16

There are more than 70 pathologic entities that have been described for the sinonasal cavity, more than half of which are malignant.1 Table 16.1 lists some of the more common benign and malignant tumors that may involve the maxillary sinus.

Benign Neoplasms

Inverted papillomas (IPs) are the most common benign sinonasal tumors, occurring with a yearly incidence of 0.2 to 0.6 per 100,000. They are more common in males (3:1), and they typically present with unilateral nasal obstruction in the fifth and sixth decades of life. They most commonly originate from the lateral nasal wall, followed by the maxillary sinus, and are bilateral in approximately 5% of the cases. Unilateral nasal polyposis should raise the suspicion of IPs. They are associated with a 9% risk of concurrent or delayed malignancy and have a rate of recurrence as high as 71% if incompletely excised.² Histologically, they appear as proliferative respiratory epithelium with inversion into the stroma, with or without squamous metaplasia, and without invasion. Cylindrical cell papillomas are less common than IPs and typically arise from the lateral nasal wall but have been described in the maxillary sinus. Because of the potential for malignancy and a high-recurrence rate, traditional surgical approaches for IPs have been lateral rhinotomy or midface degloving, but an aggressive endoscopic technique has been shown in numerous studies to be equally efficacious with less morbidity.^2,3

Table 16.1 Common Benign and Notable Malignant Primary Tumors of the Maxillary Sinuses

Malignant neoplasms of the paranasal sinuses are rare, with a yearly incidence of less than 1 per 100,000. The maxillary sinus is the most common site within the paranasal sinuses, followed by the ethmoid sinuses, sphenoid sinuses, and frontal sinuses. Risk factors for sinonasal malignancies include wood exposure, work in the leather or textile industry, and exposure to metals and chemicals including aluminum, nickel, and chromium. Heavy cigarette smoking has also been implicated, as have the Epstein-Barr virus and the human papillomavirus.1

Squamous cell carcinoma (SCC) is the most common subtype in adults, accounting for 40 to 50% of malignant sinonasal tumors, followed by adenocarcinomas (13 to 19%) and adenoid cystic carcinoma (ACC) (6 to 10%).¹ The American Joint Committee on Cancer (AJCC) staging system is used for these tumor types (Table 16.2). Treatment is most often surgery followed by adjuvant therapy (when indicated).⁴ As in ACC, it is important to ensure that adjacent nerves are free of disease in SCC, as perineural spread is not uncommon and may lead to recurrence or spread to the central nervous system. Unlike other head and neck SCCs, the degree of involvement of cervical lymph nodes is not completely clear, and therefore treatment of the neck is controversial, and will be discussed later in this chapter.

The maxillary sinus is the most common site of sinonasal ACC. Histologic patterns of ACC include cribriform, tubular, and solid; the solid subtype has the worst prognosis. The 5-year survival rates have been reported to range from approximately 60 to 70%.⁵ Rates of perineural invasion (PNI) of 20 to 80% have been described for ACC,⁶ which may be related to its high-recurrence rate despite aggressive surgical treatment and postoperative radiation.⁵ Recurrence and distant metastases are common, the lung being the most common site. In a recent series of 105 patients from MD Anderson, most patients presented with advanced stage (T3/T4) disease and 98% of the patients were node negative. Thirty percent of the patients developed distant metastases, 40% of the patients had PNI, and 65% of the patients treated with postoperative radiation eventually developed recurrence. A significant survival advantage was found for patients treated with surgery and postoperative radiation over other treatments.⁵

Table 16.2 AJCC Staging for Epithelial Malignancies of the Maxillary Sinus

Neuroendocrine tumors of the sinuses have been divided into four subtypes: esthesioneuroblastoma (ENB), sinonasal undifferentiated carcinoma (SNUC), neuroendocrine carcinoma, and small cell carcinoma (SmCC). Because of prognosis, these have been divided into ENB and non-ENB categories. ENB has the best prognosis by far, followed by SNUC and neuroendocrine carcinoma; SmCC has the worst prognosis.7 Neuroendocrine tumors of the nasal cavity and paranasal sinuses typically involve the olfactory epithelium most frequently, but cases of maxillary ENB,⁸ SmCC,⁹ SNUC,¹⁰ and neuroendocrine carcinoma have been reported.¹¹ The Kadish staging system is used for ENB (Table 16.3). Because of the patterns of failure, the treatment for ENB is usually limited to local therapy, including surgery and/or radiation, and multimodality therapy including chemotherapy for non-ENB neuroendocrine tumors due to their propensity for distant metastasis.⁷ The optimal sequence for the management of SNUC is controversial; definitive radiation may increase the resectability of a tumor, but it carries a higher risk of radiation damage to surrounding structures. Craniofacial resection, radiation, chemotherapy, and treatment of the neck should all be considered because of the propensity for cervical and distant metastases.

