Tumors of the Nose and Paranasal Sinuses

Anatomy and Pathophysiology:

Tumors of the nose and paranasal sinuses are rare among head and neck neoplasms, whether benign or malignant.

Benign Neoplasms:

The most notable benign nasal neoplasms include osteomas, papillomas, and juvenile nasopharyngeal angiofibromas.

Osteomas

Osteomas are the most common benign sinonasal tumor. They are usually asymptomatic and diagnosed incidentally due to their slow-growing nature; however, compressive symptoms can occur, along with infiltration of the orbit or cranial cavity. They most frequently occur in the frontal sinus. The pathogenesis of osteomas is not well established. Some have suggested traumatic or infectious etiologies for their development. In some cases, they may be associated with Gardner’s syndrome, which is characterized by colon polyps, osteomas of the skull, and soft tissue tumors.

Sinonasal Papillomas

Sinonasal papillomas may be classified as inverted, exophytic, or columnar. Inverted papilloma (IP) is the most common of these and is characterized by an endophytic growth pattern. The term “inverted” refers to the inversion of stratified squamous epithelium into the underlying stroma. The pathophysiology of inverted papilloma is not completely understood. Although human papillomavirus (HPV) infection has been documented in some cases, it is not a requirement for development of IP. Other theories have suggested allergic response, chronic sinusitis, or irritant exposure as possible contributing factors to IP pathogenesis. IP almost always occurs unilaterally and is characterized by local destruction rather than invasion. Carcinoma may develop synchronously or metachronously in up to 10% of cases of IP, with squamous cell carcinoma being the most common associated malignancy.

Juvenile Nasal Angiofibroma

Juvenile nasal angiofibroma (JNA) is a rare vascular tumor that typically originates at the posterolateral roof of the nose, in the pterygopalatine fossa near the sphenopalatine foramen. It is an expansile tumor that may extend into the nasopharynx, orbit, or middle cranial fossa. Some theories have suggested a hormonal etiology for JNA development, given that it exclusively affects adolescent males.

Malignant Neoplasms:

Like other regions of the head and neck, the most common malignancy of the sinonasal tract is squamous cell carcinoma. Other malignant tumors may include adenocarcinoma, olfactory neuroblastoma, melanoma, adenoid cystic carcinoma, sinonasal undifferentiated carcinoma (SNUC), sarcoma, and lymphoma. The most common site for sinonasal malignancy is the maxillary sinus, followed by the nasal cavity and the ethmoid sinus. Tobacco and alcohol use have not been associated with sinonasal malignancy, but certain chemical and particulate exposures have been documented to increase risk.

Epidemiology:

The true incidence of sinonasal osteoma is difficult to assess as many cases are asymptomatic and may never be diagnosed. It has been reported that 3% of patients undergoing computed tomography scans of the sinuses have incidental findings of osteomas. The highest incidence occurs during the second to fifth decades of life, with males being affected slightly more frequently than females. The incidence of inverted papilloma is 0.2- 1.5 cases per 100,000 individuals per year. It primarily affects middle-aged men. As mentioned previously, JNA is rare, accounting for less than 0.1% of all sinonasal tumors. It affects males exclusively, with onset typically during the second decade of life. JNA is rare after the third decade.

Sinonasal malignancies account for approximately 3% of all malignancies in the head and neck. Similar to head and neck cancer elsewhere, sinonasal malignancy is most common in males in the fifth to seventh decades of life.

Natural History

Due to the narrow dimensions of the sinonasal tract, as well as its proximity to the orbit and cranial cavity, progression of sinonasal neoplasms tends to produce significant consequences, even when benign. Among benign tumors, inverted papillomas are particularly notable for their modest but significant rate of malignant degeneration. Sinonasal malignancies are frequently diagnosed in the advanced stage due to nonspecific symptoms. While perineural spread and local extension is common, nodal metastases are rare.

Presentation

Tumors of the sinonasal tract most commonly present with nasal obstruction or epistaxis. Depending on tumor size, facial or nasal swelling may be present, with or without pain due to compression effects. Orbital involvement may result in visual impairment, orbital abscess, orbital pain, diplopia, proptosis, or epiphora (excessive tear production). Intracranial extension can produce neurologic symptoms, such as cranial nerve dysfunction, meningismus, lethargy, seizure, or cerebrospinal fluid rhinorrhea. Inverted papilloma typically presents with watery rhinorrhea in addition to nasal obstruction. Osteoma is frequently asymptomatic, but can cause frontal headache or sinus obstruction with symptoms of rhinosinusitis. The classic presentation of JNA is unilateral recurrent epistaxis in an adolescent male.

Differential Diagnosis of Rhinosinusitis:



Evaluation:

History

The patient history should include timing of onset and progression of symptoms, presence of comorbid medical conditions, and history of occupational exposures.

Physical Examination

The physical examination should include anterior rhinoscopy, rigid nasal endoscopy, and flexible fiberoptic laryngoscopy. Findings vary depending on tumor type. Inverted papillomas have a pale, polypoid appearance with wart-like papillary projections. They are most commonly based on the lateral nasal wall, although in large lesions, the site of origin may not be readily identified. Osteomas may not be visible on endoscopic examination (particularly if confined to the paranasal sinuses), but if so, they generally have a multilobulated, white appearance and firm consistency. The gross appearance of JNA is usually well-circumscribed, lobulated, and pale blue in color. Sinonasal malignancies may appear as exophytic or friable masses with ulceration.

