398 BULLETIN OF THE BUREAU OF FISHERIES. 



the disease was found in changes like those above described and affected individual or 

 small groups of follicles lying adjacent to the large arteries. (Fig. 40.) One or two 

 selected protocols of fish in which the disease was experimentally induced and properly 

 controlled show that the action of the agent causing the disease is clearly focal. Budding 

 of the wall of the follicle is early in evidence, presenting an appearance much like that 

 found in the embryo, where the formation of secondary follicles is in progress. But 

 here, instead of this budding, resulting in the formation of isolated follicles of the usual 

 type, we have the formation of irregular groups of cells, tubules, and groups of alveoli 

 of irregular shape, lined with columnar epithelium. In this way new follicles are formed 

 (fig. 36). From the very beginning there is a tendency to infiltration in the surrounding 

 structures. (Fig. 34.) 



The fact that the gland of the teleost is not encapsulated was first offered by 

 Gudernatsch as an explanation for the infiltrative character of these growths. This is 

 undoubtedly true so far as the extension of formed follicles between the muscle bundles 

 and into the tissues adjacent to the normal deposits of thyroid tissue is concerned. In 

 this way, with the inauguration of the disease, we find the growth of thyroid tissue 

 into the surrounding structure. Such growth follows in the first instance the lines of 

 least resistance and is in our opinion quite distinct from the phenomenon of the infiltra- 

 tion of adjacent cell structures by individual cells — a phenomenon which is frequently 

 found with the very first evidence of the disease. The cells of the alveoli in this stage 

 have changed from flattened to high columnar, with deeply staining protoplasm, basilar 

 nuclei often vesicular and frequently with many karyokinetic figures. Where the follicles 

 have simply grown between the muscle bundles or against opposing structures, such as 

 bone and cartilage, they are frequently flattened, usually of small size, and closely 

 grouped. Where the follicles are broken through, and groups of individual cells infiltrate 

 the surrounding structures, there is frequently marked proliferation of the interstitial 

 connective tissue. Even in the early stages great variation in the arrangement of the 

 cells is apparent. They form long, narrow tubules, the alveoli more or less irregular 

 in shape, with solid masses of cells and large irregular spaces. The follicles may or may 

 not contain colloid. In the early stage there is generally a marked diminution in colloid. 

 (Fig. 36.) 



RED-FLOOR STAGE. 



In this stage the extent of proliferating thyroid is such as to be visible as a slight 

 flush on the floor of the mouth. Histologically the spaces surrounding the vessels 

 are filled with tumor tissue. Bone, cartilage, and muscle are invaded, and the tumor 

 tissue extends toward the gill arches and backward toward the heart. A characteristic 

 of this stage is that the tumor tissue does not seek the paths of least resistance, but 

 infiltrates in other directions. (Fig. 37.) The arrangement is tubular or alveolar in 

 most instances; the epithelium is high and deeply staining. Only occasional follicles 

 with colloid are encountered. There is a well-defined connective tissue reticulum. 

 Karyokinetic figures are numerous and are found in most tumors. (Fig. 35 and 36.) 



