The Significance of Cell Type in Relation to the Aetiology of Lung Cancer

Abstract

KREYBERG (1952KREYBERG ( , 1954aKREYBERG ( , b, c, d, and 1955 has concluded that the histological types of lung cancer to be seen in Norway can be divided into two aetiologically distinct groups. The squamous cell, large cell and small cell carcinomas (including oat-cell carcinomas) form the first group. These types he thought might be histological variants of a single oncological entity and be produced largely by exposure to an external factor (or factors) which have recently increased in prevalence and to which men are principally exposed. The second group is heterogeneous and consists of adenocarcinomas, bronchiolar (alveolar cell) carcinomas and various grades of adenoma and salivary gland type tumours (including cylindromas). These different types, it was suggested, might be produced by different aetiological factors including, perhaps, developmental abnormalities, virus infection and external factors of approximately constant prevalence to which men and women are exposed equally.In Norway, Kreyberg (1955) estimated that four out of every five Group I tumours in men were related to tobacco smoking, but Group II tumours were found to be entirely unrelated to tobacco. In the U.S.A., Wynder and Graham (1950) had previously obtained evidence suggesting that smoking was more closely related to the development of "epidermoid" tumours than of adenocarcinomas and Wynder (1954) in data collected from several countries found that adenocarcinomas constituted a higher proportion of lung cancer cases among male non-smokers than among male smokers. In Britain, Doll and Hill (1952) found no statistically significant differences in either sex between the amounts smoked by patients with (i) squamous carcinoma (475 men and 18 women), (ii) oat-cell or anaplastic carcinomas (303 men and 38 women), (iii) adenocarcinoma (33 men and 10 women) and (iv) carcinoma of unclassified type (105 men and 13 women). Neither was there any significant difference in the amounts smoked between the four groups of patients in whom histological examination was made and the patients not examined histologically (441 men and 29 women). They noted, however, that in both sexes there were relatively more non-smokers and very light smokers in the small group of patients with adenocarcinoma than in any of the other groups, but the numbers were too few to be convincing.In the present study these British data have been re-examined in greater detail. Additional evidence has been obtained about some of the cases which could not previously be allocated to one or other histological group and many available specimens have been re-examined. Because of the large number of patients in the whole series a selection for re-examination was made as follows :-(i) all tumours in women, (ii) all tumours in men provisionally classified to Group

Temporal trends in non-small cell lung cancer survival in Sweden

“…Originally, adenocarcinoma was considered to occur primarily among non-smokers (Doll et al, 1957;Kreyberg, 1961), but later studies demonstrated that it is also strongly associated with smoking (Thun et al, 1997;Simonato et al, 2001;Yang et al, 2002). The increased incidence of adenocarcinoma among smokers may be explained by the widespread introduction of filter and lower-tar and nicotine cigarettes (Wynder and Muscat, 1995;Stellman et al, 1997;Thun et al, 1997).…”

Histological Types in Primary Lung Cancer: Relative Frequencies in Various Samples of a National Lung Cancer Material

“…Usually the character of the pathological material has been known to the pathologist. When observer bias is nevertheless assumed to be negligible as a cause of variation it is mainly for the following reasons: Firstly, Kreyberg, who has undertaken by far the greater part of the typing, has repeatedly demonstrated that his classification, under varying conditions, including blind trials, is highly consistent (Doll, Hill and Kreyberg, 1957;Kreyberg and Saxen, 1961 Table II shows that their age pattern a steady increase with age differs markedly from that of all histologically confirmed cases. It is indeed possible that this undetermined group or that part of it which really is primary lung cancer contains the varying histological types in proportions different from those observed in the histologically examined group.…”

Implications of Evolving Medical Science for Proof of Lung Cancer Causation

“…In the mid-20 th century, small cell and squamous cell carcinoma were the most common types of lung cancer diagnosed in many parts of the world (9). At that time, many researchers and clinicians even doubted whether adenocarcinoma was associated with cigarette smoking (10). Over time, the prevalence of adenocarcinoma has increased markedly to the point where it is now the most common major lung cancer cell type throughout much of the world (11), regularly diagnosed in both smokers and never-smokers.…”