Malignant Tumors of the Nasal Cavity 

Updated: May 23, 2019
Author: Ricardo L Carrau, MD, FACS; Chief Editor: Arlen D Meyers, MD, MBA 

Overview

Practice Essentials

Sinonasal malignant neoplasms are rare tumors that constitute about 3% of tumors in the upper respiratory tract. Only a fraction arises at the nasal cavity.[1]  Imaging is essential to staging nasal cavity tumors locally and ruling out the presence of metastases. Computer tomography (CT) scanning and magnetic resonance imaging (MRI) have replaced plain radiographs in workup because of the fine anatomic detail provided by these imaging modalities. Biopsy of the lesion is commonly performed using a rods lens endoscope in the office under topical or local anesthesia. Surgery is the mainstay of treatment for most sinonasal tumors.

Due to the contiguity of the nasal cavities with the paranasal sinuses, identifying the specific site of origin of large sinonasal tumors is often difficult. Hence, malignant tumors of the nasal cavities are often grouped with those of the paranasal sinuses. Their proximity to vital structures such as the brain, optic nerves, and internal carotid artery pose significant challenges for their treatment and may be the source of significant morbidity to the patients. Malignant tumors of the sinonasal tract are derived from diverse histologic elements within the nasal cavity. They include the following:

Epithelial

See the list below:

  • Squamous cell carcinoma

  • Transitional cell carcinoma

  • Adenocarcinoma

  • Adenoid cystic carcinoma

  • Melanoma

  • Olfactory neuroblastoma

  • Undifferentiated carcinoma

Nonepithelial

See the list below:

  • Soft-tissue sarcoma

  • Rhabdomyosarcoma

  • Leiomyosarcoma

  • Fibrosarcoma

  • Liposarcoma

  • Angiosarcoma

  • Myxosarcoma

  • Hemangiopericytoma

  • Connective tissue sarcoma

  • Chondrosarcoma

  • Osteosarcoma

  • Synovial sarcoma

Lymphoreticular tumors

See the list below:

  • Lymphoma

  • Plasmacytoma

  • Giant cell tumor

  • Metastatic carcinoma

New and emerging tumors

Released in 2017, the fourth edition of the WHO (World Health Organization) Classification of Head and Neck Tumours, volume 9 of the fourth edition of the WHO Classification of Tumours, described new, well-defined sinonasal lesions, as well as emerging, less-defined sinonasal tumors. The new lesions included the following[2] :

  • Seromucinous hamartomas
  • Nuclear protein in testis carcinomas
  • Biphenotypic sinonasal sarcomas

The emerging tumors included the following:

  • Human papillomavirus-related sinonasal carcinomas
  • SWI/SNF (SWItch/Sucrose Non-Fermentable)-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1-deficient sinonasal carcinomas
  • Renal cell–like adenocarcinomas
  • Chondromesenchymal hamartomas

Workup

Imaging is essential to staging the tumor locally and ruling out the presence of metastases. CT scanning and MRI have replaced plain radiographs because of the fine anatomic detail provided by these imaging modalities. CT scanning is superior for the evaluation of the bony architecture of the sinonasal tract and skull base. MRI is the best modality for defining soft tissue detail.

Biopsy of the lesion is commonly performed using a rods lens endoscope in the office under topical or local anesthesia. Alternatively, the sampling can be performed in the more controlled environment of an operating room when a deep biopsy is required of if profuse bleeding is anticipated.

Management

Surgery is the mainstay of treatment for most sinonasal tumors. Radiation as the sole modality of treatment is recommended for unresectable cases, poor surgical candidates, or lymphoreticular tumors. Combination therapy of surgery and adjuvant radiotherapy with or without chemotherapy is given in situations with an advanced tumor (T3 and T4), positive surgical margins, perineural spread, perivascular invasion, cervical lymphatic metastasis, and recurrent tumors. Chemotherapy may also have a palliative role for cytoreduction.

Epidemiology

Frequency

The annual incidence of nasal tumors in the United States is estimated to be less than 1 in 100,000 people per year. These tumors occur most commonly in whites, and the incidence in males is twice that of females.[3] Epithelial tumors most commonly present in the fifth and sixth decades of age.

Although tumors of the nasal cavities are equally divided between benign and malignant types, most tumors of the paranasal sinuses are malignant. Approximately 55% of sinonasal tumors originate from the maxillary sinuses, 35% from the nasal cavities, 9% from the ethmoid sinuses, and the remainder from the frontal and sphenoid sinuses. Squamous cell carcinoma is the most common malignant histologic type (approximately 70-80%) followed by adenoid cystic carcinoma and adenocarcinoma (approximately 10% each).[4]

A study by Gerth et al reported the overall incidence of malignant pediatric sinonasal tumors in the United States to be 0.052 per 100,000. The study, which utilized the Surveillance, Epidemiology, and End Results (SEER) database, found that rhabdomyosarcoma was the most frequently occurring malignancy among patients below age 20 years.[5]

Etiology

Exposures to industrial fumes, wood dust, nickel refining, and leather tanning have all been implicated in the carcinogenesis of various types of sinonasal malignant tumors. In particular, wood dust and leather tanning exposures are well associated with increased risk for adenocarcinoma.[6] Other etiologic agents have been reported including mineral oils, chromium and chromium compounds, isopropyl oils, lacquer paint, soldering and welding, and radium dial painting. Tobacco smoking is not considered to be a significant etiologic factor; however, recent studies demonstrated a higher incidence of nasal cancers in cigarette smokers.[3, 7]

Presentation

Tumors of the sinonasal tract commonly present with symptoms that are identical to those caused by inflammatory sinus disease, such as nasal obstruction, nasal discharge, epistaxis, headache, facial pain, and nasal discharge. Tumors of nasal cavities, however, tend to be diagnosed earlier than those of the paranasal sinuses because of the earlier presentation of obstructive symptoms and epistaxis.

To further complicate this issue, 9-12% of patients are frequently asymptomatic.[8] These factors contribute to a delay in diagnoses, and, hence, an advanced stage of disease at the time of diagnosis. Patients with unilateral sinonasal symptoms or those that are associated with unilateral facial swelling, diplopia or blurred vision, unilateral proptosis, and cranial neuropathies should raise a high index of suspicion for sinonasal cancer and warrant urgent evaluation.

Regional and distant metastases are infrequent even in the presence of advanced stage tumors. The incidence of cervical metastases on initial presentation varies from 1-26%, with most large series reporting less than 10%. Distant metastasis on initial presentation is even less common, with most series presenting an incidence of less than 7%.[1] The presence of regional or distant metastases is a poor prognostic sign.

A thorough head and neck examination, cranial nerve assessment, and a nasal endoscopy should be performed in all patients. Physical examination may reveal proptosis, extraocular muscle impairment, mass effect of the cheek, gingival or gingivobuccal sulcus, (eg, ill-fitting dentures) and loose dentition. Numbness or hyperesthesia of the infraorbital (V2) branch of the maxillary nerve strongly suggests malignant invasion (as in the images below).

