If we now consider briefly the principal results of our investigation, we can, in comparing the behavior of the thyroid after auto- and homeoplastic transplantation, in general recognize three stages. In the first stage, comprising the first 4 to 5 days after transplantation, there is no noticeable difference between the auto- and homeograft; both corresponding pieces behave in the main alike; large parts of both grafts become necrotic in the center; the necrosis begins shortly after the transplantation and concerns only a part of the periphery; here a narrow zone of thyroid tissue is left; it consists of one to two rows of partly well recognizable follicles. After 48 hours the first fibroblasts, polynuclear leucocytes, and lymphocytes appear in the tissue surrounding the grafts. After 72 hours these elements are present also in the center of the thyroid tissue. At the same date the first mitoses appear in the follicular epithelium; their number is, however, as yet small, but it increases markedly during the following days. After 4 days are found the first newly formed follicles, and from now on their number is increasing. Colloid is present only in small amounts in the old follicles. The central necrotic area still persists, but the masses of detritus are becoming smaller, while the number of fibroblasts and lymphocytes in the necrotic part is increasing; new blood vessels are also visible in the necrotic center.
The second stage, the stage of transition, extends over the next seven days. The earliest, at first slight, differences between the auto- and homeograft appear after 5 days; the difference is usually very definite after 12 days. During this time there is an increase in the number of follicles in the autograft and correspondingly a decrease in the size of the necrotic central area, which is caused by a gradually progressing removal of the necrotic material in the center of the piece. The follicles are lined with a high cylindrical epithelium, which contains numerous mitoses. The number of mitoses increases markedly after the 4th day and reaches a maximum between the 7th and 9th days. Newly produced colloid is always present in the autograft after the 8th day; in the newly formed follicles the colloid contains numerous vacuoles and is almost never retracted, in contradistinction to the solid retracted colloid in the old follicles, which probably was present in the follicles at the time of transplantation. At the end of this period the central part is almost entirely freed from the necrotic masses and is filled with loosely arranged connective tissue cells, between which isolated lymphocytes and polynuclear leucocytes can be found. It contains also numerous blood vessels and brown blood pigment cells.
After 5 days, with the beginning of the second stage, the first as yet rather insignificant differences become noticeable in the homeotransplants. They are as follows: (1) The number of lymphocytes is much larger in the homeo- than in the autograft. (2) The fibroblasts are increased in the central area and these fibroblasts form here very soon firm connective tissue bundles; they surround also the individual follicles or small groups of follicles and form fibrous bands, which are at this stage still very small. During the following days the number of lymphocytes increases and the fibrous connective tissue becomes more prominent, so that 7, 9, 10, and 11 days after transplantation numerous follicles are not only destroyed by the surrounding and invading lymphocytes, but in addition a part of the follicles is encircled and compressed by wide connective tissue bands. This compression is especially distinct in the central parts of the homeografts. At this stage the absence of a well developed vascular system is already noticeable in the central parts of the homeografts. It is especially noteworthy that the follicles of the homeograft which escaped destruction by the lymphocytes and connective tissue are as well preserved as in the autograft. Colloid is usually present in smaller amounts than in the autografts, even in the well preserved follicles of the homeografts.
It must, however, be stated that some variations occur in this stage in the degree of destruction of the homeotransplanted pieces. Side by side with pieces in which a marked destruction has taken place, there are other pieces which suffered as yet relatively little. But some of the above mentioned differences between the auto- and homeotransplants are always present to a smaller or larger extent. There are also certain variations in the relative strength, with which lymphocytes and connective tissue injure the follicles; in some homeotransplants the attacks on the part of the lymphocytes prevail, while in others those on the part of the connective tissue are more prominent. The homeotransplants, which are relatively little injured at this stage are spared only to be subject to a stronger attack on the part of the lymphocytes and connective tissue during the following stage.
The third stage begins approximately with the 12th day. From now on the difference between auto- and homeograft is sharply defined. In the autografts the regeneration of the thyroid tissue is steadily progressing and is nearly complete after 21 days. After this date the autograft represents throughout the picture of the normal thyroid gland; well developed follicles filled with colloid are surrounded by a very scant connective tissue. Mitoses, which begin already to decrease after the 9th day, are still present at the end of 17 days, but absent after this date. The small amount of loosely built, usually centrally located connective tissue, has no tendency to undergo a fibrous or hyaline change and does nowhere exert a compression on the follicles. It contains always a large number of blood vessels and only a few lymphocytes.
In the homeograft the secondary destruction of the follicles is progressing with great intensity after the 12th day. In contradistinction to a primary degeneration of the follicles, due to the action of substances circulating in the body fluids, which might have been expected to take place, but which in reality does not occur, and which would be followed only secondarily by a connective tissue proliferation and lymphocytic invasion, we may speak of the destruction by means of lymphocytes and connective tissue, which actually does take place, as a secondary destruction of the follicles. This secondary mode of destruction of the follicles through lymphocytes and connective tissue is found exclusively in the homeotransplant. Following this destruction the larger part of the homeografts is occupied by a fibrous, hyaline connective tissue, in which remnants of destroyed follicles in the form of clefts filled with lymphocytes are seen. In several cases the destruction of follicles through lymphocytes, which accumulate in large numbers around the follicles and destroy them very actively, prevails; in other cases the compression of the follicles through fibrous, hyaline connective tissue predominates; in other cases both factors may be about equally active. The few peripheral follicles which escaped destruction are small, probably as a result of compression through the connective tissue; but they may still show normal epithelium and nuclei and may occasionally contain traces of colloid. Newly formed colloid is not present in the homeotransplants at the third stage. It should also be mentioned that the blood supply of the homeografts, especially after the 12th day, is very much restricted and that the blood vessels are mainly located in the connective tissue surrounding the graft, and not in the central connective tissue, which exists here in a much larger quantity and is much denser than in the autograft. At this stage also we find considerable variations in the extent of the injuries, in the individual follicles. But no piece escapes the attack entirely, and those which remain relatively well preserved for a certain period will be attacked at a later date by the connective tissue, as well as by the lymphocytes of the host.
To summarize briefly, the principal result: For a short period of time after operation no difference is seen in the behavior of the thyroid after auto- and homeotransplantation. Very soon, however, a destruction of follicles begins to take place in the homeografts. This destruction is not caused by a direct primary disintegration or solution of follicles, but depends on the destructive activity of (1) the lymphocytes, and (2) of the connective tissue of the host tissue. The former invade the follicles and destroy them directly; the latter grows into the homeografts in larger quantity than into the autografts. In the former it soon becomes fibrous and hyaline; in the latter it remains cellular. The fibrous connective tissue surrounds and compresses and thus destroys the follicles. In some homeografts destruction by means of lymphocytes, in others by connective tissue, preponderates. The rapidity with which the destruction takes place in different homeotransplants also varies. A much better blood vessel supply develops in the autograft than in the homeograft.