Most tumors of the paranasal sinuses present with advanced disease, and cure rates are generally poor (≤50%). Squamous cell carcinoma (SCC) is the most frequent type of malignant tumor in the nose and paranasal sinuses (70%–80%). Papillomas are distinct entities that may undergo malignant degeneration. The cancers grow within the bony confines of the sinuses and are often asymptomatic until they erode and invade adjacent structures.[1-3]
Nodal involvement is infrequent. Metastases from both the nasal cavity and paranasal sinuses may occur, and distant metastases are found in 20% to 40% of patients who do not respond to treatment. However, locoregional recurrence accounts for most cancer deaths because most patients die of direct extension into vital areas of the skull or of rapidly recurring local disease.
Cancers of the maxillary sinus are the most common of the paranasal sinus cancers. Tumors of the ethmoid sinuses, nasal vestibule, and nasal cavity are less common, and tumors of the sphenoid and frontal sinuses are rare.
The major lymphatic drainage route of the maxillary antrum is through the lateral and inferior collecting trunks to the first station submandibular, parotid, and jugulodigastric nodes and through the superoposterior trunk to retropharyngeal and jugular nodes.
Pretreatment evaluation and staging, as well as the need for multidisciplinary planning of treatment, is very important. Generally, the first opportunity to treat patients with head and neck cancers is the most effective, although salvage surgery or salvage radiation therapy, as appropriate, may occasionally be successful.
Because most treatment failures occur within 2 years, patients must be monitored frequently and meticulously during this period. Lifetime follow-up is essential because nearly 33% of these patients develop second primary cancers in the aerodigestive tract.
Data indicate that various industrial exposures may be related to cancer of the paranasal sinus and nasal cavity. The risk of a second primary head and neck tumor is considerably increased.[4] A study has shown that a subgroup of paranasal sinus and nasal cavity SCCs are associated with human papilloma virus (HPV) infection and that HPV-positive patients may have a better prognosis than those who are HPV negative.[5]
The most common cell type for paranasal sinus and nasal cavity cancers is squamous cell carcinoma. Minor salivary gland tumors comprise 10% to 15% of these neoplasms. Malignant melanoma presents in less than 1% of neoplasms in this region. Some 5% of cases are malignant lymphomas.[1,2]
Esthesioneuroepithelioma, sometimes confused with undifferentiated carcinoma or undifferentiated lymphoma, arises from the olfactory nerves.[3]
Chondrosarcoma, osteosarcoma, Ewing sarcoma, and most soft tissue sarcomas have been reported for this region.
Inverting papilloma is considered a low-grade benign tumor with a tendency to recur and, in a small percentage of cases, to transform into a malignant tumor.
Midline granuloma, a progressively destructive condition, also involves this region.
The staging systems are clinical estimates of the extent of disease. The assessment of the tumor is based on inspection, palpation, and direct endoscopy when necessary. The tumor must be confirmed histologically, and any other pathological data obtained on biopsy may be included. The appropriate nodal drainage areas are examined by careful palpation. Computed tomographic and/or magnetic resonance imaging studies are generally required to adequately evaluate tumor extent before surgical resection or definitive radiation therapy. If a patient's disease relapses, complete restaging must be done to select the appropriate additional therapy.[1,2]
Staging for nasal cavity and paranasal sinus carcinomas is not as well established as staging for other head and neck tumors. For cancer of the maxillary sinus, the nasal cavity, and the ethmoid sinus, the AJCC has designated staging by TNM (tumor, node, metastasis) classification. Lymphomas, sarcomas, and mucosal melanomas of the paranasal sinuses and nasal cavity are not staged using this system.[3] The staging described below is used only for patients who have not had a lymph node dissection of the neck.
