The Laryngoscope Lippincott Williams & Wilkins, Inc.

, Philadelphia 2000 The American Laryngological, Rhinological and Otological Society, Inc.

Development of a Staging System for Inverted Papilloma

John H. Krouse, MD, PhD

Objectives: Inverted papillomas of the nose and sinuses are uncommon neoplasms. In the past decade there has been a trend toward the use of endoscopic surgical techniques in the management of these tumors, in contrast to the extensive open procedures recommended previously. This trend has not been without controversy, given the association of inverted papillomas with malignancy. It has been difficult to compare surgical approaches to these neoplasms, because of the absence of a uniformly applied staging system representing the extent of disease. It was the purpose of this study to develop such a system that could be easily applied in outcomes research. Study Design: This study involved an integrated literature review and a synthesis of findings from a number of studies. Methods: Previous and current clinical studies examining the treatment of inverted papilloma were reviewed. Findings were organized, and a staging system was framed based on this review. Results: A simple, easily applied staging system was developed based on the extent of tumor involvement noted on endoscopic examination of the nasal cavity and computed tomography (CT) scan evaluation. Conclusions: Stage I disease is limited to the nasal cavity alone. Stage II disease is limited to the ethmoid sinuses and medial and superior portions of the maxillary sinuses. Stage III disease involves the lateral or inferior aspects of the maxillary sinuses or extension into the frontal or sphenoid sinuses. Stage IV disease involves tumor spread outside the confines of the nose and sinuses, as well as any malignancy. Key Words: Inverted papilloma, paranasal sinuses, neoplasms, staging systems. Laryngoscope, 110:965968, 2000

INTRODUCTION
The treatment of inverted papilloma of the nose and paranasal sinuses remains a clinical challenge to otolaryngologists. Of the surgical approaches to these benign

Presented at the Meeting of the Southern Section of the American Laryngological, Rhinological, and Otological Society, Inc., St. Petersburg, Florida, January 14, 2000. From the Department of OtolaryngologyHead and Neck Surgery, University of Florida, Gainesville, Florida. Editors Note: This Manuscript was accepted for publication February 9, 2000. Send Correspondence to John H. Krouse, MD, PhD, 77 West Granada Boulevard, Ormond Beach, FL 32174, U.S.A.

neoplasms that have evolved over the past century, the generally accepted standard is medial maxillectomy through an external incision.1 The major stimulus for an aggressive surgical approach of this sort has been the association of inverted papilloma with malignancies of the nose and sinuses. The reported incidence of concurrent or sequential malignancies associated with inverted papilloma varies widely; the median rate of malignant association is approximately 9%.2 Since 1990, with the rapid expansion of endoscopic sinus surgical techniques, a number of otolaryngologists have begun to treat inverted papillomas with intranasal endoscopic approaches. With the improved visualization afforded by modern fiberoptic telescopes, and with the accurate imaging of the sinuses allowed by computed tomography (CT) scanning, surgeons have had more confidence in their ability to manage inverted papillomas endoscopically with recurrence rates similar to those seen in open surgical resections. A number of experienced sinus surgeons have presented clinical series demonstrating the effectiveness of endoscopic treatment for these tumors.27 A major problem in the critical analysis of current treatment approaches for inverted papillomaand an area of continued controversyis the inability of investigators to present studies to account for stage of disease in the analysis of their results. To address the validity of endoscopic surgical approaches in the treatment of inverted papilloma, it is vital to assess the severity of disease objectively. Only by accurately evaluating the use of various surgical techniques based on severity of disease will otolaryngologists address this persistent criticism. Despite the value of a staging system in the evaluation of treatment methods with inverted papilloma, there is no such universally applied system. In fact, there is no objective staging method that has been applied in assessing the outcome of these procedures. Therefore it was the purpose of this study to describe one such system and offer its use for critical analysis and surgical decision making.

