Malignant tumors of the nose and paranasal sinuses: A retrospective review of 291 cases.

Abstract

Malignant neoplasms of the nose and paranasal sinuses are not common among the general population. We present a retrospective study of 291 cases of malignant tumors of the nose and paranasal sinuses that were diagnosed in northern Romanian population over a period of 35 years. We review the etiology, diagnosis, prognosis, and treatment of these tumors.

Introduction

Malignant tumors of the sinonasal tract constitute less than 1% of all malignancies in the body and about 3% of all head and neck cancers." [1,2] The incidence among males is twice that of females. These tumors usually arise between the fifth and seventh decades of life. In this article, we describe a retrospective study of 291 cases of malignant tumors of the nose and paranasal sinuses that were diagnosed in a northern Romanian population during a 35-year period.

Materials and methods

We retrospectively reviewed the files of patients who had been diagnosed with a primary malignant tumor of the nose or paranasal sinuses between 1960 and 1995. Our study was conducted in the Department of Otolaryngology at the Iasi Medical Center in Romania. We compiled data on demographics (age, sex), tumor characteristics (site, histologic type, and stage), and 5-year survival for each patient.

Results

We identified 291 cases of carcinoma of the nose and paranasal sinuses. Patients ranged in age from 4 to 88 years (mean: 65), and 58% were male. The average age at diagnosis was 50 years.

Histologic typing. Histologic analysis revealed that 223 of the 291 cases (76.6%) were epithelial tumors and 68 (23.4%) were nonepithelial tumors (table 1).

Of the 223 epithelial tumors, 218 (74.9% of the total of 291 cases) were epidermoid carcinomas and five (1.7% of the total) were malignant melanomas.

Of the 218 epidermoid carcinomas, 146 (66.9%) were squamous cell carcinomas (which accounted for 50.2% of the total of 291 cases), 43 (19.7%) were undifferentiated carcinomas (14.8% of the total), 17 (7.8%) were adenocystic carcinomas (5.8% of the total), and 12 (5.5%) were adenocarcinomas (4.1% of the total).

Among the 68 nonepithelial tumors, 51 (17.5% of the total) were lymphoreticular tumors and 17 (5.8% of the total) were sarcomas.

Of the 51 lymphoreticular tumors, 43 (84.3%) were non-Hodgkin's lymphomas (14.8% of the total) and eight (15.7%) were plasmacytomas (2.7% of the total). Of the 17 sarcomas, 14 (82.4%) were fibrosarcomas (4.8% of the total), two (11.8%) were angiosarcomas (0.7% of the total), and one (5.9%) was a hemangiopericytoma (0.3% of the total). We noted that 13 of the 17 sarcomas (76.5%) had been diagnosed between 1988 and 1995.

Of the 146 squamous cell carcinomas, 106 (72.6%) arose in the maxillary antrum, 19 (13.0%) occurred in the ethmoid sinus, six each (4.1%) occurred in the frontal sinus and in the nose, and none arose in the sphenoid sinus (table 2). The remaining nine patients (6.2%) had extensive tumor spread, which made it impossible to determine the site of origin.

Five-year survival. The overall 5-year survival was poor (table 3). Among the patients with epithelial tumors, only 89 of the 218 patients (40.8%) with a carcinoma were still alive after 5 years; none of the five patients with a malignant melanoma survived to that point. Among the patients with nonepithelial tumors, 18 of the 51 with a lymphoreticular tumor (35.3%) and three of the 17 patients with a sarcoma (17.6%) survived 5 years.

Staging at diagnosis. We noted that 177 of the 218 carcinomas (81.2%) were staged as T4 at the time of diagnosis. Additionally, of the 43 cases of sinonasal non-Hodgkin's lymphoma, 11 (25.6%) were classified as stage IV-F (Ann Arbor staging system) at diagnosis, 21 (48.8%) were diagnosed at stage III-B, eight (18.6%) were diagnosed at stage II, and three cases (7.0%) were diagnosed at stage I. Finally, all of those patients with a sarcoma or melanoma had very advanced and very aggressive disease at diagnosis.

