Paranasal sinus cancer

INTRODUCTION — A range of malignancies can develop in the paranasal (maxillary, ethmoid, sphenoid, frontal) sinuses (figure 1). Adenocarcinoma and squamous cell carcinoma of the maxillary sinus and ethmoid sinus are the most common of these tumors.

The epidemiology, clinical presentation, diagnosis, and management of these tumors are discussed here. Tumors arising in the nasal cavity are discussed separately. (See "Cancer of the nasal vestibule" and "Tumors of the nasal cavity".)

EPIDEMIOLOGY AND RISK FACTORS — Cancers arising in the paranasal sinuses are rare, constituting approximately 3 percent of head and neck malignancies [1]. The majority of these tumors arise in the maxillary sinuses, and most of the remainder start in the ethmoid sinuses. Cancers of the sphenoid and frontal sinuses are extremely rare. Paranasal sinus cancers are more frequent in males than in females [1].

Factors associated with paranasal sinus cancers include [1,2]:

●Occupational exposures – Including leather, textile, wood dust, and formaldehyde.

●Air pollution [3].

●Tobacco smoke [4].

●Viruses – Human papillomavirus (HPV) infection has been associated with paranasal sinus cancer, with some evidence suggesting that it may be involved in the malignant degeneration of inverted papilloma of the paranasal sinus, a rare, usually benign condition [5,6]. Correlations have also been suggested between Epstein-Barr virus (EBV) infection and sinonasal tract lymphomas [7,8].

PATHOLOGY — Approximately one-half of paranasal malignancies are squamous cell carcinomas, and most of the remainder are adenoid cystic carcinomas, adenocarcinomas, or mucoepidermoid carcinomas [9,10]. A wide range of other tumors can originate in this region, including undifferentiated carcinoma, angiosarcomas, rhabdomyosarcomas, lymphomas, olfactory neuroblastomas (esthesioneuroblastomas), melanomas, and meningiomas. (See "Pathology of head and neck neoplasms".)

CLINICAL PRESENTATION — Paranasal sinus malignancies tend to be asymptomatic or have nonspecific sinonasal symptoms that may mimic benign disease until they invade adjacent structures. Thus, most patients have advanced disease by the time the diagnosis is established [1,11,12].

The most common symptoms include facial or dental pain, nasal obstruction, and epistaxis [1,12]. When symptoms of persistent nasal discharge and epistaxis occur in patients over age 40, cancer of the paranasal sinuses, nasal vestibule, or nasopharynx should be included in the differential diagnosis. (See "Epidemiology, etiology, and diagnosis of nasopharyngeal carcinoma", section on 'Clinical presentation'.)

Less common symptoms include cranial neuropathy (especially abnormalities of extraocular movements or trigeminal hypesthesia), chronic sinusitis, facial edema, vision loss, headache, rhinorrhea, and hyposmia. A classic triad of facial asymmetry, palpable/visible tumor in the oral cavity, and visible intranasal tumor occurs in 40 to 60 percent of patients with advanced disease [13].

Symptoms and signs depend upon the involved site and extent of disease. The bony structures between the nasal cavity, sinuses, orbits, and cranial vaults are thin and offer little resistance to cancer spread.

●In the ethmoid sinus, locally advanced lesions may extend into the anterior cranial fossa via the cribriform plate or into the orbit through the lamina papyracea. This may result in anosmia or displacement (typically upward and/or outward) of the globe.

●In the sphenoid sinus, disease may directly extend through the lateral bony wall into the cavernous sinus where cranial nerves III, IV, VI, V1, and V2 travel. It may also invade the middle cranial fossa directly or via the infraorbital nerve. Affected patients may complain of diplopia, blurred vision, proptosis, paresthesias in the distribution of the trigeminal nerve, or trismus if the pterygoid musculature is invaded. Inferior extension into the oral cavity may also cause painful loose teeth.