MATERIALS AND METHODS

An extensive, integrated review of the literature was carried out through a MEDLINE search. The parameters of the search involved prior studies that evaluated specific treatment approaches to inverted papillomas of the nose and paranasal sinuses, as well as those that described staging systems applied to

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various types of nasal and sinus disease. A portion of this study was previously reported by the author.2

Parameters of Treatment for Inverted Papilloma

Krouse2 presented an extensive review of treatment approaches for inverted papillomas of the nose and paranasal sinuses for his American Laryngological, Rhinological and Otological Society, Inc., thesis in 1997. In that review Krouse examined 1426 cases of this tumor in 33 published studies, evaluating the types of treatment chosen for various clinical presentations. The review not only attempted to assess the efficacy of various treatment approaches across studies, but also described the pathological and clinical appearance of inverted papillomas. Relevant to staging systems, Krouses study presented information on the parameters that were used by a number of surgeons in selecting appropriate surgical strategies to manage a specific tumor. The following factors appeared to be important in the selection of a surgical approach for these patients: 1) extent of tumor, 2) location of tumor, and 3) presence of malignancy. As was noted previously, the methods of treatment for inverted papillomas of the nose and paranasal sinuses gradually evolved over a number of years. Most authors over the past several decades have advocated an open, en bloc resection of the medial maxilla through one of several external approaches. It was thought that, because of the high rates of recurrence with less extensive, piecemeal approaches, and considering the association with malignancy, anything short of an en bloc, oncological dissection would be inappropriate. However, there were early suggestions that more conservative approaches might be useful in selected cases. For example, Lawson et al.8 suggested that when tumor was isolated to the lateral wall of the nasal cavity with minimal involvement of the ethmoid sinuses or maxillary antrum, a conservative procedure might be adequate to resect this neoplasm. This philosophy was also described by Woodson et al.9 With the advent of endoscopic sinus surgical techniques in the 1980s, experienced endoscopic surgeons began to approach certain inverted papillomas through a transnasal approach with endoscopic visualization. The first to report this method were Waitz and Wigand,3 who published two studies examining a clinical series treated with either an endoscopic or an open approach. They selected patients with smaller, easily approachable lesions to have surgery endoscopically, while continuing to advise external medial maxillectomy in more extensive, bulky tumors; in tumors with bony destruction; and in cases of malignant transformation. Stankiewicz and Girgis4 also explored the surgery of inverted papillomas from an endoscopic approach and noted that lesions that were confined to the nose, ethmoid sinuses, and medial wall of the maxillary sinus were more amenable to endoscopic treatment than were tumors in other locations. In fact, they reported three recurrences on the floor of the maxillary antrum, stating that this region was less readily accessible through a strict transnasal endoscopic approach. Neither Waitz and Wigand nor Stankiewicz and Girgis would employ an endoscopic approach if malignancy were present in concurrence with the inverted papilloma. Dolgin et al.10 also reviewed a series of patients who received treatment for inverted papilloma. Their patients were treated with a variety of techniques ranging from midfacial degloving and lateral rhinotomy through Caldwell-Luc procedures and endoscopic approaches. They advocated a surgical approach based on CT scan imaging and endoscopic criteria, stating that the approach for surgical removal should be based on the location and extension of the lesion [emphasis added]. These authors believed that this graduated approach was preferable because of its decreased morbidity, even if a second procedure was necessary to address a recurrence.

The trend toward the application of less aggressive endoscopic techniques in selected cases of inverted papilloma is increasing. Experienced endoscopic surgeons believe that a graduated approach to surgery is indicated based on the clinical characteristics of the tumor. The following factors, again, appear to be crucial in the selection of a surgical treatment strategy: 1) extent of tumor, 2) location of tumor, and 3) presence of malignancy. Therefore an effective clinical staging system is essential.