Discussion

Etiology. A great deal has been documented concerning the etiology of sinonasal carcinoma. Nickel-and chrome-refining processes have been implicated in the development of squamous cell and anaplastic carcinomas of the paranasal sinuses. [3,4] In fact, Pedersen et al reported that the incidence of sinonasal carcinoma in Norway was 250 times higher among nickel workers than it was among the general population; they also reported that these malignancies had a latency period of 20 years or longer. [4]

Likewise, studies have shown a significantly higher incidence of adenocarcinoma of the ethmoid sinus among furniture and wood workers and others who are chronically exposed to wood dust. [3,5,6] Shoe workers, especially those who are involved in the tanning process, have been shown to have a higher incidence of epithelial sinonasal malignancies. [7] Other industrial agents that are associated with sinonasal malignancies include thorium dioxide ([Thorotrast] a radiopaque dye used as a contrast medium within the antrum [8]), isopropyl oils, lacquer paint, solder and welding materials, and radium watch-dial paint. Tobacco and alcohol, which are major risk factors for malignant tumors arising in other areas of the upper aerodigestive tract, do not seem to play a role in sinonasal carcinogenesis.

Site. Approximately 80% of paranasal sinus tumors arise in the maxillary sinus, while about 20% occur in the ethmoid sinuses; less than 1% originate in the frontal and sphenoid sinuses and in the nose. [1,2] Because most malignant sinus tumors are discovered at an advanced stage, it is often difficult to determine their primary site of origin.

Histology. At least 80% of all sinonasal malignancies are squamous cell carcinomas. [9] Less common tumors of the nose and paranasal sinuses include adenocystic carcinomas and adenocarcinomas (8 to 10% combined). Many other malignant tumors complete the list in small numbers. They include lymphoreticular lesions (non-Hodgkin's lymphomas, plasmacytomas), sarcomas, and malignant melanomas.

Diagnosis. The diagnosis of sinonasal tumors is based on the history and physical examination. Subsequent studies are used to establish their extent and histology. Clinical presentations are quite diverse, varying according to their location and extension to adjacent structures. The most common presenting symptoms are facial or dental pain, nasal obstruction, and epistaxis. Between 9 and 12% of patients diagnosed with sinonasal malignancies are asymptomatic. [1,2] Because sinus malignancies can initially mimic benign sinus disease, the diagnosis is usually made only after the tumor has reached an advanced stage. In general, approximately 75% of all paranasal sinus tumors are staged at T3 or T4 at the time of diagnosis.

As a sinonasal tumor infiltrates surrounding structures, it gives rise to additional symptoms, such as diplopia or loss of vision as the mass compresses or invades the orbit or directly affects the optic or oculomotor nerves. Facial numbness is a sign of tumor invasion of the trigeminal nerve. Involvement of the cranial nerves is a manifestation of advanced disease and heralds a poor prognosis. [10,11] A palpable neck mass signifies metastatic adenopathy in the jugular chain and is another sign of advanced disease.

The physical examination should include a fiberoptic endoscopic evaluation. Special attention should be paid to cranial nerve function because malignant paranasal tumors are associated with a higher incidence of cranial neuropathies (34%) than is inflammatory or benign sinus disease (4 to 8%). [11]

Radiologic imaging is essential during the initial examination. Plain film can demonstrate an opacification, mass effect, and bone destruction, but it can miss 6% of malignancies. [1] Therefore, when a malignant neoplasm is suspected because of a history of exposure to known carcinogens or the presence of severe persistent pain, cranial neuropathies, or exophthalmus, the patient should be initially evaluated by computed tomography (CT). Baseline sinus radiographs are unnecessary in this setting. [12] CT is superior in evaluating the bony confines of the sinonasal tract. Because magnetic resonance imaging (MRI) differentiates soft tissue composition, it is useful in distinguishing between tumors and fluid or mucosal collections. MRI can also detect perineural spread.

