Considerable attention has been devoted to the diagnosis of small cell lung carcinoma (SCLC) and its subtypes. In the literature contradictory opinions have been published concerning the clinical implications of subtyping, largely because of the different criteria used by different pathologists. This article is a consensus report by the Pathology Committee of the International Association for the Study of Lung Cancer. The following classification of SCLC is recommended: (1) Small cell carcinoma. This subtype includes most of the tumors previously included in the oat cell and intermediate subtypes. More than 90% of untreated SCLC fall into this category. (2) Mixed small cell/large cell carcinoma. This subtype, which may be associated with a poor prognosis and response to therapy, contains a spectrum of cell types ranging from typical SCLC to larger cells having prominent nucleoli and resembling large cell carcinoma. (3) Combined small cell carcinomas. Typical SCLC elements are intimately admixed with areas of differentiated squamous cell or adenocarcinoma. This simplified classification of SCLC will facilitate uniformity in the diagnosis and further our understanding of the clinical significance of the rarer SCLC with variant morphologies.

A series of 722 lung carcinomas, surgically resected and typed some years ago according to the 1967 WHO classification, was independently reviewed by 2 observers in order to test the reproducibility of histopathological typing when using the criteria of the 1981 WHO classification. Typing was fully agreed upon in 87% of cases. Agreement was very high for squamous-cell, small-cell and adeno-carcinomas (kappa = 0.87, 0.89 and 0.85, respectively) while adenosquamous (kappa = 0.56) and large-cell (kappa = 0.71) carcinomas were more controversial categories. A consensus diagnosis was formulated for lesions with discrepant diagnoses. When comparing the final typing to the previous typing based on the 1967 WHO classification, squamous- and large-cell carcinomas were reduced respectively by 22% and 33% and adenocarcinomas increased by 94% of the original number. The 1981 "adenosquamous carcinoma" category included 2.8% of the tumours, while the corresponding 1967 category "combined epidermoid and adenocarcinoma" was empty. These changes must be taken into account when considering epidemiological studies, especially those aiming at evaluation of the secular trends of lung cancer by cell type.

Summary.-The post-operative survival in 554 lung carcinomata, classified according to the histological type, was calculated by the actuarial method. On the whole, squamous cell carcinoma was the most favourable and anaplastic small cell carcinoma the least favourable lesion. However, in tumours smaller than 4 cm, confined to the lung and with negative lymph nodes (stage I), small cell carcinoma had the highest percentage of 5 year survivors, followed by large cell carcinoma, squamous cell carcinoma and adenocarcinoma. When tumours had attained a larger size and/or spread tQ neighbouring structures and regional lymph nodes (stage II and III), the histological type was a much more determining factor in survival, squamous cell carcinoma being a significantly more favourable lesion. On the other hand, no difference in survival in relation to the histological type was found when distant metastases were probably present (stage IV). It was concluded that in assessing the role of histopathology in the prognosis of lung cancer, the mutual relationship to other pathological factors must be taken into account.

The early effects on mouse bladder epithelium of both acute and chronic stimulation by cyclophosphamide are described. Initial damage is similar to that reported in rats and dogs. The mechanism of repair, however, is somewhat different, in that it is very slow and is not followed by hyperplasia. The biological aspects of this repair mechanism are discussed.