| T Category | Maxillary Sinus T Criteria | Nasal Cavity and Ethmoid Sinus T Criteria |
|---|---|---|
| aReprinted with permission from AJCC: Nasal cavity and paranasal sinuses. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 137–47. | ||
| TX | Primary tumor cannot be assessed. | Primary tumor cannot be assessed. |
| Tis | Carcinoma in situ. | Carcinoma in situ. |
| T1 | Tumor limited to maxillary sinus mucosa with no erosion or destruction of bone. | Tumor restricted to any one subsite, with or without bony invasion. |
| 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. | 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 invades any of the following: bone of the posterior wall of maxillary sinus, subcutaneous tissues, floor or medial wall of orbit, pterygoid fossa, ethmoid sinuses. | Tumor extends to invade the medial wall or floor of the orbit, maxillary sinus, palate, or cribriform plate. |
| T4 | Moderately advanced or very advanced local disease. | Moderately advanced or very advanced local disease. |
| –T4a | Moderately advanced local disease. Tumor invades anterior orbital contents, skin of cheek, pterygoid plates, infratemporal fossa, cribriform plate, sphenoid or frontal sinuses. | Moderately advanced local disease. 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 | Very advanced local disease. 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. | Very advanced local disease. Tumor invades any of the following: orbital apex, dura, brain, middle cranial fossa, cranial nerves other than V2, nasopharynx, or clivus. |
| N Category | Clinical Node (cN) Criteria |
|---|---|
| ENE = extranodal extension. | |
| aReprinted with permission from AJCC: Nasal cavity and paranasal sinuses. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 137–47. | |
| Note: A designation of “U” or “L” may be used for any N category to indicate metastasis above the lower border of the cricoid (U) or below the lower border of the cricoid (L). | |
| 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 and ENE(‒). |
| N2 | Metastasis in a single ipsilateral node >3 cm but ≤6 cm in greatest dimension and ENE(‒); or metastases in multiple ipsilateral lymph nodes, none >6 cm in greatest dimension and ENE(‒); or in bilateral or contralateral lymph nodes, none >6 cm in greatest dimension and ENE(‒). |
| –N2a | Metastasis in a single ipsilateral node >3 cm but ≤6 cm in greatest dimension and ENE(‒). |
| –N2b | Metastases in multiple ipsilateral nodes, none >6 cm in greatest dimension and ENE(‒). |
| –N2c | Metastases in bilateral or contralateral lymph nodes, none >6 cm in greatest dimension and ENE(‒). |
| N3 | Metastasis in a lymph node >6 cm in greatest dimension and ENE(‒); or metastasis in any node(s) with clinically overt ENE(+). |
| –N3a | Metastasis in a lymph node >6 cm in greatest dimension and ENE(‒). |
| –N3b | Metastasis in any node(s) with clinically overt ENE (ENEc). |
| M Category | M Criteria |
|---|---|
| aReprinted with permission from AJCC: Nasal cavity and paranasal sinuses. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 137–47. | |
| M0 | No distant metastasis (no pathologic M0; use clinical M to complete stage group). |
| M1 | Distant metastasis. |
| Stage | TNM | Description |
|---|---|---|
| T = primary tumor; N = regional lymph node; M = distant metastasis. | ||
| aReprinted with permission from AJCC: Nasal cavity and paranasal sinuses. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 137–47. | ||
| 0 | Tis, N0, M0 | Tis = See Table 1. |
| N0 = No regional lymph node metastasis. | ||
| M0 = No distant metastasis (no pathological M0; use clinical M to complete stage group). | ||
| Stage | TNM | Description |
|---|---|---|
| T = primary tumor; N = regional lymph node; M = distant metastasis. | ||
| aReprinted with permission from AJCC: Nasal cavity and paranasal sinuses. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 137–47. | ||
| I | T1, N0, M0 | T1 = See Table 1. |
| N0 = No regional lymph node metastasis. | ||
| M0 = No distant metastasis (no pathological M0; use clinical M to complete stage group). | ||
| Stage | TNM | Description |
|---|---|---|
| T = primary tumor; N = regional lymph node; M = distant metastasis. | ||
| aReprinted with permission from AJCC: Nasal cavity and paranasal sinuses. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 137–47. | ||
| II | T2, N0, M0 | T2 = See Table 1. |
| N0 = No regional lymph node metastasis. | ||
| M0 = No distant metastasis (no pathological M0; use clinical M to complete stage group). | ||
| Stage | TNM | Description |
|---|---|---|
| T = primary tumor; N = regional lymph node; M = distant metastasis; ENE = extranodal extension. | ||
| aReprinted with permission from AJCC: Nasal cavity and paranasal sinuses. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 137–47. | ||
| III | T3, N0, M0 | T3 = See Table 1. |
| N0 = No regional lymph node metastasis. | ||
| M0 = No distant metastasis (no pathological M0; use clinical M to complete stage group). | ||
| T1, T2, T3; N1, M0 | T1, T2, T3 = See Table 1. | |
| N1 = Metastasis in a single ipsilateral lymph node, ≤3 cm in greatest dimension and ENE(‒). | ||
| M0 = No distant metastasis (no pathological M0; use clinical M to complete stage group). | ||
| Stage | TNM | Description |
|---|---|---|
| T = primary tumor; N = regional lymph node; M = distant metastasis. | ||
| aReprinted with permission from AJCC: Nasal cavity and paranasal sinuses. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 137–47. | ||
| IVA | T4a; N0, N1; M0 | T4a = See Table 1. |
| N0, N1 = See Table 2. | ||
| M0 = No distant metastasis (no pathological M0; use clinical M to complete stage group). | ||
| T1, T2, T3, T4a; N2, M0 | T1, T2, T3, T4a = See Table 1. | |
| N2 = See Table 2. | ||
| M0 = No distant metastasis (no pathological M0; use clinical M to complete stage group). | ||
| IVB | Any T, N3, M0 | Any T = See Table 1. |
| N3 = See Table 2. | ||
| M0 = No distant metastasis (no pathological M0; use clinical M to complete stage group). | ||
| T4b, Any N, M0 | T4b = See Table 1. | |
| Any N = See Table 2. | ||
| M0 = No distant metastasis (no pathological M0; use clinical M to complete stage group). | ||
| IVC | Any T, Any N, M1 | Any T = See Table 1. |
| Any N = See Table 2. | ||
| M1 = Distant metastasis. | ||
Except for patients with T1 mucosal carcinomas, the accepted method of treatment is a combination of radiation therapy and surgery. The incidence of lymph node metastases is generally low (approximately 20% of cases). Thus, routine radical neck dissection or elective neck radiation therapy is recommended only for patients presenting with positive nodes.