Staging. In 1933, Ohngren devised an early staging system for maxillary sinus cancer. [13] He drew an oblique line through the cavity of the maxillary antrum that extended from the medial canthus of the eye to the angle of the mandible when the sinus was viewed in its lateral aspect. Ohngren found that tumors that were located above the line had a worse prognosis than those below it.

Maxillary sinus cancer is included in the American Joint Committee on Cancer's (AJCC) TNM staging system. The AJCC classification, which is based on Ohngren' s original description, emphasizes the size and extension of tumors. The AJCC recommends that a tissue diagnosis be made prior to resection. This can be achieved by obtaining an intranasal biopsy specimen via endoscopic sinus surgery or by a transoral or transcutaneous procedure such as a Caldwell-Luc operation or an external ethmoidectomy.

Treatment. Most stage Tl and T2 maxillary sinus carcinomas are treated by surgery alone, provided that adequate resection margins can be obtained. Stage T3 and T4 lesions are treated with a combination of surgery and radiation therapy. Five-year survival rates have been reported to be 58% with combined therapy, 20% with surgery alone, and 16% with radiotherapy alone. [14]

The issue as to whether radiation is more effective before or after surgery remains controversial, but it appears that the effectiveness of preoperative radiation is similar to that of postoperative radiation. [15] Chemotherapy is generally reserved as a palliative measure.

The number of sinonasal tumors in our study was seemingly larger than what would be expected, as the annual incidence in our population was 1.66 cases per 100,000 persons. In the United States and in northern Israel, the annual incidence is less than 1.0 case per 100,000.

We found a very high rate of sinonasal lymphomas (14.8%), most of which where diagnosed at stage III or IV. While the rate of squamous cell carcinomas in our study was relatively low (50.2%), we believe that many of the undifferentiated carcinomas might have actually been poorly differentiated squamous cell cancers.

We found a relatively large number of sinonasal sarcomas in our series (5.8%), 76.5% of which had been diagnosed after 1988. We believe that these tumors might have been caused by the exposure of this population to the effects of the nuclear accident at Chernobyl in April 1986. Chernobyl is less than 500 km from the city of Iasi.

The population reviewed in this series resides in rural northeast Romania on the border of Moldova. The largest industries in this area are mining, lumber exporting, and metallurgy. Laborers do not work in a protected or controlled environment, especially with regard to their exposure to carcinogens. For most of these residents, screening, routine checkups by employer-provided physicians, and adequate primary care facilities do not exist. Because physicians have little access to modern imaging techniques, sinonasal tumors are usually not diagnosed until they have reached an advanced stage, when there is virtually no chance for treatment success.

References

(1.) Lewis JS, Castro EB. Cancer of the nasal cavity and paranasal sinuses. J Laryngol Otol 1972;86:255-62.

(2.) Frazell EL, Lewis JS. Cancer of the nasal cavity and accessory sinuses: A report of the management of 416 patients. Cancer 1963;16:1293-301.

(3.) Hernberg S, Westerholm P. Schultz-Larsen K, et al. Nasal and sinonasal cancer. Connection with occupational exposures in Denmark, Finland and Sweden. Scand J Work Environ Health 1983;9:315-26.

(4.) Pedersen E, Hogetveit AC, Andersen A. Cancer of respiratory organs among workers at a nickel refinery in Norway. Int J Cancer 1973;12:32-41.

(5.) Acheson ED. Cowdell RH, Hadfield E, Macbeth RG. Nasal cancer in woodworkers in the furniture industry. Br Med J 1968;2:587-96.

(6.) Klintenberg C, Olofsson J, Hellquist H, Sokjer H. Adenocarcinoma of the ethmoid sinuses. A review of 28 cases with special reference to wood dust exposure. Cancer 1984;54:482-8.

(7.) Acheson ED, Pippard EC, Winter PD. Nasal cancer in the Northamptonshire boot and shoe industry: Is it declining? Br J Cancer 1982;46:940-6.

