THE MORPHOLOGICAL APPROACH 99 



cisternae. These were found in two separate areas of the tumor cell, whereas 

 they are normally found in only one area. These may represent part of the 

 story of the hypertrophied paranuclear area. 



B. Mammary Tumors of Mice 



Although this tumor may now be listed among those associated with viruses, 

 the biological data establishing this point are more complex than those 

 available for the chicken tumors. The milk agent operates within a more 

 restricted set of conditions (sufficient hormonal stimulus and a particular 

 genetic background are essential) and the tumor itself has an extremely 

 delayed incubation period. Secondly, the spontaneous mammary tumors 

 which occur in low incidence in mice in the absence of "the milk factor" 

 nevertheless have, in many cases, a histological structure indistinguishable 

 from milk factor tumors (Dunn, 1953). In the continuing search for the 

 nature of the cancer cell attention has repeatedly focused on variations in 

 neoplastic cell structure. Nevertheless, the behavior of a group of cells has 

 remained more diagnostic than the appearance of any one cell. For this 

 reason, the recent study of Foulds (1956) is of particular value in orienta- 

 tion for a detailed study of individual cells. The restricted portion of tissue 

 which can be studied in the electron microscope field has so far prevented 

 adequate correlation of ultrastructure with the distribution of the developing 

 malignancy. 



1. "Inclusion" and Virus Particles 



Eosinophilic cytoplasmic inclusions were described by Guerin in 1955 in 

 several lines of mammary tumors. Almost at the same time, studies with the 

 higher resolution of electron microscopy (Bang and Andervont, 1953; Bang 

 et ah, 1956a,b; Bernhard et al., 1956b; Dmochowski, 1954) showed that 

 masses of intracytoplasmic particles thought to be virus could be commonly 

 found in mammary tumor cells. Direct comparison of the cytoplasmic in- 

 clusions (Bernhard et al., 1956b) and the eosinophilic inclusions showed that 

 a large part, if not the entire mass, is made up of such particles. The first 

 description of these particles is without question accreditable to Porter and 

 Thomson (1948), who found clusters of these particles with an average out- 

 side diameter of 130 nu£ and a dense center averaging 75 nut in epithelial 

 cells grown in tissue cultures from spontaneous mammary tumors. They 

 were found in three of the six tumors studied in this way. It is likely that 

 these "virus-like bodies" actually were at the surface of the cell, although 

 several clusters which appear to be within the osmium-digested cell are also 

 shown. 



Sections of infected cells, however, have the great advantage of affording 

 accurate localization of the particles. Bemarkably similar pictures were 



