History of the Procedure In 1854, Ward first described schneiderian papillomas (SPs) of the nose (ie, sinonasal papilloma).

These benign lesions were named in honor of C. Victor Schneider who, in the 1600s, demonstrated that nasal mucosa produces catarrh and not CSF and identified its origin from the ectoderm. Kramer and Som classified SPs as true nasal [2] neoplasms and described them as true papillomas, distinguishing them from inflammatory nasal polyps. Ringertz was the first to identify the tendency of SPs to invert into the underlying connective tissue stroma, which differs [3] from other types of papillomas. Problem SPs represent a unique group of benign lesions that arise from the mucosal surfaces of the sinonasal tract. These neoplastic lesions are readily identified by their histopathologic characteristics. SPs, commonly called inverting papillomas, have many synonyms (eg, epithelial papilloma, transitional cell papilloma, squamous cell papilloma). Unlike the rest of the upper respiratory tract mucosa, the sinonasal mucosa is ectodermal in origin, derived originally from the stomodeum (ie, primitive mouth) in the fourth week of gestation. Sinonasal mucosa is continuous with the mucosal lining of the nasopharynx, which is of endodermal origin but is of identical histology. Lesions with similar histologic and biologic features infrequently arise outside the nasal cavity. These represent an ectopic migration of the schneiderian membrane during embryogenesis. Extrasinonasal sites where SPs may arise include the pharynx, the lacrimal sac, and the middle-ear space. Similar to SPs, these extranasal papillomas may recur after inadequate resection. For more information, please see Medscapes Head and Neck Resource Center. Epidemiology 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. Etiology 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.
[1]

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 [4] in situ hybridization technique, demonstrated HPV 11 in 2 of their patients. Weber et al confirmed these findings in a study of 21 patients using in situ DNA hybridization, and 16 patients were [5] found to have HPV DNA. 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. Pathophysiology 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 [6] non-endoscopic transnasal excision alone (58%), for which the recurrence rates are significantly higher. 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 [7] between the recurrence and the development of malignancy. 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. Presentation 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.

Contraindications Endoscopic sinus surgery is contraindicated for tumors that arise from the lateral wall of the maxillary sinus and frontal sinus. Imaging Studies Preoperative radiographic assessment of sinonasal papillomas (SPs) plays an important role in determining extension of the disease and involvement of adjacent structures; hence, choosing the appropriate approach is important. Coronal and axial contrast-enhanced CT is considered the study of choice for assessing intranasal lesions. o As many as 75% of patients with SPs have evidence of various degrees of bone destruction. These may include thinning, remodeling, erosion, and (less commonly) sclerotic bony changes. The presence of bone destruction alone does not indicate dedifferentiation into malignancy from the SP. CT scanning is more precise than conventional radiography for identifying the areas of bony erosion. o With CT scanning, differentiating a papillomatous lesion from inspissated mucous, mucoperiosteal thickening, or polyps that result from the obstruction of a sinus drainage pathway is sometimes difficult. MRI is an alternative study that is superior to CT scanning in distinguishing papillomas from inflammation and for providing better delineation of the lesions in contrast to surrounding soft tissue. o SPs have a heterogeneous appearance on MRI. o On T1-weighted images, sinonasal papillomas appear slightly hyperintense to muscle; however, on T2-weighted images, SPs have intermediate signal intensity. o A convoluted cerebriform pattern on T2 and enhanced T1-weighted MRIs for inverting papilloma may be potentially distinctive in 80% of cases, according to Ojiri et al. o Inflammatory polyps and inspissated material in the sinuses secondary to obstruction by the papilloma are hyperintense on T2-weighted images. o Because of the findings listed above, MRI can more accurately define the true extent of the lesion and can help in treatment planning.

Diagnostic Procedures Biopsy is the most important diagnostic tool when a sinonasal papilloma is suspected. If intracranial pathology may be manifesting in the sinonasal cavity (ie, encephalocele, meningocele, meningoencephalocele), perform imaging studies before biopsy.

Histologic Findings SPs can be divided into 3 histologic subtypes: inverted, fungiform, and cylindrical (columnar). Inverted papillomas have an endophytic growth pattern found almost exclusively on the lateral nasal wall; these account for 47% of all cases of SPs. On the contrary, fungiform papillomas constitute approximately 50% of sinonasal SPs and have an exophytic type of growth. They are found mainly on the nasal septum. Cylindrical papillomas are the rarest type (35%) and are also called oncocytic SPs. On gross examination, SPs originate from a narrow or broad-based stalk. Sinonasal papillomas have an irregular, friable appearance and bleed easily. On microscopy, the fungiform type is mainly composed of thick squamous epithelium and, less frequently, respiratory epithelium arranged in papillary fronds with exophytic type of growth. By comparison, the inverted type, which has an endophytic or inverted growth pattern, consists of thickened squamous epithelium admixed with mucocytes and intraepithelial mucous cysts. The cylindrical papilloma is

composed of multilayered epithelium with an eosinophilic cytoplasm among which intraepithelial mucin cysts are identified . Medical Therapy Recognition of the propensity for recurrence and the association with malignancy has led to the evolution of treatment of sinonasal papillomas (SPs). The role of medical therapy is limited; it is used mainly as an adjunct to specific complications such as sinusitis. Radiotherapy Radiation therapy is generally not indicated in the treatment of benign papillomatous lesions. It is ineffective in the treatment of SPs, and it carries the presumed risk of malignant transformation in an otherwise benign lesion. However, radiation therapy can be used in the treatment of advanced and biologically aggressive SPs of the sinonasal tract or in those patients in whom the morbidity of the radical surgery would be intolerable. In cases in which SPs are associated with squamous cell carcinoma, radiation therapy appears to be an effective adjunctive [8] procedure. Surgical Therapy Most clinicians agree that surgery is the treatment of choice for SPs. However, no consensus has been reached on the type or extent of surgical intervention. The 3 goals of an adequate surgical procedure are to (1) allow exposure sufficient for complete resection of the tumor, (2) provide an unobstructed view for postoperative surveillance of the cavity, and (3) minimize cosmetic deformities and functional disabilities. Early attempts to treat inverting papillomas with simple and conservative procedures frequently resulted in recurrence rates of 40-80%. Included among the conservative procedures were the intranasal approach (alone or combined with the Caldwell-Luc operation) and Denker rhinotomy. This high recurrence rate combined with the possibility of the multicentric origin of SPs led many surgeons to advocate aggressive early management with medial maxillectomy by using either lateral rhinotomy or midfacial degloving. A review of the surgical anatomy in the areas of recurrences show that the most common sites of recurrence are the lateral nasal wall in the middle meatus, the nasofrontal duct area, the supraorbital ethmoid cells, the region of the lacrimal fossa, and the infraorbital or prelacrimal recess of the maxillary sinus. Many surgeons consider lateral rhinotomy with en bloc ethmoidectomy and medial maxillectomy the treatment of choice for SPs. This surgical procedure is associated with a recurrence rate lower than that of other conservative procedures. Michaux first described the lateral-rhinotomy approach in 1848, and popularized it in Moure in 1902. [9] Wong and Heeneman refined the approach with 4 subtypes. In the last 10 years, increasing numbers of authors have reported on endoscopic resection of SP. When appropriately performed, these procedures have success and recurrence rates similar to those of open medial maxillectomy. In many institutions, endoscopic or endoscopy-assisted resection, including transnasal endoscopic medial maxillectomy (TEMM), tailored to the extent of disease is becoming a common treatment. The authors [10] recently reported on the anatomic basis for TEMM as an oncologic approach for sinonasal neoplasms. A recent meta-analysis and another systematic literature review support endoscopic approach as a favorable treatment [11, 12, 13] option compared with open approaches. Intraoperative Details