DIAGNOSIS AND STAGING

Initial evaluation — The diagnosis of a paranasal sinus malignancy requires tissue for histologic evaluation and the identification of the paranasal sinus as the site of tumor origin. If a paranasal lesion is suspected, the history and physical examination should include close attention to the signs and symptoms (such as cranial nerve involvement) due to orbital extension or base of skull involvement.

The limited anatomic access of the paranasal sinuses makes early diagnosis difficult. Endoscopic examination is generally necessary to obtain a biopsy for tissue diagnosis and to assess the extent of local disease, unless there is tumor protruding into the nasal or oral cavity.

Lesions involving the maxillary sinus can be biopsied intranasally or through the gingivobuccal sulcus if the tumor extends through the anterior maxilla. Adequate examination and biopsy may require general anesthesia. Ethmoid sinus lesions are biopsied through an endoscopic or transnasal approach in the operating room, as are frontal sinus malignancies via the frontal recess. Frontal sinus trephination is rarely necessary.

Staging — Imaging studies provide important information for staging and treatment planning. Typically, both computed tomography (CT) and magnetic resonance imaging (MRI) are performed and are complementary in evaluating disease extent and in distinguishing tumor from infection, retained secretions, and granulation of scar tissue. CT offers superior definition of bone and bone invasion, while MRI gives superior soft tissue delineation and allows for visualization of cranial nerves, especially when they are involved with disease [14,15].

The eighth (2017) tumor, node, metastasis (TNM) staging system developed by the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC) defines separate T staging for tumors of the maxillary and ethmoid sinuses (table 1) [16]. There is no standard staging system for frontal or sphenoid sinus tumors. (See "Overview of the diagnosis and staging of head and neck cancer".)

Regional lymph node metastases are uncommon with early-stage disease that is confined to the sinuses [17]. The retropharyngeal nodes comprise the first echelon of lymphatic drainage for sinus malignancies. Other regional nodes that are commonly involved are the periparotid, level 1B, and level 2 nodes (figure 2) [18]. The incidence of lymph node involvement increases as tumors extend locally to adjacent sites, especially with extension into the oral cavity. Interestingly, one large series found higher rates of cervical lymph node involvement with T2 rather than T3 or T4 tumors of squamous cell histology [11]. This finding is due to the unique staging of maxillary sinus cancer, where T2 lesions are those that extend into the hard palate or nasal cavity. These areas have a richer lymphatic plexus and act more like oral cavity cancers, with a higher rate of occult metastases.

Distant metastases are uncommon at presentation. The lung, liver, and bone are the sites most frequently involved when distant metastases occur after treatment or are present at diagnosis. Chest imaging with CT can be considered clinically indicated, while positron emission tomography (PET)/CT should be considered for stage III or IV disease at presentation [11,19,20].

SQUAMOUS CELL CARCINOMA AND ADENOCARCINOMA

General approach to management — There are no randomized trials that define the optimal treatment for paranasal cancers because of the rarity of these tumors and because of their heterogeneity in both histology and site of origin. The available data are derived from single-institution, observational series. The approach described here is consistent with guidelines from the National Comprehensive Cancer Network (NCCN) [21].

Paranasal sinus cancers generally invade locally early in their natural history and have a high tendency for local recurrence. Local recurrence rates following resection are high in the absence of postoperative radiation therapy (RT), even when the original resection is thought to have been complete.

●For patients with early (stage I/II) disease (table 1), complete surgical resection is the initial step in management. Postoperative RT is indicated for those who are at increased risk of local recurrence (eg, positive or uncertain surgical margins, unfavorable histology, perineural invasion). (See 'Surgery' below and 'Radiation therapy' below.)

●For patients with locally advanced (stage III/IV) disease, initial surgical resection is preferred as the initial therapy. Postoperative adjuvant RT is indicated because of the high risk of local recurrence. (See 'Surgery' below and 'Radiation therapy' below.)

●RT or chemoradiotherapy are alternatives for patients who are not candidates for a definitive surgery.

