110. Precancerous processes. Obligate and facultative precancer. Stages of occurrence of cancer. Methods of pathoanatomical diagnostics of precancerous processes.

Precancerous, or precancerous disease, is a condition that turns into cancer with a higher degree of probability than in the general population. However, the presence of a precancerous background does not mean that it will inevitably turn into cancer. Malignancy in a condition called precancerous is observed in 0.1-5%.

The concept of obligate precancerous (precancerous conditions) includes dysplasia (dys - disorder, plasis - formation), which always occurs in the bowels of the dysregenerative process and is accompanied by insufficient and incomplete differentiation of stem tissue elements, impaired coordination between the processes of cell proliferation and maturation.

Facultative precancerous (precancerous condition) is a variety of chronic diseases accompanied by dystrophic and atrophic tissue changes involving regenerative mechanisms, dysregenerative processes and metaplasia, leading to the appearance of foci of cell proliferation, among which a focus of tumor growth may occur.

phases of cancer morphogenesis: I - precancerous conditions - facultative precancerous; II - precancerous conditions - obligate precancerous; III - preinvasive cancer -carcinoma in situ and IV - early invasive cancer.

Various chronic diseases accompanied by dystrophic and atrophic tissue changes with the inclusion of regenerative mechanisms, dysregenerative processes and metaplasia leading to the appearance of foci of cell proliferation, among which a focus of tumor growth may occur, should be attributed to the / phase of precancerous conditions, or facultative precancerous.

Phase II precancerous- precancerous conditions, or obligate precancerous. It includes dysplasia (dys - disorder, plasis - formation), which always occurs in the bowels of the dysregenerative process and is accompanied by insufficient and incomplete differentiation of tissue stem elements, impaired coordination between the processes of cell proliferation and maturation.

Dysplasia

Epithelial dysplasia was defined by WHO experts (1972) as the following triad:

1) cellular atypia;

2) impaired cell differentiation;

3) violation of the architectonics of the fabric.

Dysplasia is not limited to the appearance of cells with signs of cellular atypia, but is characterized by deviations from the normal structure of the entire tissue complex.

In most organs, the dysplastic process develops against the background of previous hyperplasia (an increase in the number of cells) associated with chronic inflammation and dysregeneration. But often hyperplasia and dysplasia of the epithelium are combined with tissue atrophy. This combination is by no means accidental, since hyperplasia and atrophy share common genetic mechanisms, which involve genes that stimulate mitotic activity and trigger cell proliferation - c-myc and bcl-2, as well as the suppressor gene p53, which blocks cell proliferation and initiates apoptosis. Therefore, in some cases, the sequential activation of these genes leads to cell proliferation and dysplasia, in others to apoptosis and cell atrophy. Dysplasia reveals distinct changes in the activity of all regulators of intercellular relationships: adhesive molecules and their receptors, growth factors, proto-oncogenes and cancer proteins produced by them.

For some organs, the term "dysplasia" is not used to characterize transient precancerous changes. Thus, to describe the transitional stages from normal to cancerous proliferations in the prostate gland, the concept of "intraepithelial neoplasia of the prostate" is used - PIN (prostatic intraepithelial neoplasia), for lining the vaginal portion of the cervix - CIN (cervical intraepithelial neoplasia), in the vagina - VaIN and vulva - VIN. For

Instead of the terms "cancer in situ" and "dysplasia", the terms "atypical glandular hyperplasia" or "adenomatosis" and "glandular hyperplasia" are used.

Most often, a three-step gradation of dysplasia is used: mild (D I), moderate (D II) and severe (D III). In this case, the severity of cellular atypia is the determining criterion for the degree of dysplasia. As the degree of dysplasia increases, the size of the nuclei increases, their polymorphism, hyperchromicity, coarsening and lumpiness of chromatin differ, an increase in the number and relative sizes of nucleoli, and an increase in mitotic activity. Over time, dysplasia may regress, be stable, or progress. The dynamics of morphological manifestations of epithelial dysplasia largely depends on the degree of its severity and duration of existence. A mild degree of dysplasia is practically unrelated to cancer; the reverse development of mild and moderate dysplasia is observed everywhere. The more pronounced the dysplasia, the less likely it is to develop back. The possibility of dysplasia turning into cancer in situ (which can be considered as an extreme degree of dysplasia) and, consequently, into cancer increases as its severity increases.

The main stages of the dynamics of multilayered squamous epithelium dysplasia and its transition to cancer:

a - normal epithelium; b - mild epithelial dysplasia; c - moderate dysplasia; d - severe dysplasia; d - cancer in situ

c) moderate dysplasia of the multilayered squamous epithelium of the cervix. From the Y2 to 2/3 height of the epithelial layer, it was replaced by cells of the germinogenic zone. Along with high mitotic activity, pathological mitoses occur. Cellular atypia is pronounced;

d) severe dysplasia. More than 2/3 of the height of the epithelial layer is replaced by cells of the basal layer. Cellular atypia and pathological mitoses are observed. A layer of mature cells is preserved in the upper row. BM is saved;

5. cancer in situ. The entire thickness of the epithelial layer is replaced by immature proliferating basal cells with cellular atypia and pathological mitoses. The BM is saved.