A nasal cavity tumor has eroded through the hard p A nasal cavity tumor has eroded through the hard palate and is causing difficulty with fitting a denture.
A nasal tumor that has eroded through the nasal bo A nasal tumor that has eroded through the nasal bone and causing deformity of the nasal bridge.

Relevant Anatomy

By examining the close relationships of the nasal cavities to the oral cavity, paranasal sinuses, orbit, nasopharynx, pterygomaxillary fissure and pterygopalatine fossa, infratemporal fossa, skull base, and intracranial fossa, one can better understand the myriad signs and symptoms caused by sinonasal tumors.

Local tumor invasion can breach the boundaries of the nasal cavity invading and destroying structures and/or following preformed pathways. The paired nasal cavities are separated by the nasal septum. Their lateral walls comprise the medial wall of the maxillary sinus and the inferior, middle, and superior turbinates. Lateral extension of tumor can infiltrate the maxillary sinus, ethmoid air cells, or even the orbit (through the lamina papyracea). Eventually, orbital involvement manifests as ocular pain, fullness of the eyelid, unilateral epiphora, diplopia, extraocular muscle limitation/diplopia, or proptosis. The floor of the nasal cavity corresponds to the hard palate of the oral cavity; thus, caudal extension of the tumor can present as palatal fullness, pain, and ulceration.

The roof of the nasal cavities is formed by the cribriform plate, which separates the dura of the anterior cranial fossa from the nasal cavity. The cribriform plate, as implied by its name, has multiple openings to accommodate the passage of olfactory filaments. Tumor can spread to the anterior cranial fossa using these openings or by perineural spread. Violation of this barrier during surgery is likely to produce a cerebrospinal fluid (CSF) leak, increasing the risk for meningitis and intracranial abscess. The nasal cavities open externally via the nares and communicate posteriorly with the nasopharynx via the choanae. The eustachian tubes open into the nasopharynx just behind the infero-lateral aspect of the choanae. Tumor extension into the nasopharynx may cause eustachian tube obstruction and secondary serous otitis media that manifests as hearing loss.

Except in the nasal vestibule, the nasal cavity is lined with pseudostratified columnar ciliated epithelium. The nasal vestibule, which corresponds to the ala of the nose, is lined with squamous epithelium containing vibrissae and sweat and sebaceous glands. A small part of the superior portion of the nasal cavity (bound by the superior turbinate laterally and the nasal septum medially) is lined by olfactory epithelium.

The pterygopalatine and infratemporal fossae are important anatomical considerations, as they are densely populated by the mastication muscles, various sensory and motor nerves, and by the blood vessels that supply the nasal cavity, oral cavity, maxillary teeth, pharynx, and ICAs. Tumor extension into these areas can cause a myriad of symptoms, such as the following:

  • Trismus (involvement of the pterygoid muscles or motor branches of the mandibular division of the trigeminal nerve)

  • Facial hypesthesia (involvement of the infraorbital nerve or other sensory branches from the maxillary and mandibular divisions of the trigeminal nerve)

  • Pain in the maxillary dentition (involvement of the anterior, middle, or posterior superior alveolar nerve branches of the maxillary division of the trigeminal nerve)

  • Severe epistaxis (involvement of the terminal branches of the internal maxillary artery)

The pterygopalatine and infratemporal fossae are also potential routes for intracranial tumor spread, via direct extension or hematogenous spread.

Prognosis

A retrospective study by Stepan et al of adult patients with sinonasal rhabdomyosarcoma found a 5-year overall survival rate of 28.4%, with better survival found in patients 35 years or younger at diagnosis (31.9% vs 24.4% for patients over age 35 years). The investigators noted that the 5-year overall survival rate between alveolar and embryonal subtypes (30.5% vs 41.6%, respectively) did not differ by a statistically significant amount but that patients with metastatic disease had worse 5-year overall survival compared with those without (14.7% vs 33.9%, respectively).[9]

 

Workup

Imaging Studies

Imaging is essential to staging the tumor locally and to ruling out the presence of metastases. Computer tomography (CT) scanning and magnetic resonance imaging (MRI) have replaced plain radiographs because of the fine anatomic detail provided by these imaging modalities. Each has its own advantages and limitations, but in most cases they are considered complementary.

CT scanning is superior for the evaluation of the bony architecture of the sinonasal tract and skull base. It helps to assess bony erosion or remodeling in critical areas such as the orbital walls, cribriform plate, fovea ethmoidalis, pterygoid plates, pterygopalatine fossa, and the walls of the sinuses. The use of contrast also reveals tumor vascularity and its relationship to the carotid artery. Disadvantages of CT scanning include its inability to differentiate tumor borders from the surrounding soft tissue and the need for ionizing radiation.

MRI is the best modality for defining soft tissue detail. It can differentiate adjacent tumor from soft tissue (eg, gadolinium enhances tumor diffusely to an intermediate degree, whereas inflamed mucosa enhances more intensely in a peripheral fashion), differentiate tumor from secretions in an opacified sinus, demonstrate perineural spread (especially adenoid cystic carcinoma), and demonstrate invasion of the dura, orbit, or brain parenchymal, as seen in the images below.

Coronal MRI T1 with contrast showing an esthesione Coronal MRI T1 with contrast showing an esthesioneuroblastoma of the right nasal cavity eroding the skull base and invading the brain. The maxillary sinus is filled with edematous mucosa.
Axial MRI T1 with contrast of the same patient in Axial MRI T1 with contrast of the same patient in Image 4 showing mucus in the right sphenoid sinus due to obstruction of the tumor.
Axial MRI T1 with contrast showing tumor in the le Axial MRI T1 with contrast showing tumor in the left maxillary sinus with perineural spread in to the left vidian canal.

Other advantages of MRI include the fact that it is less affected by the artifact effect associated with dental fillings and that it requires no exposure to ionizing radiation. MRI, however, is more expensive than CT scan and takes longer to perform, making it more prone to motion artifact. In addition, some patients cannot tolerate the procedure due to claustrophobia. Despite the proliferation of “open MRI centers,” it should be recognized that, at this time, this modality offers an inferior resolution that is invariably inadequate to evaluate tumors of the sinonasal tract. Apparent Diffusion Coefficient (ADC) mapping shows potential as an additional MRI tool to effectively differentiate benign/inflammatory lesions from malignant tumors in the sinonasal area.[10]

Angiography with carotid flow study is not routinely performed and is only reserved for surgical candidates presenting with tumors that surround the carotid artery or when sacrifice of the vessel is anticipated to obtain clear margins.[11] Balloon occlusion test of the ICA, used with SPECT, Xenon CT scan, or transcranial Doppler, offers a reasonable estimate of the risk of ischemic brain infarction if the internal carotid artery is sacrificed. These tests however, cannot predict ischemia at marginal (“watershed”) areas or embolic phenomena.

