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Classification of Tumors

*Tumor* / *Neoplasma*

For medical students2 min readUpdated 2026-10-10

Modern classification of neoplasms is based on clinical, molecular-genetic, and morphological features. Morphological tissue examination remains the primary tool for establishing an accurate diagnosis, selecting treatment tactics, and assessing prognosis.

Basis of DiagnosisMorphological structure determines treatment strategy and prognosis
TNM SystemEvaluates tumor size (T), lymph nodes (N), and metastases (M)
HistogenesisDetermines the tissue of origin from which the tumor developed
IHC MarkersProtein molecules used to verify undifferentiated cells

Clinical TNM System

Based on assessing the stage and spread of the tumor process.

Grading features is specific to different locations and typically ranges from 1 to 3. Special clinical forms of carcinomas include:

  1. Microcarcinoma — diameter less than 1 cm or absence of invasion into the lamina propria of the mucosa (often found in the thyroid and breast).
  2. "Small cancer" — a term applied to small neoplasms of the stomach.
  3. Occult tumors — hidden lesions that produced no clinical manifestations and were not diagnosed during standard examination.

Morphological Criteria and Histogenesis

Morphology is the foundation of oncological diagnosis. Tumors are divided according to the degree of cellular maturity into benign, borderline, and malignant.

Depending on the source of origin (histo- and cytogenesis), epithelial neoplasms include:

Standard hematoxylin and eosin (H&E) staining is sufficient to determine histogenesis 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 arising from the surface epithelium of the skin, mucous membranes (esophagus, vagina, urinary bladder), or bronchial tree. Externally, it has a papillary surface resembling cauliflower. Microscopically, it consists of epithelial proliferations with a fibrovascular core (connective tissue with blood vessels inside the papilla). The epithelium retains basement membrane integrity, polarity, cohesiveness, and stratification, though the number of layers increases (a sign of architectural atypia). It rarely undergoes malignant transformation, but is dangerous when localized in the larynx, urinary bladder, and skin. A variant with pronounced keratinization is called a keratoma.

Adenoma — forms from glandular tissue. It may grow outward as a finger-like projection or polyp (exophytic growth) or spread flat along the mucosa (flat adenoma with endophytic growth). Depending on the structures formed, tubular, trabecular, alveolar, papillary, and cystadenoma types are distinguished. If a developed stroma predominates in an adenoma, it is called a fibroadenoma (typical for the breast and ovaries).

Differentiation and Markers of Malignant Growth

The level of differentiation in malignant tumors is determined by three criteria: the expression of histogenesis markers, preservation of functional activity, and the degree of cellular atypia.

For example, well-differentiated squamous cell carcinoma preserves intercellular bridges and forms "cancer pearls" (extracellular keratinization). In moderately differentiated tumors, keratinization becomes intracellular, while in poorly differentiated tumors, it is virtually absent, leaving only stratification.

For precise identification of carcinomas, specific protein oncomarkers are sought using IHC:

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.

Mnemonic

The acronym TNM is easily remembered by the first letters of the English terms: T — Tumour (size of the primary tumor), N — Nodules (lymph node involvement), M — Metastases (distant metastases in organs).

Frequently asked questions

What organ-specific IHC markers exist for breast carcinoma?

For breast carcinoma, immunohistochemical markers are used to determine the receptor status and proliferative activity of the tumor. 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 2 (HER2) — a marker for targeted therapy.
  • Proliferative 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 cell structure, nuclei, and mitotic activity.

  • Cellular changes — pronounced polymorphism (variability in shape and size), appearance of giant, small primitive, and multinucleated cells.
  • Nuclear changes — hyperchromasia, polyploidy, polymorphism, irregular contours, appearance of prominent nucleoli, and an increased nuclear-cytoplasmic ratio.
  • Mitotic activity changes — increased total number of mitoses and the appearance of pathological mitotic figures.
  • Disorganization — 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 cytokeratin profile markers are used for the differential diagnosis of squamous cell carcinoma.

  • Low-molecular-weight cytokeratins — characteristic of squamous cell carcinoma (unlike adenocarcinoma, which reveals high-molecular-weight cytokeratins).
  • Cytokeratin 19 fragment (CYFRA 21-1) — used as an oncological marker to evaluate squamous cell carcinoma.

Additionally, squamous cell carcinoma antigen (SCC) and the presence of keratohyalin are determined for the diagnosis of this tumor type.

What is an inverted papilloma?

This is a special type of papilloma characterized by endophytic growth (growing inward into underlying tissues rather than outward). It can only be detected by microscopic examination.

How do carcinomas metastasize?

In the early stages, malignant cells spread primarily via the lymphatic route, forming initial metastases in regional lymph nodes. Hematogenous metastases develop at later stages.

What is the difference between exophytic and endophytic growth of an adenoma?

Exophytic growth means the tumor grows into the lumen of the organ (e.g., as an adenomatous polyp). Endophytic growth is characteristic of flat adenomas, which spread along the mucous membrane and grow deep into the wall.

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