Lateral rhinotomy approach The lateral rhinotomy approach involves a curvilinear incision between the medial canthus and the dorsum of the nose. For this procedure, start the incision under the medial end of the eyebrow, extend the incision inferiorly between the medial canthus and the nasal dorsum and along the deep nasal-cheek groove adjacent to the ala of nose. Then, swing the incision up onto the floor of the nose. The incision includes the full thickness of skin down to the periosteum. A gentle W- or Z-plasty incision can be incorporated into the medial canthus region to help prevent postoperative webbing of the soft tissue. After the skin incision is made, elevate the periosteum to expose the medial orbital wall, the anterior maxillary wall up to the infraorbital foramen, and the pyriform aperture. The nasal bones can be retracted medially after medial and lateral osteotomies are performed. To achieve en bloc resection, perform osteotomies through the inferior and anterior aspects of the medial wall of the maxilla, through the medial wall of the orbit just inferior to the frontoethmoid suture line, and through the inferior orbital rim and orbital floor. By connecting these osteotomies, the specimen can be mobilized by using a heavy, curved Mayo scissors, which can be used separate the specimen from the posterior wall of the maxillary sinus. For medial maxillectomy, include the region of the lacrimal fossa, the infraorbital rim, and the prelacrimal recess of the maxillary sinus. Divide the lateral nasal wall along the floor of the nose. Amputate the middle turbinate below its superior attachment, and remove the entire lateral wall intact after its detachment from the rest of the infraorbital rim. To avoid epiphora, which is a common postoperative complication of this procedure, always incorporate dacryocystorhinostomy. Dacryocystorhinostomy can be accomplished by catheterization of the lacrimal duct by using an indwelling silicone tube (Guibor tube) or by incising the lacrimal sac vertically and sewing the edges to the adjacent tissues. The medial canthus is usually displaced from its insertion and should be fixed to prevent unsightly telecanthus. If the tendon elevated is attached to the periosteum, it resumes its normal position after careful closure of the periosteum. Sometimes, the tendon is transected and should be tagged and approximated at the end of the procedure. Transnasal wiring is required if the lacrimal crest and adjacent bone are included in the resection. Midfacial degloving approach An alternative, versatile, and recommended approach is midfacial degloving for total excision of the SP. This approach consists of lifting the soft tissue from the mid portion of the face by means of a sublabial incision. Four types of incisions are required in the midfacial degloving approach: (1) bilateral intercartilaginous incisions, (2) a complete septocolumellar transfixion incision, (3) bilateral sublabial incisions from the maxillary tuberosity to the tuberosity, and (4) bilateral pyriform aperture incisions extending to the vestibule. These incisions facilitate exposure of the pyriform aperture and the lateral nasal wall. En bloc resection of the lateral nasal wall is easy to perform, and it affords the possibility of extending the procedure to include the sphenoethmoidectomy and the medial orbital wall as dictated by the extent of the lesion. Advantages of this approach include no external scarring, good visibility of the operative field, and simultaneous bilateral exposure. In addition, the recurrence rate of SP excised by using the midfacial degloving procedure is similar to those of lateral rhinotomy and medial maxillectomy. As with the lateral rhinotomy, the midfacial degloving approach can be combined with the craniofacial approach to treat lesions involving the base of the skull or anterior cranial fossa.

The primary limitation of the midfacial degloving approach is when surgery is required for more extensive tumors that invade the supraorbital ethmoid cells or the frontal sinus, which require a separate incision. Septal translocation through a sublabial incision is another approach that shares the same advantages of the midfacial degloving approach. It provides wide exposure with no external scarring. Endoscopic medial maxillectomy Stammberger reported the first purely endoscopic approach for treatment of SP, which was performed in 15 patients in 1981. Since then, numerous authors have reported their experience with endoscopic or endoscopyassisted endonasal approaches. More than 500 reported cases have been treated with this technique. Most reported endoscopic resections have involved piecemeal resection of the inverting papilloma followed by piecemeal resection of the lateral nasal wall. Recent literature supports the concept of piecemeal resection or debulking of the intranasal component to then allow complete subperiosteal excision of all diseased mucosa around the origin. Different endoscopic surgical strategies can be used with reported success tailored to the extent of disease. In tumors limited to the middle meatus, the anterior and posterior ethmoids, or the sphenoethmoidal recess, limited resection (less than endoscopic medial maxillectomy) may be performed. This resection includes anterior ethmoidectomy with clearance of frontal recess, posterior ethmoidectomy, large middle antrostomy, sphenoidotomy, and partial or complete middle turbinectomy. This procedure can be done en bloc. Tumors that extend from the middle meatus into the maxillary sinus or that originate from the medial wall of the maxillary sinus should be treated with TEMM that includes resection of nasolacrimal duct to allow for complete removal of the medial maxilla. A recent anatomic study revealed that 65% of the volume of maxillary sinus falls bellow the attachment of inferior turbinate to the lateral nasal wall, and the nasolacrimal canal limits the [10] visualization and access to lateral and anterior maxillary sinus wall. This forms the basis for TEMM when the maxillary sinus is involved by the tumor. Tumors that originate from or that involve the posterolateral, anterior, or inferior wall of the maxillary sinus may be managed with extended endoscopic medial maxillectomy to include these areas. Some authors have suggested the addition of a Caldwell-Luc procedure to the endoscopic approach in these circumstances. The author's technique for TEMM involves en bloc resection of the entire lateral nasal wall and the tumor under endoscopic visualization as seen in the image below.

Sagittal illustration of transnasal endoscopic medial maxillectomy (TEMM) shows the resected lateral nasal wall. Note the cavity of the maxillary sinus (M), resected ethmoid sinuses (E), nasolacrimal duct (NLD), sphenopalatine artery (SPA), and tumor (T). After general endotracheal anesthesia is administered, perform topical intranasal decongestion with 2% oxymetazoline-soaked neurosurgical pledgets. Transorally infiltrate 1% lidocaine with 1:100,000 epinephrine into

the sphenopalatine foramen. Inject the medication intranasally along the inferior meatal wall, into the turbinates, along the maxillary crest, up to the attachment of the middle turbinate, and into the tumor. Make the initial incision along the superior resection margin, which includes the ethmoids as seen in the image below. Apply bipolar cautery, then sever the attachment of the middle turbinate to the lateral nasal wall with endoscopic scissors.

Superior cut in transnasal endoscopic medial maxillectomy (TEMM) going through the anterior ethmoids (AE) along the ethmoid roof. Central circle shows the endoscopic view and the semitranslucent peripheral circle is the bird's-eye view to show the context. Image shows the middle turbinate (MT), nasolacrimal duct (NLD), Tumor (T), nasal septum (S), and inferior turbinate (IT). By using a Freer elevator, perform the dissection along the roof of the ethmoids up to the sphenoid rostrum. Identify the ethmoid arteries, and cauterize them with bipolar cautery. Next, perform inferior resection, as seen in the image below, at the inferior meatus. Cut the mucosa with the electrocautery device at the junction of the lateral wall and the floor of the nose. Perform inferior meatotomy at the anterior end of the meatus. By using a straight osteotome, osteotomize the inferior meatus up to the posterior wall of the maxillary sinus.

Inferior incision in transnasal endoscopic medial maxillectomy (TEMM) through the mucosa and soft tissue to expose the bone for osteotomy. Broken line illustrates the position of the inferior osteotomy. Image shows the nasal floor (NF), septum (S), the anterior head of inferior turbinate (IT), nasolacrimal duct (NLD)), and tumor (T). Anterior resection, as seen in the image below, includes a cut made inferiorly from the anterior attachment of the middle turbinate to include the uncinate process and the maxillary crest. The cut is continued anterior to the inferior turbinate head to connect to the inferior meatotomy cuts.

Anterior mucosal incision and osteotomy in transnasal endoscopic medial maxillectomy (TEMM) connecting the superior and the inferior cuts. Bony nasolacrimal duct is osteotomized to expose the duct (NLD). Image shows the nasal floor (NF), inferior turbinate (IT), septum (S), ethmoid sinuses (ES), and tumor (T). After the soft tissue is elevated, perform anterior osteotomy along the maxillary crest into the maxillary sinus. Then, sever the nasolacrimal duct with endoscopic scissors and include the duct in the specimen. Mobilize the lateral wall medially with progressive dissection until it is pedicled on the sphenopalatine artery (as seen in the image below). Likewise, mobilize any tumor in the sinus.

