Squamous cell lung cancer

TUMORS isolated to the nasal cavity, usually grouped with tumors of the paranasal sinuses, are uncommon. Only 16 patients with carcinoma of the nasal septum were found in a 3-center study over a 30-yr period. (1)

Risk factors for the nasal cavity and paranasal sinuses include furniture making and wood dust, (2-10) exposure to nickel, (3,8,11) textile and wool dust, (2,4-6,12) and chromium. (4) Other implicated causative agents are leather dust, (2) welding, chronic nasal disease, (7) and exposure to adhesives, cutting oils, glues, lacquers, paints, soldering fumes, and varnishes. (3,13)

The association between tobacco use and nasal cancer was demonstrated less than 2 decades ago. (14) In several studies, investigators failed to associate smoking with cancer of the nasal vestibule (2,8,10,15-17); other researchers found a weak association, (7,18) a possible association, (11,12,19) or a direct link (4,6) between tobacco use and nasal cancer. A possible connection between smoking and nasal cancer has been mentioned--but not discussed--in other publications. (3,20,21) We report herein on 9 cases that had what we considered smoking-induced carcinoma of the nasal vestibulum. In this article, we discuss the association between smoking and carcinoma of the nasal vestibulum and possible causative mechanisms.

Patients

We saw 15 patients with cancer isolated to the anterior nasal cavity in our service during the past 7 yr. One pediatric case had sarcoma, 1 patient had papillary carcinoma, 2 patients had melanoma, and 11 had squamous-cell carcinoma (SCC). Of these 11 SCC patients, 2 ceased smoking more than 2 decades prior to recognition of their tumors. Ten patients were still alive, and only 1 had cancer. Of the remaining 9 smokers, 1 was a light smoker, and 8 were heavy smokers of whom 4 continued to smoke both during and after treatment. Data for tumor differentiation were available for 7 of the 9 smokers; 4 cases were well-differentiated (cases 1, 2, 3, and 7), 2 were moderately differentiated (cases 6 and 8), and 1 (case 4) was poorly differentiated. Diagnosis was established by tissue biopsy prior to treatment, except for case 6, who had advanced disease and refused treatment. All patients denied exposure to environmental contaminants, except case 2, who worked as a wall painter and claimed minimal exposure to spray guns. All other patients were office workers.

Ages of the 9 SCC patients who smoked ranged from 55 to 89 yr (median = 68 yr); smoking ranged from 80 to 126 pack-years (median = 105 pack-years). Only 3 cases were women. Individual patient data for the 9 SCC patients who smoked at the time of diagnosis are presented in Table 1.

Discussion

Magnani et al. (2) found no association between nasal cancer and smoking. Roush et al. (8) found that there was little evidence for increasing risk for sinonasal cancer in mortality rates in the United States, despite changes in trends for cigarette smoking and for cancers of the bladder, esophagus, larynx, lung, or pharynx--all of which increased more than 2-fold during the study period. Olsen (15) studied long-term incidence of cancer of the nasal cavity and sinuses in 1,436 patients. Annual incidence was steady, which contrasted with other cancers; Olsen (15) concluded that smoking did not play a role in cancer of the nose. Haguenoer et al. (9) found no association between nasal cancer and smoking. Similarly, Hardell et al. (10) found no difference in smoking habits between nasal cancer patients and referents. Tola et al. (17) performed a case-control study to assess the etiology of nasal cancer in Finland and found no difference in smoking habits between cases and controls. These 2 latter reports may be misleading in that they describe a similar incidence of smoking between patients with nasal cancer and controls.

Elwood (14) first reported the association between cigarette smoking and nasal cancer. He found an increased relative risk of 4.9 for smokers. The study included 20 patients with cancer isolated to the nasal cavity; all had SCC. Smoking was reported by 62% of the patients with tumors in the nasal vestibule, defined as those "sufficiently near the external nares to allow some exposure to the outside environment, including sunlight." Cancer may be initiated in heavy, long-term smokers more commonly than in the normal population, as is the case in those exposed to wood dust or other carcinogenic factors. We surmise that it is cigarette smoke that insulted the nasal mucosa of our patients, and it led to carcinoma. In case 2, additional factors may have played a role.

