Chapter 17. Paranasal Sinus Neoplasms

Essentials of Diagnosis

• Symptoms and signs mimic benign sinonasal disease.
• Malignant tumors typically present at advanced stage of disease.
• Immunohistochemical markers are often required for definitive diagnosis of tumors.

General Considerations

Paranasal sinus neoplasms, both benign and malignant, are relatively rare in the head and neck. Malignant neoplasms of the paranasal sinuses account for approximately 3.0% of head and neck cancers and 0.5% of all malignant tumors. In general, these tumors are identified and treated at advanced stages as their symptoms mimic benign inflammatory conditions. The most common malignant neoplasm of the nose and paranasal sinuses is squamous cell carcinoma. This tumor most commonly arises from the maxillary antrum and secondarily from the ethmoid sinus. Treatment includes surgical resection, radiation therapy, and, rarely, chemotherapy. Benign tumors present in a similar manner and typically necessitate surgical resection and close postoperative follow-up. As nasal endoscopes are used with increasing frequency clinically, both benign and malignant tumors will ideally be identified earlier in the disease progression.

Clinical Findings

Symptoms and Signs

The most common presenting symptoms in patients with paranasal sinus neoplasms are nasal obstruction, rhinorrhea, and sinus congestion that are similar to those of patients with benign sinonasal diseases. However, as the masses grow, paranasal sinus neoplasms lead to facial pain and epistaxis. In addition, orbital symptoms, such as diplopia, proptosis, visual loss, and epiphora, can occur with either neoplastic invasion or expansion into the orbit. Entry through the skull base into the anterior cranial fossa can lead to the symptoms of headache, cranial neuropathies, and occasional frontal lobe symptoms (such as personality alterations). Tumors can also invade the maxilla and present as a hard-palate mass.

Physical Examination

The physical examination of a patient suspected to have a paranasal neoplasm should include a complete head and neck examination, which includes diagnostic nasal endoscopy. While small tumors grow silently without symptoms, persistent nasal symptoms should be evaluated with nasal endoscopy.

Nose and Paranasal Sinus

The examination of the nose and paranasal sinus cavity can reveal a nasal mass with overlying polyps or polypoid mucosa. The septum can be markedly deviated to the contralateral side because of the expansion of the neoplasm, sometimes with tumor erosion into the contralateral nasal cavity. An endoscopic evaluation is superior at evaluating the mucosa, identifying masses and drainage.

Oral Cavity

The teeth and hard palate need to be examined closely to determine if invasion into the maxilla has occurred. An expanded alveolar ridge or loose maxillary dentition indicates early bony invasion of the maxilla, and a mass on the hard palate indicates frank invasion into the maxilla.

Face and Orbit

Facial swelling and thickening of the cheek and nose skin is an indication that the neoplasm has invaded the soft tissue through the anterior bony walls. Proptosis is seen with expansion through the lamina papyracea compressing the periorbital benign disease, such as mucocele, and in malignant disease due to intraorbital invasion. Diplopia is commonly seen with proptosis, and visual loss is a sign of progressive orbital involvement; however, visual loss also can be a sign of orbital apex involvement with compression of the optic nerve.

Cranial Nerves

Cranial nerve (CN) involvement is common in advanced malignant neoplasms of the paranasal sinuses. The olfactory nerve, CN I, is involved in esthesioneuroblastomas. Other CNs involved are the optic nerve (CN II), the oculomotor nerve (CN III), the trochlear nerve (CN IV), the abducens nerve (CN VI), and supraorbital and maxillary branches of the trigeminal nerve (CN V1 and CN V2).

Other Physical Findings

Other findings that can be identified by the physical examination are serous otitis media due to eustachian tube involvement, and neck masses due to metastatic neoplastic spread into the regional lymph nodes. The most commonly involved lymph nodes are the upper jugulodigastric nodes.

Imaging Studies

Imaging is critical to identify the extent of both benign and malignant diseases. A computed tomography (CT) scan can delineate the mass well and can be sufficient for both bony and benign diseases. It is excellent for determining bony invasion but limited for distinguishing between edematous mucosa and tumor involvement and in identifying the intracranial extension of tumors. Magnetic resonance imaging (MRI) with both T1- and T2-weighted images with gadolinium enhancement is superior in determining the true involvement of the anterior cranial fossa, the skull base, and the orbit (Figure 17–1). MRI is also superior at soft-tissue delineation, can distinguish a tumor from obstructed secretions in the sinus, and complements the bony architecture information obtained from the CT scan. Both scans are often needed to ensure appropriate surgical planning.

