Differentiation and functional activity
The degree of maturity of a neoplasm directly determines its ability to perform specific tasks. Well-differentiated tumors consist of cells that maximally resemble the healthy source tissues. They retain their natural characteristics and continue to perform their routine functions. For example, carcinomas originating from endocrine glands actively produce hormones (elevated levels of these in the blood serve as an important diagnostic marker). Squamous cell carcinoma cells continue to synthesize cytokeratin, and hepatocellular carcinoma (HCC) may contain bile. In benign neoplasms, cellular structures always remain mature. Malignant well-differentiated tumors also retain the general features of the source tissue, although signs of impaired differentiation are already noticeable in them.
Anaplastic (undifferentiated) tumors completely lose their external and functional similarity to the mature structures from which they arose, regardless of histogenesis. As a rule, such rapidly growing and poorly differentiated variants are distinguished by much less pronounced functional activity.
Atypia: concept and terminology
Translated from Greek, the word atypicus means "deviation from the norm." In pathological anatomy, there are four main types of atypia: morphological, biochemical, antigenic, and functional.
To describe the loss of differentiation, two concepts are traditionally used:
- Anaplasia is the regression of tissue to an embryonic stage of development.
- Cataplasia is the resemblance to embryonic tissue. In modern medicine, this specific term is recognized as more correct, since a true regression to embryogenesis does not occur, but the tumor approaches embryonic tissue in its properties.
Morphological tissue atypia
Morphological deviations are expressed in the fact that the neoplasm does not replicate the structure of its mature tissue of origin. Tissue atypia is characterized by large-scale architectural remodeling. First of all, the normal ratio between the stroma and parenchyma of the tumor is disrupted. Tissue structures change in size and shape. As a result of disorganized growth, bizarre tissue formations of various sizes arise. This level of impairment is present in both benign and malignant tumors.
Signs of cellular atypia
The cellular level of morphological atypia has many specific signs, which can be divided into four groups:
- Changes in mitotic activity. The total number of mitotic figures increases in the tissue, and figures of pathological divisions also appear.
- Cellular polymorphism. There is a pronounced variability of elements in shape and size. Small primitive cells, giant cells (several times larger than neighboring ones), and multinucleated structures can be encountered.
- Nuclear pathology. These are the most characteristic markers. Nuclei become polyploid and hyperchromatic (darkly stained). The nuclear-cytoplasmic ratio increases sharply (nuclei are disproportionately large). Nuclear polymorphism, jagged nuclear contours, and the appearance of prominent nucleoli are noted.
- Disorganization. Anaplastic cells lose normal polarity (the ability to maintain mutual orientation), and their complexes grow in an absolutely disorganized manner.
Differences between tumors and the emergence of new functions
The key difference lies in the fact that benign neoplasms exhibit tissue atypia only. They are built from differentiated cellular elements, and mitoses are extremely rare in them. Malignant tumors exhibit both types of atypia, and their cells and nuclei are characterized by significant polymorphism.
In a number of cases, during tumor transformation, a new functional activity arises that is uncharacteristic of mature tissue. This may be the synthesis of fetal proteins (proteins not synthesized in adults) or the ectopic production of hormones by carcinomas of non-endocrine origin. For example, bronchogenic carcinoma is capable of producing corticotropin (ACTH), parathyroid hormone-related peptide, insulin, or glucagon.
Briefly: answers to topical questions
What specifically manifests as the biochemical atypia of a tumor cell?
Biochemical atypia manifests as a change in the metabolism of the tumor cell, the loss of strict metabolic specialization, and the transition to simplified regulatory mechanisms.
The main manifestations include:
- Dominance of glycolytic ATP resynthesis — the predominance of anaerobic glycolysis even in the presence of oxygen (Warburg effect) and a negative Pasteur effect, leading to metabolic acidosis.
- Disorders of intracellular regulation — intensification of substrate uptake (glucose and nitrogen "trap" phenomenon).
- Predominance of anabolic processes — ensured by auto- and paracrine regulation.
- Evasion of systemic regulation — lack of response to neurogenic and hormonal influences.
- Alteration in macromolecule synthesis — impaired synthesis of proteins and nucleic acids, and intensification of the pentose phosphate pathway.
What is antigenic atypia and what types of antigens appear during it?
Antigenic atypia is the appearance of new antigens not characteristic of normal tissue, or the loss of normal tissue-specific and histocompatibility antigens.
With this type of atypia, the following types of antigens appear:
- Tumor-specific antigens — unique tumor markers.
- Oncofetal antigens — carcinoembryonic proteins.
- Products of oncogene activity — specific molecules.
- Specific viral antigens — markers of viral origin.
- Overproduced normal proteins — excessively synthesized routine antigens.
- Stress molecules (MICA and MICB) — non-classical molecules encoded by MHC class I genes but lacking a light chain.
Antigens are also classified into B-antigens (recognized by antibodies) and T-antigens (recognized by T-lymphocytes).
Which specific fetal proteins can be synthesized by tumors?
The provided materials explicitly state that tumors can in some cases synthesize fetal proteins — proteins not synthesized in adults.
The specific list of such fetal proteins is not provided in the section on functional atypia. Among specific carcinoembryonic/oncofetal antigens, the sources mention:
- Carcinoembryonic antigen — indicated as a marker of intestinal cancer and as an antigen whose expression is described in benign prostatic hyperplasia.
- Alpha-fetoprotein — cited as an example of a carcinoembryonic organ- and tissue-specific antigen.
Other specific fetal proteins are not named in the sources.
To memorize the nuclear signs of cellular atypia, use the mnemonic "H-S-U-P-P" (or corresponding terms): Hyperchromasia, Size (high nuclear-ytoplasmic ratio), Ugly contours, Polyploidy, Polymorphism.
Class and exam questions
What is the difference between anaplasia and cataplasia?
Anaplasia implies regression to the embryonic stage, while cataplasia implies resemblance to embryonic tissue. Cataplasia is considered a more correct term since true regression to embryogenesis does not occur.
Which tumors are characterized solely by tissue atypia?
Only tissue atypia is characteristic of benign tumors. They are composed of mature cells and practically lack mitoses.
What is ectopic hormone production?
This is the production of hormones by tumors originating from non-endocrine tissues. For example, in bronchogenic carcinoma, cells can produce insulin, glucagon, or ACTH.
What else to study on this topic
- Biochemical atypia of tumors
- Antigenic atypia and diagnostic markers
- Mechanisms of fetal protein synthesis
- Pathological mitoses: types and morphology
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