Paranasal Sinus Cancer

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Paranasal sinus cancer

Definition

Paranasal sinus cancer is a disease in which cancer (malignant) cells are found in the tissues of the paranasal sinuses—the four hollow pockets of bone surrounding the nasal cavity.

Description

The paranasal sinuses, which are arranged symmetrically around the nasal cavity, include the:

frontal sinuses (in the forehead, directly above the nose)
ethmoidal sinuses (on each side of the nasal cavity, just behind the upper part of the nose)
maxillary sinuses (on each side of the nasal cavity, in the upper region of the cheek bones)
sphenoidal sinuses (behind the ethmoidal sinuses, in the center of the skull)

The paranasal sinuses, which normally contain air, are lined by mucous membranes that moisten the air entering the nose. Because they contain air, the sinuses allow the voice to echo and resonate.

Because the paranasal sinus area lies in an anatomically complex region, tumors in the paranasal sinuses can invade a variety of structures—such as the orbit (the bony cavity protecting the eyeball), the brain, the optic nerves, and the carotid arteries— even before symptoms appear.

The pharynx (throat) is divided into three sections: the nasopharynx, oropharynx, and laryngopharynx. The nasopharynx is the area behind (posterior to) the nose. The oropharynx is the area posterior to the mouth. The laryngopharynx opens into the larynx and esophagus. Usually, cancers of the paranasal sinuses originate in the lining of the nasopharynx or oropharynx. In rare cases, melanomas—a type of cancer arising from dark pigment-producing cells called melanocytes—may appear in the naso-or oropharynx. There is also an area of specialized sensory epithelium (surface layer of cells) through which the terminal branches of the olfactory nerve enter the roof of the nasal cavity, which gives rise to a very rare malignant neoplasm (growth) known as an esthesioneuroblastoma, or olfactory neuroblastoma .

Infrequently, a cancer may arise from the muscles or the soft tissues of the paranasal sinus region; these lesions are called sarcomas . Occasionally, lesions called midline granulomas (a granular-type tumor usually from lymphoid or epithelioid cells) occur; these lesions arise in the nose or paranasal sinuses and spread to surrounding tissues. Also rare are slow-growing cancers called inverting papillomas (papillae are tiny, nipple-like protuberances).

Demographics

Malignant growths of the paranasal sinuses are uncommon in the general population. Paranasal sinus cancer represents 3% of all cancers in the upper aerodigestive tract (air and food passages) and less than 1% of all malignancies in the body. The incidence of paranasal sinus cancer is about one case per 100, 000 people per year in the United States. Only about 200 new cases a year are diagnosed in the United States. The disease is more common in Asia Minor and China than in Western countries. The incidence of maxillary sinus cancer is highest in the South African Bantus and in Japan.

Paranasal sinus tumors occur about two to three times more frequently in men than women, and diagnosis usually occurs between the ages of 50 and 70. Cancers of the maxillary sinus are the most common of the paranasal sinus cancers, occurring in about 80% of individuals. Tumors of the ethmoidal sinuses are less common (about 20%), and tumors of the sphenoidal and frontal sinuses are rarest (less than 1%).

Squamous cell carcinoma (cancer that originates from squamous keratinocytes in the epidermis, the top layer of the skin) is the most frequent type of malignant tumor in the paranasal sinuses (about 80%). Adenocarcinomas (cancer that begins in cells that line certain internal organs and that have glandular, or secretory, properties) constitute 15%, and the remaining 5% are composed of all other types.

Causes and symptoms

Although the causes of paranasal sinus cancer are not known, several occupational groups have been found to have an increased risk of developing these tumors. These groups include leather and textile workers, nickel refiners, woodworkers, and manufacturers of isopropyl alcohol, chromium, and radium. Also, snuff and thorium dioxide (a radiological contrast agent) have been associated with an increased incidence of paranasal sinus cancer. It is unclear whether these factors cause cancer by direct carcinogenesis (cancer production) or by altering the normal nasal epithelial physiology.