Special Tests

A biopsy of the mass is critical both in diagnosing a malignant tumor and in determining its treatment. If the mass is easily visualized in the physician's office, then an in-office biopsy should be obtained of the mass itself and not just the overlying tissue. Considerations for this biopsy include the assurance that the lesion is not vascular or does not contain cerebrospinal fluid (CSF). These lesions are often soft, cystic, and expand with a Valsalva maneuver. A needle biopsy of these lesions can be considered if the diagnosis is still uncertain.

Differential Diagnosis

The differential diagnosis of a paranasal sinus mass is extensive (Table 17–1). The most common benign lesion of the paranasal sinuses is the inverted papilloma. The most common malignant neoplasm of the paranasal sinuses is squamous cell carcinoma. Additional tumors that are frequently seen are adenocarcinoma, adenoid cystic carcinoma, olfactory esthesioneuroblastoma, malignant mucosal melanoma, and sinonasal undifferentiated carcinoma.

Inverted Papillomas

General Considerations

An inverted papilloma, also called a schneiderian papilloma from the name of the mucosa from which it arises, is typically located on the lateral nasal wall; rarely it is found on the septum. The incidence of this tumor is between 0.5% and 7.0% of all nasal tumors. The etiology of this tumor is unclear; however, there is an association with human papilloma virus (HPV) but not to allergy or nasal polyps. Inverted papillomas typically involve the middle meatus and at least one sinus cavity; the most common sinuses involved are the maxillary and ethmoid sinuses, followed by the sphenoid and frontal sinuses.

Inverted papillomas are usually unilateral, but they have been reported to be bilateral in up to 13% of cases. These tumors can extend through the septum into the contralateral nasal cavity. Multifocal tumors have been documented in approximately 4% of cases. Whether because of multicentricity or incomplete excision, these neoplasms have a high rate of recurrence with any procedure—as high as 75%. Patients also have a 5–15% risk of developing squamous cell carcinoma within the inverted papilloma.

Clinical Findings

Patients diagnosed with inverted papillomas complain about nasal obstruction, rhinorrhea, and unilateral epistaxis. Other symptoms include facial pressure, headache, and anosmia. On gross examination, there are no clear distinguishing characteristics between an inverted papilloma and an inflammatory polyp, although an inverted papilloma may be firmer and less translucent than an “average” polyp. On histopathologic examination, the distinguishing feature of inverted papillomas is the proliferation of epithelium with fingerlike inversions into the underlying epithelium.

Staging

Several staging systems have been developed that range from tumors located solely in the nasal cavity to tumors that extend to the anterior cranial fossa or orbit. A new system has been proposed that provides prognostic information as defined by recurrence.

Treatment

Treatment consists of total excision of the tumor. The traditional approach has been a lateral rhinotomy or midfacial degloving approach to a medial maxillectomy for total tumor removal. An osteoplastic frontal sinus exploration is sometimes required for disease spreading into the frontal sinus. In order to ensure a more complete resection, a microscope can be used to improve visualization of the mucosa. Currently, most would proceed with an endoscopic approach. The procedures range from a transnasal resection to an endoscopic modified Lothrop and should be performed by an experienced surgeon. The advantage of an endoscopic approach is improved visualization of the diseased mucosa that requires resection. The tumors most amenable to endoscopic resection are those neoplasms with disease limited to the inferior or middle meatus or the middle turbinate.

An important feature in the management of patients with these neoplasms is that all of the excised specimens should be closely examined with multiple sections to rule out invasive squamous cell carcinoma. Endoscopic approaches tend to use microdebriders to facilitate the resection. In these cases, the debrided tissue fragments are collected into a container for histologic evaluation to ensure that no microscopic focus of squamous cell carcinoma is identified.

Prognosis

Recurrence rates for both the open and endoscopic approaches are comparable and have ranged from a low of 8–10% to a high of 49–75% in different studies.