TUMOURS of the lower respiratory tract have generally been regarded as bronchial tumours. However, some authors (Garland, Beier, Coulson, Heald and Stein, 1962;Lisa, Trinidad and Rosenblatt, 1965) have pointed out recently that many pulmonary tumours have a peripheral origin. A similar conclusion was reached by Mottura and Campobasso (1966) who described the histological features of 557 tumours of the lung, studied on postmortem specimens and surgical resections. They concluded that these tumours could be classified histologically under four headings: anaplastic small cell carcinoma; squamous cell carcinoma; anaplastic large cell carcinoma and adenocarcinoma. This classification is not new and is very similar to that used by other workers (Fischer, 1949;McDonald, McBurney, Carlisle and Patton, 1951;Walter and Pryce, 1955; Whitwell, 1961;Delarue, Abelanet and Paillas, 1964), but the recent work has provided a new histogenetic basis for the classification, which suggests that among the tumours of the lower respiratory tract, a distinction should be made between the true bronchogenic carcinomas, which include anaplastic small cell carcinoma and squamous cell carcinoma, and the bronchiolo-alveolar carcinomas which include anaplastic large cell carcinoma and adenocarcinoma, the latter being tumours of the lung parenchyma.On the other hand, bronchial epithelium is, in the main, a lining epithelium and its histological and ultrastructural appearances are different from bronchiolar and alveolar epithelium (Krahl, 1963;Collet, 1965). The latter are directly concerned with respiratory function and are responsible for the growth and regeneration of pulmonary tissue, both in foetal and post-natal life (Willson, 1928;Amprino, 1937;Dunnill, 1962). Consequently, it seems logical to assume that if two kinds of epithelium exist, two kinds of tumour also exist, each related to the respective type of epithelium of origin.The purpose of this present paper is to illustrate the significance of the relationship between the location of the tumour and its histological type, and to describe and to discuss some histological aspects of peripheral lung tumours. This has provided more evidence to show that tumours of the lower respiratory tract may well be of two histogenetic patterns. MATERIALS AND METHODSFive hundred and thirty-one tumours were obtained by surgical resection at the Thoracic Surgery Centre of the University of Turin. The tumours were sub-divided into hilar-parahilar and peripheral tumours, according to whether or not they were in obvious connection with the bronchial tree. To establish whether or not this connection existed, all the bronchial branches were cut and opened 57

Three mitoses of endothelial glomerular cells have been observed by electron microscopy in 3 different nephropathies (a mixed membranous and proliferative glomerulonephritis, an intracapillary glomerulonephritis, and a mixed IgG-IgM cryoglobulinemia). Further light- and electron-microscopical and autoradiographic investigations on the occurrence and nature of the dividing cells responsible for glomerular hypercellularity in glomerulonephritis have been carried out in rats with an immunocomplex-induced glomerulonephritis. A statistically significant difference between treated and control animals have been found in the number of mitoses and DNA-synthesizing nuclei. All dividing glomerular cells observed by electron microscopy were endothelial. It is therefore proved that in glomerulonephritis an actual glomerular cell proliferation does occur; proliferating cells are suggested to be endothelial in nature.

Thirteen human peripheral lung tumours have been studied in both light and electron microscopy. They were classified as epidermoid carcinoma, mucus-secreting cell adenocarcinoma, and alveolar cell adenocarcinoma, the latter made up of granular pneumocytes. Alveolar cell cancer, as defined by ultrastructural features, could assume different gross histological patterns in light microscopy, and therefore electron microscopy is required for its identification. Since neither squamous nor mucous metaplasia was observed in any alveolar cell tumour, it is tentatively suggested that all peripheral lung tumours which lack these features may be derived from granular pneumocytes, irrespective of whether they appear to be adenocarcinomata or large cell carcinomata when examined by light microscopy. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14

(Collier et al., 1958;Spjut et al., 1961;Maamies, 1966;Schottenfield, 1968;Jackman et al., 1969;Bennet et al., 1969; Slack, 1970) has been emphasized by some authors and denied by others.Higgins and Beebe (1967) found that only 4 or 5 out of 40 both clinical and pathological factors examined carried independent information predictive of cancer-free survival at 36 or 60 months. Midorikawa et al. (1968) found that it was difficult to predict the prognosis of resected lung tumours on the basis of pathological examination.This disagreement can be in part explained by the limitations of routine pathological examination (Sherwin, 1966) and more generally with the rather rough definition of some of the studied factors. A second point which seems worthwhile considering is that most of these factors have generally been taken into account one at a time. Some factors may likely play a different role in affecting prognosis whether they are or are not related to other factors.