Experimental Induction of Lymphocytic Malignancies 179 



By seventy-two hours the changes described are more definite. The cellular 

 infiltration of the Eat tissue around the genital organs and the kidneys is 

 almost entirely made up of the mononuclear cells with only an occasional 

 polymorphonuclear leukocyte. The periadrenal fat tissue is similarly in- 

 volved. 



By the fourth day the changes are unmistakable. In those areas in which 

 small collections of tumor cells were seen earlier, tumor cell infiltration is 

 heavier. In addition the tissues around the mediastinal and mesenteric 

 nodes also show beginning infiltration with tumor cells, although the archi- 

 tecture of the lymph nodes remains preserved. 



On the fifth and sixth days changes are progressing; an occasional lymph 

 node shows specific involvement. By the seventh day the mesenteric and 

 mediastinal lymph nodes show certain involvement, and the inguinal lymph 

 nodes show early changes. By the eighth day the lymph node involvement 

 becomes generalized. By the ninth day complete dissemination has occurred; 

 lymphoblastoma is fully developed. 



The progression of changes is essentially the same in all animals injected 

 with leukemic material. Significant differences could not be demonstrated 

 between the development of leukemia in those animals injected intracere- 

 brallv or intraperitoneal!)' with leukemic cell-free filtrates and those animals 

 injected with tumor cell suspensions. 



The very early lymphoblastomatous transformation in the fat tissues sur- 

 rounding different organs is striking. This occurs long before significant 

 changes can be demonstrated in such lymphoid tissues as lymph nodes, 

 thymus, and spleen. 



A contiguous involvement from the site of injection seems unlikely be- 

 cause the progression of changes in the animals injected with tumor cell 

 suspensions intraperitoneally does not differ significantly from the pro- 

 gression of changes seen in animals injected intracerebrally with cell-free 

 filtrates. This progression offers further evidence of a muticentric leukemic 

 transformation. The leukemic transformation is believed to be due in both 

 instances to the proliferation of a virus. In the case of cell-free filtrates, 

 the virus is present in free form; in the case of cell inoculation, the virus 

 is present in the cells from which it is liberated. 



CONCLUSION 



It may be concluded that leukemic cell-free filtrates elicit a lymphoid pro- 

 liferation. This lymphoid proliferation has its genesis in the mesenchymal 

 cells. The proliferation eventually leads to an irreversible overgrowth. 

 Crowding out and replacement of normal tissues take place. There is evi- 

 dence that the leukemia represents a multicentric response rather than a 

 local growth which spreads by virtue of metastases. 



