Sinonasal Papillomas

Frequency

SPs are relatively uncommon tumors of the nasal cavity, comprising 0.5-4% of all primary nasal tumors. Inverting papilloma accounts for approximately 70% of all SPs and has an incidence of 0.74-1.5 cases per 100,000 per year. Men are affected 4 times more often than women. White persons are most at risk, compared with persons of other races. Finally, although the age range for occurrence is 6-90 years, SPs are rare in children and young adults.

The etiology of SPs remains unconfirmed. Proposed causes include allergies, chronic sinusitis, airborne pollutants, and viral infection.

Allergy as a cause has been largely discredited because patients with SPs often have histories negative for allergies. In addition, sinonasal papillomas are typically unilateral.

Paranasal sinusitis is a frequent finding in patients with SPs and is considered by many authors to occur as a result of a tumor obstructing the sinuses rather than an inciting event creating the tumor.

Extrinsic factors associated with air pollution and industrial carcinogens have been considered as possible causes of SPs; however, more studies are required to achieve statistical significance. ^[4]

Viruses have long been suspected to cause these neoplastic lesions because they have a well-known tendency to produce papillomas elsewhere in the body. Human papilloma virus (HPV) is an epitheliotropic virus that has been implicated in premalignant and malignant lesions of the anogenital tract. Similarly, both the low-risk subtypes (ie, HPV 11, HPV 6) and the high-risk subtypes (ie, HPV 16, HPV 18) have been identified in SPs. Kusiak and Hudson described the presence of intracytoplasmic and intranuclear inclusion bodies in SPs. In 1987, Respler et al, using an in situ hybridization technique, demonstrated HPV 11 in 2 of their patients. ^[5]

Weber et al confirmed these findings in a study of 21 patients using in situ DNA hybridization, and 16 patients were found to have HPV DNA. ^[6] In addition, all recurrent lesions in their series were positive for HPV DNA. They theorized that the presence of HPV might affect the biological behavior of SPs. On the other hand, some studies using the hybridization technique and polymerase chain reaction have shown that HPV 6 and HPV 11 are involved in most cases of fungiform SP but are only rarely involved in cases of cylindrical and inverted papillomas.

A study by Paehler Vor der Holte et al indicated that low-risk HPV infection, particularly HPV 6, promotes the recurrence of SPs. The results further indicated that high-risk HPV infection promotes malignant progression of inverted papillomas, with the investigators finding that 15.5% and 16.7% of, respectively, inverted and oncocytic papillomas (both of which have higher malignant potential) were positive for high-risk HPV; such positivity was greater than that found in fungiform papillomas (which typically do not turn malignant). Moreover, HPV, especially high-risk HPV, occurred at higher rates in carcinomas in situ and squamous cell carcinoma ex-inverted papillomas than were seen in benign inverted papillomas. ^[7]

A study by Stoddard et al detected evidence of HPV in the sinonasal inverted papillomas of all 19 patients in the report but determined that transcriptional activity of the virus was limited (occurring in less than 1% of SP cells in 11 patients). The investigators did not find HPV transcriptional activity to be associated with the progression, recurrence, or malignant transformation of SP. ^[8]

A study by Yang et al suggested that hypermethylation and abnormal expression of the genes MIR661, PLEC, and OPA3 may contribute to the malignant transformation of sinonasal inverted papillomas. ^[9]

Clinical behavior

Sinonasal SPs are almost always unilateral. The 3 main clinical characteristic attributes of the tumors are (1) the tendency to recur, (2) their destructive capacity to surrounding structures, and (3) their propensity to be associated with malignancy.

The recurrence rate of these neoplastic lesions is highly variable (0-78%), depending mainly on the type of surgical approach and the completeness of resection. Phillips et al found that the recurrence rate after lateral rhinotomy and medial maxillectomy is low compared with after transnasal excision with the Caldwell-Luc operation (35%) or non-endoscopic transnasal excision alone (58%), for which the recurrence rates are significantly higher. ^[10] The multicentric origin of SPs has also been proposed as another factor that leads to the high recurrence rate; however, this has been documented in only a few cases.

Squamous cell carcinoma is the most common malignant neoplasm associated with SPs. Other types of malignancy rarely associated with SPs are adenocarcinoma and small cell carcinoma. Of the 3 subtypes of SPs, fungiform papillomas have not been reported to have malignant potential. Conversely, inverted papillomas have been reported to develop into carcinoma in 5-10% of cases. Cylindrical papillomas appear to have a higher frequency (14-19%) of malignancy association. No correlation is evident between the number of recurrences or the interval between the recurrence and the development of malignancy. ^[11]

A study by Nudell et al of SPs that underwent malignant transformation found that 85% were inverted papillomas and also that 85% gave rise to squamous cell carcinomas, with the rest being mucoepidermoid or sinonasal undifferentiated carcinomas. In addition, the study, of 20 patients, found that nine patients presented with carcinoma that was synchronous with the SP. ^[12]

The combined lesions of squamous cell carcinoma and SP appear to form 3 histologic categories, and most patients have lesions in the first and second groups. In the first group, the SP and the squamous cell carcinoma occupy the same anatomic region, but no evidence suggests that the papilloma gives rise to the carcinoma. In the second group, the papilloma contains a focus of invasive carcinoma. In the third group, the invasive carcinoma develops after the papilloma is resected.

A study by Yan et al suggested that overall and disease-specific survival are better in patients in whom squamous cell carcinoma of the sinonasal cavity has developed from inverted papillomas than in those in whom it has arisen de novo. The study also indicated that in patients with early T-stage sinonasal squamous cell carcinoma, those whose tumors develop from inverted papillomas have better disease-free survival than do those with de novo tumors. ^[13]

Unilateral nasal obstruction is considered the most common presenting symptom of patients with SP. Other symptoms may include epistaxis, nasal discharge, epiphora, and facial pain.

Physical examination usually reveals a unilateral polypoidal mass filling the nasal cavity and causing nasal obstruction. SPs have an irregular, friable appearance, and they often bleed when touched. They are reddish gray and may completely fill the nasal cavity, extending from the vestibule to the nasopharynx. The nasal septum is often bowed to the contralateral side. Proptosis and facial swelling sometimes develop secondary to expansion of the papillomatous lesion.

Endoscopic sinus surgery is contraindicated for tumors that arise from the lateral wall of the maxillary sinus and frontal sinus.