Staging Systems
Staging systems have been developed for a range of pathological disorders of the nose and paranasal sinuses. These systems have been proposed as a method for guiding surgical treatment in a variety of benign and malignant conditions. Cancers of the nose and paranasal sinuses. Several systems have been used to stage carcinomas of the paranasal sinuses. The most widely applied system is that described by the American Joint Committee on Cancer (AJCC).11 In this system, commonly described as the TNM (tumor, node, metastasis) system, the extent and location of the tumor are reflected in the four T stages, with T1 lesions the smallest, most contained lesions and T4 lesions the more extensive. T1 malignancies of the nose and sinuses are confined to one discrete location without bony involvement. T4 lesions are more extensive, with penetration through the bone and into contiguous regions such as the intracranial compartment. A similar system that also has practical utility was described by Carinci et al.12 In this approach, malignancies confined to one site are considered T1 lesions and tumors that extend into separate regions, including the orbit and cranium, are staged as T4. Intermediate-stage lesions extend from the nose into the sinuses or involve more than one sinus cavity. Both of these systems of staging malignancy share two characteristics. They both describe a serial staging system, with confined disease staged as T1 and intermediate tumors staged as T2 and T3 based on extent of involvement. In addition, they both stage extensive spread of disease into structures outside the confines of the sinuses as T4 lesions. Inflammatory sinus disease. Staging systems have been developed for use in the evaluation and treatment of patients with chronic sinusitis to allow comparison of clinical outcomes among different institutions and various treatment modalities. The earliest of such staging systems was proposed in 1990 by Friedman et al.13 and involved a five-stage system in which stage 0 represented the absence of disease on CT scanning and stage IV represented extensive disease. Intermediate stages were based on the location of the disease and whether that disease was contiguous or discontiguous. Kennedy14 in 1992 proposed a system in which disease limited to the ethmoid sinuses was graded as stage I and more extensive involvement was staged progressively higher, with diffuse pansinusitis graded as stage IV. A similar system was described by Levine and May.15 Gliklich and Metson16 outlined a progressive staging system in which all unilateral disease was graded as stage I, bilateral ethmoid or maxillary disease as stage II, and more advanced disease as stage III or IV. The most widely used staging system for inflammatory sinus disease is that of Lund and MacKay.17 In this system, each of six anatomical locations is graded for absence of disease, partial involvement, or complete opacification. The locations are each rated bilaterally, and a summation is completed, yielding a rating score with a range of 0 to 24. While these staging systems vary in the exact criteria used and in the assignment of specific stages, they all assign stages sequentially, progressing from limited involvement to more diffuse, extensive disease. Higher stages are assigned to more severe disease.

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Inverted papilloma. Several authors have developed staging systems specifically for use with inverted papilloma, although none has been applied in any systematic manner. The first of such systems was described by Skolnick et al.,18 who applied the tumor component of the TNM system in use for staging malignancies of the nose and sinuses. Similar to the staging noted in the AJCC system, the authors described T1 lesions as those confined to one anatomical site within the nose and T2 lesions as involving two sites within the nose. They staged any involvement of the sinuses as T3, with extension outside the nose and sinuses as T4. A similar approach was also described by Norris.19 Schneider20 described a second staging system for inverted papilloma in which the radiological appearance of the tumor was considered in determining the clinical stage. He argued that the AJCC staging system was not appropriate for use with these benign lesions. In Schneiders system, stage I was described as tumor confined to the nasal cavity, with stage IV demonstrating erosion through bone and extension into the dura or periorbita. Intermediate stages demonstrated progressive involvement into the sinuses from the nose. A third system for staging inverted papilloma was described by Schwab et al.21 In this system, which is similar to that proposed by Skolnick et al., T1 lesions were confined to the nasal cavity, T2 and T3 lesions demonstrated progressive involvement of the paranasal sinuses, and T4 lesions extended into the orbit or intracranial cavity. In each of these systems described for use with inverted papilloma, a four-stage approach was proposed, with disease isolated to the nose staged as T1, independent of the extent of the disease within the nose. In each system, involvement of structures outside of the nose and sinuses such as the brain or orbit was staged as T4. Intermediate lesions were staged as either T2 or T3, with authors differing on the assignment of levels based on varying involvement of the sinuses.

laterally or inferiorly in the maxillary sinus are more difficult to visualize and remove endoscopically and are more likely to recur than those arising more medially. The authors would be more likely to choose an external approach as tumors are noted to extend more peripherally from the lateral nasal wall. Clearly, as the extent and location of the tumor progress away from the nose and lateral nasal wall toward the periphery of the sinuses, external approaches are more commonly employed, because the risk of incomplete excision and recurrence appears higher. In addition, the presence of malignancy in the setting of inverted papilloma would generally induce the surgeon to select a more aggressive approach to the tumor. In fact, no author currently recommends an endoscopic surgical approach for malignancies of the sinuses. Surgeons uniformly prefer an external, en bloc resection in the case of malignancy.