Surgery — Surgical resection is indicated for all operable adenocarcinomas and squamous cell carcinomas arising in the maxillary or ethmoid sinuses (T1 to T4), regardless of nodal status.

Resection is often limited by tumor involvement that can result in damage to critical structures such as the eyes, brain, and cranial nerves. Advances in surgical techniques have resulted in better functional reconstructions and improved quality of life [22], and the decision of whether or not to operate depends upon the balance between survival, morbidity, and function [23-25].

Management of the orbit — Preoperative computed tomography (CT) and magnetic resonance imaging (MRI) are essential to evaluate the extent of disease and orbital involvement and to plan the surgical approach. Tumor adjacent to the periorbita (the dense periosteum surrounding the globe) was the most sensitive predictor of orbital invasion for both CT and MRI in a small study of patients with advanced sinus malignancy [26-28]. A European position paper on endoscopic management of paranasal sinus tumors suggested that orbital fat signal-suppressed (short tau inversion recovery [STIR]) images by MRI may improve detection of orbital fat infiltration [29].

Three stages of orbital invasion have been described: grade I, destruction of the medial orbital wall; grade II, invasion of the periorbital fat, extraconal; and grade III, invasion of the medial rectus, optic nerve, bulb, or eyelid skin, which implies breaching of the periorbita/periosteum. Orbital exenteration has been advocated only for those patients who present with grade III invasion; however, frozen section at the time of surgery is often necessary to confirm whether or not tumor has transgressed the periosteum [30].

Orbital exenteration does not improve survival for patients with advanced sinus malignancy that does not completely transgress the dense periorbita [31]. Although recurrence in the orbit has been associated with poor prognosis [32-34], most head and neck surgeons favor orbital preservation with periosteal resection in the case of incomplete periosteal invasion since this yields comparable survival and can maintain a functional eye [31,32,35-37]. Orbital exenteration is indicated for gross transgression of the periorbita into the intraconal fat or orbital apex. Studies also suggest that the orbit-preservation rate can be improved with strategies that incorporate neoadjuvant chemotherapy [38-41].

Endoscopic resection — Advances in surgical technique have led to an increasing use of image-guided endoscopic approaches for the resection of sinonasal tumors [22]. These techniques have largely replaced open approaches in many academic centers.

Image-guided endoscopic techniques are a multidisciplinary collaboration of otolaryngologists and neurosurgeons. They provide superior visualization, with angled endoscopes affording exposure around anatomic corners. The endoscopic method employs piecemeal tumor removal and was initially criticized for its inability to achieve an en bloc resection. Clear surgical margins (regardless of the surgical method) are a critical factor for tumor control, and both open and endoscopic techniques appear equally effective in this aspect. Endoscopic sinus surgery has been used both alone and in combination with open craniofacial surgery.

These endoscopic approaches may offer significant advantages in terms of a lower frequency of surgical complications and decreased morbidity. Advantages include lack of facial incisions, craniotomies, or facial bone osteotomies; decreased neurovascular structure manipulation; early tumor devascularization; access to deeply seated lesions; decreased hospital stay and pain; and faster recovery [29]. Brain retraction is avoidable, so postoperative brain edema and possible encephalomalacia are circumvented [42]. Nasal crusting can be a complication of both endoscopic and open approaches. This is related to disruption of the sinus mucosal lining as well as to postoperative radiation.

Endoscopic sinus surgery has also been utilized for palliation of symptoms (epistaxis, nasal obstruction, etc) in advanced sinonasal malignancies [43]. Contraindications to a pure endoscopic approach include tumors with extensive dural involvement or extension into facial or orbital soft tissues.

Several series that included patients with a variety of histologic tumor types have found that endoscopic techniques can be applied to patients with locally advanced lesions [44,45]. Similar oncologic results have been documented in numerous studies compared with traditional open approaches. As an example, one study that used propensity score analysis to control for differences in patient comorbidities and tumor size reported shorter lengths of stay but similar recurrence rates and survival rates with endoscopic approaches when compared with open approaches [46]. In another cohort study, patients undergoing endoscopic resection reported improved sinus-specific quality of life that was sustained over two years [47].

