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Background
Papillomas are very common presenting in adults between 30-50 yrs of age. Men are affected twice as common as women. Nasal obstruction is the most common presenting symptom and is usually unilateral. Local excision may lead to local recurrence in 50-70% of cases, usually within 1-2 years.
There are several types varying in histologic appearance. The identification of the type of papilloma is important as inverted and oncocytic papillomas are associated with the development of invasive squamous cell carcinomas. The recurrence does not appear to be dependent upon the histology. The length of time between recurrences does not correlate with the risk of subsequent cancer.
Human Papilloma Virus (HPV) has been identified in fungiform and inverted papillomas.
OUTLINE
EPIDEMIOLOGY CHARACTERIZATIONS SYNONYMS Schneiderian papilloma
DISEASE ASSOCIATIONS CHARACTERIZATION Occupational exposure Acta Otolaryngol 1996;116:762-765
Significantly higher degree of exposure to smokes, dust, and aerosol versus a control group
RADIOLOGY/
LABORATORYCHARACTERIZATION SERUM SQUAMOUS CELL CARCINOMA ANTIGEN
- Clinical value of serum squamous cell carcinoma antigen in the management of sinonasal inverted papilloma.
Yasumatsu R, Nakashima T, Masuda M, Kuratomi Y, Shiratsuchi H, Hirakawa N, Tomita K, Yamamoto T, Komune S.
Department of Otorhinolaryngology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Head Neck. 2005 Jan;27(1):44-8. Abstract quote
BACKGROUND: Although sinonasal inverted papilloma (IP) is a rare benign tumor, it has a tendency to recur and is sometimes associated with squamous cell carcinoma (SCC). Therefore, postoperative long-term follow-up of these patients is recommended. We previously reported that serum SCC antigen might be a useful tumor marker for sinonasal IP. In this study, we investigated whether serum SCC antigen level has a correlation with disease status and is useful in the early detection of recurrent disease.
METHODS: Blood samples for the analysis of serum SCC antigen were taken from 28 IP patients before and after surgical treatment.
RESULTS: Twenty-five (89%) of 28 cases showed evaluated serum SCC antigen levels above the upper limit. This marker level decreased in all cases after surgical resection. Four of these patients had a recurrence. None of the patients with recurrent tumor showed symptoms at the time of detection of their recurrent tumor, and recurrence was discovered from elevated levels of SCC antigen.
CONCLUSIONS: Serum SCC antigen level has a correlation with disease status of IP and has a potential to serve as a useful tool for monitoring the course of disease. SCC antigen is a reliable tumor marker in the management of sinonasal IPs.
- Serum squamous cell carcinoma antigen is a useful biologic marker in patients with inverted papillomas of the sinonasal tract.
Yasumatsu R, Nakashima T, Kuratomi Y, Hirakawa N, Azuma K, Tomita K, Cataltepe S, Silverman GA, Clayman GL, Komiyama S.
Department of Otorhinolaryngology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Cancer. 2002 Jan 1;94(1):152-8. Abstract quote
BACKGROUND: Inverted papilloma (IP) is a frequent benign sinonasal tumor that is characterized histologically by squamous metaplasia, epithelial acanthosis, and hyperplasia of the nasal epithelium. Because of its high recurrence rate and malignant transformation potential, careful long-term follow up is necessary.
METHODS: The purpose of the current report was to study the expression of squamous cell carcinoma (SCC) antigen in sinonasal IPs and to evaluate the usefulness of SCC antigen as a biologic marker for the follow-up of patients with sinonasal IP. The expression of SCCA1 in three sinonasal IP cases, three sinonasal SCC cases, and cases of normal nasal epithelium were examined by Western blot analysis, and the SCCA1 expression pattern in 31 IP specimens and 4 carcinoma in IP specimens were evaluated immunohistochemically. The serum levels of SCC antigen in 11 patients with sinonasal IP also were analyzed.
RESULTS: SCCA1 was overexpressed in all three sinonasal IP tissues compared with sinonasal SCC tissues or normal nasal epithelium. SCCA1 cytoplasmic immunoreactivity was detected in the suprabasal epidermal keratinocytes of all 31 sinonasal IP cases. In the four carcinoma in IP specimens, SCCA1 expression in the papillomatous lesion was more intense than in the cancerous lesion. The serum SCC antigen level was high in 10 of 11 patients with IP (91%) and significantly decreased after surgical resection of the tumors.
