R. Muir, del. 19 Delicate reticular and oedematous stroma FIG. 13.-Mouse. Tumour with dilated capillaries. X

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see directly that the stroma reaction is comparatively weak in the hæmorrhagic tumours, and that most of the characteristics of this group can be explained by this fact. When the transplanted epithelium has a powerful effect on the connective tissue, there is a rich new formation of connective tissue and vessels which contribute to the building up of the tumour and to its nourishment. The amount of this "specific stroma reaction" is to a certain extent characteristic for every tumour, and it is easiest to understand on the hypothesis of chemical substances with chemiotactic actions. It now seems that in analysing this reaction we may differentiate still further in accordance with the varying extent to which the connective tissues and the blood-vessels respond, so that we may speak of a fibro-plastic and an angio-plastic reaction. If the two are in equilibrium, good well-nourished carcinomata with large or small alveoli will arise. If the fibro-plastic influences preponderate, the nourishment of the cancerous cell-nests will suffer, and herein may in part be recognised a reason for a central necrosis of the epithelial masses or of the whole of a tumour as is, for example, so often the case in Jensen's tumour. Should the angio-plastic processes preponderate, there will be formed only a little connective tissue but a rich supply of vessels; and such are the phenomena, as Apolant has already described them, in the case of the hæmorrhagic tumours, for we find in them a very delicate stroma (fig. 13) which can only serve in an insufficient manner as a support and a stay to the numerous vessels. Slight stagnation can then easily lead to oedema of the tissues surrounding the vessel, increased blood-pressure to dilatations and ruptures of the vessels themselves. The nourishment of the tumour will at first be amply provided for through the good blood supply. Interferences with the nourishment first arise as the result of the oedema and hæmorrhages. Thus we can explain all the main features of the hæmorrhagic tumours from the nature of the stroma reaction. It is worthy of note that this reaction is retained most tenaciously through numerous sub-transplantations and together with the specific appearance of the epithelium preserves above all the likeness of the inoculated tumours to the sporadic tumour.

Accordingly, I believe that we may assume a special" specific stromareaction" which is an immanent and transmissible quality of some of the epithelial cells and an essential characteristic of this group of hæmorrhagic tumours in mice.

I consider it very possible that the nature of the stroma-reaction plays a prominent part in the establishment of tumour particles after implantation. A too powerful reaction can perhaps lead to absorption, a too

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weak, to insufficient nourishment and death of the implanted tissue. The nature of the stroma-reaction may have something to do with the facts that the hæmorrhagic tumours have been found so difficult to transplant and the percentage of successful inoculations has not yet risen to a maximum. With regard to transplantation, we must consider not only the power of multiplication of the epithelial cells, but also the specific stroma-reaction, and since the latter manifests itself in the tissues of the new host, we may presuppose a certain capability of reaction on their part. I think it is conceivable that this is an essential factor in determining individual susceptibility to implantation, and accordingly, that a tumour only continues to grow when it finds adequate power of response in the connective tissue to the stimulus which elicits the specific stroma-reaction. Indeed, it seems to me not impossible that the artificially induced immunity depends upon a change in the capability of the connective tissues to provide the stroma. Since experiments on such resistant animals with a view to demonstrating the presence of bodies specifically directed against the cancer cells have been unsatisfactory up till now, we must entertain such a possibility, although we must always be conscious of the hypothetical character of such representations. This possibility has already been emphasised by Bashford, Murray, and Cramer.

We see similar differences in the effects on the connective tissues in the case of human cancer, and can explain the formation of scirrhous and medullary forms of carcinoma in the same way, while certain other forms of tumour have been termed angio-plastic. Further, there are carcinomata that act directly on the connective tissue of bone causing it to proliferate, so giving rise to the so-called "osteo-plastic carcinomata."

The stand-point has been adopted above that all our hæmorrhagic tumours, even those of adenomatous structure, are malignant. The fact, also mentioned above, that they often recur after operative extirpation favours this view. Infiltrative and destructive growth is as a general rule less prominent in the mouse carcinomata than in their human equivalents, perhaps because the site where they most frequently occur, the subcutaneous tissue, is extraordinarily loose in mice and offers only very insignificant resistance to the growth of the tumours. But it is not altogether lacking, and at the margins of the hæmorrhagic tumours we find places on careful search where the columns of epithelium infiltrate the neighbouring tissue. Thus fig. 14, shows such a margin of tumour 88, infiltrating muscle fibres. In the young marginal undifferentiated