Juvenile Angiofibromas

Clinical Findings

These tumors occur primarily in young boys and are highly vascular. The primary symptoms are nasal obstruction and epistaxis. Juvenile angiofibromas originate in the posterior nasal cavity but by the time of presentation they have grown to fill the nasopharynx, often extending into the pterygopalatine fossa and infratemporal fossa. The rate of tumor growth is slow.

Treatment

The treatment consists of surgical resection and sometimes radiation therapy for persistent disease, despite a hypothesis that regression of these tumors occurs over time. To minimize blood loss, a preoperative angiogram with embolization and hypotensive anesthesia intraoperatively are recommended. Surgical approaches consist of a lateral rhinotomy and medial maxillectomy approach; the prognosis is excellent in patients who undergo these treatment methods.

Squamous Cell Carcinomas

General Considerations

Squamous cell carcinoma is the most common malignant neoplasm of the paranasal sinuses, accounting for 60–80% of paranasal sinus tumors. The etiology and epidemiology of this tumor are poorly understood, although nickel workers are at a markedly increased risk of developing these tumors.

Clinical Findings

Squamous cell carcinomas arise from a silent location and grow insidiously with little to no symptoms. At the time of diagnosis, these tumors are very large and, therefore, bode a very poor prognosis. Only when these neoplasms invade adjacent structures, causing symptoms of oral, ocular, or facial involvement, are patients accurately diagnosed and treated (Figure 17–2). These symptoms include pain in the maxillary teeth, erosion of the palate, diplopia, proptosis, and cheek paresthesias. These tumors arise most commonly in the maxillary antrum and account for up to 80% of all paranasal sinus squamous cell carcinoma. The ethmoid sinus is the second most common site of origin. Primary squamous cell carcinomas of the frontal and sphenoid sinuses are rare.

Staging

The revised staging system for maxillary sinus carcinoma, created by the American Joint Committee on Cancer (AJCC), is clinically more relevant and better at distinguishing survival results between T2–T3 and T2–T4 diseases than its previous staging system. The N stage designates regional lymph node involvement and is identical to staging of the neck in other head and neck cancers. The staging system for ethmoid sinus cancers is shown in Table 17–2.

Treatment & Prognosis

For nearly all patients, the treatment is surgical resection followed by radiation therapy. Treatment with this combination of modalities has shown markedly improved results compared to radiation therapy alone. The 5-year survival rate for patients with maxillary sinus squamous cell carcinoma who are treated with combined surgery and radiation therapy is 46–68% versus 9–19% for those patients treated with radiation therapy alone. Surgical procedures typically start with a maxillectomy and can include orbital exenteration, infratemporal fossa dissection, and craniofacial resection. Postoperative radiation therapy is administered until at least 65 Gy is delivered. Intensity-modulated radiotherapy (IMRT) allows an even greater dosage delivery while sparing crucial structures such as the optic nerve and chiasm, the pituitary gland, and the brain. The addition of chemotherapy may improve locoregional control and 5-year disease-specific survival.

Due to the rarity of ethmoid squamous cell carcinoma, all ethmoid tumors tend to be grouped together, despite different histological features. Patients with ethmoid tumors fare no better than patients with maxillary sinus tumors; the 5-year local control and disease-specific survival rates for both are similar.

Adenocarcinomas & Adenoid Cystic Carcinomas

General Considerations

Adenocarcinomas arise from the epithelial surface of the sinonasal mucosa and occur more frequently than adenoid cystic carcinomas, which arise from the minor salivary glands. Together, they represent the most common mucous gland malignant neoplasms of the paranasal sinuses. Adenoid cystic carcinomas tend to arise from the maxillary antrum and can infiltrate into the surrounding tissue. They demonstrate perineural spread into the maxillary and mandibular branches of the trigeminal nerve (CN V), with extension into the foramina ovale and rotundum. Adenoid cystic carcinomas have a low incidence of regional metastases but greater distant metastases.

Clincial Findings

Adenocarcinomas arise typically from the ethmoid sinuses. While there has been no correlation with smoking in the development of adenocarcinomas, there has been a documented association with woodworkers and leather workers. Several histological types are seen with variability in mucin production and cellular differentiation. They are similar to adenoid cystic carcinomas in their growth behavior.