Reconstruction — The goal of surgical and prosthetic reconstruction is to replace the form and function of facial and anterior skull base defects caused by surgery. Advances in tissue transfer techniques (particularly microvascular free flaps) provide reconstructive options in addition to maxillofacial prostheses. Optimal esthetic, functional, and quality of life outcomes are superior with combined approaches rather than single techniques [48].

Key issues with the management of maxillectomy defects include reconstruction of the orbital floor in order to support globe position, reconstruction of the palatal surface to separate nasal contents and to provide framework for dental rehabilitation, and reestablishment of facial symmetry [27]. Contemporary reconstruction techniques utilize custom 3D modeling (virtual surgical planning [VSP]) as well as intraoperative, image-guided navigation to ascertain position and symmetry [49]. For patients who have undergone orbital exenteration/clearance, temporalis muscle or temporoparietalis flaps can be used to line the cavity. (See "Management of acquired maxillary and hard palate defects" and "Mandibular and palatal reconstruction in patients with head and neck cancer".)

Complications — Serious postoperative complications associated with craniofacial resection can include meningitis, hemorrhage, wound infection and abscess, cerebrospinal fluid leak, pneumocephalus, trismus, and blindness [50,51].

Surgical mortality and complication rates can be significant. A multi-institution analysis of 1193 patients who underwent open craniofacial resection observed postoperative mortality and complication rates of 5 and 36 percent, respectively [51]. The risk of complications and mortality is increased substantially for patients older than 70 years [52].

State-of-the-art image-guided endoscopic/endonasal approaches to skull base malignancies are associated with decreased postoperative morbidity and mortality. In a review of 800 patients, cerebrospinal fluid leak was the most common complication (16 percent). All but one patient was repaired endoscopically. The overall incidence of cerebrospinal fluid leak in this series decreased significantly with the use of vascularized skull base reconstruction. Overall mortality was 0.9 percent [53]. Another study of 1000 patients who underwent endoscopic skull base surgery showed an overall infection rate of 1.8 percent [54].

Radiation therapy — Paranasal sinus cancers have a high tendency for local recurrence in the absence of postoperative RT, even when the original resection was thought to be complete. Although there are no randomized trials, postoperative RT is widely used and has been effective in decreasing the incidence of local recurrence [22].

The use of RT as primary therapy without surgery is generally limited to patients with unresectable disease as well as to those who are medically unsuited for major surgery.

Contemporary RT techniques — Advances in RT techniques have led to the development of highly conformal techniques that permit the delivery of therapeutic doses of radiation to paranasal sinus tumors while minimizing the dose of radiation to uninvolved normal tissues.

Widely used conformal techniques include three-dimensional conformal RT and intensity-modulated RT [55]. Charged particle irradiation (proton beam, carbon ion) may offer additional advantages for delivering maximal tumor doses while minimizing radiation to the retina and brain compared with photon-based therapy [56,57]. However, there are no prospective comparisons, and the data in these retrospective analyses often used older RT techniques. (See "General principles of radiation therapy for head and neck cancer", section on 'Three-dimensional conformal RT'.)

For patients who have undergone complete resection of their tumor and have adverse prognostic features (ie, perineural infiltration or adenoid cystic carcinoma), the dose of postoperative radiation is generally approximately 60 Gy when given on a once-daily schedule. For patients with positive tumor margins and for those that are unresectable, the prescribed doses are approximately 66 and 70 Gy, respectively, when given in 2 Gy fractions once daily. There are no randomized trials that define the dose of radiation in these patient populations, and these schedules are based upon more-extensive data from other head and neck cancers. (See "Definitive radiation therapy for head and neck cancer: Dose and fractionation considerations", section on 'Paradigms of dose and fractionation modification'.)

