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The histologic types of lung cancer in 855 patients (747 men and 107 women) from three hospitals and one international study of insulation workers were evaluated. Of these, 196 cases had asbestos exposure. About one half of the cases were diagnosed from surgical slides and one half from autopsy slides. Squamous cell carcinoma constituted the largest percentage of tumor types and was found with the same frequency in exposed and nonexposed groups. Small cell carcinoma was found in 25% of the exposed and in 15% of the nonexposed patients. Upper lung sites were involved in about two thirds of the cases with asbestos exposure and lower lobes in the other one third. There was little difference in histologic type in cases regardless of whether upper or lower lobes were involved. Cigarette smokers who smoked until their cancer diagnosis showed no difference in histologic type by amount smoked, and slight but not statistically significant differences from ex-cigarette smokers.

In a review of 1,186 cases of lung cancer found amoung 7,629 autopsied cases over a 21 year period a total of 82 peripheral cancers related to scars were found, constituting 1% of the autopsied cases and 7% of the lung tumors. 15% of all lung tumors were peripheral (vs. bronchogenic) and the percentage rose from less than 7 in the time period of 1955 to 1960 to a little more than 23 in the 1970 to 1976 time period. 45% of all peripheral lung cancers originated in a scar. Less than 2% of all lung cancers were found associated with scars in the 1955 through 1959 time period. This increased to nearly 16% in the 1970 through 1975 time period. 72% of the scar cancers were adenocarcinomas and 18% were of squamous cell type. The rest were large cell undifferentiated carcinomas and none was oat cell or small cell type. Over three-quarters of these scar cancers were found in the upper lobes and more than half were related to infarcts. Less than a quarter were related to tuberculosis scars. No relationship was found between smoking habits and scar cancer.

Forty-nine cases of lung tumor were initially classified according to the World Health Organization (WHO) system by light microscopy. Additional study by electron microscopy using only a minimum of ultrastructural features as criteria for each type made more precise classification of some of the poorly differentiated or undifferentiated tumors possible. Most significant was the finding of evidence of a second tumor type in nine of the 35 tumors previously classified as moderately to well differentiated thus reclassifying them as mixed tumors. Sixteen of the 49 tumors were reclassified and a more precise classification was made in five others. Only two cases of undifferentiated small cell tumors were available and no unequivocal neurosecretory granules could be found in either. Correlation of the more precise typing of lung tumors by electron microscopy with the clinical data and modes of therapy will provide necessary information for determining the usefulness of the WHO classification.

This study was designed to test the hypothesis that subjects with many asbestos bodies in their lungs at autopsy would also have asbestos bodies in various other organs. The subjects included 19 cases with diagnosis of asbestosis at death (two of these had mesothelioma, five had lung cancer) and 18 with pleural plaques but not asbestosis. Occupational histories were obtained from relatives. In subjects occupationally exposed to asbestos, large numbers of asbestos bodies were found in the lungs, and in most of these, asbestos bodies were found in many of the other organs examined. In the 18 cases with only pleural plaques found at autopsy, considerably fewer asbestos bodies were found in the lungs. The number of other organs with one or more asbestos bodies ranged from 32 percent to 62 percent of the sites examined. The findings seem to confirm the hypothesis of the study.

Changes are noted in the bronchial epithelium of dogs subjected to 44 and more than 420 days of experimental cigarette smoke inhalation. At the early time point goblet cells are more numerous and the surface lining cells possess fewer cilia. By 420 days the apparent number of cell layers in the epithelium is double that of the controls. The luminal surface is devoid of ciliated columnar cells and goblet cells, these being replaced by columnar and cuboidal cells whose free surface is covered by stubby projections. Basal cells are frequently columnar-shaped and mitotic figures are common. Most cells contain a profusion of cytoplasmic filaments which often appear to displace cell organelles. A “special type cell” with cell-specific granules, first described in the control, is found in great abundance in the intermediate region between the basal cells and the surface lining cells. In both osmium- and acrolein-fixed tissue the two special migratory cell types, which are so common in the controls, are rarely seen. The basement membrane is frequently interrupted by gaps through which cytoplasmic processes of basal cells protrude; a thickened zone underlying the basement membrane contains an increase in fibrillar components and multiple layers of basement membrane material.