Other physical examination elements to document in cases of sinonasal tumor include ophthalmologic examination, cranial nerve function, oral cavity examination (paying attention to any extension through the palate), and presence of cervical lymphadenopathy.

Imaging Studies

Both computed tomography (CT) and magnetic resonance imaging (MRI) are typically ordered in cases of sinonasal malignancy, as the former provides better evaluation of bony erosion, while the latter provides superior soft tissue resolution and assessment of intracranial and orbital extension. Positron emission tomography (PET)-CT may be used to assess for metastases. The choice of imaging modality in benign tumors such as IP and JNA depends on whether intracranial involvement is suspected; CT may be sufficient in cases confined to the sinonasal tract. Due to its site of origin, JNA often has the characteristic radiographic finding of bowing of the posterior maxillary sinus wall. CT is also the study of choice for evaluation of osteoma.

Biopsy

Biopsy is indicated for suspicion of inverted papilloma or malignancy; however, imaging should be obtained prior to biopsy in order to exclude a vascular lesion or encephalocele (brain tissue prolapsing into the nose through a dehiscence in the anterior cranial fossa). Vascular tumors should not be biopsied in the office setting due to the risk of hemorrhage.

Staging

Staging of paranasal sinus and nasal cavity cancer is according to the American Joint Committee on Cancer (AJCC) TNM (tumor, node, metastasis) system. The staging criteria for maxillary sinus cancer, the most common tumor location in this category, are summarized below.

AJCC TNM Staging for Maxillary Sinus Carcinoma
Primary Tumor (T)
T1	Tumor limited to maxillary sinus mucosa with no erosion or destruction of bone.
T2	Tumor causing bone erosion or destruction including extension into the hard palate and/or middle nasal meatus, except extension to posterior wall of maxillary sinus and pterygoid plates.
T3	Tumor invades any of the following: bone of the posterior wall of maxillary sinus, subcutaneous tissues, floor or medial wall of orbit, pterygoid fossa, or ethmoid sinuses.
T4a	Tumor invades anterior orbital contents, skin of cheek, pterygoid plates, infratemporal fossa, cribriform plate, or sphenoid or frontal sinuses.
T4b	Tumor invades any of the following: orbital apex, dura, brain, middle cranial fossa, cranial nerves other than maxillary division of trigeminal nerve (V2), nasopharynx, or clivus.
Nodal Metastasis (N)
NX	Regional lymph nodes cannot be assessed
N0	No regional lymph node metastasis
N1	Metastasis in a single ipsilateral lymph node, ≤3 cm in greatest dimension
N2a	Metastasis in a single ipsilateral lymph node, >3 cm but ≤6 cm in greatest dimension
N2b	Metastasis in multiple ipsilateral lymph nodes, ≤6 cm in greatest dimension
N2c	Metastasis in bilateral or contralateral lymph nodes, ≤6 cm in greatest dimension
N3	Metastasis in a lymph node, >6 cm in greatest dimension
Distant Metastasis (M)
MX	Distant metastasis cannot be assessed
M0	No distant metastasis
M1	Distant metastasis present
Staging Groups
Stage	T	N	M
I	T1	N0	M0
II	T2	N0	M0
III	T3	N0	M0
	T1-3	N1	M0
IVA	T4a	N0-1	M0
	T1-4a	N2	M0
IVB	T4b	Any N	M0
	Any T	N3	M0
IVC	Any T	Any N	M1

Treatment

The general therapeutic approach to sinonasal tumors is surgical resection. An exception is asymptomatic osteoma without orbital or intracranial extension, which may be observed with periodic radiographic monitoring. For other tumors, the choice of endoscopic versus external (open) resection depends upon the accessibility of the tumor, its extent, history of prior surgery in the region, and surgeon experience. Cases with intracranial involvement require the participation of a neurosurgical team. In the case of JNA, preoperative embolization is frequently employed to reduce the amount of intraoperative hemorrhage. Induction chemotherapy or chemoradiation is given prior to surgery in some cases of high-grade malignancy, such as SNUC, or when significant extranasal extension has occurred.

Radiation therapy is ineffective for the treatment of papillomas, but has been reported as an alternative treatment modality for JNAs that cannot be completely resected due to involvement of vital structures. Adjunct radiotherapy or chemoradiation is often given postoperatively in advanced sinonasal malignancy. Patients with unresectable malignancy or who are not surgical candidates may be treated with radiation alone.

Complications, Prognosis & Follow-Up

Osteoma has an excellent prognosis with recurrence being very rare. Postoperative surveillance is not indicated in most cases.

Reports of recurrence rates for inverted papilloma after resection range from 10-20%. Recurrence may be diagnosed 10 years or more after treatment; therefore, extended follow-up with endoscopic examinations is suggested.

Juvenile nasal angiofibroma generally has a good prognosis after surgery. Postoperative surveillance with radiographic imaging is standard, as it provides better detection of residual tumor than endoscopy. Residual tumor is typically observed via imaging, with revision surgery or radiation therapy for further growth.

The prognosis for sinonasal malignancy tends to be poor, owing to late diagnosis. More than 80% of sinonasal squamous cell carcinoma is stage III or IV at the time of diagnosis. Perineural invasion is common and clear surgical margins may be difficult to obtain in many cases given the proximity of the sinonasal tract to vital structures such as the orbit, major vessels, and brain. A 5-year survival rate of 50% has been reported in patients undergoing surgical resection with adjuvant radiotherapy. Recurrence rates for squamous cell carcinoma may be as high as 56%.