Concomitant chemotherapy and radiation is an alternative to RT alone in those patient with unresectable disease or adverse prognostic features (perineural infiltration, positive margins). (See 'Chemotherapy' below.)

Complications — The incidence of radiation retinopathy is strongly correlated with the dose of radiation to the retina.

This relationship was analyzed in a study of 186 patients who received a significant dose of radiation to the retina as part of curative therapy for head and neck cancer. Approximately two-thirds of the patients in that series were treated for cancer of the nasal cavity or paranasal sinuses, and most of the remainder had a primary nasopharyngeal cancer [58]. Radiation retinopathy developed in 31 eyes in 30 patients, resulting in blindness in 26 and decreased vision in the other five eyes. Radiation retinopathy developed in 25 of the 30 eyes that received 60 Gy or more to the retina. In contrast, only 3 of 72 eyes (4 percent) that received less than 50 Gy developed radiation retinopathy.

Observational series indicate that these conformal techniques have comparable efficacy to earlier series but with a substantially decreased incidence of blindness and other serious eye complications [22].

●As an example, 85 patients with paranasal sinus tumors were treated postoperatively over an 18-year period at a single institution [59]. Among the 53 patients treated with contemporary planning and conformal treatment techniques, there were no grade 3 or worse eye complications. Disease control was comparable to other series.

●In another series, 84 patients were treated with intensity-modulated RT, including 73 immediately following surgery and 11 for a local recurrence [60]. The five-year rates of overall and disease-specific survival were 59 and 67 percent, respectively, which was similar to that in other series. There were no cases of blindness, although one patient developed radiation-induced retinopathy and neovascular glaucoma.

Other serious complications of RT can occur include osteoradionecrosis and brain necrosis. (See "Management of late complications of head and neck cancer and its treatment" and "Delayed complications of cranial irradiation", section on 'Brain tissue necrosis'.)

Chemotherapy — Chemotherapy has been incorporated as a component of multimodality therapy with RT and/or surgery in a variety of ways. However, there are no randomized trials in patients with paranasal sinus cancers, and no definitive conclusions can be drawn about the impact of chemotherapy on outcomes.

Based on results in other squamous head and neck cancers, our approach is to consider adding chemotherapy to RT in two settings: for unresectable but curative-intent therapy in good performance status patients, and in the postoperative setting with positive margins or extracapsular extension of tumor. (See "Locally advanced squamous cell carcinoma of the head and neck: Approaches combining chemotherapy and radiation therapy".)

Several relatively large series provide an illustration of the range of outcomes:

●In a prospective study, cisplatin-based chemotherapy was given to 49 patients, including 38 with T3 or T4 disease (table 1), all of whom had resectable, previously untreated disease [61]. Chemotherapy was followed by surgery and postoperative RT in 19 of 21 responders and 23 of 28 nonresponders. The three-year overall and event-free survival rates were 69 and 57 percent, respectively. An earlier, smaller series using chemotherapy as induction yielded similar results [62].

●In a series of 39 patients with stage IVB disease (table 1), 35 patients were managed with chemotherapy plus definitive RT and four were treated with definitive RT alone [63]. Management did not include surgical resection. With a median follow-up of over seven years, the five-year disease-free and overall survival rates were approximately 15 percent.

●Another series reported the results of 46 patients treated with induction chemotherapy followed by surgery and RT or concomitant chemotherapy with RT in 22 patients [64]. The remainder had definitive RT or concomitant chemotherapy and RT with surgery for salvage. Overall 67 percent had a partial to complete response, 9 percent had stable disease, and 24 percent had progressive disease. The two-year survival was 77 percent for patients who responded and 36 percent for those with progressive disease on induction.

●In a series of 41 patients with stage III, IVA, and IVB disease, patients were managed with surgery plus postoperative RT or chemoradiation, or concomitant chemoradiation without surgery [65]. With a median follow-up of over six years, the median progression-free survival duration was 45 months, and the five-year overall survival rate was 65 percent. Outcomes were better in those patients who had undergone surgery.