Evaginations or blebs involving both layers of the nuclear envelope were observed in ciliated columnar cells of the bronchial epithelium obtained from four patients during lobectomies. These are visible with the light microscope as supranuclear vacuoles. In adjacent sections electron micrographs showed the “vacules” to be bounded by “double membranes” identical in appearance to, and in some instances continuous, with the nuclear envelope. Nuclear components extend from the nucleus into the evagination. In some cells multiple evaginations extend in a row. These may be interconnected, or only the most proximal one may be continuous with the nucleus. In some evaginations, appearing at a distance from the nucleus and with no apparent attachment to it, breakdown of the enclosing envelope suggests the possible dissolution of the entire structure into the cytoplasm thus providing a means of transfer of nuclear material.

Moderately electron-dense bodies without a limiting membrane and having a diameter of approximately 700A were observed in the cytoplasm of ciliated columnar cells in the bronchial epithelium of man. They seem to consist of aggregates of coiled filaments about 25A thick and have been termed “filosomes.” Filosomes, singly, in small groups, or in larger clusters, were found randomly distributed throughout the cytoplasm between the nucleus and the cell apex and were sometimes associated with structures resembling components of cilia. By site, the filosomes were associated with many cell organelles, especially the nucleus, and their consistont occurrence with annulate lamellae was specifically noted. The similarity of the material of the filosomes to that of structures which have been shown by others to be involved in ciliogenesis suggests a similar role for filosomes.

Electron microscopic observations in areas of fibrosis and emphysema of the lungs of dogs subjected to experimental cigarette smoking show that alterations occur both in the pleura and the lung parenchyma. In the pleura the major alteration is the increased thickness of the stroma due to large amounts of collagen present. In the lung parenchyma two major alterations appear in the interstitium of the alveolar septa where there is a complete loss or a great reduction in the number of capillaries and a marked thickening of the septa due to the increased amounts of collagen. Changes in the alveolar epithelium are slight; changes in capillary endothelium, such as rarefication of cytoplasm and blebbing of the plasmalemma, are found. More frequently noted are the changes involving the basement membrane of the alveolar epithelium which in some places appear to be greatly thickened and in others to be exceptionally thin or missing entirely. Another of the most striking alterations noted in both the pleura and parenchyma is the presence of large numbers of macrophages occurring singly, in clumps, and in granulomas. Although macrophages are found in the lungs of nonsmoking dogs they are not found in such numbers nor with the unique content observed in the lungs of smoking dogs. Crystalline-like structures are found in membrane-bound inclusions and ferritin-like particles occur both in large membrane-bound aggre-gates and lying free in the cytoplasm. Conclusive identification of these structures and their relationship to inhalation of cigarette smoke requires further study.

Hyperplasia of bronchiolar epithelium was observed in the lung parenchyma of 14 smoking dogs. Besides the increased number of cell layers in the bronchiolar epithelium, there was a virtual absence of glycogen in the cell cytoplasm. Sheetlike arrangements of squamous cells containing an abundance of tonofilament bundles were found lining alveoli. Type II cells were found adjacent to, and sometimes extending over the squamous cells. In all cases, a proliferation of type II cells was found in the alveolar epithelium, almost completely lining some alveoli. Acinarlike structures also lined by many type II cells were sometimes found near the pleura. Microinvasions of cytoplasmic processes into the underlying connective tissue often occurred through defects in the basal lamina. In some type II cells an unusual content of RER was observed. It possessed electron dense banding ≈ 180 A wide with a repeat at intervals of ≈ 540 A and was found in narrow cisternae and in bulbous dilatations of the cisternae of the RER. Fibrogranular material of the same appearance and periodicity was also found in the perinuclear space in some cells. Type II cells are further implicated as a reserve cell or stem cell in metaplastic alterations.

A study was made of histologic type of lung cancer in relation to smoking habit, year of diagnosis, age and sites of metastasis. It comprised 662 autopsies of men during the period from 1955 to 1972. As classified by the WHO system, 35.2 percent were epidermoid carcinoma, 24.6 percent were small cell carcinoma, 25.2 percent were adenocarcinoma and 14.2 percent were large cell undifferentiated carcinoma. The six non-smokers of the series were all found to be in class 3, adenocarcinoma. No clearcut and consistent relationships were observed. Although there was a steady decrease in the incidence of small cell carcinoma during this time period, this observation did not prove to be statistically significant. Small cell carcinomas increased with amount of smoking but not for all age groups. Adenocarcinomas decreased with advancing age but not in all smoking groups. Metastases were found in 96.3 percent of the cases and the sites most frequently involved were regional lymph nodes, liver, brain, distant lymph nodes, adrenals and bone. Small cell carcinomas showed the greatest percentage of involvement for those major sites and for the same sites, epidermoid carcinoma showed the lowest percentage.