Treatment

The treatment for both of these tumors consists of multimodality therapy at the advanced stages of disease. For maxillary sinus tumors, the treatment usually consists of a maxillectomy. An anterior craniofacial resection is often the recommended treatment for advanced ethmoid cancers. Postoperative radiation therapy is frequently employed in treating patients with all of these tumors.

Olfactory Esthesioneuroblastomas

General Considerations

Olfactory esthesioneuroblastomas arise from the olfactory epithelium superior to the middle turbinate. These neoplasms account for only 1–5% of all malignant tumors of the paranasal sinuses. Olfactory esthesioneuroblastomas are initially unilateral and can grow into the adjacent sinuses and the contralateral nasal cavity; they can spread to the orbit and the brain.

Classification

No TNM staging system has been created for these tumors; a clinical grouping system has been developed that has no prognostic value. This system designates the following groups: (1) Group A consists of patients with tumors limited to the nasal cavity; (2) Group B includes patients whose tumors are localized in the nasal cavity and the paranasal sinuses; and (3) patients in Group C have tumors that extend beyond both the nasal cavity and the paranasal sinuses. Metastasis to the neck is seen in approximately 10–20% of cases in all three groups.

Clinical Findings

Histologically, olfactory esthesioneuroblastomas can appear similar to both peripheral neuroblastomas and other sinonasal malignant tumors. Two features often seen on microscopy are rosettes and neurofibrillary processes. Immunocytochemical staining of the specimen, while showing tremendous variability, is an important and often necessary step in making an accurate diagnosis. Histologically, olfactory esthesioneuroblastomas do not appear to stain for keratin and epithelial membrane antigen. The most common positive immunoreactions are with neuron-specific enolase, S-100, microtubule-associated protein, Class III β-tubulin isotype, neurofilament, and synaptophysin.

Treatment & Prognosis

Patients with esthesioneuroblastomas are best treated with combined modality therapy, even if the tumors are designated as either Kadish Group A or B neoplasms. The 5-year disease-free survival for single modality therapy for patients in Kadish Groups A and B is 55% compared to 61% for patients in Kadish Group C. The local tumor control rate of combined therapy is 87% versus 51% for radiation alone, and 0% for surgery alone. Surgical resection may involve either local resection or craniofacial resection with radiation doses of 60–65 Gy postoperatively.

Malignant Mucosal Melanomas

General Considerations

Respiratory tract mucosal melanomas occur in the nasal cavity and paranasal sinuses. They are exceedingly rare, with only 0.5–1.5% of all melanomas occurring in the sinonasal cavity. These neoplasms originate from melanocytes within the submucosa and from the mucosa of the paranasal sinuses. They are located most frequently in the anterior septum, followed by the middle and the inferior turbinates. The maxillary sinus is the most common sinus cavity involved.

Clinical Findings

Epistaxis appears to be the most frequent symptom, and nasal obstruction is also common. On examination, the mass appears to be fleshy and polypoid. Tumors in the nasal cavity tend to be smaller at the time of diagnosis than tumors that arise within the sinuses. Nodal metastasis occurs in 10–20% of cases.

Staging

No TNM staging system exists for mucosal melanomas. However, a practical staging system has been developed: (1) Stage I designates localized disease, (2) Stage II indicates regional metastasis, and (3) Stage III signifies distant metastasis. The factors that influence clinical outcomes include the clinical stage, a lesion thickness >5 mm, the presence of vascular invasion, and the development of distant metastasis.

Treatment & Prognosis

The treatment consists of surgical excision followed by postoperative radiation therapy. As a result of this combined treatment approach, the 5-year disease-specific survival rate for sinonasal mucosal melanomas is approximately 47%.

Sinonasal Undifferentiated Carcinomas

Sinonasal undifferentiated carcinomas are highly aggressive tumors of the paranasal sinuses and often appear to be histologically similar to olfactory esthesioneuroblastomas. Like inverted papillomas, sinonasal undifferentiated carcinomas appear to arise from schneiderian mucosa. They grow rapidly, with extensive local invasion into the sinuses, the orbit, and the brain (Figure 17–3). Histologically, they appear to stain for keratin and epithelial membrane antigen and do not appear to have an association with Epstein–Barr virus (EBV), which would distinguish these tumors from undifferentiated nasopharyngeal carcinoma. Surgical resection with postoperative radiation therapy is the mainstay of therapy. Even with this combined approach, the prognosis is very poor.