasia, and all but 1 of the SCCAs were well differentiated. The overexpression of p53 protein was variable in each of the 5 patients. We detected HPV types 6/11 in papillomas from 3 patients, and HPV types 6/11, 16/18, and 31/33/51 in a papilloma of a fourth patient. No HPV DNA was detected in papillomas of 2 patients. We found HPV 6/11 in 4 of the carcinomas. We conclude that the spontaneous transformation of RRP to SCCA is not characterized by a histologic progression through dysplasia over time. Transformation can result in the loss of HPV expression. It does not appear that p53 is a molecular marker for monitoring the transformation process. Thus, these cancers may be very difficult to diagnose histologically and clinically early in the course of the transformation of the disease.     

巨大中耳原发内翻性乳头状瘤癌变--附1例报告及文献复习

目的探讨一种临床上较少见肿瘤———巨大中耳原发内翻性乳头状瘤癌变的临床表现、诊断、治疗及预后,并对其与鼻腔乳头状瘤之间的关系作初步探讨。方法手术加放射治疗1例中耳乳头状瘤病人,并复习相关文献。结果1例巨大中耳原发内翻性乳头状瘤病人经手术切除后放疗,随访16个月无复发。结论中耳原发乳头状瘤除和人类乳头状瘤病毒感染有关外,还有诸多其他因素影响其发生、生长,极易复发和恶变为其特点, 临床早期诊断比较困难,应引起临床医生重视,对复发者应扩大切除,防止恶变。