For patients with operable tumors, radical surgery is generally performed first to remove the bulk of the tumor and to establish drainage of the affected sinus(es). This is followed by postoperative radiation therapy. Some institutions continue to give a full dose of radiation therapy preoperatively for all patients with stage II and stage III tumors and operate 4 to 6 weeks later.[1-3] A review of published clinical results of radical radiation therapy for head and neck cancer suggested a significant loss of local control with prolonged radiation therapy; therefore, lengthening of standard treatment schedules should be avoided whenever possible.[4]
Surgical exploration may be required to determine operability.
Relative contraindications to surgery include destruction of the base of the skull (i.e., anterior cranial fossa), cavernous sinus, or the pterygoid process; infiltration of the mucous membranes of the nasopharynx; or nonresectable lymph node metastases. Surgical approaches include fenestration with removal of the bulk tumor, which is usually followed by radiation therapy or block resection of the upper jaw. A combined craniofacial approach, including resection of the floor of the anterior cranial fossa, has been used with success in selected patients.[5] Removal of the eye is performed if the orbit is extensively invaded by cancer. Clinically positive nodes, if resectable, may be treated with radical neck dissection.
Radiation therapy must be carried to high doses for any significant probability of permanent control. The treatment volume must include all of the maxillary antrum and involved hemiparanasal sinus and contiguous areas. The orbit and its contents are excluded except under unusual circumstances. Lymph nodes of the neck, when palpable, should be treated in conjunction with treatment of advanced carcinomas of the antrum. This may be unnecessary for early tumors.
Accumulating evidence has demonstrated a high incidence (>30%–40%) of hypothyroidism in patients who have received external-beam radiation therapy to the entire thyroid gland or to the pituitary gland. Thyroid function testing of patients should be considered prior to therapy and as part of posttreatment follow-up.[6,7]
Patients with recurrent disease should consider chemotherapy clinical trials. Chemotherapy for recurrent squamous cell cancer of the head and neck has been shown to be efficacious as palliation and may improve a patient's quality of life and length of survival. Various drug combinations, including cisplatin, fluorouracil, and methotrexate, are effective.[8,9]
Treatment of tumors of the paranasal sinuses and of the nasal cavity should be planned on an individual basis because of the complexity involved.
The DPYD gene encodes an enzyme that catabolizes pyrimidines and fluoropyrimidines, like capecitabine and fluorouracil. An estimated 1% to 2% of the population has germline pathogenic variants in DPYD, which lead to reduced DPD protein function and an accumulation of pyrimidines and fluoropyrimidines in the body.[10,11] Patients with the DPYD*2A variant who receive fluoropyrimidines may experience severe, life-threatening toxicities that are sometimes fatal. Many other DPYD variants have been identified, with a range of clinical effects.[10-12] Fluoropyrimidine avoidance or a dose reduction of 50% may be recommended based on the patient's DPYD genotype and number of functioning DPYD alleles.[13-15] DPYD genetic testing costs less than $200, but insurance coverage varies due to a lack of national guidelines.[16] In addition, testing may delay therapy by 2 weeks, which would not be advisable in urgent situations. This controversial issue requires further evaluation.[17]
Stage I disease includes small lesions.
