298 Conditions for Tumoiigenesis 



is autonomous and thus persists even though the extracellular stimulus 

 which may have been responsible for the atypical proliferation is no longer 

 active. So arbitrary is such a definition that it does not apply to the fibro- 

 myomata in women which stop growing and begin to regress when the ovary 

 ceases its endocrine activity. Nevertheless we, must adhere to this defini- 

 tion and must work with it, as will be recognized by all trained in human 

 pathology. 



There is scarcely any doubt that our definition applies to the experimental 

 epithelial growths elicited by estrogens. The atypical metaplastic proliferation 

 of the endometrium in rats with pluristratification and cornification may be 

 "more or les complete" (Selye, Thomson and Collip^"). But according to our 

 findings, complete metaplasia with cornification is a rare phenomenon in the 

 rat (pi. 1, fig. 1); in general the metaplastic proliferation is strictly insular 

 (pi. 1, figs. 2 and 3). The data relative to its autonomy are scarce but existent. 

 On one occasion, a guinea pig having been injected for eight months with 

 estradiol benzoate was found three months later to have a precancerous 

 transformation of the endometrium in the upper third of the uterine horn 

 (pi. 1, figs. 4 and 5). Gardner, Allen, Smith and Strong^^ have reported an in- 

 vasive epithelial tumor of the cervix in a mouse treated for eighteen months 

 with estrogens; this growth, having a cancerous aspect, proved to be trans- 

 plantable. The same investigators showed that the mammary adenocarci- 

 noma induced by estrogens is capable of growth without continued treatment 

 and that it can be successfully grafted into normal or castrated animals of 

 either sex (Gardner, Allen, Strong and Smith, see Allen and co-workers,' p. 

 567-568). 



Our definition also fully applies to the atypical connective-tissue growth 

 elicited by estrogens; both the subcutaneous sarcoma and the lymphosarcoma 

 of the thymus are transplantable (Allen, Hisaw and Gardner'). 



In the case of abdominal fibroids the situation is more complicated. It is 

 certain that under the influence of prolonged treatment with estrogens the 

 connective tissue throughout the whole body will react with proliferation. 

 Illustrative of this is the reaction in the prostate (Zuckerman^") or in the genital 

 tract of the female (Loeb, Suntzeff and Burns ;'^ Burack, Wolfe, Lansing and 

 Wright''*). In the guinea pig, fibrous strands and diffuse fibrosis can be seen 

 in the mesentery and in the parietal peritoneum at certain typical places 

 (Vargas). Thickenings are found in the renal capsule, and also in the uterine 

 subserosa (Lipschiitz and Vargas^^). For these reasons uterine and extragenital 

 fibroids induced by estrogens are to be considered as intensified local mani- 

 festations of a generalized fibrous reaction (Lipschiitz*"). These local manifesta- 

 tions are, however, typical as to their site (Lipschiitz, Iglesias and Vargas"); 

 that is, they obey certain laws as to localization not yet known to us— laws 

 which apply to tumors in general in men and animals. One should not forget 

 that extragenital abdominal fibroids have also been reported in men and 

 women, and it is remarkable that their gastric and intestinal localizations are 