Nickel workers primarily develop squamous cell carcinomas, which usually arise in the nasal cavity. Woodworkers, however, usually develop adenocarcinomas that usually arise in the ethmoidal sinuses. The incidence of adenocarinomas in these workers is 1, 000 times higher than that of the general population. Tobacco and alcohol use have not been demonstrated conclusively as a causative factor in the development of paranasal sinus tumors. However, viral agents, especially the human papilloma virus (HPV), may also play a causative role.

In patients with cancer of the head and neck, the immune system is often not functioning properly. Malignant cells are not recognized as foreign, or when recognized, the immune system does not effectively destroy cancer cells. Causes of the failure of the immune system include severe malnutrition, substances in the tumor that deactivate the immune system, or a genetic predisposition.

The symptoms of paranasal sinus cancer vary with the type, location, and stage of cancer present. Symptoms typical of early lesions often resemble those of an upper respiratory tract infection and include nasal obstruction, facial pain, and thin, watery nasal discharge (rhinorrhea), which can at times be blood-tinged. The key factor that differentiates the symptoms of an upper respiratory infection from a malignant lesion, however, is the duration of the symptoms. An upper respiratory infection generally clears up or improves dramatically in several weeks with appropriate medical care, but symptoms associated with a malignancy persist.

The most common symptoms of paranasal sinus cancer include:

persistently blocked nose
feeling of recurrent "sinus infections"
bleeding without apparent cause from the nose or the paranasal sinuses
progressive pain and swelling of the upper region of the face or around the eyes
closing up of one eye, blurred vision, or visual loss
persistent pain in the forehead, the front of the skull, or over the cheekbones
swelling in the roof of the mouth
loosening of teeth, poorly fitting dentures, or bleeding from upper teeth sockets

Tumors in the nasal cavity and paranasal sinuses metastasize (spread) to the cervical lymph nodes (lymph nodes in the neck) in about 15% of individuals.

Diagnosis

There are several steps in establishing a diagnosis of paranasal sinus cancer. The first step is a thorough medical history, followed by a physical examination. The physical examination may reveal a lesion in the nose or a submucosal (below the mucous membrane) mass arising in an adjacent sinus.

After the history and physical examination, a series of tests are performed to determine the precise nature of the suspicious growth and the extent of its spread. These tests may include:

Biopsy (the removal of a sample of tissue that appears to be suspicious) is performed after a lesion is identified. The tissue is studied under the pathologist's microscope.
Computed tomography (CT) scan, which is a series of detailed pictures with thin cross-sectional slices taken radiologically through the body and interpreted with a computer.
Nasoscopy, which utilizes an instrument called the nasoscope for examining the nasal cavity and the paranasal sinuses.
Magnetic resonance imaging study (MRI), an imaging study that consists of detailed pictures, but instead of using x rays, a powerful magnet is used to polarize electrons inside the body to obtain images, which are then interpreted by a computer.
Posterior rhinoscopy, in which the nasopharynx and the rear portion of the nose are examined using a light and a special mirror.

Although endoscopic techniques (visualizing the nasal cavity with an endoscope—a tube-like device to which an optical system is attached) have greatly improved the ability to examine the nasal cavities and the paranasal sinuses, radiographic studies are also necessary in completing the evaluation. The most important radiographic studies include CT and MRI scans, usually used in combination. The MRI scan has become the most essential radiographic test for accurate delineation of pretreatment tumor extent, and also for following up patients after treatment.

However, each scanning technique has its own advantages and limitations. The CT scan is preferred in evaluating the bony structures in the paranasal sinus area. The MRI better assesses soft-tissue differences, enabling not only the differentiation of tumor from inflammatory changes in the nose and sinuses, but also the determination of involvement of the soft tissues in, for example, the orbit, the brain, and the optic nerve.

Obtaining a biopsy is crucial to diagnosis. Endoscopic sinus surgery is widely used for obtaining tissue for biopsy. Combining endoscopic surgery with CT imaging, however, allows the surgeon access into small recesses of the nose and sinuses and along the base of the skull, making biopsy not only more accurate but also safer for the patient.

