adenomatous type may be due to increased resistance of the animal, and he describes several instances in which tumours usually alveolar, have become adenomatous when growing in animals whose resistance had been raised by a preliminary injection of normal mouse-blood, as described by Bashford, Murray, and Cramer. So far as our experience goes, no such association can be made out between histological structure and the resistance of the animals, in our experiments with this squamouscelled sarcoma. Five tumours have been examined which developed exceptionally, in 70 animals treated previously to inoculation with an emulsion of the skin of mouse-embryos, a procedure which produces a high degree of resistance to the growth of this squamous-celled carcinoma. In none of these tumours does the degree of differentiation of the parenchyma differ from that of the tumours in the control animals. In one case the tumour alveoli are small and the stroma correspondingly well developed. A slow-growing tumour in a normal mouse of the same series, exhibits the same peculiarities in even higher degree. These observations therefore do not confirm Apolant's interesting observation, and it has not yet been possible to influence the histological character of the transplanted tumours by experimental methods. Since the above was written, another spontaneous tumour (No. 164/0) has been obtained, in which widespread keratinisation is present along with adeno-carcinomatous areas. The tumour was entirely subcutaneous, and has been transplanted into 300 normal mice; sufficient time has not yet elapsed, for the result to be available for this Report. LITERATURE. APOLANT, H.-Die Epithelialen Geschwülste der Maus. Arbeiten aus dem Konig- V. HANSEMANN, D.-Studien über die Specifizität, den Altruismus und die Anaplasie der Zellen. Berlin, 1893. HERXHEIMER, G.-Ueber heterologe Cancroide. Ziegler's Beiträge, Bd. 41, 1907. JENNY.-Beiträge zur Lehre vom Carcinom. Archiv. für Klin. Chirurgie, Bd. 51, 1896. LEWIN, C.-Experimentelle Beiträge zur Morphologie und Biologie bösartiger Geschwülste bei Ratten und Mäusen. Zeitschrift für Krebsforschung, Bd. vi. 1908. LUBARSCH, O.-Einiges zur Metaplasiefrage. Verh. d. Deutsch. Path. Ges. Stuttgart, 1906. RIBBERT, H.-Lehrbuch der pothologischen Histologie. Bonn, 1901. Beiträge zur Enstehung der Geschwülste, Dritte Ergänzung zur "Geschwülstlehre." Bonn, 1908. CONTRIBUTIONS TO THE STUDY OF THE DEVELOPMENT OF SARCOMA UNDER EXPERIMENTAL CONDITIONS. BY M. HAALAND. 1. WITH the first successful transference of a carcinomatous tumour from animal to animal of the same species the question arose as to the nature of the process responsible for the development of the new growth, and especially what part was played by the introduced tissues. Hanau1 inferred from his successful transference of a squamous-cell carcinoma from rat to rat, that the transplantation of the parenchyma cells was the essential factor in the formation of a new tumour. Without directly investigating how the supporting structures of the new tumour arose he discussed the different alternatives, viz., on the one hand the possibility of transference of a connective-tissue germ, and on the other of a formative influence exercised by the carcinomatous cells on the tissues of the new host; he decided in favour of the latter alternative. Morau and Borrel3 assumed without making further inquiry that the essential part of the process is the grafting of cancer cells. Loeb described observations on the process at the site of inoculation 1 HANAU: Erfolgreiche experimentelle Uebertragungvon Carcinom. (Fortschritte der Medizin, vol. 7. 1889.) 2 MORAU: Recherches experimentales sur la transmissibilité de certains néoplasmes (Archives de Medicine expérimentale, 1894, p. 677.) 3 BORREL, A.: Epithélioses infectieuses et epithéliomas. (Annales de l'Institut Pasteur, T. xi. 1903.) LOEB, LEO: On Transplantation of Tumours. (Journal of Medical Research, vol. vi. 1901.) : Further Investigations in Transplantation of Tumours. (Ibidem, vol. viii. 1902.) of a rat-sarcoma, but his description of this difficult material is too imperfect to settle definitely what actually took place in his inoculations. To Jensen1 the credit is due of having first systematically investigated and clearly described the processes at the site of inoculation. By carefully examining small pieces of tumour at short intervals after transplantation, he proved that the new tumour-parenchyma was derived solely from that introduced. As to the fate of the introduced stroma elements, Jensen expressed himself very carefully. He observed that the hyaline degenerated connective tissue of the graft was penetrated in the course of time by fibroblasts and capillaries from the new animal, and he considered it probable that the old stroma was absorbed by degrees, but he thought it possible that a part of it may remain alive. Bashford, Murray and Cramer2 made an exhaustive study of the processes at the site of implantation for Jensen's tumour as well as for numerous other tumours of their own. They stated that the parenchyma alone possessed powers of apparently continuous proliferation in the tumours they examined. The stroma of the grafts underwent degenerative changes as a rule, and was replaced by supporting structures derived entirely from the tissues of the new host. The tissues taking part in this reaction were ultimately transformed into stroma and bloodvessels identical with those of the primary tumour. This stroma reaction is specific, i. e. constant in the several generations of the same tumour but may present peculiarities for different tumours. Later, Loewenthal and Michaelis3 studied the processes at the site of implantation for another tumour, and in the main came to the same conclusions. 1 JENSEN, C. O.: Experimentelle Undersögelser over Kraeft hos mus. Copenhagen, 1903, Experimentelle Untersuchungen über Krebs bei Mäusen. (Centralblatt für : Biolog. Selskabs Forhandlinger, 1901-02, pp. 6 & 20. Nogle forsög med kraeftsvulster. (Hospitalstidende, no. 19, 1902.) 