Key points

Introduction

Malignancies of the nose, sinus, and skull base are rare, comprising approximately 3% to 5% of cancers of the head and neck with an incidence of 0.556 cases per 100,000 in the United States. The most common histologies are squamous cell carcinoma (SCC) (52%) and adenocarcinoma (13%), whereas the most common primary sites are the nasal cavity (44%) and maxillary sinus (36%). Cancers arising in the frontal and sphenoid sinuses are very rare.

Management of these tumors is technically challenging because they often present in advanced stages. Nasal cavity tumors have improved survival outcomes compared with sinonasal and skull base tumors. Overall 5-year survivals reported range from 22% to 67%. Tumors that are superior or posterior to Ohngren line are associated with a worse prognosis due to increased incidence of skull base invasion and perineural spread. In the last few decades, advances in surgical resection techniques, as well as improved strategies to deliver adjuvant radiation (minimizing morbidity) have substantially improved the outcomes in patients with malignancies of the sinonasal tract and skull base.

Introduction

Malignancies of the nose, sinus, and skull base are rare, comprising approximately 3% to 5% of cancers of the head and neck with an incidence of 0.556 cases per 100,000 in the United States. The most common histologies are squamous cell carcinoma (SCC) (52%) and adenocarcinoma (13%), whereas the most common primary sites are the nasal cavity (44%) and maxillary sinus (36%). Cancers arising in the frontal and sphenoid sinuses are very rare.

Management of these tumors is technically challenging because they often present in advanced stages. Nasal cavity tumors have improved survival outcomes compared with sinonasal and skull base tumors. Overall 5-year survivals reported range from 22% to 67%. Tumors that are superior or posterior to Ohngren line are associated with a worse prognosis due to increased incidence of skull base invasion and perineural spread. In the last few decades, advances in surgical resection techniques, as well as improved strategies to deliver adjuvant radiation (minimizing morbidity) have substantially improved the outcomes in patients with malignancies of the sinonasal tract and skull base.

Risk factors

Risk factors associated with sinonasal SCC include occupational exposure to nickel, soft wood dust, radium, mustard gas, and asbestos. Adenocarcinomas are associated with exposure to hardwood dust, chrome pigment, textile dust, and leather work. Occupational exposure to formaldehyde is associated with an increased risk of acquiring both sinonasal adenocarcinomas and SCC. Radiation is a significant risk factor in the development of head and neck sarcomas, including sinonasal sarcomas. Significant risk factors, such as alcohol and tobacco use, have not been associated with other less common histologies in malignant sinonasal and skull base tumors.

Anatomy of the nose and sinus

The nasal cavity is bounded by the cribriform plate and the ethmoid bone superiorly and by the hard palate inferiorly. Anteriorly, it is bounded by the bony pyriform aperture and the external framework of the nose. Posteriorly, the choanae communicate with the nasopharynx. The nasal septum, which divides the 2 sides of the nasal cavity, is formed by cartilaginous and bony components. The cartilage of the septum is quadrangular in shape. Anteriorly, it connects with the nasal bones and is continuous with the anterior margins of the lateral cartilages. Inferiorly it is connected to the medial crura of the alar cartilages by fibrous tissue. It connects posteriorly to the perpendicular plate of the ethmoid and inferiorly to the vomer bone and palatine process of the maxilla. The inferior, middle, and superior turbinates are 3 bony projections from the lateral wall of the nose that help humidify as well as regulate the temperature of inhaled air. The bulla ethmoidalis is the most prominent anterior ethmoid cell.

The roof of the nasal cavity slopes downward at about a 30-degree angle from anterior to posterior. The cribriform plate forms the roof of the nasal cavity medial to the superior attachment of the middle turbinate and transmits the olfactory nerve. Lateral to the middle turbinate, the roof of the ethmoid sinuses is formed by the fovea ethmoidalis. The relationship of the cribriform plate to the fovea ethmoidalis is described by the Keros classification. Keros type I refers to the cribriform plate being in a slightly lower horizontal plane (1–3 mm) than the fovea ethmoidalis. Keros type II refers to the cribriform being moderately lower (3–7 mm) than the fovea ethmoidalis. Keros type III refers to the cribriform plate being significantly lower (8–16 mm) than the fovea ethmoidalis. These are important distinctions during surgical planning for management of tumors involving the nose and sinuses.

The paranasal sinuses are hollows in bones surrounding the nose. The bones in which they lie define the names of the sinuses. They are lined with pseudostratified ciliated columnar epithelium continuous with the mucous membranes of the nasal cavity. Cilia in the mucosa carry secretions from the sinuses into the nasal cavity. The frontal sinus drains into the anterior part of the hiatus semilunaris via the infundibulum. The hiatus semilunaris also receives secretions from the maxillary sinus and the anterior ethmoids. The posterior ethmoids drain into the superior meatus. The sphenoid sinus drains into the sphenoethmoidal recess, a space above the superior concha. The inferior meatus contains the opening of the nasolacrimal ducts, carrying tears into the nasal cavity.