CONCLUSIONS: The results of the current study indicate that SCCA1 frequently is overexpressed and may play a biologic role in the development of sinonasal IPs. Serum SCC antigen may be a useful biologic marker in patients with sinonasal IP.MRI
- Magnetic resonance imaging findings of inverted papilloma: differential diagnosis with malignant sinonasal tumors.
Maroldi R, Farina D, Palvarini L, Lombardi D, Tomenzoli D, Nicolai P.
Department of Radiology, University of Brescia, Italy.
Am J Rhinol. 2004 Sep-Oct;18(5):305-10. Abstract quote
BACKGROUND: Computed tomography and magnetic resonance imaging (MRI) are the techniques of choice for pretreatment staging in neoplasms of the sinonasal tract. In inverted papilloma (IP), the information provided by computed tomography regarding characterization of the lesion is rather nonspecific. The present retrospective study was performed in the attempt to identify distinguishing features of IP on MRI.
METHODS: MRI examinations of 23 patients affected by IP (16 primary and 7 recurrent) and 23 patients affected by malignant tumors (MT; 12 adenocarcinomas, 9 squamous cell carcinomas, and 2 neuroendocrine carcinomas) of the sinonasal tract were evaluated. IP arose from the lateral nasal wall in 17 cases, the maxillary sinus in 5 cases, and the nasal septum in 1 case. The signal intensity of IP and MT was compared with muscles on spin-echo (SE) T2 and SE T1 images; contrast enhancement was compared with nasal septum mucosa. Possible specific MRI patterns in the two groups of patients were investigated. Bone involvement was graduated as remodeling or erosion (focal, < or =15 mm; intermediate, >15 mm and < or =30 mm; extended, >30 mm). The size of the lesions was assessed by measuring the greatest diameter on MRI. Parametric statistics in the form of Student's t-test or chi-squared test was used for data comparison.
RESULTS: IP showed a columnar pattern in all 23 cases by enhanced SE T1 images and in 16 of 23 lesions (>20 mm in diameter) by SE T2. This pattern was observed in only I of the 23 MTs; pathological examination of that specimen showed multiple foci of IP associated with squamous cell carcinoma. Bone remodeling was observed in 19 of 23 IPs, which in five patients was associated with focal (two cases) or intermediate (three cases) erosion. In MT, remodeling was present, which was always combined with focal (2 cases) or extended (21 cases) erosion. A strong correlation was found between the pattern of bone changes and histology (p = 0.00001). Bone alterations did not correlate with the size of the IP. The mean size of the IPs was significantly less than that of MT (33.9+/-15.7 mm versus 59+/-16 mm; p = 0.0003).
CONCLUSION: A columnar pattern is a reliable MRI indicator of IP and reflects its histological architecture (positive predictive value of 95.8%). The combination of this finding with the absence of extended bone erosion allows for the confident discrimination of IPs from MTs.
GROSS APPEARANCE/
CLINICAL VARIANTSCHARACTERIZATION General The location of the papilloma should be included in the diagnostic report, that is lateral wall or septal
Septal tumors tend to remain localized
Lateral wall tumors may involve multiple sites with a distinct association with squamous cell carcinomaInverted papillomas do not transilluminate
VARIANTS
HISTOLOGICAL TYPES CHARACTERIZATION FUNGIFORM PAPILLOMA
(Transitional cell papilloma)Arises almost exclusively on the nasal septum
Connective tissue stalks with exophytic architecture
Epithelial lining varies from squamous, ciliated columnar, intermediate, and mucus secretingINVERTED PAPILLOMA
(Transitional cell papilloma)Almost exclusively on the lateral wall of nose and paranasal sinuses
Invaginations of surface epithelium into underlying stroma with thin and delicate basement membrane
Epithelial lining varies from squamous, ciliated columnar, intermediate, and mucus secreting
Nucelar pleomorphism in 10%
Invasive squamous cell CA in 6-14% of casesSCHNEIDERIAN CELL PAPILLOMA (Cylindrical-cell papilloma, Oncocytic Schneiderian papilloma)
Inverted architectural appearance lined by cells with abundant eosinophilic cytoplasm
Multilayerd pseudostratified columnar cells with absent or minimal epidermoid component
Mitotic activity is lowFrequently contains inspissated mucin droplets
Invasive squamous cell CA in 6-14% of casesNOTE:
Not all have mitochondrial hyperplasia and hypertrophy
Oncocytic changes can be produced by intracellular organelles or products other than mitochondria
SPECIAL STAINS/
IMMUNOPEROXIDASE/
OTHERCHARACTERIZATION CYTOKERATINS Coexpression of Cytokeratins Typical for Columnar and Squamous Differentiation in Sinonasal Inverted Papillomas
Michael J. Schwerer, etal.
