Differentiation and Functional Activity
The degree of differentiation of a neoplasm directly determines its ability to perform specific functions. Well-differentiated tumors consist of cells that closely resemble the healthy parent tissue. They retain their natural characteristics and continue to perform routine functions. For example, carcinomas originating from endocrine glands actively produce hormones (elevated blood levels 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 general features of the tissue of origin, although signs of impaired differentiation are already noticeable.
Anaplastic (undifferentiated) tumors completely lose their external and functional resemblance to the mature structures from which they arose, regardless of histogenesis. As a rule, such rapidly growing, poorly differentiated variants exhibit much lower functional activity.
Atypia: Concept and Terminology
Derived from Greek, the word atypicus means "deviation from the norm." In pathological anatomy, four main types of atypia are distinguished: morphological, biochemical, antigenic, and functional.
Two concepts are traditionally used to describe the loss of differentiation:
- Anaplasia — the reversion of tissue to an embryonic stage of development.
- Cataplasia — resembling embryonic tissue. In modern medicine, this term is considered more correct because a true reversion to embryogenesis does not occur, but the tumor acquires properties similar to embryonic tissue.
Morphological Tissue Atypia
Morphological deviations are expressed by the fact that the neoplasm does not reproduce the structure of its mature tissue of origin. Tissue atypia is characterized by extensive architectural rearrangements. First, 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 alteration is present in both benign and malignant tumors.
Features of Cellular Atypia
The cellular level of morphological atypia has many specific features, which can be divided into four groups:
- Changes in mitotic activity. The overall number of mitotic figures increases within the tissue, and pathological division figures appear.
- Cellular polymorphism. There is marked variability in the shape and size of cellular elements. Small primitive cells, giant cells (several times larger than neighboring ones), and multinucleated structures may occur.
- 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, irregular notched contours, and large nucleoli are observed.
- Disorganization. Anaplastic cells lose normal polarity (the ability to maintain mutual orientation), and their cell clusters grow in an entirely disorganized manner.
Tumor Differences and Emergence of New Functions
The key difference is that benign neoplasms exhibit only tissue atypia. They are built from differentiated cellular elements, and mitoses are extremely rare in them. Malignant tumors display both types of atypia, and their cells and nuclei feature significant polymorphism.
In some cases, novel functional activity uncharacteristic of mature tissue emerges during neoplastic transformation. This may include the synthesis of fetal proteins (proteins not synthesized in adults) or ectopic hormone production by non-endocrine carcinomas. For example, bronchogenic carcinoma is capable of producing corticotropin (ACTH), parathyroid hormone-related peptide, insulin, or glucagon.