Tumor development is a dynamic process, subject to certain regularities, which are reflected in the theory of L. Foulds tumor progression. According to L. Foulds, progression is the development of a tumor by a permanent, qualitative, irreversible change in one or more of its properties, which can be morphological structure, growth rate, functional activity, sensitivity to drugs. Such an independent progression leads to discrepancy, dissociation of individual tumor properties. Another feature of the progression – its uneven nature – is manifested in the fact that individual tumor sites can be at different stages of development. This concerns primarily the morphological structure of the tumor. The progression is based not only on qualitative changes in tumor cells, but also on the selection process with the formation of the most stable and adapted cell clones. The progression can be spasmodic, slowed down or accelerated. In this case, the overall direction of the progression does not change, only its rate can change.
Questions of tumor progression were studied mainly in the experiment. Clinical works on this topic are single. It is no coincidence that the study of tumor progression in the clinic is limited to leukemia and malignant lymphomas, that is, processes that allow monitoring the dynamics of morphological changes on a regular basis.
Differentiated carcinomas of the thyroid gland represent a unique “model” of human epithelial tumors, the development of which in clinical and morphological aspects can be studied for a long time.
For many years in the literature the opinion that thyroid cancer develops against the background of certain previous changes – goitre, adenoma, AT, has firmly taken root. The basis for this kind of judgments is mainly experimental data. It is shown that experimental tumors of the thyroid gland undergo a series of definite successive stages in their development – from diffuse hyperplasia to focal proliferates and, finally, a malignant tumor. The further direction of progression follows the path of tumor loss by cell differentiation. There is an opinion that such a pattern of development is inherent in thyroid tumors in humans. Proceeding from the well-known concept, he believes that the adenoma of the thyroid gland, as a benign tumor, should be considered as a pronounced dysplastic process, the last final stage of development of which is cancer. In the author’s opinion, 88.7% of cases of thyroid cancer were preceded by one or other background process (adenoma, thyroiditis, nodular goiter).
I.S. Ageev, who studied the characteristics of thyroid tumors in a region endemic in the goiter, found that in 86.6% of cases, thyroid cancer was preceded by a background process (nodular goiter, adenoma, thyroiditis).
Especially important etiological role in the development of malignant tumors of the thyroid gland is given to single nodular formations in the gland (nodular goiter and adenoma). Many researchers single sites in the thyroid gland take the role of even an obligate precancer.
One of the convincing arguments of supporters of the stage development of malignant tumors of the thyroid gland is the presence of structural and cytological transitional forms that are found in clinico-morphological studies.
If we consider diffuse and focal hyperplasia of thyroid epithelium as a stage of carcinogenesis, it would be natural to increase the incidence of cancer in endemic areas in the goiter. Indeed, according to some authors, thyroid cancer is more frequent in endemic areas than in areas free from endemia. However, there is another valid point of view, which denies the fact of the increase in thyroid cancer in the foci of goiter endemia.
This inconsistency of views on the incidence of thyroid cancer in the focus of goiter endemia is due to several circumstances. The information given in the literature is not always comparable. Some authors determine the incidence of cancer in relation to the number of all operated for thyroid disease in the endemic region and find malignant tumors in 4% of the observations, others calculate the incidence of cancer only among those operated for nodular formations in the thyroid and receive respectively 25-54.2 % of malignant tumors.
One can not ignore yet another immutable fact-the severity of goiter endemia is everywhere decreasing, and the incidence of thyroid cancer is steadily increasing. It is interesting to note that an increase in the number of thyroid cancer patients occurs not so much in endemic areas as in developed industrial countries (USA, Canada, Japan). As already noted, the increase in the incidence of thyroid cancer in these countries is associated with exogenous factors, primarily with radiation exposure. Consequently, there are certain objective data to explain the increase in the incidence of thyroid cancer, at least in some cases.