Metastatic workup should be performed should an extensive resection be considered in a patient with advanced stages, especially those with tumors that have invaded the soft tissues of the face and in tumors with a propensity for hematogenous metastasis, such as sarcomas. This may include CT scans of the neck, chest, and abdomen and bone scan. This extensive work up is necessary should an extensive resection be considered. A CT fused with positron emission tomography (PET/CT) is increasingly being used to evaluate for metastases and for surveillance.

Diagnostic Procedures

Biopsy of the lesion is commonly performed using a rods lens endoscope in the office under topical or local anesthesia. Alternatively, the sampling can be performed in the more controlled environment of an operating room when a deep biopsy is required of if profuse bleeding is anticipated.

Histologic Findings

Below is a brief description of the common types of nasal cavity tumors.

Benign Tumors of Epithelial Origin

Inverted papillomas

Papillomas of the nasal cavity may be classified in 3 distinct categories: inverted, fungiform, and cylindrical. Fungiform papillomas arise from the nasal septum, whereas inverted and cylindrical papillomas typically arise from the lateral nasal wall. Although benign in nature, they can extend beyond their site of origin and destroy bone and recur when incompletely excised. Malignant degeneration can occur in 5-20% of inverted papillomas. They are most commonly diagnosed in white males during the fifth to the seventh decade (mean 50 years).

Complete resection has been the criterion standard for the treatment of these lesions. Traditionally, a lateral rhinotomy with a medial maxillectomy were recommended; however, endoscopic approaches have slowly become the standard treatment. One challenge for the planning of its surgical excision is that the lesion tends to be more extensive than clinical examination suggest. In addition, 12-30% of inverted papillomas are multicentric.[12] Excision with negative margins may be difficult and incomplete removal invariably leads to recurrence. In most series using traditional approaches, the recurrence rate is 10-30%.

Refinements in endoscopic techniques have lead to a paradigm shift for the resection of inverted papilloma. Endoscopic resection offers the advantage of avoiding incisions and in most patients can be performed as ambulatory surgery. The extent of the procedure is customized accordingly to the extent of the disease, including total ethmoidectomies, wide maxillary antrostomies, sphenoidotomies, frontal recess exploration, and turbinate resection, if required. Once all visible papillomas are removed, any residual tumors are eliminated by drilling over its site of origin. In experienced hands, endoscopic resection has a recurrence rate that is equal to that of traditional techniques.[13, 14] Outcomes using endoscopic techniques compare favorably with that of open approaches.

Long-term endoscopic surveillance and frequent follow-up are crucial, regardless of the surgical technique. Recurrence is usually discovered 12-20 months after surgery but has been reported as late as 30-56 months.[13] In selected cases, endoscopic management is a useful approach with favorable outcomes and less morbidity when compared with more aggressive surgical approaches.[15]

Malignant Tumors of Epithelial Origin

Squamous cell carcinoma

Squamous cell carcinoma (SCC) is the most common malignant tumor in the sinonasal tract and is mostly found in white men in their fifth and sixth decade.[1] It most commonly arises from the lateral nasal wall followed by the nasal septum.[16] Its prognosis is related to extent and location. Those that arise from the nasal vestibule or anterior nasal septum appear to have a poorer prognosis due to its ability to infiltrate the local soft tissues of the face, such as the columella, nasal floor, or upper lip that are associated with a higher risk of regional spread to the neck nodes.[17] Histologic variants such as verrucous carcinoma, basaloid SCC, or carcinosarcoma have been described. However, the extent of disease is a more important prognostic factor than the degree of differentiation.

Treatment of SCC and most other sinonasal malignancies is based on the stage of the disease. In general, early lesions (T1-T2) are treated by either surgery or radiation therapy. Advanced diseases (T3-T4) are treated with multi-modal therapy (surgical extirpation followed by postoperative radiation or chemo-radiation therapy).[16] Elective treatment of the neck is not indicated unless clinically palpable or radiologically evident nodes exist. Nonetheless, elective treatment should be considered if the tumor extends to the soft tissues of the face or infratemporal fossa. Local recurrences occur in 30-40% of cases, while systemic metastasis occurs in 10% of patients. The 3-year and 5-year survival rates of patients with SCC of the nasal cavity were 86% and 69%, respectively.[18]

Adenocarcinoma

Adenocarcinomas (AC) make up 4-8% of all sinonasal tumors. They arise most commonly from the ethmoid sinuses and nasal cavities. Adenocarcinomas have a strong epidemiological association with hardwood dust, which partly explains the preponderance in male patients (75-90%). For reasons that are not well defined, adenocarcinomas are more prevalent in Europe (especially intestinal type), where they comprise the vast majority of paranasal malignancies.

Patterns of tumor growth and histologic differentiation have a broad relationship to their prognosis. Three basic growth forms exist: papillary, sessile, and alveolar mucoid. Papillary tumors are usually most localized and associated with the best prognosis. Sessile tumors have broad surfaces and a greater invasive propensity, resulting in a worse prognosis than the papillary type. Alveolar mucoid type, characterized by abundant mucin in which nests of individual cells reside, is the most aggressive type.

Adenocarcinomas are also divided into low-grade and high-grade according to their histological characteristics. Low-grade tumors are well differentiated with minimal mitotic activity, rarely presenting with perineural invasion or distant metastases. Their tendency is to recur locally. High-grade adenocarcinomas are poorly differentiated with nuclear pleomorphisms, and high number of mitotic activities. Up to one-third of these patients have distant metastases at initial presentation. In one study of 50 cases of sinonasal tract AC (excluding ACC and mucoepidermoid carcinoma), 78% of the 23 patients diagnosed with low-grade ethmoid AC survived with no evidence of disease at a mean follow-up of 6.3 years. Conversely, only 7% of the 27 patients with high-grade lesions had no evidence of disease; 68% of them died of disease within 3 years of initial treatment.[19]

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 the assertion that endoscopic resection is a valid treatment option to the open resection technique.[20]

The treatment of choice for local control is surgical excision. Postoperative radiotherapy is recommended for patients with positive margins and those with high-grade or advanced staged tumors. Local recurrences are more likely in patients with intracranial involvement. The 5-year disease-specific survival after surgery and postoperative radiation therapy is 55% for T1 and T2, 28% for T3, and 25% for T4 lesions.[21] Postoperative radiotherapy for adenocarcinoma still lacks clear evidence; however, a review by Lund et al demonstrated that local control rates of combined treatment strategies for advanced cases are comparable to those of surgery in less advanced cases, suggesting a positive role for postoperative radiotherapy.[22]

The use of topical 5-fluorouracil after surgical resection has been reported with good results.[23, 24] Knegt et al reported a 5-year disease-free survival of 96%, 86%, and 74% at 2, 5, and 10 years on 62 patients treated between 1976 and 1997. Almeyda reported an 86% 5-year disease-free survival on 25 patients. More studies are needed to evaluate the merits of this modality.