●In a retrospective review of 179 Italian patients treated between 1996 and 2000, chemotherapy was used in the induction setting or concomitant setting (three doses of high-dose cisplatin). Chemotherapy used in this setting was associated with a nonstatistically significant benefit in overall survival of mostly T4N0 patients [66].

Management of the neck — Cervical lymph node metastases are uncommon at presentation. In a series of 704 consecutive patients with paranasal sinus cancer treated over a 25 year period, 5 percent had cervical node disease at presentation [11]. The cumulative incidence of lymph node involvement either at presentation or within five years was approximately 14 percent.

Neck dissection and postoperative RT are recommended for all patients with cervical lymph node involvement, either at presentation or subsequently, if relapse occurs in the cervical lymph nodes. (See "Management of the neck following definitive radiotherapy with or without chemoradiotherapy in head and neck squamous cell carcinoma".)

Prophylactic treatment (neck dissection or RT) of the N0 lymph-node-negative (table 1) neck is controversial [22]. For patients who present without neck node involvement, the risk of subsequent recurrence in the neck has ranged from 3 to approximately 30 percent in different series [67]. Although prophylactic neck dissection or irradiation can reduce the incidence of neck recurrence, most such relapses are associated with other sites of involvement, and it is not clear that there is an impact on overall survival.

Factors weighing against prophylactic treatment include the low incidence of subsequent relapse, the observation that most such relapses are associated with other sites of involvement, and the lack of impact on overall survival from prophylactic treatment.

For patients who present with a T3 or T4 primary lesion, the risk of nodal involvement at presentation or subsequent neck node relapse increases substantially. Prophylactic/elective selective neck dissection has acceptable morbidity and provides valuable staging and prognostic information. In a Surveillance, Epidemiology, and End Results (SEER) database study of 927 patients with maxillary sinus squamous cell carcinoma and clinically negative lymph nodes, the five-year hazard of death was reduced by elective neck dissection for those with T3 tumors [68]. Thus, our approach is to suggest prophylactic neck treatment for patients with T3 or T4 disease. For patients who will be managed with definitive resection of the primary site, we suggest ipsilateral neck dissection, and for those who are managed with definitive RT (with or without chemotherapy), we suggest prophylactically irradiating the ipsilateral node-negative (N0) neck.

Recurrent and metastatic disease — Patients with locoregionally recurrent disease are treated with multimodality therapy, including resection, reirradiation, and concurrent chemotherapy and RT. Distant metastatic disease is typically treated with chemotherapy alone. There are insufficient data to differentiate the management of these patients from that of other head and neck cancer cases [69]. (See "Treatment of locally recurrent squamous cell carcinoma of the head and neck" and "Treatment of metastatic and recurrent head and neck cancer".)

Prognosis — Results in large series vary depending upon case mix and the time period that was analyzed. In general, five-year overall survival rates around 50 percent have been reported [11,12,70-75], with significant variation depending upon stage and histology (table 2A-B). Factors associated with a better prognosis include lower T stage, the absence of lymph node involvement, and adenocarcinoma rather than squamous cell carcinoma or undifferentiated carcinoma. Primary tumors arising in the maxillary sinus appear to have a better prognosis than those arising in the ethmoid sinus. In a SEER database review, tumors of the nasal cavity had the highest five-year disease-specific survival (67.1 percent) while tumors of overlapping sinus sites had the lowest (37.6 percent) [76,77].

Like many other cancer sites, there are racial disparities in sinonasal carcinoma. In a review of over 4000 patients, Black individuals and Hispanic individuals were at risk for poorer disease-specific survival [78]. Others found that that difference in racial survival in sinonasal cancer is related to two factors: overall stage and the use of standard-of-care treatment appropriate for stage [78,79].