Posterior cuts in transnasal endoscopic medial maxillectomy (TEMM). The nasolacrimal duct (NLD) is transected to allow medialization of the lateral nasal wall and to expose the maxillary sinus. Posterior cuts are completed in the maxillary sinus. The sphenopalatine artery is exposed. Semitranslucent bird's-eye view illustrates the ethmoid sinuses (ES) along with the lateral nasal wall that is medialized with the tumor (T). Image also shows the ethmoid roof (ER), nasal floor (NF), and sphenoid ostium (SO). Clip, cauterize, and cut the sphenopalatine artery. Cut the posterior attachment of the inferior turbinate, and remove the lateral wall along with the tumor. Remove the remaining mucosa of the ethmoids superiorly, and laterally if needed, for margin control, and remove the lining of the maxillary sinus if needed for margin control. If necessary, the lamina papyracea and adjacent medial wall of the orbit may be removed. By using 30 and 70 scopes, the entire lining of the superior and lateral wall of the maxillary sinus can be visualized, and the mucosa can be removed to clear potential multicentric disease. The anterior wall of the sphenoid sinus can easily be resected if needed. Follow-up Important in the management of sinonasal SPs is long-term follow-up. Many authors believe that most recurrences occur within the first 2 years of treatment. However, most recurrences are observed 5-10 years after treatment. Start follow-up care at regular intervals for at least 5 years after initial management. Nasal endoscopy is essential for follow-up and monitoring for disease recurrence. Complications

Complications can occur after surgical resection of sinonasal papillomas (SPs). The most serious complications are related to the orbit. Blepharitis, diplopia, and intermittent dacryocystitis have been reported after lateral rhinotomy and medial maxillectomy. Ectropion can result secondary to scarring with a downward pull of the lower lid. CSF leak can develop if the base of the skull is violated during surgery. Late complications include prolonged crusting, infection, nasocutaneous fistula, vestibular stenosis, and nasalvalve collapse. The most common complication after the midfacial degloving procedure is vestibular stenosis. Oroantral fistula, intermittent paresthesia, and prolonged crusting can also occur. Endoscopic resection poses the same risk of any endoscopic sinus surgery. Potential complications include CSF leak, orbital complications (orbital or periorbital hematoma, diplopia, injury to the optic nerve, injury to the extraocular muscle, epiphora) prolonged crusting, bleeding, infection, and synechia. Future and Controversies The advent of nasal endoscopy, with strong illumination, superior resolution, and angled visualization, together with advances in CT scanning and MRI, have led to precise identification, good localization, and successful resection of intranasal lesions (including SPs) by using an endoscopic approach. Many reports in the literature support successful treatment of SPs with endoscopic sinus surgery. Preoperative CT scanning and MRI allow for an accurate assessment of the extent of the lesion and, hence, allow for improved selection of the lesions appropriate for endoscopic resection. MRI can help in clearly distinguishing a tumor from opacification secondary to obstructive sinusitis. Endoscopic resection may include total sphenoethmoidectomy, wide meatotomy, resection of the middle turbinectomy, and visualization of the frontal sinus. Some have advocated sampling of the margins. All specimens should be sent for histopathologic examination to ensure complete removal of papillomatous lesions. Authors of a new study advocate the use of a microdebrider with endoscopic sinus surgery to resect SPs. The various tissues resected and suctioned through the microdebrider must be collected in a separate container and sent for histopathologic study to rule out malignancy. The different tissue entities resected by using the microdebrider do not lose their important morphologic features. Investigators continue to endorse the endoscopic approach as a feasible and effective approach for the treatment of sinonasal papilloma. The technique is increasing refined and tailored to the extent of the disease, and systematic and well-defined steps to reproducibly perform endoscopic medial maxillectomy are defined. Authors with long-term experience with the open approaches are also performing endoscopic approaches with comparable or improved success. The advantages of the endoscopic transnasal approach over traditional medial maxillectomy are the lack of an external scar and its related potential for cosmetic deformity; shortened hospitalization; decreased blood loss; and ability to directly visualize the precise extent of the tumor, which increases the likelihood of complete resection. Furthermore, the reported recurrence rate of SPs after endoscopic resection (approximately 17%) is comparable with that of the standard technique of lateral rhinotomy and medial maxillectomy. The endoscopic approach had already been successful in papillomatous lesions confined to the lateral nasal wall or minimally extending into adjacent paranasal sinuses. Reports also suggest its effectiveness in more advanced disease. Involvement of the maxillary sinus is no longer considered a contraindication to endoscopic or endoscopyassisted surgery. Some authors have suggested the addition of the Caldwell-Luc procedure to the endoscopic approach when the anterior or posterolateral maxillary sinus is involved. The presence of carcinoma in the

endoscopically resected specimen likely indicates a need for more aggressive treatment, depending on the size and location of the carcinomatous foci. For tumors that arise from the frontal sinus, endoscopic sinus surgery is similarly contraindicated. Detailed preoperative assessment of the extent of the lesion with CT and/or MRI helps in selecting and individualizing the approach for each patient. In addition, the skill and experience of the surgeon with regard to a particular procedure are important factors in selecting the right approach for each patient.

Background The location of the nasal cavity and the paranasal sinuses make them extremely close to vital structures. Sinonasal malignancies (SNM) can grow to considerable size before presentation, and aggressive therapy may be needed in areas close to the skull base, orbits, cranial nerves, and vital blood vessels. Problem Although rare, sinonasal malignancies (SNM) can be lesions of immense importance. They produce few if any signs while the tumor is in its early stages. This problem is exacerbated by the fact that the initial manifestations (eg, unilateral epistaxis, nasal obstruction) mimic signs and symptoms of many common but less serious conditions. Therefore, the patient and clinician often ignore or minimize the initial presentation of these tumors and treat early-stage malignancy as a benign sinonasal disorder. By the time ominous signs and symptoms (such as severe intractable headache, visual disturbance, or cranial neuropathy) occur, the neoplasm is often advanced. The anatomy of the nasal cavity and paranasal sinuses cause these tumors to manifest in advanced stages and complicate their treatment. They are located adjacent to important structures such as the skull base, orbits, cranial nerves, and vital vascular structures. The obvious morbidity and complications associated with surgical resection of such tumors can be severe. Treatment of sinonasal malignancies (SNM) is best accomplished through a multidisciplinary team. Optimally, this includes a head and neck oncologic surgeon, reconstructive surgeon, maxillofacial prosthodontist, radiation oncologist, medical oncologist, neuroradiologist, pathologist, neurosurgeon, and the patient. Epidemiology Frequency Sinonasal malignancies (SNM) are rare. They are more common in Asia and Africa than in the United States, where about 2000 Americans develop these malignancies each year. In parts of Asia, sinonasal malignancies (SNM) are the second most common head and neck cancer behind nasopharyngeal carcinoma. Men are affected 1.5 times [1] more often than women, and 80% of these tumors occur in people aged 45-85 years. Approximately 60-70% of sinonasal malignancies (SNM) occur in the maxillary sinus and 20-30% occur in the nasal cavity itself. An estimated 10-15% occur in the ethmoid air cells (sinuses), with the remaining minority of [2, 3, 4] neoplasms found in the frontal and sphenoid sinuses. Etiology Risk factors for sinonasal malignancies (SNM) have been extensively investigated. They are complicated, multifactorial, and somewhat controversial. The idea that squamous cell carcinoma (SCCA) and adenocarcinoma in this area are associated with exposure to nickel dust, mustard gas, thorotrast, isopropyl oil, chromium, or dichlorodiethyl sulfide is well established. Wood dust exposure, in particular, is found to increase the risk of SCCA [5] 21 times and the risk of adenocarcinoma 874 times. Many of these products are found in the furniture-making industry, the leather industry, and the textile industry. A careful social and employment history should be asked of [6, 7] all patients presenting with symptoms concerning for sinonasal malignancies (SNM). Viral infections and their relationship to malignancy is an interesting area that has not received sufficient investigation. Preliminary studies show that epidermal growth factor receptor (EGFR) and transforming growth factor-alpha (TGF-alpha) in elevated levels of expression may be associated with early events in inverting papilloma