Adenoid cystic carcinoma

Adenoid cystic carcinoma is the most common minor salivary gland tumor in the sinonasal tract, accounting for 14-20% of all the adenoid cystic carcinomas arising in the head and neck. Within the sinonasal tract, the maxillary sinus is the most common site of origin followed by the nasal cavities.[25, 26] It is slightly more common among women, and most patients are between 30 and 70 years of age. Lymphatic regional metastases are extremely rare.Three histological subtypes have been described: cribriform, tubular, and solid. Cribriform pattern is the most common subtype and has the classic "swiss cheese" appearance, whereby the cells are arranged in nests separated by round or oval spaces.[25] The tubular variety has the best prognosis, while the solid type exhibit the worst.Szanto et al in 1984 describes 3 grades based on the proportion of the above subtypes.[27] Grade I tumors are those comprising of tubular and cribriform patterns without any solid component. GradeIIiscomposed of mostly cribriform pattern having less than 30% solid cellular architecture. Grade III is a tumor with a predominantly solid pattern. Grade I tumors have the best prognosis and grade III tumors the worst. Grade III tumors tend to be larger, recur frequently, and have a higher incidence of perineural invasion.

Adenoid cystic carcinomas are characterized by early spread to neurovascular structures, submucosal spread, and advanced stage at the time of diagnoses. Perineural spread, a hallmark of the disease, typically involve the maxillary, mandibular, and vidian nerves. It can spread retrograde intracranially via the foramen rotundum (V2), foramen ovale (V3), and the vidian or pterygoid canal. It can also spread anterograde from the gasserian ganglion to the infratemporal and pterygopalatine fossa.

Surgical excision and postoperative radiotherapy is the usual treatment of choice for adenoid cystic carcinoma of the sinonasal tract. Getting clear surgical margins is often difficult because of the intricate anatomy of the nasal cavity and skull base; therefore, microscopic disease (positive margins) is present in up to 60% of patients.[26] Postoperative radiotherapy is strongly recommended for positive surgical margins, and for tumors of high-grade and advanced stage. Fast-neutron radiation therapy seems to yield better results than radiation using photons or electrons, resulting in better locoregional control for unresectable or recurrent ACC of the parotid gland. However, the use of this therapy is not widespread due to limited availability. In addition, this advantage does not seem to be as significant for ACC of the sinonasal tract.

Prognostic factors for ACC include tumor site, skull base invasion, stage, histopathologic type, histologic grade, and extent of tumor. The overall 5-year survival rates range from 50-86%.[25, 26] The overall recurrence rate is 51%-65%. Distant hematogenous spread occurs in 26-40% of cases and determines overall survival.[25] Some developed distant metastases, despite local control at the primary site. Lungs, liver, and bones are the most frequent target organs. The appearance of distant metastases is not necessarily associated with a rapidly fulminating clinical decline. More than 20% of patients with distant metastasis can survive 5 years or longer.[28]

Recurrence may occur 10-20 years after the initial treatment and, hence, long-term follow-up is mandatory. Unlike SCC, survival cures of patients with ACC continue to decline after 5 years.

Sinonasal undifferentiated carcinoma

Sinonasal undifferentiated carcinoma (SNUC) is a rare, aggressive malignancy first described by Frierson et al in 1986.[29] It is characterized by rapid growth, a propensity for early locoregional recurrences, and distant metastases. Men with a median age of approximately 50 years are most commonly affected. The tumor usually arises in the nasal cavities and the great majority of patients present with locally advanced tumors, including involvement of the orbit or anterior cranial fossa. Histologically, SNUC is made up of small to medium sized pleomorphic cells with a high nuclear-cytoplasmic ratio and high number of mitoses. It is part of the differential diagnosis of other small cell carcinomas such as esthesioneuroblastoma, lymphoma, rhabdomyosarcoma, and melanoma.Distinguishing these tumors often require electron microscopy or immunohistochemistry. SNUC stains positive for cytokeratin 7, 8, and 19 and neuron-specific enolase.[30]

Another important differential diagnosis is nasopharyngeal undifferentiated carcinoma. These 2 entities can be differentiated based on their immunohistochemistry and the presence of Epstein-Barr virus in the tumor tissue (absent in SNUC). Making the distinction is important, as the treatment and prognosis differ significantly. SNUC has a poorer prognosis with a median survival reported to be 18 months.[31]

The overall outcome for SNUC remains poor. An aggressive multimodality approach including surgery (for resectable disease), radiation, and platinum-based chemotherapy offers the best chance for locoregional control and cure. The optimal sequence of multimodality treatment remains unresolved. In patients with unresectable disease, chemoradiation (if performance status permits) or radiation alone can give good palliation.[30] The risk of loco-regional recurrence after treatment is 20-30%, while the risk of distant dissemination is approximately 25-30%.[32]

Olfactory neuroblastoma

Esthesioneuroblastoma (ENB), also known as olfactory neuroblastoma, is a rare tumor arising from the olfactory epithelium in the superior nasal vault. It represents 7-10% of sinonasal malignancies and has a bimodal frequency at 10-20 and 50-60 years of age, with a similar gender distribution.[16] Microscopically, the tumor is made up of round cells that are characteristically arranged into rosettes, pseudorosettes, or sheets and clusters. It expresses neuroendocrine markers such as neuron-specific enolase (NSE), chromogranin, and synaptophysin, which help to differentiate it from other small cell carcinomas. Hyams described 4 grades of differentiation based on several features such as growth, architecture, mitotic activity, nuclear pleomorphism, etc.[33]

Histologic grade of esthesioneuroblastoma seems to correlate with prognosis and impacts its treatment. A recent study found at a median follow-up of 9.6 years that median disease-free and overall survival were 5.4 and 20.5 years in low-grade ENB compared with 1.5 and 2.5 years for high-grade ENB, supporting the notion that these tumors behave as distinct entities.[34]

The prognosis is mostly related to the extent of disease and resectability on initial presentation. Several staging systems have been described to characterize the extent of ENB. The Kadish staging system was first described in 1976 and remains the most commonly used system. Nonetheless, the UCLA staging by Dulguerov and Calcaterra seems to provide better prognostication since factors such as orbital or extradural invasion are considered separately from intracranial intradural invasion.[35]

Kadish staging system is as follows:

  • Stage A tumors are confined to the nasal cavity.

  • Stage B tumors in the nasal cavity show extension into the paranasal sinuses.

  • Stage C tumors extend into the orbit, base of skull, cranial cavity or present with cervical or distant metastasis.

UCLA staging system is as follows:

  • T1 tumors involve the nasal cavity, paranasal sinuses, or both (excluding sphenoid), sparing the most superior ethmoidal air cells.

  • T2 tumors involve the nasal cavity, paranasal sinuses, or both (including the sphenoid), with extension to or erosion of the cribriform plate.

  • T3 tumors extend into the orbit or protrude into the anterior cranial fossa.

  • T4 tumors involve the brain.