Posttreatment follow-up — Patients should be monitored for evidence of recurrence following treatment, although a survival benefit has not been demonstrated for posttreatment surveillance (table 3). In general, the intensity of follow-up is greatest in the first two to three years, which is the period of greatest risk for disease recurrence. (See "Posttreatment surveillance of squamous cell carcinoma of the head and neck".)

OTHER TUMOR TYPES

Human papilloma virus-related multiphenotypic sinonasal carcinoma — Human papillomavirus (HPV)-related multiphenotypic sinonasal carcinoma (HMSC) is a sinonasal malignancy that displays strong and diffuse p16 positivity as well as high-risk HPV, usually HPV 33. HMSC has clinical and histologic features similar to those seen with sinonasal adenoid cystic cancer [80,81]. (See 'Adenoid cystic carcinoma' below.)

Adenoid cystic carcinoma — Adenoid cystic carcinomas can arise in the minor salivary glands of the paranasal sinuses. These tumors tend to spread locally through bony destruction and perineural and perivascular invasion. Adenoid cystic carcinomas have characteristically high rates of local recurrence and distant metastases (typically lung and bone), which can occur as late as 10 to 20 years following initial treatment. (See "Salivary gland tumors: Epidemiology, diagnosis, evaluation, and staging" and "Salivary gland tumors: Treatment of locoregional disease".)

Primary surgery followed by radiation therapy (RT) is recommended [82].

Sinonasal undifferentiated carcinoma — Sinonasal undifferentiated carcinoma (SNUC) is a rare, poorly differentiated, rapidly growing malignancy that arises from the mucosa of the nasal cavity or paranasal sinuses. (See "Pathology of head and neck neoplasms", section on 'Sinonasal undifferentiated carcinoma'.)

SNUC is associated with a poor prognosis, generally presenting with locally advanced disease and a high frequency of distant metastases, even when local disease control can be obtained. There are no clinical trials to guide treatment for patients with SNUC, and data are derived either from small single-institution series, meta-analyses of such reports, or larger database studies. (See "Tumors of the nasal cavity", section on 'Sinonasal undifferentiated and small cell carcinoma'.)

As an example, a National Cancer Database (NCDB) study identified 435 patients with SNUC between 2004 and 2012 [83]. Approximately 60 percent of cases arose in the paranasal sinuses, the remainder arose in the nasal cavity; only 6 percent had T1 or T2 lesions at presentation. The cumulative five-year survival rate was 42 percent. Multivariate analysis indicated that trimodality therapy (optimal surgical resection combined with chemoradiotherapy) was associated with better outcomes than surgery or surgery plus RT alone. A similar study of 460 patients using the NCDB found the best survival in those undergoing surgery with postoperative chemoradiotherapy [84]. However, no patient undergoing surgery and adjuvant treatment with positive surgical margins survived to five years. These results suggest that surgery should be limited to patients in whom negative margins can be reliably obtained.

Single-institution series support a role for trimodality therapy including maximal surgical resection and adequate radiation dosing [85-89]. The optimal sequencing of these therapies is not known and may differ with patient presentation. Some experts offer surgical resection followed by chemoradiotherapy, while others offer induction chemotherapy followed by surgery and/or chemoradiotherapy. As an example, one observational study suggested that response to induction chemotherapy could be used to select patients for definitive therapy with either surgery of chemoradiotherapy [90]. This strategy has also been proposed for tumors at all head and neck sites, not just the paranasal sinus, with the vast majority of supporting data in patients with squamous cell carcinoma. However, it is a potentially risky strategy for patients with T1 and T2 primaries, especially SNUCs, which often do not respond to drug therapy, as it runs the risk of converting resectable disease into unresectable disease for nonresponders to chemotherapy. Further details on the use of induction chemotherapy in SNUC are discussed separately. (See "Tumors of the nasal cavity", section on 'Induction chemotherapy'.)

Inverted papilloma — Inverted papilloma is a benign, locally aggressive neoplasm that is associated with squamous cell carcinoma in approximately 5 percent of cases [91,92].