DISCUSSION
Based on the considerations mentioned in the Results section, a staging system was developed that would allow otolaryngologists to segregate patients into easily definable categories based on extent and location of disease. This system is presented in Table I. The use of such a staging system would be very beneficial in allowing an objective assessment of outcomes in patients treated with differing approaches or with similar approaches by different surgeons. The present staging system involves the use of both CT imaging of the nose and paranasal sinuses in the coronal and axial planes and thorough endoscopic examination. In cases in which it is unclear whether opacity on CT scan may reflect tumor extension or inspissated secretions trapped behind an ostium occluded by tumor, magnetic resonance imaging (MRI) scanning can be helpful in clarifying the situation and in planning a surgical approach.

RESULTS
It is clear from various staging systems applied to benign and malignant processes in the nose and paranasal sinuses that three primary factors are important in assessing the stage of the disease: 1) the location of the disease, 2) the extent of the disease within the nose and sinuses, and 3) the presence of malignancy. In all staging systems, minimal extent of disease is graded as a lesser stage than diffuse tumor involvement. Furthermore, disease that fills the sinuses diffusely is graded as more advanced. In malignant processes, and when disease violates the natural anatomical boundaries of the nose and sinuses and extends into the orbits, facial soft tissues, or intracranial compartment, the disease is staged at the most advanced level. It is also clear from a review of the recent studies that have examined the use of endoscopic surgical techniques in the excision of inverted papillomas that similar issues are relevant in the choice of a surgical approach. Location of the tumor, extent of involvement, and extension outside the nose and sinuses are primary factors involved in determining whether an inverted papilloma will be resectable through an endoscopic approach. For example, Waitz and Wigand3 noted that advanced lesions and those arising peripherally within the sinuses should be excised through an external approach. They noted that when the peripheral extent of the tumor cannot be visualized endoscopically, an external procedure is preferable. Stankiewicz and Girgis4 also stated that papillomas arising Laryngoscope 110: June 2000

TABLE I. Staging System for Inverted Papilloma. T1 Tumor totally confined to the nasal cavity, without extension into the sinuses. The tumor can be localized to one wall or region of the nasal cavity, or can be bulky and extensive within the nasal cavity, but must not extend into the sinuses or into any extranasal compartment. There must be no concurrent malignancy T2 Tumor involving the ostiomeatal complex, and ethmoid sinuses, and/or the medial portion of the maxillary sinus, with or without involvement of the nasal cavity. There must be no concurrent malignancy T3 Tumor involving the lateral, inferior, superior, anterior, or posterior walls of the maxillary sinus, the sphenoid sinus, and/or the frontal sinus, with or without involvement of the medial portion of the maxillary sinus, the ethmoid sinuses, or the nasal cavity. There must be no concurrent malignancy T4 All tumors with any extranasal/extrasinus extension to involve adjacent, contiguous structures such as the orbit, the intracranial compartment, or the pterygomaxillary space. All tumors associated with malignancy

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CONCLUSION
In the evaluation of surgical approaches to disease, it is important to account for differences in the severity of the disease when comparing various treatment approaches. To accurately determine treatment outcomes, an assessment of the preoperative extent and nature of the disease is critical. For this reason, staging systems are an essential aspect of the evaluative process in various inflammatory and neoplastic processes, including inverted papilloma. The staging system that is proposed in this study is an easily applied instrument, which can facilitate both treatment planning and comparison of surgical outcomes among patients with inverted papilloma of the nose and paranasal sinuses. With the current increase in the frequency of transnasal endoscopic surgical approaches to these tumors in recent years, a staging system such as the one described in the present study will allow a comparison of the safety and efficacy of these approaches with more traditional extranasal techniques. It will also address the persistent criticism that the severity of disease is not comparable among patients treated with open and endoscopic approaches. Clinical trials will be necessary to examine the sensitivity, accuracy, efficacy, and ease of use of this staging system in various populations of patients with inverted papilloma.
6. 7. 8. 9. 10.

11. 12. 13.

14. 15. 16. 17. 18. 19. 20. 21.

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