Maxillary sinus tumors are small lesions of the infrastructure.
Treatment options for stage I maxillary sinus tumors include the following:
Ethmoid sinus tumors are usually extensive when diagnosed.[1-3]
Treatment options for stage I ethmoid sinus tumors include the following:
Treatment options for stage I sphenoid sinus tumors include the following:
For nasal cavity tumors (squamous cell carcinomas), treatment preferences are either surgery or radiation therapy, which have equal cure rates.
Treatment options for stage I nasal cavity tumors include the following:
Treatment options for stage I inverting papillomas include the following:
Treatment options for stage I melanomas and sarcomas include the following:
Treatment options for stage I midline granulomas include the following:
Treatment options for stage I nasal vestibule tumors include the following:
Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
Stage II disease includes small and moderately advanced lesions.
Treatment options for stage II maxillary sinus tumors include the following:
Ethmoid sinus tumors are usually extensive when diagnosed.[1-3]
Treatment options for stage II ethmoid sinus tumors include the following:
Treatment options for stage II sphenoid sinus tumors include the following:
For nasal cavity tumors (squamous cell carcinomas), treatment preferences are either surgery or radiation therapy, which have equal cure rates.[4]
Treatment options for stage II nasal cavity tumors include the following:
Treatment options for stage II inverting papillomas include the following:
Treatment options for stage II melanomas and sarcomas include the following:
Treatment options for stage II midline granulomas include the following:
Treatment options for stage II nasal vestibule tumors include the following:
Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
Stage III disease includes small and moderately advanced lesions.
Treatment options for stage III maxillary sinus tumors include the following:
Treatment options for stage III ethmoid sinus tumors include the following:
Treatment options for stage III sphenoid sinus tumors include the following:
Nasal cavity tumors are squamous cell carcinomas.
Treatment options for stage III nasal cavity tumors include the following:
Treatment options for stage III inverting papillomas include the following:
Treatment options for stage III melanomas and sarcomas include the following:
Treatment options for stage III midline granulomas include the following:
Treatment options for stage III nasal vestibule tumors include the following:
Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
Stage IV disease includes advanced lesions.
Treatment options for stage IV maxillary sinus tumors include the following:
Treatment options for stage IV ethmoid sinus tumors include the following:
Treatment options for stage IV sphenoid sinus tumors include the following:
Nasal cavity tumors are squamous cell carcinomas.
Treatment options for stage IV nasal cavity tumors include the following:
Treatment options for stage IV inverting papillomas include the following:
Treatment options for stage IV melanomas and sarcomas include the following:
Treatment options for stage IV midline granulomas include the following:
Treatment options for stage IV nasal vestibule tumors include the following:
Neoadjuvant chemotherapy as used in clinical trials has been used to shrink tumors and to render them more definitively treatable with either surgery or radiation therapy. This chemotherapy is given before the other modalities; therefore, the designation of neoadjuvant is used to distinguish it from standard adjuvant therapy, which is given after or during definitive therapy with radiation or after surgery. Many drug combinations have been used in neoadjuvant chemotherapy.[6-8]
Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
Chemotherapy for recurrent head and neck squamous cell cancer has shown promise. Chemotherapy may be indicated when there is recurrence in either distant or local disease after primary surgery or radiation therapy, and when there is residual disease after primary treatment.[1,2] Survival may be improved in those achieving a complete response to chemotherapy.[3] Combined-modality therapy with platinum and radiation therapy has been used in clinical trials such as UMCC-8810.[4]
Treatment options for recurrent maxillary sinus tumors include the following:
Treatment options for recurrent ethmoid sinus tumors include the following:
Treatment options for recurrent sphenoid sinus tumors include the following:
For nasal cavity tumors (squamous cell carcinomas), salvage is possible in approximately 25% of patients.
Treatment options for recurrent nasal cavity tumors include the following:
Treatment options for recurrent inverting papillomas include the following:
Treatment options for recurrent melanomas and sarcomas include the following:
Treatment options for recurrent midline granulomas include the following:
Treatment options for recurrent nasal vestibule tumors include the following:
Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Treatment Option Overview for Paranasal Sinus and Nasal Cavity Cancer
Added Fluorouracil dosing as a new subsection.
This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of adult paranasal sinus and nasal cavity cancer. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.
This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Paranasal Sinus and Nasal Cavity Cancer Treatment are:
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The preferred citation for this PDQ summary is:
PDQ® Adult Treatment Editorial Board. PDQ Paranasal Sinus and Nasal Cavity Cancer Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/head-and-neck/hp/adult/paranasal-sinus-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389272]
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