Case Reports Inverted Papilloma Associated With Squamous Cell Carcinoma and Adenocarcinoma: Case Report and Review of the Literature Joseph E. Kerschner, MD, Neal D. F&ran,
MD, DMD, and Victor Chancy, MD
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Inverted papilloma is an uncommon nasal lesion that has a known association with carcinoma. We present the first case of an inverted papilloma associated with both a squamous cell carcinoma and an adenocarcinoma. We also discuss pertinent clinical aspects of this lesion and current treatment options. CASE REPORT A 76-year-old white woman presented to her otolaryngologist with a history of nasal congestion and persistent headache. The patient was noted to have right-sided polyposis, and a computed tomography (CT) scan was obtained. This showed a right-sided intranasal mass and no bony erosion, The patient was taken to the operating room and underwent a polypectomy and right functional endoscopic ethmoidectomy and antrostomy. The pathology results showed inverted papilloma with squamous cell carcinoma in situ arising from the papilloma and adenocarcinoma in situ as a separate lesion (Fig 1). The patient was referred to the head and neck service at the University of South Florida. After review of the pathology, it was decided that the patient should undergo a medial maxillectomy, which was performed through a facial degloving approach. Final pathology results indicated no further inverted papilloma or carcinoma from the medial maxillectomy specimen. The patient has
From the Division of Otolaryngology-Head and Neck Surgery and the Department of Pathology, College of Medicine University of South Florida Tampa, FL. Address reprint requests to Neal D. Futran, MD, DMD, Department of Otolaryngology-Head and Neck Surgery, University of Washington, 1959 NE Pacific, Rm BB1165, Seattle, WA 98195. Copyright 0 1996 by W.B. Saunders Company 0196-0709/96/l 704-0007$5.00/O American
and is without follow-up.
DISCUSSION Nasal papillomas were first described by Ward1 in 1854. Subsequently, several classifications of nasal papillomas have been proposed.2 Hyams3 divided these lesions into inverted papillomas, fungiform papillomas, and cylindrical cell papillomas. This categorization was based on different histological appearances, anatomic sites, and clinical behavior. Fungiform papillomas, which primarily arise on the septum, have also been referred to as septal papillomas. Cylindrical cell papillomas are also classified as oncocytic papillomas. Some institutions suggest that the histological differences are not significant enough to warrant separate classifications and describe all nasal papillomas as inverted papillomas.2 Inverted papilloma is known to predominantly affect males. Most series report a 65% to 85% male preponderance.3-5 This lesion is rare in the pediatric population and has a peak incidence in patients in their sixth to seventh decade.2*4 In the past, several risk factors for inverted papilloma have been proposed including allergy, environmental carcinogens, sinusitis, and polyposis. 2,6*7However, many recent reviews discount these factors as playing a significant role.4s5s8In Phillips’ review,4 a significant smoking history was identified in 75% of the patients with inverted papilloma. Other reports have linked the human papilloma vi-
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Fig 1. Narrow black arrow showing inverted papilloma. Larger black arrow showing squamous cell carcinoma in situ. White arrow showing adenocarcinoma in situ (hematoxylineosin stain; original magnification x40).
rus with the development and malignant progression of inverted papilloma.gJO A majority of inverted papillomas arise on the lateral nasal well, most commonly in the vicinity of the middle turbinate. Most lesions extend from the lateral nasal wall to involve the sinuses. Usually the maxillary or ethmoid sinuses are affected, but frontal and sphenoid involvement occurs as well. Only rarely is disease limited to the sinuses without nasal involvement.2-4 Some reports discuss septal origination of inverted papillomas,5J’ however, Hyams3 states that none of the inverted papillomas in his review originated on the septum. Other reviews which have found a significant number of lesions originating from the septum tend to include all nasal papillomas.2 Multicentric lesions have been reported in inverted papilloma, and bilateral disease is cited as being present from less than 1% to 4% of cases.3l4 Inverted papillomas have also been reported in areas outside the sinonasal tract. The finding of lesions in the oropharynx, lacrimal sac, and middle ear have been attributed to ectopic migration of schneiderian mucosa.8,11 Clinical presentation of inverted papillomas vary, but generally patients present with unilateral nasal obstruction.4JJ2 Other symptoms include: epistaxis, anosmia, nasal discharge, facial pain or headache, epiphora, and visual changes.8z12
CT is an important part of the work-up in patients with inverted papilloma. CT gives a good estimation of the extent of disease and helps in the planning of resection. Clinically, inverted papillomas are locally destructive with a high recurrence rate of 25% to 75% reported in earlier reviews.3J3 Many of the recurrences were likely caused by an incomplete excision of the lesion. More aggressive surgical extirpation, primarily through the use of lateral rhinotomy and medial maxillectomy, has reduced recurrence rates to the range of 10% to 15%.4,8 The schneiderian mucosa which gives rise to inverted papillomas originates from the ectoderm of the olfactory plates. Inverted papillomas have a characteristic appearance with an endophytic growth and marked hypertrophy of the squamous epithelium. The epithelial cells are uniform with normal maturation patterns.14 The association between inverted papilloma and malignancy has long been recognized. Essentially all of these malignancies have been squamous cell carcinoma. Mention of associated adenocarcinoma and small cell carcinoma has been made.4 However, we were unable to identify any reports or reviews identifying a case of malignancy other than squamous cell carcinoma. It is likely that carcinomas, other than squamous cell carcinoma, found with inverted papillomas are simply