2 BASHFORD, E. F., MURRAY, J. A., & CRAMER, W.: Source of the Constituent Elements of New Growths obtained by Artificial Propagation. (2nd Scientific Report of the Imperial Cancer Research Fund.-Part II. Taylor & Francis, London, 1905.) : Stroma is a Specific Reaction on the part of the Host. (Ibidem.) : Comparison between the Transmission of an Infective Granuloma of the Dog and Carcinoma of the Mouse. (Ibidem.) LOEWENTHAL, W., & MICHAELIS, L.: Ueber den Krebs der Mäuse. (Zeitschrift für Krebsforschung, Band iv. Heft 3, 1906.) It seems then to be a well established observation that as a rule the stroma degenerates after transplantation, and only the introduced parenchyma is capable of further growth; the new stroma is formed as a specific reaction on the part of the host. This fact is in perfect agreement with observations in human pathology. The transplantation of tumours from animal to animal is to a certain extent analogous to the formation of metastases in the spontaneously affected individual. It has often been shown that in secondary deposits of carcinoma the new growth proceeds entirely from the parenchyma cells, while the stroma of the metastatic nodule is supplied either from the stroma of the invaded organ or from a newly formed reaction-tissue. From these observations it follows that the stroma of a carcinomatous tumour is to be considered as a normal tissue, while the parenchyma alone possesses malignant properties. These points having been ascertained it was a most surprising new fact, discovered by Ehrlich and Apolant1, that the stroma in certain transplantable mouse carcinomata gave rise to a new and distinct kind of tumour-tissue, viz. a transplantable sarcoma. Ehrlich and Apolant observed this phenomenon in three different instances; in each instance the tumours had been propagated over a prolonged period of time and through numerous generations as carcinomata, without showing any sign of being mixed-tumours. In one case the change occurred in the 9th generation, i. e. after 9 months propagation as a carcinoma; in another only after 67 generations, i. e. after 2 years propagation as a carcinoma; in this latter case, however, the sarcomatous change was preceded by a marked increase in the amount of connective tissue, extending through more than 20 generations. The change consists in a sudden appearance of a sarcomatous tissue between the alveoli of the carcinoma and replacing the original stroma. In succeeding generations the sarcomatous tissue ousts the carcinomatous and entirely supplants it after a shorter or longer time, and ultimately a pure sarcoma is obtained. The time necessary for the completion of the process varied in Ehrlich and Apolant's cases. In one a pure sarcoma was obtained quickly, namely, after one or two generations of mixed tumour; in another after three or four generations; in the third the mixed tumour persisted for more than nine months through ten to fourteen generations before a pure sarcoma 1 EHRLICH, P., & APOLANT, H.: Beobachtungen über maligne Mäusetumoren. (Berliner klin. Wochenschrift, 1905, no. 28.) APOLANT, H.: Die epithelialen Geschwülste der Maus. (Arbeiten aus dem Königlichen Institut für experimentelle Therapie zu Frankfurt a/M. Heft 1, 1906. N was obtained *. The results of the histological examination convinced Ehrlich and Apolant that their tumours were not mixed-tumours from the outset. They also rejected the possibility of the new tumours being infective granulomata. In their first paper they entertained two main possibilities in explanation of the unexpected appearance of a sarcoma :(1) "In the course of continued propagation the chemical metabolism of the carcinoma cells becomes altered so that substances are formed which have a stimulative action on the connective-tissue cells and incite them to metaplastic growth; (2) During the continued propagation connective-tissue cells are transplanted along with the carcinoma cells, and in the course of the numerous passages through strange hosts from animal to animal the connective-tissue cells acquire a power of proliferation ultimately attaining to that responsible for tumour formation." To the second suggested explanation Bashford remarked that as his investigations had shown that the stroma in the transplanted tumours as a rule degenerated and the new stroma was formed de novo from the inoculated animal, this hypothesis was in contradiction to the facts. Up to the present no evidence to the contrary has been adduced by other investigators. In later publications Ehrlich and Apolant seem to have dropped this second explanation and have developed the first a little further. In a paper in the Berliner Klinische Wochenschrift, No. 2, 19062, the cause of the sarcomatous change is sought in "a stimulating influence proceeding from the carcinomatous cells, which in a certain stage of the development determines the sarcomatous transformation of the connective tissue scaffolding of the tumour." Ehrlich himself has not defined more clearly what he implies by "a certain stage of the development." 3 In summarising Ehrlich's and his own observations on this subject, Apolant writes that the life of a transplantable carcinoma may be confined within time limits in the case even of the most virulent carcinomata such as those which had been supplanted by sarcomata The absolute time is not stated for the two first cases. 1 BASHFORD, MURRAY, & CRAMER: Einige Ergebnisse der experimentellen Krebsforschung. (Berl. klin. Wochenschrift, 1905, no. 46.) 2 EHRLICH & APOLANT: Weitere Erfahrungen über die Sarkomentwicklung bei Mäusecarcinomen. (Ibidem, 1906, no. 2.) 3 APOLANT, H. Die experimentelle Erforschung der Geschwülste. (Handbuch der pathogenen Mikroorganismen by Kolle and Wasserman. 1ster Ergänzungsband, 1906, p. 456.) |