Am J Clin Pathol 2001;115:747-754 Abstract quote
Cytokeratin (CK) expression was studied in 22 sinonasal inverted papillomas. Columnar (respiratory) epithelium in inverted papillomas abundantly expressed CK7, CK8, CK18, and CK19. Immunoreactivity for CK5/14 and CK17 was found in basal and parabasal/ suprabasal cells. Transitional (cuboidal) and squamous epithelium in inverted papillomas comparably expressed CK7, CK8, CK18, and CK19. In addition CK13 was found in subluminal and surface cells. Immunoreactivity for CK5/14 and CK17 involved all layers of the epithelium.
In nonpapillomatous nasal mucosa adjacent to inverted papillomas, CK expression in columnar (respiratory) epithelium exactly matched the findings in inverted papillomas. Transitional (cuboidal) and squamous epithelium in nonpapillomatous mucosa were negative for CK7, CK8, CK18, and CK19. CK13 was expressed in subluminal and surface cells. Immunoreactivity for CK5/14 and CK17 was restricted to basal and parabasal/suprabasal cells.
Conclusively, transitional (cuboidal) and squamous epithelium in inverted papillomas but not in the adjacent mucosa coexpress CKs typical for columnar and squamous differentiation.
p53
Expression of p53 in inverted papilloma and malignancy associated with inverted papilloma.
Gujrathi C, Pathak I, Freeman J, Asa S.
Department of Otolaryngology, Mount Sinai Hospital, Toronto, ON.
J Otolaryngol. 2003 Feb;32(1):48-50. Abstract quote
OBJECTIVE: To determine the association of p53 protein in malignant cases of inverted papilloma compared with cases of benign inverted papilloma of the sinonasal tract.
DESIGN: Case-control study of archived pathologic material.
SETTING: Tertiary care hospital.
METHODS: Archived pathologic material of cases of malignancy associated with inverted papilloma and controls of benign inverted papilloma were obtained from Mount Sinai Hospital. These were subjected to immunohistochemistry for p53. Clinical correlation was obtained by retrospective chart review.
MAIN OUTCOME MEASURES: Staining of pathologic specimens for p53 and survival or recurrence.
RESULTS: Four of the five cases of malignancy associated with inverted papilloma demonstrated overexpression of p53. None of the benign cases of inverted papilloma demonstrated overexpression. Only two of the five patients with malignancy associated with inverted papilloma were alive at 2 years.
CONCLUSIONS: Overexpression of p53 may serve as a marker for malignant transformation of inverted papilloma.
- Immunohistochemistry of p53 in sinonasal inverted papilloma and associated squamous cell carcinoma.
Fang SY, Yan JJ, Ohyama M.
Department of Otolaryngology, National Cheng Kung University, Tainan, Taiwan.
Am J Rhinol. 1998 Mar-Apr;12(2):119-24. Abstract quote
Gene mutation of p53 is documented in head and neck cancer. No reports exist relating human sinonasal inverted papilloma (IP) and its transformation to squamous cell carcinoma (SCC).
Using immunohistochemical techniques improved by an antigen retrieval method, p53 protein was analyzed in the following subjects: 16 IP, 12 SCC arising in IP, and 15 SCC alone subjects. Both the intensity (PI) and rate (PR) of positive p53 immunostaining were evaluated using a quantitative AutoCAD program.
We correlated p53 protein expression with clinical features. p53 immunoreactivity is significantly lower in IP than in SCC specimens. Both the IP and SCC portions of IP synchronous SCC subjects showed similar p53 protein expression. SCC arising in IP shows a lower p53 immunoreactivity than SCC alone. Alteration of p53 protein may have an important role in the early stages of IP malignant transformation and prove a potential biomarker for risk assessment.
Low p53 immunoreactivity, indicating the presence of a wild-type p53, may correlate with the prognosis for SCC arising in IP. However, further clinical trials are required to investigate this possibly worthwhile prognostic marker.
