The authors reviewed treatment results in patients with nasal and paranasal sinus carcinoma from a large retrospective cohort and conducted a systematic literature review.

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Nasal and paranasal sinus carcinoma: are we making progress? A series of 220 patients and a systematic review.

Maxillary sinus carcinomas: natural history and results of postoperative radiotherapy.

This review updates the evidence that the human papillomavirus (HPV) is involved in the development of benign and malignant sinonasal lesions. Since the early 1980s, when evidence was provided on the possible involvement of HPV in the aetiology of both benign respiratory papillomas and squamous cell carcinomas, a substantial number of studies have explored this issue. To date, 33.3% of sinonasal papillomas and 21.7% of sinonasal carcinomas analysed have been shown to be positive for HPV. Many elements of the data parallel the observations made in HPV lesions at other mucosal sites, such as malignant transformation and frequent recurrence after radical treatment; the fact that low risk HPV types 6 and 11 are usually confined to benign lesions, whereas the reverse is true for the oncogenic HPV types 16 and 18; and the presence of squamo-columnar junctions and squamous cell metaplasia in the sinonasal system. The discrepancies reported by several studies might result in part from technical reasons, but it is also possible that sinonasal lesions have a heterogeneous aetiology (HPV related and non-related) and/or that some novel (yet unidentified) HPV types exist in these lesions, which are detected by some studies but not by others.

https://jcp.bmj.com/content/jclinpath/56/3/174.full.pdf

HPV infections in benign and malignant sinonasal lesions.

Between October 1964 and December 1983, 48 patients with malignant tumors of the nasal cavity (31), ethmoid sinus (13), or sphenoid sinus (4) were treated with curative intent by radiation therapy. There were 21 squamous cell carcinomas, 14 minor salivary gland tumors (adenocarcinoma, adenoid cystic carcinoma, and mucoepidermoid carcinoma), 3 malignant melanomas, 2 soft tissue sarcomas, and 8 esthesioneuroblastomas. Forty-two patients were treated with irradiation alone and six with planned combined irradiation and surgery. The 10-year actuarial local control rate for Stage I (limited to site of origin; 7 patients) was 100%; for Stage II (extension to adjacent sites, e.g., adjacent sinuses, orbit, pterygomaxillary fossa, nasopharynx; 19 patients) was 53%; and for Stage III (destruction of skull base or pterygoid plates, or intracranial extension; 22 patients) was 30%. Of 24 failures at the primary site, 10 occurred greater than 24 months after completion of irradiation. With the exception of adenoid cystic carcinoma (17% local control at 15 years), the ultimate local control rates for all histologies were in the range of 40% to 60%. Of 7 patients with documented intracranial extension, 3 (43%) remained free from local recurrence 3.5, 4, and 9 years after treatment. The 5-, 10-, 15-, and 20-year uncorrected actuarial survival rates for all 48 patients were 52%, 30%, 22%, and 22%, respectively. Continuous disease-free survival according to stage at 10 years was 86% for Stage I, 42% for Stage II, and 22% for Stage III. The single failure in a patient with Stage I disease was a lymph node metastasis that was successfully managed by radical neck dissection. The orbit was grossly invaded by tumor prior to treatment in 22 patients (46%). Sixteen (33%) of 48 patients developed unilateral blindness secondary to radiation retinopathy or optic neuropathy; in the majority of these patients the complication was anticipated because the ipsilateral eye was irradiated to a high dose. Four patients (8%) unexpectedly developed bilateral blindness 17, 35, 46, and 90 months following treatment owing to optic nerve injury. A discussion of possible means of avoiding this latter, unacceptable complication is included.

Malignant tumors of the nasal cavity and ethmoid and sphenoid sinuses.

Purpose: To evaluate the incidence and prognostic significance of lymph node metastasis in maxillary sinus carcinoma. Methods and Materials: We reviewed the records of 97 patients treated for maxillary sinus carcinoma with radiotherapy at Stanford University and at the University of California, San Francisco between 1959 and 1996. Fifty-eight patients had squamous cell carcinoma (SCC), 4 had adenocarcinoma (ADE), 16 had undifferentiated carcinoma (UC), and 19 had adenoid cystic carcinoma (AC). Eight patients had T2, 36 had T3, and 53 had T4 tumors according to the 1997 AJCC staging system. Eleven patients had nodal involvement at diagnosis: 9 with SCC, 1 with UC, and 1 with AC. The most common sites of nodal involvement were ipsilateral level 1 and 2 lymph nodes. Thirty-six patients were treated with definitive radiotherapy alone, and 61 received a combination of surgical and radiation treatment. Thirty-six patients had neck irradiation, 25 of whom received elective neck irradiation (ENI) for N0 necks. The median follow-up for alive patients was 78 months. Results: The median survival for all patients was 22 months (range: 2.4–356 months). The 5- and 10-year actuarial survivals were 34% and 31%, respectively. Ten patients relapsed in the neck, with a 5-year actuarial risk of nodal relapse of 12%. The 5-year risk of neck relapse was 14% for SCC, 25% for ADE, and 7% for both UC and ACC. The overall risk of nodal involvement at either diagnosis or on follow-up was 28% for SCC, 25% for ADE, 12% for UC, and 10% for AC. All patients with nodal involvement had T3–4, and none had T2 tumors. ENI effectively prevented nodal relapse in patients with SCC and N0 neck; the 5-year actuarial risk of nodal relapse was 20% for patients without ENI and 0% for those with elective neck therapy. There was no correlation between neck relapse and primary tumor control or tumor extension into areas containing a rich lymphatic network. The most common sites of nodal relapse were in the ipsilateral level 1–2 nodal regions (11/13). Patients with nodal relapse had a significantly higher risk of distant metastasis on both univariate ( p = 0.02) and multivariate analysis (hazard ratio = 4.5, p = 0.006). The 5-year actuarial risk of distant relapse was 29% for patients with neck control versus 81% for patients with neck failure. There was also a trend for decreased survival with nodal relapse. The 5-year actuarial survival was 37% for patients with neck control and 0% for patients with neck relapse. Conclusion: The overall incidence of lymph node involvement at diagnosis in patients with maxillary sinus carcinoma was 9%. Following treatment, the 5-year risk of nodal relapse was 12%. SCC histology was associated with a high incidence of initial nodal involvement and nodal relapse. None of the patients presenting with SCC histology and N0 necks had nodal relapse after elective neck irradiation. Patients who had nodal relapse had a higher risk of distant metastasis and poorer survival. Therefore, our present policy is to consider elective neck irradiation in patients with T3–4 SCC of the maxillary sinus.

Lymph node metastasis in maxillary sinus carcinoma.

Thirty-eight patients with carcinoma of the paranasal sinuses received primary therapy consisting of external beam megavoltage irradiation alone or in combination with surgery at the Stanford University Medical Center, Division of Radiation Therapy, during the period between 1956-1974. Doses of radiation ranged from 5560 rad over 5 1/2 weeks to 8050 rad over seven weeks. Relapse free survival is 37% and absolute survival 32% at five years. Twenty of 38 patients developed local failure and four patients died with metastatic disease but local control. Serious complications included two cases each of osteoradionecrosis and optic nerve injury. The data are analysed regarding dose, radiotherapeutic technique, patterns of relapse and complications.

Steven E. Bush

Papers

Carcinoma of the Paranasal Sinuses