Andersen et al. (11) studied exposure to nickel compounds and smoking in relation to the incidence of lung and nasal cancers. Of the 32 cases of nasal cancer observed, 1.8 were expected (standardized incidence ratio = 18). Although the study suggested a multiplicative effect of smoking and nickel exposure, the small number of never-smokers precluded any definite conclusions. Ng (12) performed a case-referent study of cancer of the nasal cavity and sinuses in Hong Kong. Smokers had slightly, but not statistically significant, elevated relative risks of nasal cancer. Nylander and Dement (19) reviewed the carcinogenic effects of wood dust that are also associated with tobacco smoke. They stated that an association between smoking, wood-dust exposure, and nasal cancer was observed in some studies; other investigators, whose work was reviewed in the study by Nylander and Dement, (19) however, found no such association. Nylander and Dement (19) also concluded that smoking likely contributes to nasal cancers.

Hayes et al. (18) reported a case-control study of 116 patients with sinonasal cancer. Smoking was associated with elevated, but not statistically significant, risks for SCC and adenocarcinoma. Excess risk for SCC was most evident among recent (< 9 yr) smokers. Zheng et al. (7) found that cigarette smoking was not associated with an overall increased risk of nasal cancer. The risks for SCC were, however, elevated among smokers, although the results were not statistically significant.

Brinton et al. (4) found that excess risks were 20% for cigarette smokers and nearly 50% for users of snuff, although these findings were not significant. Cigarette smoking was most strongly associated with SCC, and there was a linear relationship between risk and smoking (yr). Patients who smoked for more than 50 yr had a 3-fold excess risk. Although Elwood (14) reported an association between smoking and all types of cancers, he was the first to report an association between SCC of the nose and smoking.

Zheng et al. (6) reviewed 168 nasal-cancer--related deaths in the United States in 1985 among white men who were at least 45 yr of age. A 20% excess risk was associated with smoking; the risk increased as the number of cigarettes smoked increased and as the duration of smoking increased. A significant excess risk was also observed among nonsmokers who were married to spouses who smoked. A significantly reduced risk was noted among individuals who had quit smoking for at least 10 yr.

Bosch et al. (20) reviewed 40 patients (median age = 51 yr) with nasal cancer over a 15-yr period, 82% of whom smoked from an early age (median age = 14 yr), and noted an association between nasal cancer and smoking. Doll (3) affirmed that most studies on this subject include discussions about sinonasal cases, rather than isolated nasal cases. Doll (3) concluded that cigarette smoking causes some SCC of the nasal cavity despite the small numbers studied. LeLiever et al. (21) discussed carcinoma of the nasal septum in a series of 22 patients, of whom 82% had SCC. Of the 15 patients for whom smoking histories were obtained, 14 were positive for SCC; no additional details were provided.

In 1979, Roush (22) was the first to address the epidemiology of cancer of the nose and paranasal sinuses in the head and neck literature. No association with smoking was found, but the mechanisms of exposure to occupational agents described may be applicable to cigarette smoke. For example, inhaled contaminants may disturb the normal physiology of the nasal epithelium; different agents may compromise the respiratory ciliary and mucosal blanket. The author stated that several large cohort studies on cigarette smoking failed to report an elevated risk for sinonasal cancer, although this may be because there was inattention to this rare cancer, or because researchers combined it with additional cancer sites.

Reif et al. (23) studied the incidence of cancer of the nasal cavity and sinuses in pet dogs exposed to environmental tobacco smoke. Long-nosed dogs had a greater incidence of nasal cancer than short- and medium-nosed dogs, thus supporting an association between tobacco smoke and nasal cancer.