(IP) carcinogenesis. Human papillomavirus (HPV) and Epstein-Barr virus (EBV) infection may also be an early event [8, 9, 10] in a multistep process of malignant transformation of inverting papilloma (IP). Pathophysiology Inverted papilloma Although inverted papilloma (IP) is a benign lesion in most cases, it can be a locally aggressive tumor with malignant potential, and for this reason the authors have included it in the discussion. Gross examination reveals a red-to-tan mass in the nasal cavity. As opposed to benign reactive nasal polyps, inverted papilloma (IP) is commonly unilateral. Therefore, whenever a surgeon encounters a patient with a unilateral polypoid mass, the surgeon should have a high index of suspicion for inverted papilloma (IP). More than 90% of inverted papilloma (IP) are attached to the lateral wall, although they can also arise in the maxillary, frontal, or ethmoid sinuses. Full extent of the lesion can often not be determined without radiographic imaging. Biopsy is ultimately necessary. Approximately 10% of inverted papillomas (IP) harbor squamous cell carcinoma. Histologic [11] evaluation demonstrates hyperplastic multilayered squamous-to-columnar epithelium with or without atypia. Treatment of inverted papilloma (IP) is wide surgical resection, usually a medial maxillectomy, but the specific method of excision has evolved over the past several decades from open procedures to endoscopic surgery. Endoscopic approaches have the advantage of no visible scar, less pain, reduced epiphora, and, in most cases, less blood loss. Multiple studies have shown similar safety and recurrence rates between endoscopic resection and [12, 13, 14, 15] open approaches. Not all lesions, however, are amenable to endoscopic resection. Oikawa (2007) studied recurrence rates in endoscopically resected inverted papilloma (IP) and recommended external surgery for inverted papilloma (IP) that extends into the frontal sinus, supraorbital recess, or outside the paranasal sinuses, [16] regions that are difficult to access endoscopically. Cannady (2007) further recommended a modification of the Krause staging for IP as follows: Modified Krause staging o A Inverted papilloma (IP) confined to the nasal cavity, ethmoid sinus, or medial maxillary wall o B Inverted papilloma (IP) with involvement of any maxillary wall (other than the medial wall) or frontal sinus or sphenoid sinus o C Inverted papilloma (IP) with extension beyond the paranasal sinuses

These authors found that tumors in group A were amenable to complete endoscopic resection and low recurrence rates (RR) of (3%). Those tumors in group B could be resected endoscopically but often required adjunctive procedures (Caldwell-Luc approaches or osteoplastic frontal sinusotomy, respectively) for removal and RR of 20%. [17] Those tumors in group C always required open approaches, and RR were closer to 35%. Squamous cell carcinoma Squamous cell carcinoma (SCCA) constitutes over 80% of all malignancies that arise in the nasal cavity and paranasal sinuses. Approximately 70% occurs in the maxillary sinus, 12% in the nasal cavity, and the remainder in [18] the nasal vestibule and remaining sinuses. Several variants of carcinoma are often considered variants of squamous cell carcinoma of the nasal cavity and paranasal sinuses. These include verrucous carcinoma, basaloid squamous cell carcinoma, spindle cell carcinoma, and transitional or cylindrical cell carcinoma. The unqualified term squamous cell carcinoma is used to indicate [19] malignancies that have the standard features widely understood to represent that entity.

The presentation is, as with all of the entities described here, extremely varied and may include a nasal mass or obstruction, rhinorrhea, epistaxis, cranial neuropathies, or pain. Long-standing lesions may alter the patient's facial features in a detectable manner, causing asymmetry or proptosis. Visual disturbances and paresthesias are not uncommon. On occasion, malocclusive phenomenon occurs with a notable mass effect arising from the floor of the maxilla and hard palate. On clinical evaluation, the appearance is a function of the stage of the tumor. At first, it may be little more than a mass or small ulcer. With advanced disease, large ulceration, necrosis, heaped edges, and bone and soft-tissue invasion may be observed. Biopsy is necessary to classify any lesion. Wegener granulomatosis and other nonneoplastic diseases may simulate the signs, symptoms, and appearance of SCCA. Histologic examination reveals sheets, ribbons, and individual squamous, polyhedral, or round-to-ovoid cells with various degrees of keratinization. Prognosis is improved in those patients presenting with ethmoid primaries, early lesions treated with both [20] radiation and surgery, and with history of inverted papilloma. Unlike other SCCA of the head and neck, lymph node involvement is rare and selective lymph node dissection is not advocated. The overall 5-year survival rate is [18, 21, 22, 23] 60-64%, and the recurrence rate is estimated at 31%. Adenoid cystic carcinoma Adenoid cystic carcinoma (ACC) is of salivary origin and is the second most common sinonasal malignancy, accounting for 10% of cases. Three histological subtypes are based on growth patters: tubular, cribriform, and solid. These subtype distinctions are important because the solid form portends a much worse prognosis than either cribriform or tubular. Cervical lymph node involvement is rare and elective neck dissection is not indicated in most cases. Perineural invasion is common and is present in 40-60% of cases. Late recurrence and distant metastasis are frequent and can occur decades after initial presentation. Surgery is the mainstay of therapy with postoperative radiation reserved for advanced disease, perineural involvement, or positive margins. Chemotherapy does not currently have a role in treatment. Although no scientific studies specifically address neutron beam radiotherapy for ACC of the sinonasal region, studies involving ACC in other areas of the head and neck have shown improved local control rates over traditional radiation. No [24, 25, 26] overall survival benefit has been shown. Recurrence is common, occurring in up to 55% of cases. Overall [27] disease-specific 5-year survival rates were respectively 63% and 70% in the MD Anderson experience. Adenocarcinoma and its variants Adenocarcinoma of the nasal cavity and paranasal sinuses is historically important and is associated with specific risk factors including exposure to wood dust, lacquers, and other organic compounds. Both low- and high-grade adenocarcinoma can cause obstructive symptoms, rhinorrhea, or epistaxis. However, pain, paresthesias, and oral ulceration are far more common in the high-grade, poorly differentiated tumors. Regardless of grade, local destruction of the orbits and skull base is frequently seen. Distant metastases are rare. When they do occur, the lung, liver, and bone are the sites most often involved. Metastases to the cervical lymph nodes are uncommon, even with poorly differentiated tumors. Treatment is surgical excision with wide margins and postoperative radiotherapy for advanced disease or positive margins. One study evaluated the outcome and prognosis of 44 patients treated for sinonasal adenocarcinoma with endoscopic resection followed by radiotherapy. After 5-year follow-up, the overall survival rate was 63%, the