Table 16.3 Kadish Staging for Olfactory Esthesioneuroblastoma

Nonepithelial soft tissue malignancies of the paranasal sinuses are rare and include many subtypes, many of which have only been published as case reports and series.1 Rhabdomyosarcoma is the most common paranasal sinus malignancy in childhood and is classified as parameningeal when involving the sinuses. It is divided into four subtypes: (1) embryonal, which presents early in life; (2) alveolar, which presents in the second decade of life; (3) pleomorph and; (4) mixed.¹ The embryonal form has the best prognosis. Sinonasal rhabdomyosarcoma presents in adults as well, but much less frequently. Prognosis is worse than in children, with a 5-year survival rate of 30% for adults compared with approximately 70% for children, according to a study of 171 patients and literature review in Italy.¹² However, this may represent differences in histologic subtypes and treatment regimens. Multimodality therapy is required for the treatment of these aggressive tumors; chemoradiation is the treatment of choice for advanced tumors, with surgical intervention for residual disease. Early stage tumors may be resected initially if there is no skull base invasion; complete excision is possible, and cosmetic deformity is minimal.¹³

Sinonasal tract mucosal malignant melanoma (STMMM) may have an appearance similar to that of neuroendocrine and soft tissue tumors described above, but immunohistochemical stains are positive for S-100, melan A, tyrosinase, and HMB-45. It is a rare tumor that accounts for only up to 2% of all melanomas and 4% of head and neck melanomas; it typically presents in the sixth to seventh decades of life. Compared with other melanomas and mucosal melanomas, it has a poorer prognosis, with a 5-year survival rate of only 20 to 40% and a high propensity for distant metastasis (> 50%). Several staging systems have been proposed for STMMM, including the widely used system proposed by Ballantyne, which classifies localized melanomas (stage I), those with cervical lymphadenopathy (stage II), and those with distant metastases (stage III),¹⁴ and the AJCC maxillary sinus staging system⁴ (Table 16.1). A recent publication from the MD Anderson Cancer Center reported a 5-year survival rate of 27.3% for tumors specifically within the maxillary sinus. Treatment is typically multimodality, involving surgical resection, postoperative radiation, and sometimes chemotherapy. However, in the MD Anderson series, overall survival was not improved with radiation chemotherapy, or immunotherapy, although locoregional recurrence was less in patients treated with > 54 Gy than in patients treated with 30 to 50 Gy.¹⁵

Benign and malignant tumors of odontogenic origin can also involve the maxillary sinus via extension from the maxillary alveolus. They may arise at any age and are classified into three categories by the World Health Organization according to the odontogenic tissue of origin.¹⁶ Tumors may present with similar signs and symptoms to other maxillary sinus tumors, but may also present with dental symptoms including alveolar swelling or pain, loose teeth, or change in occlusion. Although benign odontogenic tumors and cysts grow slowly, malignant tumors may present more rapidly and with pain or paresthesias. Odontogenic tumors vary in radiographic appearance depending on their origin, but they are based on erupted or unerupted maxillary teeth. The most common odontogenic tumor is the odontoma, a well-differentiated tumor based on mesenchymal and epithelial tooth elements. It is treated with simple removal, has no malignant potential, and does not recur. Ameloblastoma is the second most common tumor of odontogenic origin, is epithelial in origin, and is aggressively invasive. It is more common in the mandible than in the maxilla. Treatment is excision along with a rim of normal tissue due to its high rate of recurrence.¹⁶ Keratocysticodontogenic tumors, formerly known as odontogenickeratocysts, are aggressive, recurrent parakeratinized epithelial cysts that may occur sporadically or be associated with Gorlin syndrome. Aggressive surgical treatment may be required for cure.

Numerous metastatic tumors to the paranasal sinuses have been described, most frequently from the kidney, and the maxillary sinus is the most frequently affected sinus.¹⁷ Endoscopic biopsy should confirm the diagnosis, and treatment should be directed at relieving symptoms. Hematopoietic malignancies, including lymphomas, may also arise within the sinonasal tract, including the maxillary sinus. The role of the surgeon is diagnostic, and treatment should entail expedient referral to a medical oncologist.

Prognosis

Tumors of the maxillary sinus commonly present with advanced stage because of minimal symptomatology until expansion beyond its boundaries. Ohngren noted in 1933 that tumors of the paranasal sinuses that arise superior to an imaginary line drawn from the medial canthus to the angle of the mandible had a worse prognosis than those arising inferior to the line. Poor prognostic factors in carcinomas of the maxillary sinus have been found to be advanced age, advanced T stage (T4), node positivity (associated with distant metastases), and male sex.^18,19 A study from Memorial Sloan-Kettering Cancer Center recently demonstrated that PNI is common in ACC, SCC, and SNUC (55, 60, and 30%, respectively). The study found that PNI is associated with positive margins, but its effect on survival is disputed.⁶ Field cancerization seen in other head and neck primaries appears to be less significant in sinonasal tumors. A review of 2475 patients treated for sinonasal head and neck SCC at Johns Hopkins University revealed 0.2% incidence of a second sinonasal primary cancer.20 In addition, although its role has not been defined, investigators at the MD Anderson Cancer Center found that in stage III/IV SCCs of the paranasal sinuses, response to induction chemotherapy was predictive of better prognosis and improved treatment outcome in patients treated with definitive surgical treatment or concurrent chemoradiotherapy.²¹ Local failure remains the most common cause of mortality in patients with maxillary sinus cancers; 5-year local control rates fall in the 55 to 60% range, and 5-year overall survival rate has been reported to be approximately 45% in a recent review of the literature.²²