Treatment team

Patients with paranasal sinus cancer are usually treated by a team of specialists using a multifaceted approach. Each patient receives a treatment plan that is tailored to fit his or her requirements, specifically the patient's overall constitution, grade, and stage of disease. Usually, however, the treatment team includes:

an otorhinolaryngologist (ear, nose, and throat specialist)
an oncologist (cancer specialist)
a radiotherapist (x-ray treatment specialist)

If extensive surgery is required, a plastic and reconstructive surgeon may also serve as part of the treatment team.

Clinical staging, treatments, and prognosis

Paranasal sinus cancer staging involves carefully establishing the degree of cancer spread. If the cancer has spread, it is also necessary to establish the extent of spread and organ involvement.

Cancer grading is a microscopic issue; the pathologist determines the degree of aggressiveness of the cancer. The term well-differentiated means less aggressive; the terms moderately differentiated, intermediately aggressive, and poorly differentiated mean more aggressive.

Both grading and staging help the physician establish the prognosis (degree of seriousness of the disease) and likely outcome.

Staging

Staging may involve additional imaging tests such as CT scan of the brain, abdominal ultrasound, bone scan, or chest x ray . Although no clear-cut staging protocol exists for the relatively uncommon cancers of the paranasal sinuses, the following practical staging exists for cancer of the maxillary sinuses, the most common cancer of this area:

Stage I: The cancer is confined to the maxillary sinus, with no bony erosion or spread to the lymph nodes.
Stage II: The cancer has begun to destroy the surrounding bones but without spread to the lymph nodes.
Stage III: The cancer has spread no further than the bones around the sinus and to one node on the same side of the neck, and is no greater than 3 cm (1.1 in) in size, or has spread to the cheek, the rear portion of the sinus, the eye socket, or the ethmoidal sinus (spread to lymph nodes on the same side of the neck may or may not be present).
Stage IV: The cancer has spread to the eye, other sinuses, or tissues adjacent to the sinuses (spread to lymph nodes on the same side of the neck may or may not be present). The cancer may have spread within the sinus itself or to surrounding tissues, to lymph nodes in the neck on one or both sides, to any node larger than 6 cm (2.3 in), or to other parts of the body. Recurrent maxillary sinus cancer—either in the same location or in a different one after primary treatment has been completed—is also in this category.

Treatment options

The major treatment options for paranasal sinus cancer include:

Surgery. May be necessary for the removal of a section of the nasal cavity or the paranasal sinus at any stage of the disease. Also, some lymph node dissection may be required in the neck, depending upon the staging and grading. May be combined with radiotherapy at any stage, depending on the type of cancer and its location.
Radiotherapy. Also called radiation therapy , radiotherapy is sometimes used alone in stage I and II disease, or in combination with surgery in any stage of the disease. In the early stages of paranasal sinus cancer, radiotherapy is considered the alternative local therapy to surgery. Radiotherapy involves the use of high energy, penetrative rays to destroy cancer cells in the zone treated. Radiation therapy is also employed for palliation (control of symptoms) in patients with advanced cancer. Teletherapy (external radiation) is administered via a machine remote from the body while internal radiation (brachytherapy) is given by implanting a radioactive source into the cancerous tissues. Patients may or may not require both types of radiation. Radiotherapy usually takes just five to ten minutes per day, five days a week for about six weeks, depending upon the type of radiation used.
Chemotherapy . Usually reserved for stage III and IV disease. Besides local therapy, the best attempt to control cancer cells circulating in the body is by using systemic therapy (therapy that affects the entire body) in the form of injections or oral medications. This form of treatment, called chemotherapy, is given in cycles (each drug or combination of drugs is usually administered every three to four weeks). Chemotherapy may also be used in combination with surgery, radiotherapy, or both.

At the forefront of research into head and neck cancer, molecular biology and gene therapy are providing new insights into the basic mechanisms of cancer genesis and treatment. The detection of various oncogenes (genes that can induce tumor formation) in head and neck cancer is also progressing rapidly. Gene therapy trials, still in their infancy as of 2001, are also introducing genetic material to help the immune system recognize cancer cells.