(8.) Keane WM, Atkins JP Jr.. Wetmore R, Vidas M. Epidemiology of head and neck cancer. Laryngoscope 1981;91:2037-45.

(9.) Goepfert H, Luna MA, Lindberg RD. White AK. Malignant salivary gland tumors of the paranasal sinuses and nasal cavity. Arch Otolaryngol 1983;109:662-8.

(10.) Ketcham AS. Surgical treatment of patients with advanced cancer of the paranasal sinuses. In: Neoplasia of Head and Neck: A Collection of Papers Presented at the 17th Annual Clinical Conference on Cancer in 1972 at the M.D. Anderson Hospital and Tumor Institute, University of Texas System Cancer Center, Houston. Chicago: Mosby Year-Book, 1974.

(11.) Weisberger EC, Dedo HH. Cranial neuropathies in sinus disease. Laryngoscope 1977;87:357-63.

(12.) Jing BS, [Goepfert] H, Close LG. Computerized tomography [of] paranasal sinus neoplasms. Laryngoscope 1978;88:1485-503.

(13.) Ohngren LG. Malignant tumours of the maxillo-ethmoid region. Acta Otolaryngol Suppl 1933;19:1.

(14.) St-Pierre 5, Baker SR. Squamous cell carcinoma of the maxillary sinus: Analysis of 66 cases. Head Neck Surg 1983;5:508-13.

(15.) Jesse RH. Preoperative versus postoperative radiation in the treatment of squamous carcinoma of the paranasal sinuses. Am J Surg 1965;110-552-6.

(16.) Cheng VS. Wang CC. Carcinomas of the paranasal sinuses: A study of sixty-six cases. Cancer 1977;40-3038-41.

(17.) Bridger MW, Beale FA, Bryce DP. Carcinom [sic] of the paranasal sinuses--a review of 158 cases. J Otolaryngol 1978:7:379-88.

                  Types of tumors in 291 patients with
                            sinonasal cancer
                                        Pct. of       Pct. of
                             No. cases  subtotal  total (n = 291)
Epithelial
Carcinomas                      218      100.0         74.9
Squamous cell carcinomas        146       66.9         50.2
Undifferentiated carcinomas      43       19.7         14.8
Adenocystic carcinomas           17        7.8          5.8
Adenocarcinomas                  12        5.5          4.1
Malignant melanomas               5      100.0          1.7
Nonepithelial
Lymphoreticular tumors           51      100.0         17.5
Non-Hodgkin's Iymphomas          43       84.3         14.8
Plasmacytomas                     8       15.7          2.7
Sarcomas                         17      100.0          5.8
Fibrosarcomas                    14       82.4          4.8
Angiosarcomas                     2       11.8          0.7
Hemangiopericytomas               1        5.9          0.3
                 Site distribution (%) of squamous cell
              carcinoma of the nose and paranasal sinuses
                   reported in selected large series
                    No. of   Maxillary  Ethmoid  Frontal  Sphenoid
Author             patients   antrum     sinus    sinus    sinus
Lewis and Castor,    538        58%       10%      1%        1%
[1972.sup.1]
Cheng and Wang,       66        76        16        2        6
[1977.sup.16]
Bridger et al,       158        70        22        4        4
[1978.sup.17]
Goldenberg et al,    146       72.6      13.0      4.1       0
2000 [*]
Author             Nose  Unknown
Lewis and Castor,  30%     0%
[1972.sup.1]
Cheng and Wang,     0       0
[1977.sup.16]
Bridger et al,      0       0
[1978.sup.17]
Goldenberg et al,  4.1     6.2
2000 [*]
(*.)Present study.
                  Number (%) of patients who achieved
                            5-year survival
Type of malignancy                 n (%)
Carcinomas (n = 218)             89 (40.8)
Malignant melanomas (n = 5)          0
Lymphoreticular tumors (n = 51)  18 (35.3)
Sarcomas (n = 17)                3 (17.6)