disease-specific survival rate was 82%, and the recurrence-free survival rate was 60%. These results add support to [28] the assertion that endoscopic resection is a valid treatment option to the open resection technique. The rarity of lymph node metastasis makes elective neck dissection unnecessary. The prognosis for low-grade adenocarcinoma is far better than that for high-grade tumors of the sinonasal area. High-grade adenocarcinomas have a reported survival rate of less than 35% at 3 years, while low-grade [29, 30, 31] adenocarcinoma has a 5-year survival rate of approximately 80%. Malignant melanoma Malignant melanoma is a rare disorder of the nasal cavity and paranasal sinus mucosa. It accounts for less than 1% of all malignant melanomas and less than 4% of nasal malignancies. In general, mucosal melanoma of the head and neck accounts for 55% of all mucosal melanomas; 80% are found within the nasal vault and 20% in the sinuses. Melanoma rarely metastasizes to this anatomic region; however, a careful clinical search is still indicated to rule [32] out metastatic disease. Positive LAD is found in over 26% of patients on presentation. Clinical appearance of the lesion is that of a firm, gray-white or pink-to-black, ulcerated mass. Black coloration is a rarity, and its absence does not rule out melanoma without biopsy. Histologically, mucosal melanoma can be extraordinarily variable in appearance. Immunohistochemistry often plays an important role and is often positive for S-100, HMB-45, Melan-A, Tyrosinase, or pigment epitheliumderived factor. The primary therapeutic modality is surgical resection with wide local margins. Although no formal randomized trials have shown benefit to radiation therapy in sinonasal melanoma, large retrospective studies demonstrate improved locoregional control. Postoperative radiation is therefore often recommended for advanced disease. [33, 34] Chemotherapy is currently only used for disseminated disease and palliation. Despite optimal therapy, median survival is less than 2 years. Beyond the typical negative risk factors of large size, deep thickness, and large volume, a review from the Mayo clinic found statistically significant survival benefit from location of the primary on the [35, 36] nasal septum, compared with the sinuses or lateral nasal wall. Sinonasal neuroendocrine tumors Sinonasal neuroendocrine tumors are a unique and often confusing group of sinonasal malignancies (SNM) including esthesioneuroblastoma (ENB), sinonasal undifferentiated carcinoma (SNUC), neuroendocrine carcinoma (NEC), and small cell carcinoma (SmCC). Although important histologic differences exist between these tumors, most experts agree that the largest distinction should be made between ENB and non-ENB types because of the [37] much more favorable clinical outcome of ENB compared with the other 3. Part of the confusion comes from the multiple names given to each of these tumors and the histological overlap between the tumors. Recent immunohistochemical stainings have shown these tumors to be distinct entities. M.D. Anderson Cancer Center compared their findings of 72 patients with sinonasal endocrine tumors over a 20year period and found the overall survival of ENB was 93% at 5 years, compared with 62%, 64%, and 28% for SNUC, NEC, and SmCC, respectively. These results occurred despite the fact that most patients with ENB were treated with local therapy alone (surgery and/or radiotherapy) versus more aggressive approaches for non-ENB tumors, [38, 39] including surgery, radiation, chemotherapy, and treatment of the regional lymph nodes. Esthesioneuroblastoma Esthesioneuroblastoma (ENB), frequently called olfactory neuroblastoma, is an uncommon but frequently studied tumor of the sinonasal tract. It constitutes 3% of all endonasal tumors. Its presentation is similar to other sinonasal malignancies (SNM); nasal obstruction and epistaxis being the most common presenting symptoms. Most patients present in the fifth decade of life. ENB most commonly originates from olfactory cells near the cribriform plate.

ENB commonly manifests at an advanced stage, possibly because early symptoms in this location are either not present or ambiguous. Levine and colleagues at the University of Virginia have one of the longest and most consistent single institution series of patients with ENB, and 64% of their patients present with stage C disease. A retrospective literature review by Broich et al of 945 patients found 18% of patient presenting with Kadish stage A, 32% with stage B, and 50% presenting with stage C. Treatment of ENB changed dramatically in the 1970s with the advent of the craniofacial resection (CFR), which significantly increased 5-year survival. In the review by Broich, survival rates at 5 years were 72%, 62%, and 53%, [40] respectively, for Kadish Stage A, B, and C tumors. A meta-analysis by Dulguerov et al of publications between 1990 and 2000 compared surgery alone, radiation alone, and surgery combined with postoperative radiation and found a statistically significant benefit to combined surgery and radiation; the 5-year survival was 65%, 48%, and [41] 37% for combined therapy, surgery, and XRT, respectively. Levine and colleagues advocate similar treatment for stage A and B tumors with the addition of chemotherapy for stage C tumors. This is based on the belief that ENB shares certain biological characteristics with other chemosensitive endocrine tumors. Chemotherapy effectiveness at Mayo Clinic was reviewed in 10 stage C patients [42] and the best tumor response was in high-grade tumors, while minimal response was found in low-grade tumors. Despite good 5- and 10-year disease-free survival rates, late recurrence is common, occurring in approximately one third of cases, with a mean time to recurrence of 6 years. Despite a 34% recurrence rate, Levine reported 5-and 15year survival rates after treatment for recurrent disease of 89% and 86%, respectively. Cervical lymph node metastasis at the time of presentation is less than 5%, but long-term cervical involvement ranges from 15-30%. Prophylactic treatment of the N0 neck is recommended in select cases by Levine and Dulguerov, but no further guidance has been given. A similar retrospective review by Diaz et al from M.D. Anderson of 30 patients found 100% regional recurrence of stage C tumors at 10 years, but 77% overall survival [43, 44, 45] rate despite the high recurrence rate. Sinonasal undifferentiated carcinoma Sinonasal undifferentiated carcinoma (SNUC) is an uncommon neoplasm of the sinonasal region. The name is derived from the lack of clear-cut distinguishing histologic features of this lesion. Given the aggressive nature of this tumor, the location and frequent advanced stage of the tumor at presentation, it is rarely treated with resection alone. Studies show the 5-year survival rate is closer to 43-63%. Unlike ENB, early recurrence is common and response to re-treatment is poor. For this reason, 2-year disease-free survival is similar to 5-year survival. A study of 10 patients treated at one institution over a 10-year period found that surgery should usually only be [46] considered when residual resectable disease is found after neoadjuvant chemotherapy. Another study by Chen et al of 21 patients with SNUC found surgery followed by postoperation XRT and chemotherapy to be effective when complete surgical margins could be obtained, increasing local control rates [47, 48, 49, 50] from 24% to 74% at 5 years. Overall survival was also increased from 40% to 50% at 5 years. Small cell neuroendocrine carcinoma Small cell neuroendocrine carcinoma (SmCC), similar to oat-cell carcinoma of the lungs, is reported to arise in the nasal cavity and paranasal sinuses in patients ranging aged 26-77 years. The fact that the tumor is almost always in an advanced stage by the time it comes to attention reflects it aggressive nature. Several sinuses are nearly always involved. Cervical lymph nodes and pulmonary metastases may also be involved.

Treatment is multimodal, including regiment combinations of surgery, chemotherapy, and radiation therapy. Despite maximal efforts and individualized therapy, the prognosis is poor. Median survival, as extrapolated from several studies, is less than 2 years. Verrucous carcinoma Verrucous carcinoma is a type of squamous carcinoma grossly characterized by a fungating appearance with complex papillary infoldings. On histologic examination, this low-grade malignant neoplasm is composed of well-differentiated, keratinized squamous epithelium with a hyperplastic, or abundantly cellular, appearance. An important issue related to verrucous carcinoma is the potential to progress to the more aggressive traditional squamous cell carcinoma. Verrucous carcinomas cause damage by local invasion but do not metastasize unless they contain a component of squamous cell carcinoma. On extensive examination, 20% of these lesions have demonstrated classical squamous cell carcinoma in at least one area. The rate of local invasion is also slower than [51] with that usually observed with squamous cell carcinoma. One important and often overlooked feature of verrucous carcinoma of the head and neck is their frequent association with synchronous or metachronous tumors. These take the form of epithelial malignancies or premalignancies in the upper aerodigestive tract, with a rate as high as 37%. This association must always be considered during patient follow-up. Lymphomas and related conditions This category of malignant neoplasia of the sinuses and nasal cavity is complicated, poorly understood, evolving, controversial, and extensive. In general, non-Hodgkin lymphomas are primarily found in patients in their 60s and 70s and manifest with symptoms of obstruction. Rhinorrhea and epistaxis may also be present. After the type of tumor is established, treatment is usually radiation therapy and chemotherapy, as established by protocol. The prognosis in general is variable for patients with non-Hodgkin lymphoma and, depending on the type and stage ranges, median survival [52] ranges from less than 1 year to close to 80% at 5 years. Another controversial type of malignant lymphoid tumor is T-cell/natural killercell lymphoma. It has had numerous names throughout its history, including lethal midline granuloma, midline malignant reticulosis, lymphomatoid granulomatosis, angiocentric lymphoproliferative lesion, and T-cell/natural killercell lymphoma. [53, 54] Given the current knowledge, this lesion is probably best categorized as a T-cell/natural killercell lymphoma. The tumor is a destructive sinonasal lesion associated with obstructive symptoms, bone and soft-tissue destruction, and hemorrhage. It is strongly associated with the Epstein-Barr virus and is most common in Asia and Latin America, with a patient age at presentation of 13-80 years. Treatment has included radiation with or without chemotherapy. The chemotherapeutic regimen often includes combinations of cyclophosphamide, doxorubicin, vincristine, and prednisone. Because of past confusion about to how to categorize this disease, scientifically rigid data to ascertain the prognosis are not available. At present, the prognosis must still be considered poor, and the 5-year survival rate is less than 70% at best. Salivary-type neoplasms