Further, we can not talk about the role of background processes in the development of cancer without taking into account age-related changes in the thyroid gland. There are numerous and convincing data, according to which in women over 50 years, nodes in the thyroid gland are detected in 50-90% of observations. It is also known that in
The thyroid gland increases with age the frequency of autoimmune processes. Consequently, for women of the older age group (over 50 years), these background processes are largely regular age-related changes. Therefore, the tendency to consider all these processes as a pre-conflict seems at least controversial.
Meanwhile, single nodular formations in the thyroid gland by many clinicians are considered as an obligate pre-cancer. According to the literature, the incidence of cancer among single sites ranges from 2.8% to 54.2%.
It is clear that these contradictory information can not give an idea of what is the real danger of malignization of single nodular thyroid formations. In addition, the definition by clinicians of the very fact of malignancy of nodular goiter (or adenoma) seems highly subjective.
There are numerous clinical observations when patients with thyroid cancer tell that a node in the thyroid gland lasted for a long time (10 years or more), and this was regarded by doctors as a nodular goiter or adenoma. Based on such anamnestic data, in fact, the conclusion is made about malignancy. However, the long-term existence of a node in the thyroid gland does not give grounds for talking about its malignancy. As MF Glazunov rightly wrote, the duration of growth, which counts even for many years, by itself still does not speak in any way in favor of the tumor nature of the process. In other words, if the patient has a node in the thyroid gland, then there is no reason to think about cancer only because the node exists for 5 or even 10 years.
Further, it is necessary to emphasize that the overall incidence of goitre, especially in endemic areas, is in no way comparable to the incidence of thyroid cancer. Assuming that 30% of the nodal goiter is malignant, the number of patients suffering from malignant thyroid tumors, must be immeasurably greater than we observe in reality.
This apparent contradiction, in our opinion, is largely due to the misinterpretation of certain clinical data. First of all, it should be recalled that the nodal nontoxic goiter (or adenoma) and differentiated thyroid cancer (up to a certain stage) have a completely similar clinical picture. Differentiated carcinomas of the thyroid gland are often very slow growth rate. All this gives grounds to assert that with differentiated thyroid cancer with a prolonged anamnesis, as a rule, we are not talking about malignant goiter, but about slowly growing carcinoma. Therefore, it is more correct speak not about the frequency of malignant nodular goiter, but about the incidence of cancer among single nodes in the thyroid gland. In other words, we are talking about how often thyroid cancer clinically proceeds as a single node in the gland thick.
One of the arguments in favor of malignant nodular goiter is the acceleration of node growth at some stage of its development. However, in most cases this is an anamnestic attribute, the reliability of which is relative. In the same cases, when the patient observing the patient objectively marks a noticeable increase in the node over a certain period of time, this can be explained by one of the manifestations of a tumor progression.
The possibility of developing thyroid cancer in the unchanged thyroid gland is confirmed by the following circumstances.
There is a variant of differentiated thyroid cancer, the first clinical manifestation of which are regional metastases, and the primary tumor is so small that it is not palpable, and sometimes it can not be probed even during revision of the gland during surgery. We called this option metastatic. According to our data, a metastatic variant was observed in 58% of patients with papillary thyroid cancer. In these observations, the primary tumor had small, sometimes microscopic dimensions, despite a long history, which averaged 4.7 years, and 16% had even more than 10 years.
In the group of children operated by us for thyroid cancer, no one had a goiter or a change in the thyroid gland, which could be regarded as a background for tumor development. According to T. Winship, in children 50% of single nodes in the thyroid gland turn out to be malignant tumors. Can we on the basis of these data talk about a higher frequency of malignancy of nodular goiter in childhood? Of course not. It must also be emphasized that the history of children with thyroid cancer is usually noticeably shorter than that of adults.
Finally, we can give another very strong argument. Thyroid cancer is often a random sectional finding. Naturally, in such cases there was no goitre anamnesis. These clinical data seem to us quite convincing and allow us to assert that the development of cancer Nodular goiter and thyroid cancer is possible in unchanged gland and that goitre or adenoma is not an obligatory stage of human carcinogenesis of the thyroid gland.