ALTERNATIVE AND COMPLEMENTARY TREATMENTS.

Alternative and complementary therapies may also be used at any stage of the disease. Alternative treatments are treatments used instead of conventional treatments. Complementary therapies are used in addition to conventional treatments. Although not specifically used in treating paranasal sinus cancer, there is much anecdotal (non-scientific) evidence for a number of alternative cancer therapies. Some insurance plans cover complementary therapies, such as acupuncture.

The safest and most accepted of these complementary therapies include:

acupuncture
biofeedback
diet that includes fresh fruit, vegetables, and whole grains
massage
meditation, prayer, or creative visualization
vitamins (especially antioxidants A, E, and C), minerals, and herbs

The National Center for Alternative and Complementary and Alternative Medicine, part of the National Institutes of Health, discusses some alternative and complementary cancer treatments on its web site <http://www.nccam.nih.gov>.

Prognosis

The high mortality rate and poor prognosis association with paranasal sinus cancer is related to late diagnosis. Most lesions (75%) are at an advanced stage at the time of definitive diagnosis. Surgical treatment alone may be sufficient for stage I or II lesions if adequate surgical margins are obtained. However, for advanced tumors, combined therapy with radical surgical excision and postoperative radiotherapy has been demonstrated to improve the five-year survival rate.

The primary cause of death is failure of local control. Most paranasal sinus cancers grow rapidly and invade nearby tissues but are slow to spread to distant sites. Thus, patients with advanced disease usually die from a local recurrence of their tumor, even after aggressive treatment.

Coping with cancer treatment

Cancer treatments such as radiotherapy and chemotherapy not only destroy cancer cells but also damage healthy tissue. The effects of radiation depend upon the dose of radiation, the size of the area radiated, and the number and size of each fraction. When doses are fractionated, the total dose of radiation therapy is divided into several smaller, equal doses delivered over a period of several days.

The most common side effect of radiotherapy is extreme fatigue . Although rest is encouraged, most radiotherapists advise patients to move around as much as possible. Another common side effect is radiation dermatitis— the skin covering the radiated area becomes red, dry, itchy, and may show signs of scaling. This skin problem is associated only with teletherapy (external radiation therapy).

Radiation also may cause nausea and vomiting , diarrhea , and urinary discomfort. There may also be a decrease in white blood cells, which are needed to fight infection. Usually the radiotherapist can suggest the drugs and diet necessary to alleviate these problems.

Chemotherapy drugs may cause a wide spectrum of side effects. The severity of these symptoms vary with each drug and with each individual. Some of the most common side effects of chemotherapy include:

diarrhea
hair loss (alopecia )
hearing loss
skin rashes
tingling and numbness in the fingers and toes
vomiting

Most of these side effects are treatable, temporary, and recede after therapy ends. However, the attitude of the patient is very important during cancer therapy. The better psychologically prepared the patient is for treatment, the better the chances of experiencing decreased side effects.

If extensive surgery is required, reconstruction and rehabilitation by specialized physicians can improve the patient's quality of life.

Clinical trials

As of 2001, 35 clinical trials involving paranasal sinus cancer were operating in the United States. Clinical trials can be located at the web site <http://www.clinicaltrials.gov>, a service of the National Institutes of Health and the National Library of Medicine.

Some of the new drugs under investigation for advanced, recurrent, or metastatic head and neck cancer—either alone, in combination, with concurrent radiotherapy, or with standard chemotherapy drugs such as fluorouracil (5-FU), paclitaxel , or cisplatin —include:

A10 and AS2-1 (antineoplastons)
Dimesna (chemoprotective agent)
Fenretinide (retinoid, or vitamin A derivative)
Filgrastim (G-CSF or granulocyte colony-stimulating factor; increases white blood cells)
Flavopiridol (cyclin-dependent kinase [Cdk] inhibitor; kinases plays a role in cell cycle regulation and tumor formation)
Gemcitabine (antimetabolite)
ONYX-015 (genetically engineered cold virus)
C225/cetuximab (monoclonal antibody)
Oxaliplatin (platinum compound; chemotherapeutic agent)
SU5416 (angiogenesis inhibitor)

Prevention

The causes of paranasal sinus cancer are unknown. However, avoiding environmental risk factors such as heavy smoking or drinking, or inhaling wood dust or other toxic substances (such as isopropyl alcohol, chromium, or radium) on a regular basis may decrease the chances of developing this form of cancer.