synchronous lesions and not truly associated with one another. The incidence of associated squamous cell carcinoma and inverted papilloma has varied greatly from less than 5% to more than ~o%.~J~-‘~ In most large series, the incidence has been between 5% and 15%.334J5 The associated squamous cell carcinoma can present in three different forms. It may arise from the papilloma itself, thought to be a malignant degeneration of the papilloma. Histological studies of these lesions have shown a transition from the benign papilloma to the malignant squamous cell carcinoma.3 Squamous cell carcinoma has also been found in conjunction with the papilloma specimen as a separate lesion. These are thought to be synchronous lesions and not a degeneration of the papilloma. Also squamous cell carcinoma may develop in the area of papilloma after treatment has been given. We believe our case is the first to show a squamous cell carcinoma originating from an inverted papilloma with an additional adenocarcinoma found within the specimen. Treatment of inverted papilloma is currently a topic of some debate. The traditional standard of care has been the lateral rhinotomy and medial maxillectomy. As mentioned, this has had a significant impact in lowering the recurrent rate of inverted papilloma. The midfacial degloving approach has also been advocated to provide excellent exposure for medial maxillectomy while avoiding the lateral rhinotomy scar.18,1g More recently, some investigators have advocated a role for endoscopic treatment of inverted papilloma.20-22 Longer follow-up of this approach will determine its efficacy. In cases where an associated malignancy is known to exist, medial maxillectomy generally allows for a good surgical margin. Radiation therapy also plays a role in the treatment of inverted papilloma associated with malignancy. In summary, inverted papilloma can be a destructive lesion with a high rate of recurrence if incompletely resected. Current standard treatment is an en bloc resection with medial maxillectomy. There is also a significant incidence of malignancy associated with inverted papilloma, and this must be considered when planning treatment.
REFERENCES 1. Ward N: A mirror of the practice of medicine and surgery in the hospitals of London: London Hospital. Lancet 2:480-482,1854 2. Weissler MC, Montgomery WW, Montgomery SK, et al: Inverted papilloma. Ann Otol Rhino1 Laryngol95:215221,1986 3. Hyams VJ: Papillomas of the nasal cavity and paranasal sinuses: A clinicopathological study of 315 cases. Ann Otol Rhino1 Laryngol80:192-206,197l 4. Phillips P, Gustafson RO, Facer GW: The clinical behavior of inverting papilloma of the nose and paranasal sinuses: Report of 112 cases and review of the literature. Laryngoscope 100:463-469,199O 5. Dolainy SR. Zaveri VD. Casiano RR. et al: Different options for treatment of inverting papilloma of the nose and paranasal sinuses: A report of 41 cases. Laryngoscope 102:231-236,1992 6. Lawson W, Biller HF, Jacobson A: The role of conservative surgery in the management of inverted papilloma. Laryngoscope 93:148-155,1983 7. Myers EN, Schramm VL Jr., Barnes EL: Management of inverted papilloma of the nose and paranasal sinuses. Laryngoscope 91:2071-2084, 1981 8. Myers EN, Fernau JL, Johnson JT, et al: Management of inverted papilloma. Laryngoscope 100:481-490,199O 9. Brandewein M, Steinberg B, Thung S, et al: Human papillomavirus 6/11 and l6/18 in schneiderian inverted papillomas.Cancer 63:1708-1713,1989 10. Weber RS, Shillitoe EJ, Robbins T, et al: Prevalence of human papilloma virus in inverted nasal papillomas. Arch Otolarvngol Head Neck Surg 114:23-26,1988 11. Roberts WH, Dinges DL, Hanly MG: Inverted papilloma of the middle ear. Ann Otol Rhino1 Larvnaol102:890i v 892,1993 12. Pelausa EO, Fortier MAG: Schneiderian papilloma of the nose and paranasal sinuses: The University of Ottawa experience. J Otolaryngol21:9-15,1992 13. Batsakis JG: Tumors of the Head and Neck (ed 2). Baltimore, MD, Williams &Wilkins, 1979, pp 132-137 14. Wenig BM: Atlas of Head and Neck Pathology. Philadelphia, PA, Saunders, 1993, pp 29-33 15. Lawson W, LeBenger J, Som P, et al: Inverted papilloma: An analysis of 87 cases. Laryngoscope 99:117124,1989 16. Osborn DA: Transitional cell growths of the upper respiratory tract. J Laryngol 70:574-588,1956 17. Yamaguchi KT, Shapshay SM, Incze JS, et al: Inverted papillomas and squamous cell carcinoma. J Otolaryngol8:171-178,1979 18. Maniglia AJ: Indications and techniques of midfacial degloving: A 15-year experience. Arch Otolaryngol Head Neck Surg 112:750-752,1986 19. Sachs ME, Conley J, Rabuzzi DD, et al: Degloving approach for total excision of inverted papilloma. Laryngoscope 94:1595-1598,1984 20. McCary WS, Gross CW, Reibel JF, et al: Preliminary report: Endoscopic versus external surgery in the management of inverting papilloma. Laryngoscope 104:415-419, 1994 21. Stankiewcz J, Girgis S: Endoscopic surgical treatment of nasal and paranasal sinus inverted papilloma. Presented at the American Academy of OtolaryngologyHead and Neck Surgery, Washington, DC, 1992 22. Waitz G, Wigand ME: Results of endoscopic sinus surgery for the treatment of inverted papillomas. Laryngoscope 102:917-922,1992