Surgical excision is the treatment of choice. Among the various surgical approaches, an anterior skull base resection (via craniofacial, or endoscopic or endoscopic-assisted approach) is considered the criterion standard. It allows for good oncologic resection with tumor-free margins. Recent improvements in endonasal endoscopic techniques, both extirpative and reconstructive, have allowed their use for the resection of ENB.[36, 37]

Although the extent of resection remains unchanged, the endonasal endoscopic approach spares the patient of the potential sequelae and side effects associated with a traditional craniofacial resection. The addition of postoperative radiation therapy has improved the therapeutic results.[38] The 5-year disease-free survival for all stages is 65% after combined surgery with radiotherapy.

In a large series of 50 patients reported by University of Virginia, the disease-free survival was 86.5% and 82.6% at 5 and 15 years, respectively. Their protocol differs in that they advocate preoperative radiation for Kadish Stage A or B and in that they add neoadjuvant chemotherapy for Kadish Stage C. In their series, 12 patients developed locoregional recurrence; while 5 patients developed distant metastases. The mean time to recurrence was 6 years; thus, the authors stressed the importance of long-term follow-up.[39]

Mucosal melanoma

Melanoma of the head and neck is, in general, a rapidly lethal neoplasm. Although 20% of all melanomas originate in the head and neck, less than 1% arises from the sinonasal tract. They are most commonly found in the nasal cavity followed by the maxillary sinus and oral cavity.[1] Within the nasal cavity, it is often found on the nasal septum or inferior turbinate and spreads submucosally with little erosion of adjacent cartilage and bone. Their pigmentation and clinical appearance varies considerably, ranging from normal pigmentation to being heavily pigmented, and they can be polypoid, exophytic, or ulcerated. The immunostains most commonly used to confirm the diagnosis are S-100 and HMB-45.[40]

Most mucosal melanomas manifest with disease confined to the primary site; however, they are commonly at an "advanced" staged due to their depth of invasion. The possibility of regional or distant metastases must be considered in all cases. One third of all patients have neck metastases, and their presence strongly suggests distant spread. More than half the patients have a local recurrence and often show distant metastases thereafter.[40] Distant metastases are usually rapidly fatal, although some patients achieve long-term control with aggressive salvage surgery for local recurrence.

Survival is primary impacted by advanced T stage and the presence of regional metastases.[41] Other prognostic factors include site (nasal septum has a better prognosis than maxillary sinus and lateral nasal wall), volume, and thickness.[40] However, the overall prognosis and survival rates are poor. The median survival is 19-21 months, and the overall 5-year survival is about 22%.[40, 42] Most patients succumb to the disease within the first 36 months.[42]

Surgical resection with clear margins is the treatment of choice. Currently, no effective therapy for sinonasal mucosal melanoma exists, and the prognosis remains grim regardless of treatment modality. The incidence of local recurrence is high, even with fresh frozen section to ensure complete excision. The aim of radiotherapy is to improve locoregional control,[43] but some studies have failed to show any improvement in local control or overall survival.[40, 42] Nevertheless, both surgery alone and surgery combined with postoperative irradiation are superior to radiation therapy alone.[40] Adjuvant therapies such as systemic interferons and vaccines are under investigations.

Malignant Nonepithelial Tumors

Although the metastatic potential and oncologic outcome of sarcomas arising in the sinonasal tract is variable among the different histologic types, the local behavior of sarcomas is similar. Sarcomas infiltrate and advance further than what the naked eye or imaging can appreciate. This often leads to an inadequate resection and subsequently to a local recurrence. Wide excision is necessary to improve the local control, but this may be difficult to achieve due to the proximity of vital structures to the sinonasal.

Neurogenic sarcomas

Neurogenic sarcomas are rare in the head and neck and are most commonly associated with neurofibromatosis. They are locally aggressive and frequently present with distant metastases. Surgical resection is the mainstay treatment with radiation and chemotherapy reserved for incomplete removal, inoperable cases, or recurrences.[44] The 5-year survival rate is around 60%. Those associated with neurofibromatosis have the poorest prognosis, with a 5-year survival rate around 30%.[44]

Rhabdomyosarcoma

Rhabdomyosarcomas involve the head and neck region in 35-45% of cases. The sinonasal tract is involved in 10% of cases, affecting the head and neck.[45] Histologically, they are classified into 5 major categories: embryonal (most common), alveolar, botryoidembryonal, spindle cell embryonal, and anaplastic. The embryonal and alveolar varieties are more common in children and young adults, while the anaplastic type is more common in adults. Rhabdomyosarcomas in adults have a less favorable outcome, with a 5-year survival rate of only 35%.[46]

Rhabdomyosarcomas of the sinonasal tract are classified as nonorbitalparameningeal and behave more aggressively than those arising in other locations. Systemic and regional metastases are common. Treatment includes a multimodality approach involving a combination of chemotherapy, radiation, and surgery.[47] For early superficial nonorbital lesions, wide excision is recommended, provided that function and cosmesis can be preserved. This is often difficult because of the anatomic constraints in the head and neck region. The Intergroup Rhabdomyosarcoma Studies IV showed that aggressive surgical management is not necessary. A successful treatment for the large majority of patients with localized parameningeal sarcoma can be achieved with intensive chemotherapy and radiation.[48] Conversely, adults are usually treated by wide surgical excision. Radiation is recommended for positive margins or inoperable or recurrent disease. Chemotherapy only has a palliative role.

Fibrosarcoma

Fibrosarcoma is a tumor arising from fibroblast and has a spectrum that ranges from low-grade to higher-grade tumors. Radiation and trauma have been implicated as possible etiologic factors. The treatment of choice is wide surgical excision for previously untreated tumors. Radiation is recommended for involved margins or recurrent or inoperable tumors.

Chondrosarcoma

Chondrosarcomas are slow-growing tumors that arise from cartilaginous structures. Approximately 5-10% are located in the head and neck, mostly in the maxilla and mandible. These tumors are graded from I to III on the basis of the rate of mitoses, cellularity, and nuclear size. The size of the tumor and grading correlate with the local aggressiveness, rate of metastasis, and ultimate survival. Surgical removal with wide margins is the treatment of choice. Gross total removal with postoperative radiation is recommended for those involving vital structures and for those exhibiting a high histological grade.

Hemangiopericytoma

Hemangiopericytomas are rare perivascular tumors with variable malignant potential. They arise from the pericytes of Zimmerman in the walls of capillaries. Vascular pericytes are of mesenchymal origin that spiral around capillaries and postcapillaryvenules. They are believed to be capable of differentiating into smooth muscle cells. They possess contractile properties and are able to modify the lumen of blood vessels to regulate blood flow.

Hemangiopericytoma invade locally and metastasize in 10-15% of cases. Sixteen percent are found in the head and neck, with about 50 reported cases arising in the sinonasal tract.[49] The primary treatment is surgical excision. Life-long follow-up is required to evaluate local recurrence and late metastases.

