Cell Origin and Differentiation
Any neoplasm has its own tissue (histogenesis) and cellular (cytogenesis) origin. Only proliferating somatic cells—pluripotent or unipotent precursors—undergo transformation.
A tumor cell always attempts to replicate the phenotype of its precursor, but does so in a distorted form due to a differentiation block:
- Low-level block (at the level of unipotent cells): typical of benign tumors. Cells mature, phenotypic heterogeneity is minimal, and the tissue appears mature.
- High-level block (at the level of pluripotent cells): typical of malignant neoplasms. Pronounced heterogeneity develops, up to the emergence of chimeric cells with multiple differentiation lineages.
While cytogenesis has been studied in detail for hemoblastoses (based on stem cell theory), for many solid tumors (such as gastric or lung cancer) the exact precursor cells remain a subject of scientific debate.
Parenchyma, Stroma, and Matrix
The structure of a tumor is based on two components:
- Parenchyma — the pool of actual tumor cells resulting from malignant transformation followed by clonal proliferation.
- Stroma — the connective tissue framework providing nutrition (trophism), support, and modulation. Includes cells, blood vessels, nerve endings, and extracellular matrix.
The stromal matrix is divided into basement membranes (types IV, VI, and VII collagens, laminin, fibronectin, heparan sulfate) and the proper connective tissue matrix (types I and III collagens, proteoglycans).
Depending on the ratio of these components, two types of neoplasms are distinguished:
- Organoid tumors: feature both parenchyma and a developed stroma (typical for carcinomas). The stroma may be scant, with sparse capillaries (medullary carcinoma), or, conversely, form dense fibrous fields in which cells are barely distinguishable (scirrhous carcinoma).
- Histoid tumors: parenchyma sharply predominates. Stroma is virtually absent, represented only by thin nutritive capillaries (typical of sarcomas).
Stroma Formation and Angiogenesis
The stroma is formed 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 secrete growth factors. A critical role is played by the Volkmann factor—a group of fibroblast growth factors that stimulate vascular wall element proliferation and neoangiogenesis.
- Autocrine and paracrine regulation: certain oncoproteins (e.g., c-sis, c-myc) express receptors for growth factors, triggering a proliferation cascade.
- Matrix synthesis: transformed cells can secrete collagens themselves. Malignant tumors frequently synthesize collagen 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). A shift in the balance between enzymes and their inhibitors ensures infiltrative growth.
- Cell migration: hematogenous cells (monocytes, lymphocytes, plasma cells, mast cells) actively infiltrate the stroma, and the tumor cells themselves may undergo epithelial-mesenchymal transition.
Neoplasm Growth Patterns
The behavior of a neoplasm directly depends on its degree of malignancy.
Regarding surrounding tissues, the following are distinguished:
- 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.
- Infiltrating (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.
Briefly: answers to topical questions
What enzymes does the tumor secrete for extracellular matrix degradation and invasion?
To degrade the extracellular matrix and achieve invasion, tumor cells secrete proteolytic enzymes and their activators.
Enzymes involved in the destruction of the basement membrane and matrix include:
- collagenase;
- cathepsin;
- elastase;
- glycosaminogly hydrolase;
- plasmin.
Active synthesis of collagenases and elastases shifts the dynamic balance, promoting infiltrative growth and tumor penetration into adjacent tissues.
What types of tumor growth are distinguished depending on the number of origin sites?
Depending on the number of origin sites (the number of primary neoplasm nodes), two main types of tumor growth are distinguished:
- Unicentric growth — the tumor arises from a single focus and grows from one place as a single node.
- Multicentric growth — the tumor arises simultaneously or sequentially from multiple growth foci in different areas of the tissue.
Unicentric growth is characteristic of early stages of tumors of monoclonal origin, whereas multicentric growth is more common in neoplasms of polyclonal origin.
What types of tumor growth are distinguished in relation to surrounding tissues?
In relation to surrounding tissues, two main types of tumor growth are distinguished: expansive and infiltrative.
| Growth type | Characteristic |
|---|---|
| Expansive | The tumor grows "within itself", does not invade or destroy surrounding tissues, but merely displaces them. Forms a connective tissue pseudocapsule. Characteristic of benign tumors. |
| Infiltrating (invasive) | Characterized by invasion into adjacent tissues and destruction of surrounding structures. Typical of malignant neoplasms. Vascular invasion provides the potential for metastasis. |
To avoid confusing growth patterns in hollow organs, focus on the prefixes: EXOphytic — grows OUTWARD (into the lumen, bulging out), ENDOphytic — hides INWARD (grows through and infiltrates the wall itself).
Class and exam questions
How does histogenesis differ from cytogenesis?
Histogenesis indicates the tissue origin of a tumor, while cytogenesis refers to the specific precursor cell. Cytogenesis is considered a more precise concept, but for many solid tumors, it remains a matter of debate.
Why do benign tumors consist of mature cells?
They develop from unipotent cells with a low-level differentiation block. Consequently, their phenotype is minimally distorted and structurally close to the normal parent tissue.
What is the difference between medullary and fibrous cancer?
These are extreme variants of stroma development in organoid tumors. In medullary carcinoma, the stroma is sparse (narrow layers and capillaries), whereas in fibrous carcinoma (scirrhus), dense fields of connective tissue suppress the parenchyma.
What else to study on this topic
- Stem cell theory in the pathogenesis of hemoblastoses
- Phenotypic heterogeneity and chimera cell formation
- Epithelial-mesenchymal transition of the tumor cell
- Dynamic equilibrium of collagenases and elastases in invasive growth
- Stages of hematogenous cell migration into the neoplasm stroma
Master the entire topic in the "Pathological Anatomy" course
This is a summary. The course covers everything tested in classes and exams.
- Complete guide on "Structure and Types of Tumor Growth" and 4,414 more pages for this subject
- Assignments and quizzes after every topic — just like in a colloquium
- AI tutor answers questions on the topic anytime
- 153 video lessons on the subject
Other topics in the section "Tumor Growth"
Free video lessons: pathological anatomyShort lessons with study notes — no registration required.
Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.