Special concerns

Although surgical treatment of squamous cell carcinoma of the head and neck offers the best chance for cure in many patients, the results of the surgery have often been extremely disfiguring and functionally debilitating. The changes in facial appearance and loss of ability to speak, swallow, and breathe normally can be devastating, both physically and psychologically.

If the anticipated surgical defect is large, often a reconstructive team will harvest tissue from a distant site in the body to use as a graft while the oncology team is removing the cancer. Initially, reconstructive teams were more concerned with simply closing the surgical defect and re-establishing a more natural form. Increasingly, the focus has been to re-establish normal function.

Resources

BOOKS

Abeloff, Martin D., James O. Armitage, Allen S. Licter, and John E. Niederhuber. "Paranasal Sinuses and Nose." In Clinical Oncology, 2nd ed. New York: Churchill Living stone, 2000: 1297-1299.

Harrison, Louis B., Roy B. Sessions, and Waun Ki Hong, eds. Head and Neck Cancer: A Multidiscplinary Approach. Philadelphia: Lippincott Williams & Wilkins, 1999.

Schantz S. P., L. B. Harrison, and A. A. Forastiere. "Tumors of the Nasal Cavity and Paranasal Sinuses, Nasal Pharynx, Oral Cavity, and Oropharynx." In Cancer: Principles and Practice of Oncology, 5th ed. DeVita, V. T. Jr, S. Hellman, and S.A. Rosenberg, eds. Philadelphia: Lippincott-Raven Publishers, 1997: 741-801.

PERIODICALS

Lee, Misa M., et al. "Multimodality Therapy in Advanced Paranasal Sinus Carcinoma: Superior Long-Term Results." Cancer Journal from Scientific American 5 (August 1999): 219-223.

Khuri, Fadlo et al. "A Controlled Trial of Intratumor ONYX-015, a Selectively Replicating Adenovirus, in Combination with Cisplatin and 5-Fluorouracil in Patients With Recurrent Head and Neck Cancer." Nature Medicine. 6 (August 2000): 879-885.

ORGANIZATIONS

American Cancer Society, 1599 Clifton Road, NE, Atlanta, GA 30329-4251. <http://www.cancer.org> Phone: 1-800-ACS-2345.

National Cancer Institute. Public Inquiries Office, Building 31, Room 10A03, 31 Center Drive, MSC 2580, Bethesda, MD 20892-2580. <http://www.nci.nih.gov>. Phone: 1-800-4-CANCER.

National Center for Complementary and Alternative Medicine (NCCAM), NCCAM Clearinghouse, P.O. Box 8218, Silver Springs, MD 20907-8218, <http://www.nccam.nih.gov> Phone: 1-888-644-6226.

OTHER

<http://www.clinicaltrials.gov> (List of clinical trials)

Cancernet (List of organizations and web sites offering information and services for cancer patients and their families)<http://www.cancernet.nci,nih.gov/cancerlinks.html>

<cancersource.com> (Cancer resources for patients and families)

Genevieve Slomski, Ph.D.

KEY TERMS

Adenopathy

—Large or swollen lymph glands.

Adjuvant therapy

—Treatment (such as chemotherapy, radiation therapy, or hormone therapy) given after the primary treatment to increase the chances of a cure.

Adenocarcinoma

—Cancer that begins in cells that line certain internal organs and that have glandular (secretory) properties.

Angiogenesis inhibitor

—A substance that prevents the growth of new blood vessels.

Antimetabolite

—A chemical very similar to one required in normal biochemical reactions in cells; an antimetabolite can stop or slow down the reaction.

Antineoplaston

—A substance isolated from normal human blood and urine and tested as a type of treatment for some tumors and AIDS. Treatment is considered experimental in 2001.