Lymphoma

Lymphoma of the sinonasal tract accounts for 5.8-8% of the extranodal lymphomas in the head and neck area. Although rare, they are still the most common nonepithelial malignant tumors of the nose. It is a disease of the very young or the aging adult. With advances in immunochemistry, they are classified according to the cell of origin into B-cell, T cell, or NK-T cell lymphomas.[50]

The T/NK-cell lymphoma T-cell lymphomas are typically found in the nasal cavity and are more common in Asian and South American countries. Patients present at a younger age. These lymphomas have an aggressive, angioinvasive growth pattern that result in necrosis and bony erosion. It has been termed in the past as midline lethal granuloma, which is a progressive, destructive lesions affecting the midline of the face. With advancement in immunohistochemistry, they have been determined to be of T-cell or natural killer (NK) origin. T/NK-T-cell sinonasal lymphomas are associated with Epstein-Barr virus infection. It is postulated that once EBV infection occur, the NK /T cell are activated and recruited to the nasal mucosa. A single clone of T or NK cell, influenced by other possible molecular accidents, continues to proliferate and ultimately leads to NK/T cell lymphoma.

By contrast, B-cell lymphomas are typically located in the paranasal sinuses and have a slight predominance in Western countries. They are believed to arise from sinonasal mucosa–associated lymphoid tissue (MALT) that resides in the subepithelium. MALT contains specialized clusters of lymphocytes next to mucosal surfaces. It is characterized by a chronic inflammatory infiltrate.

Clinically, NK/T-cell lymphomas can be distinguished from B-cell lymphomas by location (as mentioned above) and appearance. NK/T-cell lymphomas often cause severe destruction of the nasal septum and midline facial structures. They are characterized by unrelenting ulceration and necrosis. The tumor cells frequently infiltrate and destroy blood vessels, causing ischemic necrosis. Conversely, B-cell lymphomas tend to surround, but not invade, blood vessels. Extensive necrosis and ulceration are extremely rare.

The treatment includes radiation therapy for localized lesions and chemotherapy for systemic involvement or to prevent systemic recurrence. A good response is achieved with local radiotherapy alone, often with complete tumor regression. However, the incidence of metastasis and local recurrence is high (up to 49%). With the addition of chemotherapy, such as cyclophosphamide, hydroxydaunomycin, Oncovin, and prednisone (CHOP), a reduction in recurrence and metastasis and improved survival rates are observed. Patients treated with chemotherapy alone have a higher risk of local recurrence. Bone marrow transplant in a few patients that were refractory to the combined treatment yielded mixed results. For high-grade aggressive lymphomas, the central nervous system is at risk for tumor involvement. The current recommendation is to radiate the CNS only if disease involvement is documented by lumbar puncture and MRI, not prophylactic ally.

The 5-year overall survival rate for all subtypes is 52%. A younger age, early stage of disease, and the use of combination chemoradiotherapy correlate with a better prognosis. Although univariate analyses demonstrate that T-cell lymphomas are associated with a lower cure rate, a higher relapse rate, and a worse overall survival rate, tumor immunophenotype is not an independent prognostic factor based on multivariate analyses.

Extramedullary plasmacytoma

Extramedullaryplasmacytoma refers to a malignant plasma cell tumor growing outside the bone marrow. They involve the head and neck region in 80-90% of the cases, and around 40% of them arise in the sinonasal tract. They are more common in the sixth to seventh decades. Extramedullaryplasmacytomas tend to spread locally, and can be found in the cervical nodes in less than 25% of the cases. Most of these lesions respond to radiation therapy in doses of 4000-5000 cGy administered over 4-5 weeks.

Metastatic Tumors

Metastatic tumors to the sinonasal tract produce symptoms similar to those of primary tumors. The most common sources are the kidneys, breasts, and lungs. Maxillary sinus is the most frequent site affected by metastases followed by ethmoid, frontal, and sphenoid sinus in descending order. Their treatment is palliative, using radiation, surgery, or chemotherapy to relieve obstructive and compressive symptoms or pain.

Staging

Staging of nasal cavity and paranasal sinus carcinomas is not as well established as for other head and neck tumors. For cancer of the nasal cavity and the ethmoid sinus, the American Joint Committee on Cancer (AJCC) has designated a staging system using the TNM classification.[51] This staging system differentiates resectable (T4a) from unresectable (T4b) tumors by recognizing recent surgical advances and limitations, as follows:

  • TX: Primary tumor cannot be assessed

  • T0: No evidence of primary tumor

  • Tis: Carcinoma in situ

  • T1: Tumor restricted to any one subsite, with or without bony invasion

  • T2: Tumor invading two 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

The AJCC also recommends a different system for soft-tissue sarcomas. This system includes a histologic grading system that differs from the system used for epithelial tumors. Grading is considered the most significant prognostic factor in patients with mesenchymal tumors and is based on the number of mitoses, degree of cellularity, amount of stroma, degree of maturation, nuclear pleomorphism, and presence or absence of necrosis.

 

Treatment

Medical Therapy

Surgery is the mainstay of treatment for most sinonasal tumors. Radiation as the sole modality of treatment is recommended for unresectable cases, poor surgical candidates, or lymphoreticular tumors. Combination therapy of surgery and adjuvant radiotherapy with or without chemotherapy is given in situations with an advanced tumor (T3 and T4), positive surgical margins, perineural spread, perivascular invasion, cervical lymphatic metastasis, and recurrent tumors. Chemotherapy may also have a palliative role for cytoreduction.[52]

Radiation therapy

Radiation may be used as a single modality, as an adjunct to surgery, or as palliative therapy. It is the primary treatment for lymphoreticular tumors and in patients who are poor surgical candidates, refuse surgical treatment, or have tumors that are deemed inoperable. As an adjunct to surgery, it can be given preoperatively or postoperatively with similar oncological results. Preoperative radiation is given in cases of bulky tumor to help decrease the tumor volume that would have resulted in severe cosmetic and functional morbidity with resection. We favor giving radiation therapy after surgery, as a smaller volume of tumor cells exist, the margins of the non-radiated tumor can be better defined during surgery, and the postoperative wound healing is more predictable.

Radiological response to radiotherapy is used as a means to assess treatment response, but evidence suggests that early response is not a significant prognostic indicator, albeit there is a tendency for improved outcomes in sinonasal squamous cell carcinoma that shows an early response.[53]

Chemotherapy

The role of chemotherapy for the treatment of tumors of the sinonasal tract is usually adjunctive to radiotherapy (radiosensitizer) or palliative, using its cytoreductive effect to relieve pain, obstruction, or to debulk a massive external lesion. It is increasingly being given concurrently with radiation and used in patients at high risk of recurrence, such as those with positive margins after resection, perineural spread, or extracapsular spread in regional metastases.

Surgical Therapy

Surgery

Surgical resection is usually performed with curative intent. Oftentimes, obtaining wide surgical margins may not be possible because of the proximity of critical structures. Postoperative radiation is then recommended to reduce the incidence of local recurrence. In some cases, palliative excision or debulking may be considered to alleviate intractable pain, or to relieve decompression of the optic nerve or orbit, or to drain obstructed paranasal sinuses.

