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Absrracr. By subcutaneous serial transplantations of induced pulmonary tumors of mice a tumor progression has previously been correlated with the age of the tumors. The progression showed alterations from an alveolar-lining-type adenoma through papillary structures and different carcinomas to a spindle cell carcinoma in the final stage. Based on this report, 448 spontaneous pulmonary tumors in conventional and specific-pathogen-free Han:NMRI mice in different stages of life were classified. Six different types of pulmonary tumors were identified and compared with the age of the host. With increasing age of the host the pulmonary tumor tends to develop towards ultimate malignancy. Such a timedependent transformation occurs regularly, as shown by a statistical analysis. A progression of primary spontaneous pulmonary tumors in mice is indicated as well. Anhand von Serientransplantationen und histologischen Untersuchungen konnte KIMURA [ 151 nachweisen, dass induzierte murine Lungentumoren mit zunehmendem Alter einer Urnwandlung vom einfachen alveolaren Adenom uber verschiedene papillare Strukturen bis hin zum undifferenzierten Karzinom unterliegen. Diese Befunde haben uns veranlasst, die seit 1967 im Zentralinstitut fur Versuchstierzucht bei Mausen des Auszuchtstammes Han : NMRI diagnostizierten Lungentumoren in Anlehnung an die Untersuchungen von KIMURA [ 151 histologisch zu klassifizieren und nach Altersstufen zu gruppieren. Es sollte festgestellt werden, ob und gegebenenfalls welche Tumortypen in den einzelnen Altersklassen dominieren und ob die Ergebnisse Ruckschlusse auf eine Tumorprogression auch bei spontanen Lungentumoren der Mause erlauben.

A pulmonary tumor with a light microscopic appearance typical of bronchiolar-alveolar cell carcinoma was studied with the electron microscope. The tumor was composed of cells which were remarkably similar to Type 11 alveolar lining cells (granular pneumocytes). Some investigators doubt the existence of alveolar cell carcinoma as a distinct entity, and advocate lumping together all such tumors with pulmonary adenocarcinomas. Evidence presented here and elsewhere, however, indicates that some bronchiolar-alveolar cell carcinomas are composed of cells with the ultrastructural characteristics of granular pneumocytes. Classification of these neoplasms should take electron microscopic findings into account, since ultrastructural differences between tumors with similar light microscopic appearances may eventually be correlated with varying patterns of clinical disease.

A bronchial neoplasm consisted of cells with abundant, finely granular, eosinophilic cytoplasm. Ultrastructurally, this granularity was due to mitochondrial hyperplasia thus fulfilling the criterion of a true oncocyte. Although the terms “pulmonary oncocytoma” and “oncocytic carcinoid” have been used in the past, this is apparently the first pulmonary tumor in which mitochondrial hyperplasia has been demonstrated thereby confirming the accuracy of the term oncocytoma in this particular instance. The bronchial mucosal glands adjacent to the tumor contained numerous foci of oncocytes and are considered the most likely source of the neoplasm.

We have had the impression that primary atypical pneumonia has been considered a disease easy to diagnose and simple to handle. This has been due, at least in part, to the very low mortality and the lack of effective specific therapy. It is hoped that this will serve to emphasize the following points: 1. Frequently it is very difficult, if not impossible, to differentiate primary atypical pneumonia from pneumococcic pneumonia. This should be done, if possible, in order that specific therapy be administered if indicated and withheld if not indicated. 2. Primary atypical pneumonia might often simulate pulmonary tuberculosis in its various manifestations and on rare occasion might be confused with pulmonary tumor. 3. It might well be impossible to differentiate primary atypical pneumonia from bronchiectasis during the acute stage. In a case of suspected bronchiectasis following primary atypical pneumonia, it is well to allow a period of observation and repeat the bronchogram before deciding upon surgical treatment of the bronchiectasis. The importance of differentiating primary atypical pneumonia from this and the conditions mentioned above is self-evident.

A patient in this case was an 89-year-old man. A hematoma as large as a child's head occurred in tne pulmonary parenchyma due to the chronic rupture of the arteriosclerotic aneurysm of the descending thoracic aorta, with a resultant absence of the typical symptoms of aortic aneurysm. Continuous hemoptysis, tracheophony and pulmonary tumor-like roentogenogrpahic features were noted. Atypical cells which were believed to be malignant tumor cells were detected in sputum. These findings made it considerably difficult to discriminate aortic aneurysm and pulmonary tumor. These respective clinical findings were evaluated on the basis of autopsy findings.

Following closely in the wake of the discovery that cancer of the skin can be produced experimentally by the repeated application of tar, attempts have been made, through the years, to induce cancer in practically all of the other body organs. It may be said, that, as a general rule, where a potent tar can be applied repeatedly, or where a sufficient quantity of it can be placed so as to remain immobile for a sufficient length of time, cancer may be induced in a varyingly high percentage of instances. There are regions, however, that tend to defy the experimenter. Among such locations are the lungs. The physical difficulty of applying tar directly to the lung structures is apparent and requires no explanation. The difficulties in the way of making repeated direct applications of tar to the same lung are even more obvious. A survey of the literature shows that the earliest experimental attack on the problem of experimental tar cancer of the lung was made by Murphy and Sturm (1), who noted that when mice were tarred in various skin areas they developed primary tumors of the lung. In one of their groups of mice these investigators observed a 78.3 per cent incidence of primary lung tumors in tarred animals, though no tumors occurred in a control series. Murphy and Sturm designate these lung tumors as “a distinct type of epithelial tumor” and furnish reasons for believing that they are primary neoplasms. Care was taken to kill the animals early enough in life to avoid the possible complicating factor of primary lung tumors incident to age rather than to tar. The authors furnish no dogmatic explanation for the development of the tumors, but they strongly incline to the belief that the tar painting has the constitutional effect of lowering the resistance of the animals, and that local irritation (caused by inhaled particles of shavings, sawdust and chopped food), grafted on the lowered resistance, induces pulmonary tumor formation