Pleomorphic adenomas, mucoepidermoid carcinoma, and other salivary gland neoplasms may arise in the nasal cavity and paranasal sinuses. On gross and histologic evaluation, they are similar to the corresponding salivary gland tumors found elsewhere. Pleomorphic adenomas are excised with wide margins if feasible. Recurrences are re-excised, often to good effect. The behavior of mucoepidermoid carcinoma is a function of the stage, grade, size, and resection margins of the tumor. High-grade mucoepidermoid is similar to squamous cell carcinoma because it is mostly epithelia in content. Sarcoma Sarcomas of the sinonasal tract are rare. Given that the nasal cavity and paranasal sinuses contain nerves, blood vessels, lymphatics, smooth and skeletal muscle, fibrous tissue, bone and fat, malignant mesenchymal tumors occasionally develop. Fibrosarcomas, leiomyosarcomas, rhabdomyosarcomas, liposarcoma, malignant peripheral nerve-sheath tumors, and other lesions have been reported. Of these tumors, rhabdomyosarcoma deserves special consideration because it is one of the more frequent sinonasal malignancies in children, although it has also [55, 56] been reported in adults. The symptoms are similar to those of other tumors in this area and sarcoma is usually in an advanced stage at the time of presentation. Bone and extensive soft-tissue destruction is not unusual. Rhabdomyosarcomas may be classified into several subtypes. Therapy is controversial and has included a strong reliance on a combination of radiation therapy and chemotherapy. Despite current optimal therapy, 50% of [57] patients die from this disease. Pediatric sinonasal tumors are most commonly sarcomas and have a 70% response rate to multimodal therapy. Metastatic tumors Metastatic tumors to the nasal cavity and paranasal sinuses are well documented but uncommon. As expected, tumors that most frequently metastasize to this bony region are those that are well known to metastasize to other bones. These are the traditional metastatic tumors that seem to home in on bone and include prostate, breast, [59] kidney, lung, and thyroid. In addition, melanomas, GI adenocarcinoma, and hepatocellular carcinoma are all reported to metastasize to the head and neck region. Whenever one suspects such a malignancy, performing an appropriate evaluation to search [60] for a primary is imperative. Of particular importance are 2 metastatic lesions that may cause confusion. The first is the clear-cell variant of renal cell carcinoma. Its appearance can be similar to the clear-cell variant of a mucoepidermoid carcinoma. Although the pathologist should be able to distinguish these lesions, special studies, such as immunohistochemical studies and possible electron microscopy, may be required. The second metastatic neoplasm that may become problematic for the diagnostician is colorectal adenocarcinoma. This lesion may be indistinguishable from the colonic variant of primary sinus adenocarcinoma. Recognizing the presence of a colonic or intestinal type of primary adenocarcinoma should automatically lead to an intelligent clinical and radiologic evaluation to distinguish a primary sinonasal tumor from a metastatic colorectal neoplasm. Presentation
[58]

Initial presenting symptoms include epistaxis, nasal obstruction, recurrent sinusitis, cranial neuropathy, sinus pain, facial paresthesia, proptosis, diplopia, or an asymptomatic neck mass. Often, these mimic signs of conditions more common and less serious than malignant tumors of the sinuses. The patient often ignores early symptoms, or the clinician may minimize them, treating early-stage malignancies as infectious diseases. By the time ominous signs and symptoms (eg, severe intractable headache, visual disturbances) occur, the neoplasms are advanced and require complex management. In addition to malignant neoplasms causing local destruction of the tissues, infectious diseases of the sinuses (eg, mucormycosis in diabetes) can cause similar destruction. In addition, certain autoimmune diseases (eg, Wegener granulomatosis) can also manifest with new growth and malignant behavior. Finally, benign growths from outside the sinonasal tract in adjacent areas may lead to aggressive signs and symptoms and require radical and destructive therapy. Meningiomas may grow into the sinuses, and orbital tumors may extend into adjacent paranasal sinuses. Even benign conditions, such as juvenile angiofibromas or nasal gliomas, may lead to death if not recognized and appropriately treated. This article limits itself to sinonasal malignancies (SNM) that arise from host tissues and are considered locally invasive, destructive, and possibly metastatic. Relevant Anatomy As with all areas of the head and neck, the relevant anatomy is extremely complex, and the various important structures are close to each other. The fine details of the anatomy of the nasal cavity and paranasal sinuses are beyond the scope of this article. However, the most important anatomic and geometric relationships of these regions are discussed below. These regions include the nasal cavity, the frontal sinuses, the sphenoid sinuses, the maxillary sinuses, and the ethmoid sinuses. Nasal cavity The cribriform plate of the ethmoid bone forms the superior aspect of the nasal sinus. Branches of the olfactory nerves pierce through this plate as they enter the nasal cavity. The inferior aspect is the superior surface of the hard palate. The lateral walls are formed by portions of the ethmoid, maxilla, palatine, lacrimal, and medial pterygoid plates of the sphenoid, nasal, and inferior turbinate bones. The walls are covered with highly vascular pseudo erectile tissue with immense capacity for serious hemorrhage. The anterior aspect is an ill-defined area artificially separated from the external nose by the upper and lower lateral cartilages and the nares. The posterior aspect is defined as the posterior choanae, where the soft palate and hard palate join. Anything posterior to this is considered the nasopharynx. Frontal sinuses The frontal sinuses are usually paired, but may show focal fusion. In fact, the frontal sinuses are remarkable for their size and shape variations. On average they are each approximately 7 mL in volume and conical to funnel shaped, with the apex oriented superiorly; asymmetry is common. The superior aspect is an ill-defined stopping point of the cavity in the frontal bone. The inferior aspect is variable but almost always covers some portion of the ipsilateral orbital roof. The lateral aspects of the sinus or cavity gradually fade into more or less porous aspects of the frontal bone. The anterior aspect is bounded by the frontal bone. The posterior border is made by a table of bone separating the frontal sinus from the anterior cranial fossas. Sphenoid sinuses