Traditionally, the surgical resection is carried out in an en bloc fashion and usually via an open approach. The types of resection and surgical approaches used will depend on tumor size and its extension.

Tumors confined to the nasal cavity can be assessed via a variety of approaches including transanasal endoscopic, sublabial, lateral rhinotomy approaches or a combination of endoscopic and open techniques. Advanced tumors may require orbital exenteration, partial or total maxillectomy or anterior cranial base resection. Resection of the anterior skull base is considered the criterion standard for malignant tumors that are in contact with or transgress the anterior skull base. Select patients selected patients may be treated using endonasal-endoscopic approaches. Resections may be extended laterally to join a temporal craniotomy to include the pterygoid plates, the pterygopalatine fossa, and the floor of the middle cranial fossa en bloc.

Bony erosion of the orbital walls does not constitute an indication for orbital exenteration. In rare cases, the periorbita has been breached by tumor requiring an orbital exenteration. The prognosis in these cases is usually poor.

Absolute contraindications for surgery include those patients who are not medically fit due to medical or nutritional problems, presence of distant metastases, invasion of the prevertebral fascia, invasion of the cavernous sinus by a high-grade malignancy, involvement of the carotid artery in a high-risk patient (as determined by carotid flow studies), and bilateral invasion of the optic nerves or optic chiasm. Relative contraindications include invasion of the brain and intracranial involvement of neural structures by adenoid cystic carcinoma. These situations usually have a poor prognosis, but in selected patients a surgical resection may offer significant palliation or local control.

Recent advances in preoperative imaging, intraoperative navigation system, endoscopic instrumentation, and hemostatic materials have made endoscopic resection of nasal and paranasal sinus tumors a viable alternative to the traditional techniques. Its role in resecting small lesions confined to the nasal cavity is well established. With increasing experience, endoscopic endonasal approaches have expanded beyond the nasal cavity and paranasal sinuses to areas such as the infratemporal fossa and cranial cavity. Endoscopic techniques can be used alone or in combination with open approaches, according to the different degree of involvement of the anterior skull base.

A retrospective study by Swegal et al indicated that endoscopic resection of sinonasal mucosal melanoma produces similar results to those of open resection and can therefore provide an alternative approach to treatment of the disease. The study, which involved 25 patients, including 12 individuals who underwent the endoscopic procedure and 13 who underwent open resection, reported disease-free survival rates of 1.2 and 1.9 years, respectively, with the number of local, distance, and multiple failures being similar between the two groups.[54]

The primary concern about using an entirely endoscopic approach to resect malignant sinonasal tumors is the adherence of oncological principles. Although the instrumentation may be different, the surgical strategy and goals are similar. En bloc excision of the entire tumor is not necessary; rather, the authors perform a sequential layered resection of the area of invasion. The cribriform plate and its attached dura from the posterior wall of the frontal sinus back to the planumsphenoidale and between the orbits can be resected sequentially with adequate margins. Frozen sections are used to confirm clear margins.

In order to reach the area of invasion, debulking the tumor first is frequently necessary. This does not violate normal tissue planes because the tumor is residing in an air-filled cavity. Currently, no evidence exists that debulking increases the risk of local recurrence. Examples of other neoplasms that are removed in a piecemeal without compromise of results include laser resection of pharyngeal and laryngeal squamous cell carcinomas and microscopically controlled excision of skin cancers in Moh’s technique.

Expansion of the indications to use an endonasal endoscopic approach for the resection of advanced sinonasal tumors that have transgressed the skull base followed the development of more effective means of reconstruction to seal off the intracranial cavity from the nasal cavity. The nasoseptal flap is the biggest advance in the reconstruction of the skull base in endoscopic sinus surgery.[55] It drastically decreases the rate of cerebrospinal fluid leak. Other pedicled flaps that have been described for reconstruction include the tranasionpericranial flap, transpterygoidtemporoparietal fascia flap, inferior turbinate flap, and palatal flap.

Advantages of the endoscopic approach include the avoidance of facial incisions, low morbidity, and shorter length of hospital stay. Early oncologic outcomes are at least equivalent to those of open approaches, although long-term follow-up and larger cohorts of patients are needed before it gains universal acceptance.[56, 57]  However, a retrospective study by Hagemann et al did find that in patients with stage T3 sinonasal cancer, endoscopic resection resulted in significantly better overall and disease-specific survival rates in the long-term than did open craniofacial surgery.[58]

Contraindications to a completely endoscopic endonasal approach include invasion of the orbit, involvement of superficial tissues such as the anterior and lateral portion of the frontal sinus, anterior wall of the maxillary sinus and nasal bones, and invasion of the skin.

Reconstruction

Wide resection of tumors of the nasal cavity and paranasal sinuses can result in facial disfigurement and speech and swallowing difficulties. The main goals of postsurgical rehabilitation of these massive multilayered defects are primary wound healing, preservation or reconstruction of the facial contour, and restoration of oronasal separation, thus facilitating speech and swallowing and separation of the nasal cavity from the cranial cavity. Functional considerations take precedence over aesthetics.Reconstruction options range from simple closure to the use of free tissue grafts (fat, cadaveric acellular dermis, fascia) to the use of vascularized flaps such as pedicled regional flaps (eg, pectoralis major, latissimusdorsi, trapezius) or free microvascular flaps (eg, radial forearm, anterolateral thigh), as seen in the images below. Flaps are recommended to replace resected facial skin, to provide support for the orbit or brain, or to isolate the cranial cavity from the nasal cavity. Adental obturator or prosthesis is commonly used for oronasal separation, although in patients undergoing a free flap the fistula is usually corrected as part of the reconstruction.

In lateral rhinotomy, a straight incision is made In lateral rhinotomy, a straight incision is made at the naso-maxillary junction followed by a curvilinear incision around the nasal ala.
A Weber-Ferguson incision is usually indicated for A Weber-Ferguson incision is usually indicated for a total maxillectomy.
A cranial base resection with a view of the anteri A cranial base resection with a view of the anterior skull base and nasal cavity from the top.

Follow-up

Routine, long-term follow-up is necessary for proper oncological surveillance. Examination of the treated site can help to identify recurrence or even a new primary tumor. Rigid or flexible endoscopy can help to facilitate this evaluation in a postoperative patient. Abnormal findings or new symptoms that are suspicious for recurrence warrant further radiological evaluation (CT scan, MRI, or both).

Complications

Surgical

The extensive nature of surgical resection can cause a variety of complications including bleeding, cerebrospinal fluid leak, infection (including intracranial abscess and meningitis), and blindness.

