Clinical TNM system
Based on the assessment of the stage and spread of the tumor process.
- T (tumour) — dimensions of the primary lesion.
- N (lymph nodules) — involvement of regional and distant lymph nodes.
- M (organ metastases) — presence of secondary deposits in other organs.
Grading of features is specific to different locations and usually ranges from 1 to 3. Special clinical forms of carcinomas are distinguished:
- Microcarcinoma — diameter less than 1 cm or absence of invasion into the lamina propria of the mucosa (often found in the thyroid and mammary glands).
- "Small cancer" — a term applied to small gastric neoplasms.
- Occult tumors — hidden lesions that did not manifest clinically and were not diagnosed during standard examination.
Morphological criteria and histogenesis
Morphology is the foundation of cancer diagnostics. Tumors are divided according to the degree of cell maturity into benign, borderline, and malignant.
According to the source of origin (histo- and cytogenesis), epithelial neoplasms are classified as:
- From covering epithelium (squamous and transitional): benign (papillomas) and malignant (squamous cell and transitional cell carcinoma).
- From glandular epithelium: benign (adenomas, adenomatous polyps) and malignant (adenocarcinomas, for which 3 levels of differentiation are distinguished).
To determine histogenesis, standard hematoxylin and eosin staining is sufficient in most cases. If cells are poorly differentiated, special methods are used: immunohistochemistry (IHC), PCR, genome analysis, and electron microscopy.
Benign epithelial tumors
Papilloma — an organ-nonspecific tumor originating from the covering epithelium of the skin, mucous membranes (esophagus, vagina, urinary bladder), or bronchial tree. Externally, it has a papillary surface, visually resembling cauliflower. Microscopically, it consists of epithelial proliferations with a fibrovascular core (connective tissue with blood vessels inside the papilla). The epithelium retains the integrity of the basement membrane, polarity, complexity, and stratification, but the number of layers increases (a sign of tissue atypia). It rarely undergoes malignant transformation, but is dangerous when localized in the larynx, urinary bladder, and skin. A variant with prominent keratinization is called a keratoma.
Adenoma — forms from glandular tissue. It may grow outward in the form of a finger-like projection or polyp (exophytic) or spread along the mucosa (flat adenoma with endophytic growth). Depending on the structures formed, tubular, trabecular, alveolar, papillary types, and cystadenomas are distinguished. If a developed stroma predominates in the adenoma, it is called a fibroadenoma (typical for the mammary gland and ovaries).
Differentiation and markers of malignant growth
The level of differentiation of malignant tumors is determined by three criteria: the prominence of histogenesis markers, the preservation of functional activity, and the degree of cellular atypia.
For example, in well-differentiated squamous cell carcinoma, intercellular bridges are preserved and "cancer pearls" (extracellular keratinization) are formed. In moderately differentiated carcinoma, keratinization becomes intracellular, while in poorly differentiated carcinoma, it is practically absent, leaving only stratification.
For accurate identification of carcinomas, specific protein tumor markers are sought using IHC:
- Group markers: cytokeratins.
- Organ-specific markers: thyroglobulin (thyroid gland), CEA (intestine), CA19-9 (ovaries), racemase and tyrosine (prostate gland).
- Neuroendocrine markers: chromogranins, synaptophysin, neuron-specific enolase (NSE), and CD57.
It is important to remember that IHC is an auxiliary method. Morphological verification remains primary, as metaplasia and transdifferentiation of cells can occur during tumor progression.
Briefly: answers to topical questions
What organ-specific IHC markers exist for breast carcinoma?
Immunohistochemical markers that determine the receptor status and proliferative activity of the tumor are used for breast carcinoma. The main markers include:
- Estrogen receptors (ER) — determine sensitivity to hormone therapy.
- Progesterone receptors (PR) — indicate response to hormonal treatment.
- Human epidermal growth factor receptor type 2 (HER2) — a marker for targeted therapy.
- Proliferative activity index (Ki67).
Additional prognostic markers include receptors for epidermal growth factor (EGFR), transforming growth factor alpha (TGF-α), as well as bcl-2 and p27 proteins.
What signs of cellular atypia are characteristic of malignant tumors?
Malignant neoplasms are characterized by a number of morphological signs of cellular atypia affecting the structure of cells, nuclei, and mitotic activity.
- Cellular changes — pronounced polymorphism (variability in shape and size), the appearance of giant, small primitive, and multinucleated cells.
- Nuclear changes — hyperchromia, polyploidy, polymorphism, irregular contours, appearance of large nucleoli, and an increased nuclear-cytoplasmic ratio.
- Changes in mitotic activity — an increase in the total number of mitoses and the appearance of pathological mitotic figures.
- Disruption of organization — loss of normal polarity and disorganized growth of cell complexes.
What types of cytokeratins are used for the differential diagnosis of squamous cell carcinoma?
Specific markers of the cytokeratin profile are used for the differential diagnosis of squamous cell carcinoma.
- Low-molecular-weight cytokeratins — characteristic of squamous cell carcinoma (in contrast to adenocarcinoma, where high-molecular-weight cytokeratins are detected).
- Cytokeratin 19 fragment (CYFRA 21-1) — used as a tumor marker to assess squamous cell carcinoma.
Additionally, squamous cell carcinoma antigen (SCC) and the presence of keratohyalin are determined for the diagnosis of this tumor type.
The abbreviation TNM is easily decoded by the first letters of the English terms: T — Tumour (size of the tumor itself), N — Nodules (lymph node involvement), M — Metastases (distant metastases in organs).
Class and exam questions
What is inverted papilloma?
This is a special variety of papilloma characterized by endophytic growth (growing deep into underlying tissues rather than outward). It can only be detected by microscopic examination.
How do carcinomas metastasize?
In the initial stages, malignant cells spread predominantly via the lymphogenous route, forming the first metastases in regional lymph nodes. Hematogenous metastases develop at later stages.
What is the difference between exophytic and endophytic adenoma growth?
Exophytic growth means that the tumor grows into the lumen of an organ (for example, in the form of an adenomatous polyp). Endophytic growth is characteristic of flat adenomas, which spread along the mucous membrane and grow deep into the wall.
What else to study on this topic
- Molecular-genetic criteria for the classification of neoplasms
- Structural features and levels of differentiation of adenocarcinomas
- Mechanisms of tissue and cellular atypia
- Tumor profiling and signature using immunohistochemistry
- Organ-specific tumors of the endocrine system, kidneys, and liver
Master the entire topic in the "Pathological Anatomy" course
This is a summary. The course covers everything tested in classes and exams.
- Complete study guide on "Tumor Classification" and 4,414 more pages of the 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.