Cellular Origin and Differentiation
Every neoplasm has a specific tissue origin (histogenesis) and cellular origin (cytogenesis). Transformations exclusively affect proliferating somatic cells—multipotent or unipotent precursors.
Tumor cells always attempt to mimic the phenotype of their precursor, but do so in an aberrant manner due to a differentiation block:
- Low-level block (at the unipotent cell level): Typical of benign tumors. Cells mature, phenotypic heterogeneity is minimal, and the tissue appears mature.
- High-level block (at the multipotent cell level): Typical of malignant neoplasms. Pronounced heterogeneity emerges, even leading to chimeric cells with multiple differentiations.
While cytogenesis is studied in detail for hematologic malignancies (based on stem cell biology), the exact precursor cells for many solid tumors (e.g., gastric or lung cancer) remain a subject of scientific debate.
Parenchyma, Stroma, and Matrix
Tumor structure is based on two components:
- Parenchyma: The pool of neoplastic cells resulting from malignant transformation and subsequent clonal proliferation.
- Stroma: The connective tissue framework providing nutrition (trophism), support, and modulation. It includes cells, blood vessels, nerve endings, and the extracellular matrix.
The stromal matrix is divided into basement membranes (collagens types IV, VI, VII, laminin, fibronectin, heparan sulfate) and the proper connective tissue matrix (collagens types I and III, proteoglycans).
Depending on the ratio of these components, two types of neoplasms are distinguished:
- Organoid tumors: Contain both parenchyma and developed stroma (typical for carcinomas). The stroma may be sparse with rare capillaries (medullary carcinoma) or, conversely, form dense fibrous fields where cells are barely distinguishable (scirrhus).
- Histioid tumors: Parenchyma sharply predominates. Stroma is practically absent, represented only by delicate nutritional capillaries (typical for sarcomas).
Stromal Formation and Angiogenesis
The stroma forms from pre-existing normal connective tissue precursors of the surrounding tissues with the active participation of the tumor itself. This is a complex, multi-stage process:
- Cytokine secretion: Tumor cells release growth factors. The Volkmann factor (a group of fibroblast growth factors stimulating vascular wall element proliferation and neoangiogenesis) plays a crucial role.
- Autocrine and paracrine regulation: Certain oncoproteins (e.g., c-sis, c-myc) express growth factor receptors, triggering a proliferative cascade.
- Matrix synthesis: Transformed cells can secrete collagens themselves. Malignant tumors often synthesize collagens characteristic of embryonic organ development (e.g., type III collagen in lung cancer, type IV in renal cell carcinoma, type II in chondrosarcoma).
- Invasion and degradation: To invade tissues, the tumor secretes proteolytic enzymes (collagenases, elastases). Shifting the balance between enzymes and their inhibitors ensures infiltrative growth.
- Cellular migration: Hematogenous cells (monocytes, lymphocytes, plasmacytes, mast cells) actively infiltrate the stroma, while tumor cells themselves may undergo epithelial-mesenchymal transition.
Neoplastic Growth Patterns
The behavior of a neoplasm directly depends on its degree of malignancy.
Regarding surrounding tissues, growth patterns include:
- Expansive growth: The tumor grows "within itself," pushing aside and displacing healthy tissues. A pseudocapsule of connective tissue forms around it. This is a classic sign of benign tumors.
- Infiltrative (invasive) growth: Cells invade adjacent tissues, destroying their structures. Characteristic of malignant neoplasms.
If a tumor develops in hollow organs (stomach, intestines, bronchi), its growth is classified relative to the lumen:
- Exophytic: The mass grows into the organ lumen, gradually filling its cavity.
- Endophytic: The tumor infiltrates the organ wall itself, spreading deep into the tissues.