Treatment for inverted papilloma is primarily surgical resection, which is increasingly accomplished using endoscopic approaches [93-95]. RT is added if it is associated with squamous cell carcinoma or if it is incompletely resected. Local recurrence is common. (See "Pathology of head and neck neoplasms", section on 'Schneiderian papillomas'.)

Olfactory neuroblastoma — Olfactory neuroblastomas, also known as esthesioneuroblastomas, arise from the olfactory epithelium and invade into the paranasal sinuses. The management of olfactory neuroblastoma is discussed separately. (See "Olfactory neuroblastoma (esthesioneuroblastoma)".)

Lymphoma — Lymphoma of the paranasal sinuses is most commonly a diffuse large B-cell lymphoma, though nasal-type natural killer (NK)/T-cell non-Hodgkin lymphoma is also seen. Combination chemotherapy and RT is suggested; the role of central nervous system prophylaxis is debated [96-99]. (See "Clinical presentation and initial evaluation of non-Hodgkin lymphoma", section on 'Head and neck'.)

Melanoma — Sinonasal melanoma of the paranasal sinus has a particularly poor prognosis [100]. Primary treatment is surgical, and postoperative RT is sometimes used for close or positive margins [101]. (See "Locoregional mucosal melanoma: Epidemiology, clinical diagnosis, and treatment", section on 'Mucosal melanoma of the head and neck'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Head and neck cancer".)

SUMMARY AND RECOMMENDATIONS

●Incidence – Paranasal sinus cancers are rare tumors that encompass multiple histologies. (See 'Epidemiology and risk factors' above and 'Pathology' above.)

●Clinical presentation – Paranasal sinus cancers tend to be asymptomatic or have nonspecific sinonasal symptoms that mimic benign disease until they invade adjacent structures. Most patients have advanced disease by the time the diagnosis is established. (See 'Clinical presentation' above.)

●Approach to management – Treatment needs to incorporate information about both histology and anatomic site of origin. (See 'Pathology' above and 'General approach to management' above.)

●Management of adenocarcinoma and squamous cell carcinoma – Adenocarcinoma and squamous cell carcinoma of the maxillary sinus and ethmoid sinus are the most common of these tumors. Aggressive surgical resection remains the mainstay of treatment. Combined modality approaches (radiation therapy [RT], chemotherapy) have been added to improve local control for patients at high risk of recurrence. (See 'Squamous cell carcinoma and adenocarcinoma' above.)

•For patients with early (stage I or II) paranasal sinus cancer, we recommend surgical resection (Grade 1B). For patients who are not candidates for a major surgical procedure, definitive intensity-modulated RT is an appropriate alternative. While proton therapy has some theoretical advantages in dose distribution, there are little data to support widespread use. We suggest postoperative RT for patients with T1 and T2 lesions with close or positive margins, high-grade histology, and other adverse prognostic features, including perineural, lymphatic, and perivascular invasion (Grade 1B).

•For patients with locoregionally advanced (stage III and IV) paranasal sinus cancer, we recommend a combined modality approach that includes surgical resection followed by adjuvant RT, rather than surgical resection or RT alone (Grade 1B).

•For patients with stage III and IV disease and a clinically negative neck (N0), we suggest prophylactic treatment of the neck nodes with either lymph node dissection or RT (Grade 2C). (See 'Surgery' above and 'Radiation therapy' above and 'Management of the neck' above.)

•For patients with clinical involvement of the cervical lymph nodes, we recommend neck dissection with postoperative RT (Grade 1B). (See 'Management of the neck' above.)

•Induction and/or concurrent chemoradiation therapy approaches may have a role in the management of patients with paranasal sinus cancer. However data are too limited to make definitive recommendations, and such treatment should be undertaken only after joint surgical, radiation oncology, and medical oncology evaluation. (See 'Chemotherapy' above.)

●Treatment of other histologies – Management of patients with other tumor histologies is tumor specific. (See 'Other tumor types' above.)