FURTHER OBSERVATIONS AND EXPERIMENTS ON THE SO-CALLED THYROID CARCINOMA OF THE BROOK TROUT (SALVELINUS FONTINALIS) AND ITS RELATION TO ENDEMIC GOITRE.
FURTHER OBSERVATIONS AND EXPERIMENTS ON THE SO-CALLED THYROID CARCINOMA OF THE BROOK TROUT (SALVELINUS FONTINALIS) AND ITS RELATION TO ENDEMIC GOITRE.
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DOI：
10.1084/jem.13.4.455
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发表时间：
1911-04-01
期刊：
影响因子：
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通讯作者：
Lenhart CH
中科院分区：
文献类型：
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作者：
Marine D;Lenhart CH
通过对鳟鱼甲状腺的一系列观察，从孵化时到四岁或以上的鱼，我们已经能够一步步追踪甲状腺增生的发展过程。在这些孵化场鳟鱼中，在卵外生命第二个月末，可以从解剖学上识别出甲状腺过度生长。在这些鱼生活的条件下，甲状腺过度生长逐渐增加，首先填充主动脉腔，然后侵入周围的骨骼和肌肉。在我们的系列中，这种向邻近组织的延伸直到卵子外生命的第四个月才被识别出来。当然，根据一般卫生条件、食物、水供应等，首次注意到周围组织侵入的时间在不同年份和不同孵化场有很大差异。如果像通常那样在鱼的整个快速生长期继续生长，临床上可能首先通过甲状腺组织扩散到粘膜下层时咽底变红来发现。随后，腹侧出现明显的外部甲状腺肿。这些可能早在生命第六个月时就出现了。与哺乳动物一样，甲状腺在生长期最活跃，在生命的第二年和第三年出现最多数量的可见甲状腺肿。在年长的鱼中，甲状腺再次变得不那么活跃，并且有自发恢复的趋势。无论是在非常年轻的鱼还是年长的鱼中，甲状腺生长的解剖学外观都没有显着的变化，除了明显取决于鱼的年龄、机械因素（如甲状腺肿的大小）和复杂因素（如感染、出血、变性等）之外。因此，不存在在年老的鱼中诊断癌症的解剖学基础，而在患有甲状腺增生的最年轻的鱼中也存在这种基础。所有侵袭、非典型细胞生长等的出现都是非包膜上皮组织沿着阻力最小的路径逐渐生长和随后延伸的结果。在许多较大的甲状腺肿中，或多或少存在明显的甲状腺增生区域，其组织学上与周围的甲状腺组织不同，我们将其视为良性肿瘤，与人类甲状腺肿中所见的良性肿瘤相当。我们将它们归类为肿瘤，因为它们不像普通增生那样与碘发生反应。将这些肿瘤称为癌症超出了我们目前的知识范围，而且是不合理的，尽管与哺乳动物肿瘤的类比表明某些肿瘤可能会发展为真正的癌。最常见的良性肿瘤类型是树状乳头状瘤及其多种变型。由于上述原因，感染是较大甲状腺肿的常见并发症。在解释所遇到的组织学状况时有必要认识到这一因素，否则，使用哺乳动物标准，观察到的一些外观很容易被误认为是肉瘤。碘对甲状腺增生早期、中期、晚期的影响已有研究。所有阶段都与碘发生反应，温和程度似乎比较严重程度更快。因此，早期阶段需要两到三周的时间进行复旧，而晚期阶段可能需要一到两个月的时间。因此，该过程比哺乳动物增生中的碘反应时间慢。真正的肿瘤不会像普通增生那样与碘发生反应。感染或其他并发症会改变反应。与碘的反应是甲状腺功能性增生的特异性测试。由于我们无法找到该过程中不与碘发生反应的任何阶段，因此我们必须得出结论，没有任何阶段可以在生物学上被视为癌症。正如碘总是会阻止增生并导致甲状腺恢复到胶体或静止状态（从该状态开始，甲状腺可能会经历第二次、第三次或更多次增生，就像哺乳动物一样）一样，当鱼被转移到自然环境中时，也会发生自发复旧。这种自发对合已在实验中得到遵循，并且在从流中随机获取的示例中也可见到。除了真正的肿瘤之外，我们从未见过这条规则的例外。如上所述，康复并不意味着甲状腺肿消失；而是意味着甲状腺肿消失了。它意味着生长停止并且活跃的增生返回到胶体或静止阶段。甲状腺增生是一种代偿反应，其确切原因仍有待寻找。没有证据表明它在鱼类或人类中具有传染性或传染性。目前所有的生物学数据都支持这样的观点：鱼类甲状腺肿与哺乳动物甲状腺肿一样，都是代谢和营养紊乱的症状表现。影响甲状腺生长的三个主要条件在某种程度上仍然不清楚；即有限的供水、过度拥挤以及过度喂养高度人工和不完整的食物。观察到的孵化场的水本质上不会产生甲状腺肿，因为鱼不会患甲状腺肿，除非至少同时存在过度喂食和不完整食物的因素。另一方面，如果过度喂食和过度拥挤得到纠正，它们就会恢复，尽管它们仍留在同一水中。因此，食物似乎是导致有利于甲状腺肿发展的营养缺陷的主要因素。目前不可能表明食物中的哪些元素可能有问题，例如相对食物价值是否缺乏、过量或不成比例。
In a series of observations upon the thyroids of brook trout, extending from the time of hatching to fish of four or more years old, we have been able to follow step by step the development of thyroid hyperplasia. In these hatchery trout, thyroid overgrowth may be recognized anatomically at the end of the second month of extra-oval life. Under the conditions in which these fish live, the thyroid overgrowth progressively increases, at first filling the aortic space and then invading the surrounding bone and muscle. In our series, this extension into the adjacent tissues was not recognizable until the fourth month of extra-oval life. The time when invasion of the surrounding tissues is first noticed is, of course, subject to great variation in different years and different hatcheries, depending on the general hygienic conditions, food, water supply, etc. If the growth continues, as it usually does, throughout the rapid growing period of the fish, it may first be detected clinically by a reddening of the pharyngeal floor as the thyroid tissue spreads to the submucosa. Later, definite external goitres appear ventrally. These may be present as early as the sixth month of life. The thyroid being, as in mammals, most active during the growing period, the greatest number of visible goitres appear during the second and third years of life. In older fish the thyroid again becomes less active and there is a tendency toward spontaneous recovery. There is no noteworthy change in the anatomical appearance of the thyroid growth, whether seen in very young or in older fish, other than that clearly dependent on the age of the fish, mechanical factors, as size of the goitre, and complicating factors, as infection, hemorrhage, degeneration, etc. There