The proximity of the eye can also lead to potentially severe ophthalmic complications. Sacrifice of the nasolacrimal duct during a maxillectomy and subsequent stenosis of the lacrimal sac opening may lead to epiphora. Performing a dacryocystorhinostomy during resection can prevent this complication. Limitation of extraocular eye movement may occur after trauma to the muscle, its motor innervation, or upon entrapment in craniofacial osteotomies. This latter complication should be managed by urgent surgical release. Limitation of extraocular muscle movement due to edema or neuromuscular contusion is managed expectantly. Alternating eye patching may alleviate diplopia.The optic nerve may be compressed during the mobilization of the specimen or during craniofacial resection. High-dose steroids and emergent surgical decompression are recommended. Enophthalmos or hypophthalmos may develop because of the loss of the inferior orbital and/or medial support and can be prevented with appropriatereconstructive techniques.

Radiation therapy

Traditionally, external beam radiation fields include the anterior (eyelids, conjunctiva, lacrimal gland and apparatus, cornea, lens, and the rest of the anterior chamber) and posterior orbital segments. This can result in orbital complications in close to 100% of patients. Anterior segment irradiation may lead to dry eye, severe keratitis, panophthalmitis, and blindness within a year. Enucleation may be necessary for uncontrolled panophthalmitis or a painful eye. If the anterior segment is spared, a delayed loss of vision may still develop in 3-5 years due to postradiation retinopathy or optic neuropathy.The incidence of these complications is related to total dose and fractionation and increase with the use of concomitant chemoradiation. They are rare below 3500 cGy, 50-65% with 6000-7000 cGy, and above 85% with 8000 cGy. Other common side effects from radiation therapy include xerostomia, mucositis, trismus, and osteonecrosis.

Over the past 2 decades, 3D conformal radiation therapy and, more recently, intensity modulated radiation therapy (IMRT) have replaced conventional external beam. These techniques minimize the dose delivered to vitals structures close to the tumor. As a result, side effects from high-dose radiation have decreased, and the patients’ quality of life has improved. This is achieved without compromising the clinical outcome for the patients.[59]

With IMRT, the incidence of optic nerve and other ocular complications have greatly decreased.[21, 60, 61, 62] Claus et al compared the complication rates of external beam radiation with 3D-conformation and IMRT in 47 patients who underwent postoperative radiation following resection of adenocarcinoma of the ethmoid sinuses. Radiation-induced severe dry eye syndrome, characterized by chronic conjunctivitis and keratitis, and accompanied by a significant decrease of the vision was observed in 7 cases, all of whom were treated with conventional radiation techniques. Enucleation of the eye was necessary in one patient to control the symptoms. Another 2 patients had optic neuropathy. No neuropathy was found in the group treated with IMRT.[21] Chen et al reported a longitudinal study of 127 patients treated with RT from 1960-2005 at UCSF. The incidence of grade 3 and 4 late ocular toxicity among patients treated with conventional RT, 3D CRT, and IMRT was 20%, 9%, and 0%,respectively.[60] In another series by Hoppe et al, none of the patients who underwent IMRT developed Grade 3–4 late ocular complications.[61] As the experience with IMRT increases, the late complication rates are anticipated to also continue to decrease.

The North American Skull Base Society is currently investigating the role of high-dose IMRT and concomitant cisplatin chemotherapy with or without surgery for advanced paranasal cancers. The protocol is under development with the goal to determine the feasibility of nonsurgical therapy for these tumors in a multi-institution setting.[59]

Wound complications

Wound complications include bleeding, infection (skin, meningitis, or intracranial abscess), and loss of reconstructive flaps or skin grafts. Crusting in the nasal cavity after surgery or irradiation is a common problem and may lead to infection. Frequent irrigation with normal saline solution can soften the crust and maintain nasal hygiene. Meningitis or intracranial abscess is more likely in the presence of a CSF fistula, which can occur after destruction of the skull base and disruption of the dura mater. Treatment involves intravenous antibiotics, drainage of intracranial abscess, and repair of the fistula with dural graft or vascularized flap, if available. Osteoradionecrosis of the maxilla or mandible can occur in up to 10% of patients with poor dentition and recently extracted dentition. Antibiotics and local debridement of the necrotic bone will be needed.

Outcome and Prognosis

The prognosis of treatment outcome depends on several important factors as follow:

  • Tumor histopathology is an important independent prognostic factor. Low-grade esthesioneuroblastoma, adenocarcinomas, and chondrosarcomas have the best prognosis, while malignant melanoma has the worst outcome. Other high-grade tumors such as squamous cell carcinoma and adenocarcinoma have an intermediate survival rate.

  • Extent of disease. Invasion into dura and brain has a poor prognosis associated with a high incidence of local recurrence and a worse survival rate.

  • Surgical margins. Obtaining clear surgical margins intraoperatively has a prognostic value that is independent of tumor type and extent of the disease.

Overall survival at 5 years, according to a large study by Patel et al, was best for low-grade neoplasms such as esthesioneuroblastoma (78%) and low-grade sarcomas (69%), intermediate for high-grade sarcomas (57%), adenocarcinoma (52%), salivary malignancies (46%), and squamous cell carcinoma (44%), and worst for undifferentiated/ anaplastic carcinoma (37%) and mucosal melanoma (18%).[63]

The aforementioned study by Gerth et al found the overall 5-year survival rate in patients below age 20 years to be 62.5%, with the lowest survival rates occurring among patients aged 1-4 years and 15-19 years (median survival 205 and 104 mo, respectively).[5]

Future and Controversies

Treatment of the orbit

Before the 1970s, the classic surgical treatment for sinonasal cancers in close proximity to the orbit involved radical excision with orbital exenteration. The introduction of orbital preservation surgery has decreased the indications and need for removal of orbital structures. The main concerns are the oncological safety of orbital preservation and the function of the preserved eye.

Controversy remains regarding which is the limit of the degree of orbital invasion that allows the safe sparing of the orbital contents. Most studies do not show any statistically significant difference in local recurrence or actuarial survival between those patients who undergo orbital preservation and those who do not.[1] Some propose that the eye can be safely preserved in most patients with ethmoid or maxillary sinus cancer invading the orbital wall, including malignancies that invade the orbital soft tissues with penetration through the periorbita, provided that they can be completely dissected away from the orbital fat.[64] Indications for orbital exenteration include involvement of the orbital apex, unresectable full thickness invasion through periorbita into the retrobulbar fat, extension into the extraocular eye muscles, and invasion of the bulbar conjunctiva or sclera.

Malposition of the globe and nonfunctional eyes often result when patients have not had an adequate and rigid reconstruction of the orbital floor. Rigid reconstruction of the bony orbit using titanium mesh with or without calvarial bone grafts is recommended; these are then covered with local, regional, or microvascular free flaps.

Future

The role of endoscopic sinus surgery for the resection of malignant tumors of the nasal cavity and paranasal sinuses will continue to evolve and the results closely scrutinized. More long-term results, comparing its results with traditional surgery such as craniofacial resection are needed. Surgeons embracing this approach need to understand the limits of this approach and continue to adhere to oncological principles.

The use of IMRT will continue to gain acceptance and probably will be the standard mode of radiation treatment given for all head and neck patients in the future. Reductions in short-term acute toxicities are well established, but late complications need to be continuously evaluated. The emergence of proton therapy may further reduce the complications due to radiation therapy.