The sphenoid sinuses are unique among the paranasal sinuses because they do not arise as invaginations of the nasal cavity. Instead, they originate from embryonic rests in the nasal capsule. They are not discernible on imaging studies or autopsy until an individual is aged 2-4 years. The sinuses are full size at the age of 20 years. At this age, they each have a volume of approximately 8 mL. Orientation, geometry, position, and extent of the sinus vary so greatly that any generalization of fixed borders can give a wrong impression. The sphenoid sinus lies immediately beneath and often anterior to the sella turcica, which encases the pituitary gland. Impressions from the carotid arteries inferiorly along the lateral sinus walls and the optic nerve superiorly can be found within the sphenoid sinus. The bony walls, floor, or ceiling of the sphenoid sinus may be dehiscent, exposing the optic nerve or carotid arteries. Maxillary sinuses These are paired sinuses located anteriorly on either side of the nose just below the orbits. The structure is that of a pyramid with the base located at the nasal wall. They each have a volume of 10-20 mL. The orbital floor including the infraorbital nerve constitutes the roof or superior aspect of the maxillary sinus. The floor of the maxillary sinus is initially at the level of the nasal floor. As time passes and as the sinus undergoes progressive pneumatization, it approaches the apex of the maxillary canine tooth. In fact, extraction of the canine tooth sometimes results in an oroantral window. The nasal cavity is at the most medial aspect of the maxillary sinus. Thin bone with rich vascular turbinate tissue lines the maxillary sinus at the most medial border. The anterior aspect is the anterior wall of the maxilla is simply the thin bony plate running from the root of the canine to the floor of the orbit. The posterior aspect of the maxillary sinus is where the converging walls of the lateral, inferior, medial, and superior walls meet below the orbits. Ethmoid sinuses The ethmoid sinuses are the most variable of all the paranasal sinuses. For this reason, imaging must be performed in any individual before any operation involving this area is undertaken. The ethmoid sinuses are a series of variably interconnected air cells within bone. On average, 10 such air cells compose each of the paired ethmoid sinuses. Portions of the superior aspect of the ethmoid sinus lie directly below the anterior cranial fossa. Regarding the inferior aspect, the orbits lie directly beneath these structures over much of their extent. They can extend into the superior wall of the maxillary sinus. In terms of the medial aspect, the lateral boney wall of the nasal cavity and the middle turbinate are the medial wall of the ethmoid. The lateral aspect of the ethmoid air cells varies in thickness. It is the medial wall of the orbit; because of its extremely thin dimension, it is called the lamina papyracea (ie, paper plate). The anterior-most air cells of the ethmoid are actually bone perforated with an opening that is so curved it is called the hiatus semilunaris. This opening drains the frontal sinus and the maxillary sinus. The sphenoid sinus lies posteriorly over the middle aspect of the ethmoid bone. Lymph node drainage The lymphatic drainage of the sinuses and nasal cavity include levels I-III. In addition, the retropharyngeal lymph nodes can be site of drainage for the posterior ethmoids, posterior nasal cavity, and sphenoid sinuses. Treatment of the N0 neck in sinonasal malignancy (SNM) is typically not recommended. A retrospective study of 704 patients with sinonasal malignancies (SNMs) of the ethmoid and maxillary sinus by Cantu (2008) found only a

1.6% lymph node involvement of the ethmoid sinuses at presentation and 8.3% in the maxillary sinus. They did note, however, that undifferentiated carcinoma had a much higher metastasis rate and tumors of the floor of the maxillary sinus also metastasized more frequently (hypothesized to be caused by its rich lymphatic supply, similar [61] to the mouth). They also found a much higher lymph node (LN) metastasis rate in T2 versus T3 and T4 tumors. A study of SCCA of the maxillary sinus by Tiwari (2000) also found a relatively low incidence of neck disease at [18] 4.1%. In the N0 neck, judgment should be used by the tumor board in deciding appropriate treatment. Patients with the following criteria would likely benefit from selective lymph node dissection (LND): aggressive histologic types (SCCA and undifferentiated carcinoma); T2 or greater tumors; tumors of rich lymph supply, including the nasal vault and floor of maxillary sinus. Contraindications Therapy of sinus and nasal cavity malignancy is often multimodal. Radiation therapy, surgery, and chemotherapy are usually administered in combination. The location of the anatomic structures in question may make the outcome of surgery intolerable to some patients. These locations are adjacent and connected to the orbits, brain, skull base, hard palate, and the carotid sheath. Careful discussion with the patient and family is important before any therapeutic procedure is undertaken. Laboratory Studies As with other head and neck cancers, liver enzymes are usually obtained to assess for distant disease in addition to a chest radiograph or CT scan to evaluate for pulmonary metastasis. In the case of a nasal cavity or paranasal sinus mass or erosion, an antineutrophil cytoplasmic antibody (ANCA) test for possible Wegener granulomatosis should be considered. This condition often mimics a neoplasm. Consultation with multiple specialties should be considered because these tumors involve complex structures throughout the face and skull base. Consult neurosurgery as needed for skull base involvement and possible intracranial extension. Consult ophthalmology to document visual acuity, evaluation of any extra ocular motility disturbances, and proptosis. In addition, after surgery the ophthalmologist may be called upon to assist with treatment of epiphora or dry eye syndrome. Consult a dentist to evaluate for dental extraction in preparation for radiotherapy. Consult a prosthodontist if maxillectomy is expected, and consult speech pathology as needed. Imaging Studies Imaging studies depend on the differential diagnosis. Plain radiography, CT scanning, and MRI all provide information. Each has its own advantages and limitations. With the ubiquitous nature of the acute and chronic inflammation disease in the sinonasal cavity and the complex anatomy of the sinonasal tract, these tumors are often difficult to diagnose and treat. Magnetic resonance imaging (MRI) is vital in the establishing the presence or absence of factors that determine resectability such as orbital invasion, perineural spread, skull base invasion, intracranial [62] extension, and invasion of the masticator and parapharyngeal spaces by tumor. One of MRIs greatest uses is in helping to demonstrate the distinction tumor and retaining secretions in the multiple sinus cavities. Special emphasis should be placed on MRI evaluation of perineural invasion in adenoid cystic carcinoma [63] because these can track down the nerve in over 60% of cases. Esthesioneuroblastoma (ENB) on MRI often shows peritumoral cysts capping of the intracranial portion of the tumor, which is strongly [64] suggestive of the diagnosis.

CT scan has a higher accuracy at determining both bony remodeling and erosion of the skull base and sinuses. Osteolysis can often be observed with SCCA, metastatic disease, sarcoma, and SNUC. Boney remodeling is more often seen with salivary gland tumors, large cell lymphoma, melanoma, and ENB. In [62] addition, chronic or acute inflammatory sinus disease may also cause boney remodeling. Finally, CT scanning is slightly more accurate than MRI in demonstration of orbital invasion due to its ability to evaluate both the bony orbital wall and adjacent fat.

The authors opinion is that both CT scanning and MRI should be performed prior to surgical intervention to help assist in preliminary staging, surgical planning, and defining respectability in close consultation with the neuroradiologist. In addition, as most landmarks and normal anatomy after surgery are disrupted, recurrence is difficult to identify on imaging. Therefore, postoperative baseline imaging is recommended for comparison tumor surveillance. Apparent Diffusion Coefficient (ADC) mapping shows potential as an additional MRI tool to effectively [65] differentiate benign/inflammatory lesions from malignant tumors in the sinonasal area. Positron emission tomography is still in its infancy, and little has been studied regarding its use in sinonasal [66] malignancies (SNM). Diagnostic Procedures Biopsy is the only 100% accurate means of obtaining a tissue diagnosis. Remember that the turbinates and the possibility of a juvenile angiofibroma may both lead to extensive bleeding. In addition, patients with midline nasal masses may include intranasal dermoids, gliomas, and meningoencephalocele with direct communication with the anterior cranial fossa. Should the surgeon suspect these neoplasms, proper imaging and other tests should be performed before biopsy. A biopsy should be performed on highly suspicious vascular tumors in the OR under controlled conditions where bleeding can be more safely controlled.