exists, therefore, no anatomical basis for the diagnosis of cancer in the older fish that is not also present in the youngest fish with thyroid hyperplasia. All the appearances of invasion, atypical cell growth, etc. are the results of the progressive growth and consequent extension of a non-encapsulated epithelial tissue along the paths of least resistance. In many of the larger goitres there are more or less distinct areas of thyroid hyperplasia, histologically different from the surrounding thyroid tissue, which we look upon as benign tumors comparable to the benign tumors seen in human goitres. We class them as tumors because they do not react with iodin as does the ordinary hyperplasia. To call these tumors cancer is going beyond our present knowledge and is unjustified, even though analogy with mammalian tumors suggests that certain ones might proceed to true carcinomata. The most common type of the benign tumors is the arborescent-papillomatous form and its many modifications. Infection is a frequent complication in the larger goitres, for the reasons given. It is necessary to recognize this factor in interpreting the histological conditions met with, as otherwise, using mammalian standards, some of the appearances observed could easily be mistaken for sarcoma. The effect of iodin on the thyroid hyperplasia has been studied in the early, middle, and late stages. All stages react with iodin, the mild degrees seemingly more rapidly than the severer degrees. Thus the early stages undergo involution in from two to three weeks, while the late stages may require one to two months. The process, therefore, is slower than the iodin reaction time in mammalian hyperplasia. True tumors do not react with iodin as does ordinary hyperplasia. Infection or other complication modifies the reaction. The reaction with iodin is a specific test for functional hyperplasia of the thyroid. As we have not been able to find any stage in the process that does not react with iodin, we must conclude that there is none that may be looked upon biologically as cancer. Just as iodin invariably stops the hyperplasia and causes the thyroid to return to the colloid or resting state (from which it may undergo hyperplasia a second, third, or more times, exactly as in mammals), so also spontaneous involution occurs when the fish are transferred to a natural environment. This spontaneous involution has been followed in experiments and has been seen in examples taken at random from the streams. We have never seen an exception to this rule, save in the case of true tumors. As pointed out above, recovery does not imply a disappearance of the goitre; it implies a cessation of growth and return of the active hyperplasia to the colloid or resting stage. Thyroid hyperplasia is a compensatory reaction, the exact cause of which is still to be sought. There is no evidence that in fish or in man it is either infectious or contagious. All the biological data at present available favor the view that fish goitre in common with mammalian goitre is the symptomatic manifestation of a metabolic and nutritional disturbance. There are three major conditions which, in some way still obscure, influence the thyroid growth; namely, a limited water supply, overcrowding, and overfeeding with a highly artificial and incomplete food. The water of the hatchery observed is not intrinsically goitre-producing, as the fish will not develop goitre unless at least the factor of overfeeding with an incomplete food operates at the same time. On the other hand, they recover if the overfeeding and overcrowding are corrected, although they remain in the same water. Therefore it seems probable that the food is the major factor acting to bring about a fault of nutrition favorable for goitre development. It is impossible at this time to suggest what elements in the food may be at fault, whether, for example, it is deficiency or excess or disproportion in the relative food values.