Sensory innervation of the nose is provided by the trigeminal nerve. The ophthalmic division (V1) provides ethmoidal branches to the anterior part of the nose, the floor of the nose, and the sphenoid and ethmoid sinuses. V1 also provides innervation to the frontal sinus via the supraorbital branch. The maxillary division (V2) of the trigeminal nerve innervates the lateral wall of the nose and the maxillary sinus via its infraorbital branch.

The nasal cavity and paranasal sinuses have a rich blood supply, primarily from the sphenopalatine branch of the internal maxillary artery. The internal maxillary artery enters the nose from the pterygopalatine fossa, posterior to the maxillary sinus. The facial artery perfuses the vestibule of the nose through the superior labial branch and the ophthalmic branch of the internal carotid artery supplies the roof of the nose and the nasal septum through the anterior and posterior ethmoidal arteries.

Anatomy of the anterior skull base

The anterior skull base is often invaded in cases of sinonasal carcinoma. It is defined as the bony partition between the frontal lobes of the brain in the anterior cranial fossa and the midline and paramedian facial structures, including nasal cavity and orbits.

The gyri of the frontal lobes overlie most of the anterior cranial fossa; the ocular gyri and gyrus rectus lie lateral to the midline. The floor of the anterior cranial fossa is composed of ethmoid, sphenoid, and frontal bones. Anteriorly, it forms the crista galli and cribriform plate of the ethmoid bone covering the upper nasal cavity. The crista galli defines the midline of the anterior skull base. Posteriorly, it forms the planum sphenoidale. Laterally, the frontal bone and lesser wing of the sphenoid form the roof or the orbit and the optic canal; they blend medially into the anterior clinoid process. The cribriform plate is the thinnest portion of the ethmoid bone and transmits the first cranial nerve to the olfactory fossa through multiple foramina.

Tumor of the sinonasal region readily invades the infratemporal fossa, situated inferiorly to the temporal fossa. The temporalis muscle is located in the temporal fossa and inserts into the coronoid process and the mandibular ramus. Distally, the temporalis muscle traverses deep to the zygomatic arch and forms the lateral wall of the infratemporal fossa. The roof of the infratemporal fossa is the floor of the middle cranial fossa. The boundaries of the infratemporal fossa include the maxillary sinus anteriorly, the parotid gland posterolaterally, the ascending ramus of the mandible and the temporalis muscle laterally, the zygomatic arch and the greater wing of the sphenoid posteriorly, as well as the pterygoid fascia. It includes the parapharyngeal space (containing the internal carotid artery, internal jugular vein, cranial nerves VI to XII) and the masticator space, which contains the maxillary and mandibular branches of the trigeminal nerve, the internal maxillary artery, the pterygoid venous plexus, and the pterygoid muscles. The infratemporal fossa is connected to the middle cranial fossa via multiple foramina (eg, carotid canal, jugular foramen, foramen spinosum, foramen ovale, foramen lacerum).

Sinonasal carcinomas

Jackson and colleagues originally described the signs and symptoms of sinonasal tumors, with or without involvement of the skull base, in a retrospective study of 115 subjects. These results were validated by a separate study from Memorial Sloan-Kettering. Their prevalence, in descending order, are nasal obstruction (61%), localized pain (43%), epistaxis (40%), swelling (29%), nasal discharge (26%), epiphora (19%), palate lesion (10%), diplopia (8%), cheek numbness (8%), decreased vision (8%), neck mass (4%), proptosis (3%), and trismus (2%). These manifestations can be used to assess extent of the tumor. The presence of palpable neck masses, trismus, and hearing loss indicate metastatic adenopathy, pterygoid invasion, and eustachian tube invasion, all of which portend a worse prognosis.

SCC is by far the most common of the paranasal sinus tumors. It can arise de novo or in association with inverted papillomas, which account for approximately 10% of the cases. Approximately 70% occur in the maxillary sinus, with 12% in the nasal cavity. Although most lesions are moderately differentiated on presentation, they are typically aggressive. The 5-year overall survival of sinonasal SCC ranges from 43% to 59%. The rate of lymph node metastases of sinonasal SCC is approximately 10%. The verrucous subtype has a fungating appearance and carries a better prognosis. In addition, a subset of sinonasal SCC is associated with human papillomavirus (HPV) infection (up to 20% of cases in a recent study). HPV-positive sinonasal SCC seems to have a significantly better prognosis (80% vs 30% 5-year overall survival). SCC is the only epithelial tumor for which TNM staging criteria are established, in view of the rarity of the other subtypes ( Table 1 ). Management is typically primary surgical resection with or without adjuvant radiation. In cases of advanced unresectable disease, primary chemoradiotherapy is used. Either response or stable disease with primary chemoradiotherapy is suggestive of a favorable outcome. Advanced T classification, bone or neural invasion, intracranial extension, dural or brain involvement, or positive margins are indications for adjuvant radiation as part of combined modality treatment. Depending on the histology and stage of disease, induction, as well as postoperative chemotherapy has been used.