Histologic Findings The important histologic features are discussed in detail for the individual neoplasms in the Clinical section. Staging Staging of nasal cavity and paranasal sinus carcinomas is not as well established as for other head and neck tumors. Two generally accepted staging systems are currently in use. The Kadish staging system is used specifically for Esthesioneuroblastoma because this often involves the skull base and intracranial extension. For cancer of the maxillary sinus, the nasal cavity, and the ethmoid sinus, the American Joint Committee on Cancer (AJCC) has designated staging by TNM classification. No broadly accepted staging systems for frontal and sphenoid sinus [67] cancer currently exist. Maxillary sinus Primary tumor (T) T1 - Tumor limited to maxillary sinus mucosa with no erosion or destruction of bone T2 - Tumor causing bone erosion or destruction including extension into the hard palate and/or the middle of the nasal meatus, except extension to the posterior wall of maxillary sinus and pterygoid plates T3 - Tumor invades any of the following: bone of the posterior wall of maxillary sinus, subcutaneous tissues, floor or medial wall of orbit, pterygoid fossa, ethmoid sinuses T4a - Tumor invades anterior orbital contents, skin of cheek, pterygoid plates, infratemporal fossa, cribriform plate, sphenoid or frontal sinuses

T4b - Tumor invades any of the following: orbital apex, dura, brain, middle cranial fossa, cranial nerves other than maxillary division of trigeminal nerve (V2), nasopharynx, or clivus

Nasal cavity and ethmoid sinus Primary tumor (T) T1 - Tumor restricted to any one subsite, with or without bony invasion T2 - Tumor invading 2 subsites in a single region or extending to involve an adjacent region within the nasoethmoidal complex, with or without bony invasion T3 - Tumor extends to invade the medial wall or floor of the orbit, maxillary sinus, palate, or cribriform plate T4a - Tumor invades any of the following: anterior orbital contents, skin of nose or cheek, minimal extension to anterior cranial fossa, pterygoid plates, sphenoid or frontal sinuses T4b - Tumor invades any of the following: orbital apex, dura, brain, middle cranial fossa, cranial nerves other than (V2), nasopharynx, or clivus

Regional lymph nodes (N) N1 - Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension N2 - Metastasis in a single ipsilateral lymph node, more than 3 cm but 6 cm or less in greatest dimension; or in multiple ipsilateral lymph nodes, 6 cm or less in greatest dimension; or in bilateral or contralateral lymph nodes, 6 cm or less in greatest dimension N2a - Metastasis in a single ipsilateral lymph node more than 3 cm but 6 cm or less in greatest dimension N2b - Metastasis in multiple ipsilateral lymph nodes, 6 cm or less in greatest dimension N2c - Metastasis in bilateral or contralateral lymph nodes, 6 cm or less in greatest dimension N3 - Metastasis in a lymph node more than 6 cm in greatest dimension
[68]

Kadish Staging for esthesioneuroblastoma .

Stage A: The tumor is limited to the nasal fossa. Stage B: The tumor extends to the paranasal sinuses. Stage C: The tumor extends beyond the paranasal sinuses Approach Considerations

As with other types of cancers, a multimodality approach in consultation with a tumor board is recommended, including head and neck surgeon and a neurosurgeon when indicated and a neuroradiologist, pathologist, radiation oncologist, and medical oncologist as active members. Although multiple surgical and adjuvant approaches are available, a balance should be found in attempting to preserve cosmetic, oral, and nasal function. When possible, the orbit should be preserved and reconstructed. Despite these seemingly competing needs, first and foremost should be the goal of a safe and complete eradication of disease, when possible. Although the detailed operative approaches for theses tumors are beyond the scope of this text, the authors have outlined the different options below. A surgical review of techniques is as follows: 1 Medial maxillectomy endoscopic

2 Lateral rhinotomy 3 Anterior maxillary punch 4 Craniofacial resection 5 Transfacial with midface degloving 6 Infratemporal fossa approach Treatment for recurrence includes surgery, chemotherapy, and/or radiation therapy. Complications Complications of treating sinus malignancies are related to the surgery and reconstruction. Surgical complications include clinically significant bleeding, CSF leak, infection, anosmia, dysgeusia, and other cranial nerve damage. Bleeding Bleeding may occur if control of the large vessels is overlooked. This problem may occur if the artery is initially in vasospasm and if no active bleeding is noted until after surgery. The anterior and posterior ethmoid and sphenopalatine arteries may be cauterized, clipped, or ligated to prevent or control bleeding. If needed, interventional radiology may be requested to assist with intra-arterial coiling to control bleeding. CSF leaks During surgery, CSF leaks may occur near the skull base. Appropriate management starts with identification. Symptoms may include clear rhinorrhea, salty taste in the mouth, halo sign, or reservoir sign. Once noted, identification of the leak can be made endoscopically or with intrathecal injection of fluorecin. Tests, such as a test for tau or beta transferrin, may be most specific but may take days for results to be processed. Conservative management with bed rest and a lumbar drain can be used for the first 5 days in addition to placement on antibiotics. If resolution has not occurred, surgical intervention should be used, including patching with a dermal allograft, turbinate bone, and nasal mucosa. Mucosal flaps can be elevated and used to close the leaks with interpositioned bone or cartilage. For large leaks, a spinal drain may be necessary to allow grafts and sealing techniques to solidify and integrate. Epiphora Epiphora is a common complication of surgery caused by obstruction in the lacrimal outflow tract. This can happen because of damage to the lacrimal puncta, sack, or duct. Care should be taken to marsupialize the lacrimal duct if it is lacerated or damaged in surgery to prevent outflow obstruction. Follow-up endoscopic or open dacryocystorhinostomy may be necessary. Diplopia Diplopia is a known complication in any surgery involving the orbital cone. Proper repair of the orbital floor is a key to prevent this complication, but in some cases it is unavoidable even with meticulous reconstruction. In cases of diplopia, prism lenses are usually the simplest method for correction, as surgical correction by ophthalmology can

be complicated by prior scarring from surgery and radiation treatment. Ophthalmology consultation is standard of care. Reconstruction One of the most difficult decisions made during surgery is when to take or leave the orbit. Suarez (2007) reviewed [69] the literature and had 3 recommendations. First, close scrutiny of the periorbita is key when deciding for or against exenteration. Although the lamina papyracea and lacrimal bones can be invaded and destroyed quite quickly, the periorbitum is a much better barrier to invasion. So despite bony destruction, if the periorbita is considered intact, they make the argument for orbital preservation and reconstruction. Once the periorbital has been violated, orbital exenteration is required because few barriers to spread exist within the orbital contents. Second, take into account the cancer histology. When dealing with more aggressive histology such as adenocarcinoma and SCCA, a lower threshold for choosing exenterations would be expected, as opposed to ENB with less local regional recurrence rates. Third, reconstruction is essential for large defects resulting from [69] total orbital floor resection involving 2 or more orbital walls to prevent displacement and dysfunction of the eye. If the eye is preserved, postoperative radiation is usually recommended. Current treatments are precise in XRT delivery and preserving orbital function. Nonetheless, patients should be counseled that despite surgical orbital [70] preservation, impairment can occur from XRT, including optic atrophy, cataracts, dry eye, and ectropion. In the ideal cases, reconstruction preserves form and function. A free rectus flap or other distant tissue may be required to protect vital structures, or facial prosthetics may be used. Facial prosthesis can be offered to improve cosmetic results, but meticulous maintenance of the prosthesis by the team and patient is imperative. Facial disfiguration is one of the most important patient concerns and can lead to considerable social and psychological stress. This outcome must be dealt with initially and on an ongoing basis. Flap reconstruction, instead of wearing a prosthesis during recovery, is an option for patients undergoing reconstruction for maxillectomy defects; however, it is associated with a longer recovery time, higher procedure costs, and increased risk of surgical complications. Additionally, the patient must be under the care of a highly experienced surgeon. The surgeon and reconstructive team should make individualized decisions after considering [71] the extent of the maxillectomy defect and the need for radiation therapy. Outcome and Prognosis Survival rates for patients with maxillary sinus cancer average about 40% over 5 years. Early-stage tumors have a cure rate of up to 80%. Patients with unresectable tumors treated with radiation have a survival rate of less than 20%. Survival rates for ethmoid tumors have improved slightly because of advances in skull-base surgery. Future and Controversies Although intra-arterial chemotherapy was used in the past, it was only recently shown to be consistently effective. With the advent of thiosulfate, a neutralizer of cisplatin, physicians can now deliver large doses of intra-arterial chemotherapy more safely than before. High-dose cisplatin is administered by means of the arterial blood supply of the tumor. A simultaneous infusion of thiosulfate prevents the systemic effects of cisplatin. Intra-arterial chemotherapy is used with radiation and had promising results in preserving organs and in managing bulky nodal disease.

Given the anatomy of the paranasal sinuses and their blood supply, intra-arterial chemotherapy may be an effective method of treating sinus malignancies.