General concepts of tumors
Neoplasia is an uncontrolled monoclonal proliferation of cells, where all cells originate from a single mother cell and are its clones. A tumor is a pathological excessive mass of tissue with uncoordinated, unregulated, and autonomous growth that continues even after the removal of the factor that induced it.
Tumor growth is based on damage to the genome of progenitor cells. Tumor cells acquire two key properties: autonomous growth (uncontrolled division) and atypia—alterations in structure, metabolism, function, antigenic characteristics, and mechanisms of reproduction. Tumor growth is associated with the concepts of anaplasia (reversal of development, loss of differentiation) and cataplasia (acquisition of new properties).
According to the WHO, up to 90% of tumors are associated with exposure to external factors—carcinogens—and only about 10% are due to hereditary predisposition.
Etiology and carcinogenesis
Etiological factors of tumor growth are carcinogens:
- Chemical (about 75% of cases): tobacco smoke, benzpyrene, aniline dyes, aflatoxins; divided into direct and indirect.
- Physical: ultraviolet radiation (skin cancer), ionizing radiation.
- Viral: DNA viruses (Epstein-Barr virus, hepatitis B and C viruses, papillomavirus), RNA viruses (retroviruses).
- Microbial: Helicobacter pylori (gastric lymphomas).
Carcinogenesis is a multistep process involving sequential genetic events.
Tumor structure
A tumor has a two-component structure: parenchyma and stroma. The parenchyma is represented by tumor cells and determines the biological behavior and pathological consequences of the neoplasm. The stroma consists of connective tissue, blood vessels, and an inflammatory infiltrate, providing blood supply and structural support.
The parenchyma induces angiogenesis via angiogenin and the formation of extracellular matrix, particularly type IV collagen.
Based on the ratio of components, tumors are classified as organoid (with well-developed parenchyma and stroma), histioid (predominance of parenchyma, thin-walled vessels), and fibrous carcinoma (scirrhous carcinoma) with predominance of stroma. Based on similarity to the parent tissue, tumors are divided into homologous and heterologous.
Benign and malignant tumors
Benign tumors consist of well-differentiated cells morphologically similar to the parent tissue. They are characterized by slow expansive growth with the formation of a pseudocapsule, clear demarcation, absence of metastases, and good curability. Regression and malignant transformation are possible. Examples: fibroma, chondroma, adenoma, papilloma (suffix "-oma").
Malignant tumors are composed of poorly differentiated cells morphologically distinct from the original tissue. They are characterized by rapid infiltrative growth, tissue destruction, the ability to metastasize, and systemic effects on the body (paraneoplastic syndrome, cachexia). They are distinguished into:
- Carcinomas—from epithelial tissue (e.g., gastric adenocarcinoma);
- Sarcomas—from mesenchymal tissue (connective, bone, cartilage).
Tumors with locally destructive growth occupy an intermediate position: they infiltrate tissue but do not metastasize.
Types of atypia and growth
Several forms of atypia are distinguished:
- Tissue atypia—disruption of the parenchyma-to-stroma ratio and structural shapes; typical of benign tumors.
- Cellular atypia—polymorphism or monomorphism, nuclear hyperchromasia, pathological mitoses, loss of polarity, giant cells; typical of malignant tumors.
- Ultrastructural atypia—changes in ribosomes, mitochondria, and other organelles.
- Metabolic atypia—dominance of glycolysis, accumulation of glycogen, cholesterol, lactic acid.
- Histochemical atypia—alteration of proteins, lipids, enzymes (e.g., elevated acid phosphatase in prostate cancer).
- Antigenic atypia—appearance of new antigens (alpha-fetoprotein in liver cancer).
- Functional atypia—hypo-, hyper-, or dysfunction.
Types of growth: expansive (pushing aside healthy tissues, pseudocapsule), appositional (transformation of surrounding cells into tumor cells), infiltrative (invasion and destruction of tissues), as well as exophytic and endophytic, unicentric and multicentric.
Metastasis and morphogenesis
Pathways of metastasis:
- Lymphogenous—predominantly for carcinomas;
- Hematogenous—typical of sarcomas;
- Implantation—along serous cavities;
- Perineural—along nerve sheaths.
Tumor cells destroy the vascular wall, form tumor emboli, circulate, and settle in distant organs, forming secondary nodes. The liver is a frequent target for metastases due to the specifics of its blood supply.
Precancerous changes: dystrophy, hyperplasia, metaplasia (replacement of one type of epithelium by another, e.g., intestinal metaplasia in the lower third of the esophagus), and dysplasia (impaired differentiation with cellular atypia). A distinction is made between obligate precancer (hereditary intestinal polyposis, hereditary breast cancer) and facultative (e.g., cervical erosion). The latent period between precancer and cancer can reach 30–40 years and applies only to obligate precancer.
Theories of morphogenesis include Shabad's theory (somatic cell mutation) and Willis's theory (multiple growth points).
Clinical aspects and TNM classification
Tumors exert local (compression, destruction) and general effects, including hormonal effects and cachexia. Secondary changes in the tumor include necrosis, hemorrhage, inflammation, mucinous degeneration, and petrification (especially after chemotherapy or radiation therapy).
The international TNM classification:
- T (tumor)—size and extent of the primary tumor;
- N (nodus)—involvement of regional lymph nodes;
- M (metastasis)—presence of distant metastases.
Tumor markers are used for diagnosis and monitoring: PSA (prostate-specific antigen) in prostate cancer, CA-125 in ovarian cancer, alpha-fetoprotein in liver cancer.
Key points
- A tumor is an autonomous monoclonal proliferation of cells with atypia and independence from regulatory influences.
- Up to 90% of tumors are caused by carcinogens: chemical, physical, viral, and microbial.
- A tumor consists of parenchyma (determines behavior) and stroma (support and blood supply).
- Benign tumors are well-differentiated, grow expansively, and do not metastasize; malignant tumors are poorly differentiated, infiltrative, and metastatic.
- Carcinomas develop from epithelium, sarcomas from mesenchyme.
- Types of atypia: tissue, cellular, ultrastructural, metabolic, histochemical, antigenic, functional.
- Metastatic pathways: lymphogenous, hematogenous, implantation, perineural.
- TNM classification and tumor markers (PSA, CA-125, AFP) form the basis of clinical assessment of neoplasms.