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES Respiratory epithelial adenomatoid hamartoma Ann Otol Rhinol Laryngol 1995;104:639-645
Polypoid or exophytic
Primarily occurs on the nasal septum
Do not transilluminate
Small to medium sized round to oval glands lined by respiratory ciliated epithelium admixed with mucin-secreting goblet cells
Thick and hyalinized basement membrane
Stroma is well vascularized, edematous, or fibrotic
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSTIC FACTORS Adv Anat Pathol 2001;8:53-64
Finding of obvious keratinization is associated with a high degree of recurrence and association with either metachronous or synchronous squamous cell carcinoma
METASTASIS Laryngoscope 1995;105:178-183
Mean interval between onset of inverted papillomas and squamous cell carcinoma was 63 months (range 6 months to 13 years)
Of 92/991 inverted papillomas, (9.3%) had associated carcinoma
69.2% were synchronous arising within the papillomaMalignancies arising in oncocytic schneiderian papillomas: a report of 2 cases and review of the literature.
Maitra A, Baskin LB, Lee EL.
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Arch Pathol Lab Med 2001 Oct;125(10):1365-7 Abstract quote
Oncocytic schneiderian papillomas (OSPs) are uncommon benign neoplasms that arise from the sinonasal schneiderian epithelium. Malignancies arising in OSPs are rare, and, to our knowledge, only 14 such instances have been reported in the medical literature.
We report 2 additional cases--a small cell carcinoma and a sinonasal undifferentiated carcinoma arising in OSPs and presenting synchronously with the benign neoplasm. The potential for malignant transformation in OSPs is small, but warrants that these papillomas be completely excised to exclude a coexisting carcinoma.
- Recurrence and malignant degeneration of 89 cases of inverted papilloma diagnosed in a non-tertiary referral population between 1975 and 1995: clinical predictors and p53 studies.
Jardine AH, Davies GR, Birchall MA.
Department of Otolaryngology, University of Bristol and South and West Cancer Intelligence Unit, Bristol, UK.
Clin Otolaryngol Allied Sci. 2000 Oct;25(5):363-9. Abstract quote
Eighty-nine patients with sinonasal inverted papilloma presenting between 1975 and 1995 were reviewed with the aims of studying predictors of tumour behaviour and correlating outcome with p53 expression.
Correlation of clinical, radiological features and p53 status was made using chi2 and multiple logistic regression analysis with recurrence and malignant degeneration as the main outcome measures. Two patients had synchronous malignancy but no malignant degeneration was seen. There was no significant difference in recurrence between minor intranasal procedures and more extensive surgery for the first event. Younger patients were more likely to recur. (P = 0.0493, odds ratio 0.43). Those who smoked showed a trend towards multiple recurrence. p53 was expressed in 41% but did not predict recurrence. Morbidity was related to the extent of surgery.
Inverted papilloma presenting to a non-tertiary centre is more benign than previously reported. Initial management by less extensive endoscopic surgery may reduce morbidity.RECURRENCE J Laryngol Otol 1998;112:758-764
Recurrence Rates following surgery for lateral wall Schneiderian Papillomas
20-100% 0-33% (Additional 8% required follow-up extranasal resection) 0-63% 0-4% Laryngoscope 1990;100:462-469
82% (112 patients total) with inverted papillomas had involvement of both the nasal cavity and one or more sinuses
- Sinonasal papillomas: clinicopathologic review of 40 patients with inverted and oncocytic schneiderian papillomas.
Kaufman MR, Brandwein MS, Lawson W.
Departments of Otolaryngology, Mount Sinai School of Medicine, New York, New York 10029, USA.
Laryngoscope. 2002 Aug;112(8 Pt 1):1372-7. Abstract quote
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.STAGING Cancer 1976;37:1571-1576
Limited to the nasal cavity Limited to the nasal cavity and paranasal sinuses Extending beyond paranasal sinuses, resectable Extending beyond paranasal sinuses, nonresectable
- Staging of surgical approach of sinonasal inverted papilloma.
Katori H, Tsukuda M.
Department of Otolaryngology, Yokohama City University Medical Center, 4-57 Urafune-chou, Minami-ku, Yokohama 232-0024, Japan.
Auris Nasus Larynx. 2005 May 28; [Epub ahead of print] Abstract quote
In this study, we tried to make the staging of surgical approach of inverted papilloma (IP) and investigated the recurrence rate of IP.
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.
Fourteen (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.