Primary intestinal type adenocarcinoma is the second most common sinonasal tumor. It is chiefly found in the ethmoid sinuses. It arises from the epithelial surface of the sinonasal mucosa. This tumor is associated with woodworkers and leather workers. Adenocarcinomas of the sinonasal tract are a diverse group of malignancies that have been classified according to Barnes into papillary, colonic, solid, mucinous, and mixed. According to Kleinsasser and Schroeder, they have also been classified into well differentiated (papillary, tubular, and papillary-tubular type), moderately differentiated (papillary-mucinous and papillary-tubular-mucinous type), and poorly differentiated (mucinous, alveolar goblet cell, signet-ring type). These tumors, when advanced, are treated with surgery followed by adjuvant radiation. Despite aggressive therapy, there is a high recurrence rate (38%). As with most sinonasal carcinomas, cervical metastases are rare. Recurrence and distant metastasis diminish overall survival. Although adjuvant radiation improved local control, it has not been shown to improve survival outcomes.

Adenoid cystic carcinoma is a salivary gland tumor. Although more common in the major salivary glands, it has been shown to grow insidiously in the paranasal sinuses. Such cancers are typically diagnosed in an advanced stage. Their proximity to vital structures (eg, dura, brain, orbit, and central nerves), as well as propensity for perineural invasion, makes resection with clear margins less likely. Adenoid cystic carcinoma in the sinuses, much like its counterpart in salivary glands, has a high propensity for perineural spread and is associated with intracranial extension, positive surgical margins, and poor prognosis.

The sinonasal tumors with neuroendocrine differentiation consist primarily of esthesioneuroblastomas (ENBs), sinonasal undifferentiated carcinoma (SNUC), sinonasal neuroendocrine carcinoma (SNEC), and small cell carcinoma (SmCC), with respective 5-year survival rates of 93%, 62%, 64%, and 28%. Although SNEC and SNUC seem to have a similar clinical behavior, SmCC is clearly more aggressive. Their propensity for distant metastasis and poor prognosis warrant consideration of adjuvant systemic therapy that is mindful of the impact of treatment on the quality of remaining life. The rarity of the disease has frustrated development of clinical trials.

ENB is a rare tumor with the incidence estimated at approximately 0.4 per million people per year. ENB is derived from olfactory neuroepithelium and is responsible for approximately 6% of tumors in the nasal cavity and paranasal sinuses. The age distribution is bimodal, occurring most commonly during the second and sixth decades of life. Neck metastases reported in up to 25% of patients, whereas distant metastases are estimated to occur in 17%. In general, these tumors are treated with a combination of surgery and adjuvant radiation. The validated Kadish staging system is the most commonly used for ENB ( Table 2 ).

SNUCs are derived from schneiderian epithelium and are characterized by fast progression, extensive tissue destruction, and a poor prognosis. Their rapid growth and aggressive behavior often results in extensive local invasion into the sinuses, orbit, and brain. Surgical resection followed by adjuvant radiation has historically been the mainstay of treatment; however, the recent emergence of aggressive trimodality therapy (incorporating surgery followed by postoperative chemoradiotherapy) has improved local-regional control and overall survival.

Sinonasal mucosal melanoma (SMM) is exceedingly rare. It derives from melanocytes in neural crest cells. SMM accounts for 4% to 13% of sinonasal malignant tumors. The 5-year overall survival rate ranges from 17% to 35%. Cervical metastases have been observed in 6% to 22% of patients; distant metastases are relatively uncommon (4%–10%). Surgery to achieve clear margins, when feasible, is the mainstay of treatment. Meleti and colleagues found that rates of locoregional recurrence of head and neck mucosal melanoma were higher with surgery alone than with the combination of surgery with postoperative radiotherapy. These results have been confirmed in other studies. Elective neck dissection is not routinely recommended. Chemotherapy fails to prolong survival but is often used as palliative treatment of those with advanced disease.

Management

A very high index of suspicion is necessary to diagnose sinonasal or skull base malignancies at an early stage because many of these tumors do not cause symptoms until they reach a critical size and extension. A suspicious lesion should be biopsied and imaged before embarking on surgical planning. Computed tomography (CT) and MRI are complementary and essential in many cases and should be obtained in axial, coronal, and sagittal planes. A fine-cut CT scan has the advantage of detecting bone erosion whereas MRI with gadolinium-based IV-contrast and with fat-suppression software is used to differentiate tumor from adjacent soft tissue. Evaluation for distant metastases should include CT of the chest and abdomen or a PET study.

Complete surgical excision, with or without postoperative radiotherapy, is the treatment of choice for most sinonasal and skull base carcinomas. Surgery is the most effective single-modality treatment of sinonasal cancers. Tumor extension to the cavernous sinus, internal carotid artery, optic chiasm, extensive brain parenchymal involvement, or distant metastasis are relative contraindications to surgical management. Adjuvant radiotherapy with or without chemotherapy is standard in advanced cases to improve local control but early stage lesions of the sinonasal tract show no survival benefit from the addition of adjuvant radiotherapy.