The mammary tumor incidence has been published for breeding females of the inbred A strain of mice. No attempt was made, however, to determine the proportion of autopsied animals which had primary lung tumors. The present report includes additional observations on the mammary tumor as well as pulmonary tumor incidence in breeding and virgin females. Origin of the Stock This strain of mice was started in 1921 by Dr. L. C. Strong (1936), who crossed a female secured from Dr. Little to a male obtained from Dr. Bagg. Matings have been primarily brother-to-sister, with an occasional daughter-to-father cross. A selection experiment was started by Strong during 1928 following the 28th generation of inbreeding. Descendants of female No. 13623 and her daughter No. 14424 have received the designation “Strong A” line. The offspring of female No. 13622 have been called the “Strong A2” line (Strong, 1934, 1936). Representatives of this stock were given to the writer by Dr. Strong in 1927. The line upon which the present observations are based is descended from female No. 13623 and her daughter No. 15317 of Strong's stock. Since 1930 (Bittner) this line of the Strong albino stock has been called the “A” stock. All the individuals considered in this report received Purina fox chow. Observations The number of breeding females living beyond the age at which the first mammary tumor was observed was 536 (Table I). Of this number, 454 or 84.7 per cent had mammary tumors, and of these 32 (4.3 per cent) also had primary lung tumors. The average age was 11.8 ± 0.1 and 12.5 ± 0.4 months respectively. Nine or 1.7 per cent had primary lung tumors only; average age 17.5 months.

SummaryA significant increase in the incidence of pulmonary tumors is recorded in A strain mice following subcutaneous injection of 10 mg sodium desoxycholate. No such response was indicated following similar treatment with cholic acid.

Summary A case is reported of ten year survival after thoractomy for inoperable bronchogenic carcinoma. Apparent spontaneous regression has been followed by freedom from development of a new pulmonary tumor in spite of the patient's continued smoking. Immunologic factors affecting this course are suggested by the demonstration of immune lymphocytes in the patient's peripheral blood which depress the growth of tumor cells from a donor with lung cancer.

Studies with several chemically-induced animal tumors have demonstrated that implantation of tumor cells in admixture with viable Bacillus Calmette-Guerin (BCG) prevents their growth in genetically compatible hosts [1, 3, 5]. Deliberate infection of established local tumors may also lead to their suppression [1, 7] and the inhibition of metastases [7]. The mechanism of this tumor inhibition is not yet understood, although factors other than immunostimulation are involved, since intimate contact between BCG organisms and tumor cells is necessary [1, 5] and may contribute to this effect.

Publisher Summary This chapter reviews an investigation concerning primary pulmonary neoplasms in animals. The terms of reference exclude metastatic neoplasms of the lung and more generalized neoplasms with incidental localization in the lung, such as lymphosarcoma or hemangioendothelioma. Most of the experimental work has been performed with the adenomatous pulmonary tumor of the mouse, and most of the observations and the conclusions perforce must be limited to mice. The chapter discusses that recent reports on the induction of pulmonary tumors in rats and in guinea pigs allow the extension of investigations to other species. Reports on pulmonary tumors in larger animals are limited to descriptions of individual cases and a few, mostly unsuccessful, attempts to induce the tumors. Cancer research, as all biological research, is dependent upon the availability of proper materials and techniques for its work. The chief material has been the mouse, and the chief techniques have been the transplantation and the induction of neoplasms. On this basis, a large portion of the history of cancer research can be divided into three main periods: 1890-1918, morphology-transplantation era; 1918-1935, genetics-tar tumor era; and the modern period since 1935.

In the short paper by Heston and Schneiderman that appeared on page 109, SCIENCE, January 30, there is an error at about the middle of column 2. The chemical name for the mustard oil should be "allyl iso-thiocyanate" and not "ethyl iso-thicyanate," as printed. This is our error.

Roentgenographic studies revealed multifocal nodular lesions within the lungs of a 28-year-old woman who also had a ruptured tubal pregnancy. Pulmonary biopsy studies revealed the lesions to be decidua-like. Hematogenous metastasis from the placental site during an earlier pregnancy is favored over other possibilities for origin of the tissue. However, the possibility that the patient had a peculiar form of pulmonary tumor has not been entirely excluded. The patient has been observed for 5 years postoperatively and has remained asymptomatic, although the pulmonary lesions have remained stabilized as determined by follow-up roentgenographic studies.

Permanent cardiac pacemakers are implanted so that the electrodes in contact with the heart are connected to a power source located elsewhere on the chest. This battery pack is usually placed in a subcutaneous pouch which overlies the right or left pectoral muscles. In this position it obscures the lung underlying the area when it is examined on a posteroanterior chest roentgenogram. Recently, an 80-year-old man who had previously had an artificial pacemaker implanted for complete heart block was found to have a malignant pulmonary tumor in this area (Fig. 1). The decision to use radiation as treatment for the tumor was complicated by the uncertain effect the radiation would have on the performance of the pacemaker. Pacemaker Radiation In order to determine the effect of radiation on similar pacemakers, two separate units were subjected to direct irradiation from a cobalt-60 teletherapy source. A ventricular demand type pacemaker2 was given a total dose of 10,000 rads, and a P-wave synchronous pacemaker3 ...

In the short paper by Heston and Schneiderman that appeared on page 109, SCIENCE, January 30, there is an error at about the middle of column 2. The chemical name for the mustard oil should be "all...