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.SURVIVAL Cancer 1976;37:1571-1576
Mean disease free survival was 29 months in patients with carcinoma
Mean disease free interval was 12.5 months (0 months-5 years) for patients who died with the disease57% disease free survival 14% disease free survival TREATMENT Adv Anat Pathol 2001;8:53-64
In general:
Should not be managed as totally benign lesions
Best opportunity for successful control is with the first surgical procedure
The more open the approach, the better the accessibility, the more complete the resection, and less chance for recurrence
Indiscriminate application of lesser surgical approaches, including endoscopic surgery, may result in higher recurrence ratesLateral rhinotomy approach is generally regarded by most surgeons as the reference standard
- Endoscopic and endoscope-assisted resections of inverted sinonasal papillomas.
Wolfe SG, Schlosser RJ, Bolger WE, Lanza DC, Kennedy DW.
Department of Otohinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, PA, USA.
Otolaryngol Head Neck Surg. 2004 Sep;131(3):174-9. Abstract quote
OBJECTIVE: To evaluate the success of endoscopic and endoscope-assisted resection of inverted sinonasal papillomas and to assess the indications for adjunctive external procedures.
STUDY DESIGN: Retrospective chart review.
RESULTS: Fifty patients were treated surgically during the 10-year study period and had greater than 1 year of follow-up care. These patients had a recurrence rate of 14% (7/50) with a mean follow-up of 31.1 months. Of these 7 patients with recurrences, 3 were treated primarily at this institution, and 4 had been treated prior to referral. Recurrence was 11% (3/27) for primary resections and 17% (4/23) for secondary resections. Average time to recurrence was 11.7 months. Of the patients, 38% (19/50) had adjunctive external procedures either during the initial resection or for the management of recurrent disease.
CONCLUSIONS: Endoscopic and endoscope-assisted resections of inverted papilloma are effective techniques for managing inverted papilloma. The intraoperative findings, most importantly the site(s) of tumor attachment, dictate whether an endoscopic procedure is sufficient to complete resect the inverted papilloma or whether an adjunctive external procedure is required. Appropriate patient selection and an aggressive surgical approach are necessary for the management of these neoplasms.
- Different endoscopic surgical strategies in the management of inverted papilloma of the sinonasal tract: experience with 47 patients.
Tomenzoli D, Castelnuovo P, Pagella F, Berlucchi M, Pianta L, Delu G, Maroldi R, Nicolai P.
Department of Otorhinolaryngology, University of Brescia, Brescia, Italy.
Laryngoscope. 2004 Feb;114(2):193-200. Abstract quote
OBJECTIVE: To demonstrate the potentials and limitations of three different endoscopic procedures employed for treatment of inverted papilloma (IP) of the sinonasal tract.
STUDY DESIGN: Retrospective analysis of a cohort of patients treated at two University hospitals.
METHODS: From January 1992 to June 2000, 47 patients with IP underwent endoscopic resection. Preoperative workup included multiple biopsies of the lesion and imaging evaluation by computed tomography or magnetic resonance imaging. Massive skull base erosion, intradural or intraorbital extension, extensive involvement of the frontal sinus, abundant scar tissue caused by previous surgery, or the concomitant presence of squamous cell carcinoma were considered absolute contraindications for a purely endoscopic approach. Three types of resection were used: ethmoidectomy with wide antrostomy and sphenoidotomy (type 1) for IPs confined to the middle meatus, medial maxillectomy with ethmoidectomy and sphenoidotomy (type 2) for IPs partially invading the maxillary sinus, and a Sturmann-Canfield operation (type 3) for IPs involving the mucosa of the alveolar recess or of the anterolateral corner of the maxillary sinus. All patients were followed by periodic endoscopic evaluations.
RESULTS: Type 1, 2, and 3 resections were performed in 26, 15, and 6 patients, respectively. No recurrences were observed after a mean follow-up of 55 (range 30-132) months. One patient, who underwent a type 2 resection, developed a stenosis of the lacrimal pathways requiring endoscopic dacryocystorhinostomy.
CONCLUSIONS: Our experience confirms that endoscopic surgery is an effective and safe method of treatment for most IPs. The availability of different endoscopic techniques allows the entity of the dissection to be modulated in relation to the extent of disease. Strict application of selection criteria, meticulous use of subperiosteal dissection in the involved areas, and regular follow-up evaluation are key elements for success.Ann Otol Rhinol Laryngol 1971;80:192-206
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Fungiform papilloma-Microscopic Photo
Inverted papilloma-Microscopic Photo
Carcinoma arising within a papilloma-Microscopic Photo
Last Updated June 9, 2005
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